Home Medicine Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis
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Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis

  • Róbert Rostás EMAIL logo , István Fekete , László Horváth , Sándor Márton and Klára Fekete
Published/Copyright: June 29, 2024
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Open Medicine
From the journal Open Medicine Volume 19 Issue 1

Abstract

Objective

Our aim was to examine the significance of single-fiber electromyography (SFEMG) in patients diagnosed with amyotrophic lateral sclerosis (ALS) and determine the best correlating parameter with SFEMG parameters and clinical scales across different muscles including facial muscles.

Methods

SFEMG examinations were conducted on the extensor digitorum (ED), frontalis, and orbicularis oculi muscles. Mean jitter, percentage of increased jitter, fiber density (FD), and impulse blocking percentage were compared to reference values and functional scales.

Results

Significant differences (p < 0.001) were observed between the patients’ SFEMG results and reference values in all muscles. Significant correlations were found between SFEMG parameters and clinical scales, particularly when considering both FD and jitter. A notable value of the ALS Functional Rating Scale Revised (ALSFRS-R) was detected in all muscles: 31 points in the ED muscle, 30 in the orbicularis oculi muscle, and 31 in the frontalis muscle. Below this ALSFRS-R threshold, the percentage of increased jitter was higher, while FD remained relatively low.

Conclusion

SFEMG examination emerges as a valuable tool for better understanding ALS and holds potential for assessing prognosis. Combined jitter and FD analysis showed the strongest correlation with clinical scales. In addition to the ED muscle, the orbicularis oculi muscle may be important in the assessment.

Keywords: amyotrophic lateral sclerosis; fiber density; jitter; orbicularis oculi muscle; frontalis muscle

1 Introduction

Amyotrophic lateral sclerosis (ALS) is the most common incurable motor neuron disease (MND) in adults, which is characterized by dysfunction of the upper motor neuron (UMN) and the lower motor neuron (LMN) resulting in progressive weakness and wasting of muscles in the bulbar, limb, thoracic, and abdominal regions [1]. In a recent publication, according to data from a meta-analysis, the standardized global incidence of ALS was 1.68 per 100,000 person-years of follow-up. Nevertheless, it may vary in different regions: in Europe and North America, it ranges between 1.71 and 1.89 per 100,000, in Asian populations 0.73 and 0.94 per 100,000, and a much higher figure, 2.25 per 100,000 was found in Oceania [2]. ALS phenotypes seem to be similar in different populations, even across Europe according to ALS registries these might be different [3]. The demographic projections indicate that the number of affected individuals aged above 60 years is going to increase and as a consequence of this, the global count of patients grappling with MND, notably ALS, is anticipated to witness an upward trajectory [1,4,5,6,7]. ALS is also known to emerge differently in different regions; it might also have subtle differences, as different registries in Europe pointed out. In ALS, the process of denervation involves a breakdown in communication between motor neurons and the muscle fibers they typically innervate. Subsequently, surviving motor neurons attempt to compensate for this disruption by establishing new connections known as reinnervation [3]. Based on previous literature, the single-fiber electromyography (SFEMG) examination may serve as a suitable tool for detecting these neuropathological abnormalities [8].

The clinical diagnosis of ALS requires the presence of progressive degeneration of UMN or LMN throughout the neuraxis. Electrodiagnostic evaluation is essential in the early stages of ALS, especially when UMN or, more frequently, LMN signs may be hidden [9]. Neurophysiological diagnostic tools play a substantial role in confirming the diagnosis of ALS. Nevertheless, more detailed examinations might be necessary in the early stages of the disease when symptoms first manifest in the patient. Peripheral nerve conduction studies (NCS) and electromyography (EMG) are appropriate diagnostic tools that confirm key pathological features of ALS, as outlined in the El Escorial criteria [10,11], and help differential diagnostics [9,10,11]. Other neurophysiological tests are available to examine the integrity of the nervous system, including SFEMG [12].

SFEMG has demonstrated its diagnostic value in neuromuscular disorders, particularly in cases of myasthenia gravis, and is the most sensitive technique for detecting neuromuscular transmission defects [8,12]. The process of denervation–reinnervation is the pathological hallmark of the ALS [3,9]. Denervation involves the disconnection between motor neurons and muscle fibers they normally control. In response to such disconnection, surviving motor neurons try to compensate by forming new connections, referred to as reinnervation. The presence of abnormal jitter, fiber density (FD), and impulse blocking show a positive correlation with weakness and muscle atrophy [13]. This is likely due to the existence of immature sprouting of nerve terminals and the degree of reinnervation [14].

Classification according to the presenting symptoms can be done, and bulbar-onset, limb-onset (upper and lower), pure upper limb onset, and pure lower limb onset subtypes are usually distinguished [3].

After diagnosing a patient with ALS, the first question from the patient and family is usually associated with the time of survival. Although the progression of ALS can differ considerably, the average duration from symptom onset is approximately 3 years, but it can vary from 2 to 10 or even 20 years [14]. Survival may be influenced by several factors like clinical symptoms at onset, rate of progression, early presence of respiratory failure, nutritional status of the patient, etc. By following our patients more closely, some factors (e.g., nutritional status, respiratory failure) might be treated or their severity reduced [3]. One of the primary reasons is that recognizing the disease in a timely manner and estimating the prognosis allow for the opportunity of appropriate treatment and adequate support, which could improve both quality of life and disease outcomes [15]. Additionally, early diagnosis assists patients and their families in accessing the necessary therapies, support, and resources.

Estimating the prognosis may be crucial, not only from a social aspect but also from the aspect of treatment and clinical trials as well [3,16]. Besides, functional scales like ALS Functional Rating Scale Revised (ALSFRS-R) [17] other measurable methods might be useful [18,19].

The objective of this study was to examine the alterations and clinical significance of SFEMG in patients diagnosed with ALS in different muscles and find the best correlating parameter with clinical scales. Contrary to limb muscles, facial muscles tend to be relatively spared during the early stages of the disease, so our aim was also to find alterations of SFEMG parameters in facial muscles as well. We hypothesize that SFEMG in ALS might give supportive information and better insight into the pathomechanism of the disease and we assume that the findings in the facial muscles are important in this.

2 Materials and methods

2.1 Patients and data

The study was conducted at the Department of Neurology, University of Debrecen, over an inclusion period from June 1, 2018, to June 30, 2022. The neurophysiology unit, serving as a tertiary center, covers a catchment area of 600,000 residents within a 90 km radius.

In this study, patients meeting the Awaji criteria following the initial diagnosis of ALS were enrolled [10,11]. Each patient exhibited progressive motor impairment within 1 year of diagnosis. Notably, all patients displayed clinical signs of UMN and LMN dysfunction in at least one body region, as confirmed by repeated clinical assessments. The definitive diagnosis of ALS and voluntary participation in the examinations constituted the inclusion criteria. Additionally, confirmation of LMN dysfunction was established through EMG in all enrolled patients. Cases of other types of MNDs, as well as those who did not give consent, were considered exclusion criteria.

To exclude other potential causes of neuropathies that may mimic ALS, motor and sensory NCS were carried out in all patients. To rule out any structural abnormalities of the brain or spinal cord that may potentially mimic ALS, all patients in our study underwent cranial and cervical high-resolution 3-T magnetic resonance tomography. Additionally, cerebrospinal fluid and blood tests were conducted in all cases to exclude the presence of other diseases.

Considering the initial symptoms, the patients were categorized into the following subgroups: bulbar-onset and limb-onset. As ALS symptoms are typically asymmetrical, we created additional subgroups within the limb-onset category to compare our data. These subgroups included patients whose right upper limb (RUL), left upper limb (LUL), right lower limb (RLL), and left lower limb (LLL) were affected. By chance the patients reported themselves to be right handed. So, we did not create dominant and non-dominant groups.

ALSFRS-R score [17] and the Medical Research Council (MRC) strength scale for the extensor digitorum (ED) muscle [18,19] were used to assess functional status and compare the subgroups.

