A national evaluation analysis and expert interview study of real-world data sources for research and healthcare decision-making.

Real-world data (RWD) can provide intel (real-world evidence, RWE) for research and development, as well as policy and regulatory decision-making along the full spectrum of health care. Despite calls from global regulators for international collaborations to integrate RWE into regulatory decision-making and to bridge knowledge gaps, some challenges remain. In this work, we performed an evaluation of Austrian RWD sources using a multilateral query approach, crosschecked against previously published RWD criteria and conducted direct interviews with representative RWD source samples. This article provides an overview of 73 out of 104 RWD sources in a national legislative setting where major attempts are made to enable secondary use of RWD (e.g. law on the organisation of research, "Forschungsorganisationsgesetz"). We were able to detect omnipresent challenges associated with data silos, variable standardisation efforts and governance issues. Our findings suggest a strong need for a national health data strategy and data governance framework, which should inform researchers, as well as policy- and decision-makers, to improve RWD-based research in the healthcare sector to ultimately support actual regulatory decision-making and provide strategic information for governmental health data policies.

In situ electrochemical regeneration of nanogap hotspots for continuously reusable ultrathin SERS sensors.

Surface-enhanced Raman spectroscopy (SERS) harnesses the confinement of light into metallic nanoscale hotspots to achieve highly sensitive label-free molecular detection that can be applied for a broad range of sensing applications. However, challenges related to irreversible analyte binding, substrate reproducibility, fouling, and degradation hinder its widespread adoption. Here we show how in-situ electrochemical regeneration can rapidly and precisely reform the nanogap hotspots to enable the continuous reuse of gold nanoparticle monolayers for SERS. Applying an oxidising potential of +1.5 V (vs Ag/AgCl) for 10 s strips a broad range of adsorbates from the nanogaps and forms a metastable oxide layer of few-monolayer thickness. Subsequent application of a reducing potential of -0.80 V for 5 s in the presence of a nanogap-stabilising molecular scaffold, cucurbit[5]uril, reproducibly regenerates the optimal plasmonic properties with SERS enhancement factors ≈106. The regeneration of the nanogap hotspots allows these SERS substrates to be reused over multiple cycles, demonstrating ≈5% relative standard deviation over at least 30 cycles of analyte detection and regeneration. Such continuous and reliable SERS-based flow analysis accesses diverse applications from environmental monitoring to medical diagnostics.

Patient stratification using plasma cytokines and their regulators in sepsis: relationship to outcomes, treatment effect and leucocyte transcriptomic subphenotypes.

RATIONALE: Heterogeneity of the host response within sepsis, acute respiratory distress syndrome (ARDS) and more widely critical illness, limits discovery and targeting of immunomodulatory therapies. Clustering approaches using clinical and circulating biomarkers have defined hyper-inflammatory and hypo-inflammatory subphenotypes in ARDS associated with differential treatment response. It is unknown if similar subphenotypes exist in sepsis populations where leucocyte transcriptomic-defined subphenotypes have been reported. OBJECTIVES: We investigated whether inflammatory clusters based on cytokine protein abundance were seen in sepsis, and the relationships with previously described transcriptomic subphenotypes. METHODS: Hierarchical cluster and latent class analysis were applied to an observational study (UK Genomic Advances in Sepsis (GAinS)) (n=124 patients) and two clinical trial datasets (VANISH, n=155 and LeoPARDS, n=484) in which the plasma protein abundance of 65, 21, 11 circulating cytokines, cytokine receptors and regulators were quantified. Clinical features, outcomes, response to trial treatments and assignment to transcriptomic subphenotypes were compared between inflammatory clusters. MEASUREMENTS AND MAIN RESULTS: We identified two (UK GAinS, VANISH) or three (LeoPARDS) inflammatory clusters. A group with high levels of pro-inflammatory and anti-inflammatory cytokines was seen that was associated with worse organ dysfunction and survival. No interaction between inflammatory clusters and trial treatment response was found. We found variable overlap of inflammatory clusters and leucocyte transcriptomic subphenotypes. CONCLUSIONS: These findings demonstrate that differences in response at the level of cytokine biology show clustering related to severity, but not treatment response, and may provide complementary information to transcriptomic sepsis subphenotypes. TRIAL REGISTRATION NUMBER: ISRCTN20769191, ISRCTN12776039.

