medRxiv : the preprint server for health sciences最新文献

{"title":"Comparison of Nanopore with Illumina Whole Genome Assemblies of the Epstein-Barr Virus in Burkitt Lymphoma.","authors":"Isaac E Kim, Abebe A Fola, Enrique Puig, Titus K Maina, Sin Ting Hui, Hongyu Ma, Kaleb Zuckerman, Eddy Agwati, Alec Leonetti, Rebecca Crudale, Micah A Luftig, Ann M Moormann, Cliff Oduor, Jeffrey A Bailey","doi":"10.1101/2025.02.21.25322471","DOIUrl":"10.1101/2025.02.21.25322471","url":null,"abstract":"<p><p>Endemic Burkitt lymphoma (eBL) is one of the most prevalent cancer in children in sub-Saharan Africa, and while prior studies have found that Epstein-Barr virus (EBV) type and variation may alter the tumor driver genes necessary for tumor survival, the precise relationship between EBV variation and EBV-associated tumorigenesis remains unclear due to lack of scalable, cost-effective, viral whole-genome sequencing from tumor samples. This study introduces a rapid and cost-effective method of enriching, sequencing, and assembling accurate EBV genomes in BL tumor cell lines through a combination of selective whole genome amplification (sWGA) and subsequent 2-tube multiplex polymerase chain reaction along with long-read sequencing with a portable sequencer. The method was optimized across a range of parameters to yield a high percentage of EBV reads and sufficient coverage across the EBV genome except for large repeat regions. After optimization, we applied our method to sequence 18 cell lines and 3 patient tumors from fine needle biopsies and assembled them with median coverages of 99.62 and 99.68%, respectively. The assemblies showed high concordance (99.61% similarity) to available Illumina-based assemblies. The improved method and assembly pipeline will allow for better understanding of EBV variation in relation to BL and is applicable more broadly for translational research studies, especially useful for laboratories in Africa where eBL is most widespread.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural history of patients with autosomal dominant <i>WFS1</i> pathogenic variants associated with sensorineural hearing loss and optic atrophy.","authors":"Jessica P Roberts, Abby F Tang, Daniela Hernandez, Brianna Carman, Liam Oiknine, Cris Brown, Stacy Hurst, Fumihiko Urano","doi":"10.1101/2025.02.23.25322342","DOIUrl":"10.1101/2025.02.23.25322342","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Autosomal dominant pathogenic variants in the WFS1 gene can cause a broad spectrum of WFS1-related disorders. These disorders present with a range of phenotypic manifestations, including isolated low-frequency sensorineural hearing loss, optic nerve atrophy accompanied by low- to mid-frequency sensorineural hearing loss, isolated diabetes mellitus, and early-onset cataracts. In general, WFS1-related disorders represent a milder spectrum of conditions linked to pathogenic WFS1 variants, except for Hattersley-Urano syndrome, which is characterized by early-onset diabetes mellitus, optic nerve atrophy, cataracts, hypotonia, intellectual disability, and developmental delay. By contrast, autosomal recessive WFS1 variants result in Wolfram Syndrome type 1, a rare neurodegenerative disorder characterized by early-onset diabetes mellitus, optic nerve atrophy, arginine vasopressin deficiency, hearing loss, and cerebellar and brainstem atrophy. Although WFS1-related disorders have been increasingly recognized, additional data are needed to understand their clinical progression and long-term outcomes. Our study aims to expand knowledge on the severity and progression of WFS1-related disorders by reviewing clinical data from patients with autosomal dominant pathogenic WFS1 variants.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Approach: &lt;/strong&gt;We obtained clinical data from the Washington University International Registry and Clinical Study for Wolfram Syndrome and related disorders and the Endoplasmic Reticulum Disease Patient Registry and Biorepository. We included participants with autosomal dominant WFS1 pathogenic variants who were diagnosed with optic nerve atrophy and sensorineural hearing loss. Eleven participants with autosomal dominant WFS1 variants meeting these criteria were identified.