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Introduction/aims: One of the most distinct clinical features of facioscapulohumeral muscular dystrophy (FSHD) is facial weakness. It leads to diminished facial expression and functional impairments. Despite its clinical relevance, little else is known about orofacial muscle involvement. We therefore evaluated orofacial muscle involvement in a sizeable cohort of FSHD participants with muscle ultrasound., Methods: Muscle ultrasound images of the following orofacial muscles were scored visually and quantitatively: depressor anguli oris (DAO), orbicularis oris (OO), buccinator, temporalis, masseter, digastric, zygomaticus major and minor bilaterally, and the geniohyoid. Reliability analyses of both visual and quantitative evaluations were performed. Ultrasound results were correlated with other measures: the FSHD clinical score, facial weakness score, and facial function scale., Results: We included 107 FSHD participants (male 54%; age 52 ± 14 years), of whom 92% showed signs of facial weakness. The reliability of visual ultrasound analysis varied widely (κ 0.0-1.0). Quantitative ultrasound reliability was high (intraclass correlation analysis ≥ 0.96). The DAO, buccinator, OO, temporalis, and zygomaticus minor muscles were affected most often (15%-39%). The digastric, geniohyoid, zygomaticus major, and masseter muscles were least often affected (<5%). The ultrasound compound score correlated weakly to moderately with other outcome measures used (ρ = 0.3-0.7)., Discussion: This study adds to the understanding of orofacial weakness in FSHD, confirming the involvement of the muscles of facial expression in FSHD using ultrasound. We showed that orofacial muscle ultrasound is feasible and reliable when quantitatively assessed. Future studies should evaluate orofacial muscle ultrasound longitudinally, alongside clinical and patient-reported facial weakness outcome measures, to assess their potential as outcome measures., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

Muscle weakness following anterior cruciate ligament reconstruction (ACLR) increases the risk of posttraumatic osteoarthritis (OA). However, focusing solely on muscle weakness overlooks other aspects like muscle composition, which could hinder strength recovery. Intramuscular fat is a non-contractile element linked to joint degeneration in idiopathic OA, but its role post-ACLR has not been thoroughly investigated. To bridge this gap, we aimed to characterize quadriceps volume and intramuscular fat in participants with ACLR (male/female = 15/9, age = 22.8 ± 3.6 years, body mass index [BMI] = 23.2 ± 1.9, time since surgery = 3.3 ± 0.9 years) and in controls (male/female = 14/10, age = 22.0 ± 3.1 years, BMI = 23.3 ± 2.6) while also exploring the associations between intramuscular fat and muscle volume with isometric strength. Linear mixed effects models assessed (I) muscle volume, (II) intramuscular fat, and (III) strength between limbs (ACLR vs. contralateral vs. control). Regression analyses were run to determine if intramuscular fat or volume were associated with quadriceps strength. The ACLR limb was 8%-11% smaller than the contralateral limb (p < 0.05). No between-limb differences in intramuscular fat were observed (p = 0.091-0.997). Muscle volume but not intramuscular fat was associated with strength in the ACLR and control limbs (p < 0.001-0.002). We demonstrate that intramuscular fat does not appear to be an additional source of quadriceps dysfunction following ACLR and that muscle size only explains some of the variance in muscle strength., (© 2024 Orthopaedic Research Society.)

Purpose: To establish the prevalence and agreement between reported and observed leg weakness in people with sciatica. To establish which factors mediate any identified difference between reported and observed leg weakness in people with sciatica., Methods: 68 people with a clinical diagnosis of sciatica, records from spinal service, secondary care NHS Hospital, England, UK reviewed. Primary outcome measures were the sciatica bothersome index for reported leg weakness and the Medical Research Council scale for observed weakness. Agreement was established with Cohen's Kappa and intraclass correlation coefficient. Potential factors that may mediate a difference between reported and observed weakness included leg pain, sciatica bothersome index sensory subscale, age, hospital anxiety and depression subscale for anxiety., Results: 85% of patients reported weakness but only 34% had observed weakness. Cohen's Kappa (0.066, 95% CI - 0.53, 0.186; p = 0.317)] and ICC 0.213 (95% CI - 0.26, 0.428, p = 0.040) both showed poor agreement between reported and observed weakness. The difference between reported and observed measures of weakness was mediated by the severity of leg pain (b = 0.281, p = 0.024) and age (b = 0.253, p = 0.042)., Conclusion: There is a high prevalence of reported leg weakness in people with sciatica, which is not reflected in observed clinical measures of weakness. Differences between reported and observed weakness may be driven by the severity of leg pain and age. Further work needs to establish whether other objective measures can detect patient reported weakness., (© 2024. The Author(s).)

Background: Handgrip strength (HGS) weakness and asymmetry were recently reported to be associated with age-related health conditions. However, little is known about their combined effects on depression. We aimed to explore the joint association of HGS asymmetry and weakness with depressive symptoms in Chinese middle and older aged population., Methods: 8700 participants aged ≥45 years were enrolled from China Health and Retirement Longitudinal Study (2015-2018). HGS weakness was determined as maximal HGS < 28 kg in males and <18 kg in females. HGS asymmetry was measured by HGS ratio and was defined using two different rules. Specifically, HGS ratio < 0.90 or >1.10 (10 % rule) and <0.80 or >1.20 (20 % rule) were considered as asymmetry. Participants were classified into four groups: normal and symmetric HGS, asymmetry only, weakness only, and both weakness and asymmetry. Depressive symptoms were assessed by the 10-item Center for Epidemiologic Studies Depression Scale, with scores ≥12 defined as depression. The logistic regression and multiple linear regression models were conducted to estimate the associations between HGS status and depressive symptoms., Results: The three-year incidence of depression was 19.2 %. After adjusting for covariates, compared to normal and symmetric HGS, participants with both HGS asymmetry and weakness showed the greatest risk of incident depression (10 % rule: OR 1.55, 95 % CI 1.19-2.02; 20 % rule: OR 1.71, 95 % CI 1.16-2.50). The coexistence of asymmetry and weakness was related to a significant increase in depression score (10 % rule: β 0.96, 95 % CI 0.38-1.54; 20 % rule: β 0.94, 95 % CI 0.08-1.81). The complete case analysis supported the results, and the associations were not modified by age, sex, and hand dominance., Limitations: Depressive assessment was based on self-reported screening instrument., Conclusions: The presence of both HGS asymmetry and weakness was associated with a higher risk of depression. Examining HGS asymmetry along with weakness may aid in identifying individuals at risk of depression to enable early interventions., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Real-world data were employed to determine clinical characteristics of patients with myasthenia gravis (MG) with differing degrees of muscle weakness, as defined using the Myasthenia Gravis Foundation of America (MGFA) classification system., Methods: Data were drawn from the Adelphi MG Disease Specific Programme (DSP)™, a multinational (United States, France, Germany, Italy, Spain, United Kingdom) survey completed by physicians and their patients with MG in 2020. The association between MGFA class and impairment in activities of daily living (ADL) was tested using linear regression adjusting for sex and Charlson Comorbidity Index. Bivariate comparisons were performed for each individual item. A range of other clinical characteristics were also explored according to MGFA class., Results: Among 1232 patients, those in MGFA class I had significantly lower ADL impairment versus class II or III/IV (adjusted for sex and Charlson Comorbidity Index) (p < 0.01). However, heterogeneity occurred within each MGFA class. Bulbar symptoms (impaired speech, difficulty swallowing, and/or difficulty chewing/choking on food) were reported in some class I patients (mild in 1.1-1.9% and moderate in 0.3-1.1% of patients) and class II patients (mild in 8.5-16.4%, moderate in 4.7-7.4%, and severe in 0.3-0.9% of patients), and shortness of breath was reported in some class I (mild in 0.5% of patients) and class II patients (mild in 9.8%, moderate in 4.8%, and severe in 0.3% of patients). Conversely, in 11.2-19.2% of class III/IV patients, bulbar symptoms and shortness of breath reported were only mild in severity. In line with this finding, despite significant correlations between MGFA class and several clinical characteristics, patients across every class were at risk of experiencing myasthenic crisis or hospitalization, experiencing comorbidities including anxiety and depression, and not being in remission., Conclusions: Although MGFA class correlates with greater ADL impairment and presence of other clinical characteristics, there is variability between patients in each class in terms of symptoms experienced, overall disease burden, and the precise nature of ADL impairment., (© 2024. The Author(s).)

