bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting Molecular Collagen Defects from the Initiation of Knee Osteoarthritis
Authors: Huang Kui , Qiu Rongmao , Fang Yijie , Zhu Dantian , Li Xiaojing , Lv Zhongyang , Jia Taoyu , Fei Yuxiang , Zhou Daoning , Wu Wenjun , Huang Yongjie , Zhao Suwen , Zhu Yongqiao , Li Shaolin , Shi Dongquan , Li Yang 
Published: June 2024

AbstractKnee osteoarthritis (OA) is the most prevalent degenerative joint disease. When morphological changes become apparent on radiographs, no approved treatment can reverse the disease process. Early diagnosis is an unmet need demanding new molecular and imaging biomarkers to define OA from the earliest stages. In this context, we focus on collagen, the most basic building block of all joint tissues, and interrogate how OA development affects collagen’s molecular folding, a previously underexplored area. Here, through whole-joint mapping with a peptide that recognizes unfolded collagen molecules, we report the discovery of collagen denaturation in cartilage before proteolysis and major histopathological degeneration in animal models and patients. Mechanistically, we reveal that such molecular collagen defects can be driven by mechanical overloading without collagenase degradation and are intimately associated with glycosaminoglycan loss. We showcase the advantages of using collagen denaturation as an early-stage OA hallmark for in vivo therapeutic evaluation and molecular magnetic resonance imaging (MRI) of subtle joint defects that are challenging to detect with conventional morphology-based MRI. These results highlight biomolecular integrity as a crucial dimension for characterizing joint degeneration and a molecular foundation for diagnosing early-stage OA and beyond.
Beyond the numbers: A phenomenological analysis of women’s childbirth experiences in Spain’s evolving healthcare system
Authors: Palau-Costafreda Roser , Nar-Devi Sonia , Gil-Poisa Maria , Pajares Manso Amaia , Vela Ana España , Gutiérrez Noemí Obregón , Escuriet Ramon , Julià Mireia , Graells-Sans Ariadna 
Published: June 2024

AbstractBackgroundChildbirth is a transformative experience, yet a considerable percentage of women worldwide encounter negative birth events, affecting maternal wellbeing and mental health. The choice of birth setting significantly impacts outcomes, with midwifery-led units often associated with lower intervention rates and higher satisfaction levels. The recent introduction of midwifery-led units in Spain presents a unique opportunity to explore the impact of this model within a medicalized healthcare context.AimTo capture the depth and diversity of women’s voices, understanding factors influencing their perceptions of childbirth experiences following the introduction of the first midwifery-led unit in the Spanish Healthcare System.MethodsA qualitative study with a phenomenological approach within the constructivist paradigm. Four focus groups were conducted including nineteen women who gave birth in a hospital with both an obstetric and a midwifery-led unit.FindingsThree main themes were identified; ‘Shaping birth expectations’, highlighting the influence of cultural and social contexts on women’s childbirth expectations; ‘The childbirth essentials’, incorporating fundamental characteristics related to the model of care; and ‘Navigating the protective factors’, considering the pivotal role of midwives in delivering compassionate and respectful care.ConclusionThese findings offer valuable insights into childbirth experiences, advocating for a transformation of the medicalized healthcare system in Spain through the integration of midwifery-led units. By prioritising women’s voices and addressing systemic inequalities, healthcare policymakers can enhance maternal care practices and foster positive childbirth experiences for all women.
A genome-wide cross-trait analysis identifies causal relationship and shared loci of food preference with obesity
Authors: Yao Shi , Wu Hao , Bao Peng , Qian Long , Han Ji-Zhou , Wang Yan , Feng Si-Fan , Cai Yu-Jie , Guo Jing , Ke Xin , Shi Wei , Ma Fu-Bin , Liang Qiu-Hao , Dong Shan-Shan , Guo Yan , Zhu Dong-Li , Cui Li-Li 
Published: June 2024