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The 11 cases included five distinct autosomal dominant WFS1 variants: c.923C&gt;G (p.Ser308Cys), c.2051C&gt;T (p.Ala684Val), c.2389G&gt;T (p.Asp797Tyr), c.2456A&gt;C (p.Gln819Pro), and c.2590G&gt;A (p.Glu864Lys). Among these, the p.Gln819Pro variant has not been previously reported in the literature. The median age of optic atrophy diagnosis was 10 years (quartiles: 6.0 and 19.0 years). Visual acuity did not significantly differ between the left (OS) and right (OD) eyes (p = 0.8901). The least square best-corrected visual acuity (BCVA) mean for the right eye was 0.2114 ± 0.01903 and for the left eye, 0.2153 ± 0.01903. Age was not significantly related to best eye BCVA (p = 0.9196), with an estimated change of -0.0002 (95% CI [-0.003, 0.003]) per year. Patient age was also not correlated with binocular BCVA (p = 0.5994), with an estimated change of 0.00075 (95% CI [-0.0021, 0.0036]) per year. Mean retinal nerve fiber layer (RNFL) thickness was not significantly related to age (p = 0.1604), with an estimated annual change of 0.1486 (95% CI [-0.659, 0.363]). However, removing an influential outlier resulted in a significant relationship between RNF","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of Machine Learning Models for Adverse Events after Cardiac Surgery.","authors":"Qingchu Jin, Saeed Amal, Jaime B Rabb, Felistas Mazhude, Venkatesh Shivandi, Robert S Kramer, Douglas B Sawyer, Raimond L Winslow","doi":"10.1101/2025.02.24.25322811","DOIUrl":"10.1101/2025.02.24.25322811","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Early recognition of adverse events after cardiac surgery is vital for treatment. However, the widely used Society of Thoracic Surgery (STS) risk model has modest performance in predicting adverse events and only applies &lt;80% of cardiac surgeries.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To develop and validate machine learning (ML) models for predicting outcomes after cardiac surgery.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design setting and participants: &lt;/strong&gt;ML models, referred as Roux-MMC model, were developed and validated using a retrospective cohort extracted from the STS Adult Cardiac Surgery Database (ACSD) at Maine Medical Center (MMC) between January 2012 to December 2021. It was further validated on a prospective cohort of MMC between January 2022 to February 2024. The performance of Roux-MMC model is compared with the STS model. &lt;b&gt;Exposure&lt;/b&gt; cardiac surgery.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;Postoperative outcomes: mortality, stroke, renal failure, reoperation, prolonged ventilation, major morbidity or mortality, prolonged length of stay (PLOS) and short length of stay (SLOS). Primary measure: area under the receiver-operating curve (AUROC).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A retrospective cohort of 9,841 patients (median [IQR] age, 67 [59-74] years; 7,127 [72%] males) and a prospective cohort of 2,305 patients (median [IQR] age, 67 [59-73] years; 1,707 [74%] males) were included. In the prospective cohort, the Roux-MMC model achieves performance for prolonged ventilation (AUROC 0.911 [95% CI, 0.887-0.935]), PLOS (AUROC 0.875 [95% CI, 0.848-0.898]), renal failure (AUROC 0.878 [95% CI, 0.829-0.921]), mortality (AUROC 0.882 [95% CI, 0.837-0.920]), reoperation (AUROC 0.824 [95% CI, 0.787-0.860]), SLOS (AUROC 0.818 [95% CI, 0.801-0.835]) and major morbidity or mortality (AUROC 0.859 [95% CI, 0.832-0.884]). The Roux-MMC model outperforms the STS model for all 8 outcomes, achieving 0.020-0.167 greater AUROC. The Roux-MMC model covers all cardiac surgery patients, while the STS model applies to only 65% in the retrospective and 77% in the prospective cohorts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion and relevance: &lt;/strong&gt;We developed ML models to predict 8 postoperative outcomes on all cardiac surgery patients using preoperative and intraoperative variables. The Roux-MMC model outperforms the STS model in the prospective cohort. The Roux-MMC model is built on STS ACSD, a data system used in ∼1000 US hospitals, thus, it has the potential to easily applied in other hospitals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key points: &lt;/strong&gt;&lt;b&gt;Question&lt;/b&gt; . Can a predictive model be developed using preoperative and intraoperative variables from the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) to accurately predict adverse events after cardiac surgery? &lt;b&gt;Findings.