Objectives: Handgrip strength (HGS) is accepted as a predictor of overall health status and a biomarker of aging, besides negative health outcomes and mortality. While differences in HGS between the dominant and non-dominant hands are expected, substantial discrepancies may signal impaired muscle function. This study aims to investigate whether handgrip asymmetry can serve as a reliable indicator of frailty in a diverse population of older adults., Design: Cross-sectional study., Setting and Participants: A total of 512 patients aged 65 years and older who were admitted to the geriatric medicine outpatient clinic of a university hospital were enrolled in the study., Methods: The Clinical Frailty Scale (CFS) was used to assess the overall level of frailty of the study population. The highest recorded HGS values from the non-dominant and dominant hand were used to calculate the HGS ratio. Those with a HGS ratio of dominant and non-dominant hand <0.90 or >1.10 were defined as HGS asymmetry., Results: Of the whole study group, 61.1% was female and the mean age was 73.2 ± 6.1 years. The ratio of the participants living with frailty was 57.6% (n = 219). The number of patients with HGS asymmetry was 264 (51.6%), and 48.4% (n = 248) of the study population had symmetric HGS. The normal and symmetric HGS was found in 40.2% of the non-frail group, whereas it was 23.7% in patients living with frailty. Furthermore, the ratio of low and asymmetric HGS was 16.3% in the non-frail group, and 35.0% in the patients living with frailty (p < 0.001). The presence of asymmetric and low HGS increased the risk of frailty three times independently of other confounding factors (OR:3.08; 95% CI:1.48-6.43; p = 0.003)., Conclusions and Implications: Identifying HGS asymmetry along with low HGS as potential indicators of frailty may provide clinicians with a clear and quantifiable criterion for assessing older patients., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Myotonic dystrophy type 1 (DM1) is a heterogeneous neuromuscular disorder characterized by progressive muscle weakness and myotonia. This study investigates the progression of muscular strength and function over a four-year period. Patients with DM1 were examined at baseline and four years later. The following metrics were assessed over time: muscle strength (Medical Research Council-sumscore), hand-grip strength (Martin-Vigorimeter), hand-grip relaxation time (myotonia), and limitations in activities of daily living and (DM1Activ C questionnaire). A total of 648 patients entered the registry. Recruitment and follow-up is ongoing. In our manuscript, we focus on, 187 patients who were followed for 4 years. A significant decline in MRC sum score was observed, with distal muscles showing more deterioration. Hand-grip strength decreased significantly, with notable differences between sex and phenotype classified by disease onset. Surprisingly, an improvement of myotonia was observed. Follow-up analysis revealed a significant interaction between myotonia and grip-strength over time. Thus, the improvement in myotonia is likely explained by decreased in grip strength. Finally, there was a significant reduction in DM1Activ C score, indicating decreased activity and social participation. This study demonstrated variability in disease progression depending on sex, phenotype and disease status. This research demonstrates a nuanced pattern of disease progression, highlighting the need to combine different outcome measures to fully understand the complexity of DM1., Competing Interests: Declaration of competing interest L. la Fontaine reports no competing interests. J. Bruijnes reports no competing interests. F. Smulders reports no competing interests. C. Gorissen-Brouwers reports no competing interests. I. Karnebeek reports no competing interests. H. Braakman reports no competing interests. S. Klinkenberg reports no competing interests. K. Mul conducted consultancy services for Avidity Biosciences. All reimbursements were received by Radboudumc. Dr. Mul did not personally benefit financially from these activities. P ‘t Hoen received grants from the ZonMW foundation. All reimbursements were received by the Radboud university medical center. P. ‘t Hoen did not personally benefit financially from these activities. S. van Kuijk reports no competing interests. B. van Engelen received grants from the Prinses Beatrix Spierfonds. Consultancy services for Fulcrum, Avidity, Dyne, and Arrowhead. All reimbursements were received by Radboudumc. B van Engelen did not personally benefit from these activities. I. Merkies received grants from Grifols and Lamepro. Consultancy services for Talecris, CSL, Behring, Novartis, Octafarma, UCB and Argenx. I. Merkies did not personally benefit financially from these activities. C. Faber received grants from the Prinses Beatrix Spierfonds. Consultancy services for Biogen, Vertex, Olipass, and Sangamo. All reimbursements were received by MUMC+. C. Faber did not personally benefit financially from these activities., (Copyright © 2024. Published by Elsevier B.V.)

Mechanical ventilation (MV) is used to support ventilation and pulmonary gas exchange in patients during critical illness and surgery. Although MV is a life-saving intervention for patients in respiratory failure, an unintended side-effect of MV is the rapid development of diaphragmatic atrophy and contractile dysfunction. This MV-induced diaphragmatic weakness is labelled as 'ventilator-induced diaphragm dysfunction' (VIDD). VIDD is an important clinical problem because diaphragmatic weakness is a risk factor for the failure to wean patients from MV. Indeed, the inability to remove patients from ventilator support results in prolonged hospitalization and increased morbidity and mortality. The pathogenesis of VIDD has been extensively investigated, revealing that increased mitochondrial production of reactive oxygen species within diaphragm muscle fibres promotes a cascade of redox-regulated signalling events leading to both accelerated proteolysis and depressed protein synthesis. Together, these events promote the rapid development of diaphragmatic atrophy and contractile dysfunction. This review highlights the MV-induced changes in the structure/function of diaphragm muscle and discusses the cell-signalling mechanisms responsible for the pathogenesis of VIDD. This report concludes with a discussion of potential therapeutic opportunities to prevent VIDD and suggestions for future research in this exciting field., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Introduction/aims: Amyotrophic lateral sclerosis (ALS) exhibits selective muscle weakness. The weak shoulder and arm sparing signs, assessed by a single experienced neurologist, have been reported to be superior to previous signs in sensitivity and specificity. However, it is unknown whether the same results are observed when assessed by multiple neurologists., Methods: Subjects were retrospectively identified from our department's inpatient database from 2014 to 2023. Medical Research Council (MRC) scores of the deltoid (Del), biceps brachii (BB), triceps brachii (TB), and first dorsal interosseous (FDI) muscles were evaluated. The weak shoulder sign was defined as positive when Del was weaker than BB and TB. The arm sparing sign was defined as positive when both Del and FDI were weaker than BB and TB. Sensitivity was analyzed in all ALS patients and in subgroups based on the region of symptom onset, presence or absence of upper motor neuron (UMN) signs, and the Japanese ALS Severity Classification., Results: Seventy-one patients with ALS were identified. Eight neurologists and three neurology residents evaluated each patient's MRC scores. The weak shoulder and arm sparing signs were observed in 72% and 48% of patients, respectively, with no significant difference in sensitivity across patient subgroups., Discussion: The weak shoulder and arm sparing signs showed high and moderate sensitivity, respectively, consistent with a previous report, even when evaluated by multiple examiners. This expands the clinical utility and increases the reliability of these signs, potentially contributing to accurate ALS diagnosis when combined with other clinical features and objective assessments., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