With ALSFRS-R scoring 12 physical functions, in 4 domains are tested: speech, salivation, swallowing, handwriting, nutrition and the use of the hand when eating, dressing and hygiene, turning in bed, walking, climbing stairs, dyspnoea, orthopnoea, respiratory insufficiency. Each item is scored on a scale between 0 and 4, where a score of 4 signifies unimpaired functionality, while a score of 0 denotes severe impairment. The scores are then summed up to obtain a total score that ranges between 0 and 48. Elevated scores correlate with heightened levels of functional self-sufficiency, whereas diminished scores correlate with more pronounced deteriorations in functional capacity [17,20,21]. MRC scale is a frequently employed method to evaluate muscle strength, ranging from Grade 5 (normal) to Grade 0 (absence of visible contraction) [18,19].

2.2 SFEMG

Volitional SFEMG was performed using a disposable SF needle electrode with a recording diameter of 25 μm. During the examination, the subjects were in a relaxed state, either comfortably reclining in a chair or lying down in a supine position. The examination was conducted in a quiet, electrically shielded, and temperature-controlled room in the neurophysiology laboratory at the Department of Neurology. The single-fiber EMG test was evaluated using a 9031A006401 Keypoint Clinical System (Natus Medical, Pleasanton, CA, USA). A disposable SFEMG needle electrode (Spes MEdica, Genova, Italy 0.45 (26G) × 37 mm) was used in all cases. Prior to the SFEMG testing, neither the healthy control individuals nor the ALS patients received any medication that could potentially affect the results of the SFEMG study.

Selective recordings of single muscle fiber potentials were performed in the ED muscle in all patients to obtain measurements of mean jitter, percentage of increased jitters, FD, and percentage of impulse blocking. ED was chosen because it was clinically intact at the time of the examination. Clinically detectable unequivocal LMN signs were detected in the RUL group, this is why we showed the analysis also with the exclusion of the RUL group. No denervation, fasciculation, or polyphasic waves were present in the ED muscle. Since we have done voluntary SFEMG we needed to choose muscles that the patient could innervate and maintain constant force for this purpose ED muscle was suitable in all patients. Jitter was calculated on the basis of the mean consecutive difference, while blocks were determined by the count of dropped discharges during consecutive discharges. The percentage of increased jitter and percentage of blocking was calculated from the 20 analyzed potential pairs (numbers of pathological findings/20). FD was defined as the number of single musclefibers from one motor unit within the electrode’s uptake area. Since the facial muscles tend to be relatively spared – at least at the early stages of the course of ALS – we also performed SFEMG examinations of the right frontalis muscle in eight cases and the right orbicularis oculi muscle in seven cases. The limited number of participants may be due to the fact that the needling test involving facial muscles is considered more uncomfortable than similar assessments involving skeletal muscles. Consequently, part of the patient population refused to participate in the frontal and orbicularis oculi.

For jitter analysis, we used age-adjusted healthy controls (N = 26) (without any diseases affecting the neuromuscular system), according to reference values used [22].

The electrode position was delicately adjusted to optimize the action potential (AP) amplitudes; for accurate jitter measurements, all relevant APs should exhibit sharply rising phases and sufficient amplitudes.

Twenty potential pairs of APs were measured and recorded from various parts of the muscle, utilizing three to four skin insertions.

During an SFEMG examination, APs greater than 200 µV are inferred to originate from muscle fibers within 300 µm of the recording surface. By measuring the mean number of time-locked APs with an amplitude of greater than 200 µV and a rise time of less than 300 µs at multiple sites, we can calculate FD, which quantifies the local concentration of muscle fibers within the motor unit [23,24].

FD measurements were made by observing the signals on the screen. As the patient voluntarily activated the muscle, the electrode was positioned to record the AP with maximum amplitude from one muscle fiber. This AP triggers an oscilloscope sweep and is delayed for display, allowing the counting of synchronized APs with amplitudes over 200 µV [23,24].

APs are recorded at 20 separate sites within a muscle, minimum at 3 separate insertion sites. FD represents the mean number of APs, including the triggering AP, counted in the 20 sites.

2.3 Statistical analysis

We used the SPSS for Windows 19.0 program suite (SPSS Inc., Chicago, USA). for statistical analyses. In this study, we employed a multivariate analysis of variance test and pairwise comparison to examine the interplay between age, gender, and duration, as well as the ALSFRS-R and ED strength score of MRC within distinct ALS subgroups. We compared the data obtained during the SFEMG examination with the data in the normal range [21] using the Mann–Whitney test. In cases where a normal distribution was observed, we applied the Student’s t-test. Furthermore, we assessed the correlation between the results of the functional tests and the SFEMG indices using the Spearman’s rank test. Statistical significance was considered if p < 0.05.

  1. Informed consent: All of the participants signed an informed consent to take part in the protocol, which was approved by the local ethics committee (RKEB5036-2018).

  2. Ethical statement: The study was approved by the Regional and Institutional Ethics Committee of University of Debrecen Clinical Centre (protocol number: RKEB5036-2018).

3 Results

3.1 Baseline characteristics

The study included a cohort of 26 patients who were enrolled based on meeting the Awaji criteria following the initial diagnosis of ALS [10,11]. Of the 26 patients enrolled, 12 were females (aged 45–78, mean age 62 years) and 14 males (aged 49–84 years, mean age 60 years). Healthy controls (N = 26) were age and gender (12 females, 14 males) matched.

Patients’ data on disease duration, ALSFRS-R score, and MRC strength score in the ED muscle concerning bulbar and limb grouping are summarized in Table 1. Table 2 contains further details of the limb-onset groups. We did not find any statistically significant differences among the subgroups in terms of gender distribution, and duration of the disease (Tables 1 and 2). In the bulbar group, patients were more than 10 years younger on average (Tables 1 and 2).

Table 1

Patient characteristics in different subgroups among the examined ALS patients

Bulbar-onset Limb-onset p
Number of patients 8 18 —
Number of female/male 5/3 7/11 0.27
Age (years) (mean ± SD) 57.5 ± 10.0 68.0 ± 11 0.015
Disease duration (from onset to referral, examination) (month) (mean ± SD) 6.5 ± 1.2 5.94 ± 1.51 0.42
(minimum; maximum) (6; 8) (4; 8)
ALSFRS-R (mean ± SD) 30.4 ± 2.13 34.1 ± 4.7 0.048
(minimum; maximum) (30; 34) (28; 43)
MRC score in left ED m. (mean ± SD) 4.1 ± 0.83 4.05 ± 0.73 0.85
MRC score in right ED m. (mean ± SD) 4.25 ± 0.88 3.89 ± 0.83 0.36

The bold values indicate statistically significant p values.

Table 2

Patient characteristics in different subgroups among the examined ALS patients. The p values were calculated between the subgroups within the rows. The statistical analysis is given in the ‘Materials and methods’

Onset symptoms Bulbar Right upper limb Left upper limb Right lower limb Left lower limb p
Number of patients 8 5 4 4 5 —
Number of female/male 5/3 2/3 1/3 2/2 1/4 0.56
Age (years) (mean ± SD) 57.5 ± 10.0 67 ± 11.81 69.75 ± 5.35 64.5 ± 15.79 70.4 ± 12.83 0.21
Disease duration (from onset to referral, examination)(months) (mean ± SD) 6.5 ± 1.2 5.4 ± 1.52 5.75 ± 1.26 7.25 ± 0.50 5.6 ± 1.67 0.19
ALSFRS-R (mean ± SD) 30.4 ± 2.13 35.8 ± 4.68 38.75 ± 2.87 31.5 ± 3.48 30.8 ± 2.17 0.008
MRC score in left ED m. (mean ± SD) 4.61 ± 0.83 4.4 ± 0.54 4.5 ± 0.57 4.25 ± 0.5 3.8 ± 0.45 0.4
MRC score in right ED m. (mean ± SD) 4.25 ± 0.88 4.2 ± 1.09 4.25 ± 0.5 3.25 ± 1 3.8 ± 0.84 0.29

The bold values indicate statistically significant p values.

Comparing subgroups and functional scales, significant differences were observed when comparing the ALSFRS-R scores among the subgroups (Table 1).

When comparing the LUL and RUL groups, we did not find a statistically significant difference. However, significant differences were observed when comparing the LUL group with all the other subgroups. Similarly, a significant difference was found between the RUL groups.

