Jenny Hedberg-Graff, Fredrik Granström, Marianne Arner
et al.
Abstract Background Our aim was to investigate change over time of passive range of motion (pROM) in the upper limbs of children with cerebral palsy (CP), treated or not treated with botulinum neurotoxin-A (BoNT-A). Methods Data from 2000 to 2017 were collected from the Cerebral Palsy follow-up program and registry in Sweden (CPUP) for children with spastic or dyskinetic CP. Mixed models were used to analyse changes in pROM from the first, until the last measurement for five upper limb movements. Results The study involved 496 children with CP, aged 1–15 years (median 2 years, Interquartile range = 4). Of these, 22% had received at least one BoNT-A treatment. Contractures were classified as red (severe) or yellow (moderate) based on the Traffic Light system within CPUP. About 36% developed upper limb contractures before age 15. Early BoNT-A treatment (< 4 years) implied better pROM outcomes over time compared with later treatment, after adjusting for pROM category, CP subtype and level of manual ability. Conclusions Upper limb contractures can develop during growth in children with CP affecting one third of this population. Early monitoring of pROM can detect the first signs of muscle shortening before contractures are established. Our findings suggest that early BoNT-A treatment may help maintain pROM in children with CP.
João Alberto de Souza Ribeiro, Luciana Aparecida Giacomini
Work-related musculoskeletal disorders (WMSDs) are a major occupational health burden, yet early functional alterations are often difficult to capture with symptom-only screening or with predominantly structural imaging. Infrared thermography (IRT) provides a noncontact, nonionizing, physiologically grounded readout of superficial heat exchange that is strongly influenced by microperfusion and autonomic vasomotor control. We conducted an integrative narrative review with traceable study-level compilation to synthesize physiological foundations for thermal-signal interpretation, minimum requirements for acquisition standardization and Quality Control, and occupational applications for screening, risk characterization, and longitudinal monitoring, including multimodal integration. The final included corpus comprised 247 studies spanning diverse designs and contexts, with substantial heterogeneity in devices, regions of interest (ROIs), environmental conditions, thermal metrics, and reporting completeness. Across the evidence, interpretability was consistently dependent on protocol stability and on ROI-based, within-subject metrics [bilateral asymmetry, task-induced temperature difference (ΔT), and recovery dynamics] rather than isolated absolute thresholds. Occupational applications have most often targeted repetitive upper-limb demands, computer-based work, and cold challenge/rewarming paradigms in vibration-exposed populations. We provide an operational checklist aligned with guideline recommendations and propose a pragmatic multimodal workflow integrating IRT with functional measures [surface electromyography (sEMG), strength], structural/perfusion modalities (ultrasonography), and patient-reported outcomes. Future priorities include multicenter harmonization, occupation- and task-specific reference profiles, and prospective validation of decision rules under real-world conditions.
Abstract Objective This study aimed to evaluate the effectiveness of extracorporeal shock wave therapy (ESWT) and high-intensity laser therapy (HILT) in managing calcaneal spur-related symptoms. These non-invasive modalities were compared in terms of their ability to reduce pain and improve functional outcomes. Methods In this randomized clinical trial, patients diagnosed with calcaneal spur based on clinical and radiographic findings were randomly assigned to receive ESWT or HILT. Participants were randomized into two groups to receive either ESWT or HILT, complemented by standardized exercise regimens. Pain intensity was measured using the Visual Analog Scale (VAS), and functional outcomes were assessed with the Foot Function Index (FFI) at baseline, post-treatment, and three months post-treatment. Results Both groups showed significant improvements in pain and functional outcomes. In the ESWT group, VAS scores for initial step pain decreased from 7.8 ± 1.0 to 4.0 ± 1.0 post-treatment and further to 3.4 ± 1.0 at three months (p = 0.002). The HILT group demonstrated a similar trend, with scores reducing from 7.5 ± 1.2 to 4.2 ± 1.1 post-treatment and 3.5 ± 0.9 at follow-up (p = 0.001). Total FFI scores improved significantly in both groups, with the ESWT group showing a larger reduction (58.8 to 19.7; p = 0.033) compared to the HILT group (57.4 to 35.4; p = 0.046). No significant adverse events were reported in either group. Conclusion ESWT and HILT are effective non-invasive options for treating calcaneal spur with ESWT providing slightly greater functional benefits. Clinical trial registration Not applicable
Orthopedic surgery, Diseases of the musculoskeletal system
Oliver Distler, Madelon C Vonk, Arata Azuma
et al.
