bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of cell differentiation and growth underlies the shift from bud protection to light capture in cauline leaves
Authors: Le Gloanec Constance , Gómez-Felipe Andrea , Alimchandani Viraj , Branchini Elvis , Bauer Amélie , Routier-Kierzkowska Anne-Lise , Kierzkowski Daniel 
Published: August 2024

Abstract
Plant organs have evolved into diverse shapes for specialized functions despite emerging as simple protrusions at the shoot apex. Cauline leaves serve as photosynthetic organs and protective structures for emerging floral buds. However, the growth patterns underlying this dual function remain unknown. Here, we investigate the developmental dynamics shaping Arabidopsis (Arabidopsis thaliana) cauline leaves underlying their functional diversification from other laminar organs. We show that cauline leaves display a significant delay in overall elongation compared with rosette leaves. Using live imaging, we reveal that their functional divergence hinges on early modulation of the timing of cell differentiation and cellular growth rates. In contrast to rosette leaves and sepals, cell differentiation is delayed in cauline leaves, fostering extended proliferation, prolonged morphogenetic activity, and growth redistribution within the organ. Notably, cauline leaf growth is transiently suppressed during the early stages, keeping the leaf small and unfolded during the initiation of the first flowers. Our findings highlight the unique developmental timing of cauline leaves, underlying their shift from an early protective role to a later photosynthetic function.
O-Glycosylation of a male seminal fluid protein influences sperm binding and female postmating behavior
Authors: Zhang Liping , Ten Hagen Kelly G 
Published: August 2024

Abstract
Glycoproteins are abundant within the human reproductive system and alterations in glycosylation lead to reproductive disorders, suggesting that glycans play an important role in reproductive function. In this study, we used the Drosophila reproductive system as a model to investigate the biological functions of O-glycosylation. We found that O-glycosylation in the male accessory glands, an organ responsible for secreting seminal fluid proteins, plays important roles in female postmating behavior. The loss of one O-glycosyltransferase, PGANT9, in the male reproductive system resulted in decreased egg production in mated females. We identified one substrate of PGANT9, lectin-46Ca (CG1656), which is known to affect female postmating responses. We further show that the loss of lectin-46Ca O-glycosylation affects its ability to associate with sperm tails, resulting in reduced transfer within the female reproductive system. Our results provide the first example that O-glycosylation of a seminal fluid protein affects its ability to associate with sperm in vivo. These studies may shed light on the biological function of O-glycans in mammalian reproduction.
Bending-driven patterning of solid inclusions in lipid membranes: Colloidal assembly and transitions in elastic 2D fluids
Authors: Xin Weiyue , Santore Maria M 
Published: August 2024

Abstract
Biological or biomimetic membranes are examples within the larger material class of flexible ultrathin lamellae and contoured fluid sheets that require work or energy to impose bending deformations. Bending elasticity also dictates the interactions and assembly of integrated phases or molecular clusters within fluid lamellae, for instance enabling critical cell functions in biomembranes. More broadly, lamella and other thin fluids that integrate dispersed objects, inclusions, and phases behave as contoured 2D colloidal suspensions governed by elastic interactions. To elucidate the breadth of interactions and assembled patterns accessible through elastic interactions, we consider the bending elasticity-driven assembly of 1–10 μm solid plate-shaped Brownian domains (the 2D colloids), integrated into a fluid phospholipid membrane (the 2D fluid). Here, the fluid membranes of giant unilamellar vesicles, 20–50 μm in diameter, each contain 4–100 monodisperse plate-domains at an overall solid area fraction of 17 ± 3%. Three types of reversible plate arrangements are found: persistent vesicle-encompassing quasi-hexagonal lattices, persistent closely associated chains or concentrated lattices, and a dynamic disordered state. The interdomain distances evidence combined attractive and repulsive elastic interactions up to 10 μm, far exceeding the ranges of physio-chemical interactions. Bending contributions are controlled through membrane slack (excess area) producing, for a fixed composition, a sharp cooperative multibody transition in plate arrangement, while domain size and number contribute intricacy.
Long-term surveillance study of rituximab originator treated patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)
Authors: Uchida Lisa , Jones Rachel B , Smith Rona M , Nodale Marianna , Bond Simon , Loechel Claudia , King Maria , Luqmani Raashid , Gray David , Barrett Joe , Jayne David R W 
Published: August 2024

Abstract

Objectives
Rituximab is used for remission induction and the prevention of relapse in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). This study evaluated the incidence of safety events and compared time to first serious adverse event (SAE) between a rituximab cohort and a cohort treated with non-rituximab therapies in a real-life setting.

