bluuebunny/crossref_metadata_2025_split huggingface dataset:
A moonlighting job for α-globin in blood vessels
Authors: Abbineni Prabhodh S. , Baid Srishti , Weiss Mitchell J. 
Published: June 2024

AbstractRed blood cells express high levels of hemoglobin A tetramer (α2β2) to facilitate oxygen transport. Hemoglobin subunits and related proteins are also expressed at lower levels in other tissues across the animal kingdom. Physiological functions for most nonerythroid globins likely derive from their ability to catalyze reduction–oxidation (redox) reactions via electron transfer through heme-associated iron. An interesting example is illustrated by the recent discovery that α-globin without β-globin is expressed in some arteriolar endothelial cells (ECs). α-globin binds EC nitric oxide (NO) synthase (eNOS) and degrades its enzymatic product NO, a potent vasodilator. Thus, depletion of α-globin in ECs or inhibition of its association with eNOS causes arteriolar relaxation and lowering of blood pressure in mice. Some of these findings have been replicated in isolated human blood vessels, and genetic studies are tractable in populations in which α-thalassemia alleles are prevalent. Two small studies identified associations between loss of α-globin genes in humans and NO-regulated vascular responses elicited by local hypoxia-induced blood flow or thermal stimulation. In a few larger population-based studies, no associations were detected between loss of α-globin genes and blood pressure, ischemic stroke, or pulmonary hypertension. In contrast, a significant positive association between α-globin gene copy number and kidney disease was detected in an African American cohort. Further studies are required to define comprehensively the expression of α-globin in different vascular beds and ascertain their overall impact on normal and pathological vascular physiology.
NGS-based stratification refines the risk stratification in T-ALL and identifies a very-high-risk subgroup of patients
Authors: Simonin Mathieu , Vasseur Loïc , Lengliné Etienne , Lhermitte Ludovic , Cabannes-Hamy Aurélie , Balsat Marie , Schmidt Aline , Dourthe Marie-Emilie , Touzart Aurore , Graux Carlos , Grardel Nathalie , Cayuela Jean-Michel , Arnoux Isabelle , Gandemer Virginie , Huguet Françoise , Ducassou Stéphane , Lhéritier Véronique , Chalandon Yves , Ifrah Norbert , Dombret Hervé , Macintyre Elizabeth , Petit Arnaud , Rousselot Philippe , Lambert Jérôme , Baruchel André , Boissel Nicolas , Asnafi Vahid 
Published: June 2024

Abstract
We previously reported a better outcome in adult and pediatric T-cell acute lymphoblastic leukemia (T-ALL) harboring NOTCH1 and/or FBXW7 mutations without alterations of K-N-RAS and PTEN genes. Availability of high-throughput next-generation sequencing (NGS) strategies led us to refine the outcome prediction in T-ALL. Targeted whole-exome sequencing of 72 T-ALL–related oncogenes was performed in 198 adults with T-ALLs in first remission from the GRAALL-2003/2005 protocols and 242 pediatric patients with T-ALLs from the FRALLE2000T. This approach enabled the identification of, to our knowledge, the first NGS-based classifier in T-ALL, categorizing low-risk patients as those with N/F, PHF6, or EP300 mutations, excluding N-K-RAS, PI3K pathway (PTEN, PIK3CA, and PIK3R1), TP53, DNMT3A, IDH1/2, and IKZF1 alterations, with a 5-year cumulative incidence of relapse (CIR) estimated at 21%. Conversely, the remaining patients were classified as high risk, exhibiting a 5-year CIR estimated at 47%. We externally validated this stratification in the pediatric cohort. NGS-based classifier was highly prognostic independently of minimal residual disease (MRD) and white blood cell (WBC) counts, in both adult and pediatric cohorts. Integration of the NGS-based classifier into a comprehensive risk-stratification model, including WBC count at diagnosis and MRD at the end of induction, enabled the identification of an adverse-risk subgroup (25%) with a 5-year CIR estimated at 51%, and a favorable-risk group (32%) with a 5-year CIR estimated at 12%. NGS-based stratification combined with WBC and MRD sharpens the prognostic classification in T-ALL and identifies a new subgroup of patients who may benefit from innovative therapeutic approaches. The GRAALL-2003/2005 studies were registered at www.ClinicalTrials.gov as #NCT00222027 and #NCT00327678.
Foxo1 is an iron-responsive transcriptional factor regulating systemic iron homeostasis
Authors: Xu Teng , Zhang Xu , Zhao Wenting , Shi Jiaxin , Wan Sitong , Zhang Yan , Hao Yanling , Sun Mingyue , He Jingjing , Jiang Li , Wang Hao , Gao Hong , Luo Junjie , Luo Yongting , An Peng 
Published: June 2024

