bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality indicators prospectively associated with falls in inpatient rehabilitation facilities
Authors: Wright Jonathan Robert , D’Ausilio Jamie , Cappaert Thomas , Lau Jeffery D. 
Published: September 2024

Abstract

Objective
Retrospective studies suggest quality indicators (QI) are associated with falls in inpatient rehabilitation facilities (IRFs), but this claim has not yet been validated prospectively. The aim of this study was to analyze the associations between QI codes and falls in a prospective sample.

Design
For this prospective observational cohort study, we followed 658 patients from 4 IRFs who were consecutively admitted and discharged over a 6-month period. On admission, we collected patients’ QI codes, and then, tracked whether they fell during their IRF stay.

Results
Univariable logistic regressions revealed that most individual QI items for communication, self-care, and mobility were significantly associated with falls. In a multivariable model with 6 different QI items, only patients’ performance going up and down 1 step was significantly associated with falls. To explain this finding, we investigated the relationships between these QI items and found 3 of them to be highly correlated.

Conclusions
Most individual QI items appear prospectively associated with falls. Patients with lower QI codes are more likely to fall. Combining QI items (such as expression and toileting) may improve fall-risk assessment, but some QI items may be too interrelated to use together.
Estimating the prevalence of Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) – a systematic review
Authors: Ward Joseph A. , Calderbank Thomas , Tang Chee Chee , Goddard Naveen V , MacNeill Fiona A , Tasoulis Marios K , Khan Aadil A. 
Published: September 2024

Introduction:
Assessment of BIA-ALCL prevalence is challenged by a lack of population-level data for the prevalence of breast implants in the wider population. Absence of such data obscures the true prevalence of BIA-ALCL and hinders informed consent consultations. We performed a systematic review to synthesise data from published studies reporting BIA-ALCL cases in defined patient populations to better inform the evidence base.

Methods:
PubMed and Embase were searched to obtain studies reporting the prevalence of BIA-ALCL in defined patient cohorts with breast implants where case prevalence was calculable. Study characteristics, the number of BIA-ALCL cases and total sample size were extracted and used to calculate the prevalence of BIA-ALCL per 100,000 implanted patients.

Results:
Of 1,477 publications identified by the search, 38 studies incorporating 28 cohort and 6 registry studies satisfied the inclusion criteria encompassing a total population sample of 17,038,371 patients and 1,170 BIA-ALCL patients. The prevalence of BIA-ALCL was found to be 30.54 per 100,000 implanted patients with textured implants (1 case per 3,274 implanted patients) and 6.70 per 100,000 implanted patients with implants of any-type (1 case per 14,925 implanted patients).

Conclusions:
By synthesising the published literature, this work provides a determination of BIA-ALCL prevalence using study- and population-level data where the prevalence of breast implants is known. The accurate determination of BIA-ALCL prevalence is of fundamental importance for patients undergoing implant-related surgery to enable the provision of valid informed consent.
CIRCULATING HEPARAN SULFATE PROFILES IN PEDIATRIC ACUTE RESPIRATORY DISTRESS SYNDROME
Authors: Sallee Colin J. , Maddux Aline B. , Hippensteel Joseph A. , Markovic Daniela , Oshima Kaori , Schwingshackl Andreas , Mourani Peter M. , Schmidt Eric P. , Sapru Anil 
Published: September 2024