Methods
Rituximab surveillance study in vasculitis was a retrospective observational study of patients with AAV who received rituximab (MabThera) or other treatments between 2003 and 2017 at a specialist vasculitis clinic. The primary endpoint was time to first SAE.

Results
392 patients were enrolled: 247 in the rituximab and 145 in the control cohorts with a total follow up of 2217 person-years (mean study duration 5.7 years). Mean age was 61 years, 77% had granulomatosis with polyangiitis (GPA). There were differences in baseline characteristics (disease duration and prior immunosuppressive use) between groups. 134/247 patients (54%) in the rituximab and 58/145 (40%) of controls experienced at least one SAE. Time to first SAE was shorter in the rituximab group (hazard ratio (HR) 1.55, 95% CI 1.07–2.26, P = 0.022). Predictors of first SAE were higher vasculitis damage index and the presence of chronic pulmonary or kidney disease. The risk of serious infection was higher in the rituximab group (relative risk (RR) 2.12, 95% CI 1.31–3.43).

Conclusion
Over 40% of patients with AAV experienced at least one SAE. Although shorter time to first SAE and higher risk of infection were observed in the rituximab group, baseline imbalances necessitate a careful interpretation of these results.
Kidney whole-transcriptome profiling in primary antiphospholipid syndrome reveals complement, interferons and NETs-related gene expression
Authors: Tektonidou Maria G , Verrou Kleio-Maria , Gakiopoulou Harikleia , Manoloukos Menelaos , Lembessis Panagiotis , Hatzis Pantelis , Sfikakis Petros P 
Published: August 2024

Abstract

Objective
Pathogenesis of antiphospholipid syndrome (APS) remains poorly elucidated. We aimed to evaluate for the first time kidney transcriptome profiles in primary APS vs systemic lupus erythematosus (SLE) and control subjects.

Methods
We performed RNA sequencing on archival formalin-fixed paraffin-embedded kidney biopsies from APS (n = 4), SLE (n = 5) and control (n = 3) individuals, differential gene expression analysis (DGEA) and enrichment analysis using gene ontology (GO) and CORUM, KEGG and Reactome pathway databases.

Results
Two-dimensional projection showed a distinct gene profile in primary APS vs control kidneys samples, but similar to SLE. DGEA in APS vs controls returned 276 upregulated and 217 downregulated genes, while the comparison between APS and SLE identified 75 upregulated and 111 downregulated genes. In 276 upregulated genes, enriched GO terms were (innate) immune response, inflammatory response, leucocyte and lymphocyte activation, cytokine production and T cell activation. CORUM and KEGG revealed complement-related genes (C3, C4A, C4B). Expression levels showed logFC values of 2.25 (P = 1.58e-05) for C3, 2.17 (P = 2.69e-06) for C4A and 2.135 (P = 3.7e-06) for C4B in APS vs controls, without differences between APS and SLE. Interferon (IFN) alpha/beta signalling was revealed by Reactome. Expression levels of nine IFN-regulated genes found upregulated in APS vs control kidneys (P-values ≤ 0.001 for all). Examining neutrophil-extracellular traps (NETs)-related gene expression, 13 of 15 upregulated NETs-related genes exhibited higher expression in APS vs controls but not vs SLE.

Conclusion
Complement, interferon and NETs-related genes are highly expressed in APS kidney tissues, similarly to SLE, pointing out the role of innate immunity in APS nephropathy pathogenesis and potential treatment targets.
De novo manifestations during adalimumab treatment in Behçet’s syndrome
Authors: Esatoglu Sinem Nihal , Sonmez Ozge , Ucar Didar , Kaymaz Elif , Ozguler Yesim , Ugurlu Serdal , Seyahi Emire , Melikoglu Melike , Fresko Izzet , Hamuryudan Vedat , Uygunoglu Ugur , Kutlubay Zekayi , Hatemi Ali Ibrahim , Celik Aykut Ferhat , Hatemi Gulen 
Published: August 2024

Abstract

Objectives
Treatment response may be variable across organ manifestations of Behçet’s syndrome (BS). We aimed to determine the frequency of de novo manifestations during adalimumab treatment.