Abstract We used data from the SENSCIS and SENSCIS-ON trials to assess decline in forced vital capacity (FVC) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) who received long-term treatment with nintedanib and the effect of switching patients from placebo to nintedanib. In the SENSCIS trial, patients were randomised to receive nintedanib or placebo until the last patient reached week 52 but for ≤ 100 weeks. In SENSCIS-ON, the extension to SENSCIS, all patients received open-label nintedanib. Per protocol, the off-treatment period between these trials was ≤ 12 weeks. We assessed the trajectory of FVC in patients who received nintedanib in SENSCIS and continued nintedanib in SENSCIS-ON (n = 197) and in patients who received placebo in SENSCIS and initiated nintedanib in SENSCIS-ON (n = 231). The last on-treatment measurement in SENSCIS and the baseline measurement of SENSCIS-ON were considered anchor measurements. In patients who received nintedanib in SENSCIS, the mean decline in FVC in the 52 weeks prior to the last on-treatment measurement in SENSCIS was − 41.5 mL and the mean decline in FVC from baseline to week 52 of SENSCIS-ON was − 58.3 mL. In patients who received placebo in SENSCIS, the mean decline in FVC in the 52 weeks prior to the last on-treatment measurement in SENSCIS was − 96.8 mL and the mean decline in FVC from baseline to week 52 of SENSCIS-ON (when patients received nintedanib) was − 42.8 mL. These findings illustrate the progressive nature of SSc-ILD and support the efficacy of nintedanib in slowing decline in lung function over the long term.
Coconut tree diseases are a serious risk to agricultural yield, particularly in developing countries where conventional farming practices restrict early diagnosis and intervention. Current disease identification methods are manual, labor-intensive, and non-scalable. In response to these limitations, we come up with DeepSeqCoco, a deep learning based model for accurate and automatic disease identification from coconut tree images. The model was tested under various optimizer settings, such as SGD, Adam, and hybrid configurations, to identify the optimal balance between accuracy, minimization of loss, and computational cost. Results from experiments indicate that DeepSeqCoco can achieve as much as 99.5% accuracy (achieving up to 5% higher accuracy than existing models) with the hybrid SGD-Adam showing the lowest validation loss of 2.81%. It also shows a drop of up to 18% in training time and up to 85% in prediction time for input images. The results point out the promise of the model to improve precision agriculture through an AI-based, scalable, and efficient disease monitoring system.
Genetic mutations can disrupt protein structure, stability, and solubility, contributing to a wide range of diseases. Existing predictive models often lack interpretability and fail to integrate physical and chemical interactions critical to molecular mechanisms. Moreover, current approaches treat disease association, stability changes, and solubility alterations as separate tasks, limiting model generalizability. In this study, we introduce a unified framework based on multiscale commutative algebra to capture intrinsic physical and chemical interactions for the first time. Leveraging Persistent Stanley-Reisner Theory, we extract multiscale algebraic invariants to build a Commutative Algebra neural Network (CANet). Integrated with transformer features and auxiliary physical features, we apply CANet to tackle three key domains for the first time: disease-associated mutations, mutation-induced protein stability changes, and solubility changes upon mutations. Across six benchmark tasks, CANet and its gradient boosting tree counterpart, CATree, consistently attain state-of-the-art performance, achieving up to 7.5% improvement in predictive accuracy. Our approach offers multiscale, mechanistic, interpretable,and generalizable models for predicting disease-mutation associations.
Adriano Hyeda, Élide Sbardellotto Mariano da Costa, Sérgio Candido Kowalski
Abstract Background Disability insurance represents a significant economic burden within Brazil’s social security system, yet long-term cost trends across disease groups remain understudied, hindering informed prevention and management strategies. Hospital costs, which account for approximately 40% of direct healthcare expenses, were selected as a comparative reference to contextualize the economic burden of disability insurance. Objective This study analyzes long-term cost trends of newly granted disability insurance by disease groups in Brazil, comparing them to public health system hospitalization expenses. Method This ecological time series study applied the inflection point regression model and Annual Average Percentage Change (AAPC) analysis, utilizing open-access federal government datasets. Annual rates and costs of disability insurance and hospitalizations were examined, categorized by International Classification of Diseases, 10th Revision (ICD-10) groups, and standardized per insured individuals and the general population. Results Between 2010 and 2019, the rate of temporary disability insurance granted (406 per 10,000 insureds) was 94% higher than permanent disability insurance (24 per 10,000), with women showing slightly higher rates but men incurring higher costs. The overall annual average rate of granted disability insurance (430 per 10,000 insureds) and its costs (BRL 5,084 per 100 insureds) were lower than those of hospitalizations (525 per 10,000 and BRL 5,870 per 100 Brazilians, respectively). Disabilities due to injuries, musculoskeletal disorders, and mental health problems had the highest rates (126, 89, and 40 per 10,000 insureds, respectively) and costs (BRL 1,455, 1,076, and 533 per 100 insureds, respectively). Neoplasms showed the only increasing trend in granted rates (AAPC 2.5%). The cost growth of granted disability insurance (AAPC 6.2%) was twice that of hospitalization costs (AAPC 2.9%), with disability insurance costs surpassing hospitalization expenses by 2018. Although most disease groups exhibited stable or declining trends in granted rates, costs increased across nearly all conditions. Conclusion The rising costs of disability insurance in Brazil highlight the growing economic burden of non-medical expenses and the need for evidence-based policies focused on prevention, management, and the sustainability of the social security system.