AbstractFood preferences play a pivotal role in dietary choices and body weight regulation, yet the causal relationships and complex pathways linking food liking to obesity remain elusive. Here, we employed a two-sample Mendelian randomization (MR) analysis and pleiotropic analysis to explore the causalities and shared loci between 187 food preferences (N=161,625) and five obesity-related phenotypes (N=100,716 to 322,154). MR analysis revealed a causal association between two food-liking phenotypes and increased body mass index (BMI), specifically, onion liking (β, 0.286; 95% CI, 0.185 to 0.387;P= 2.80×10−8), and highly palatable food liking (β, 0.266; 95% CI, 0.140 to 0.391;P= 3.31×10−5). Multivariable MR analysis indicated that the impact of onion liking on BMI persisted even after conditioning on actual onion intake, suggesting a degree of independence in dietary preferences’ influence. Pleiotropic analysis under a composite null hypothesis detected 32 pleiotropic loci and six colocalized loci in these two trait pairs. Candidate pleiotropic genes associated with onion liking-BMI highlighted biological pathways primarily involved in the sensory perception of smell. These findings enhance our comprehension of the intricate relationship between food preferences and obesity.
Voluntary Medical Male Circumcision’s (VMMC) Strategy for HIV prevention in Sub-Saharan Africa, prevalence, risks, costs, benefits and best practice: A scoping review of progress and unfolding insights
Authors: Maibvise Charles , Munangatire Takaedza , Tomas Nector , Ashipala Daniel O. , Dlamini Priscilla S. 
Published: June 2024

ABSTRACTCampaigns to scale up Voluntary Medical Male Circumcision (VMMC) for the prevention of HIV transmission has been going on for years in selected Southern African countries, following recommendations from the World Health Organisations. Despite significant strides made in the initiative and its proven benefits, controversies surrounding the strategy have never ceased, and its future remains uncertain especially as some countries near their initial targets. Over the years, as the campaigns unfolded, a lot of insights have been generated in favour of continuing the VMMC campaigns, while some insights portray the impression that the strategy is not worthy the risks and effort required, or enough has been done, as the targets have been achieved. This article proposes a scoping review that aims at synthesizing and consolidating that evidence into a baseline for a further systematic review aimed at developing sound recommendations for the future of the VMMC strategy for HIV prevention. The scoping review will target all scientific literature published on the Web of Science, Cochrane Library, Scopus, Science Direct, PubMed as well as WHO Institutional Repository for Information Sharing (IRIS) since 2011. The review shall be guided by Arksey and O’Malley’s (2005) framework for scoping reviews, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist shall be followed. Discussion of the findings is envisioned to yield evidence that can be further analysed to give insights about risk/cost-benefits ratios of the strategy at this point in time as well best clinical practices for the VMMC procedure, to inform the future of the strategy.
Do silver-chitosan nanocomposites promote bacterial resistance to silver or common antibiotics?
Authors: Sihtmäe Mariliis , Laanoja Jüri , Otsus Maarja , Vija Heiki , Kahru Anne , Kasemets Kaja 
Published: June 2024

ABSTRACTSilver-containing nanomaterials are versatile antimicrobials for slowing down the rapid increase of nosocomial infections caused by antibiotic-resistant bacteria. However, silver can also promote resistance in bacteria to both silver itself and conventional antibiotics. Despite this, the topic is still poorly studied.Silver-chitosan nanocomposites (nAgCSs) with a primary size of ∼50 nm and weight ratios of 1:1 (nAgCS-1) and 1:3 (nAgCS-3) were synthesised and studied for potential antimicrobials, such as wound dressings, antimicrobial coatings. These nAgCSs exhibited antibacterial efficacy at level of 6.25–14.6 mg Ag/L level (minimal inhibitory concentration, MIC) againstEscherichia coliandStaphylococcus aureusbeing comparable to the efficiency of AgNO3(MIC 3.13–7.29 mg Ag/L) or benzalkonium chloride (MIC 0.91–6.25 mg/L). Low molecular weight chitosan also demonstrated antibacterial activity againstS. aureus(MIC 25 mg/L), though it was less effective againstE. coli(MIC 70 mg/L). Notably, nAgCS-3 was almost as efficient as AgNO3againstS. aureus(MIC 6.25–7.29 mg/L) and benzalkonium chloride againstE. coli(MIC 6. mg/L). Confocal laser scanning microscopy revealed a noticeable aggregation ofS. aureuscells caused by exposure to nAgCS-3, an effect that was less pronounced inE. coli.The development of bacterial resistance to nAgCSs and AgNO3and cross-resistance to 14 conventional antibiotics upon continuous exposure (up to 5 weeks) to sub-inhibitory concentrations (EC20) of the studied silver compounds was examined. No resistance development was observed for the studied silver compounds and antibiotics in eitherE. coliorS. aureus. Thus, silver-chitosan nanocomposites show promise as efficient and not AMR-inducing compounds for antimicrobial applications, such as wound dressings and surfaces.
Mitochondrial oxidant stress promotes α-synuclein aggregation and spreading in mice with mutated glucocerebrosidase
Authors: Vitola Pietro La , Szegö Eva M , Pinto-Costa Rita , Rollar Angela , Harbachova Eugenia , Schapira Anthony HV , Ulusoy Ayse , Di Monte Donato A 
Published: June 2024

