bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparative Analysis of Patient-Reported Outcomes Following Free Tissue Transfer, Partial Foot Amputation, and Below-Knee Amputation in High-Risk Limb Salvage Patients
Authors: Lava Christian X. , Huffman Samuel S. , Li Karen R. , DiBello John R. , Ply Christopher M. , Rohrich Rachel N. , Steinberg John S. , Atves Jayson N. , Fan Kenneth L. , Youn Richard C. , Attinger Christopher E. , Evans Karen K. 
Published: September 2024

Background
The surgical decision for limb-salvage with free tissue transfer (FTT), partial foot amputation (PFA), or below-knee amputation (BKA) for complex lower extremity (LE) wounds hinges on several factors, including patient choice and baseline function. However, patient-reported outcome measures (PROMs) on LE function, pain, and QoL for chronic LE wound interventions are limited. Thus, the study aim was to compare PROMs in patients who underwent FTT, PFA, or BKA for chronic LE wounds.

Methods
PROMs were collected via QR code for all adult chronic LE wound patients who presented to a tertiary wound center between June 2022 and June 2023. A cross-sectional analysis of patients who underwent FTT, PFA, or BKA was conducted. The 12-Item Short Survey (SF-12), PROM Information System Pain Intensity (PROMIS-3a), and Lower Extremity Functional Scale (LEFS) were completed at 1, 3, and 6 months and 1, 3, and 5 years postoperatively. Patient demographics, comorbidities, preoperative characteristics, and amputation details were collected.

Results
Of 200 survey sets, 71 (35.5%) underwent FTT, 51 (25.5%) underwent PFA, and 78 (39.0%) underwent BKA. Median postoperative time points of survey completion between FTT (6.2 months, IQR: 23.1), PFA (6.8 months, IQR: 15.5), and BKA (11.1 months, IQR: 21.3) patients were comparable (P = 0.8672). Most patients were male (n = 92, 76.0%) with an average age and body mass index (BMI) of 61.8 ± 12.6 years and 30.3 ± 7.0 kg/m2, respectively. Comorbidities for FTT, PFA, and BKA patients included diabetes mellitus (DM; 60.6% vs 84.2% vs 69.2%; P = 0.165), peripheral vascular disease (PVD; 48.5% vs 47.4% vs 42.3%; P = 0.790), and chronic kidney disease (CKD; 12.1% vs 42.1% vs 30.8%; P = 0.084). No significant differences were observed between FTT, PFA, and BKA patients in mean overall PROMIS-3a T-scores (49.6 ± 14.8 vs 54.2 ± 11.8 vs 49.6 ± 13.7; P = 0.098), LEFS scores (37.5 ± 18.0 vs 34.6 ± 18.3 vs 38.5 ± 19.4; P = 0.457), or SF-12 scores (29.6 ± 4.1 vs 29.5 ± 2.9 vs 29.0 ± 4.0; P = 0.298).

Conclusion
Patients receiving FTT, PFA, or BKA for chronic LE wounds achieve comparable levels of LE function, pain, and QoL postoperatively. Patient-centered functionally based surgical management for chronic LE wounds using interdisciplinary care, preoperative medical optimization, and proper patient selection optimizes postoperative PROMs.
Comparison of Normal Human Skin and Hypertrophic Scar Tissue Samples of Different Ages, Locations, and Stages of Maturity
Authors: Lv Tao , Zhang Peichao , Shi Huirong , Zhang Jiaojiao , Zhang Zhiying , Huo Ran 
Published: September 2024

Background
Scars disrupt the normal structure and function of the skin. The primary goal of plastic surgery is to prevent and reduce scarring. Therefore, we aimed to establish a comparison scheme between normal skin (NS) tissues of different ages and locations; hypertrophic scars (HTS) of different ages, locations, and maturities; and NS and HTS tissues to provide evidence on scar severity for improving treatment evaluation.

Methods
Various methods including histology, immunohistochemistry, and immunofluorescence were employed to compare the general appearance, macrophage infiltration, fibroblast activity, degree of angiogenesis, and collagen fiber type and arrangement in human-sourced NS and HTS tissues of different ages, locations, and maturities in seven patients (three with NS and four with HTS) from the Department of Burn and Plastic Surgery of the Shandong Provincial Hospital from January 2019 to December 2020.

