bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of the Antigen-Specific CD8+ TCR Repertoire across the Life Span: Evidence for Clonal Homogenization of the Old TCR Repertoire
Authors: Rudd Brian D. , Venturi Vanessa , Davenport Miles P. , Nikolich-Žugich Janko 
Published: January 2011

Abstract
Defects in T cell responses against pathogens and reduced diversity of TCRs have been described at both extremes of the life span. Yet, we still lack information on how Ag-specific T cell populations are maintained and/or altered from birth to old age. In this study, for the first time to our knowledge, we provide insight into Ag-specific TCR repertoire changes over the life span at the single-cell level. We have examined the TCR diversity of the primary CD8+ T cell response to the immunodominant HSV-1 epitope HSV glycoprotein B 495–502 (HSV gB498–505; SSIEFARL) (gB-8p) in neonatal, adult, and old C57BL/6 mice. The global distinctive features of the gB-8p–specific TCR repertoire were preserved in mice of different ages. However, both old and especially neonatal mice exhibited significant decreases in TCR diversity compared with that of adult mice. Still, although the neonatal Ag-specific repertoire comprised expectedly shorter germline-biased CDR3β lengths, the repertoire was surprisingly complex, and only a minority of responding cells lacked random nucleotide additions. Changes with aging included increased use of the already dominant TCRVβ10 family, a trend for lower content of the TCR containing the germline WG motif in the CDR3, and a remarkable sharing of one dominant clonotype between individual old mice, implying operation of selective mechanisms. Implications for the rational design of vaccines for neonates and the elderly are discussed.
Cutting Edge: The Murine High-Affinity IgG Receptor FcγRIV Is Sufficient for Autoantibody-Induced Arthritis
Authors: Mancardi David A. , Jönsson Friederike , Iannascoli Bruno , Khun Huot , Van Rooijen Nico , Huerre Michel , Daëron Marc , Bruhns Pierre 
Published: January 2011

Abstract
K/BxN serum-induced passive arthritis was reported to depend on the activation of mast cells, triggered by the activating IgG receptor FcγRIIIA, when engaged by IgG1 autoantibodies present in K/BxN serum. This view is challenged by the fact that FcγRIIIA-deficient mice still develop K/BxN arthritis and because FcγRIIIA is the only activating IgG receptor expressed by mast cells. We investigated the contribution of IgG receptors, IgG subclasses, and cells in K/BxN arthritis. We found that the activating IgG2 receptor FcγRIV, expressed only by monocytes/macrophages and neutrophils, was sufficient to induce disease. K/BxN arthritis occurred not only in mast cell-deficient Wsh mice, but also in mice whose mast cells express no activating IgG receptors. We propose that at least two autoantibody isotypes, IgG1 and IgG2, and two activating IgG receptors, FcγRIIIA and FcγRIV, contribute to K/BxN arthritis, which requires at least two cell types other than mast cells, monocytes/macrophages, and neutrophils.
Sustaining Mediterranean Irrigated Agriculture under a Changing Climate
Authors: Rodríguez-Díaz Juan Antonio , Topcu Sevilay 
Published: January 2011

Irrigated agriculture is crucial for food security and rural development in the Mediterranean region, but it will be significantly affected by climate change. Evaluating the present and future agroclimatic conditions and predicting the impacts on irrigation requirements for the dominant crops in the region may help to develop more appropriate adaptation strategies. This paper describes the expected changes in climate and assesses the irrigation requirement for key crops grown across the region, using a case study in a typical river basin in Spain. Milder but wetter winters and more extreme hot, dry summers are anticipated. Evapotranspiration, crop water requirements and irrigation needs for major crops are expected to increase by as much as 30% by the 2080s.
Van Der Waals Hybrid Integration of 2D Semimetals for Broadband Photodetection
Authors: Li Xue , Liu Kunxuan , Wu Di , Lin Pei , Shi Zhifeng , Li Xinjian , Zeng Longhui , Chai Yang , Lau Shu Ping , Tsang Yuen Hong 
Published: February 2025