AbstractMutations of the glucocerebrosidase-encoding gene,GBA1, are common risk factors for Parkinson’s disease. Although only a minority of mutation-carrying individuals develops the disease, the mechanisms of neuronal vulnerability predisposing to pathology conversion remain largely unclear. In this study, heterozygous expression of a common glucocerebrosidase variant, namely the L444P mutation, was found to exacerbate α-synuclein aggregation and spreading in a mouse model of Parkinson-like pathology targeting neurons of the medullary vagal system. These neurons are primary sites of α-synuclein lesions in Parkinson’s disease and were shown here to become more vulnerable to oxidative stress after L444P expression. Nitrative burden paralleled the enhanced formation of reactive oxygen species within vagal neurons expressing mutated glucocerebrosidase, as indicated by pronounced accumulation of nitrated α-synuclein. A causal relationship linked mutation-induced oxidative stress to enhanced α-synuclein pathology that could indeed be rescued by neuronal overexpression of the mitochondrial antioxidant enzyme superoxide dismutase 2. Further evidence supported a key involvement of mitochondria as sources of reactive oxygen species as well as targets of oxidative and nitrative damage within L444P-expressing neurons. Scavenging of oxygen species by superoxide dismutase 2 effectively counteracted deleterious nitrative reactions and prevented nitrated α-synuclein burden. Taken together, these findings support the conclusion that enhanced vulnerability to mitochondrial oxidative stress conferred by glucocerebrosidase mutations should be considered an important mechanism predisposing to Parkinson’s disease pathology, particularly in brain regions targeted by α-synuclein aggregation and involved in α-synuclein spreading.
The L,D-transpeptidation pathway is inhibited by antibiotics of the β-lactam class in Clostridioides difficile
Authors: Paiva Ana M. Oliveira , Courtin Pascal , Charpentier Glenn , Soutourina Olga , Chapot-Chartier Marie-Pierre , Peltier Johann 
Published: June 2024

SummaryThe resistance ofClostridioides difficileto the β-lactam antibiotics cephalosporins, which target the peptidoglycan (PG) assembly, is a leading contributor to the development ofC. difficileinfections.C. difficilehas an original PG structure with a predominance of 3→3 cross-links generated by L,D-transpeptidases (LDTs).C. difficileforms spores and we show that the spore cortex PG contains exclusively 3→3 cross-links. PG and spore cortex ofC. difficilecells were largely unaffected by the deletion of the three predicted LDTs, revealing the implication of a new family of LDTS. The D,D-carboxypeptidases producing the essential LDT substrate were inactivated by cephalosporins, resulting in the inhibition of the L,D-transpeptidation pathway. In contrast, the participation of penicillin-binding proteins (PBPs) to PG cross-linking increased in the presence of the antibiotics. Our findings highlight that cephalosporin resistance is not primarily mediated by LDTs and illustrate the plasticity of the PG biosynthesis machinery inC. difficile.
The developing Human Connectome Project fetal functional MRI release: Methods and data structures
Authors: Karolis Vyacheslav R. , Cordero-Grande Lucilio , Price Anthony N. , Hughes Emer , Fitzgibbon Sean P. , Kyriakopoulou Vanessa , Uus Alena , Harper Nicholas , Prokopenko Denis , Bridglal Devi , Moore Jucha Willers , Wilson Sian , Pietsch Maximilian , Christiaens Daan , Deprez Maria , Williams Logan Z.J. , Robinson Emma C. , Makropoulos Antonis , Farahibozorg Seyedeh-Rezvan , O’Muircheartaigh Jonathan , Rutherford Mary A. , Rueckert Daniel , Edwards A. David , Arichi Tomoki , Smith Stephen M. , Duff Eugene , Hajnal Joseph V. 
Published: June 2024

