bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferroptosis regulates hemolysis in stored murine and human red blood cells
Authors: D’Alessandro Angelo , Keele Gregory R. , Hay Ariel , Nemkov Travis , Earley Eric J. , Stephenson Daniel , Vincent Matthew , Deng Xutao , Stone Mars , Dzieciatkowska Monika , Hansen Kirk C. , Kleinman Steven , Spitalnik Steven L. , Roubinian Nareg , Norris Philip J. , Busch Michael P. , Page Grier P. , Stockwell Brent R. , Churchill Gary A. , Zimring James C. 
Published: November 2024

Abstract
Red blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. However, the genetic underpinnings of RBC metabolic heterogeneity and extravascular hemolysis at population scale are incompletely understood. On the basis of the breeding of 8 founder strains with extreme genetic diversity, the Jackson Laboratory diversity outbred population can capture the impact of genetic heterogeneity in like manner to population-based studies. RBCs from 350 outbred mice, either fresh or stored for 7 days, were tested for posttransfusion recovery, as well as metabolomics and lipidomics analyses. Metabolite and lipid quantitative trait loci (QTL) mapped &gt;400 gene-metabolite associations, which we collated into an online interactive portal. Relevant to RBC storage, we identified a QTL hotspot on chromosome 1, mapping on the region coding for the ferrireductase 6-transmembrane epithelial antigen of the prostate 3 (Steap3), a transcriptional target to p53. Steap3 regulated posttransfusion recovery, contributing to a ferroptosis-like process of lipid peroxidation, as validated via genetic manipulation in mice. Translational validation of murine findings in humans, STEAP3 polymorphisms were associated with RBC iron content, lipid peroxidation, and in vitro hemolysis in 13 091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. QTL analyses in humans identified a network of gene products (fatty acid desaturases 1 and 2, epoxide hydrolase 2, lysophosphatidylcholine acetyl-transferase 3, solute carrier family 22 member 16, glucose 6-phosphate dehydrogenase, very long chain fatty acid elongase, and phospholipase A2 group VI) associated with altered levels of oxylipins. These polymorphisms were prevalent in donors of African descent and were linked to allele frequency of hemolysis-linked polymorphisms for Steap3 or p53. These genetic variants were also associated with lower hemoglobin increments in thousands of single-unit transfusion recipients from the vein-to-vein database.
PROTEA study: a protocol for a randomised controlled trial evaluating the efficacy, immune effects and cost-effectiveness of oral bacterial lysate (OM-85) therapy to protect moderate-late preterm infants from respiratory tract infections and wheezing
Authors: van Duuren Inger C. , Smits Hermelijn H. , Duijts Liesbeth , Penders John , Tramper-Stranders Gerdien A. 
Published: November 2024

Infants, children and adults born moderate-late preterm (after 30–36 weeks of pregnancy) are at increased risk of respiratory infections, wheezing and lower lung function leading to increased medication use and hospitalisation. Risk-factors frequently present in this population are, at least in part, associated with (lack of) exposure to microbes and subsequent perturbations in microbiome and immune system development.This manuscript presents the protocol of the double blinded, randomised, placebo-controlled Protea trial, which will demonstrate whether treatment with immunomodulatory bacterial lysates (OM-85) can reduce lower respiratory tract infections and wheeze in the first year of life. The follow-up Protea-2 trial will identify possible carry-over effects of OM-85 treatment, and investigate the clinical effect of continued treatment in the second year of life. Infants included are otherwise healthy infants born after 30 to 36 week of gestation, excluding those small for gestational age (<3rd percentile). They are recruited shortly after birth in 22 medical centres in the Netherlands.Participants will take OM-85 or placebo starting from 6–10 weeks of life till age 1 (Protea study) or 2 (Protea-2 study) and are closely monitored regarding respiratory health through e-applications. Biological samples, lung function measurements and detailed information on covariates will be collected at ages 2, 6, 12 and 24 months. Biological samples will aid in estimating the impact of bacterial lysate administration on immune cell composition, activation and maturation, vaccination responses, and microbiome diversity and maturation. Participant recruitment has started in March 2022.
Exploring the roles of airway dipeptidyl peptidase 1 in obstructive airway disease
Authors: Tanabe Naoya , Matsumoto Hisako , Kogo Mariko , Morimoto Chie , Nomura Natsuko , Hayashi Yusuke , Sakamoto Ryo , Oguma Tsuyoshi , Nagasaki Tadao , Sunadome Hironobu , Sato Atsuyasu , Sato Susumu , Ohashi Kai , Tsukahara Takamitsu , Hirai Toyohiro 
Published: November 2024

