bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epididymal mRNA expression profiles for the protein disulfide isomerase gene family: Modulation by development and androgens
Authors: Fernandes Samuel G. , Ferreira Lucas G. A. , Benham Adam M. , Avellar Maria Christina W. 
Published: August 2024

AbstractBackgroundThe endoplasmic reticulum (ER) is the central hub for protein quality control, where the protein disulfide isomerases (PDIs), encoded by at least 21 genes, play a pivotal role. These multifunctional proteins contribute to disulfide bond formation, proper folding, and protein modifications, and may act as hormone‐binding proteins (e.g., steroids), influencing hormone biology. The interplay between ER proteostasis, PDIs, and epididymis—a crucial site for sperm maturation—remains largely understudied.ObjectivesThis study characterizes transcriptional signatures of Pdi genes in the epididymis.Material and methodsTranscriptional profiles of selected Pdi genes were assessed in adult Wistar rat tissues, and epididymis under different experimental conditions (developmental stages, surgical castration, and efferent ductules ligation [EDL]). In silico bioinformatic analyses identified expression trends of this gene family in human epididymal segments.ResultsP4hb, Pdia3, Pdia5, Pdia6, Erp44, Erp29, and Casq1 transcripts were detected in both reproductive and non‐reproductive tissues, while Casq2 exhibited higher abundance in vas deferens, prostate, and heart. Pdilt, highly expressed in testis, and Pdia2, highly expressed in heart, showed minimal mRNA levels in the epididymis. In the mesonephric duct, epididymal embryonic precursor, P4hb, Pdia3, Pdia5, Pdia6, and Erp29 mRNAs were found at gestational day (GD) 17.5. Except for Erp29, which remained stable, these Pdi transcript levels increased from GD17.5 to GD20.5, when epididymal morphogenesis occurs, and were maintained to varying degrees in the epididymis during postnatal development. Surgical castration downregulated P4hb, Pdia3, Pdia5, Pdia6, Pdilt and Erp29 transcripts, an effect reversed by testosterone replacement. Conversely, transcript levels remained unaffected by EDL, except P4hb, which was reduced in caput epididymis. All 21 PDI genes exhibited diverse transcriptional profiles across the human epididymis.Discussion and conclusionThe findings lay the foundations to explore Pdi genes in epididymal biology. As a considerable proportion of male infertility cases are idiopathic, targeting hormonal regulation of protein quality control in epididymis represents a route to address male infertility and advance therapeutic interventions in this domain.
Nature lifts when feeling low: Daily high and low awe nature clips decrease repetitive negative thinking and dampening and increase subjective happiness in adults
Authors: Bogaert Liesbeth , Joye Yannick , Dejonckheere Egon , Goossens Ine , Mertens Kaat , Raes Filip 
Published: August 2024

AbstractExposure to nature can enhance mental well‐being, making nature‐based interventions promising for the treatment and prevention of mental health problems like depression. Given the decreased self‐focus and sense of self‐diminishment associated with awe, the present study investigated the impact of exposure to awe‐evoking nature on two key risk and maintenance factors of depression—repetitive negative thinking (RNT) and dampening of positive feelings—and on subjective happiness. In a randomized controlled trial, we tested the effects of exposure to awe‐evoking nature clips through a 1‐week intervention, consisting of watching a 1‐min clip on a daily basis of either awe‐evoking (n high awe = 108) or more mundane nature scenes (n low awe = 105). Before, immediately after (post‐intervention) and 1 week after the intervention (follow‐up), participants completed self‐report scales probing RNT, dampening, and subjective happiness. Results indicated significant decreases in these outcomes at post‐intervention and follow‐up in both groups. We discuss study limitations, touch upon future research ideas, and reflect upon the role of nature for clinical applications.
Long‐term safety and efficacy of filgotinib for the treatment of moderately to severely active ulcerative colitis: Interim analysis from up to 4 years of follow‐up in the SELECTION open‐label long‐term extension study
Authors: Feagan Brian G. , Matsuoka Katsuyoshi , Rogler Gerhard , Laharie David , Vermeire Séverine , Danese Silvio , Loftus Edward V. , Beales Ian , Schreiber Stefan , Kim Hyo Jong , Faes Margaux , de Haas Angela , Masior Tomasz , Rudolph Christine , Peyrin‐Biroulet Laurent 
Published: August 2024