AbstractRecent advances in fetal fMRI present a new opportunity for neuroscience to study functional human brain connectivity at the time of its emergence. Progress in the field however has been hampered by the lack of openly available datasets that can be exploited by researchers across disciplines to develop methods that would address the unique challenges associated with imaging and analysing functional brain in utero, such as unconstrained head motion, dynamically evolving geometric distortions, or inherently low signal-to-noise ratio. Here we describe the developing Human Connectome Project’s release of the largest open access fetal fMRI dataset to date, containing 275 scans from 255 fetuses and spanning the period of 20.86 to 38.29 post-menstrual weeks. We present a systematic approach to its pre-processing, implementing multi-band soft SENSE reconstruction, dynamic distortion corrections via phase unwrapping method, slice-to-volume reconstruction and a tailored temporal filtering model, with attention to the prominent sources of structured noise in the in utero fMRI. The dataset is accompanied with an advanced registration infrastructure, enabling group-level data fusion, and contains outputs from the main intermediate processing steps. This allows for various levels of data exploration by the imaging and neuroscientific community, starting from the development of robust pipelines for anatomical and temporal corrections to methods for elucidating the development of functional connectivity in utero. By providing a high-quality template for further method development and benchmarking, the release of the dataset will help to advance fetal fMRI to its deserved and timely place at the forefront of the efforts to build a life-long connectome of the human brain.
Examining heterogeneity in dementia using data-driven unsupervised clustering of cognitive profiles
Authors: Kumar Sayantan , Oh Inez Y. , Schindler Suzanne E. , Ghoshal Nupur , Abrams Zachary , Payne Philip R.O. 
Published: June 2024

AbstractDementia is characterized by a decline in memory and thinking that is significant enough to impair function in activities of daily living. Patients seen in dementia specialty clinics are highly heterogenous with a variety of different symptoms that progress at different rates. Recent research has focused on finding data-driven subtypes for revealing new insights into dementia’s underlying heterogeneity, compared to analyzing the entire cohort as a single homogeneous group. However, current studies on dementia subtyping have the following limitations: (i) focusing on AD-related dementia only and not examining heterogeneity within dementia as a whole, (ii) using only cross-sectional baseline visit information for clustering and (iii) predominantly relying on expensive imaging biomarkers as features for clustering. In this study, we seek to overcome such limitations, using a data-driven unsupervised clustering algorithm named SillyPutty, in combination with hierarchical clustering on cognitive assessment scores to estimate subtypes within a real-world clinical dementia cohort. We use a longitudinal patient data set for our clustering analysis, instead of relying only on baseline visits, allowing us to explore the ongoing temporal relationship between subtypes and disease progression over time. Results showed that subtypes with very mild or mild dementia were more heterogenous in their cognitive profiles and risk of disease progression.
The C-terminal activating domain promotes Panx1 channel opening
Authors: Henze Erik , Ehrlich Jacqueline J. , Robertson Janice L. , Kawate Toshimitsu 
Published: June 2024

ABSTRACTPannexin 1 (Panx1) constitutes a large pore channel responsible for the release of ATP from apoptotic cells. Strong evidence indicates that caspase-mediated cleavage of the C-terminus promotes the opening of the Panx1 channel by unplugging the pore. However, this simple pore- plugging mechanism alone cannot account for the observation that a Panx1 construct ending before the caspase cleavage site remains closed. Here, we show that a helical region located immediately before the caspase cleavage site, referred to as the "C-terminal activating domain (CAD)," plays a pivotal role in facilitating Panx1 activation. Electrophysiology and mutagenesis studies uncovered that two conserved leucine residues within the CAD plays a pivotal role. Cryo- EM analysis of the construct ending before reaching the CAD demonstrated that the N-terminus extends into an intracellular pocket. In contrast, the construct including the CAD revealed that this domain occupies the intracellular pocket, causing the N-terminus to flip upward within the pore. Analysis of electrostatic free energy landscape in the closed conformation indicated that the intracellular side of the ion permeation pore may be occupied by anions like ATP, creating an electrostatic barrier for anions attempting to permeate the pore. When the N-terminus flips up, it diminishes the positively charged surface, thereby reducing the drive to accumulate anions inside the pore. This dynamic change in the electrostatic landscape likely contributes to the selection of permeant ions. Collectively, these experiments put forth a novel mechanism in which C-terminal cleavage liberates the CAD, causing the repositioning of the N-terminus to promote Panx1 channel opening.
Single-Mitochondrion Sequencing Uncovers Distinct Mutational Patterns and Heteroplasmy Landscape in Mouse Astrocytes and Neurons
Authors: Kadam Parnika S , Yang Zijian , Lu Youtao , Zhu Hua , Atiyas Yasemin , Shah Nishal , Fisher Stephen , Nordgren Erik , Kim Junhyong , Issadore David , Eberwine James 
Published: June 2024