Abstract
The liver plays a crucial role in maintaining systemic iron homeostasis by secreting hepcidin, which is essential for coordinating iron levels in the body. Imbalances in iron homeostasis are associated with various clinical disorders related to iron deficiency or iron overload. Despite the clinical significance, the mechanisms underlying how hepatocytes sense extracellular iron levels to regulate hepcidin synthesis and iron storage are not fully understood. In this study, we identified Foxo1, a well-known regulator of macronutrient metabolism, which translocates to the nucleus of hepatocytes in response to high-iron feeding, holo-transferrin, and bone morphogenetic protein 6 (BMP6) treatment. Furthermore, Foxo1 plays a crucial role in mediating hepcidin induction in response to both iron and BMP signals by directly interacting with evolutionally conserved Foxo binding sites within the hepcidin promoter region. These binding sites were found to colocalize with Smad-binding sites. To investigate the physiological relevance of Foxo1 in iron metabolism, we generated mice with hepatocyte-specific deletion of Foxo1. These mice exhibited reduced hepatic hepcidin expression and serum hepcidin levels, accompanied by elevated serum iron and liver nonheme iron concentrations. Moreover, high-iron diet further exacerbated these abnormalities in iron metabolism in mice lacking hepatic Foxo1. Conversely, hepatocyte-specific Foxo1 overexpression increased hepatic hepcidin expression and serum hepcidin levels, thereby ameliorating iron overload in a murine model of hereditary hemochromatosis (Hfe−/− mice). In summary, our study identifies Foxo1 as a critical regulator of hepcidin and systemic iron homeostasis. Targeting Foxo1 may offer therapeutic opportunities for managing conditions associated with aberrant iron metabolism.
Comprehensive analysis of the expression profiles of mRNA, lncRNA, circRNA, and miRNA in primary hair follicles of coarse sheep fetal skin
Authors: Tian Dehong , Pei Quanbang , Jiang Hanjing , Guo Jijun , Ma Xianghua , Han Buying , Li Xue , Zhao Kai 
Published: June 2024

Abstract
Background
The Qinghai Tibetan sheep, a local breed renowned for its long hair, has experienced significant deterioration in wool characteristics due to the absence of systematic breeding practices. Therefore, it is imperative to investigate the molecular mechanisms underlying follicle development in order to genetically enhance wool-related traits and safeguard the sustainable utilization of valuable germplasm resources. However, our understanding of the regulatory roles played by coding and non-coding RNAs in hair follicle development remains largely elusive.

Results
A total of 20,874 mRNAs, 25,831 circRNAs, 4087 lncRNAs, and 794 miRNAs were annotated. Among them, we identified 58 DE lncRNAs, 325 DE circRNAs, 924 DE mRNAs, and 228 DE miRNAs during the development of medullary primary hair follicle development. GO and KEGG functional enrichment analyses revealed that the JAK-STAT, TGF-β, Hedgehog, PPAR, cGMP-PKG signaling pathway play crucial roles in regulating fibroblast and epithelial development during skin and hair follicle induction. Furthermore, the interactive network analysis additionally identified several crucial mRNA, circRNA, and lncRNA molecules associated with the process of primary hair follicle development. Ultimately, by investigating DEmir’s role in the ceRNA regulatory network mechanism, we identified 113 circRNA–miRNA pairs and 14 miRNA–mRNA pairs, including IGF2BP1-miR-23-x-novel-circ-01998-MSTRG.7111.3, DPT-miR-370-y-novel-circ-005802-MSTRG.14857.1 and TSPEAR-oar-miR-370-3p-novel-circ-005802- MSTRG.10527.1.