Based on these results, it is evident that patients in the LUL subgroup exhibited the mildest clinical symptoms, whereas those in the bulbar subgroup had the most severe symptoms.

We also compared the subgroups based on the MRC strength score on the ED muscle, both on the left and right sides. Differences were not significant among the groups if MRC scores in ED were compared (Tables 1 and 2).

3.2 SFEMG

The values obtained from the SFEMG examination of all ALS patients (N = 26) in the three examined muscles were compared with healthy controls (N = 26) (Table 3). Significant differences were observed in the mean jitter, mean percentage of increased jitter, FD, and blocking percentage (Table 3). In Table 3, we show a detailed summary of the parameters within the bulbar-onset and limb-onset groups; the only significant difference could be detected in ED muscle by the mean jitter and increased jitter percentage, but the sample numbers of the subgroups (e.g., 2) by the muscle alone are imbalanced and small which might result in misleading interpretations.

Table 3

SFEMG parameters among the examined ALS patients and healthy controls

ED muscle Mean jitter (ms) Increased jitter percentage Block percentage FD
Healthy controls (N = 26) 32.5 ± 2.8 0% 0% 1.3 ± 0.1
ALS patients (N = 26) 54.4 ± 4 30.9% ± 14.2% 15.4% ± 10.7 2.6 ± 0.45
p -value <0.001 <0.001 <0.001 <0.001
Bulbar-onset (N = 8) 56.74 ± 4.42 39.38 ± 16.69% 16.88 ± 11.93% 2.38 ± 0.35
Limb-onset (N = 18) 53.34 ± 3.4 27.11% ± 11.59% 14.72% ± 10.36% 2.66 ± 0.47
p -value 0.04 0.039 0.64 0.15
Orbicularis oculi muscle
Healthy controls (N = 26) 35.7 ± 2.8 0% 0% 1.2 ± 0.1
ALS patients (N = 7) 51.5 ± 3.0 23.6% ± 11.1% 15.7% ± 37 2.2 ± 0.23
p -value <0.001 <0.001 <0.001 <0.001
Bulbar-onset (N = 2) 53.4 ± 3.39 32.5 ± 10.61% 22.5 ± 17.68% 2.1 ± 0.28
Limb-onset (N = 5) 42.68 ± 13.86 26.67% ± 5.77% 13.0% ± 12.04% 2.2 ± 0.23
p -value 0.35 0.37 0.43 0.64
Frontalis muscle
Healthy controls (N = 26) 37.9 ± 2.6 0% 0% 1.3 ± 0.13
ALS patients (N = 8) 51.24 ± 2.4 23.75% ± 6.94% 23.13% ± 8% 2.14 ± 0.15
p -value <0.001 <0.001 <0.001 <0.001
Bulbar-onset (N = 4) 51.78 ± 1.16 26.25 ± 4.79% 27.5 ± 5.0% 2.18 ± 0.13
Limb-onset (N = 4) 45.7 ± 13.2 25.0% ± 5.0% 18.75% ± 8.54% 2.1 ± 0.18
p -value 0.39 0.73 0.13 0.5

The bold values indicate statistically significant p values.

Comparing ALSFRS-R and the indices of the SFEMG examination of the ED muscle, a significant negative correlation (Table 4) was found in both the percentage of increased jitter (r = −0.953) (Figure 1) and blocking percentage (r = −0.829) (Figure 2) (p < 0.001 in all cases). FD was positively correlated with ALSFRS-R (r = 0,919; p < 0.001) (Figure 3). All results show a very strong correlation. A significant correlation was also detected between the percentage of increased jitters and FD (r = 0.89, p < 0.001) (Figure 4).

Table 4

Correlation between the clinical scales and neurophysiological parameters

Parameter Mean jitter Increased jitter (%) Block (%) FD
ED m. all patients N = 26 ALSFRS-R r = −0.901 r = −0.953 r = −0.829 r = 0.919
p < 0.0001 p < 0.0001 p < 0.0001 p < 0.0001
MRC in ED r = −0.441 r = −0.469 r = −0.729 r = 0.53
m. p = 0.024 p = 0.02 p < 0.0001 p = 0.005
Increased — — — r = −0.89
jitter % p < 0.0001
ED m. RUL group excluded N = 21 ALSFRS-R r = −0.340 r = −0.96 r = −0.824 r = 0.901
p = 0.09 p < 0.0001 p < 0.0001 p < 0.0001
MRC in ED r = −0.437 r = −0.464 r = −0.789 r = 0.42
m. p = 0.055 p = 0.03 p < 0.0001 p = 0.06
Increased — — — r = −0.888
Jitter % p < 0.0001
Frontalis m. N = 8 ALSFRS-R r = −0.805 r = −0.798 r = −0.877 r = 0.798
p = 0.016 p = 0.02 p = 0.004 p = 0.02
MRC in ED r = −0.252 r = −0.007 r = 0.189 r = 0.425
m. p = 0.55 p = 0.99 p = 0.65 p = 0.29
Increased — — — r = −0.513
jitter % p = 0.19
Orbicularis oculi m. N = 7 ALSFRS-R r = −0.964 r = −0.954 r = −0.963 r = 0.918
p = 0.0005 p < 0.0001 p = 0.0005 p = 0.004
MRC in ED r = −0.934 r = −0.864 r = −0.904 r = 0.187
m. p = 0.003 p = 0.01 p = 0.005 p = 0.02
Increased — — — r = −0.817
Jitter % p = 0.03
Figure 1 Correlation between ALSFRS-R and percentage of increased jitter in the examined muscles (ED m.: p < 0.0001, frontalis m.: p = 0.02, orbicularis oculi m. p < 0.0001).
Figure 1

Correlation between ALSFRS-R and percentage of increased jitter in the examined muscles (ED m.: p < 0.0001, frontalis m.: p = 0.02, orbicularis oculi m. p < 0.0001).

Figure 2 Correlation between ALSFRS-R and percentage of blocks in the examined muscles (ED m.: p < 0.0001, frontalis m.: p = 0.004, orbicularis oculi m.: p = 0.005).
Figure 2

Correlation between ALSFRS-R and percentage of blocks in the examined muscles (ED m.: p < 0.0001, frontalis m.: p = 0.004, orbicularis oculi m.: p = 0.005).

Figure 3 Correlation between ALSFRS-R and FD in the examined muscles (p < 0.0001 in all).
Figure 3

Correlation between ALSFRS-R and FD in the examined muscles (p < 0.0001 in all).

Figure 4 Correlation between FD and percentage of increased jitter in the examined muscles (ED m.: p < 0.0001, m. frontalis: p = 0.19, m. orbicularis oculi p = 0.03.
Figure 4

Correlation between FD and percentage of increased jitter in the examined muscles (ED m.: p < 0.0001, m. frontalis: p = 0.19, m. orbicularis oculi p = 0.03.

The right ED muscle might have been affected and the SFEMG parameters might have been more pathological in the RUL group, so we wanted to perform an analysis excluding this subgroup, to see the alterations. When the RUL-onset group was excluded, the correlations were as follows: ALSFRSR compared to jitter percentage (r = −0.96), and block percentage (r = −0.824) (Table 4). A significant negative correlation was found in the following indices obtained from the SFEMG examination of the frontal muscle and between the ALSFRS-R: mean jitter r = −0.805; p < 0.01; mean percentage of increased jitter r = −0.798; p = 0.02 (Figure 1); and blocking percentage r = −0.877; p = 0.004 (Figure 2). The FD was positively correlated with ALSFRS-R (r = 0.798; p = 0.02) (Figure 3 and Table 4). With EMG examination no denervation, fasciculation or polyphasic potentials (indicating reinnervation) were detected among the factors that might influence the result of SFEMG. Therefore, the observed variations during the SFEMG examination are not due to EMG abnormalities.