Javier Poyatos-García, Patricia Soblechero-Martín, Alessandro Liquori
et al.
Abstract Background Gene editing therapies in development for correcting out-of-frame DMD mutations in Duchenne muscular dystrophy aim to replicate benign spontaneous deletions. Deletion of 45–55 DMD exons (del45–55) was described in asymptomatic subjects, but recently serious skeletal and cardiac complications have been reported. Uncovering why a single mutation like del45–55 is able to induce diverse phenotypes and grades of severity may impact the strategies of emerging therapies. Cellular models are essential for this purpose, but their availability is compromised by scarce muscle biopsies. Methods We introduced, as a proof-of-concept, using CRISPR-Cas9 edition, a del45–55 mimicking the intronic breakpoints harboured by a subset of patients of this form of dystrophinopathy (designing specific gRNAs), into a Duchenne patient’s cell line. The edited cell line was characterized evaluating the dystrophin expression and the myogenic status. Results Dystrophin expression was restored, and the myogenic defects were ameliorated in the edited myoblasts harbouring a specific del45–55. Besides confirming the potential of CRISPR-Cas9 to create tailored mutations (despite the low cleavage efficiency of our gRNAs) as a useful approach to generate in vitro models, we also generated an immortalized myoblast line derived from a patient with a specific del45–55. Conclusions Overall, we provide helpful resources to deepen into unknown factors responsible for DMD-pathophysiology.
Rebecca Simonsson, Johan Högberg, Jakob Lindskog
et al.
Abstract Background Treatment volume can impact outcomes after surgical procedures of the knee between surgeons with high- and low-patient-volumes. However, the difference between physical therapeutic clinics with high- and low-volumes has not been widely researched. This registry study aims to investigate how patient volume affects knee function outcomes after anterior cruciate ligament (ACL) reconstruction at physical therapy (PT) clinics in terms of odds for a second ACL injury, return to pre-injury level of activity, perceived knee function, and recovery of strength and hop performance. Method Data were extracted from the Project ACL, a local rehabilitation registry. High- and low-volume clinics were defined based on the number of patients who attended different clinics. High-volume clinics were defined as those with > 100 patient registrations in Project ACL during the study period while low-volume clinics were those with ≤ 100 patient registrations. High- and low-volume clinics were compared, based on muscle function and patient-reported outcomes across 4 follow-ups, 2-, 4-, 8-, and 12 months, during the first year after ACL reconstruction, and odds of second ACL injury up to 2 years after ACL reconstruction. Result Of the 115 rehabilitation clinics included, 111 were classified as low-volume clinics and included 733 patients, and 4 as high-volume clinics which included 1221 patients. There were 31 (1.6%) second ACL injuries to the ipsilateral or contralateral side within the first 12 months and 68 (4.0%) within 2 years. No difference in the incidence of a second ACL injury, within 12 months follow-up odds ratio (OR) 0.95 [95% CI 0.46–1.97] or within 2 years follow-up OR 1.13 [95% CI 0.68–1.88], was found between high- and low-volume clinics. There were early (2 months) and non-clinically relevant differences in patient-reported outcomes (PROs) and physical activity levels early after ACL reconstruction in favor of high-volume clinics. One year after ACL reconstruction, no differences were observed between high- and low-volume clinics in terms of PROs, muscle function, and return to pre-injury level of activity. Conclusion No clinically relevant difference in the incidence of secondary ACL injuries in patients who underwent rehabilitation after ACL reconstruction at high- or low-volume physical therapist clinics was found. In addition, no clinically relevant differences in outcomes were found during the first year in terms of patient-reported outcomes, recovery of muscle function, or return to pre-injury level of activity.