Conclusions
Our study offers novel insights into the distinct expression patterns of various transcription types during hair follicle morphogenesis, establishing a solid foundation for unraveling the molecular mechanisms that drive hair development and providing a scientific basis for selectively breeding desirable wool-related traits in this specific breed.
NmTHC: a hybrid error correction method based on a generative neural machine translation model with transfer learning
Authors: Wang Rongshu , Chen Jianhua 
Published: June 2024

Abstract
Backgrounds
The single-pass long reads generated by third-generation sequencing technology exhibit a higher error rate. However, the circular consensus sequencing (CCS) produces shorter reads. Thus, it is effective to manage the error rate of long reads algorithmically with the help of the homologous high-precision and low-cost short reads from the Next Generation Sequencing (NGS) technology.

Methods
In this work, a hybrid error correction method (NmTHC) based on a generative neural machine translation model is proposed to automatically capture discrepancies within the aligned regions of long reads and short reads, as well as the contextual relationships within the long reads themselves for error correction. Akin to natural language sequences, the long read can be regarded as a special “genetic language” and be processed with the idea of generative neural networks. The algorithm builds a sequence-to-sequence(seq2seq) framework with Recurrent Neural Network (RNN) as the core layer. The before and post-corrected long reads are regarded as the sentences in the source and target language of translation, and the alignment information of long reads with short reads is used to create the special corpus for training. The well-trained model can be used to predict the corrected long read.

Results
NmTHC outperforms the latest mainstream hybrid error correction methods on real-world datasets from two mainstream platforms, including PacBio and Nanopore. Our experimental evaluation results demonstrate that NmTHC can align more bases with the reference genome without any segmenting in the six benchmark datasets, proving that it enhances alignment identity without sacrificing any length advantages of long reads.

Conclusion
Consequently, NmTHC reasonably adopts the generative Neural Machine Translation (NMT) model to transform hybrid error correction tasks into machine translation problems and provides a novel perspective for solving long-read error correction problems with the ideas of Natural Language Processing (NLP). More remarkably, the proposed methodology is sequencing-technology-independent and can produce more precise reads.
Genomic exploration of the fermented meat isolate Staphylococcus shinii IMDO-S216 with a focus on competitiveness-enhancing secondary metabolites
Authors: Sosa-Fajardo Ana , Díaz-Muñoz Cristian , Van der Veken David , Pradal Inés , Verce Marko , Weckx Stefan , Leroy Frédéric 
Published: June 2024

Abstract
Background
Staphylococcus shinii appears as an umbrella species encompassing several strains of Staphylococcus pseudoxylosus and Staphylococcus xylosus. Given its phylogenetic closeness to S. xylosus, S. shinii can be found in similar ecological niches, including the microbiota of fermented meats where the species may contribute to colour and flavour development. In addition to these conventional functionalities, a biopreservation potential based on the production of antagonistic compounds may be available. Such potential, however, remains largely unexplored in contrast to the large body of research that is available on the biopreservative properties of lactic acid bacteria. The present study outlines the exploration of the genetic basis of competitiveness and antimicrobial activity of a fermented meat isolate, S. shinii IMDO-S216. To this end, its genome was sequenced, de novo assembled, and annotated.

Results
The genome contained a single circular chromosome and eight plasmid replicons. Focus of the genomic exploration was on secondary metabolite biosynthetic gene clusters coding for ribosomally synthesized and posttranslationally modified peptides. One complete cluster was coding for a bacteriocin, namely lactococcin 972; the genes coding for the pre-bacteriocin, the ATP-binding cassette transporter, and the immunity protein were also identified. Five other complete clusters were identified, possibly functioning as competitiveness factors. These clusters were found to be involved in various responses such as membrane fluidity, iron intake from the medium, a quorum sensing system, and decreased sensitivity to antimicrobial peptides and competing microorganisms. The presence of these clusters was equally studied among a selection of multiple Staphylococcus species to assess their prevalence in closely-related organisms.