ABSTRACT

Introduction: Sepsis-induced degradation of endothelial glycocalyx heparan sulfate (HS) contributes to the pulmonary microvascular endothelial injury characteristic of acute respiratory distress syndrome (ARDS) pathogenesis. Our objectives were to (1) examine relationships between plasma indices of HS degradation and protein biomarkers of endothelial injury and (2) identify patient subgroups characterized by distinct profiles of HS degradation in children with ARDS. Methods: We analyzed prospectively collected plasma (2018–2020) from a cohort of invasively mechanically ventilated children (aged >1 month to <18 years) with ARDS. Mass spectrometry characterized and quantified patterns of HS disaccharide sulfation. Protein biomarkers reflective of endothelial injury (e.g., angiopoietin-2, vascular cell adhesion molecule-1, soluble thrombomodulin) were measured with a multiplex immunoassay. Pearson correlation coefficients were used to construct a biomarker correlation network. Centrality metrics detected influential biomarkers (i.e., network hubs). K-means clustering identified unique patient subgroups based on HS disaccharide profiles. Results: We evaluated 36 patients with pediatric ARDS. HS disaccharide sulfation patterns, 6S, NS, and NS2S, positively correlated with all biomarkers of endothelial injury (all P < 0.05) and were classified as network hubs. We identified three patient subgroups, with cluster 3 (n = 5) demonstrating elevated levels of 6S and N-sulfated HS disaccharides. In cluster 3, 60% of children were female and nonpulmonary sepsis accounted for 60% of cases. Relative to cluster 1 (n = 12), cluster 3 was associated with higher oxygen saturation index (P = 0.029) and fewer 28-day ventilator-free days (P = 0.016). Conclusions: Circulating highly sulfated HS fragments may represent emerging mechanistic biomarkers of endothelial injury and disease severity in pediatric ARDS.
A Qualitative Exploration of Women With Cystic Fibrosis and Urinary Incontinence
Authors: Vargas Laura , Kazmerski Traci M. , von Berg Karen , Patterson Danielle , West Natalie , Bradley Megan 
Published: September 2024

Importance
Women with cystic fibrosis (CF) historically experience a high prevalence of urinary incontinence (UI). However, this area is understudied, especially in the modern era of highly effective modulator therapy (HEMT).

Objective
This study aimed to explore the UI experiences, knowledge, care-seeking behavior, and treatment preferences of women with CF.

Study Design
We recruited women aged ≥18 years through the CF Foundation's Community Voice national registry if they had a diagnosis of CF and reported UI. Participants underwent individual, semistructured interviews exploring their experiences, attitudes, and preferences toward UI that were audiorecorded and transcribed. Two coders performed thematic analysis using deductive and inductive coding approaches.

Results
Twenty-six participants completed interviews (average age, 45.1 years; range, 24–61 years). Key themes included the following: (1) most women with CF and UI report low bother from symptoms likely related to stress UI, and HEMT has greatly improved UI symptoms and decreased bother; (2) most women with CF and UI had previously discussed UI symptoms with family and/or peers but had not sought care due to stigma or low priority; (3) women with CF and UI had minimal knowledge about UI in general and how it relates to CF; (4) most desired broad screening for UI from their CF team and improved multidisciplinary care; and (5) highly effective UI treatment options with low-time commitment and easily accessible resources are desired.

Conclusions
Women with CF and UI report low knowledge and care-seeking behavior related to this condition and desire improved care provision. Importantly, HEMT may improve UI symptoms among people with CF.
Impact of Age on Perioperative Complications After Obliterative Vaginal Surgery
Authors: Mowers Erin E. , Vargas Laura G. , Shepherd Jonathan P. , Bonidie Michael J. , Ackenbom Mary F. 
Published: September 2024

Importance
Obliterative vaginal surgery is often reserved for older patients with prolapse, but the effect of age as an independent risk factor for perioperative complications in this cohort is poorly understood.

Objective
The aim of this study was to assess the association between age and perioperative complications in women undergoing obliterative vaginal surgery.

Study Design
This was a retrospective cohort study that included 371 patients undergoing colpocleisis between 2010 and 2013 at a single academic medical center. Seventy demographic and clinical variables, including complications within 12 weeks of surgery, were analyzed. The χ2 and Fisher exact tests were used for categorical variables. Student t and Mann-Whitney U tests were used for continuous variables. Univariate logistic regression was performed to identify predictors of perioperative complications, and candidate variables with P < 0.2 were used in multivariate logistic regression.

Results
The mean patient age was 75.4 ± 6.4 years (range, 59–94 years). One hundred ten (29.7%) patients experienced at least 1 complication, the most common of which was urinary tract infection (n = 47, 12.7%). In the final multivariable model, only age (odds ratio, 1.05 per year; 95% confidence interval, 1.01–1.08) remained a significant predictor of perioperative complications. A cut point of age ≥70.5 years maximized sensitivity and specificity for predicting complications.