&lt;/b&gt; Machine learning (ML) models developed and validated on a retrospective cohort of 9,841 patients. In the prospective validation cohort, models demonstrated good discrimin","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan T cells, Helper T cells, and Regulatory T cells are Associated with Negative Symptoms in Persons with Anti-Gliadin Antibody Positive Schizophrenia and Related Disorders.","authors":"Deepak Salem, Sarah M Clark, Daniel J O Roche, Nevil J Singh, Monica V Talor, Robert W Buchanan, Valerie Harrington, Zhenyao Ye, Shuo Chen, Deanna L Kelly","doi":"10.1101/2025.02.24.25322815","DOIUrl":"10.1101/2025.02.24.25322815","url":null,"abstract":"<p><strong>Background: </strong>About one in three persons with a schizophrenia related disorder (SRD) have elevated anti-gliadin IgG antibodies (AGA). This AGA positive (AGA+) subgroup of SRD clinically has a higher burden of negative symptoms and are symptoms associated with high functional impairments with a lack of effective therapeutics. Alterations in T cells have been demonstrated in SRD, and we have previously shown regulatory T cells (Tregs) are increased and correlate with fewer negative symptoms in persons with SRD compared with healthy controls.</p><p><strong>Methods: </strong>To further elucidate the role of the immune system in AGA+ SRD pathology, we investigated the relationship of T cells and negative symptoms in 26 medicated and clinically stable persons with SRD. Participants had blood drawn; AGA-IgG measured by ELISA (AGA positive defined as ≥20 U); had flow cytometry performed to quantify proportions of pan T cells (CD3+), helper T cells (CD3+CD4+), Tregs (CD3+CD4+CD25+Foxp3+), and activated Tregs (aTregs) (CD3+CD4+CD25+Foxp3+RA-); had serum cytokines measured; and completed the Scale for the Assessment of Negative Symptoms (SANS) to measure negative symptoms.</p><p><strong>Results: </strong>46% of persons with SRD in this study were AGA+ and, in this group specifically, pan-T cells were correlated with worse SANS total, anhedonia, alogia, and avolition (p<0.05), while helper T cells and Tregs were correlated with less negative symptoms (respectively, SANS total and alogia; SANS total, anhedonia, alogia; P<0.05). AGA+ persons with SRD also had several elevated serum cytokines, corresponding with a broadly pro-inflammatory phenotype.</p><p><strong>Conclusions: </strong>These hypothesis-generating findings highlight T cell dysfunction in AGA+ positive SRD, suggesting Tregs protecting against negative symptom severity but also an unidentified other T cell population to possibly be driving negative symptom severity.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distress is positively associated with induced secondary hyperalgesia in people with suppressed HIV.","authors":"Luyanduthando Mqadi, Gillian J Bedwell, Ncumisa Msolo, Gwendoline Arendse, Maia Lesosky, Peter R Kamerman, Mark R Hutchinson, Andrew Schrepf, Robert R Edwards, John A Joska, Romy Parker, Victoria J Madden","doi":"10.1101/2025.01.27.25321015","DOIUrl":"10.1101/2025.01.27.25321015","url":null,"abstract":"<p><p>Pain and distress are frequently reported by people with HIV. Although pain is widely acknowledged to contribute to distress, distress may also contribute to pain and its persistence. Given the evidence supporting a relationship between distress and clinical pain, the current study investigated the relationships between distress, secondary hyperalgesia (SH), and persistent pain in people with HIV, reporting pain (n=19) or being pain free (n=26). We anticipated that SH is an important link between distress and persistent pain, with distress potentially exacerbating pain by increasing