Conclusions
Such factors possibly translate in an improved adaptation and competitiveness of S. shinii IMDO-S216 which are, in turn, likely to improve its fitness in a fermented meat matrix.
Syndromic case definitions for lower respiratory tract infection (LRTI) are less sensitive in older age: an analysis of symptoms among hospitalised adults
Authors: Kwiatkowska Rachel , Chatzilena Anastasia , King Jade , Clout Madeleine , McGuinness Serena , Maskell Nick , Oliver Jennifer , Challen Robert , Hickman Matthew , Finn Adam , Hyams Catherine , Danon Leon ,   the AvonCAP Research Group, Morley Anna , Langdon Amelia , Turner Anabella , Mattocks Anya , Osborne Bethany , Grimes Charli , Mitchell Claire , Adegbite David , Bridgeman Emma , Scott Emma , Perkins Fiona , Bayley Francesca , Ruffino Gabriella , Valentine Gabriella , Tilzey Grace , Campling James , Wright Johanna Kellett , Brzezinska Julia , Cloake Julie , Milutinovic Katarina , Helliker Kate , Maughan Katie , Fox Kazminder , Minou Konstantina , Ward Lana , Fleming Leah , Morrison Leigh , Smart Lily , Wright Louise , Grimwood Lucy , Bellavia Maddalena , Vasquez Marianne , Gonzalez Maria Garcia , Jeenes-Flanagan Milo , Chang Natalie , Grace Niall , Manning Nicola , Griffiths Oliver , Croxford Pip , Sequenza Peter , Lazarus Rajeka , Walters Rhian , Marlow Robin , Heath Robyn , Antico Rupert , Arachchge Sandi Nammuni , Suppiah Seevakumar , Mona Taslima , Riaz Tawassal , Mackay Vicki , Maseko Zandile , Taylor Zoe , Friedrich Zsolt , Szasz-Benczur Zsuzsa 
Published: June 2024

AbstractBackgroundLower Respiratory Tract Infections (LRTI) pose a serious threat to older adults but may be underdiagnosed due to atypical presentations. Here we assess LRTI symptom profiles and syndromic (symptom-based) case ascertainment in older (≥ 65y) as compared to younger adults (< 65y).MethodsWe included adults (≥ 18y) with confirmed LRTI admitted to two acute care Trusts in Bristol, UK from 1st August 2020- 31st July 2022. Logistic regression was used to assess whether age ≥ 65y reduced the probability of meeting syndromic LRTI case definitions, using patients’ symptoms at admission. We also calculated relative symptom frequencies (log-odds ratios) and evaluated how symptoms were clustered across different age groups.ResultsOf 17,620 clinically confirmed LRTI cases, 8,487 (48.1%) had symptoms meeting the case definition. Compared to those not meeting the definition these cases were younger, had less severe illness and were less likely to have received a SARS-CoV-2 vaccination or to have active SARS-CoV-2 infection. Prevalence of dementia/cognitive impairment and levels of comorbidity were lower in this group.After controlling for sex, dementia and comorbidities, age ≥ 65y significantly reduced the probability of meeting the case definition (aOR = 0.67, 95% CI:0.63–0.71). Cases aged ≥ 65y were less likely to present with fever and LRTI-specific symptoms (e.g., pleurisy, sputum) than younger cases, and those aged ≥ 85y were characterised by lack of cough but frequent confusion and falls.ConclusionsLRTI symptom profiles changed considerably with age in this hospitalised cohort. Standard screening protocols may fail to detect older and frailer cases of LRTI based on their symptoms.
Prevalence and characteristics of amblyopia, strabismus, and refractive errors among patients aged 3–16 years in Shanghai, China: a hospital-based population study
Authors: Wu Jiali , Wang Ning 
Published: June 2024

Abstract
Background
Functional visual impairments in children are primarily caused by amblyopia or strabismus. This study aimed to determine the prevalence and clinical profile of amblyopia and strabismus among individuals aged 3–16 years in Shanghai, China.

Methods
From February 2023 to February 2024, this hospital-based, cross-sectional study included data of children who visited the Ophthalmology Department of Shanghai General Hospital. Comprehensive ocular examinations included visual acuity measurement after cycloplegic refraction, slit lamp examination, cover test, and dilated fundus examination. Descriptive statistics were performed to estimate the proportion and clinical characteristics of amblyopia and strabismus.

Results
A total of 920 children were enrolled in our study. Among them, 223 (24.24%) children were identified as amblyopia. Unilateral amblyopia occupied 57.85%, and bilateral amblyopia occupied 42.15%. Most participants were within the age range of 5–10 years (75.97% for unilateral amblyopia, and 70.21% for bilateral amblyopia). Anisometropia was the primary cause of unilateral amblyopia (68.99%). Most amblyopic children have high hyperopia (38.76% for unilateral amblyopia, and 39.89% for bilateral amblyopia). 30 (3.26%) children were diagnosed with strabismus, and 19 (63.3%) of them were aged 5–10 years. Seven of the children had both strabismus and amblyopia.