Conclusions
Among women undergoing obliterative vaginal surgery, age is a predictor of perioperative complications. Each increasing year of age increases the complication likelihood by 1.05-fold, such that an 85-year-old woman is 1.05^20 or 2.65 times more likely than a 65-year-old woman to have a complication. A cut point of ≥70.5 years best predicted complications. Despite this association, severe perioperative complications following obliterative surgery are rare.
Generalizable Morphological Profiling of Cells by Interpretable Unsupervised Learning
Authors: Murthy Rashmi Sreeramachandra , Stassen Shobana V. , Siu Dickson M. D. , Lo Michelle C. K. , Yip Gwinky G. K. , Tsia Kevin K. 
Published: September 2024

AbstractThe intersection of advanced microscopy and machine learning is revolutionizing cell biology into a quantitative, data-driven science. While traditional morphological profiling of cells relies on labor-intensive manual feature extraction susceptible to biases, deep learning offers promising alternatives but struggles with the interpretability of its black-box operation and dependency on extensive labeled data. We introduce MorphoGenie, an unsupervised deep-learning framework designed to address these challenges in single-cell morphological profiling. Enabling disentangled representation learning integrated with high-fidelity image reconstructions, MorphoGenie possesses a critical attribute to learn a compact, generalizable and interpretable latent space. This facilitates the extraction of biologically meaningful features without human annotation, additionally overcoming the "curse of dimensionality" inherent in manual methods. Unlike prior models, MorphoGenie introduces a systematic approach to mapping disentangled latent representations to fundamental hierarchical morphological attributes, ensuring both semantic and biological interpretability. Moreover, it adheres to the concept of combinatorial generalization—a core principle of human intelligence— which greatly enhances the model’s capacity to generalize across a broad spectrum of imaging modalities (e.g., quantitative phase imaging and fluorescence imaging) and experimental conditions (ranging from discrete cell type/state classification to continuous trajectory inference). The framework offers a new, generalized strategy for unbiased and comprehensive morphological profiling, potentially revealing insights into cellular behavior in health and disease that might be overlooked by expert visual examination.
The p97-UBXD8 complex maintains peroxisome abundance by suppressing pexophagy
Authors: Montes Iris D. , Amirthagunanathan Suganthan , Joshi Amit S. , Raman Malavika 
Published: September 2024

AbstractPeroxisomes are vital organelles involved in key metabolic functions in eukaryotic cells. Their significance is highlighted by peroxisome biogenesis disorders; severe childhood diseases marked by disrupted lipid metabolism. One mechanism regulating peroxisome abundance is through selective ubiquitylation of peroxisomal membrane proteins that triggers peroxisome degradation via selective autophagy (pexophagy). However, the mechanisms regulating pexophagy remain poorly understood in mammalian cells. Here we show that the evolutionarily conserved AAA-ATPase p97 and its membrane embedded adaptor UBXD8 are essential for maintaining peroxisome abundance. From quantitative proteomic studies we reveal that loss of UBXD8 affects many peroxisomal proteins. We find depletion of UBXD8 results in a loss of peroxisomes in a manner that is independent of the known role of UBXD8 in ER associated degradation (ERAD). Loss of UBXD8 or inhibition of p97 increases peroxisomal turnover through autophagy and can be rescued by depleting key autophagy proteins or overexpressing the deubiquitylating enzyme USP30. Furthermore, we find increased ubiquitylation of the peroxisomal membrane protein PMP70 in cells lacking UBXD8 or p97. Collectively, our findings identify a new role for the p97-UBXD8 complex in regulating peroxisome abundance by suppressing pexophagy.
Identification of conserved and tissue-restricted transcriptional profiles for lipid associated macrophages (LAMs)
Authors: Xu Yingzheng , Hillman Hannah , Chang Michael , Ivanov Stoyan , Williams Jesse W. 
Published: September 2024