Results
The thicknesses of the epidermis and dermis of NS tissues varied with age and location. The epidermis of the upper arms, face, and upper eyelids of NS tissues sequentially thickened, whereas the dermis was sequentially thinner. Several glandular structures were identified in the upper eyelids but rarely in the face and upper arms. Histological changes in HTS tissue of different ages, locations, and maturity occur as scar formation time is prolonged, accompanied by increased CD86 levels and fibrosis. As the scar matured, connexin and VEGFR2 expression decreased, indicating reduced inflammation, fibroblast activity, and angiogenesis. The comparison between NS and HTS tissue also revealed significant differences; the positive expression of VEGFR2 and total collagen in HTS tissue was higher than that in NS tissue.

Conclusions
We discovered significant differences among NS, HTS, and NS and HTS tissues of different ages, locations, and maturities. Further, this study may provide a basis for clarifying the treatment effect of different methods for HTS compared with those for NS, efficiently individualizing patients' treatment plans and ultimately shortening the scar treatment process.
Skeletal and Soft Tissue Surgeries in the Long-term Management of Patients With Syndromic Craniosynostosis
Authors: Moshal Tayla , Roohani Idean , Jolibois Marah , Lasky Sasha , Stanton Eloise W. , Vallurupalli Medha , Wolfe Erin M. , Munabi Naikhoba C.O. , Hammoudeh Jeffrey A. , Urata Mark M. 
Published: September 2024

Background
Soft tissue procedures are often crucial for normalizing the long-term facial appearance in patients with syndromic craniosynostosis, yet they are underrepresented in the literature and existing treatment algorithms. This study evaluated secondary soft tissue surgeries in relation to skeletal operations in patients with syndromic craniosynostosis.

Methods
A retrospective review evaluated patients with syndromic craniosynostosis treated at a tertiary children's hospital from 2003 to 2023. Craniofacial skeletal and soft tissue procedures were assessed for timing and frequency. Skeletal surgeries included redo fronto-orbital advancements, monobloc advancement/distraction ± facial bipartition, and LeFort III or III/I advancement/distraction. Soft tissue surgeries encompassed oculoplastic procedures, scalp reconstruction, fat grafting, and septorhinoplasty.

Results
Of 106 patients with syndromic craniosynostosis, 57 (57.8%) underwent ≥1 secondary skeletal operation, and 101 (95.3%) underwent ≥1 soft tissue procedures, averaging 3.7 ± 3.3 soft tissue procedures per patient. Patients who underwent secondary forehead advancement had significantly higher rates of subsequent lateral canthopexy (71.4% vs 25.6, P < 0.001), ptosis reconstruction (17.9% vs 7.7%, P = 0.025), and frontotemporal fat grafting (50.0% vs 15.4%, P < 0.001) than those who did not. Patients who underwent midface advancement surgery had significantly higher rates of subsequent lateral canthopexy (65.4% vs 11.1%, P < 0.001), medial canthopexy (7.7% vs 0.0%, P = 0.038), scalp reconstruction (36.5% vs 16.7%, P = 0.020), frontotemporal fat grafting (34.6% vs 14.8%, P = 0.018), malar fat grafting (11.5% vs 0.0%, P = 0.010), and septorhinoplasty (26.9% vs 1.9%, P < 0.001) than those who did not. Specifically, LeFort III or III/I advancement/distractions were significantly associated with higher rates of subsequent septorhinoplasties (33.3% vs 1.6%, P < 0.001). The mean follow-up was 10.2 ± 7.0 years.

Conclusions
This study revealed an intricate interplay between skeletal and soft tissue surgery in patients with syndromic craniosynostosis. Exploring techniques to reduce the need for further corrective surgery and anticipating necessary secondary interventions may improve patient counseling and outcomes.
Management of Pediatric Type III Tibial Shaft Fractures
Authors: MacIsaac Molly F. , Wright Joshua M. , Halsey Jordan N. , Fitzgerald Ryan E. , Snyder Christopher W. , Rottgers S. Alex 
Published: September 2024

Background
Pediatric open tibial fractures represent a challenging subset of injuries with limited literature to guide management. For children, the epidemiology, management, and outcomes of tibial-shaft fractures have not been fully described.

Methods
A retrospective analysis of the Trauma Quality Improvement Program Data Bank from 2017–2020 was used to query demographics, injury patterns, and management strategies in pediatric open tibial fractures. Fractures were compared by age group (0–5, 6–12, 13–17 years) and type (I/II vs type III). A subgroup analysis was performed on patients with type III open fractures.