SummaryBackgroundFilgotinib, an oral, once‐daily, Janus kinase 1 preferential inhibitor, is an approved treatment for moderately to severely active ulcerative colitis.AimsThe aim of this study is to assess the safety and efficacy of continued filgotinib therapy over ~4 years in the long‐term extension of the phase 2b/3 SELECTION trial (SELECTIONLTE; NCT02914535).MethodsIn this interim analysis of SELECTIONLTE, SELECTION completers (week 10 responders to filgotinib who completed the maintenance study) continued their assigned treatment (double‐blind filgotinib 200 mg [FIL200] or filgotinib 100 mg) and SELECTION week 10 non‐responders received open‐label FIL200. We assessed safety by adverse events (AEs), and efficacy by partial Mayo Clinic Score (pMCS), inflammatory biomarkers and health‐related quality of life (HRQoL). We compared safety and efficacy between achievers and non‐achievers of a multi‐component endpoint, comprehensive disease control (CDC), comprising symptomatic, endoscopic, inflammatory biomarker and HRQoL improvements.ResultsData for completers (n = 250) and non‐responders (n = 372) were reported for ≤202 weeks. AE occurrences were low and consistent with previous analyses. The as‐observed proportion of FIL200‐treated patients in pMCS, biomarker and HRQoL remission during SELECTIONLTE remained high among completers (week 144: 80.0%, 86.4% and 86.0%, respectively) and increased among non‐responders (week 192: 62.1%, 76.7% and 59.3%, respectively). Significantly higher proportions of CDC achievers at SELECTION week 58 achieved pMCS, IBDQ and corticosteroid‐free pMCS remission than non‐achievers, up to LTE week 96.ConclusionsFilgotinib induced and maintained symptomatic remission and improved HRQoL over 4 years. Safety results showed a proven long‐term benefit–risk profile. FIL200‐treated CDC achievers had better long‐term outcomes than non‐achievers.
Does BioAge identify accelerated aging in individuals with bipolar disorder? An exploratory study in the FACE‐BD cohort
Authors: Etain Bruno , Marie‐Claire Cynthia , Spano Luana , Bellivier Frank , Leboyer Marion , Gard Sébastien , Lefrere Antoine , Belzeaux Raoul , Courtet Philippe , Dubertret Caroline , Schwan Raymund , Aubin Valerie , Roux Paul , Polosan Mircea , Samalin Ludovic , Haffen Emmanuel , Olié Emilie , Godin Ophelia ,   FondaMental Advanced Centers of Expertise in Bipolar Disorders (FACE‐BD) Collaborators
Published: August 2024

AbstractBackgroundIndividuals with bipolar disorders (BD) have an estimated loss of life expectancy around 10–15 years. Several laboratory‐measured biomarkers of accelerated aging exist (e.g., telomere length), however with a questionable transferability to bedside. There is a need for easily and inexpensively measurable markers of aging, usable in routine practice, such as BioAge.MethodsWe calculated BioAge that estimates biological age based on routine blood tests and a physical exam, in a sample of 2220 outpatients with BD. We investigated associations between BioAge Acceleration (BioAgeAccel), which is an indicator of accelerated aging, and sociodemographic variables, clinical variables, and current psychotropic medication use.ResultsMean chronological age was 40.2 (±12.9). Mean BioAge was 39.1 (±12.4). Mean BioAgeAccel was 0.08 (±1.8). A minority of individuals (15%) had a BioAgeAccel above 2 years. Multivariable analyses suggested strong associations between a higher BioAgeAccel and younger age, male sex, overweight and sleep disturbances. Regarding current psychotropic medication use, discrepancies between univariate and multivariate analyses were observed.ConclusionsA minority of individuals with BD had an accelerated aging as measured by BioAge. We identified associations with potentially modifiable factors, such as higher body mass index and sleep disturbances, that are however nonspecific to BD. These results require replications in independent samples of individuals with BD, and comparisons with a control group matched for age and gender. Longitudinal studies are also required to test whether any change in metabolic health, or sleep might decrease BioAgeAccel.
National Surgical Quality Improvement Program audit of contemporary perioperative care for radical cystectomy
Authors: Pfail John , Capellan Jasmin , Passarelli Rachel , Kaldany Alain , Chua Kevin , Lichtbroun Benjamin , Srivastava Arnav , Golombos David , Jang Thomas L. , Pitt Henry A. , Packiam Vignesh T. , Ghodoussipour Saum 
Published: August 2024