Methods
We conducted a chart review of all BS patients who received adalimumab in our centre between 2008 and 2023. Demographic data, reasons for initiating adalimumab, concurrent medications, previous treatments, and outcomes were recorded. We defined de novo manifestations as new BS manifestations that occurred for the first time during treatment with adalimumab. For patients with vascular involvement, a new vascular event at another vessel was also considered as a de novo manifestation.

Results
Among the 335 patients, a de novo manifestation developed in 14 (4%) patients. De novo manifestations were vascular involvement in five patients, arthritis in three, anterior uveitis in two, nervous system involvement in two, gastrointestinal involvement in one, and epididymitis in one patient. The primary reasons for adalimumab treatment were vascular involvement in five patients, uveitis in four, arthritis in three, mucocutaneous involvement in one, and epididymitis in one patient. Upon the development of de novo manifestation, adalimumab was switched to another biologic in four patients, dose was intensified in three, colchicine, conventional immunosuppressives and/or glucocorticoids were added in five, and topical eye drops were added in two patients, leading to remission of de novo manifestations in all patients.

Conclusion
De novo manifestations were infrequent (4%) among BS patients treated with adalimumab. Of these, 57% were major organ involvement, mainly vascular involvement. None of the patients developed posterior uveitis.
Association of rare single-nucleotide variant MUC5B rs35705950 with interstitial lung disease in Japanese rheumatoid arthritis
Authors: Higuchi Takashi , Oka Shomi , Shimada Kota , Tsunoda Shinichiro , Ito Satoshi , Okamoto Akira , Fujimori Misuzu , Nakamura Tadashi , Katayama Masao , Suzuki Michita , Saisho Koichiro , Shinohara Satoshi , Matsui Toshihiro , Migita Kiyoshi , Nagaoka Shouhei , Tohma Shigeto , Furukawa Hiroshi 
Published: August 2024

Abstract

Objectives
RA is sometimes complicated by interstitial lung disease (ILD) with a poor prognosis. A single-nucleotide variant (SNV) in MUC5B was associated with ILD in European RA patients. However, associations of this SNV were not found in Japanese RA patients, because its frequency in Japanese populations is very low. We investigated the associations of candidate SNVs including the MUC5B variant with ILD in Japanese RA.

Methods
Genotyping of MUC5B rs35705950, MUC2 rs7934606, MAD1L1 rs12699415 and PPFIBP2 rs6578890 in Japanese RA patients was conducted for association analyses.

Results
MUC5B rs35705950 was associated with usual interstitial pneumonia (UIP) (P = 0.0039, Pc = 0.0156, odds ratio [OR] 10.66, 95% CI 2.05–55.37) or ILD (P = 0.0071, Pc = 0.0284, OR 7.33, 95% CI 1.52–35.44) in Japanese RA under the allele model. MUC2 rs7934606 was associated with UIP (P = 0.0072, Pc = 0.0288, OR 29.55, 95% CI 1.52–574.57) or ILD (P = 0.0037, Pc = 0.0148, OR 22.95, 95% CI 1.27–416.13) in RA. Haplotype analyses suggested the primary association of MUC5B rs35705950 with UIP in Japanese RA. No significant association of MAD1L1 rs12699415 or PPFIBP2 rs6578890 with UIP, nonspecific interstitial pneumonia, or ILD in RA was observed.

Conclusion
MUC5B rs35705950 is associated with, and might be involved in the pathogenesis of ILD, especially UIP, in Japanese RA.
Stress-induced increase in heart-rate during sleep as an indicator of PTSD risk among combat soldiers
Authors: Simon Lisa , Levi Shlomi , Shapira Shachar , Admon Roee 
Published: August 2024

Abstract

Study Objectives
Discerning the differential contribution of sleep behavior and sleep physiology to the subsequent development of posttraumatic-stress-disorder (PTSD) symptoms following military operational service among combat soldiers.