SERS Sensing of Dopamine with Fe(III)-Sensitized Nanogaps in Recleanable AuNP Monolayer Films.

Sensing of neurotransmitters (NTs) down to nm concentrations is demonstrated by utilizing self-assembled monolayers of plasmonic 60 nm Au nanoparticles in close-packed arrays immobilized onto glass substrates. Multiplicative surface-enhanced Raman spectroscopy enhancements are achieved by integrating Fe(III) sensitizers into the precisely-defined <1 nm nanogaps, to target dopamine (DA) sensing. The transparent glass substrates allow for efficient access from both sides of the monolayer aggregate films by fluid and light, allowing repeated sensing in different analytes. Repeated reusability after analyte sensing is shown through oxygen plasma cleaning protocols, which restore pristine conditions for the nanogaps. Examining binding competition in multiplexed sensing of two catecholamine NTs, DA and epinephrine, reveals their bidentate binding and their interactions. These systems are promising for widespread microfluidic integration enabling a wide range of continuous biofluid monitoring for applications in precision health.

Microstructural Alterations in Tract Development in College Football and Volleyball Players: A Longitudinal Diffusion MRI Study.

BACKGROUND AND OBJECTIVES: Repeated impacts in high-contact sports such as American football can affect the brain's microstructure, which can be studied using diffusion MRI. Most imaging studies are cross-sectional, do not include low-contact players as controls, or lack advanced tract-specific microstructural metrics. We aimed to investigate longitudinal changes in high-contact collegiate athletes compared with low-contact controls using advanced diffusion MRI and automated fiber quantification. METHODS: We examined brain microstructure in high-contact (football) and low-contact (volleyball) collegiate athletes with up to 4 years of follow-up. Inclusion criteria included university and team enrollment. Exclusion criteria included history of neurosurgery, severe brain injury, and major neurologic or substance abuse disorder. We investigated diffusion metrics along the length of tracts using nested linear mixed-effects models to ascertain the acute and chronic effects of subconcussive and concussive impacts, and associations between diffusion changes with clinical, behavioral, and sports-related measures. RESULTS: Forty-nine football and 24 volleyball players (271 total scans) were included. Football players had significantly divergent trajectories in multiple microstructural metrics and tracts. Longitudinal increases in fractional anisotropy and axonal water fraction, and decreases in radial/mean diffusivity and orientation dispersion index, were present in volleyball but absent in football players (all findings |T-statistic|> 3.5, p value <0.0001). This pattern was present in the callosum forceps minor, superior longitudinal fasciculus, thalamic radiation, and cingulum hippocampus. Longitudinal differences were more prominent and observed in more tracts in concussed football players (n = 24, |T|> 3.6, p < 0.0001). An analysis of immediate postconcussion scans (n = 12) demonstrated a transient localized increase in axial diffusivity and mean/radial kurtosis in the uncinate and cingulum hippocampus (|T| > 3.7, p < 0.0001). Finally, within football players, those with high position-based impact risk demonstrated increased intracellular volume fraction longitudinally (T = 3.6, p < 0.0001). DISCUSSION: The observed longitudinal changes seen in football, and especially concussed athletes, could reveal diminished myelination, altered axonal calibers, or depressed pruning processes leading to a static, nondecreasing axonal dispersion. This prospective longitudinal study demonstrates divergent tract-specific trajectories of brain microstructure, possibly reflecting a concussive and repeated subconcussive impact-related alteration of white matter development in football athletes.

Persistent Pain as an Early Indicator for Operative Carpal Tunnel Revision after Primary Release: A Retrospective Analysis of Recurrent and Persistent Carpal Tunnel Syndrome.