AbstractHybrid heterostructures are pivotal in the advanced broadband detection technology. The emergence of 2D semimetals has expanded the range of materials in heterostructures beyond conventional narrow‐gap materials for room‐temperature broadband detection applications due to their extraordinary optical and electrical properties. This review outlines the cutting‐edge and latest advancements in broadband photodetectors (PDs) engineered from heterostructures that synergistically combine 2D semimetals with several different dimensional materials. It begins with a fundamental investigation, offering an in‐depth explanation of the essential material properties and a summary of synthesis methodologies. Then, the discussion advances to provide an analytical overview of the categorization, underlying photodetection mechanism, and figures‐of‐merit of these advanced PDs. Subsequently, the narrative shifts to a comprehensive analysis of heterogeneous integrated devices. The review further highlights the diverse optoelectronic applications of broadband PDs, spanning image sensing, optical communication, position‐sensitive detection, integrated sensing and computing, spintronics, and computational spectroscopy are thoroughly highlighted. Finally, the review concludes by addressing the challenges and opportunities in advancing 2D semimetal materials for photodetection.
Tailoring UV Responsivity and Quantum Efficiency of ZnO Nanorod‐Polymer‐Dispersed Cholesteric Liquid Crystal Heterostructure‐Based Photodetector Device
Authors: Pathinti Ramadevi Suguru , Thyda Lavanya , Thangaraju Kuppusamy , Mishra Yogendra Kumar , Vallamkondu Jayalakshmi 
Published: February 2025

AbstractThe development of an advanced ultraviolet (UV) photodetector that integrates a polymer‐dispersed cholesteric liquid crystal (PDCLC) with a ZnO nanorods (ZNRs) heterostructure is reported. The ZNRs are synthesized via a hydrothermal method and then spin‐coated with PDCLC, resulting in a photodetector with notably enhanced electrical and optical performance. Under 365 nm UV illumination at 5 mW cm−2 and 10 V, the PDCLC‐coated ZNRs array achieved a high photocurrent density of 171 µA cm−2, showcasing significant gains over devices without PDCLC. The novel ZNRs‐PDCLC heterostructure demonstrated a remarkable responsivity of 172.21 mA W−1 and an external quantum efficiency (EQE) of 58.44%, a substantial improvement compared to ZNRs‐only (72.27 mA W−1, 23.39% EQE) and ZnO seed layer‐based devices (14.48 mA W−1, 4.8% EQE). This enhancement stems from the PDCLC effective sensitization, which promotes charge carrier activation and energy band alignment in ZnO, resulting in a dynamic, time‐responsive photodetection. These findings underscore the potential of ZNRs‐PDCLC heterostructures to drive advances in high‐performance UV photodetectors.
Efficient Site‐Directed Mutagenesis Mediated by Primer Pairs with 3’‐Overhangs
Authors: Mousavi Negar , Zhou Ethan , Razavi Arezousadat , Ebrahimi Elham , Varela‐Castillo Paulina , Yang Xiang‐Jiao 
Published: February 2025

AbstractSite‐directed mutagenesis is an essential tool in molecular biology, protein engineering, plasmid engineering and synthetic biology. While the QuickChange method has been one of the most employed methods for site‐directed mutagenesis, it is hindered by low efficiency and frequent introduction of unwanted mutations at the primer sites, raising the urgent need for new, more efficient, and reliable methods. Here, we present an optimized site‐directed mutagenesis protocol that leverages partially complementary primer pairs with 3’‐overhangs to improve mutagenesis efficiency and reduce error rates. Our method significantly enhances success rates, achieving an average efficiency of ∼50% with some instances approaching the ideal threshold of 100%, while also minimizing the time required for mutant generation. Typically, only 3 colonies need to be analyzed per mutagenesis reaction, and a skillful trainee can engineer 1 to 2 dozen mutant plasmids within a week. In addition, with an in‐house protocol for preparing highly competent bacterial cells, we have further increased the reliability and cost‐effectiveness of the method. Notably, such competent cells have been kept in a liquid nitrogen tank for >12 years with minimal loss of competency. Thus, this refined method offers a robust, efficient, and scalable solution for high‐precision gene modification in vitro, with broad applications in protein and plasmid engineering. © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: In vitro site‐directed mutagenesis using an optimized primer design strategyBasic Protocol 2: Preparation of high‐efficiency chemocompetent DH5α cells for transformation of mutagenized plasmid productsBasic Protocol 3: Transformation of chemocompetent DH5α cells and obtaining bacterial colonies with correctly mutagenized plasmid productsAlternate Protocol: Transformation if glycerol stocks are unavailable
Matricaria chamomilla L. Ameliorates Asthma by Protecting OVA‐Induced Rats and LPS‐Induced Human Bronchial Epithelial Cells Through Suppressing Autophagy and Apoptosis
Authors: Peng Jun , Zhao Feicui , Kang Xiaolong , Aierken Nadire , Li Qian 
Published: February 2025