BackgroundDipeptidyl peptidase 1 (DPP1) exacerbates airway neutrophilic inflammation in bronchiectasis, which is characterized by airway dysfunction and dilation and chronic bacterial infection. However, little is known about the pathogenetic roles of DPP1 in obstructive airway diseases, including chronic obstructive pulmonary disease (COPD), asthma, and asthma-COPD overlap (ACO). Here, we tested the hypothesis that airway DPP1 could enhance neutrophilic inflammation and affect mucus plugging, airway dilation, and the airway microbiome in patients with these diseases.MethodsThe sputum DPP1, cell differential count, and microbiome were cross-sectionally evaluated in patients with COPD, asthma with airflow limitation, and ACO. Sputum high mobility group box 1 (HMGB1) was measured to estimate airway epithelial damage. Chest computed tomography (CT) was also performed to visually assess mucus plugs and airway dilation with the Reiff score and quantify the total airway count and wall area percentage.ResultsSixty-eight patients were classified into high-DPP1/high-neutrophil, low-DPP1/high-neutrophil, and low-neutrophil groups (n=17, 37, and 14) based on sputum DPP1 levels and neutrophil percentages. The rate of mucus plugging and the relative abundance of the phylum Firmicutes were significantly lower, and the level of sputum HMGB1 was significantly greater in the high-DPP1/high-neutrophil group than in the low-DPP1/high-neutrophil group. Moreover, airway dilation without mucus plugging was observed only in the high-DPP1/high-neutrophil subgroup (prevalence, 29%).ConclusionsHigh sputum DPP1 levels may reduce colonization by the phylum Firmicutes and mucus plugging, but increase airway epithelial damage, which could induce airway dilation without mucus plugging in patients with obstructive airway disease with neutrophilic inflammation.
Endobronchial valve treatment improves diaphragm function in severe emphysema patients
Authors: ter Haar Else A.M.D. , Slebos Dirk-Jan , Bakker J.T. , Augustijn Sonja W.S. , Dijkstra Linze J. , Hartman Jorine E. 
Published: November 2024

Rationale and aimDiaphragm dysfunction is common in severe emphysema patients, primarily due to hyperinflation, placing the diaphragm at a mechanical disadvantage. Endobronchial valve (EBV) treatment is a bronchoscopic procedure to reduce hyperinflation, and thus potentially restore diaphragm function in this patient population. Our aim was to investigate the effect of EBV treatment on diaphragm function.Patients and methodsA prospective cohort study was performed in which diaphragm function was measured at baseline and 6 weeks after EBV treatment by ultrasonic assessment to measure diaphragm motion and diaphragm thickening fraction (dTF), surface electromyography (sEMG) to quantify diaphragm activity, and maximal inspiratory pressure (MIP) to assess diaphragm strength.ResultsTwenty-five patients were included, with a mean age of 64±7 years. Residual volume (−0.85±0.49 Liter, p<0.001) decreased significantly post EBV treatment, with a significant increase in MIP (+0.6 kPa, range −1.2–2.8, p=0.001). Diaphragm motion on the treated side during tidal breathing significantly decreased (−3.3 mm, range −24.7–14.6, p=0.023). There were no significant changes in dTF on the treated side. Diaphragm activity (sEMG) for tidal breathing (−1.7 µV, p=0.004, range −8.8–5.8), maximal inspiration (−4.1 µV, p=0.004, range −42.3–16.0), and sniff manoeuvre (−6.1 µV, p=0.027, range −42.2–24.2) all significantly decreased.ConclusionOur results show that diaphragm function significantly improves after EBV treatment in severe emphysema patients. This emphasizes the physiological interaction between hyperinflation and diaphragm function, suggesting that reducing hyperinflation can at least partially reverse diaphragm dysfunction.
Comparison of commonly used software pipelines for analyzing fungal metabarcoding data
Authors: Rzehak Theresa , Praeg Nadine , Galla Giulio , Seeber Julia , Hauffe Heidi Christine , Illmer Paul 
Published: November 2024

Abstract
Background
Metabarcoding targeting the internal transcribed spacer (ITS) region is commonly used to characterize fungal communities of various environments. Given their size and complexity, raw ITS sequences are necessarily processed and quality-filtered with bioinformatic pipelines. However, such pipelines are not yet standardized, especially for fungal communities, and those available may produce contrasting results. While some pipelines cluster sequences based on a specified percentage of base pair similarity into operational taxonomic units (OTUs), others utilize denoising techniques to infer amplicon sequencing variants (ASVs). While ASVs are now considered a more accurate representation of taxonomic diversity for prokaryote communities based on 16S rRNA amplicon sequencing, the applicability of this method for fungal ITS sequences is still debated.