Between the ALSFRS-R and the indices of the SFEMG examination of the orbicularis oculi muscle, a significant negative correlation was found in the mean jitter (r = −0.964), in the mean percentage of increased jitter r = −0.954 and blocking percentage r = −0.963 and, respectively, p < 0.001 in all cases. These results show a very strong correlation. Similarly, as in the case of the ED muscle and the frontal muscle, the FD was positively correlated with ALSFRS-R in this instance as well (r = 0,918; p < 0.01), resulting in a very strong correlation. Figure 5 shows the correlation between the percentage of increased jitter, FD, and ALSFRS-R. The percentage of increased jitter increases and FD decreases in more severe stages of the disease, marked by more severe ALSFRS-R scores. In all muscles, a notable value of ALSFRS-R can be detected: 31 points in the ED muscle, 30 in the orbicular oculi muscle, and 31 in the frontal muscle. This shift from around 30 points signifies the commencement of a process wherein reinnervation capacities are depleted, coinciding with a reduction in FD.

Figure 5 Correlation between ALSFRS-R, FD, and increased jitter % in ED muscle, frontalis muscle, and orbicularis oculi muscle.
Figure 5

Correlation between ALSFRS-R, FD, and increased jitter % in ED muscle, frontalis muscle, and orbicularis oculi muscle.

Since the examination of the ED muscle was performed on the right side for all patients, we compared their results with the right-sided MRC score of the ED (Table 4). ED muscle strength and the following three SFEMG indices showed significant negative correlation: mean jitter (r = −0.441; p = 0.02, moderate correlation) mean percentage of increased jitter (r = −0.469; p = 0.02 moderate correlation) and blocking percentage (r = −0.729; p < 0.001 strong correlation). Excluding the RUL-onset group from the analysis, similar results were detected (Table 4), although significance was not reached. In case of the orbicularis oculi muscle examining the correlations between the MRC score in the ED muscle with the percentage of jitter, blocks, and FD, we found a significant correlation in all respects (Table 4), but in the frontalis muscle only in case of jitter percentage. In the frontalis muscle, jitter percentage and FD did not show a significant correlation either (Figure 6, Table 4).

Figure 6 Correlation in frontal muscle and orbicularis oculi muscle between increased jitter percentage, FD and block percentage, and MRC score in ED muscle.
Figure 6

Correlation in frontal muscle and orbicularis oculi muscle between increased jitter percentage, FD and block percentage, and MRC score in ED muscle.

Disease duration did not show a significant correlation with ALSFRS-R in the examined cohort (Table 5).

Table 5

Correlation between ALSFRS-R in all patients and subgroups with disease duration

ALSFRS-R All patients, N = 26 Bulbar-onset group, N = 8 Limb-onset group, N = 18
Disease duration r = −0.34 p = 0.09 r = −0.422 p = 0.297 r = −0.28 p = 0.26

4 Discussion

Despite adequate information about case history and a comprehensive physical examination, many ALS patients are diagnosed only in the late stage. Our aim was to find such hallmarks with the help of SFEMG. These might help to optimize the supporting care of patients living with ALS and might also help in clinical trials. All these can lead to a better quality of life for a longer period of time, which is of great importance for patients and their families alike [3,15,25].

In our study, the only significant difference between the subgroups of bulbar-onset and limb-onset was mean age. The patients of the “bulbar” subgroup were significantly younger. Although some patients were already in a severe condition, the time between disease onset to referral did not differ much. The disease duration did not show a significant correlation with the functional status, which might be due to the sample size. But also, important to note, that the minimum–maximum time was 5–8 months, which is very narrow, and cannot differentiate well between rapid and less rapid progression. This is contrary to the findings in a Spanish study, where they found a correlation between the disease duration and SFEMG findings, but the time was much higher (21−13 months) [26]. Unfortunately, especially in four patients suffering from the bulbar type, the progression was very rapid. Also, as many patients were in a poor overall condition on arrival, we think that our study is important in early diagnosis. On the basis of the onset symptoms and time of onset – always established according to the history of the patient (auto and hetero) – the first symptoms might have appeared much earlier, but the disease was not recognized or it might have been ignored by the patient. Time is important in estimating survival: in a publication on a referral ALS series, the authors claim the progression of ALSFRS-R during the whole disease and the first 100 days after diagnosis is closely related to the length of time [25]. In our study, the worst ALSFRS-R scores were found in the bulbar group. Compared with the limb-onset group, the prognosis in the bulbar subgroup was worse, similar to those reported in a review by Kiernan [3]. MRC score in ED muscle did not show significant differences among the groups. Since ALS is usually asymmetric and the symptoms in the dominant limb might also be suggestive of a worse prognosis [27] RUL, RLL, LUL, and LLL, subgroups were created for comparison. Because our patients were right-handed, we could not create a dominant and non-dominant group. Nevertheless, there was no difference in the onset of symptoms between the two limb sides (Table 2). The longest time from onset to referral was found in the lower-limb onset group, but it was not significant; the symptoms were probably more alarming in the other subgroups. When ALSFRS-R results were compared among the subgroups, the worst data were seen in the two lower limb groups (LLL, RLL) and were similar to those in the bulbar-onset group. The slight difference between LUL and RUL might be explained by the dominance of the upper limb [27]. Devine et al. assume based on their investigations that limb dominance may be a significant factor underlying the onset and spread of ALS [27]. This finding might certainly be due to a small sample size. But, as we mentioned above, it might have an impact on the prognosis as well [27]. The correlation between SFEMG findings and functional status may contribute to the cautious implication that it might be useful even in estimating prognosis. According to our findings, we think that SFEMG might be useful in the neurophysiological arsenal similar to other studies [13,28,29]. Limb dominance may reflect underlying neuronal vulnerabilities [27]. According to another opinion, a poorer prognosis in lower limb-onset ALS might be correlated to the risk of thromboembolic disease and infections due to immobility [30]. By comparing MRC scores in ED muscle, it could be seen that if the right limb was affected the scores were lower, also showing the importance of sides in ALS [30].

Despite the fact that the facial muscles were clinically unaffected, compared to the healthy controls’ mean jitter, mean percentage of increased jitter, FD, and blocking percentage, significant differences were observed in all patients, aligning with findings from other studies in the field [28]. These parameters might be useful in the early stage of ALS or when the diagnosis is uncertain, e.g., because the patient had sensory neuropathy due to other reasons. Incorporating facial muscle SFEMG examination may be also logical, since we do not expect FD to be increased in the face in polyneuropathies. In the publication of Liu et al. remarkably increased jitter, impulse blocking with increased FD supports the diagnosis of ALS rather than cervical spondylosis [28]. In cases like that, SFEMG might be a supportive tool [29]. Comparing the SF EMG parameters detailed in the three muscles separately among the subgroups of bulbar- and limb-onset cannot be interpreted unequivocally because of the small sample size.

We also correlated the results of SFEMG studies with the ALSFRS-R and the MRC score in ED. Our results revealed a significant negative correlation between the functional status and comparison of mean jitter, percentage of increased jitter, and blocking percentage. Conversely, FD showed a significant positive correlation with the functional scales, indicating a gradual decrease in FD values as the disease progressed. We assume that SFEMG findings in a given patient at a specific time point may contribute to the estimation of the prognosis of the disease, since it correlates with the ALSFRS-R, which is a prognostic factor, with cautious interpretation [29,31,32]. Our findings were similar to those of Imam, who assumed that a higher FD value might be predictive of a better prognosis [29]. An increase in FD might suggest reinnervation before muscle biopsy findings would confirm it [8]. It might be interpreted also as a consequence of possible ephaptic activation of neighboring fibers resulting in increased FD. They do not necessarily appear as a fiber-type grouping in biopsies [8]. Therefore, we assume that FD and jitter have to always be analyzed together (Table 4 and Figure 5) because this way these two parameters together might serve as better prognostic factors. All correlations were significant in the ED and orbicularis oculi muscles. As for the frontalis muscle, the correlation was not significant, but the trend was similar. We have observed a notable value of ALSFRS-R value of 30 in the examined muscles, the percentage of increased jitter is high, and FD is already low. This delineates the initiation of a process where reinnervation capacities are exhausted, coupled with a decline in FD. The observed percentages of increased jitter further emphasize the significance of this point. Reinnervation at this stage is probably not so intense, already severe in instability in the neuromuscular junction can be detected because of the denervation, and the clinical score indicates a severe condition. In ALS according to animal studies, the remodeling of the neuromuscular junction is dynamic. A study by Dantes and McComas showed that the sizes of the motor unit potentials continued to increase as the disease progressed, and later the sprouting by surviving motor axons remained proportional to the numbers of denervated muscle fibers available for adoption [33] and the compensatory reinnervation may not last [33,34]. A possible tool for monitoring could also be motor unit size index, which measures a clinically relevant reinnervation effect [34].