ABSTRACTThe rising prevalence of asthma has heightened awareness of the benefits of functional foods and nutraceuticals for managing the condition. Matricaria chamomilla L., a plant with various health benefits, is commonly consumed as tea in China and other countries. We previously reported the chemical composition and anti‐asthma effect of the active fraction of M. Chamomile (MC). This study investigated the protective mechanism of MC on asthma using an ovalbumin (OVA)‐induced asthma model in rats and lipopolysaccharide (LPS)‐induced human bronchial epithelial cells (16HBE). The effect of MC on asthmatic rats was evaluated through biochemical and histological analyses. Following treatment with MC in OVA‐induced asthmatic rats, improvements were observed in behavioral measures, total and differential cell counts of leukocytes in bronchoalveolar lavage fluid (BALF), inflammatory cell infiltration, and the structural integrity of lung and bronchial tissues. Additionally, immunohistochemical analysis revealed an increase in the protein expression level of Kif3a, while the expression levels of LC‐3B, BECN1, and Caspase‐3 were decreased. Furthermore, the effect of MC on autophagy was analyzed using an LPS‐induced 16HBE cell model. MC reduced cell damage and determined the optimal treatment concentration at 200 μg/mL for 48 h; LPS‐induced cell apoptosis was reversed by MC using flow cytometry analysis. Autophagy flux was measured through mRFP‐GFP‐LC3 adenovirus, and MC blocked the autophagic flux of 16HBE cells induced by LPS. The mRNA and protein expression of LC3‐II, BECN1, and Cleaved Caspase‐3 were decreased, whereas Kif3a was increased following treatment with MC. The protective effect of co‐treatment with 3‐MA and MC was more significant, and MC exhibited similar efficacy to 3‐MA in inhibiting autophagy. Hence, MC is a potential autophagy inhibitor, which could inhibit over‐activated autophagy levels to enhance Kif3a expression, thereby decreasing apoptosis to against asthma. M. Chamomile is a promising pharmaceutical and dietary supplement candidate for the amelioration of asthma.
Synchronous clear cell renal cell carcinoma and classic Hodgkin lymphoma
Authors: Christie‐Nguyen Phuoc , Ahmed Ahmed A , Ibrahim Nourhan , Armstrong Jacob , Mai Brenda 
Published: February 2025

IntroductionThe coexistence of renal cell carcinoma and classic Hodgkin lymphoma is exceedingly rare, with only two documented cases. Here, we present the third case diagnosed in our institution.Case presentationA 46‐year‐old man presented with right flank pain, fever, mild pancytopenia, and renal mass on computed tomography scan, suggesting renal malignancy. Despite intravenous antibiotics and extensive workup for recurrent fever, his condition did not improve. A bone marrow biopsy revealed rare large EBV‐positive B cells. Surprisingly, imaging only showed minimal intraabdominal lymphadenopathy in the perinephric region. Subsequent surgery confirmed clear cell renal cell carcinoma in the kidney and scattered large, atypical cells consistent with classic Hodgkin lymphoma in the suprahilar lymph node.ConclusionThis case presents a rare case of classic Hodgkin lymphoma occurring in the perirenal region. When clinicians encounter unexplained symptoms in patients with primary tumors, additional biopsies should be considered for possible secondary malignancy.
Epidemiology of hallux valgus surgery in Italy: A nationwide study from 2001 to 2016
Authors: Longo Umile Giuseppe , Papalia Rocco , Mazzola Alessandro , De Salvatore Sergio , Marinozzi Andrea , Campi Stefano , Piergentili Ilaria , D'Hooghe Margaux , Zaffagnini Stefano , Samuelsson Kristian , Denaro Vincenzo 
Published: February 2025

AbstractPurposeThis study intended to estimate the annual number of hallux valgus surgical procedures in Italy and the patients' epidemiological features. A secondary goal was to compare the demographic differences in access to hallux valgus surgery amongst three Italian macroregions.MethodsThe analysis was conducted by using the National Hospital Discharge Records database provided by the Italian Ministry of Health.Results721,514 surgical procedures for Acquired Hallux valgus were performed. The cumulative incidence was 88.2 procedures for every 100,000 Italian residents. The highest number of procedures was found in the 60–64 age class. 91.2% of patients were females. The mean length of hospitalisation was 2.1 ± 2.2 days. Patients aged 95–99 had more days of hospitalisation on average. 51.9% of procedures were performed in the North, 25.7% in the Centre and 22.4% in the South. 98.5% of patients from the North received surgical treatment in the same macroregion of domicile: 90% in the Centre and 78.5% in the South. The main primary procedure was: bunionectomy with soft tissue correction and osteotomy of the first metatarsal (79.9%, 77.51 International Classification of Diseases, Ninth Revision, Clinical Modification code).ConclusionsThe socio‐economic burden of hallux valgus surgery in Italy is relevant. The incidence of hallux valgus surgery has progressively increased between 2001 and 2012 and decreased from 2012 to 2016. A geographically unequal distribution of procedures between the three Italian macroregions was pointed out. Migratory flows of patients from the South to the North for undergoing the procedure were observed.Level of EvidenceLevel III.
Analysis of C4 Concentrations to Predict Impact of Patient‐Reported Diarrhea Associated With the Ileal Bile Acid Transporter Inhibitor Linerixibat
Authors: Carreño Fernando , Mehta Rashmi , de Souza Andrea Ribeiro , Collins Jon , Swift Brandon 
Published: February 2025