the responsiveness of neurons in the central nervous system to nociceptive signalling. Our primary hypothesis was that self-reported distress would be positively associated with the induced surface area (primary measure) and magnitude (secondary measure) of SH. The secondary hypothesis was that individuals with persistent pain would display greater induced SH compared to those who reported being pain-free. The results showed that distress was positively associated with the surface area (p=0.02) and the magnitude (p=0.01) of induced SH. However, participants with persistent pain showed no difference in the surface area of SH compared to pain-free participants (p=0.87), and those with pain displayed a marginally lower magnitude of SH (p=0.05). These findings suggest that distress may be a worthy target of interventions in people exposed to acutely painful events. While this relationship may not be specific to people with HIV, further research is needed to establish its relevance to people without HIV.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11838949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonstandard coding of deceased-donor kidney out-of-sequence allocation leads to underrecognition of allocation deviations.","authors":"Emma G Tucker, Miko E Yu, Joel T Adler, David C Cron, Prateek V Sahni, Jesse D Schold, Sumit Mohan, Syed Ali Husain","doi":"10.1101/2025.02.24.25322786","DOIUrl":"10.1101/2025.02.24.25322786","url":null,"abstract":"<p><p>Out-of-sequence (OOS) allocation, the process by which organ procurement organizations (OPOs) can deviate from standard rank lists of potential recipients to expeditiously allocate deceased-donor kidneys, is rising in the U.S. We aimed to determine whether current OPO reporting practices obscure the extent of OOS allocation. Using match-run data for all U.S. deceased-donor kidney transplants from 2021-2023, we defined \"miscoded\" OOS (mOOS) allocation transplants as those with use of the 799 or 898 OPO- initiated refusal codes (\"other, specify\") with free text responses clearly indicating OOS allocation, and compared these to \"explicit\" OOS (eOOS) allocation, wherein OOS transplants are appropriately coded using refusal codes 861-863. We found that the prevalence of mOOS allocation increased from 2021 (122 transplants) to 2023 (430 transplants) and accounted for 12% of all OOS transplants by 2023. Organs allocated via mOOS had a lower median KDPI than those allocated via eOOS (51% vs 55%, p <0.01). While an increasing number of OPOs used mOOS throughout the study period, the practice remained concentrated overall, with 5 \"outlier\" OPOs performing 66% of mOOS allocations in 2023. These findings highlight the need for stricter oversight of organ allocation and underscore the responsibility of the OPTN to ensure proper data reporting.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Traumatic Encephalopathy Neuropathologic Change is Infrequent Following Isolated Moderate-Severe Traumatic Brain Injury.","authors":"E Selmanovic, A Pruyser, A C Seifert, B N Delman, E L Thorn, R Folkerth, K Dams-O'Connor","doi":"10.1101/2025.02.24.25322800","DOIUrl":"10.1101/2025.02.24.25322800","url":null,"abstract":"<p><p>Chronic traumatic encephalopathy-neuropathologic change (CTE-NC) has been primarily studied in contact sport athletes with repetitive head impacts (RHI). An association with isolated traumatic brain injury (TBI) is less clear. We systematically reviewed the autopsied cohort of Late Effects of TBI (LETBI), characterized primarily by isolated TBI but also including RHI, for features of CTE-NC. A consecutive series of 44 brains underwent comprehensive neuropathologic evaluation, exceeding recommended CTE consensus protocols. Of the 44, 6 (13.6%) (age range, 3 ^rd -7 ^th decades; median, 6 ^th decade) had CTE-NC, forming the basis for this exploratory analysis. Ex vivo neuroimaging (in 4 of 6) highlighted traumatic and white matter microvascular lesions, facilitating histological sampling of subtle neuropathologies that might otherwise have been missed by conventional sectioning. Macroscopically, 5 had cortical (contusional) and white matter (torsional) volume