These findings are interesting because our patients had no symptoms in any of their facial muscles. Contrary to limb muscles, facial muscles tend to be relatively spared during the early stages of the disease, so we were curious to investigate whether we could detect any differences in these muscles with SFEMG examinations. Axonal-stimulating SFEMG studies were performed in the frontalis muscle by Watanabe et al. and stated that in the relatively preserved frontalis muscle in ALS, jitter was significantly increased, possibly caused by dysfunction of the presynaptic neuromuscular junction and motor nerve terminals [35].

For this purpose, we conducted SFEMG examinations of the frontalis muscle and the orbicularis oculi muscle. In case of the frontalis muscle and orbicularis oris muscle, all parameters (Table 3) were within the reference values [22] but differed significantly from the data in healthy controls. However, it should be remembered that the low number of cases might contribute to these results. In our study when correlations concerning increased jitter percentage, FD, and block percentage and ALSFRS-R scores were examined, a significantly strong correlation was detected in both of the facial muscles, but when the parameters are correlated to MRC score in ED, it can be detected only in orbicularis oculi muscle (Figure 6, Table 4). Independently of the small sample size, the orbicularis oculi muscle appears more preferable than the frontal muscle to support early neurophysiological abnormality in a clinically unaffected muscle.

We assume that the findings in the facial muscles are important, although the sample is size small. Contrary to limb muscles, the cause for spared extraocular muscles is the difference in the expression of Wnts, described in a publication by [36]. The family of Wnt proteins plays a role in neuromuscular development and regeneration in extraocular and limb muscles, particularly at the level of neuromuscular junctions [36]. The study suggested that these proteins played a role in the pathophysiology of ALS [36]. Their data supported the presence of preserved Wnts in the neuromuscular junctions of extraocular muscles [36,37]. Nevertheless, in later stages, a possible dying back mechanism might be responsible for the lesion of the extraocular muscles. Microinjury of Piezo2 on muscle spindle proprioceptive terminals is supposed to be the underlying pathomechanism [38]. Our patients were examined in an early stage (6 months from symptom-onset), and their facial muscles were clinically preserved. Using a diagnostic tool specialized for neuromuscular junction abnormalities, we found pathological responses and strong correlations with ALSFRS-R and MRC scores in ED. This is the level where Wnt proteins are expressed [36]. Our findings suggest that with the help of combined jitter and FD analysis, the pathological changes can be detected before the appearance of clinical symptoms. We also assume that the orbicularis oculi muscle might be the best choice to support an early neurophysiological abnormality among clinically unaffected muscles.

5 Limitations

We are aware of the limitations of the study. Regarding research on SFEMG in ALS patients, only a relatively small number of patients have been involved [28,29] which limits the generalizability of the results. Unfortunately, when performing subgroup analysis, the sample size became smaller, which contributed to a weaker statistical power. Due to the real-life scenario there was an imbalance between right and left handedness, all patients enrolled were right-handed by chance. Nevertheless, every additional study result, even with a small number of participants, can significantly contribute to a more precise understanding of the role of SFEMG in the diagnosis of ALS. Our studies encompassed not only neurophysiological findings but also results of physical examination. We encountered challenges during the studied time interval due to the COVID-19 pandemic, which made it difficult to diagnose potential patients and access and examine those already diagnosed with ALS, while also disrupting our research processes. Although many patients had already severe symptoms, this also reflects the real-life scenario, at the time of the verified diagnosis the patients already have severe symptoms. However, it is important to note that all these patients were examined within a single center and region, resulting in a homogeneous study population. Nevertheless, other SFEMG studies in ALS encompass similar study population [26,28,29,35]. Given the rarity of the disease and the limited number of cases, it is essential to follow up with patients for an extended period and expand the study to include a larger sample of patients diagnosed with ALS.

6 Conclusion

Based on our results, we can assert that – in line with previous literature – SFEMG examination is a valuable tool in better understanding ALS and might be a potential tool in the future for assessing prognosis. According to our experience, a combined analysis of data jitter and FD gives the best correlation with clinical scales, and besides the ED muscle, the orbicularis oculi muscle is also important in the assessment.

Acknowledgments

The authors are grateful to Ferenc Mechler who made contributions to the conception of the work. Unfortunately, he passed away before the manuscript was drafted. The authors are thankful to the patients for participating in the examinations.

  1. Funding information: This research received no external funding.

  2. Author contributions: RR, KF, and IF led the initiative. RR, IF, and KF were involved in investigation, data curation, data analysis, and writing the original draft. HL was involved in the statistical analysis and figure and table formatting. MS was involved in the statistical analysis. All authors approved the final version.

  3. Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

  4. Data availability statement: The data presented in this study are available on request from the corresponding author. The data are not publicly available due to ethical reasons.

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Received: 2024-02-04
Revised: 2024-06-10
Accepted: 2024-06-10
Published Online: 2024-06-29