AbstractMacrophages are essential immune cells present in all tissues, and are vital for maintaining tissue homeostasis, immune surveillance, and immune responses. Considerable efforts have identified shared and tissue-specific gene programs for macrophages across organs during homeostasis. This information has dramatically enhanced our understanding of tissue-restricted macrophage programming and function. However, few studies have addressed the overlapping and tissue-specific responses of macrophage subsets following inflammatory responses. One subset of macrophages that has been observed across several studies, lipid-associated macrophages (LAMs), have gained interest due to their unique role in lipid metabolism and potential as a therapeutic target. LAMs have been associated with regulating disease outcomes in metabolically related disorders including atherosclerosis, obesity, and nonalcoholic fatty liver disease (NAFLD). In this study, we utilized single-cell RNA sequencing (scRNAseq) data to profile LAMs across multiple tissues and sterile inflammatory conditions in mice and humans. Integration of data from various disease models revealed that LAMs share a set of conserved transcriptional profiles, includingTrem2andLpl, but also identified key sets of tissue-specific LAM gene programs. Importantly, the shared LAM markers were highly conserved with human LAM populations that also emerge in chronic inflammatory settings. Overall, this analysis provides a detailed transcriptional landscape of tissue-restricted and shared LAM gene programs and offers insights into their roles in metabolic and chronic inflammatory diseases. These data may help instruct appropriate targets for broad or tissue-restricted therapeutic interventions to modulate LAM populations in disease.
A Global Assessment of Plant-Mite Mutualism and its Ecological Drivers
Authors: Myers Andrew , Martin Bruce , Yonenaga Jenna , Agrawal Anurag A. , Weber Marjorie G. 
Published: September 2024

ABSTRACTMutualisms are mediated by adaptive traits of interacting organisms and play a central role in the ecology and evolution of species. Thousands of plant species possess tiny structures called “domatia” that house mites which protect plants from pests, yet these traits remain woefully understudied. Here we release a worldwide database of species with mite domatia and provide the first evaluation of the phylogenetic and geographic distribution of this mutualistic trait. With >2,500 additions based on digital herbarium scans and published reports, we increased the number of known species with domatia by 27% and, importantly, documented their absence in >4,000 species. We show that mite domatia likely evolved hundreds of times among flowering plants, occurring in an estimated ∼10% of woody species representing over a quarter of all angiosperm families. Contrary to classic hypotheses about the evolutionary drivers of mutualism, we find that mite domatia evolved more frequently in temperate regions and in deciduous lineages; this pattern is concordant with a large-scale geographic transition from predominantly ant-based plant defense mutualisms in the tropics to mite-based defense mutualisms in temperate climates. Our data also reveal a previously undescribed pattern of evolutionary convergence in domatia morphology, with tuft-form domatia more likely to evolve in dry temperate habitats and pit domatia were more likely to evolve in wet tropical environments. We have shown climate-associated drivers of mite domatia evolution, demonstrating their utility and power as an evolutionarily replicated system for the study of plant defense mutualisms.
Unveiling allopolyploidization-driven genome duplications through progressive analysis of deep genome skimming data
Authors: Xie Si-Yu , Lin Xiao-Hua , Wang Jun-Ru , Ma Dai-Kun , Zhang Yu , Xu Chao , Ma Hong , Li Pan , Chen Duo-Yuan , Zhong Xin , Ge Bin-Jie , Hodel Richard G.J. , Zhao Liang , Liu Bin-Bin 
Published: September 2024

AbstractWhole-genome duplication (WGD) events are widespread across the Web of Life (WoL). Given the prevalence of WGDs in the polyploidPrunus(Rosaceae), this economically- and agriculturally-important angiosperm lineage provides an excellent model for exploring this mode of reticulation. We used the polyploidPrunusto demonstrate a progressive strategy for analyzing Deep Genome Skimming (DGS) data in the presence of WGDs. Phylogenomic discordance analyses indicated that allopolyploidization, rather than Incomplete Lineage Sorting (ILS), played a dominant role in the origin and dynamics of polyploidPrunus. This study underscores how a progressive strategy to identify WGD events at different depths in a phylogenetic tree reveals the nuances of evolutionary mechanisms driving allopolyploidization. We inferred that the continued uplift of the Himalayas from the Middle to Late Miocene drove the rapid diversification of the Eastern Asia endemicMaddeniaclade, by facilitating frequent hybridization and allopolyploidization, specifically introgression between the Himalayas-Hengduan and the Central-Eastern China clades.
Rfx3 controls outer hair cell differentiation, maintenance, and hair bundle formation by regulating the expression ofInsm1, Ikzf2, andTriobpgenes
Authors: Zhang Penghui , Wang Yafan , Guo Xiang , Ma Lu , Zeng Xiangyao , Feng Zhili , Liu Jinlei , Yan Mengzhen , Gao Yushan , Dong Jieran , Li Junhong , Ling Jie , Wu Hong , Jing Qianchen , Feng Yong , Li Jun 
Published: September 2024