ObjectiveTo examine the impact of increased compliance to contemporary perioperative care measures, as outlined by enhanced recover after surgery (ERAS) guidelines, among patients undergoing radical cystectomy (RC).Patients and MethodsFrom the National Surgical Quality Improvement Program database we captured patients undergoing RC between 2019 and 2021. We identified five perioperative care measures: regional anaesthesia block, thromboembolism prophylaxis, ≤24 h perioperative antibiotic administration, absence of bowel preparation, and early oral diet. We stratified patients by the number of measures utilised (one to five). Statistical endpoints included 30‐day complications, hospital length of stay (LOS), readmissions, and optimal RC outcome. Optimal RC outcome was defined as absence of any postoperative complication, re‐operation, prolonged LOS (75th percentile, 8 days) with no readmission. Multivariable regressions with Bonferroni correction were performed to assess the association between use of contemporary perioperative care measures and outcomes.ResultsOf the 3702 patients who underwent RC, 73 (2%), 417 (11%), 1010 (27%), 1454 (39%), and 748 (20%) received one, two, three, four, and five interventions, respectively. On multivariable analysis, increased perioperative care measures were associated with lower odds of any complication (odds ratio [OR] 0.66, 99% confidence interval [CI] 0.6–0.73), and shorter LOS (β −0.82, 99% CI −0.99 to −0.65). Furthermore, patients with increased compliance to contemporary care measures had increased odds of an optimal outcome (OR 1.38, 99% CI 1.26–1.51).ConclusionsAmong the measures we assessed, greater adherence yielded improved postoperative outcomes among patients undergoing RC. Our work supports the efficacy of ERAS protocols in reducing the morbidity associated with RC.
Tumor‐derived mitochondrial formyl peptides suppress tumor immunity through modification of the tumor microenvironment
Authors: Waki Kayoko , Ozawa Miyako , Ohta Keisuke , Komatsu Nobukazu , Yamada Akira 
Published: August 2024

AbstractMitochondrial N‐formylpeptides are released from damaged or dead cells to the extracellular spaces and cause inflammatory responses. The role of mitochondrial N‐formylpeptides in aseptic systemic inflammatory response syndromes induced by trauma or cardiac surgery has been well investigated. However, there are no reports regarding the role of mitochondrial N‐formylpeptides in cancer. In this study, we investigated the role of tumor cell‐derived mitochondrial N‐formylpeptides in anti‐tumor immunity using knockout murine tumor cells of mitochondrial methionyl‐tRNA formyltransferase (MTFMT), which catalyze N‐formylation of mitochondrial DNA‐encoded proteins. There was no apparent difference among the wild‐type and MTFMT‐knockout clones of E.G7‐OVA cells with respect to morphology, mitochondrial dynamics, glycolysis and oxidative phosphorylation, oxygen consumption rate, or in vitro cell growth. In contrast, in vivo tumor growth of MTFMT‐knockout cells was slower than that of wild‐type cells. A reduced number of myeloid‐derived suppressor cells and an increase of cytotoxic T‐lymphocytes in the tumor tissues were observed in the MTFMT‐knockout tumors. These results suggested that tumor cell‐derived mitochondrial N‐formylpeptides had a negative role in the host anti‐tumor immunity through modification of the tumor microenvironment.
Overcoming Barriers to Remission in Severe Eosinophilic Asthma: Two‐Year Real‐World Data With Benralizumab
Authors: Jackson David J. , Burhan Hassan , Rupani Hitasha , Pfeffer Paul E. , Clifton Ian J. , Faruqi Shoaib , Dhariwal Jaideep , Patel Pujan , Morris Tamsin , Lipworth Joseph , Watt Michael , Lupton Charlotte , Dube Sabada , Hickey Joe , Nanzer Alexandra M. 
Published: August 2024