loss, with septal lesions and hydrocephalus ex vacuo (i.e., structural lesions of moderate-severe TBI). Microscopically, tau-immunopositive neuronal and astrocytic pathology in a perivascular arrangement within sulcal depths met current pathognomonic criteria for CTE-NC in 5 (3 \"low\" and 2 \"high\" burden); 1 had more limited findings considered \"suspicious\" for CTE-NC. Five of 6 cases with any CTE-NC reported substantial exposure to RHI, through contact sport ranging over at least 16 years. One case had no known exposure to RHI: this case (death: 6th decade) had 2 isolated severe TBIs (sustained 30y and 3y prior to death). Of note, one case with \"high\" CTE also had Alzheimer Disease Neuropathologic Change (high stage), Lewy Body Disease (limbic), and TDP43 accumulation (\"polyproteinopathy\"). Aging-related tau astrogliopathy, mostly subpial, was seen in 4 cases. Glial tau was also noted around old cavitary contusions in 2. These findings converge with prior studies demonstrating that CTE is largely associated with RHI and is infrequent among individuals with isolated TBI.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic profiling of plasma extracellular vesicles identifies signatures of innate immunity, coagulation, and endothelial activation in septic patients.","authors":"Chanhee Park, Taekyung Ryu, Rashida Mohamed-Hinds, Kyungdo Kim, Jin Hyeok Kim, Lin Zou, Brittney Williams, Chan Hyun Na, Wei Chao","doi":"10.1101/2025.02.21.25322420","DOIUrl":"10.1101/2025.02.21.25322420","url":null,"abstract":"<p><p>Plasma extracellular vesicles (EVs) are cell-derived lipid particles and reportedly play a role in sepsis pathogenesis. This study aimed to identify EV cargo proteins in septic patients and explore their association with key sepsis pathophysiology. Plasma EVs were subjected to Tandem Mass Tag (TMT)-based quantitative proteomic analysis. We identified 522 differentially expressed (DE) EV proteins in septic patients (n=15) compared to the healthy controls (n=10). The KEGG analysis of the DE proteins revealed multiple functional pathways linked to sepsis, <i>e.g.,</i> complement/coagulation, platelet activation, phagosome, inflammation, and neutrophil extracellular trap formation. Weighted Gene Coexpression Network Analysis of 1,642 EV proteins identified nine unique protein modules, some of which were highly correlated with the sepsis diagnosis and diverse plasma markers, including organ injury, inflammation, coagulopathy, and endothelial activation. Cell type-specific enrichment analysis revealed the cellular origins of EVs, including immune and epithelial cells, neurons, and glial cells. Thus, the current study discovered complex proteomic signatures in plasma EVs that are closely associated with key pathophysiological responses in sepsis. These findings support the importance of EV cargo proteins in the patients' immune responses, coagulation, and endothelial activation and lay the foundation for future mechanistic study of plasma EVs in sepsis pathogenesis.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perceptions of Telerehabilitation Among Patients Receiving Physical Therapy for Spine Pain.","authors":"Kevin H McLaughlin, Olivia Caan, Richard L Skolasky","doi":"10.1101/2025.02.24.25322777","DOIUrl":"10.1101/2025.02.24.25322777","url":null,"abstract":"<p><strong>Importance: </strong>Telerehabilitation was widely used during the COVID-19 pandemic to maintain access to physical therapy. However, its use has declined since the pandemic, potentially due to changes in patient demand.</p><p><strong>Objective: </strong>To explore patients' beliefs, attitudes, and preferences regarding telerehabilitation for spine pain treatment.</p><p><strong>Design: </strong>Email or telephone administered survey.</p><p><strong>Setting: </strong>Outpatient physical therapy network affiliated with an academic healthcare system.</p><p><strong>Participants: </strong>Patients recently evaluated for spine pain by a physical therapist (n=100).</p><p><strong>Main outcomes and measures: </strong>Survey items addressed patients' perceptions of telerehabilitation effectiveness, preferences for care delivery, barriers to telerehabilitation, and factors influencing telerehabilitation use.