Purpose: This study aimed to investigate the respiratory physiological changes resulting from short-term inspiratory resistance training (R-IMT) and inspiratory threshold training (T-IMT) in patients with chronic obstructive pulmonary disease (COPD) and to compare the mechanisms of the two training methods., Patients and Methods: A total of 75 stable patients with COPD combined with inspiratory muscle weakness were randomly allocated to three groups: R-IMT (n = 26), T-IMT (n = 24), and control (n = 25). Before and after 8 weeks of inspiratory muscle training(IMT), cardiopulmonary exercise tests were conducted to assess respiratory patterns, respiratory central drive, exercise tolerance, and ventilation efficiency., Results: After 8 weeks of IMT, Inspiratory muscle strength, represented by MIP (maximum inspiratory mouth pressure) and exercise capacity increased during exercise in both IMT groups (P < 0.05). In the R-IMT group, inspiratory time (Ti) prolonged (P < 0.05), tidal volume (Vt) increased (P < 0.05), ventilation efficiency (represented by ventilation-center coupling) increased (P < 0.05) during exercise. Conversely, the T-IMT group did not exhibit any of these changes after IMT (P > 0.05)., Conclusion: In summary, the improvement in exercise tolerance was associated with an increase in inspiratory muscle reserve in both R-IMT and T-IMT. However, only R-IMT was associated with deeper and slower breathing, as well as improved ventilation efficiency., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: It has long been of interest to characterize the components of the motor abnormality in the arm after stroke. One approach has been to decompose the hemiparesis phenotype into negative signs, such as weakness, and positive signs, such as intrusion of synergies. We sought to identify the contributions of weakness and flexor synergy to motor deficits in sub-acute stroke., Methods: Thirty-three sub-acute post-stroke participants and 16 healthy controls performed two functional arm movements; one within flexor synergy (shoulder and elbow flexion), and the other outside flexor synergy (shoulder flexion and elbow extension). We analyzed upper limb 3D kinematics to assess both overall task performance and intrusion of pathological synergies. Weakness and spasticity were also measured., Results: Both tasks produced similar impairments compared to controls. Analysis of elbow and shoulder multi-joint coordination patterns revealed intrusion of synergies in the out-of-synergy reaching task based on the time spent within a flexion-flexion pattern and the correlation between shoulder and elbow angles. Regression analysis indicated that both weakness and synergy intrusion contributed to motor impairment in the out-of-synergy reaching task. Notably, the Fugl-Meyer Assessment (FMA) was abnormal even when only weakness caused the impairment, cautioning that it is not a pure synergy scale., Conclusions: Weakness and synergy intrusion contribute to motor deficits in the sub-acute post-stroke period. An abnormal FMA score cannot be assumed to be due to synergy intrusion. Careful kinematic analysis of naturalistic movements is required to better characterize the contribution of negative and positive signs to upper limb impairment after stroke., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The musculoskeletal models have been improved to estimate accurate knee compression force (KCF) and have been used to reveal the causal relationship between KCF and muscle weakness. Previous studies have explored how muscle weakness influences the KCF during gait; however, the influence of muscle weakness is possibly larger during activities that require deeper knee flexion (e.g., stair ambulation) than other activities (e.g., gait) because of the small knee contact area of articular surfaces., Research Question: To explore how muscle weakness influences the KCF during stair ambulation., Methods: Ten young adults performed stair ascent and descent tasks at a comfortable speed. Based on a previous study, we created muscle weakness models of rectus femoris (RF), vastus muscles (VAS), gluteus medius (Gmed), and gluteus maximus (Gmax), and the medial and lateral KCF (KCFmed and KCFlat) during stair ambulation were calculated., Results: Similar to the gait, the Gmed weakness increased KCFmed and decreased KCFlat during stair ascent and descent. Whereas, unlike the gait, the Gmax weakness increased KCFmed during stair ascent and the VAS weakness decreased KCFmed and KCFlat during stair ascent and descent. Moreover, the percentage changes in KCF were similar (or large) during stair ambulation compared with those during gait., Significance: Considering the KCF alterations caused by each muscle weakness, the weaknesses in Gmax and Gmed might lead to cartilage loss and pain in the knee, and the VAS weakness might lead to low stability of the knee. The symptom during stair ambulation might help precisely identify the muscle requiring rehabilitation., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To describe the association of handgrip strength asymmetry and weakness with cognitive function among Chinese middle-aged and older adults., Study Design: We used data from four waves (2011, 2013, 2015, and 2018) of the China Health and Retirement Longitudinal Study. Handgrip strength was measured at baseline. Handgrip strength asymmetry was defined on the basis of the ratio of handgrip strength of the non-dominant hand to that of the dominant hand (i.e. non-dominant/dominant): a ratio of <0.9 defined as dominant handgrip strength asymmetry and >1.1 as non-dominant handgrip strength asymmetry. Weakness was defined as a handgrip strength of <28 kg for males or <18 kg for females., Main Outcome Measures: Cognitive function with its two core dimensions (episodic memory and mental status) at each wave was assessed and standardized., Results: 9333 participants (48.3 % female, age 58.2 ± 9.0 years) were included. Non-dominant but not dominant handgrip strength asymmetry was significantly associated with poorer cognitive function at baseline (β = -0.121, -0.092, and -0.132 for mental status, episodic memory, and global cognition, respectively). In longitudinal analyses over 2 years, dominant handgrip strength asymmetry significantly slowed cognitive decline (β = -0.078 and -0.069 for mental status and global cognition, respectively), and non-dominant handgrip strength asymmetry accelerated cognitive decline (β = 0.053 and 0.043 for episodic memory and global cognition, respectively). Weakness was associated with poorer cognitive function at baseline and cognitive decline over 2, 4, and 7 years (all P < 0.05)., Conclusions: In middle-aged and older adults, non-dominant handgrip strength asymmetry and weakness were associated with poorer cognitive function and predicted accelerated cognitive decline. Dominant handgrip strength asymmetry may be beneficial for maintaining cognitive function., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Dropped head syndrome (DHS) is followed by severe cervical extension muscle weakness that results in chin-on chest deformity. However, maintaining a neutral cervical position can be temporarily possible, and the diagnosis of DHS might sometimes be difficult. The purpose of the present study is to examine a novel clinical test (DHS test) as the diagnostic utility for objective evaluation that focuses on cervical extension condition in the prone position., Methods: One hundred subjects were diagnosed with isolated neck extensor myopathy (INEM)-DHS at our hospital (17 men and 83 women, mean age 75.0 ± 8.5 years), and 62 subjects were enrolled as age-matched controls. The DHS test consisted of three examinations; the first was "Ceiling gazing test" in standing position, the second was horizontal gazing in "Sphinx prone position test", and the third was horizontal gazing in "Hands and knees prone position test". We investigated the sensitivity and specificity of the DHS test for DHS., Results: The patients showing positive in the INEM-DHS group were 63/100 in Ceiling gaze test, 73/100 in the Sphinx prone position test, and 91/100 in the Hands and knees prone position test. In the control group, 0/62 patients presented positive in the Ceiling gaze test, 4/62 in the Sphinx prone position test, and 0/62 in the Hands and knees prone position test. Sensitivity and specificity of the DHS test were 63.0%/100%, 73.0%/93.5%, and 91.0%/100% in the Ceiling gaze test, Sphinx position prone position test, and Hands and knees prone position test, respectively., Conclusion: The prone position cervical extension test (DHS test) would be useful as a novel objective diagnostic tool for INEM-DHS., Competing Interests: Declaration of competing interest All authors declare that there are no personal or professional conflicts of interest related to the preparation and publication of this manuscript., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Rationale: Diaphragm muscle weakness might underlie persistent exertional dyspnea, despite normal lung and cardiac function in individuals who were previously hospitalized for acute coronavirus disease (COVID-19) illness. Objectives: The authors sought, first, to determine the persistence and pathophysiological nature of diaphragm muscle weakness and its association with exertional dyspnea 2 years after hospitalization for COVID-19 and, second, to investigate the impact of inspiratory muscle training (IMT) on diaphragm and inspiratory muscle weakness and exertional dyspnea in individuals with long COVID. Methods: Approximately 2 years after hospitalization for COVID-19, 30 individuals (11 women, 19 men; median age, 58 years; interquartile range [IQR] = 51-63) underwent comprehensive (invasive) respiratory muscle assessment and evaluation of dyspnea. Eighteen with persistent diaphragm muscle weakness and exertional dyspnea were randomized to 6 weeks of IMT or sham training; assessments were repeated immediately after and 6 weeks after IMT completion. The primary endpoint was change in inspiratory muscle fatiguability immediately after IMT. Measurements and Main Results: At a median of 31 months (IQR = 23-32) after hospitalization, 21 of 30 individuals reported relevant persistent exertional dyspnea. Diaphragm muscle weakness on exertion and reduced diaphragm cortical activation were potentially related to exertional dyspnea. Compared with sham control, IMT improved diaphragm and inspiratory muscle function (sniff transdiaphragmatic pressure, 83 cm H 2 O [IQR = 75-91] vs. 100 cm H 2 O [IQR = 81-113], P  = 0.02), inspiratory muscle fatiguability (time to task failure, 365 s [IQR = 284-701] vs. 983 s [IQR = 551-1,494], P  = 0.05), diaphragm voluntary activation index (79% [IQR = 63-92] vs. 89% [IQR = 75-94], P  = 0.03), and dyspnea (Borg score, 7 [IQR = 5.5-8] vs. 6 [IQR = 4-7], P  = 0.03). Improvements persisted for 6 weeks after IMT completion. Conclusions: To the best of the authors' knowledge, this study is the first to identify a potential treatment for persisting exertional dyspnea in long COVID and provide a possible pathophysiological explanation for the treatment benefit. Clinical trial registered with www.clinicaltrials.gov (NCT04854863, NCT05582642).

Aim: The aim of the study was to determine the respiratory muscle strength of stroke patients and compare them with healthy individuals., Method: The study was conducted with 171 patients who had a stroke between 2017 and 2021 and 32 healthy controls. Respiratory muscle strength and inspiratory and expiratory mouth pressure (MIP and MEP) were measured using the portable MicroRPM device (Micro Medical, Basingstoke, UK)., Results: The stroke group exhibited significantly lower values in both MIP for men (p<0.001) and women (p=0.013) and maximal expiratory pressure for men (p<0.001) and women (p=0.042), compared with the healthy control group. Notably, there was a significant difference in the MIPmen (p=0.026) and MEPmen (p=0.026) values when comparing the reference values, which were calculated based on age and sex, with those of the healthy group. The baseline values calculated according to age for stroke patients were as follows: MIPmen 31.68%, MIPwomen 63.58%, MEPmen 22.54%, and MEPwomen 42.30%., Conclusion: This study highlights the significant respiratory muscle weakness experienced by stroke patients, with gender-specific differences. It highlights the importance of incorporating respiratory assessments and interventions into stroke rehabilitation protocols to improve the overall health and well-being of stroke patients.