© 2024 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  79. miR-let-7a inhibits sympathetic nerve remodeling after myocardial infarction by downregulating the expression of nerve growth factor
  80. Immune response analysis of solid organ transplantation recipients inoculated with inactivated COVID-19 vaccine: A retrospective analysis
  81. The H2Valdien derivatives regulate the epithelial–mesenchymal transition of hepatoma carcinoma cells through the Hedgehog signaling pathway
  82. Clinical efficacy of dexamethasone combined with isoniazid in the treatment of tuberculous meningitis and its effect on peripheral blood T cell subsets
  83. Comparison of short-segment and long-segment fixation in treatment of degenerative scoliosis and analysis of factors associated with adjacent spondylolisthesis
  84. Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK/mTOR/NLRP3 pathway
  85. Methylation regulation for FUNDC1 stability in childhood leukemia was up-regulated and facilitates metastasis and reduces ferroptosis of leukemia through mitochondrial damage by FBXL2
  86. Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis
  87. Risk factors of postoperative airway obstruction complications in children with oral floor mass
  88. Expression levels and clinical significance of serum miR-19a/CCL20 in patients with acute cerebral infarction
  89. Physical activity and mental health trends in Korean adolescents: Analyzing the impact of the COVID-19 pandemic from 2018 to 2022
  90. Evaluating anemia in HIV-infected patients using chest CT
  91. Ponticulus posticus and skeletal malocclusion: A pilot study in a Southern Italian pre-orthodontic court
  92. Causal association of circulating immune cells and lymphoma: A Mendelian randomization study
  93. Assessment of the renal function and fibrosis indexes of conventional western medicine with Chinese medicine for dredging collaterals on treating renal fibrosis: A systematic review and meta-analysis
  94. Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer
  95. New target-HMGCR inhibitors for the treatment of primary sclerosing cholangitis: A drug Mendelian randomization study
  96. Population pharmacokinetics of meropenem in critically ill patients
  97. Comparison of the ability of newly inflammatory markers to predict complicated appendicitis
  98. Comparative morphology of the cruciate ligaments: A radiological study
  99. Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator
  100. Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study
  101. SHP-1 mediates cigarette smoke extract-induced epithelial–mesenchymal transformation and inflammation in 16HBE cells
  102. Acute hyper-hypoxia accelerates the development of depression in mice via the IL-6/PGC1α/MFN2 signaling pathway
  103. The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma
  104. Physical fitness and blood parameters outcomes of breast cancer survivor in a low-intensity circuit resistance exercise program
  105. Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery
  106. Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism
  107. Analysis of the risk factors of the radiation-induced encephalopathy in nasopharyngeal carcinoma: A retrospective cohort study
  108. Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review
  109. Evaluation of upper airway ultrasonographic measurements in predicting difficult intubation: A cross-section of the Turkish population
  110. Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer
  111. Postural stability after operative reconstruction of the AFTL in chronic ankle instability comparing three different surgical techniques
  112. Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis
  113. Frequency and clinicopathological correlation of gastrointestinal polyps: A six-year single center experience
  114. ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation
  115. Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts
  116. Effectiveness of nutritional support for clinical outcomes in gastric cancer patients: A meta-analysis of randomized controlled trials
  117. The relationship between IFN-γ, IL-10, IL-6 cytokines, and severity of the condition with serum zinc and Fe in children infected with Mycoplasma pneumoniae
  118. Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
  119. Sleep quality associate with the increased prevalence of cognitive impairment in coronary artery disease patients: A retrospective case–control study
  120. Dioscin protects against chronic prostatitis through the TLR4/NF-κB pathway
  121. Association of polymorphisms in FBN1, MYH11, and TGF-β signaling-related genes with susceptibility of sporadic thoracic aortic aneurysm and dissection in the Zhejiang Han population
  122. Application value of multi-parameter magnetic resonance image-transrectal ultrasound cognitive fusion in prostate biopsy
  123. Laboratory variables‐based artificial neural network models for predicting fatty liver disease: A retrospective study
  124. Decreased BIRC5-206 promotes epithelial–mesenchymal transition in nasopharyngeal carcinoma through sponging miR-145-5p
  125. Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway
  126. Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis
  127. Tibial periosteum flap combined with autologous bone grafting in the treatment of Gustilo-IIIB/IIIC open tibial fractures
  128. The application of intravenous general anesthesia under nasopharyngeal airway assisted ventilation undergoing ureteroscopic holmium laser lithotripsy: A prospective, single-center, controlled trial
  129. Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a
  130. Role of FOXM1 and AURKB in regulating keratinocyte function in psoriasis
  131. Parental control attitudes over their pre-school children’s diet
  132. The role of auto-HSCT in extranodal natural killer/T cell lymphoma
  133. Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy
  134. Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin
  135. ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway
  136. The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study
  137. The unusual location of primary hydatid cyst: A case series study
  138. Intraoperative changes in electrophysiological monitoring can be used to predict clinical outcomes in patients with spinal cavernous malformation
  139. Obesity and risk of placenta accreta spectrum: A meta-analysis
  140. Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism
  141. NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages
  142. The effect of COVID-19 lockdown on admission rates in Maternity Hospital
  143. Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China
  144. Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis
  145. Therapeutic role of respiratory exercise in patients with tuberculous pleurisy
  146. Effects of CFTR-ENaC on spinal cord edema after spinal cord injury
  147. Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells
  148. DMD mutations in pediatric patients with phenotypes of Duchenne/Becker muscular dystrophy
  149. Combination of C-reactive protein and fibrinogen-to-albumin ratio as a novel predictor of all-cause mortality in heart failure patients
  150. Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease
  151. Ferroptosis-related prognostic model of mantle cell lymphoma
  152. Observation of choking reaction and other related indexes in elderly painless fiberoptic bronchoscopy with transnasal high-flow humidification oxygen therapy
  153. A bibliometric analysis of Prader-Willi syndrome from 2002 to 2022
  154. The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study
  155. Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction
  156. Role of COX6C and NDUFB3 in septic shock and stroke
  157. Trends in disease burden of type 2 diabetes, stroke, and hypertensive heart disease attributable to high BMI in China: 1990–2019
  158. Purinergic P2X7 receptor mediates hyperoxia-induced injury in pulmonary microvascular endothelial cells via NLRP3-mediated pyroptotic pathway
  159. Investigating the role of oviductal mucosa–endometrial co-culture in modulating factors relevant to embryo implantation
  160. Analgesic effect of external oblique intercostal block in laparoscopic cholecystectomy: A retrospective study
  161. Elevated serum miR-142-5p correlates with ischemic lesions and both NSE and S100β in ischemic stroke patients
  162. Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study
  163. Risk factors for progressive kyphosis after percutaneous kyphoplasty in osteoporotic vertebral compression fracture
  164. Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke
  165. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia
  166. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro
  167. Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis
  168. Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway
  169. Differences in mortality risk by levels of physical activity among persons with disabilities in South Korea
  170. Review Articles
  171. Cutaneous signs of selected cardiovascular disorders: A narrative review
  172. XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis
  173. A narrative review on adverse drug reactions of COVID-19 treatments on the kidney
  174. Emerging role and function of SPDL1 in human health and diseases
  175. Adverse reactions of piperacillin: A literature review of case reports
  176. Molecular mechanism and intervention measures of microvascular complications in diabetes
  177. Regulation of mesenchymal stem cell differentiation by autophagy
  178. Molecular landscape of borderline ovarian tumours: A systematic review
  179. Advances in synthetic lethality modalities for glioblastoma multiforme
  180. Investigating hormesis, aging, and neurodegeneration: From bench to clinics
  181. Frankincense: A neuronutrient to approach Parkinson’s disease treatment
  182. Sox9: A potential regulator of cancer stem cells in osteosarcoma
  183. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients
  184. Advanced neuroimaging and criminal interrogation in lie detection
  185. Maternal factors for neural tube defects in offspring: An umbrella review
  186. The chemoprotective hormetic effects of rosmarinic acid
  187. CBD’s potential impact on Parkinson’s disease: An updated overview
  188. Progress in cytokine research for ARDS: A comprehensive review
  189. Utilizing reactive oxygen species-scavenging nanoparticles for targeting oxidative stress in the treatment of ischemic stroke: A review
  190. NRXN1-related disorders, attempt to better define clinical assessment
  191. Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review
  192. Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis
  193. Iron in ventricular remodeling and aneurysms post-myocardial infarction
  194. Case Reports
  195. Sirolimus potentiated angioedema: A case report and review of the literature
  196. Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report
  197. Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
  198. Complete heart block associated with hepatitis A infection in a female child with fatal outcome
  199. Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review
  200. Four years of natural progressive course: A rare case report of juvenile Xp11.2 translocations renal cell carcinoma with TFE3 gene fusion
  201. Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China – A case series
  202. Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy
  203. Anti-HMGCR myopathy mimicking facioscapulohumeral muscular dystrophy
  204. Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review
  205. Letter to the Editor