ABSTRACTLinerixibat, an ileal bile acid transporter (IBAT) inhibitor, is being evaluated for the treatment of pruritus in primary biliary cholangitis (PBC). Diarrhea is commonly reported with this drug class as IBAT inhibition redirects bile acids (BA) to the colon. Serum 7‐alpha‐hydroxy‐4‐cholesten‐3‐one (C4) measurement is a validated method to identify BA diarrhea. To inform dose selection, we characterized the relationship between linerixibat dose, C4 levels, and patient‐reported bother on the gastrointestinal symptom rating scale (GSRS) diarrhea question. A kinetic‐pharmacodynamic model was developed using data from five Phase 1/2 trials, to describe the effect of linerixibat dose (1–180 mg) and regimen (once/twice daily) on C4 concentrations over time. GSRS data from patients with PBC and pruritus in the Phase 2b GLIMMER study (NCT02966834) were used to develop a proportional odds model to predict the probability of a score of 1–7 (no–very severe discomfort) to the question “Have you been bothered by diarrhea during the past week?” in relation to linerixibat dose. The two models were linked to describe the linerixibat dose‐C4‐diarrhea bother relationship. Models were validated using graphical and numerical assessment and visual predictive checks. Linerixibat caused dose‐dependent increases in C4 until saturation (~180 mg total daily dose). Increased C4 concentrations trended with increased GSRS diarrhea scores. Simulations demonstrated increases in moderate‐to‐very severe (≥ 4) diarrhea scores with increasing linerixibat dose. Increases in patient‐reported diarrhea scores were linerixibat dose‐dependent. Selecting an optimal dose that maximizes linerixibat's ability to improve pruritus while minimizing patient‐reported diarrhea bother is important to support treatment adherence.
Post pubertal outcome after use of oral mucosa in urethral reconstruction for hypospadias in prepubertal boys: a systematic review
Authors: Tsachouridis George , Nijman Rien , de Kort Laetitia M. O. , de Graaf Petra 
Published: February 2025

Abstract
Oral mucosa graft urethroplasty (OMGU) is a surgical technique used in complex hypospadias repair. However, long-term outcomes in prepubertal boys, particularly through and after puberty, are not well established. To systematically review the long-term outcomes of OMGU in prepubertal boys with hypospadias, focusing on changes observed after puberty. A systematic literature search was conducted in PubMed, Embase, and Cochrane Library. Studies reporting long-term outcomes of OMGU in prepubertal boys with hypospadias were included. The quality of evidence was assessed using the ROBINS-I tool. Three studies of moderate quality met the inclusion criteria. Outcomes were mixed, with some patients experiencing favorable results and others facing complications such as meatal stenosis, urethral strictures, and fistulas. The scarcity of high-quality, long-term studies highlights a significant knowledge gap in this area. This systematic review reveals insufficient evidence to establish the long-term efficacy and safety of OMGU in prepubertal boys with hypospadias, particularly concerning pubertal development and post-pubertal outcomes. Future research should prioritize prospective, longitudinal studies with larger sample sizes and standardized outcome measures to address these critical gaps in understanding.
Unforeseen nodal upstaging in patients undergoing segmentectomy without frozen section: a multicenter retrospective cohort study
Authors: Huang Lin , Brunelli Alessandro , Stefanous Demetrios , Zanfrini Edoardo , Donlagic Abid , Gonzalez Michel , Petersen René Horsleben 
Published: February 2025

Abstract

Objective
The study aimed to evaluate the risk of unforeseen nodal upstaging (pN+) after pulmonary segmentectomy without intraoperative frozen section.