Purpose: Generalized muscle weakness is the primary characteristic of sarcopenia. Handgrip strength (HGS) is widely employed to detect muscle weakness. However, knee extension strength (KES) declines much earlier and more pronounced than HGS, and there is a stronger correlation between KES and functional performance. Therefore, KES may be a more appropriate proxy for identifying muscle weakness compared to HGS. The purpose of this review was to clarify the KES measurement towards a standardized approach and summarize the cut-off points for KES., Methods: A literature search was conducted in Web of Science, PubMed, Elsevier, Scopus and Medline databased up to July 10th, 2023., Results: A total of 12 articles were ultimately included in this review, which proposed various cut-off points for KES. Notably, these studies exhibited high heterogeneities, including diverse living settings for participants, KES measurement, methods for KES normalization, methodologies for determining cut-off points and study designs., Conclusions: No consensus on cut-off points for KES was reached due to the heterogeneities in KES measurement and normalized methods among studies. To enhance the comparability among studies and facilitate the sarcopenia screening framework, a standardized approach for KES measurement and KES normalization are needed. Regarding KES measurement, the hand-held dynamometer-based isometric KES is easy to access and ideally suited for both clinical and community settings, while isokinetic KES, representing the gold standard, is preferred for research settings. Additionally, it is suggested to normalize isometric KES to body weight (BW), while normalizing isokinetic KES to allometrically scaled BW., (© 2024. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Background: Neuroanatomical staging of sporadic amyotrophic lateral sclerosis (ALS) indicates that neurodegeneration may spread corticofugally., Methods: We conducted an observational study to define the initial sites of disease onset and the clinical progression ('spreading patterns') of motor deficits in a cohort of 910 ALS patients in Germany., Results: Mean age of ALS onset was 59.0 ± 12.6 years for males and 61.2 ± 10.5 years for females, the mean ALSFRS-R was 35.1 ± 9.2, and 7.7% of the cohort reported a family history. Onset of motor symptoms was bulbar/upper limb in 26.8%/35.9%, the right arm initially being slightly more often affected than the left (18.5% vs.16.3%). Testing on concordance of handedness and onset in the dominant arm did not reach significance. Lower limb onset was observed in 37.3%. Unilateral limb onset patients reported horizontal spreading about three times more often than vertical spreading. 71/244 bulbar onset patients reported spreading pattern to the legs, and 17/339 lumbar onset patients reported spreading secondarily to the bulbar region., Discussion: Our results indicate that, although the phenotype of so-called 'spinal' or 'intraspinal' spreading predominated, we also observed an additional clinical spreading pattern: 29.1% of patients with bulbar onset experienced spreading clinically to the legs (vice versa in 5.0% of lumbar onset patients). For obvious neuroanatomical reasons, this pattern hardly can be explained solely by a 'spinal' or an 'intraspinal' pattern of spreading. Instead, these findings complement insights from previous clinical and clinicopathological studies supporting a cortical initiation of ALS., (© 2024. The Author(s).)

Background: Several studies have reported disproportionate wasting of the flexor muscles of the lower limbs (LL) compared to the extensors in patients with amyotrophic lateral sclerosis (ALS). However, these studies have involved small sample sizes (n 〈100), and their findings have been inconsistent. Thus, it remains uncertain whether a distinct pattern of LL muscle weakness is specific to ALS., Aims: To investigate the muscle weakness pattern in the LL at the knee, ankle, and toes in a large cohort of ALS patients and evaluate the relationship between the pattern of muscle strength and the extent of upper (UMN) and lower (LMN) motoneuron impairment., Material and Methods: The strength of flexor and extensor muscle was evaluated in 1250 legs of newly diagnosed ALS patients at the knee, ankle, and foot toes. UMN and LMN burden were assessed using validated scores. Within-subjects ANOVA considering the type of muscle (flexor/extensor) and anatomical sites (knee/ankle/toes) and mixed-factorial ANOVA were conducted to explore the impact of UMN and LMN impairments on the muscle weakness pattern., Results: Muscle strength showed a significant decline from proximal to distal regions. Indeed both flexor and extensor muscles at the knee outperformed those at the ankle and toes. Within each site, extensor muscles exhibited less strength than flexor, except at the knee. Patients with heightened UMN impairment showed a more marked difference between flexors and extensors within each site, with extensor muscles being more compromised at the ankle and toes. Higher LMN impairment corresponded to a more pronounced weakness in flexor muscles at the ankle and toes compared to those at the knee., Conclusions: The extensor muscle at the knee and the flexors at the foot and toes displayed relative resistance to ALS disease. UMN impairment amplified the differences between flexor and extensor muscles within each site, while LMN impairment demonstrated a clear distal-to-proximal vulnerability., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: To evaluate the association between handgrip strength (HGS) weakness and asymmetry with incident hip fracture among older Chinese adults., Methods: Data was obtained from the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study (CHARLS). HGS weakness was defined as maximal HGS 〈 28 kg in men and < 18 kg in women. HGS asymmetry was defined as the HGS ratio < 0.9 or 〉 1.1. Participants were categorized into normal HGS, weakness only, asymmetry only, and both weakness and asymmetry. Given the sex differences in HGS, the association between HGS weakness and asymmetry was analyzed by sex using the multivariable logistic regression models., Results: A total of 4789 participants aged ≥ 60 years old without hip fracture at baseline were included in the final analysis. Over the four-year follow-up, there were 152 (3.17 %) participants having incident hip fractures, of which 69 (2.90 %) were men and 83 (3.45 %) were women. Compared to the normal group, men with both weakness and asymmetry had a significantly higher risk of incident hip fracture in the fully adjusted model (adjusted odds ratio (OR): 2.31, 95 % confidence interval (CI):1.17-4.52). There was no significant association between HGS asymmetry and weakness with hip fracture in women., Conclusions: Our findings indicated that among the Chinese population, men with both HGS weakness and asymmetry were associated with increased odds of hip fracture, while no significant association was observed in women., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The liver is a vital organ involved in nutrient metabolism, hormone regulation, immunity, cytokine production, and gut homeostasis. Impairment in liver function can result in malnutrition, chronic inflammation, decreased anabolic hormone levels, and dysbiosis. These conditions eventually cause an imbalance in osteoblast and osteoclast activities, resulting in bone loss. Osteoporosis is a frequent complication of chronic liver disease (CLD) that adversely affects quality of life and increases early mortality. Sarcopenia is another common complication of CLD characterized by progressive loss of skeletal muscle mass and function. Assessment criteria for sarcopenia specific to liver disease have been established, and sarcopenia has been reported to be associated with an increase in the risk of liver disease-related events and mortality in patients with CLD. Owing to their similar risk factors and underlying pathophysiological mechanisms, osteoporosis and sarcopenia often coexist (termed osteosarcopenia), progress in parallel, and further exacerbate the conditions mentioned above. Therefore, comprehensive management of these musculoskeletal disorders is imperative. This review summarizes the clinical implications and characteristics of osteoporosis, extending to sarcopenia and osteosarcopenia, in patients with CLD caused by different etiologies., (© 2024. The Japanese Society Bone and Mineral Research.)

Purpose: Many modern-day children are at risk of pediatric dynapenia (muscle weakness). We examined the effects of a 12-week resistance training (RT) program on neuromuscular function and body composition parameters in pubertal children with a risk of dynapenia., Methods: Twelve children (13.4 ± 0.9 y) with dynapenia performed a progressive RT program consisting of knee extension and flexion, bench press, abdominal crunch, back extension, lateral pull-down, elbow flexion, and upright row (1-2 sets of 10-15 repetitions/exercise) twice/week for 12 weeks. Outcome measures included one-repetition maximum (1-RM) strength, maximal voluntary isometric contraction (MVIC) torque, rate of torque development (RTD), electromyographic (EMG) activity, muscle thickness (MT), muscle quality (MQ) assessed by echo intensity (MQ EI ) of the knee extensors and specific tension of MVIC torque to thigh fat-free mass (MQ ST ), and total and regional body and bone composition assessed by dual-energy X-ray absorptiometry. Changes in the measures before and after the 12-week RT and associations among the measures were analyzed by linear mixed models., Results: Significant (p < 0.05) increases in 1-RM (63.9 ± 4.5%), MVIC torque (16.3 ± 17.8%), MT (18.8 ± 5.5%) and MQ (MQ EI : -25.9 ± 15.2%; MQ ST : 15.1 ± 18.8%;) were evident from pre- to post-training. Total fat-free mass (FFM) increased by 2.3 ± 3.2% from baseline (p = 0.01), but no changes (p > 0.05) in the other measures were observed. Significant (p < 0.05) associations between the changes in 1-RM and/or MVIC torque and the changes in quadriceps MT, MQ EI , MQ ST and total body FFM were evident., Conclusions: The 12-week RT was effective for improving neuromuscular and body composition parameters, and thereby reversed the risk of pediatric dynapenia., (© 2024. The Author(s).)

Abstract: McGrath, R, McGrath, BM, Jurivich, D, Knutson, P, Mastrud, M, Singh, B, and Tomkinson, GR. Collective weakness is associated with time to mortality in Americans. J Strength Cond Res 38(7): e398-e404, 2024-Using new weakness cutpoints individually may help estimate time to mortality, but their collective use could improve value. We sought to determine the associations of (a) each absolute and body size normalized cut point and (b) collective weakness on time to mortality in Americans. The analytic sample included 14,178 subjects aged ≥50 years from the 2006-2018 waves of the Health and Retirement Study. Date of death was confirmed from the National Death Index. Handgrip dynamometry measured handgrip strength (HGS). Men were categorized as weak if their HGS was <35.5 kg (absolute), <0.45 kg·kg -1 (body mass normalized), or <1.05 kg·kg -1 ·m -2 (body mass index [BMI] normalized). Women were classified as weak if their HGS was <20.0 kg, <0.337 kg·kg -1 , or <0.79 kg·kg -1 ·m -2 . Collective weakness categorized persons as below 1, 2, or all 3 cutpoints. Cox proportional hazard regression models were used for analyses. Subject values below each absolute and normalized cutpoint for the 3 weakness parameters had a higher hazard ratio for early all-cause mortality: 1.45 (95% confidence interval [CI]: 1.36-1.55) for absolute weakness, 1.39 (CI: 1.30-1.49) for BMI normalized weakness, and 1.33 (CI: 1.24-1.43) for body mass normalized weakness. Those below 1, 2, or all 3 weakness cut points had a 1.37 (CI: 1.26-1.50), 1.47 (CI: 1.35-1.61), and 1.69 (CI: 1.55-1.84) higher hazard for mortality, respectively. Weakness determined by a composite measure of absolute and body size adjusted strength capacity provides robust prediction of time to mortality, thus potentially informing sports medicine and health practitioner discussions about the importance of muscle strength during aging., (Copyright © 2024 National Strength and Conditioning Association.)