Results
Here we compared the performance of two commonly used pipelines DADA2 (inferring ASVs) and mothur (clustering OTUs) on fungal metabarcoding sequences originating from two different environmental sample types (fresh bovine feces and pasture soil). At a 99% OTU similarity threshold, mothur consistently identified a higher fungal richness compared to DADA2. In addition, mothur generated homogenous relative abundances across multiple technical replicates (n = 18), while DADA2 results for the same replicates were highly heterogeneous.

Conclusions
Our study highlights a potential pipeline-associated bias in fungal metabarcoding data analysis of environmental samples. Based on the homogeneity of relative abundances across replicates and the capacity to detect OTUs/ASVs, we suggest using OTU clustering with a similarity of 97% as the most appropriate option for processing fungal metabarcoding data.
Housing conditions and COVID-19 in Barcelona: do they change by gender?
Authors: Perez Gloria , Forcadell-Diez Lluís , Reyes Alexia , Perez Catherine , Bartoll Xavier , Borrell Carme 
Published: November 2024

Abstract
Background
Evidence has linked poor housing conditions to negative health outcomes. However, in urban contexts characterized by social vulnerability and population-level inequalities, the gender perspective is often overlooked, despite evidence showing that housing conditions impact men and women differently in terms of health. This study aimed to describe the association between housing conditions and the prevalence of COVID-19 among men and women in Barcelona, Spain.

Methods
An observational cross-sectional study was conducted using the 2021 Barcelona Health Survey. The study population consisted of non-institutionalized residents over 14 years of age in Barcelona. The survey was administered to a sample of 3,545 participants during the COVID-19 pandemic, between February 2021 and February 2022. Crude and adjusted prevalence ratios of COVID-19 (aPR), along with 95% confidence intervals (95% CI), were estimated using multivariate Poisson regression models with robust variance. The analysis was stratified by gender.

Results
A significant gradient was observed across age groups for both men and women, with higher COVID-19 prevalence in younger categories. The prevalence was notably higher among individuals born in low-income countries, particularly for women (aPR 1.62). We also identified a significant association between housing conditions, vulnerability factors, and COVID-19 prevalence in both men and women. Living with four or more cohabitants was associated with higher prevalence (aPR 1.96 for women and 1.89 for men), as was the presence of dampness in the home (aPR 1.34 for women and 1.27 for men). Additionally, energy poverty was significantly associated with higher COVID-19 prevalence in women (aPR 1.36), but not in men.

Conclusion
This study highlights the association between housing conditions and COVID-19 in Barcelona, with a pronounced impact on young people, women from low-income countries, and women experiencing energy poverty.
A review of multiple diagnostic approaches in the undiagnosed diseases network to identify inherited metabolic diseases
Authors: Furuta Yutaka , Tinker Rory J. , Hamid Rizwan , Cogan Joy D. , Ezell Kimberly M. , Oglesbee Devin , DeBerardinis Ralph J. , Phillips John A. ,   the Undiagnosed Diseases Network
Published: November 2024

Abstract
Background
The number of known inherited metabolic diseases (IMDs) has been expanding, and the rate of diagnosis is improving with the development of innovative approaches including next generation sequencing (NGS). However, a substantial proportion of IMDs remain undetected by traditional diagnostic approaches. We aim to highlight the spectrum of IMDs diagnosed by the Undiagnosed Diseases Network (UDN) and to learn from the UDN diagnostic processes that were able to detect IMDs.

Methods
We conducted a retrospective analysis of 757 UDN participants diagnosed from 2015 until 2023 using the cohort database, which were divided into a cohort with IMDs (n = 194; 27%) and a cohort whose phenotypes were not explained by an IMD (n = 563; 73%), based on the International Classification of Inherited Metabolic Disorders (ICIMD). Then, we divided the causes of the metabolic 194 diagnoses into seven groups that included all the ICIMD categories. We inspected which clinical and laboratory approaches contributed to a final UDN diagnosis. We also present a UDN case example from each group to highlight the diagnostic yields that resulted from combining newer diagnostic approaches in the UDN and illustrate potential pitfalls of current NGS methods.