BACKGROUND: Prolonged symptoms of carpal tunnel syndrome (CTS) after primary carpal tunnel release (CTR) can reduce the quality of life and lead to multiple referrals across specialties. The following study aimed to identify differences in symptoms, signs, and intraoperative findings between recurrent and persistent CTS cases to avoid undesired outcomes after primary CTR. METHODS: A retrospective analysis was conducted on revision CTRs performed between 2005 and 2015 using literature-based definitions for recurrent (a relapse of symptoms occurs following a symptom-free period of ≥3 months) and persistent (symptoms persisting longer than three months after surgical release) CTS. The parameters assessed were symptoms, clinical signs, and intraoperative findings. RESULTS: Out of 53 cases, 85% (n = 45) were external referrals, whereby our own revision rate was 0.67% (n = 8/1199). Paresthesia and numbness were frequent in both groups; however, abnormal postoperative pain was reported more often in persistent cases (86%; n = 30/35) in comparison to recurrent cases (50%; n = 9/18; p = 0.009). Scarring around the median nerve was observed in almost all recurrent cases (94%; n = 17/18) and in 40% (n = 14/35) of persistent cases (p < 0.001). Incomplete division of the palmar ligament was the primary cause for revision in the persistent cohort (49%; n = 17/35). CONCLUSIONS: For patients experiencing symptoms for more than three months after CTR, primarily presenting as pain, it is advisable to consider referring the patient to a certified hand clinic for additional evaluation.

Undergraduate Skills Training in Pandemic Times: Where Is the Future of Medical Education?

BACKGROUND: The COVID-19 pandemic forced medical programs to rapidly switch to remote teaching from scratch, impacting hands-on skills training. This study compared the efficacy of a hybrid online format to a regular in-person session for a mandatory surgical skills class. METHODS: Third-year undergraduate medical students attending the surgical skills class in the winter semester of 2020/21 at the Medical University of Graz were randomly assigned to either the hybrid or in-person class, depending on their course schedule and government regulations. The hybrid class involved online videos, one-on-one peer tutoring, and an Objective Structured Clinical Examination (OSCE). Pre- and post-class self-assessments were conducted to evaluate their theoretical and practical knowledge of a single interrupted suture. RESULTS: The study included 85 students in the regular in-person class and 50 in the hybrid class. A pre-class assessment revealed higher self-assessments in the hybrid class for theoretical and practical knowledge, but a post-class assessment showed no significant difference. The advantages and disadvantages of both modalities were identified, providing valuable insights for future curriculum development. CONCLUSIONS: Both teaching modes were effective for undergraduate surgical skills training. This study recommends implementing positive aspects of both the hybrid and in-person formats while recognizing their respective limitations.

Controlling Atomic-Scale Restructuring and Cleaning of Gold Nanogap Multilayers for Surface-Enhanced Raman Scattering Sensing.

We demonstrate the reliable creation of multiple layers of Au nanoparticles in random close-packed arrays with sub-nm gaps as a sensitive surface-enhanced Raman scattering substrate. Using oxygen plasma etching, all the original molecules creating the nanogaps can be removed and replaced with scaffolding ligands that deliver extremely consistent gap sizes below 1 nm. This allows precision tailoring of the chemical environment of the nanogaps which is crucial for practical Raman sensing applications. Because the resulting aggregate layers are easily accessible from opposite sides by fluids and by light, high-performance fluidic sensing cells are enabled. The ability to cyclically clean off analytes and reuse these films is shown, exemplified by sensing of toluene, volatile organic compounds, and paracetamol, among others.

The Efficacy of Regeneration Oil and Almond Oil on Split-Thickness Skin Graft Donor Sites: A Single-Blinded Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Essential oils are a complementary treatment and can play an important role in scar care. The aim of this study was to evaluate and compare the efficacy of a new essential oil (regeneration oil) with a control group on scar quality in healed split-thickness skin graft donor sites. MATERIALS AND METHODS: A single-center blinded randomized controlled study was performed on 30 patients with healed split-thickness skin graft donor site. The patients were randomly allocated into blended regeneration oil (n = 14) and pure almond oil (n = 16) groups. Application of the assigned oil occurred twice a day for 6 months. Scarring (Patient and Observer Scar Assessment Scale), itching (ITCH Assessment Scale) and scar discoloration (colorimetry) of the donor sites were assessed after 1, 3 and 6 months. RESULTS: We found no statistically significant differences between the groups in any applied parameter. We observed comparable outcomes (scar quality, itchiness, colorit) in healed split-thickness skin graft donor sites for both oils. CONCLUSIONS: Regeneration oil and control oil presented comparable results regarding scar quality, itchiness and colorit in healed split-thickness skin graft donor sites after 6 months of application. Both oils are suitable for skin/scar care in split-thickness skin graft donor sites.