Methods
We conducted a retrospective analysis for consecutive patients who underwent segmentectomy for clinical stage IA1-2 non-small cell lung cancer (cIA1-2 NSCLC) in three centers between January 2017 and December 2022. A backward stepwise logistic regression analysis for variables with P < 0.1 in univariable analysis was performed to predict pN+. Kaplan–Meier analysis with log-rank test evaluated the discrepancy for overall (OS) and recurrence-free survivals (RFS).

Results
Among 478 patients included in the final analysis, 19 (4.0%) had pN+, including 10 (2.1%) pN1, 6 (1.3%) pN2, and 3 (0.6%) pN1+2. With a median follow-up of 23.5 months (interquartile range 12.6–39.0), patients with pN+ had poorer OS compared to those with pN0 (3-year OS: 70.2% vs. 89.7%, P = 0.002). However, there was no significant difference in RFS and recurrence. The maximum standardized uptake value (SUVmax) of tumor in positron emission tomography scan ≥ 4.5 (versus < 4.5) was the only independent factor for pN + (odds ratio 3.5). Patients with a SUVmax ≥ 4.5 had 7.3% pN+, which was associated with poorer OS and similar RFS and recurrence compared to pN0. In contrast, those with a SUVmax < 4.5 had 2.2% pN+, which had comparable recurrence and survival to pN0.

Conclusion
Unforeseen nodal upstaging in segmentectomy for cIA1-2 NSCLC is low. Frozen section of lymph nodes may be necessary for lesions with high metabolic activity.
Analysis of Attitudes Toward Breastfeeding and Spiritual Life During Pregnancy in Türkiye: A Qualitative Study
Authors: Dinçer Yeliz , Erciyas Şeyma Kilci 
Published: February 2025

Abstract
It is crucial for nurses to understand the meaning of spirituality, which can become more pronounced during pregnancy, childbirth, and breastfeeding, and to take a supportive approach to breastfeeding attitudes during pregnancy. This study aimed to explore pregnant women’s attitudes and spiritual experiences in Türkiye regarding breastfeeding. A qualitative inductive content analysis design was employed. Seventeen pregnant women (36–39-week gestation) were admitted to a maternity hospital in Zonguldak, Türkiye. They were selected using purposive sampling. Data were collected through semi-structured, face-to-face, in-depth interviews and analyzed using an inductive content analysis approach. The mean age of the participants was 27.41 years, and ten participants were primiparous. Multiparous participants had previously breastfed for a mean duration of 19.1 months. Three main themes emerged: “Breastfeeding and life,” “Spiritual life and breastfeeding,” and “Cultural synthesis.” Considering the impact of spirituality on breastfeeding during pregnancy, these findings may help nurses recognize pregnant women’s spiritual needs and value the protective role of spirituality. Understanding these dimensions could improve the quality of support provided by healthcare professionals and potentially enhance breastfeeding outcomes.
The disservice of publishing preliminary results based on a premature hypothesis – Semmelweis’ ordeal revisited
Authors: Lynøe Niels , Juth Niklas , Eriksson Anders 
Published: February 2025

Abstract
In an interesting article, Dr Zuzana Parusniková claimed: (i) that Semmelweis’ colleagues did not recognise the importance of his animal experiments, (ii) that the resistance to Semmelweis’ hypothesis and results was due mainly to applying mono-causality and (iii) Semmelweis inability to communicate, (iv) that the New Vienna Medical School applied evidence-based medicine, and (v) that the philosophy of Karl Popper is the best interpretation of Semmelweis’ scientific approach. Here, we present some factual aspects of Semmelweis’ text from 1861 and discuss Dr Parusniková’s claims against this backdrop. We conclude that Semmelweis might intentionally have abstained from communicating his hypothesis and results between 1847 and 1849 – including the results from his animal experiments – as he thought that they would eventually be understood and accepted. Semmelweis’ hypothesis was that cadaveric matters and decaying particles were the cause of childbed fever and increased maternal mortality. This hypothesis might have been controversial, but we claim that the major reason for the resistance was eminence-based and induced by the publication of preliminary and suboptimal results, based on a premature version of his hypothesis. If the New Vienna Medical School had been influenced by evidence-based medicine, we believe that Semmelweis’ empirical results would have been accepted - as they were based on an almost randomised controlled trial - and if the results had not been associated with his hypothesis but instead had focused on a black box procedure. We agree that the philosophy of Popper might be appropriate when analysing Semmelweis’ scientific approach when abandoning low-level theories. However, to understand the resistance against Semmelweis’ hypothesis and results, it is not sufficient to refer to a Pickwickian discussion; a Kuhnian framework is more adequate.