AbstractThe RFX family of transcription factors plays crucial roles in the regulation of ciliogenesis and organ development. Mutations of RFX transcription factors lead to various genetic diseases, including ciliopathies and hearing loss, although the underlying mechanisms remain unclear. This study comprehensively analyzed the expression patterns of RFX family members during different inner ear developmental stages. Rfx3 and Rfx7 were identified as the dominantly expressed members in cochlear hair cells, exhibiting alternative splicing variants and dynamic subcellular localization at different stages. Integration of single-cell transcriptomics, ChIP-seq, and ATAC-seq data indicates that Rfx3 functions as either a transcriptional activator or repressor, binding to numerous genes related to ciliogenesis, hair bundle structures, and planar cell polarity. Rfx3 regulates the spatiotemporal expression of hair bundle geneTriobpin hair cells by binding to and modulating its intronic enhancer. Additionally, Rfx3 binds to hair cell differentiation and fate determination genesTbx2,Insm1, andIkzf2. The results demonstrate that Rfx3 and Rfx7 are dominantly expressed in outer hair cells, with their subcellular localization shifting to cytoplasm at later developmental stages. This suggests a previously unknown function of Rfx3 and Rfx7 beyond transcriptional regulation, highlighting their complex roles in hair cell differentiation and maintenance.
Tirzepatide for Lipodystrophy
Authors: Meral Rasimcan , Celik Guler Merve , Kaba Diarratou , Prativadi Jeevitha , Frontera Eric D , Foss-Freitas Maria Cristina , Nachawi Noura , Broome David T , Lightbourne Marissa , Brown Rebecca J , Taylor Simeon I , Oral Elif A 
Published: September 2024

AbstractBackgroundLipodystrophy encompasses a group of rare disorders associated with severe metabolic disease. These disorders are defined by abnormal fat distribution, with near-total (generalized lipodystrophy, GL) or partial (partial lipodystrophy, PL; i.e. familial partial lipodystrophy, FPLD) absence of adipocyte mass leading to a decreased ability to store lipids safely. Excess lipids are more likely to be stored in non-adipose tissues, which leads to the metabolic manifestations. We have recently shown that glucagon-like peptide-1 agonists are associated with metabolic improvements in FPLD. We hypothesized that tirzepatide, a dual incretin, may also lead to metabolic improvement in patients with lipodystrophy.MethodsObservational cohort of patients with PL or GL who received tirzepatide clinically were tracked in the context of ongoing natural history studies.ResultsSeventeen patients received tirzepatide, 14 with FPLD (ages within 30-74 years; 12 female 2 male). After a median 8.7 months of follow-up, BMI (medianΔ -1.7; range -5.9 to 0.9 kg/m2;p=0.008), HbA1c (medianΔ -1.1%; range -6.3 to -0.1%;p<0.001), triglycerides [medianΔ - 65 mg/dL (-0.73 mmol/L); range -3820 to 43 mg/dL (-43.2 to 0.49 mmol/L);p=0.003] and total daily insulin requirements (medianΔ -109; range -315 to 0 units/day;p=0.002) were significantly reduced. Three patients with acquired GL (Ages within 35-64 years; all female) also demonstrated a robust response to tirzepatide with reduced BMI (22.2->20.9; 26.2->25.4; 19.5->17.6 kg/m2), HbA1c (8.5%->7.0%; 10.2%->7.8%; 9.1%->6.5%), triglycerides (91->80; 641->293; 1238->100 mg/dL or 1.03->0.90; 7.24->3.31; 14.0->1.13 mmol/L), and total daily insulin requirement (85->0; 0->0; 1000->750 units/day). Three patients did not tolerate dose escalation due to gastroesophageal reflux.ConclusionsTirzepatide may be an effective treatment for patients with lipodystrophy.