Methods
Longitudinal design with three measurement time points: during basic training week (T1), during intensive stressed training week (T2), and following military operational service (T3). Participating soldiers were all from the same unit, ensuring equivalent training schedules and stress exposures. During measurement weeks soldiers completed the Depression Anxiety and Stress Scale (DASS) and the PTSD Checklist for DSM-5 (PCL-5). Sleep physiology (sleep heart-rate) and sleep behavior (duration, efficiency) were monitored continuously in natural settings during T1 and T2 weeks using wearable sensors.

Results
Repeated measures ANOVA revealed a progressive increase in PCL-5 scores from T1 and T2 to T3, suggesting an escalation in PTSD symptom severity following operational service. Hierarchical linear regression analysis uncovered a significant relation between the change in DASS stress scores from T1 to T2 and subsequent PCL-5 scores at T3. Incorporating participants’ sleep heart-rate markedly enhanced the predictive accuracy of the model, with increased sleep heart-rate from T1 to T2 emerging as a significant predictor of elevated PTSD symptoms at T3, above and beyond the contribution of DASS stress scores. Sleep behavior did not add to the accuracy of the model.

Conclusion
Findings underscore the critical role of sleep physiology, specifically elevated sleep heart-rate following stressful military training, in indicating subsequent PTSD risk following operational service among combat soldiers. These findings may contribute to PTSD prediction and prevention efforts.
The glucocorticoid receptor elicited proliferative response in human erythropoiesis is BCL11A-dependent
Authors: Mazzarini Maria , Cherone Jennifer , Nguyen Truong , Martelli Fabrizio , Varricchio Lilian , Funnell Alister P W , Papayannopoulou Thalia , Migliaccio Anna Rita 
Published: August 2024

Abstract
Prior evidence indicates that the erythroid cellular response to glucocorticoids (GC) has developmental specificity, namely, that developmentally more advanced cells that are undergoing or have undergone fetal to adult globin switching are more responsive to GC-induced expansion. To investigate the molecular underpinnings of this, we focused on the major developmental globin regulator BCL11A. We compared: (1) levels of expression and nuclear content of BCL11A in adult erythroid cells upon GC stimulation; (2) response to GC of CD34+ cells from patients with BCL11A microdeletions and reduced BCL11A expression, and; (3) response to GC of 2 cellular models (HUDEP-2 and adult CD34+ cells) before and after reduction of BCL11A expression by shRNA. We observed that: (1) GC-expanded erythroid cells from a large cohort of blood donors displayed amplified expression and nuclear accumulation of BCL11A; (2) CD34 + cells from BCL11A microdeletion patients generated fewer erythroid cells when cultured with GC compared to their parents, while the erythroid expansion of the patients was similar to that of their parents in cultures without GC, and; (3) adult CD34+ cells and HUDEP-2 cells with shRNA-depleted expression of BCL11A exhibit reduced expansion in response to GC. In addition, RNA-seq profiling of shRNA-BCL11A CD34+ cells cultured with and without GC was similar (very few differentially expressed genes), while GC-specific responses (differential expression of GILZ and of numerous additional genes) were observed only in control cells with unperturbed BCL11A expression. These data indicate that BCL11A is an important participant in certain aspects of the stress pathway sustained by GC.
Defining the Pathobiomes Associated with Drippy Blight in Colorado and Drippy Nut in California
Authors: Raymond Hope , Sitz Rachael A. , Pearse Ian S. , Caballero Jorge R. Ibarra , Lalande Bradley M. , Stewart Jane E. 
Published: August 2024

Drippy blight, an emergent bacterial disease of oaks, was described recently from urban oaks in the Front Range of Colorado, U.S.A. This disease, which causes branch dieback and oozing of bacterial exudates from cankers, is caused by Lonsdalea quercina and primarily affects red oaks, with northern red oak ( Quercus rubra) being the most susceptible. Drippy nut is a similar, less acute condition that exists in California, U.S.A., and affects acorns of interior live oak ( Q. wislizenii) and coastal live oak ( Q. agrifolia). The objective of this study was to compare the microbial communities of drippy blight in Colorado to those of drippy nut in California and to determine whether other pathogenic fungal or bacterial taxa are associated with the diseases. Symptomatic and asymptomatic tissues were sampled in California and Colorado, and metagenomic analyses were performed to describe the fungal and bacterial communities. We found a suite of bacterial species, dominated by taxa within the genus Zymobacter, that were associated with symptomatic tissues for both drippy nut and drippy blight. L. quercina is the main pathogenic associate of both diseases. We found fungal yeasts associated with symptomatic tissues, and although not pathogens, these taxa were present in the pathobiome of drippy nut and drippy blight in California and Colorado. We did, however, identify taxa belonging to Gnomoniopsis, a known pathogen, associated with California symptomatic samples. Our study found an overlapping suite of bacterial associates of drippy blight and drippy nut, though more variation occurred within the fungal genera associated with these oak diseases. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Evidence of Differential Attainment in Canadian Medical School Admissions: A Scoping Review
Authors: Ngo Thuy-Anh , Choi Joshua , McIntosh Alexander , Elma Asiana , Grierson Lawrence 
Published: August 2024