Results
These 194 cases of IMDs included examples from 21/25 (84%) of the ICIMD categories. Of the UDN subjects 164/194 (85%) were diagnosed with IMDs through NGS.

Conclusion
The spectrum of IMDs detected in the UDN cohort is large and growing and appropriate use of newer multiple diagnostic approaches should further increase diagnosis of IMDs that are presently missed by the traditional laboratory screening methods.
How does emotional insecurity affect non-suicidal self-injury among Chinese early adolescents: a longitudinal study
Authors: Ni Xingcan , Liang Qiao , Liao Xiaoyan , Wang Huahua , Yu Chengfu 
Published: November 2024

Abstract
Background
Non-suicidal self-injury (NSSI) is a serious public health concern. Emotional insecurity is a crucial predictor of NSSI among adolescents. However, few studies have elucidated the specific mechanisms between emotional insecurity and NSSI.

Methods
This study employed a longitudinal research design, using a sample of 886 Chinese early adolescents (Mage at T1 = 10.62 years, SD = 0.77 years; 47.40% females), and conducted two surveys six months apart to examine the mediating role of peer exclusion between emotional insecurity and NSSI, as well as the moderating effect of school climate.

Results
The results indicated that peer exclusion significantly mediated the connection between emotional insecurity and adolescent NSSI. Moreover, school climate significantly moderated the connection between emotional insecurity and peer exclusion. Specifically, the impact of emotional insecurity on peer exclusion was significant only in adolescents who reported a negative school climate, but non-significant in those who reported a positive school climate.

Conclusions
These findings provide a robust theoretical foundation and practical insights to help inform the prevention of and interventions for NSSI in adolescents.
The BrEasT cancer afTER-CARE (BETTER-CARE) programme to improve breast cancer follow-up: design and feasibility study results of a cluster-randomised complex intervention trial
Authors: Horn Anna , Wendel Julia , Franke Isabella , Bauer Armin , Baumeister Harald , Bendig Eileen , Brucker Sara Y. , Deutsch Thomas M. , Garatva Patricia , Haas Kirsten , Heil Lorenz , Hügen Klemens , Manger Helena , Pryss Rüdiger , Rücker Viktoria , Salmen Jessica , Szczesny Andrea , Vogel Carsten , Wallwiener Markus , Wöckel Achim , Heuschmann Peter U. ,   the BETTER-CARE Study Group, Ast Alexander , Belke Kerstin , Beurer Björn , Bolkenius Petra , Freese Kristina , Frumkin Nora , Gnauert Karsten , Graf Heiko , Hackmann John , Hartmann Corinna , Hesse Tobias , Hopp Melanie , Keil Elke , Lehnert Antje , Müller Cordula , Mundhenke Christoph , Niestroj Hue Phan , Nixdorf Antje , Pankert Kilian , Perez Sibylle , Radosa Julia , Rezek Daniela , Seldte Jens-Paul , Stalzer Gabriele , Sykorova Zuzana , Tenger Martin , Volmer Léa , Würfel Katharina , Zorr Andreas 
Published: November 2024

Abstract

Background
The risk of breast cancer patients for long-term side effects of therapy such as neurotoxicity and cardiotoxicity as well as late effects regarding comorbidities varies from individual to individual. Personalised follow-up care concepts that are tailored to individual needs and the risk of recurrences, side effects and late effects are lacking in routine care in Germany.

Methods
We describe the methodology of BETTER-CARE, a parallel-arm cluster-randomised controlled trial conducted at 15 intervention and 15 control centres, aiming to recruit 1140 patients, and the results of the pilot phase. The needs- and risk-adapted complex intervention, based on existing development frameworks, includes a multidisciplinary network and digital platforms for symptom and need documentation and just-in-time adaptive interventions. The control group comprises usual care according to clinical guidelines. The primary outcome is health-related quality of life (EORTC QLQ-C30 global health), and secondary outcomes include treatment adherence.

Results
The 2-month pilot phase comprising 16 patients in one intervention and one control pilot centre demonstrated the feasibility of the BETTER-CARE approach.

Discussion
BETTER-CARE is a feasible intervention and study concept, investigating individualised needs- and risk-adapted breast cancer follow-up care in Germany. If successful, the approach could be implemented in German routine care.