ABSTRACTBackgroundBenralizumab has been reported to lead to clinical remission of severe eosinophilic asthma (SEA) at 1 year in some patients. However, whether this is maintained over a longer term remains unclear. Additionally, the impact of pulmonary and extrapulmonary comorbidities on the ability to meet remission is poorly understood.MethodsClinical outcomes including remission of SEA with benralizumab at 1 and 2 years were assessed retrospectively in a real‐world UK multi‐centre severe asthma cohort. The presence of clinically relevant pulmonary and extrapulmonary comorbidities associated with respiratory symptoms was recorded. Analyses to identify factors associated with the ability to meet remission were performed.ResultsIn total, 276 patients with SEA treated with benralizumab including 113 patients who had switched from a previous biologic to benralizumab were included. Overall, clinical remission was met in 17% (n = 31/186) and 32% (n = 43/133) of patients at 1 and 2 years, respectively. This increased to 28% at 1 year and 49% at 2 years once patients with pulmonary and/or extrapulmonary comorbidities were excluded. Body mass index (BMI) and maintenance OCS (mOCS) use demonstrated a negative association with clinical remission at 1 (BMI: OR: 0.89, 95% CI: 0.82–0.96, p < 0.01; mOCS: OR: 0.94, 95% CI: 0.89–0.99, p < 0.05) and 2 years (BMI: OR: 0.93, 95% CI: 0.87–0.99, p < 0.05; mOCS: OR: 0.95, 95% CI: 0.89–0.99, p < 0.05).ConclusionsIn this long‐term, real‐world study, patients with SEA demonstrated the ability to meet and sustain clinical remission when treated with benralizumab. The presence of comorbidities including obesity, which are known to be independently associated with respiratory symptoms, reduced the likelihood of meeting clinical remission.
Advances in gut–brain organ chips
Authors: Zhang Yu , Lu Si‐Ming , Zhuang Jian‐Jian , Liang Li‐Guo 
Published: August 2024

AbstractThe brain and gut are sensory organs responsible for sensing, transmitting, integrating, and responding to signals from the internal and external environment. In‐depth analysis of brain–gut axis interactions is important for human health and disease prevention. Current research on the brain–gut axis primarily relies on animal models. However, animal models make it difficult to study disease mechanisms due to inherent species differences, and the reproducibility of experiments is poor because of individual animal variations, which leads to a significant limitation of real‐time sensory responses. Organ‐on‐a‐chip platforms provide an innovative approach for disease treatment and personalized research by replicating brain and gut ecosystems in vitro. This enables a precise understanding of their biological functions and physiological responses. In this article, we examine the history and most current developments in brain, gut, and gut–brain chips. The importance of these systems for understanding pathophysiology and developing new drugs is emphasized throughout the review. This article also addresses future directions and present issues with the advancement and application of gut–brain‐on‐a‐chip technologies.
The fifth edition of the WHO‐Classification – what is new for cutaneous lymphomas?
Authors: Melchers Susanne , Albrecht Jana D. , Kempf Werner , Nicolay Jan P. 
Published: August 2024

SummaryThe recently published 5th edition of the “World Health Organization classification of hematolymphoid tumors: lymphoid neoplasms” provides a hierarchical reorganization. In general, new (definitive) entities as well as tumor‐like lesions were included.Primary cutaneous B‐cell lymphomas (CBCL) received a thorough review. A new class/family of cutaneous follicle center lymphomas was defined. Primary cutaneous marginal zone lymphoma is now presented as a separate entity independent from extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue. In primary cutaneous T‐cell lymphoma, former provisional entities were upgraded to definite entities. Sézary Syndrome was sorted into the class/family of mature T‐cell and NK‐cell leukemias. Additionally, a newly formed entity of primary cutaneous peripheral T‐cell lymphoma, NOS was created for CTCL entities that do not fit into the already described CTCL entities.The increasing importance of genomic and molecular data has already been recognized in classifying leukemias and systemic lymphomas. However, in PCL the genomic landscape has not yet been fully described and validated. Therefore, future research is necessary to describe the genomic and molecular mechanisms underlying the disease entities more clearly. This would both meet a diagnostic need and valuably contribute to future classification schemes.
Neurocardiac pathologies associated with potassium channelopathies
Authors: Singh Veronica , Auerbach David S. 
Published: August 2024