Abstract

Purpose
In Canada, many groups (e.g., Black, Indigenous, rural backgrounds) have historically faced and continue to encounter systemic barriers in accessing the medical profession. These barriers often manifest in performance disparities, known as differential attainment, during medical school admissions. This scoping review summarizes the nature and extent of evidence on the association of differential attainment in medical school admissions selection tools and outcomes with applicant social identity in the Canadian context.

Method
The authors used Arksey and O’Malley’s scoping review framework to summarize research studies published between 2000 and 2022 with empirical evidence of differential attainment in admissions selection tools and outcomes with respect to a range of applicant social identity categories. The authors recorded whether studies adopted a structuralist and/or intersectional perspective.

Results
Ultimately, 15 studies were included in the review. While the evidence on differential attainment associated with social identity in Canadian medical education was heterogeneous, numerous studies highlight differential attainment in the admissions process associated with applicant race and/or ethnicity (6 studies), age (5 studies), gender (4 studies), socioeconomic status (3 studies), geographic location (4 studies), and rural or urban background (5 studies). These attainment differences were reported at 3 phases of the admissions process (invitation to interview, offer of admission, and acceptance of offer) and were driven by several admissions selection tools, including grade point average, Medical College Admission Test score, and interview performance.

Conclusions
The review highlights evidence that suggests systemic, structural inequities in admissions systems manifest as differential attainment in Canadian medical school admissions. Based on this evidence, those who identify as Black or Indigenous and those with low socioeconomic status or rural backgrounds were generally more adversely affected. Admission practices must be studied and improved so medical education systems can better avow equality and human dignity and achieve equity goals.
In-office Maximal Voluntary Ventilation Testing Demonstrates Pulmonary Improvement Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis
Authors: Jalloh Hulaimatu , Andras Lindsay M. , Redding Greg , Villamor Gabriela A. , Yang Joshua , Skaggs David L. 
Published: August 2024

Objective:
Pulmonary function can be impaired in patients with adolescent idiopathic scoliosis (AIS). Maximal voluntary ventilation (MVV) has been shown to be more strongly correlated with major coronal curve, and a more easily obtained measurement of pulmonary function, than forced vital capacity (FVC). We evaluated changes in pulmonary function using these 2 measures in patients with AIS in relation to changes in major coronal curves over time.

Methods:
Forty-seven patients with AIS with thoracic curves ≥10 degrees performed pulmonary function tests using the Carefusion MicroLoop Spirometer at enrollment and 1 year later. Major coronal curve worsening >5 degrees was considered curve progression.

Results:
At enrollment, 47 patients had a mean major coronal curve of 38 degrees (range: 10 to 76 degrees). One year later, 17 patients had undergone posterior spinal fusion, 9 had curve progression >5 degrees, and 21 had no progression. MVV and major coronal curve were negatively correlated (r = -0.36, P = 0.01) at enrollment. After fusion, the major coronal curve improved by a mean of 41 degrees, and MVV improved by 23% (P < 0.01), but FVC did not improve significantly (6%, P = 0.29). In stable curves, MVV improved 12% (P = 0.01) and FVC improved 9% (P = 0.007). In patients without surgery whose curves progressed an average of 11 degrees, there was no significant change in MVV or FVC (P > 0.44).

Conclusion:
This is the first study using office-based spirometry in an orthopaedic clinic showing improved pulmonary function with posterior spinal fusion and growth in patients with AIS. It is notable that MVV improved after spinal fusion, but FVC did not, as MVV appears to be a more sensitive measurement for the assessment of pulmonary function in these patients.

Level of Evidence:
Level II.