Radiological Influencing Factors in the Diagnosis of Painful Habitual Instability of the Thumb Basal Joint as a Precursor of Carpometacarpal Arthritis of the Thumb-A Retrospective Study.

BACKGROUND: Painful habitual instability of the thumb basal joint (PHIT) is a rarely diagnosed condition that can severely impair hand function. Furthermore, it can increase the risk of developing carpometacarpal arthritis of the thumb (CMAOT). Clinical examination and radiographic imaging provide the foundation for a correct diagnosis, but early detection is still challenging. We investigated two objective, radiographically obtainable parameters as potential risk factors for PHIT. METHODS: Clinical data and radiographic images of 33 patients suffering from PHIT were collected and compared to those of 35 people serving as the control group. The two main objectives, the slope angle and the bony offset of the thumb joint, were gathered from the X-rays and statistically analyzed. RESULTS: The analysis showed no differences between the study and the control group concerning the slope angle. Gender and the bony offset, on the other hand, had a significant influence. Female sex and higher offset values were associated with an increased risk of PHIT. CONCLUSIONS: The results of this study prove a connection between a high bony offset and PHIT. We believe this information can be valuable in early detection and will allow more efficient treatment of this condition in the future.

Textured vs. Smooth Breast Implants Using the Jones Criteria-What Is the Currently Available Evidence for BIA-ALCL?: A Systematic Review.

Breast-Implant-Associated Anaplastic Large-Cell Lymphoma (BIA-ALCL) is a rare low-incidence type of T-cell non-Hodgkin lymphoma, arising in the capsule around breast implants, and predominantly associated with the use of macro-textured breast implants. The purpose of this study was to use an evidence-based approach to systematically identify clinical studies comparing smooth and textured breast implants in women with regard to the risk of developing BIA-ALCL. METHODS: A literature search in PubMed in April 2023 and the article reference list of the French National Agency of Medicine and Health Products decision from 2019 were screened for applicable studies. Only clinical studies where the Jones surface classification could be applied (required information: breast implant manufacturer) for comparison of smooth and textured breast implants were considered. RESULTS: From a total of 224 studies, no articles were included due to the lack of fit to the strict inclusion criteria. CONCLUSIONS: Based on the scanned and included literature, implant surface types in relation to the incidence of BIA-ALCL were not evaluated in clinical studies and data from evidence-based clinical sources plays a minor to no role in this context. An international database that combines breast implant-related data from (national, opt-out) medical device registries is, therefore, the best available option to obtain relevant long-term breast implant surveillance data on BIA-ALCL.

Workflow assessment of an augmented reality application for planning of perforator flaps in plastic reconstructive surgery: Game or game changer?

Objective: In contrast to the rising amount of financial investments for research and development in medical technology worldwide is the lack of usability and clinical readiness of the produced systems. We evaluated an augmented reality (AR) setup under development for preoperative perforator vessel mapping for elective autologous breast reconstruction. Methods: In this grant-supported research pilot, we used magnetic resonance angiography data (MR-A) of the trunk to superimpose the scans on the corresponding patients with hands-free AR goggles to identify regions-of-interest for surgical planning. Perforator location was assessed using MR-A imaging (MR-A projection) and Doppler ultrasound data (3D distance) and confirmed intraoperatively in all cases. We evaluated usability (System Usability Scale, SUS), data transfer load and documented personnel hours for software development, correlation of image data, as well as processing duration to clinical readiness (time from MR-A to AR projections per scan). Results: All perforator locations were confirmed intraoperatively, and we found a strong correlation between MR-A projection and 3D distance measurements (Spearman r = 0.894). The overall usability (SUS) was 67 ± 10 (=moderate to good). The presented setup for AR projections took 173 min to clinical readiness (=availability on AR device per patient). Conclusion: In this pilot, we calculated development investments based on project-approved grant-funded personnel hours with a moderate to good usability outcome resulting from some limitations: assessment was based on one-time testing with no previous training, a time lag of AR visualizations on the body and difficulties in spatial AR orientation. The use of AR systems can provide new opportunities for future surgical planning, but has more potential for educational (e.g., patient information) or training purposes of medical under- and postgraduates (spatial recognition of imaging data associated with anatomical structures and operative planning). We expect future usability improvements with refined user interfaces, faster AR hardware and artificial intelligence-enhanced visualization techniques.