Trial registration
German Clinical Trial Register DRKS00028840. Registered on April 2022.
Bio-inspired one-pot synthesis of luminescent silver nanoparticles and its significant utility as a fluorescence nano sensor for analysis of two adjunctive COVID-19 drugs
Authors: Mostafa Yasmeen E. , Elsebaei Fawzi , Metwally Mohammed El-Sayed 
Published: November 2024

AbstractThis study reveals one-step green synthesis of plant inspired silver nanoparticles (Ag-NPs). The synthesis procedure relies on the bio-reduction of Ag+ to Ag0 using orange waste (orange peel) extract as cheap, readily available, sustainable, biocompatible feedstocks as a reducing and stabilizing agent. The prepared Ag-NPs passed through a full characterization procedure for better confirmation and elucidation of optical and structural properties. The fluorescence of the prepared Ag-NPs has a quantum yield of 17.15% enabling its potential use in chemical sensing of drugs. Ag-NPs are conceived to be used as a fluorescent nano sensor for sensitive, ecofriendly, rapid spectrofluorimetric determination of two recent direct oral anticoagulants, namely, rivaroxaban (RIV) and edoxaban tosylate monohydrate (EDT); COVID-19 adjunctive drugs in their raw materials and pharmaceutical tablets. The fluorescence of the prepared Ag-NPs at 333 nm $${(\uplambda }_{\text{ex}}=258 \text{nm})$$

(
λ

ex

=
258
nm
)

was found to be substantially quenched in existence of increasing concentrations of each drug. The quenching mechanisms were studied and explained. The validation of the method revealed linear correlation over the ranges of 0.5–10 µg/ml with an excellent regression correlation (r = 0.9999) for both drugs with minimum detection limits of 0.14 and 0.16 µg/ml for rivaroxaban and edoxaban tosylate monohydrate, correspondingly. Three different metrics were employed for verifying the greenness profile of the presented study. The findings of the greenness assessment were congruent and compatible with the green synthesis procedure, ecofriendly analysis, and the exclusion of using organic solvents and noxious materials opening an avenue for green synthesis of nanoparticles instead of chemical and physical methods.
Neoantigen DNA vaccines are safe, feasible, and induce neoantigen-specific immune responses in triple-negative breast cancer patients
Authors: Zhang Xiuli , Goedegebuure S. Peter , Chen Michael Y. , Mishra Rashmi , Zhang Felicia , Yu Yik Yeung , Singhal Kartik , Li Lijin , Gao Feng , Myers Nancy B. , Vickery Tammi , Hundal Jasreet , McLellan Michael D. , Sturmoski Mark A. , Kim Samuel W. , Chen Ina , Davidson Jesse T. , Sankpal Narendra V. , Myles Stephanie , Suresh Rama , Ma Cynthia X. , Foluso Ademuyiwa , Wang-Gillam Andrea , Davies Sherri , Hagemann Ian S. , Mardis Elaine R. , Griffith Obi , Griffith Malachi , Miller Christopher A. , Hansen Ted H. , Fleming Timothy P. , Schreiber Robert D. , Gillanders William E. 
Published: November 2024

Abstract
Background
Neoantigen vaccines can induce or enhance highly specific antitumor immune responses with minimal risk of autoimmunity. We have developed a neoantigen DNA vaccine platform capable of efficiently presenting both HLA class I and II epitopes and performed a phase 1 clinical trial in triple-negative breast cancer patients with persistent disease on surgical pathology following neoadjuvant chemotherapy, a patient population at high risk of disease recurrence.

Methods
Expressed somatic mutations were identified by tumor/normal exome sequencing and tumor RNA sequencing. The pVACtools software suite of neoantigen prediction algorithms was used to identify and prioritize cancer neoantigens and facilitate vaccine design for manufacture in an academic GMP facility. Neoantigen DNA vaccines were administered via electroporation in the adjuvant setting (i.e., following surgical removal of the primary tumor and completion of standard of care therapy). Vaccines were monitored for safety and immune responses via ELISpot, intracellular cytokine production via flow cytometry, and TCR sequencing.

Results
Eighteen subjects received three doses of a neoantigen DNA vaccine encoding on average 11 neoantigens per patient (range 4–20). The vaccinations were well tolerated with relatively few adverse events. Neoantigen-specific T cell responses were induced in 14/18 patients as measured by ELISpot and flow cytometry. At a median follow-up of 36 months, recurrence-free survival was 87.5% (95% CI: 72.7–100%) in the cohort of vaccinated patients.

Conclusion
Our study demonstrates neoantigen DNA vaccines are safe, feasible, and capable of inducing neoantigen-specific immune responses.

Clinical trial registration number
NCT02348320.