AbstractBackgroundMitochondrial (mt) heteroplasmy can cause adverse biological consequences when deleterious mtDNA mutations accumulate disrupting ‘normal’ mt-driven processes and cellular functions. To investigate the heteroplasmy of such mtDNA changes we developed a moderate throughput mt isolation procedure to quantify the mt single-nucleotide variant (SNV) landscape in individual mouse neurons and astrocytes In this study we amplified mt-genomes from 1,645 single mitochondria (mts) isolated from mouse single astrocytes and neurons to 1. determine the distribution and proportion of mt-SNVs as well as mutation pattern in specific target regions across the mt-genome, 2. assess differences in mtDNA SNVs between neurons and astrocytes, and 3. Study cosegregation of variants in the mouse mtDNA.Results1. The data show that specific sites of the mt-genome are permissive to SNV presentation while others appear to be under stringent purifying selection. Nested hierarchical analysis at the levels of mitochondrion, cell, and mouse reveals distinct patterns of inter- and intra-cellular variation for mt-SNVs at different sites. 2. Further, differences in the SNV incidence were observed between mouse neurons and astrocytes for two mt-SNV 9027:G>A and 9419:C>T showing variation in the mutational propensity between these cell types. Purifying selection was observed in neurons as shown by the Ka/Ks statistic, suggesting that neurons are under stronger evolutionary constraint as compared to astrocytes. 3. Intriguingly, these data show strong linkage between the SNV sites at nucleotide positions 9027 and 9461. fConclusionThis study suggests that segregation as well as clonal expansion of mt-SNVs is specific to individual genomic loci, which is important foundational data in understanding of heteroplasmy and disease thresholds for mutation of pathogenic variants.
Months-long stability of the head-direction system
Authors: Carrasco Sofia Skromne , Viejo Guillaume , Peyrache Adrien 
Published: June 2024

ABSTRACTSpatial orientation is a universal ability that allows animals to navigate their environment. In mammals, the head-direction (HD) system is an essential component of the brain’s navigation system, yet the stability of its underlying neuronal code remains unclear. Here, by longitudinally tracking the activity of the same HD cells in freely moving mice, we show that the internal organization of population activity in the HD system was preserved for several months. Furthermore, the HD system developed a unique mapping between its internal organization and spatial orientation in each environment. This was not affected by visits to other environments and was stabilized with experience. These findings demonstrate that stable neuronal code supports the sense of direction and forms long-lasting orientation memories.
Genotypic and Phenotypic Analyses ShowRalstonia solanacearumCool Virulence is a Quantitative Trait Not Restricted to “Race 3 biovar 2”
Authors: Dewberry Ronnie J. , Sharma Parul , Prom Jessica L. , Kinscherf Noah A. , Lowe-Power Tiffany , Mazloom Reza , Zhang Xuemei , Liu Haijie , Arif Mohammad , Stulberg Michael , Heath Lenwood S. , Eversole Kellye , Beattie Gwyn A. , Vinatzer Boris A. , Allen Caitilyn 
Published: June 2024

AbstractMostRalstonia solanacearumspecies complex strains cause bacterial wilts in tropical or subtropical zones, but the group known as Race 3 biovar 2 (R3bv2) is cool virulent and causes potato brown rot at lower temperatures. R3bv2 has invaded potato-growing regions around the world but is not established in the United States. Phylogenetically, R3bv2 corresponds to a subset of theR. solanacearumphylotype IIB clade, but little is known about the distribution of the cool virulence phenotype within phylotype IIB. Therefore, genomes of 76 potentially cool virulent phylotype IIB strains and 30 public genomes were phylogenetically analyzed. A single clonal lineage within the sequevar 1 subclade of phylotype IIB that originated in South America has caused nearly all brown rot outbreaks worldwide. To correlate genotypes with relevant phenotypes, we quantified virulence of tenRalstoniastrains on tomato and potato at both 22°C and 28°C. Cool virulence on tomato did not predict cool virulence on potato. We found that cool virulence is a quantitative trait. Strains in the sequevar 1 pandemic clonal lineage caused the most disease, while other R3bv2 strains were only moderately cool virulent. However, some non-R3bv2 strains were highly cool virulent and aggressively colonized potato tubers. Thus, cool virulence is not consistently correlated with strains historically classified as R3bv2 group. To aid detection of sequevar 1 strains, this group was genomically delimited in the LINbase web server and a sequevar 1 diagnostic primer pair was developed and validated. We discuss implications of these results for the R3bv2 definition.