  206. Letter to the Editor: Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  207. Erratum
  208. Erratum to “Bladder-embedded ectopic intrauterine device with calculus”
  209. Retraction
  210. Retraction of “XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis”
  211. Corrigendum
  212. Corrigendum to “Investigating hormesis, aging, and neurodegeneration: From bench to clinics”
  213. Corrigendum to “Frankincense: A neuronutrient to approach Parkinson’s disease treatment”
  214. Special Issue The evolving saga of RNAs from bench to bedside - Part II
  215. Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
  216. Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening
  217. Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment
  218. Special Issue Advancements in oncology: bridging clinical and experimental research - Part I
  219. Ultrasound-guided transperineal vs transrectal prostate biopsy: A meta-analysis of diagnostic accuracy and complication rates
  220. Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer
  221. SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins
  222. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE
  223. Analysis of postoperative complications in bladder cancer patients
  224. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study
  225. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part I
  226. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma
  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
  228. Single-cell analysis identified key macrophage subpopulations associated with atherosclerosis
https://doi.org/10.1515/med-2024-0990
Keywords for this article
amyotrophic lateral sclerosis; fiber density; jitter; orbicularis oculi muscle; frontalis muscle
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. EDNRB inhibits the growth and migration of prostate cancer cells by activating the cGMP-PKG pathway
  3. STK11 (LKB1) mutation suppresses ferroptosis in lung adenocarcinoma by facilitating monounsaturated fatty acid synthesis
  4. Association of SOX6 gene polymorphisms with Kashin-Beck disease risk in the Chinese Han population
  5. The pyroptosis-related signature predicts prognosis and influences the tumor immune microenvironment in dedifferentiated liposarcoma
  6. METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC
  7. Identification and validation of molecular subtypes and prognostic signature for stage I and stage II gastric cancer based on neutrophil extracellular traps
  8. Novel lumbar plexus block versus femoral nerve block for analgesia and motor recovery after total knee arthroplasty
  9. Correlation between ABCB1 and OLIG2 polymorphisms and the severity and prognosis of patients with cerebral infarction
  10. Study on the radiotherapy effect and serum neutral granulocyte lymphocyte ratio and inflammatory factor expression of nasopharyngeal carcinoma
  11. Transcriptome analysis of effects of Tecrl deficiency on cardiometabolic and calcium regulation in cardiac tissue
  12. Aflatoxin B1 induces infertility, fetal deformities, and potential therapies
  13. Serum levels of HMW adiponectin and its receptors are associated with cytokine levels and clinical characteristics in chronic obstructive pulmonary disease
  14. METTL3-mediated methylation of CYP2C19 mRNA may aggravate clopidogrel resistance in ischemic stroke patients
  15. Understand how machine learning impact lung cancer research from 2010 to 2021: A bibliometric analysis
  16. Pressure ulcers in German hospitals: Analysis of reimbursement and length of stay
  17. Metformin plus L-carnitine enhances brown/beige adipose tissue activity via Nrf2/HO-1 signaling to reduce lipid accumulation and inflammation in murine obesity
  18. Downregulation of carbonic anhydrase IX expression in mouse xenograft nasopharyngeal carcinoma model via doxorubicin nanobubble combined with ultrasound
  19. Feasibility of 3-dimensional printed models in simulated training and teaching of transcatheter aortic valve replacement
  20. miR-335-3p improves type II diabetes mellitus by IGF-1 regulating macrophage polarization
  21. The analyses of human MCPH1 DNA repair machinery and genetic variations
  22. Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy
  23. Comprehensive analysis based on the disulfidptosis-related genes identifies hub genes and immune infiltration for pancreatic adenocarcinoma
  24. Changes of serum CA125 and PGE2 before and after high-intensity focused ultrasound combined with GnRH-a in treatment of patients with adenomyosis
  25. The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis
  26. Development and validation of a novel model to predict pulmonary embolism in cardiology suspected patients: A 10-year retrospective analysis
  27. Downregulation of lncRNA XLOC_032768 in diabetic patients predicts the occurrence of diabetic nephropathy
  28. Circ_0051428 targeting miR-885-3p/MMP2 axis enhances the malignancy of cervical cancer
  29. Effectiveness of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke
  30. The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci
  31. Evaluating the impact of childhood BMI on the risk of coronavirus disease 2019: A Mendelian randomization study
  32. Lactate dehydrogenase to albumin ratio is associated with in-hospital mortality in patients with acute heart failure: Data from the MIMIC-III database
  33. CD36-mediated podocyte lipotoxicity promotes foot process effacement
  34. Efficacy of etonogestrel subcutaneous implants versus the levonorgestrel-releasing intrauterine system in the conservative treatment of adenomyosis
  35. FLRT2 mediates chondrogenesis of nasal septal cartilage and mandibular condyle cartilage
  36. Challenges in treating primary immune thrombocytopenia patients undergoing COVID-19 vaccination: A retrospective study
  37. Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway
  38. Phospholipid transfer protein ameliorates sepsis-induced cardiac dysfunction through NLRP3 inflammasome inhibition
  39. Postoperative cognitive dysfunction in elderly patients with colorectal cancer: A randomized controlled study comparing goal-directed and conventional fluid therapy
  40. Long-pulsed ultrasound-mediated microbubble thrombolysis in a rat model of microvascular obstruction
  41. High SEC61A1 expression predicts poor outcome of acute myeloid leukemia
  42. Comparison of polymerase chain reaction and next-generation sequencing with conventional urine culture for the diagnosis of urinary tract infections: A meta-analysis
  43. Secreted frizzled-related protein 5 protects against renal fibrosis by inhibiting Wnt/β-catenin pathway
  44. Pan-cancer and single-cell analysis of actin cytoskeleton genes related to disulfidptosis
  45. Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1
  46. Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model
  47. Clinical analysis of incomplete rupture of the uterus secondary to previous cesarean section
  48. Abnormal sleep duration is associated with sarcopenia in older Chinese people: A large retrospective cross-sectional study
  49. No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study
  50. Identification and validation of autophagy-related genes in SSc
  51. Long non-coding RNA SRA1 suppresses radiotherapy resistance in esophageal squamous cell carcinoma by modulating glycolytic reprogramming
  52. Evaluation of quality of life in patients with schizophrenia: An inpatient social welfare institution-based cross-sectional study
  53. The possible role of oxidative stress marker glutathione in the assessment of cognitive impairment in multiple sclerosis
  54. Compilation of a self-management assessment scale for postoperative patients with aortic dissection
  55. Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation
  56. Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study
  57. Clinical characteristics and assessment of risk factors in patients with influenza A-induced severe pneumonia after the prevalence of SARS-CoV-2
  58. Analgesia nociception index is an indicator of laparoscopic trocar insertion-induced transient nociceptive stimuli
  59. High STAT4 expression correlates with poor prognosis in acute myeloid leukemia and facilitates disease progression by upregulating VEGFA expression
  60. Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study
  61. HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis
  62. Mesenchymal stem cell-derived exosomal miR-26a induces ferroptosis, suppresses hepatic stellate cell activation, and ameliorates liver fibrosis by modulating SLC7A11
  63. Endovascular thrombectomy versus intravenous thrombolysis for primary distal, medium vessel occlusion in acute ischemic stroke
  64. ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis
  65. Prognostic value of EIF5A2 in solid tumors: A meta-analysis and bioinformatics analysis
  66. The role of enhanced expression of Cx43 in patients with ulcerative colitis
  67. Choosing a COVID-19 vaccination site might be driven by anxiety and body vigilance
  68. Role of ICAM-1 in triple-negative breast cancer
  69. Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2
  70. HLA-DRB5 promotes immune thrombocytopenia via activating CD8+ T cells
  71. Efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome
  72. Efficacy of tacrolimus monotherapy in primary membranous nephropathy
  73. Mechanisms of Tripterygium wilfordii Hook F on treating rheumatoid arthritis explored by network pharmacology analysis and molecular docking
  74. FBXO45 levels regulated ferroptosis renal tubular epithelial cells in a model of diabetic nephropathy by PLK1
  75. Optimizing anesthesia strategies to NSCLC patients in VATS procedures: Insights from drug requirements and patient recovery patterns
  76. Alpha-lipoic acid upregulates the PPARγ/NRF2/GPX4 signal pathway to inhibit ferroptosis in the pathogenesis of unexplained recurrent pregnancy loss
  77. Correlation between fat-soluble vitamin levels and inflammatory factors in paediatric community-acquired pneumonia: A prospective study
  78. CD1d affects the proliferation, migration, and apoptosis of human papillary thyroid carcinoma TPC-1 cells via regulating MAPK/NF-κB signaling pathway
  79. miR-let-7a inhibits sympathetic nerve remodeling after myocardial infarction by downregulating the expression of nerve growth factor
  80. Immune response analysis of solid organ transplantation recipients inoculated with inactivated COVID-19 vaccine: A retrospective analysis
  81. The H2Valdien derivatives regulate the epithelial–mesenchymal transition of hepatoma carcinoma cells through the Hedgehog signaling pathway
  82. Clinical efficacy of dexamethasone combined with isoniazid in the treatment of tuberculous meningitis and its effect on peripheral blood T cell subsets
  83. Comparison of short-segment and long-segment fixation in treatment of degenerative scoliosis and analysis of factors associated with adjacent spondylolisthesis
  84. Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK/mTOR/NLRP3 pathway
  85. Methylation regulation for FUNDC1 stability in childhood leukemia was up-regulated and facilitates metastasis and reduces ferroptosis of leukemia through mitochondrial damage by FBXL2
  86. Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis
  87. Risk factors of postoperative airway obstruction complications in children with oral floor mass
  88. Expression levels and clinical significance of serum miR-19a/CCL20 in patients with acute cerebral infarction
  89. Physical activity and mental health trends in Korean adolescents: Analyzing the impact of the COVID-19 pandemic from 2018 to 2022
  90. Evaluating anemia in HIV-infected patients using chest CT