Orthopedic surgery, Diseases of the musculoskeletal system
Skeletal muscle is one of the leading frameworks of the musculo-skeletal system, which works in synergy with the bones. Long skeletal muscles provide stability and mobility to the human body and are primarily composed of proteins. Conversely, improper functioning of various skeletal muscles leads to diseases and disorders, namely, age-related muscle disorder called sarcopenia, a group of genetic muscle disorders such as muscular dystrophies, and severe muscle wasting in cancer known as cachexia. However, skeletal muscle has an excellent ability to undergo hypertrophy and enhanced functioning during sustained exercise over time. Indeed, these processes of skeletal muscle regeneration/hypertrophy, as well as degeneration and atrophy, involve an interplay of various signaling pathways. Myostatin is one such chemokine/myokine with a significant contribution to muscle regeneration or atrophy in multiple conditions. In this review, we try to put together the role and regulation of myostatin as a function of muscle regeneration extrapolated to multiple aspects of its molecular functions.
Daniel Ordonez-Apraez, Mario Martin, Antonio Agudo
et al.
We present a comprehensive study on discrete morphological symmetries of dynamical systems, which are commonly observed in biological and artificial locomoting systems, such as legged, swimming, and flying animals/robots/virtual characters. These symmetries arise from the presence of one or more planes/axis of symmetry in the system's morphology, resulting in harmonious duplication and distribution of body parts. Significantly, we characterize how morphological symmetries extend to symmetries in the system's dynamics, optimal control policies, and in all proprioceptive and exteroceptive measurements related to the system's dynamics evolution. In the context of data-driven methods, symmetry represents an inductive bias that justifies the use of data augmentation or symmetric function approximators. To tackle this, we present a theoretical and practical framework for identifying the system's morphological symmetry group $\G$ and characterizing the symmetries in proprioceptive and exteroceptive data measurements. We then exploit these symmetries using data augmentation and $\G$-equivariant neural networks. Our experiments on both synthetic and real-world applications provide empirical evidence of the advantageous outcomes resulting from the exploitation of these symmetries, including improved sample efficiency, enhanced generalization, and reduction of trainable parameters.
The advancement of computer-aided detection systems had a significant impact on clinical analysis and decision-making on human disease. Lung cancer requires more attention among the numerous diseases being examined because it affects both men and women, increasing the mortality rate. LeNet, a deep learning model, is used in this study to detect lung tumors. The studies were run on a publicly available dataset made up of CT image data (IQ-OTH/NCCD). Convolutional neural networks (CNNs) were employed in the experiment for feature extraction and classification. The proposed system was evaluated on Iraq-Oncology Teaching Hospital/National Center for Cancer Diseases datasets the success percentage was calculated as 99.51%, sensitivity (93%) and specificity (95%), and better results were obtained compared to the existing methods. Development and validation of algorithms such as ours are important initial steps in the development of software suites that could be adopted in routine pathological practices and potentially help reduce the burden on pathologists.
Sun-Joon Yoo, Kyung-Hyun Kim, Dong-Kyu Chin
et al.
Objective This study aimed to evaluate the radiologic and clinical outcomes of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and conventional posterior lumbar interbody fusion (PLIF) at the L5–S1. Methods We retrospectively reviewed patients who underwent posterior lumbar fusion (MIS-TLIF and PLIF) at only the L5–S1 and were followed up for more than 12 months. Age, sex, body mass index (BMI), bone mineral density (BMD), diagnosis, comorbid conditions, fusion rate, perioperative results, and pre- and postoperative radiographic parameters at the L5–S1 level, pelvic parameters and degree of spondylolisthesis, and clinical results were analyzed. Results A total of 102 patients (46 male, 56 female) with a mean age of 57.1 years were evaluated. Fifty and fifty-two patients underwent MIS-TLIF and PLIF surgeries, respectively. Radiologic parameters increased from their preoperative measures at the last follow-up study; similarly, there were no intergroup differences. The fusion rates in the MIS-TLIF and PLIF groups were 86% and 82.7%, respectively. The subsidence rates in the MIS-TLIF and PLIF groups were 6% and 3.8%, respectively. There was no intergroup difference in terms of fusion rate and subsidence. Clinical outcomes also gradually improved after surgery in both groups without intergroup differences. Conclusion In L5–S1 posterior spinal surgery, there was no significant difference between MIS-TLIF and conventional PLIF. Considering the operation time and estimated blood loss, MIS-TLIF is more effective than PLIF surgery in terms of postoperative health care and economics.