Conclusion
The proportion of patients with amblyopia and strabismus was determined as 24.24% and 3.26% in our study. Anisometropia was the leading cause of unilateral amblyopia, whereas high hyperopia was a crucial refractive error in the amblyopic population. These findings shed light on further longitudinal studies targeting the age-related changes in amblyopia, strabismus and refraction errors. Therefore, efforts should be made to manage uncorrected refractive errors, amblyopia, and strabismus among children in Shanghai.
Contextual determinants of multiple sexual partnerships amongst young people in South Africa: a multilevel analysis
Authors: Ugwu Nebechukwu H. , Odimegwu Clifford O. 
Published: June 2024

Abstract
Background
Risky sexual behaviour (RSB), particularly multiple sexual partnerships (MSP) continues to be a major public health concern and has been linked to the increasing STIs, including HIV/AIDS in many parts of sub-Saharan Africa (SSA), suggesting that there is an association between contextual factors and multiple sexual partnering. However, in South Africa, this association is not well established in recent literature. Hence, this study examined the contextual factors contributing to multiple sexual partnerships among young people in South Africa.

Materials and methods
Data was extracted from the 2016 South Africa Demographics and Health Survey (2016 SADHS). A cross-sectional study of 3889 never-married young people. Descriptive and inferential statistics as well as multilevel logistic regression were used to analyse the data on never-married young people aged 15 to 24 years.

Results
The results indicated that at the individual level, young males (61.7%) were significantly more likely than their female counterparts (56.1%) to engage in multiple sexual partners, although, the difference was not as significant as expected. At the community level clustering, the likelihood of exposure to multiple sexual partnerships significantly increased among females (OR = 1.47; 95% CI: 1.25–1.73) but decreased among their male counterparts (OR = 0.73; 95% CI: 0.58–0.92), in particular, family disruption, residential instability, and ethnic diversity led young people to engage in multiple sexual partnerships.

Conclusions
There is a need to intensify programmes aimed at considering appropriate policy options to reduce the prevalence of multiple sexual partnerships. Adopting the implications of these findings is essential for a developmental strategy towards achieving the sustainable development goal of ending STIs among young people in South Africa.
An analytical framework for breast cancer public policies in Sub-Saharan Africa: results from a comprehensive literature review and an adapted policy Delphi
Authors: Gbenonsi Gloria Yawavi , Martini Jessica , Mahieu Céline 
Published: June 2024

Abstract
Background
Breast cancer is the leading cause of death from cancer in women and is a major public health problem worldwide. Despite the lower incidence rates of breast cancer in resource-limited settings, especially sub-Saharan Africa, there is a higher mortality rate compared to high-resource countries where the disease has a higher incidence. This makes breast cancer the second deadliest cancer in African women. These poor results reflect the weakness in public health policies. The aim of this paper is to contribute to the effective control of breast cancer by designing a framework for a comprehensive and systemic analysis of these policies in Sub-Saharan Africa.

Methods
This research is based on a literature review that adopted a systematic approach followed by a modified policy Delphi involving breast cancer experts in Sub-Saharan Africa. We included narrative reviews and systematic reviews/meta-analyses published between 2015 and 2022 as well as official documents in the analysis. We integrated the World Health Organization’s health system building blocks with Walt and Gilson’s policy analysis triangle to analyse the information collected and develop our analytical framework.

Results
A total of 22 reviews and documents were included in the study. Sixteen breast cancer experts from Sub-Saharan Africa participated in the first Delphi round, and nine participated in the second round. The different components identified for a comprehensive and systemic analysis of effective breast cancer policies can be classified into policy content divided according to the health system building blocks and related policy processes; individual, organized national and international policy stakeholders; and policy contexts.

Conclusion
This study enabled the design of a framework suitable for the comprehensive and systemic analysis of breast cancer control policies in Sub-Saharan Africa. This framework can be used as a checklist for stakeholders to guide the planning, implementation and evaluation of policies and specific breast cancer control programmes at the national and facility levels.