  91. Ponticulus posticus and skeletal malocclusion: A pilot study in a Southern Italian pre-orthodontic court
  92. Causal association of circulating immune cells and lymphoma: A Mendelian randomization study
  93. Assessment of the renal function and fibrosis indexes of conventional western medicine with Chinese medicine for dredging collaterals on treating renal fibrosis: A systematic review and meta-analysis
  94. Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer
  95. New target-HMGCR inhibitors for the treatment of primary sclerosing cholangitis: A drug Mendelian randomization study
  96. Population pharmacokinetics of meropenem in critically ill patients
  97. Comparison of the ability of newly inflammatory markers to predict complicated appendicitis
  98. Comparative morphology of the cruciate ligaments: A radiological study
  99. Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator
  100. Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study
  101. SHP-1 mediates cigarette smoke extract-induced epithelial–mesenchymal transformation and inflammation in 16HBE cells
  102. Acute hyper-hypoxia accelerates the development of depression in mice via the IL-6/PGC1α/MFN2 signaling pathway
  103. The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma
  104. Physical fitness and blood parameters outcomes of breast cancer survivor in a low-intensity circuit resistance exercise program
  105. Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery
  106. Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism
  107. Analysis of the risk factors of the radiation-induced encephalopathy in nasopharyngeal carcinoma: A retrospective cohort study
  108. Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review
  109. Evaluation of upper airway ultrasonographic measurements in predicting difficult intubation: A cross-section of the Turkish population
  110. Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer
  111. Postural stability after operative reconstruction of the AFTL in chronic ankle instability comparing three different surgical techniques
  112. Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis
  113. Frequency and clinicopathological correlation of gastrointestinal polyps: A six-year single center experience
  114. ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation
  115. Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts
  116. Effectiveness of nutritional support for clinical outcomes in gastric cancer patients: A meta-analysis of randomized controlled trials
  117. The relationship between IFN-γ, IL-10, IL-6 cytokines, and severity of the condition with serum zinc and Fe in children infected with Mycoplasma pneumoniae
  118. Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
  119. Sleep quality associate with the increased prevalence of cognitive impairment in coronary artery disease patients: A retrospective case–control study
  120. Dioscin protects against chronic prostatitis through the TLR4/NF-κB pathway
  121. Association of polymorphisms in FBN1, MYH11, and TGF-β signaling-related genes with susceptibility of sporadic thoracic aortic aneurysm and dissection in the Zhejiang Han population
  122. Application value of multi-parameter magnetic resonance image-transrectal ultrasound cognitive fusion in prostate biopsy
  123. Laboratory variables‐based artificial neural network models for predicting fatty liver disease: A retrospective study
  124. Decreased BIRC5-206 promotes epithelial–mesenchymal transition in nasopharyngeal carcinoma through sponging miR-145-5p
  125. Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway
  126. Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis
  127. Tibial periosteum flap combined with autologous bone grafting in the treatment of Gustilo-IIIB/IIIC open tibial fractures
  128. The application of intravenous general anesthesia under nasopharyngeal airway assisted ventilation undergoing ureteroscopic holmium laser lithotripsy: A prospective, single-center, controlled trial
  129. Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a
  130. Role of FOXM1 and AURKB in regulating keratinocyte function in psoriasis
  131. Parental control attitudes over their pre-school children’s diet
  132. The role of auto-HSCT in extranodal natural killer/T cell lymphoma
  133. Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy
  134. Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin
  135. ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway
  136. The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study
  137. The unusual location of primary hydatid cyst: A case series study
  138. Intraoperative changes in electrophysiological monitoring can be used to predict clinical outcomes in patients with spinal cavernous malformation
  139. Obesity and risk of placenta accreta spectrum: A meta-analysis
  140. Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism
  141. NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages
  142. The effect of COVID-19 lockdown on admission rates in Maternity Hospital
  143. Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China
  144. Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis
  145. Therapeutic role of respiratory exercise in patients with tuberculous pleurisy
  146. Effects of CFTR-ENaC on spinal cord edema after spinal cord injury
  147. Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells
  148. DMD mutations in pediatric patients with phenotypes of Duchenne/Becker muscular dystrophy
  149. Combination of C-reactive protein and fibrinogen-to-albumin ratio as a novel predictor of all-cause mortality in heart failure patients
  150. Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease
  151. Ferroptosis-related prognostic model of mantle cell lymphoma
  152. Observation of choking reaction and other related indexes in elderly painless fiberoptic bronchoscopy with transnasal high-flow humidification oxygen therapy
  153. A bibliometric analysis of Prader-Willi syndrome from 2002 to 2022
  154. The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study
  155. Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction
  156. Role of COX6C and NDUFB3 in septic shock and stroke
  157. Trends in disease burden of type 2 diabetes, stroke, and hypertensive heart disease attributable to high BMI in China: 1990–2019
  158. Purinergic P2X7 receptor mediates hyperoxia-induced injury in pulmonary microvascular endothelial cells via NLRP3-mediated pyroptotic pathway
  159. Investigating the role of oviductal mucosa–endometrial co-culture in modulating factors relevant to embryo implantation
  160. Analgesic effect of external oblique intercostal block in laparoscopic cholecystectomy: A retrospective study
  161. Elevated serum miR-142-5p correlates with ischemic lesions and both NSE and S100β in ischemic stroke patients
  162. Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study
  163. Risk factors for progressive kyphosis after percutaneous kyphoplasty in osteoporotic vertebral compression fracture
  164. Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke
  165. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia
  166. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro
  167. Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis
  168. Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway
  169. Differences in mortality risk by levels of physical activity among persons with disabilities in South Korea
  170. Review Articles
  171. Cutaneous signs of selected cardiovascular disorders: A narrative review
  172. XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis
  173. A narrative review on adverse drug reactions of COVID-19 treatments on the kidney
  174. Emerging role and function of SPDL1 in human health and diseases
  175. Adverse reactions of piperacillin: A literature review of case reports
  176. Molecular mechanism and intervention measures of microvascular complications in diabetes
  177. Regulation of mesenchymal stem cell differentiation by autophagy
  178. Molecular landscape of borderline ovarian tumours: A systematic review
  179. Advances in synthetic lethality modalities for glioblastoma multiforme
  180. Investigating hormesis, aging, and neurodegeneration: From bench to clinics
  181. Frankincense: A neuronutrient to approach Parkinson’s disease treatment
  182. Sox9: A potential regulator of cancer stem cells in osteosarcoma
  183. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients
  184. Advanced neuroimaging and criminal interrogation in lie detection
  185. Maternal factors for neural tube defects in offspring: An umbrella review
  186. The chemoprotective hormetic effects of rosmarinic acid
  187. CBD’s potential impact on Parkinson’s disease: An updated overview
  188. Progress in cytokine research for ARDS: A comprehensive review
  189. Utilizing reactive oxygen species-scavenging nanoparticles for targeting oxidative stress in the treatment of ischemic stroke: A review
  190. NRXN1-related disorders, attempt to better define clinical assessment
  191. Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review
  192. Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis
  193. Iron in ventricular remodeling and aneurysms post-myocardial infarction
  194. Case Reports
  195. Sirolimus potentiated angioedema: A case report and review of the literature
  196. Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report
  197. Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
  198. Complete heart block associated with hepatitis A infection in a female child with fatal outcome
  199. Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review
  200. Four years of natural progressive course: A rare case report of juvenile Xp11.2 translocations renal cell carcinoma with TFE3 gene fusion
  201. Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China – A case series
  202. Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy
  203. Anti-HMGCR myopathy mimicking facioscapulohumeral muscular dystrophy
  204. Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review
  205. Letter to the Editor
  206. Letter to the Editor: Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  207. Erratum
  208. Erratum to “Bladder-embedded ectopic intrauterine device with calculus”
  209. Retraction
  210. Retraction of “XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis”
  211. Corrigendum
  212. Corrigendum to “Investigating hormesis, aging, and neurodegeneration: From bench to clinics”
  213. Corrigendum to “Frankincense: A neuronutrient to approach Parkinson’s disease treatment”
  214. Special Issue The evolving saga of RNAs from bench to bedside - Part II
  215. Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
  216. Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening
  217. Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment
  218. Special Issue Advancements in oncology: bridging clinical and experimental research - Part I
  219. Ultrasound-guided transperineal vs transrectal prostate biopsy: A meta-analysis of diagnostic accuracy and complication rates
  220. Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer
  221. SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins
  222. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE
  223. Analysis of postoperative complications in bladder cancer patients
  224. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study
  225. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part I
  226. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma
  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
  228. Single-cell analysis identified key macrophage subpopulations associated with atherosclerosis
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