Neurosciences. Biological psychiatry. Neuropsychiatry, Diseases of the musculoskeletal system
Complex diseases are caused by a multitude of factors that may differ between patients. As a result, hypothesis tests comparing all patients to all healthy controls can detect many significant variables with inconsequential effect sizes. A few highly predictive root causes may nevertheless generate disease within each patient. In this paper, we define patient-specific root causes as variables subject to exogenous "shocks" which go on to perturb an otherwise healthy system and induce disease. In other words, the variables are associated with the exogenous errors of a structural equation model (SEM), and these errors predict a downstream diagnostic label. We quantify predictivity using sample-specific Shapley values. This derivation allows us to develop a fast algorithm called Root Causal Inference for identifying patient-specific root causes by extracting the error terms of a linear SEM and then computing the Shapley value associated with each error. Experiments highlight considerable improvements in accuracy because the method uncovers root causes that may have large effect sizes at the individual level but clinically insignificant effect sizes at the group level. An R implementation is available at github.com/ericstrobl/RCI.
Qiaolan Deng, Jin Hyun Nam, Ayse Selen Yilmaz
et al.
Genome-wide association studies (GWAS) have successfully identified a large number of genetic variants associated with traits and diseases. However, it still remains challenging to fully understand functional mechanisms underlying many associated variants. This is especially the case when we are interested in variants shared across multiple phenotypes. To address this challenge, we propose graph-GPA 2.0 (GGPA 2.0), a novel statistical framework to integrate GWAS datasets for multiple phenotypes and incorporate functional annotations within a unified framework. We conducted simulation studies to evaluate GGPA 2.0. The results indicate that incorporating functional annotation data using GGPA 2.0 does not only improve detection of disease-associated variants, but also allows to identify more accurate relationships among diseases. We analyzed five autoimmune diseases and five psychiatric disorders with the functional annotations derived from GenoSkyline and GenoSkyline-Plus and the prior disease graph generated by biomedical literature mining. For autoimmune diseases, GGPA 2.0 identified enrichment for blood, especially B cells and regulatory T cells across multiple diseases. Psychiatric disorders were enriched for brain, especially prefrontal cortex and inferior temporal lobe for bipolar disorder (BIP) and schizophrenia (SCZ), respectively. Finally, GGPA 2.0 successfully identified the pleiotropy between BIP and SCZ. These results demonstrate that GGPA 2.0 can be a powerful tool to identify associated variants associated with each phenotype or those shared across multiple phenotypes, while also promoting understanding of functional mechanisms underlying the associated variants.
Elena Kozhemyakina, Minjie Zhang, Andreia Ionescu
et al.
ObjectiveTo generate knockin mice that express a tamoxifen‐inducible Cre recombinase from the Prg4 locus (Prg4GFPCreERt2 mice) and to use these animals to fate‐map the progeny of Prg4‐positive articular cartilage cells at various ages.MethodsWe crossed Prg4GFPCreERt2 mice with Rosa26floxlacZ or Rosa26mTmG reporter strains, admin‐istered tamoxifen to the double heterozygous offspring at different ages, and assayed Cre‐mediated recom‐bination by histochemistry and/or fluorescence microscopy.ResultsIn 1‐month‐old mice, the expression of the Prg4GFPCreERt2 allele mirrored the expression of endogenous Prg4 and, when tamoxifen was admin‐istered for 10 days, caused Cre‐mediated recombination in ∼70% of the superficial‐most chondrocytes. Prg4GFPCreERt2‐expressing cells were mostly confined to the top 3 cell layers of the articular cartilage in 1‐month‐old mice, but descendants of these cells were located in deeper regions of the articular cartilage in aged mice. On embryonic day 17.5, Prg4GFPCreERt2‐expressing cells were largely restricted to the superficial‐most cell layer of the forming joint, yet at ∼1 year, the progeny of these cells spanned the depth of the articular cartilage.ConclusionOur results suggest that Prg4‐expressing cells located at the joint surface in the embryo serve as a progenitor population for all deeper layers of the mature articular cartilage. Also, our findings indicate that Prg4GFPCreERt2 is expressed by superficial chondrocytes in young mice, but expands into deeper regions of the articular cartilage as the animals age. The Prg4GFPCreERt2 allele should be a useful tool for inducing efficient Cre‐mediated recombination of loxP‐flanked alleles at sites of Prg4 expression.