Results
A total of 3480 open tibial fractures were identified, 3049 were type I/II, and 431 were type III. Motor vehicle accidents (48%) were the most common mechanism of injury (P < 0.001). Subanalysis of 128 type IIIb/c tibial fractures revealed local flap reconstruction (25%) skin graft (25%), and free tissue transfer were the most common management strategies and soft-tissue coverage was achieved after 162 hours (interquartile range = 109–231). Negative pressure wound therapy was utilized in 63% of cases but used in isolation in only 23% of cases. Immediate fixation with intramedullary nailing was more frequently used in the 13–17 age group while plate fixation was more commonly used in younger age groups.

Conclusions
Soft-tissue management patterns following open tibial shaft fractures mirror those seen in adult cohorts. The median time to achieve soft-tissue coverage exceeds the traditional 72-hour target advocated by Godina. Age-based variation is seen in orthopedic management of these fractures based on growth maintenance concerns.
Prolapse Treatment–Related Decisional Conflict After New Patient Visits
Authors: Shinnick Julia K. , Jackson Araba A. , Stanley Russel , Serna-Gallegos Tasha , Boyd Brittni , Joseph Ivrose , Das Deepanjana , Pancheshnikov Anna , Scarpaci Matthew M. , Sung Vivian W. 
Published: September 2024

Importance
Patients with pelvic organ prolapse are often tasked with deciding between treatments. Decisional conflict is a measure of factors that go into effective decision making.

Objective
This study aimed to compare prolapse treatment–related decisional conflict reported by underrepresented patients (URPs) to non-URPs after new patient visits.

Study Design
A multicenter cohort study of new patients counseled regarding management of prolapse from July 2021 to December 2022 was performed. Participants completed the Decisional Conflict Scale (DCS), a validated measure of modifiable factors in decision making. Higher scores indicate feeling less comfortable with decisions. Race and ethnicity were viewed as social constructs. A URP was defined as self-identification with a non-White race or Hispanic ethnicity. Alpha was set at 0.05, power 80%, to detect an effect size of 0.4 between mean DCS scores.

Results
A total of 207 participants (103 URPs, 49.8%), with a mean age of 63.4 ± 11.9 years and mean body mass index of 29.7 ± 6.9 (calculated as weight in kilograms divided by height in meters squared), completed the study. Much of the URP group self-identified as Hispanic (50/103, 48.5%) and/or Black (39/103, 37.9%), and 30 of 103 (29.1%) had an interpreter at their visit. A greater proportion of non-URPs had a prior hysterectomy (16.1% difference; P = 0.017) and prolapse surgery (18/204, 10.5% difference; P = 0.020). A greater proportion of URPs had hypertension (23.6% difference; P = <0.001). There were no differences in the other pelvic floor disorders, prolapse stage, or treatments selected (all P > 0.05). The mean DCS scores were not different between groups (URP, 12.9 ± 12.3 vs non-URP, 11.6 ± 14.9; P = 0.31). Household income, education, and insurance were not associated with DCS scores (all P > 0.05).

Conclusions
Decisional Conflict Scale scores were not significantly different between groups. Possible differences between subgroups warrant further investigation.
Urinary Incontinence in Nulliparous Female Elite Athletes: A Mixed Methods Exploration
Authors: Gan Zoe S. , Bilger Andrea , Smith Ariana L. 
Published: September 2024

Importance
Urinary incontinence (UI) occurs in 40–50% of nulliparous female elite athletes. However, causative factors, management, and perceptions of UI in this population are suboptimally understood.

Objectives
The objectives of this study were to (1) identify factors that precipitate UI in nulliparous female elite athletes and (2) explore management strategies for UI and its effect on sports performance and quality of life.

Study Design
This was a cross-sectional, mixed-methods study in Division 1, college-aged nulliparous female athletes. Surveys assessed demographics, sport characteristics, relevant medical history, bladder symptoms during exercise, and validated genitourinary symptom questionnaires (Lower Urinary Tract Dysfunction Network Symptom Index-29, Female Genitourinary Pain Index). Data were compared between symptomatic athletes (who had ever experienced urinary leakage during exercise) and asymptomatic athletes. Symptomatic athletes discussed their experiences with UI in focus groups.