Minimally Invasive Treatment of Trapeziometacarpal Osteoarthritis: Results of a Blinded Randomized Controlled Trial.

BACKGROUND: Surgical therapy for widespread first carpometacarpal (CMC1) arthritis permanently alters the physiologic anatomy of the hand. The injection of autologous substances into the thumb saddle joint could achieve temporary pain relief and delay surgical indications. This trial aimed to compare the pain-reducing effects of autologous fat and/or platelet-rich plasma (PRP) with saline 0.9% in the infiltration therapy of carpometacarpal arthritis of the thumb (CMC1 arthritis). METHODS: A blinded, randomized controlled trial was conducted. Ninety-five patients with CMC1 arthritis were included in the study. The mean follow-up period was 2 years. Participants were injected with 1.5 mL of autologous fat, PRP, autologous fat and PRP, or 0.9% saline solution into the CMC1 joint, depending on the group allocation. The primary outcome of this study was the evaluation of pain reduction in each treatment group. RESULTS: The combination of fat and PRP was the only treatment that resulted in a significantly greater reduction in pain compared with 0.9% saline ( P = 0.003). Similarly, fat and PRP in combination was the only therapy group to achieve clinically relevant Quick Disabilities of Arm, Shoulder, and Hand score reduction, and the only group that showed a significantly better Medical Outcomes Study 36-Item Short-Form Health Survey score than 0.9% saline ( P = 0.016). No major complications were noted. CONCLUSIONS: In addition to pain reduction, the combination of autologous fat and PRP yields a relevant improvement in hand function and a corresponding improvement in quality of life. This treatment seems to be a viable and safe alternative to short-acting glucocorticoids. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

How to use X-ray templating to guide minimally invasive screw removal.

A How to Do It article describing the use of X-ray templating to guide minimally invasive surgical screw removal. By calibrating X-ray measurements using the screw itself as a template marker, we propose a method to reduce incision size and operative time to minimise the risks associated with screw removal.

Plasmonic Sensing Assay for Long-Term Monitoring (PSALM) of Neurotransmitters in Urine.

A liquid-based surface-enhanced Raman spectroscopy assay termed PSALM is developed for the selective sensing of neurotransmitters (NTs) with a limit of detection below the physiological range of NT concentrations in urine. This assay is formed by quick and simple nanoparticle (NP) "mix-and-measure" protocols, in which FeIII bridges NTs and gold NPs inside the sensing hotspots. Detection limits of NTs from PreNP PSALM are significantly lower than those of PostNP PSALM, when urine is pretreated by affinity separation. Optimized PSALM enables the long-term monitoring of NT variation in urine in conventional settings for the first time, allowing the development of NTs as predictive or correlative biomarkers for clinical diagnosis.

Clinical Applications of Three-Dimensional Printing in Upper Extremity Surgery: A Systematic Review.

Three-dimensional printing for medical applications in surgery of the upper extremity has gained in popularity as reflected by the increasing number of publications. This systematic review aims to provide an overview of the clinical use of 3D printing in upper extremity surgery. METHODS: We searched the databases PubMed and Web of Science for clinical studies that described clinical application of 3D printing for upper extremity surgery including trauma and malformations. We evaluated study characteristics, clinical entity, type of clinical application, concerned anatomical structures, reported outcomes, and evidence level. RESULTS: We finally included 51 publications with a total of 355 patients, of which 12 were clinical studies (evidence level II/III) and 39 case series (evidence level IV/V). The types of clinical applications were for intraoperative templates (33% of a total of 51 studies), body implants (29%), preoperative planning (27%), prostheses (15%), and orthoses (1%). Over two third of studies were linked to trauma-related injuries (67%). CONCLUSION: The clinical application of 3D printing in upper extremity surgery offers great potential for personalized approaches to aid in individualized perioperative management, improvement of function, and ultimately help to benefit certain aspects in the quality of life.

Introducing the "SIMline"-A Simulation Course in the Management of Severe Burns as a Tool in Undergraduate Medical Education.