Background: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder with systemic implications, potentially affecting musculoskeletal health. This study aimed to assess shoulder muscle strength and joint repositioning accuracy in individuals with T2DM, exploring potential correlations and shedding light on the musculoskeletal consequences of the condition. The objectives were two-fold: (1) to assess and compare shoulder strength and joint repositioning accuracy between individuals with T2DM and asymptomatic counterparts, and (2) to examine the correlation between shoulder strength and joint repositioning accuracy in individuals with T2DM., Methods: A cross-sectional study enrolled 172 participants using the convenience sampling method, including 86 individuals with T2DM and an age-matched asymptomatic group ( n  = 86). Shoulder strength was assessed using a handheld dynamometer, while joint repositioning accuracy was evaluated with an electronic digital inclinometer., Results: Individuals with T2DM exhibited reduced shoulder muscle strength compared to asymptomatic individuals ( p  < 0.001). Additionally, joint repositioning accuracy was significantly lower in the T2DM group ( p  < 0.001). Negative correlations were observed between shoulder strength and joint repositioning accuracy in various directions (ranging from -0.29 to -0.46, p  < 0.001), indicating that higher muscle strength was associated with improved joint repositioning accuracy in individuals with T2DM., Conclusion: This study highlights the significant impact of T2DM on shoulder muscle strength and joint repositioning accuracy. Reduced strength and impaired accuracy are evident in individuals with T2DM, emphasizing the importance of addressing musculoskeletal aspects in diabetes management. The negative correlations suggest that enhancing shoulder muscle strength may lead to improved joint repositioning accuracy, potentially contributing to enhanced physical functioning in this population., Competing Interests: The authors declare there are no competing interests., (©2024 Reddy et al.)

We assessed the feasibility of implementing a virtually guided Neuromuscular Electrical Stimulation (NMES) protocol over the tibialis anterior (TA) muscle while collecting heart rate (HR), Numeric Pain Rating Scale (NPRS), and quality of contraction (QoC) data. We investigated if HR, NPRS, and QoC differ ON and OFF the TA motor point and explored potential relationships between heart rate variability (HRV) and the NPRS. Twelve healthy adults participated in this cross-sectional study. Three NMES trials were delivered ON and OFF the TA motor point. HR, QoC, and NPRS data were collected. There was no significant difference in HRV ON and OFF the motor point ( p > 0.05). The NPRS was significantly greater OFF the motor point ( p < 0.05). The QoC was significantly different between motor point configurations ( p < 0.05). There was no correlation between the NPRS and HRV ( p > 0.05, r = -0.129). We recommend non-electrical methods of measuring muscle activity for future studies. The NPRS and QoC can be administered virtually. Time-domain HRV measures could increase the validity of the protocol. The variables should be explored further virtually to enhance the protocol before eventual ICU studies.

Introduction: Fibromyalgia syndrome (FMS) is a chronic pain syndrome, prevalent in women more than men. The main symptoms are widespread musculoskeletal pain, fatigue, and weakness. To date, the pathophysiological mechanisms are unclear, and there are several pathogenic theories elucidating this condition. In this review, we summarized articles published in the past few years, regarding the effect of musculoskeletal dysfunction on FMS. We focused on the musculoskeletal system and central nervous system (CNS) disarrays.

Skeletal muscle weakness is a debilitating consequence of many malignancies. Muscle weakness has a negative impact on both patient wellbeing and outcome in a range of cancer types and can be the result of loss of muscle mass (i.e. muscle atrophy, cachexia) and occur independently of muscle atrophy or cachexia. There are multiple cancer specific triggers that can initiate the progression of muscle weakness, including the malignancy itself and the tumour environment, as well as chemotherapy, radiotherapy and malnutrition. This can induce weakness via different routes: 1) impaired intrinsic capacity (i.e., contractile dysfunction and intramuscular impairments in excitation-contraction coupling or crossbridge cycling), 2) neuromuscular disconnection and/or 3) muscle atrophy. The mechanisms that underlie these pathways are a complex interplay of inflammation, autophagy, disrupted protein synthesis/degradation, and mitochondrial dysfunction. The current lack of therapies to treat cancer-associated muscle weakness highlight the critical need for novel interventions (both pharmacological and non-pharmacological) and mechanistic insight. Moreover, most research in the field has placed emphasis on directly improving muscle mass to improve muscle strength. However, accumulating evidence suggests that loss of muscle function precedes atrophy. This review primarily focuses on cancer-associated muscle weakness, independent of cachexia, and provides a solid background on the underlying mechanisms, methodology, current interventions, gaps in knowledge, and limitations of research in the field. Moreover, we have performed a mini-systematic review of recent research into the mechanisms behind muscle weakness in specific cancer types, along with the main pathways implicated., (Copyright © 2024 Karolinska Institutet. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Physical decline can be associated with the onset of depressive symptoms in later life. This study aimed to identify physical and lifestyle risk factors for depressive symptom trajectories in community-dwelling older adults., Methods: Participants were 553 people aged 70-90 years who underwent baseline physical, psychological and lifestyle assessments. Group-based trajectory analysis was used to identify patterns of depressive symptom development over 6 years of follow-up. Strengths of associations between baseline functional test performances and depressive symptom trajectories were evaluated with univariable ordinal models. Subsequently, the adjusted cumulative odds ratio for the association between identified risk factors, demographic factors and baseline anti-depressant use were measured using multivariable ordinal logistic regression., Results: Three distinct depressive symptom trajectories were identified: a low-and-stable course (10% of participants), a low-and-increasing course (81%) and a moderate-and-increasing course (9%). Timed Up and Go test time was the strongest risk factor of depressive symptom trajectory, followed by Five Times Sit-to-Stand test performance, planned physical activity levels, and knee extension strength (adjusted standardised ORs 1.65, 95% CI 1.34-2.04; 1.44, 95% CI 1.16-1.77; 1.44, 95% CI 1.17-1.76 and 1.41, 95% CI 1.15-1.73 respectively). After adjusting for age, sex, body mass index and baseline anti-depressant use, Timed Up and Go test performance and knee extension strength were independently and significantly associated with depressive trajectories., Conclusions: Timed Up and Go test times, Five Times Sit-to-Stand test performance, planned physical activity levels and knee extension strength are associated with three discrete depressive symptom trajectories. These clinical tests may help identify older adults aged 70-90 years at risk of developing depressive symptoms and help guide subsequent strength and mobility interventions., (© 2024 AJA Inc’.)

Aim: Patients undergoing haemodialysis have reduced muscle strength and impaired activities of daily living (ADL). We examined possible relationship between difficult ADL and corresponding muscle weakness in elderly haemodialysis patients., Methods: This was a single-centre, cross-sectional study. Patient-reported ADL difficulty was examined using a questionnaire in six ADL using upper limbs (eating, grooming and dressing) and lower limbs (bathing, toileting and locomotion). We measured six muscle strengths by dynamometers of shoulder flexion, shoulder abduction, elbow flexion, handgrip, hip abduction and knee extension. The muscle strength with the lowest Z-score was considered as the weakest muscle strength for the patient., Results: The six scores of ADL difficulty were all inversely associated with the six muscle strengths in the 81 total participants of whom 71 individuals (87.7%) had any ADL difficulty. Among the six measurements of muscle strength, handgrip strength showed the highest associations with all ADL difficulties. In 25 patients who perceived that the most difficult ADL was an activity using upper limbs, the common weakest muscle strengths were the hip abduction, handgrip and elbow flexion. In 44 patients who perceived that the most difficult ADL was an activity using lower limbs, knee extension was the most prevalent weakest muscle strength., Conclusion: This study suggested preferential relationship between the most difficult ADL and corresponding muscle weakness in elderly haemodialysis patients. This finding may be useful in prevention and treatment., (© 2024 Asian Pacific Society of Nephrology.)