Results
Symptomatic athletes (33/67, 49%) had more asthma (21% vs. 2.9%, P = 0.027) and constipation (15% vs. 0%, P = 0.025), were more sexually active (76% vs. 44%, P = 0.008), and had worse overall urinary symptoms and genitourinary pain than asymptomatic athletes. They described both stress and urgency incontinence precipitated by various factors, including running, jumping, sustained efforts, and stressful situations. Many described voiding frequently before and during exercise. Despite increasing normalization of UI in the female athlete population since the onset of adolescence and variable degrees of bother, interest in improving symptom management was common.

Conclusions
Urinary incontinence in nulliparous female elite athletes may be multifactorial given its association with medical, behavioral, exercise-specific, and environmental conditions, which may be explored longitudinally to inform prevention and treatment strategies.
Out-of-sync evolutionary patterns and mutual interplay of major and minor capsid proteins in norovirus GII.2
Authors: Xu Ruiquan , Xue Liang , Wang Jingmin , Chen Yiqing , Cao Yingwen , Gao Junshan , Gao Hui , Du Qingyao , Kou Xiaoxia , Yu Lin 
Published: September 2024

An erratum of this article has been published full details can be found at 10.1099/jgv.0.002074.
Human noroviruses are the most common cause of viral gastroenteritis, resulting annually in 219 000 deaths and a societal cost of $60 billion, and no antivirals or vaccines are available. The minor capsid protein may play a significant role in the evolution of norovirus. GII.4 is the predominant genotype of norovirus, and its VP2 undergoes epochal co-evolution with the major capsid protein VP1. Since the sudden emergence of norovirus GII.2[P16] in 2016, it has consistently remained a significant epidemic strain in recent years. In the construction of phylogenetic trees, the phylogenetic trees of VP2 closely parallel those of VP1 due to the shared tree topology of both proteins. To investigate the interaction patterns between the major and minor capsid proteins of norovirus GII.2, we chose five representative strains of GII.2 norovirus and investigated their evolutionary patterns using a yeast two-hybrid experiment. Our study shows VP1–VP2 interaction in GII.2, with critical interaction sites at 167–178 and 184–186 in the highly variable region. In the intra-within GII.2, we observed no temporal co-evolution between VP1 and VP2 of GII.2. Notable distinctions were observed in the interaction intensity of VP2 among inter-genotype (P<0.05), highlighting the divergent evolutionary patterns of VP2 within different norovirus genotypes. In summary, the interactions between VP2 and VP1 of GII.2 norovirus exhibit out-of-sync evolutionary patterns. This study offered valuable insights for further understanding and completing the evolutionary mechanism of norovirus.
Exploiting pleiotropy to enhance variant discovery with functional false discovery rates
Authors: Bass Andrew J. , Wallace Chris 
Published: September 2024

AbstractThe cost of acquiring participants for genome-wide association studies (GWAS) can limit sample sizes and inhibit discovery of genetic variants. We introduce the surrogate functional false discovery rate (sfFDR) framework which integrates summary statistics of related traits to increase power. The sfFDR framework provides estimates of FDR quantities such as the functional local FDR andq-value, and uses these estimates to derive a functionalp-value for type I error rate control and a functional local Bayes’ factor for post-GWAS analyses (e.g., fine mapping and colocalization). Compared to a standard analysis, sfFDR substantially increased power (equivalent to a 60% increase in sample size) in a study of obesity-related traits from the UK Biobank, and discovered eight additional lead SNPs near genes linked to immune-related responses in a rare disease GWAS of eosinophilic granulomatosis with polyangiitis. Collectively, these results highlight the utility of exploiting related traits in both small and large studies.
Stroke recognition in medical emergency calls: A novel sensitivity definition as a basis for developing artificial intelligence decision support
Authors: Iversen Emil , Ihle-Hansen Hege , Halle Kari Krizak , Lundervold Alexander Selvikvåg , Myrmel Lars , Vestbø Anders Strand , Fromm Annette , Autenried Cristian , Brattebø Guttorm 
Published: September 2024