Background: Management of burn injuries presents a complex and challenging situation for medical staff, especially for inexperienced young doctors. However, training on how to treat burn victims in the clinical setting is rarely taught in undergraduate medical classes. We have created the "SIMline", a simulation training program explicitly designed for coaching medical students in burn management. Methods: A total of 43 students participated in the "SIMline" course, which took place at the training facility at the Medical University of Graz, between 2018 and 2019. The course provided theoretical classes, practical exercises, and a full-scale care process simulation training. The learning progress of the students was monitored via a formative integrated test. Results: Students showed great progress throughout the course of the "SIMline" program, as their test scores improved by an average of 88%. The passing rate was 0% at the first exam (prior to course) as compared to 87% at the final exam, taken after the training. Conclusions: Comprehensive practical training programs in burn care are underrepresented in medical education. The "SIMline" course presents a novel and effective approach in training medical students in burn management. However, follow-up evaluation is necessary to confirm long-term educational benefits.

Changes in pectoralis major stiffness and thickness following radiotherapy for breast cancer: A 12-month follow-up case series.

Radiotherapy (RT) is a common and often essential treatment for breast cancer, but has been associated with pectoralis major (PM) muscle fibrosis and atrophy. In an initial prospective evaluation, we assessed muscle stiffness and muscle thickness of the sternocostal and clavicular regions of the PM with ultrasound shear wave elastography and B-mode imaging. Changes in PM muscle stiffness and thickness following RT can be detected within the first twelve months of RT completion. These parameters may potentially be useful for screening of patients who would benefit from post-RT physical therapy. Further studies with larger sample sizes that include patients who receive nodal radiation are necessary to confirm these findings.

Autologous Fat and Platelet-Rich Plasma Injections in Trapeziometacarpal Osteoarthritis: A Systematic Review and Meta-Analysis.

BACKGROUND: For the treatment of carpometacarpal arthritis of the thumb, various therapies are used. Infiltration therapy with autologous substances such as platelet-rich plasma and autologous fat have recently gained increasing attention because of beneficial pain-reducing effects in arthritis and the associated regenerative potential. However, the extent of clinical evidence in this area and how well autologous substances work in terms of pain reduction and improvements in hand function remain unclear. METHODS: A systematic review and meta-analysis were conducted to evaluate the current evidence and to provide more insight into pain reduction and improvement in hand function after infiltration of autologous substances. The authors identified 11 clinical trials, of which we included eight in the meta-analysis. RESULTS: Autologous substances achieved a good and long-lasting pain reduction, which may also be accompanied by corresponding improvement in hand function. Autologous substances appear to be more effective than corticoid infiltrations. The infiltration of autologous fat seems to be particularly promising in more advanced stages of carpometacarpal arthritis of the thumb. Our meta-analysis showed a mean pain reduction of 2.4 to 3 in visual analogue scale score and a reduction of 18 to 19 points in the Disabilities of the Arm, Shoulder, and Hand questionnaire after infiltration with autologous substances. CONCLUSION: Both platelet-rich plasma and autologous fat infiltration offer an efficient and long-lasting, minimally invasive therapy option in the treatment of carpometacarpal arthritis of the thumb.

Identifying the molecular drivers of ALS-implicated missense mutations.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressively fatal, neurodegenerative disease associated with both motor and non-motor symptoms, including frontotemporal dementia. Approximately 10% of cases are genetically inherited (familial ALS), while the majority are sporadic. Mutations across a wide range of genes have been associated; however, the underlying molecular effects of these mutations and their relation to phenotypes remain poorly explored. METHODS: We initially curated an extensive list (n=1343) of missense mutations identified in the clinical literature, which spanned across 111 unique genes. Of these, mutations in genes SOD1, FUS and TDP43 were analysed using in silico biophysical tools, which characterised changes in protein stability, interactions, localisation and function. The effects of pathogenic and non-pathogenic mutations within these genes were statistically compared to highlight underlying molecular drivers. RESULTS: Compared with previous ALS-dedicated databases, we have curated the most extensive missense mutation database to date and observed a twofold increase in unique implicated genes, and almost a threefold increase in the number of mutations. Our gene-specific analysis identified distinct molecular drivers across the different proteins, where SOD1 mutations primarily reduced protein stability and dimer formation, and those in FUS and TDP-43 were present within disordered regions, suggesting different mechanisms of aggregate formation. CONCLUSION: Using our three genes as case studies, we identified distinct insights which can drive further research to better understand ALS. The information curated in our database can serve as a resource for similar gene-specific analyses, further improving the current understanding of disease, crucial for the development of treatment strategies.