Objectives: To investigate muscle strength and the prevalence of muscle weakness in adults with interstitial lung diseases (ILDs) compared to healthy subjects., Design: Cross-sectional (description of clinical features)., Setting: Public referral center (University Hospital)., Participants: One hundred and twelve adults with ILD (n=48, 60±10yr, 68% female) and healthy counterparts (control group, n=64, 57±10yr, 58% female) (N=112)., Intervention: Not applicable., Main Outcome Measure(s): Muscle strength and prevalence of muscle weakness in adults with ILD. Muscle strength was assessed via maximal isometric voluntary contraction of dominant upper and lower limb muscle groups. Data from the control group were used to generate reference equations. Muscle weakness was defined as a muscle strength value below the lower limit of normal calculated using data from the control group. Data were expressed as mean ± SD or median [interquartile range] according to the data distribution., Results: Compared to the control group, adults with ILD had lower muscle strength for all muscle groups assessed (values presented as %predicted: pectoralis major 75[57-86]%; quadriceps 72[58-87]%; latissimus dorsi 76[57-103]%; deltoid 74[64-98]%; biceps brachii 78[64-91]%; triceps brachii 84[62-101]%; P≤.001 for all). Prevalence of muscle weakness in people with ILD was 40% for pectoralis major, 25% for latissimus dorsi, 16% for triceps brachii, 20% for biceps brachii, 27% for deltoid and 46% for quadriceps., Conclusions: Adults with ILD present a generalised reduction in peripheral Muscle strength, ranging between 20% to 46% of people depending on the muscle group assessed. and it was more prevalent in lower limb muscles., (Copyright © 2024 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Sarcopenia is a musculoskeletal disease involving the reduction of muscle mass, strength, and performance. Handgrip strength (HGS) measurements included in frailty assessments are great biomarkers of aging and are related to functional deficits. We assessed the association between potential influencing factors and HGS asymmetry in older Peruvian adults., Methods: We used a database of the Peruvian Naval Medical Center &quot;Cirujano Santiago Távara&quot; located in Callao, Peru. All the patients included were ≥60 years old and had an HGS measurement in the dominant and non-dominant hand., Results: From a total of 1,468 patients, 74.66% had HGS asymmetry. After adjustment, calf circumference weakness (adjusted prevalence ratio [aPR]=1.08; 95% confidence interval [CI], 1.01-1.15), falls risk (aPR = 1.08; 95% CI, 1.02-1.16), and an altered Lawton index (aPR=0.92; 95% CI, 0.84-0.99) were associated with HGS asymmetry., Conclusion: Our findings suggest that HGS asymmetry should be measured along with other geriatric assessments used to evaluate health outcomes in the elderly to enhance health promotion and prevention aimed at preserving muscle strength to curb functional limitations in the elderly.

Background: Although loss of muscle mass may be associated with general weakness, intolerance to physical activity and fatigue, it is underestimated and poorly understood in patients with sarcoidosis., Aim: To compare the quadriceps femoris muscle (QFM) thickness measured by ultrasonography (US) between the female patients with sarcoidosis and controls, secondly to assess the correlation between the muscle strength, fatigue and QFM thickness., Design: Observational, case-control study., Setting: Physical Medicine and Rehabilitation Department of a University Hospital., Population: Thirty-one women with sarcoidosis and 27 healthy volunteers were included in the study., Methods: The participants were evaluated for the following outcomes: 1) handgrip strength; 2) QFM thickness measured using US; and 3) sonographic thigh adjustment ratio (STAR). The sarcoidosis group was also evaluated with the 30-second chair stand test (30s-CST) and Fatigue Severity Scale (FSS)., Results: The QFM thickness and STAR values of the patients with sarcoidosis were significantly lower than those of the controls (P=0.0001). However, no statistically significant difference was observed between the handgrip strengths of the groups (P=0.581). There was no statistically significant correlation between the STAR values and handgrip strength in the sarcoidosis group; however, there was a significant positive correlation between the STAR values and 30s-CST (r=0.467, P=0.008)., Conclusions: Loss of muscle mass is one of the musculoskeletal conditions in patients with sarcoidosis that may be associated with nonspecific symptoms, such as general debility, intolerance to physical activity, and fatigue. In the present study, no difference was observed in hand grip strength between the groups, while we found that QFM thickness was affected in patients with sarcoidosis when compared to the controls. The ultrasonographic QFM evaluation seems to be an innovative tool which may be used at all stages of sarcoidosis patient follow-up., Clinical Rehabilitation Impact: The grip strength is a commonly used test to detect muscle weakness, but onset of a decrease in muscle mass in the lower extremities may occur earlier. Considering the increased burden of musculoskeletal problems in this population, performing 30s-CST and sonographic QFM thickness is practical methods to identify risky patients.

Critical illness survivors commonly face impairments, such as intensive care unit-acquired weakness (ICUAW) which is characterized by muscle weakness and sensory deficits. Despite these symptoms indicating potential balance deficits, systematic investigations and validated assessments are lacking. Therefore, we aimed to assess balance function using the Mini-BESTest, evaluate its psychometric properties, and identify associated variables. Balance was assessed post-ICU discharge (V1) and at discharge from inpatient neurorehabilitation (V2) in patients with ≥ 5 days of invasive ventilation. Mini-BESTest measurement characteristics were evaluated in an ambulatory subgroup. A multiple linear regression was conducted. The prospective cohort study comprised 250 patients (34% female, 62 ± 14 years, median ICU stay 55 days). Median Mini-BESTest scores improved significantly from V1 (5 (IQR 0-15)) to V2 (18.5 (10-23)) with a large effect size. Excellent inter-rater and test-retest reliabilities of the Mini-BESTest were observed (ICC = 0.981/0.950). Validity was demonstrated by a very high correlation with the Berg Balance Scale (ρ = 0.90). No floor or ceiling effects were detected. Muscle strength, cognitive function, cerebral disease, critical illness polyneuropathy/myopathy, and depression were significantly associated with balance. Despite significant improvements during the rehabilitation period, balance disorders were prevalent in critical illness survivors. Ongoing therapy is recommended. Due to its excellent psychometric properties, the Mini-BESTest is suitable for use in critical illness survivors.Registration: The study was registered at the German Clinical Trials Register (DRKS00021753, date of registration: 2020-09-03)., (© 2024. The Author(s).)

Background: Late-onset Pompe disease (LOPD) patients may still need ventilation support at some point of their disease course, despite regular recombinant human alglucosidase alfa treatment. This suggest that other pathophysiological mechanisms than muscle fibre lesion can contribute to the respiratory failure process. We investigate through neurophysiology whether spinal phrenic motor neuron dysfunction could contribute to diaphragm weakness in LOPD patients., Material and Methods: A group of symptomatic LOPD patients were prospectively studied in our centre from January 2022 to April 2023. We collected both demographic and clinical data, as well as neurophysiological parameters. Phrenic nerve conduction studies and needle EMG sampling of the diaphragm were perfomed., Results: Eight treated LOPD patients (3 males, 37.5%) were investigated. Three patients (37.5%) with no respiratory involvement had normal phrenic nerve motor responses [median phrenic compound muscle action potential (CMAP) amplitude of 0.49 mV; 1st-3rd interquartile range (IQR), 0.48-0.65]. Those with respiratory failure (under nocturnal non-invasive ventilation) had abnormal phrenic nerve motor responses (median phrenic CMAP amplitude of 0 mV; 1st-3rd IQR, 0-0.15), and were then investigated with EMG. Diaphragm needle EMG revealed both myopathic and neurogenic changes in 3 (60%) and myopathic potentials in 1 patient. In the last one, no motor unit potentials could be recruited., Conclusions: Our study provide new insights regarding respiratory mechanisms in LOPD, suggesting a contribution of spinal phrenic motor neuron dysfunction for diaphragm weakness. If confirmed in further studies, our results recommend the need of new drugs crossing the blood-brain barrier., Competing Interests: Declaration of competing interest Miguel Oliveira Santos and Mamede de Carvalho received support from Sanofi. The other authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Muscle weakness has been associated to insulin resistance and metabolic syndrome in the general population. However, it is still unclear whether this association is maintained in older adults. This study investigated correlations between low handgrip strength (HGS) and metabolic syndrome, or some of its components, in older adults through a systematic review of the literature. Searches were conducted in the Virtual Health Library Regional Portal, Scopus, Cochrane, Embase, MEDLINE/ PubMed, SciELO, and Web of Science databases for relevant studiesinvestigating muscle weakness (measured by hand dynamometer) and metabolic syndrome or its components in older adult populations, published up to September 2023. From the 2050 references initially identified, 20 studies, comprising a total of 31,264 older adults of both genders, completely met the inclusion/exclusion criteria. Eighteen studies showed that lower HGS was associated with metabolic syndrome or some of its risk factors, such as abdominal obesity, hyperglycemia, insulin resistance, dyslipidemia, or high blood pressure. Two studies found that older men with high blood pressure had increased HGS. Most studies included in this systematic review revealed a significant correlation between reduced HGS and metabolic syndrome or some of its components, especially abdominal obesity and insulin resistance. We conclude that below-average HGS can be associated with metabolic syndrome in older adults.

Objective: Inspiratory muscle strength (IMS) appears to be reduced in subjects with chronic Chagas heart disease (CHD), especially in the presence of heart failure (HF). However, only one study about IMS and inspiratory muscle endurance (IME) in those with CHD without heart failure is available. This study aimed to compare IMS and IME in subjects with CHD in the presence and absence of HF., Methods: This is a cross-sectional study in which 30 CHD adult patients were divided into CHD-CC group (initial phase of CHD, without HF; n = 15) and CHD-HF group (advanced phase of CHD, with HF; n = 15). We assessed IMS by maximum inspiratory pressure (MIP) and IME by incremental (Pthmax) and constant load (TLim) tests. Reduced IMS and IME were considered by predicted MIP values <70% and Pthmax/MIP <75%, respectively., Results: Inspiratory muscle weakness (IMW) was more frequent in CHD-HF than in CHD-CC (46.7% vs. 13.3%; p = 0.05), and both groups had high frequencies of reduced IME (93.3% CHD-CC vs. 100.0% CHD-HF; p = 0.95). Age-adjusted logistic regression analysis using HF as a dependent variable showed that HF was associated with an increased chance of IMW compared with the CHD-CC group (OR = 7.47; p = 0.03; 95% CI 1.20-46.19)., Conclusion: This study suggests that, in patients with CHD, HF is associated with IMW, and that reduction of IME is already present in the initial phase, similar to the advanced phase with HF., (© 2024 John Wiley & Sons Ltd.)