</p><p><strong>Results: </strong>Patients viewed telerehabilitation as effective for treating spine pain but not as effective as in-clinic physical therapy. Patients reported a preference for receiving care in-clinic care or using a hybrid model, rather than receiving care through telerehabilitation alone. Barriers to telerehabilitation included a lack of awareness of who offers telerehabilitation and uncertainty about its effectiveness. Patients indicated that evidence supporting telerehabilitation effectiveness would increase their likelihood of using telerehabilitation in the future. Patients also reported that transportation challenges or increased COVID-19 rates would encourage them to use telerehabilitation in the future.</p><p><strong>Conclusions: </strong>The results of this survey suggest that patients with spine pain believe telerehabilitation may be an effective treatment approach, but they are skeptical about using telerehabilitation instead of in-clinic physical therapy. These results also suggest that patients are open to hybrid approaches that incorporate telerehabilitation, as well as using telerehabilitation if circumstances prevented them from receiving their care in-clinic. The largest patient concern surrounding telerehabilitation seems to be the lack of evidence supporting its effectiveness.</p><p><strong>Relevance: </strong>This study suggests that patients believe telerehabilitation will continue to play an important role post-pandemic. However, comparative effectiveness research is needed to address patient concerns surrounding the effectiveness of telerehabilitation and guide informed decision-making.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SmART-TBI: A fully remote protocol for a randomized placebo-controlled double-blinded clinical trial for a dietary supplement to improve sleep in Veterans.","authors":"Jonathan E Elliott, Savanah J Sicard, Cosette Olivo, Hannah A Cunningham, Arlynn E Ekis, Katherine L Powers, Jessica S Brewer, Jennifer D'Silva, Sarah Happ, Andrea Hildebrand, Akiva Cohen, Miranda M Lim","doi":"10.1101/2025.02.22.25322722","DOIUrl":"10.1101/2025.02.22.25322722","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is associated with chronic sleep disturbances and cognitive impairment, with limited effective therapeutic strategies. Our previous work showed dietary supplementation with branched chain amino acids (BCAAs; isoleucine, leucine, valine), the primary substrate for <i>de novo</i> glutamate/GABA synthesis in the CNS, restored normal sleep-wake patterns and improved cognitive function in rodents. Our recent pilot work in humans showed preliminary feasibility/acceptability and limited efficacy for BCAAs to improve sleep in Veterans with TBI. However, these pilot data were limited in sample size, treatment dosages/duration, and therefore unable to establish efficacy or provide insight into dosing/duration parameters. The present study, SmART-TBI (supplementation with amino acid rehabilitative therapy in TBI: NCT04603443 ), represents a fully powered, placebo-controlled, double-masked randomized clinical trial (target n=120). Covariate adaptive randomization controlling for age, sex, TBI recency, pain, depression, and PTSD, allocated participants 1:1:1:1 to four groups comprising 3 BCAA doses ('high' 30g b.i.d.; 'medium' 20g b.i.d.; and 'low' 10g b.i.d.) and one placebo-control (rice protein, 10g b.i.d.). Outcome measures were assessed following a 2-week baseline period; after 4 weeks, 8 weeks, and 12 weeks of intervention; and after 4 weeks and 12 weeks post-intervention. Primary outcomes were feasibility and acceptability of the protocol. Exploratory outcomes included preliminary efficacy in improving sleep, assessed via a combination of actigraphy, mattress-sensors, sleep diaries (all analyzed daily), as well as pre- and post-BCAA overnight polysomnography for sleep staging, cognition, and quality of life measures. Results indicated high feasibility and acceptability of this fully remote protocol among Veterans with TBI.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}