AbstractBackgroundThe sensitivity of emergency medical communication centers (EMCC) for stroke detection varies widely. However, few studies offer detailed insights into the entirety of prehospital pathways in patients with stroke. Therefore, this study aimed to lay the foundation for artificial intelligence (AI) decision support tools in EMCCs by exploring their ability to detect strokes in medical emergency calls, describe a novel method for stroke sensitivity calculation in the EMCC, and identify factors associated with stroke recognition during a call.MethodsIn total, 1,164 patients with stroke in the catchment area of Bergen EMCC in 2018 and 2019 were included, and a dataset from the EMCC was established manually and linked with data from the Norwegian Stroke Registry (NSR) for analysis. Descriptive statistics, Chi-square test for categorical variables, Mann–Whitney U test for continuous variables, and multivariate logistic regression (LR) were performed on data obtained from patients primarily assessed by EMCC (n=838).ResultsUsing a novel method, we found a stroke detection sensitivity of 76.8% in our study, compared to the 63.4% when using the traditional sensitivity detection method. LR analysis showed a positive association between stroke suspicion and ischemic strokes (odds ratio [OR]=0.317 [0.209–0.481]; p<0,001, with ischemic stroke as the reference) and wake-up strokes (OR=1.716 [1.110–2.653]; p=0.015). Among the NSR symptoms, only aphasia/dysarthria was positively associated with stroke suspicion (OR=1.600 [1.087–2.353]; p=0.017), while leg paresis (OR=0.609 [0.390–0.953]; p=0.009) and vertigo (OR=0.376 [0.204–0.694]; p=0.002) were negatively associated.ConclusionsThis study introduced a novel and more accurate method for calculating EMCC stroke sensitivity, which is relevant for developing decision support tools, such as AI. Moreover, we identified factors of particular interest for future EMCC research that are relevant to developing AI decision-support tools.Clinical trialshttps://clinicaltrials.gov/study/NCT04648449
Single-cell multi-omics reveals tumor microenvironment factors underlying poor immunotherapy responses in ALK-positive lung cancer
Authors: Baek Seungbyn , Sung Euijeong , Kim Gamin , Hong Min Hee , Lee Chang Young , Shim Hyo Sup , Park Seong Yong , Kim Hye Ryun , Lee Insuk 
Published: September 2024

AbstractAnaplastic lymphoma kinase (ALK) rearrangement is a major oncogenic driver in non-small cell lung cancer (NSCLC). While ALK tyrosine kinase inhibitors have shown promising therapeutic effects, overcoming resistance with immunotherapy becomes necessary when resistance develops. However, various clinical trials have revealed that their efficacies remain limited. To investigate the tumor microenvironment (TME) factors contributing to poor immune checkpoint blockade responses in ALK-positive patients, we performed single-cell RNA and ATAC sequencing on lung adenocarcinoma (LUAD) tumors with and without ALK rearrangements. Integrative analysis with additional public LUAD cohorts revealed distinct immune landscapes in ALK-positive tumors, marked by enriched innate immunity and depleted adaptive immunity. ALK-positive malignant cells exhibit higher stemness and aggressive phenotype. Tumor-associated macrophages (TAMs) in these tumors predominantly maintain pro-tumoral M2-like states, reinforcing immune suppression. B cells show reduced immune reactivity and impaired tertiary lymphoid structure formation, while CD8+T cells display bystander-like signatures and reduced tumor reactivity. Single-cell chromatin accessibility profiles combined with regulatory network analysis suggest that differences in transcription factor activities, rather than chromatin accessibility, may underlie T cell dysfunction. These findings provide insights into the immunosuppressive TME of ALK-positive LUAD, potentially explaining the failure of recent immunotherapy trials and highlighting targets for improving efficacy.
Decoding Biomolecular Condensate Dynamics: An Energy Landscape Approach
Authors: Biswas Subhadip , Potoyan Davit A 
Published: September 2024

AbstractA significant fraction of eukaryotic proteins contain low-complexity sequence elements with unknown functions. Many of these sequences are prone to form biomolecular condensates with unique material and dynamic properties. Mutations in low-complexity regions often result in abnormal phase transitions into pathological solid-like states. Therefore, understanding how the low-complexity sequence patterns encode the material properties of condensates is crucial for uncovering the cellular functions and evolutionary forces behind the emergence of low-complexity regions in proteins. In this work, we employ an alphabet-free energy landscape framework of the stickers and spacers to dissect how the low complexity patterns of proteins encode the material properties of condensates. We find a broad phase diagram of material properties determined by distinct energy landscape features, showing that periodic repeat motifs promote elastic-dominated while random sequences are viscous-dominated properties. We find that a certain degree of sticker periodicity is necessary to maintain the fluidity of condensates, preventing them from forming glassy or solid-like states. Finally, we show that the energy landscape framework captures viscoelastic trends seen in the recent experiments on prion domains and makes predictions for systematic variation of protein condensate viscoelasticity via altering the periodicity and strength of sticker motifs.TOC Graphic