Clinical management of whiplash-associated disorders is challenging and often unsuccessful, with over a third of whiplash injuries progressing to chronic neck pain. Previous imaging studies have identified muscle fat infiltration, indicative of muscle weakness, in the deep cervical extensor muscles (multifidus and semispinalis cervicis). Yet, kinematic and muscle redundancy prevent the direct assessment of individual neck muscle strength, making it difficult to determine the role of these muscles in motor dysfunction. The purpose of this study was to determine the effects of deep cervical extensor muscle weakness on multi-directional neck strength and muscle activation patterns. Maximum isometric forces and associated muscle activation patterns were computed in 25 test directions using a 3-joint, 24-muscle musculoskeletal model of the head and neck. The computational approach accounts for differential torques about the upper and lower cervical spine. To facilitate clinical translation, the test directions were selected based on locations where resistance could realistically be applied to the head during clinical strength assessments. Simulation results reveal that the deep cervical extensor muscles are active and contribute to neck strength in directions with an extension component. Weakness of this muscle group leads to complex compensatory muscle activation patterns characterized primarily by increased activation of the superficial extensors and deep upper cervical flexors, and decreased activation of the deep upper cervical extensors. These results provide a biomechanistic explanation for movement dysfunction that can be used to develop targeted diagnostics and treatments for chronic neck pain in whiplash-associated disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density (aBMD). However, the prevalence of muscle strength deficits is not well documented, and the associations of muscle strength with aBMD are unknown in this population. Therefore, this study aimed to investigate the prevalence of upper- and lower-body muscle strength deficits and to examine the associations of upper- and lower-body muscle strength with age-, sex, and race-specific aBMD Z-scores at the total body, total hip, femoral neck, and lumbar spine., Methods: This cross-sectional study included 116 pediatric cancer survivors (12.1 ± 3.3 years old, mean ± SD; 42.2% female). Upper- and lower-body muscle strength were assessed by handgrip and standing long jump test, respectively. Dual‑energy X‑ray absorptiometry was used to measure aBMD (g/cm 2 ). Associations between muscle strength and aBMD were evaluated in multivariable linear regression models. Logistic regression was used to evaluate the contribution of muscle strength (1-decile lower) to the odds of having low aBMD (Z-score ≤ 1.0). All analyses were adjusted for time from treatment completion, radiotherapy exposure, and body mass index., Results: More than one-half of survivors were within the 2 lowest deciles for upper- (56.9%) and lower- body muscle strength (60.0%) in comparison to age- and sex-specific reference values. Muscle strength deficits were associated with lower aBMD Z-scores at all sites (B = 0.133-0.258, p = 0.001-0.032). Each 1-decile lower in upper-body muscle strength was associated with 30%-95% higher odds of having low aBMD Z-scores at all sites. Each 1-decile lower in lower-body muscle strength was associated with 35%-70% higher odds of having low aBMD Z-scores at total body, total hip, and femoral neck., Conclusion: Muscle strength deficits are prevalent in young pediatric cancer survivors, and such deficits are associated with lower aBMD Z-scores at all sites. These results suggest that interventions designed to improve muscle strength in this vulnerable population may have the added benefit of improving aBMD., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Background: The weakness of the tibialis anterior remains to be a controversial topic. There has been no study that used electrophysiological assessment of the function of the lumbar and sacral peripheral motor nerves. The aim is to evaluate surgical outcomes in patients with weakness of the tibialis anterior using neurological and electrophysiological assessments., Methods: We enrolled 53 patients. Tibialis anterior weakness was quantified by muscle strength, as assessed using a manual muscle test on a scale of 1 through 5, with scores <5 indicating weakness. Postoperative improvement in muscle strength was classified as excellent (5 grades recovered), good (more than one grade recovered), or fair (less than one grade recovered)., Results: Surgical outcomes for tibialis anterior function were categorized as "excellent" in 31, "good" in 8, "fair" in 14 patients. Significant difference in outcomes were observed depending on diabetes mellitus status, type of surgery, and the compound muscle action potentials amplitudes of the abductor hallucis and extensor digitorum brevis (p < 0.05). Surgical outcomes were classified into two groups, patients with excellent and good outcomes (Group 1) and patients with fair outcome (Group 2). Using the forward selection stepwise method, sex and the compound muscle action potentials amplitudes of the extensor digitorum brevis were identified as significant factors for their positive association with Group 1 status. The diagnostic power of the predicted probability was as high as 0.87 in terms of area under curve of the receiver operating characteristic curve., Conclusions: There was a significant correlation between the prognosis of tibialis anterior weakness and sex and the compound muscle action potentials amplitude of extensor digitorum brevis, suggesting that recording the compound muscle action potentials amplitude of extensor digitorum brevis will aid the outcome assessment of future surgical interventions for tibialis anterior weakness., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Chronic obstructive pulmonary disease is a systemic disease characterized not only by respiratory symptoms but also by physical deconditioning and muscle weakness. One prominent manifestation of this disease is the decline in respiratory muscle strength. Previous studies have linked the genotypes of insulin-like growth factor 1 and 2 (IGF-1 and IGF-2) to muscle weakness in other populations without this disease. However, there is a notable knowledge gap regarding the biological mechanisms underlying respiratory muscle weakness, particularly the role of IGF-1 and IGF-2 genotypes in this pulmonary disease. Therefore, this study aimed to investigate, for the first time, the association between IGF-1 and IGF-2 genotypes with respiratory muscle strength in individuals with chronic obstructive pulmonary disease. In addition, we analyzed the relationship between oxidative stress, chronic inflammation, and vitamin D with respiratory muscle strength., Methods: A cross sectional study with 61 individuals with chronic obstructive pulmonary disease. Polymerase chain reaction of gene polymorphisms IGF-1 (rs35767) and IGF-2 (rs3213221) was analyzed. Other variables, related to oxidative stress, inflammation and Vitamin D were dosed from peripheral blood. Maximal inspiratory and expiratory pressure were measured., Results: The genetic polymorphisms were associated with respiratory muscle strength ( 3.0 and 3.5; = 0.57). Specific genotypes of IGF-1 and IGF-2 presented lower maximal inspiratory and expiratory pressure (<0.05 for all). Oxidative stress, inflammatory biomarkers, and vitamin D were not associated with respiratory muscle strength., Conclusion: The polymorphisms of IGF-1 and IGF-2 displayed stronger correlations with respiratory muscle strength compared to blood biomarkers in patients with chronic obstructive pulmonary disease. Specific genotypes of IGF-1 and IGF-2 were associated with reduced respiratory muscle strength in this population., Competing Interests: The authors declare no conflict of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Objective: We aimed to determine hip and lower-leg muscle strength in people after ACL injury compared with an uninjured control group (between people) and the uninjured contralateral limb (between limbs)., Design: Systematic review with meta-analysis., Data Sources: MEDLINE, EMBASE, CINAHL, Scopus, Cochrane CENTRAL and SportDiscus to 28 February 2023., Eligibility Criteria: Primary ACL injury with mean age 18-40 years at time of injury. Studies had to measure hip and/or lower-leg muscle strength quantitatively (eg, dynamometer) and report muscle strength for the ACL-injured limb compared with: (i) an uninjured control group and/or (ii) the uninjured contralateral limb. Risk of bias was assessed according to Cochrane Collaboration domains., Results: Twenty-eight studies were included (n=23 measured strength ≤12 months post-ACL reconstruction). Most examined hip abduction (16 studies), hip extension (12 studies) and hip external rotation (7 studies) strength. We found no meaningful difference in muscle strength between people or between limbs for hip abduction, extension, internal rotation, flexion or ankle plantarflexion, dorsiflexion (estimates ranged from -9% to +9% of comparator). The only non-zero differences identified were in hip adduction (24% stronger on ACL limb (95% CI 8% to 42%)) and hip external rotation strength (12% deficit on ACL limb (95% CI 6% to 18%)) compared with uninjured controls at follow-ups >12 months, however both results stemmed from only two studies. Certainty of evidence was very low for all outcomes and comparisons, and drawn primarily from the first year post-ACL reconstruction., Conclusion: Our results do not show widespread or substantial muscle weakness of the hip and lower-leg muscles after ACL injury, contrasting deficits of 10%-20% commonly reported for knee extensors and flexors. As it is unclear if deficits in hip and lower-leg muscle strength resolve with appropriate rehabilitation or no postinjury or postoperative weakness occurs, individualised assessment should guide training of hip and lower-leg strength following ACL injury., Prospero Registration Number: CRD42020216793., Competing Interests: Competing interests: KMC holds a research grant from Levin Health. BP, AGC and EKR are Associate Editors at the British Journal of Sports Medicine. KMC is a Senior Advisor to the British Journal of Sports Medicine., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: COVID-19 patients experience respiratory muscle damage, leading to reduced respiratory function and functional capacity often requiring mechanical ventilation which further increases susceptibility to muscle weakness. Inspiratory muscle training (IMT) may help mitigate this damage and improve respiratory function and functional capacity. Methods: We studied the effects of IMT on muscle damage biomarkers, respiratory function, and functional capacity in COVID-19 recovered young adults, successfully weaned from mechanical ventilation. Participants were randomly allocated to either an IMT ( n = 11) or control (CON; n = 11) intervention for 4 weeks. The IMT group performed 30 dynamic inspiratory efforts twice daily, at 50% of their maximal inspiratory mouth pressure (P Mmax ) while the CON group performed 60 inspiratory efforts at 10% of p Mmax daily. Serum was collected at baseline, week two, and week four to measure creatine kinase muscle-type (CKM), fast skeletal troponin-I (sTnI) and slow sTnI. Results: Time × group interaction effects were observed for CKM and slow sTnI, but not for fast sTnI. Both were lower at two and 4 weeks for the IMT compared to the CON group, respectively. Time × group interaction effects were observed for forced expiratory volume in 1s, forced vital capacity, P Mmax and right- and left-hand grip strength. These were higher for the IMT compared to the CON group. Conclusion: Four weeks of IMT decreased muscle damage biomarkers and increased respiratory function and grip strength in recovered COVID-19 patients after weaning from mechanical ventilation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Congenital myasthenic syndromes (CMS) are a group of rare but often treatable inherited disorders of neuromuscular transmission characterized by fatigable skeletal muscle weakness. In this paper we present the largest phenotypic analysis to date of a cohort of patients carrying the pathogenic variant c.1327delG in the CHRNE gene, leading to CHRNE-CMS., Objective: This study aims to identify the phenotypic variability in CMS associated with c.1327delG mutation in the CHRNE gene., Methods: Disease specific symptoms were assessed using specific standardized tests for autoimmune myasthenia (Quantitative Myasthenia Gravis score) as well as patient-reported scales for symptom severity. Evaluated clinical manifestations included ocular symptoms (ophthalmoparesis and ptosis), bulbar weakness, axial muscle weakness, proximal and distal muscle weakness, and respiratory function. Patients were allocated into three groups according to clinical impression of disease severity: mild, moderate, and severe., Results: We studied 91 Bulgarian Roma patients, carrying the same causative homozygous CHRNE c.1327delG mutation. Bulbar weakness was present in patients throughout all levels of severity of CHRNE-CMS in this study. However, difficulties in eating and swallowing are more prominent characteristics in the moderate and severe clinical phenotypes. Diplopia and ptosis resulting from fatigue of the extraocular muscles were permanent features regardless of disease severity or age. Levels of axial, proximal and distal muscle weakness were variable between disease groups. The statistical analysis showed significant differences between the patients in the three groups, emphasizing a possible variation in symptom manifestation in the evaluated patient population despite the disease originating from the same genetic mutation. Impairment of respiratory function was more prominent in severely affected patients, which might result from loss of compensatory muscle function in those individuals., Conclusion: Results from our study indicate significant phenotypic heterogeneity leading to mild, moderate, or severe clinical manifestation in CHRNE-CMS, despite the genotypic homogeneity.