AbstractVoltage‐gated potassium channels are expressed throughout the human body and are essential for physiological functions. These include delayed rectifiers, A‐type channels, outward rectifiers, and inward rectifiers. They impact electrical function in the heart (repolarization) and brain (repolarization and stabilization of the resting membrane potential). KCNQx and KCNHx encode Kv7.x and Kv11.x proteins, which form delayed rectifier potassium channels. KCNQx and KCNHx channelopathies are associated with both cardiac and neuronal pathologies. These include electrocardiographic abnormalities, cardiac arrhythmias, sudden cardiac death (SCD), epileptiform discharges, seizures, bipolar disorder, and sudden unexpected death in epilepsy (SUDEP). Due to the ubiquitous expression of KCNQx and KCNHx channels, abnormalities in their function can be particularly harmful, increasing the risk of sudden death. For example, KCNH2 variants have a dual role in both cardiac and neuronal pathologies, whereas KCNQ2 and KCNQ3 variants are associated with severe and refractory epilepsy. Recurrent and uncontrolled seizures lead to secondary abnormalities, which include autonomics, cardiac electrical function, respiratory drive, and neuronal electrical activity. Even with a wide array of anti‐seizure therapies available on the market, one‐third of the more than 70 million people worldwide with epilepsy have uncontrolled seizures (i.e., intractable/drug‐resistant epilepsy), which negatively impact neurodevelopment and quality of life. To capture the current state of the field, this review examines KCNQx and KCNHx expression patterns and electrical function in the brain and heart. In addition, it discusses several KCNQx and KCNHx variants that have been clinically and electrophysiologically characterized. Because these channel variants are associated with multi‐system pathologies, such as epileptogenesis, Kv7 channel modulators provide a potential anti‐seizure therapy, particularly for people with intractable epilepsy. Ultimately an increased understanding of the role of Kv channels throughout the body will fuel the development of innovative, safe, and effective therapies for people at a high risk of sudden death (SCD and SUDEP).
Fatigue‐induced stress redistribution in prestressed concrete beams modeled using the constitutive hypothesis of inter‐aggregate degradation
Authors: Baktheer Abedulgader , Esfandiari Soheil , Aguilar Mario , Becks Henrik , Classen Martin , Chudoba Rostislav 
Published: August 2024

AbstractDespite of intensive research on concrete fatigue, the transfer of fatigue characteristics determined at the material level to the structural level remains a challenging issue. In this paper, the propagation of fatigue‐induced damage through the concrete structure is analyzed using a microplane fatigue model for concrete recently developed by the authors. To this end, our recent experimental study in which the fatigue propagation was monitored at the structural level represented by prestressed concrete beams is used to derive a general interpretation of the stress redistribution process using of the developed model. The numerical studies show that the developed microplane fatigue model provides a powerful computational tool for in‐depth analysis of the correspondence between the fatigue behavior at the material and structural scales in a wide range of load configurations. In addition, the thermodynamically based constitutive model allows for the quantification of the energy dissipation during the process, revealing the possibility of deriving material‐specific energetic characteristics that can further help to make the predictions of fatigue life more accurate.
‘None of Them Know Me’: A Qualitative Study of the Implications of Locum Doctor Working for Patient Experience
Authors: Ferguson Jane , Stringer Gemma , Walshe Kieran , Donnelly Ailsa , Grigoroglou Christos , Allen Thomas , Kontopantelis Evangelos , Ashcroft Darren M. 
Published: August 2024

ABSTRACTIntroductionThere have been some concerns about the impact of temporary doctors, otherwise known as locums, on patient safety and the quality of care. Despite these concerns, research has paid little attention to the implications of locum working on patient experience.MethodsA qualitative semi‐structured interview study was conducted with 130 participants including locums, people working with locums and patients with experience of being seen or treated by locums. Analysis was conducted using a reflexive thematic approach and abductive analysis to position themes against wider knowledge.ResultsThree main themes were constructed through analysis: (1) Awareness and disclosure; patients were not always aware if their doctor was a locum, and there was some debate about whether patients had a right to know, particularly if locum working presented quality and safety risks. (2) Continuity and accessibility of care; access was regarded as priority for acute conditions, but for long‐term or serious conditions, patients preferred to see a permanent doctor who knew their history, although it was acknowledged that locums could provide fresh perspectives. (3) Communication and practice; locums and patients described how consultations were approached differently when doctors worked as locums. Patients evaluated their interactions based on how safe they felt with practitioners.ConclusionPatients reported that they were unlikely to have continuity of care with any doctors delivering care, regardless of their contractual status. Locums sometimes provided new perspectives on care which could be beneficial for patient outcomes, but for patients with long‐term, complex or serious conditions continuity of care was important, and these patients may avoid or delay seeking care when locums are the only available option.Patient or Public ContributionPatients and carers were involved in our study from inception to dissemination. Our Patient and Public Involvement (PPI) forum was involved throughout project design and planning and gave us feedback and guidance on research materials and outputs (e.g., study protocol, participant information sheets, survey tools, interview schedules, emerging findings). Our PPI forum co‐produced our patient interview schedule, two members of our PPI forum led the patient focus groups and all were involved in analysis of patient interviews. Our PPI Chair was involved in the preparation of this manuscript.