Individuals with neurological disorders often exhibit altered manual dexterity and muscle weakness in their upper limbs. These motor impairments with tremor lead to severe difficulties in performing Activities of Daily Living (ADL). There is a critical need for ADL-focused robotic training that improves individual's strength when engaging with dexterous ADL tasks. This research introduces a new approach to training ADLs by employing a novel robotic rehabilitation system, Spherical Parallel INstrument for Daily Living Emulation (SPINDLE), which incorporates Virtual Reality (VR) to simulate ADL tasks. The study results present the feasibility of training individuals with movements similar to ADLs while interacting with the SPINDLE. A new game-based robotic training paradigm is suggested to perform ADL tasks at various intensity levels of resistance as needed. The proposed system can facilitate the training of various ADLs requiring 3-dimensional rotational movements by providing optimal resistance and visual feedback. We envision this system can be utilized as a table-top home device by restoring the impaired motor function of individuals with tremor and muscle weakness, guiding to improved ADL performance and quality of life.

Neck muscle weakness due to amyotrophic lateral sclerosis (ALS) can result in dropped head syndrome, adversely impacting the quality of life of those affected. Static neck collars are currently prescribed to hold the head in a fixed upright position. However, these braces are uncomfortable and do not allow any voluntary head-neck movements. By contrast, powered neck exoskeletons have the potential to enable head-neck movements. Our group has recently improved the mechanical structure of a state-of-the-art neck exoskeleton through a weighted optimization. To evaluate the effect of the structural changes, we conducted an experiment in which patients with ALS were asked to perform head-neck tracking tasks while using the two versions of the neck exoskeleton. We found that the neck muscle activation was significantly reduced when assisted by the structurally enhanced design compared to no assistance provided. The improved structure also improved kinematics tracking performance, allowing users to better achieve the desired head poses. In comparison, the previous design did not help reduce the muscle effort required to perform these tasks and even slightly worsened the kinematic tracking performance. It was also found that biomechanical benefits gained from using the structurally improved design were consistent across participants with both mild and severe neck weakness. Furthermore, we observed that participants preferred to use the powered neck exoskeletons to voluntarily move their heads and make eye contact during a conversation task rather than remain in a fixed upright position. Each of these findings highlights the importance of the structural design of neck exoskeletons in achieving desired biomechanical benefits and suggests that neck exoskeletons can be a viable method to improve the daily life of patients with ALS.

Background: The joint associations of handgrip strength (HGS) weakness and asymmetry with cognitive decline remain understudied in older adults., Objective: To investigate the associations between HGS weakness, asymmetry, and lower cognitive function in a nationally representative sample of older Americans., Methods: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey 2011-2014. Weakness was defined as HGS <26 kg for men and <16 kg for women. Asymmetry was determined by calculating the ratio of dominant to non-dominant HGS. Participants with an HGS ratio <0.90 or >1.10 were classified as having any HGS asymmetry. Those with an HGS ratio >1.10 exhibited dominant HGS asymmetry, while those with an HGS ratio <0.90 displayed nondominant HGS asymmetry, respectively. Lower cognitive functioning was defined as global cognitive composite scores more than 1 standard deviation below the mean. Covariate-adjusted logistic regression models were used to analyze the associations between HGS asymmetry/weakness and lower cognitive functioning., Results: Compared to individuals with non-weak and symmetric HGS, those with any HGS asymmetry alone and weakness alone had 1.017 (95% confidence interval [CI]: 0.707-1.463) and 1.391 (95% CI: 0.542-3.571) greater odds for cognitive decline, while co-occurrence of both HGS asymmetry and weakness was associated with 3.724 (95% CI: 1.711-8.107) greater odds for lower cognitive function after controlling for confounders., Cnclusions: Individuals exhibiting both diminished and asymmetrical HGS demonstrated an elevated susceptibility to cognitive impairment, thereby implying that the inclusion of HGS asymmetry assessment in conjunction with weakness evaluation may enhance the accuracy of prognosticating cognitive decline.

Purpose: The purpose of this investigation was to compare the quality of neural drive and recruited quadriceps motor units' (MU) action potential amplitude (MUAP AMP ) and discharge rate (mean firing rate (MFR)) relative to recruitment threshold (RT) between individuals with anterior cruciate ligament reconstruction (ACLR) and controls., Methods: Fourteen individuals with ACLR and 13 matched controls performed trapezoidal knee extensor contractions at 30%, 50%, 70%, and 100% of their maximal voluntary isometric contraction (MVIC). Decomposition electromyography (dEMG) and torque were recorded concurrently. The Hoffmann reflex (H-reflex) and central activation ratio (CAR) were acquired bilaterally to detail the proportion of MU pool available and volitionally activated. We examined MUAP AMP -RT and MFR-RT relationships with linear regression and extracted the regression line slope, y-intercept, and RT range for each contraction. Linear mixed effect modelling used to analyze the effect of group and limb on regression line slope and RT range., Results: Individuals with ACLR demonstrated lower MVIC torque in the involved limb compared to uninvolved limb. There were no differences in H-reflex or CAR between groups or limbs. The ACLR involved limb demonstrated smaller mass-normalized RT range and slower MU firing rates at high contraction intensities (70% and 100% MVIC) compared to uninvolved and control limbs. The ACLR involved limb also demonstrated larger MU action potentials in the VM compared to the contralateral limb. These differences were largely attenuated with relative RT normalization., Conclusions: These results suggest that persistent strength deficits following ACLR may be attributable to a diminished quadriceps motor neuron pool and inability to upregulate the firing rate of recruited MUs., Competing Interests: David A. Sherman is an owner of Live4 Physical Therapy and Wellness. The authors declare that they have no other competing interests., (© 2023 Sherman et al.)