bluuebunny/crossref_metadata_2025_split huggingface dataset:
Online sexual, reproductive, and transgender healthcare for LGBTQI+ youth: A scoping review
Authors: McLeod Julie , Estcourt Claudia S. , Flowers Paul , Gibbs Jo , MacDonald Jennifer 
Published: August 2024

AbstractBackgroundLesbian, gay, bisexual, trans, queer, questioning, intersex, and other sexual and gender minority (LGBTQI+) youth have poor sexual and reproductive health outcomes and low uptake of sexual and reproductive healthcare (SRHC). Online SRHC and transgender healthcare could overcome known barriers to in-person SRHC, such as confidentiality concerns. Therefore, we aimed to describe existing literature on online SRHC and transgender healthcare for LGBTQI+ youth, synthesise study findings, and make recommendations for future research.MethodsWe conducted a scoping review following the Joanna-Briggs Institute methodology. Eligibility were online SRHC and transgender healthcare for LGBTQI+ youth (aged 10-35 years) in high-income countries. Search strings were framed around the eligibility criteria and 265 search terms were selected to identify published literature from nine databases. Searches were exported to Rayyan and studies screened by two reviewers. Data from included studies were extracted to Excel and analyzed descriptively.ResultsOf 91 included papers, 41 were quantitative, 26 were qualitative, and 24 were mixed methods. Seventy-one papers focused on sexual health (HIV/sexually transmitted infection (STI) prevention 52/71; HIV management 9/71; sexual healthper se9/71; and HIV stigma reduction 2/71); 3/91 on reproductive health (pregnancy prevention 2/3); 2/91 sexual and reproductive health; and 16/91 on transgender health (gender identity/transitionper se8/16; gender affirming care 8/16). Papers explored the provision of or engagement with education/information (72/91); non-clinical support (56/91, e.g., reminders for HIV/STI testing); and clinical care (18/91) for sexual health (10/18, e.g., home HIV/STI self-sampling kits 6/10) or transgender health (8/18, i.e., eConsultation with a healthcare provider 8/8). Studies targeted young men who have sex with men (62/91) for sexual health; trans and gender diverse youth (26/91) for transgender healthcare (16/26) and sexual health (14/26); LGBTQI+ youth (6/91); and young sexual minority women (4/91) for reproductive health (3/4) and sexual and reproductive health (1/4).ConclusionsThere is a large and varied literature base for online SRHC and transgender healthcare for LGBTQI+ youth. However, most research focused on sexual healthcare, particularly HIV/STI prevention, for men who have sex with men. Very little explored reproduction or sexual health other than HIV prevention. Young sexual minority women and trans and gender diverse youth are notably under-researched for online SRHC. Research is needed to understand how to enhance the potential of online healthcare for LGBTQI+ youth.
Locating the Missing Chlorophyllsfin Far-red Photosystem I
Authors: Consoli Giovanni , Tufail Fiazall , Leong Ho Fong , Viola Stefania , Davis Geoffry A. , Medranda Daniel , Rew Nicholas , Hofer Michael , Simpson Paul , Sandrin Marco , Chachuat Benoit , Nelson Jenny , Renger Thomas , Murray James W. , Fantuzzi Andrea , Rutherford A. William 
Published: August 2024

AbstractThe discovery of chlorophyllf-containing oxygenic photosynthesis, with its long-wavelength photochemistry, represented a new low-energy paradigm. However, subsequent structural studies on chlorophyllf-containing Photosystem I (PSI) found five chlorophyllsfbut none among the photochemically active pigments and concluded that chlorophyllfplays no photochemical role. Here we report a cryo-EM structure (2.01 Å) of far-red PSI fromChroococcidiopsis thermalisPCC 7203, showing all eight chlorophyllsf, including the redox active A-1B. Simulations of absorption difference spectra induced by charge separation indicate that the A-1Bchlorophyllfabsorbs at 755 nm. The chlorophyllfsites, some wavelength assignments, and conserved far-red-specific amino acids, provide functional insights, including redox tuning of chlorophyllfas the primary donor and far-red excitation energy-sharing over the PSI trimer.
A vaccine antigen central in influenza A(H5) virus antigenic space confers subtype-wide immunity
Authors: Kok Adinda , Wilks Samuel H. , Tureli Sina , James Sarah L. , Bestebroer Theo M. , Burke David F. , Funk Mathis , van der Vliet Stefan , Spronken Monique I. , Rijnink Willemijn F. , Pattinson David , de Meulder Dennis , Rosu Miruna E. , Lexmond Pascal , van den Brand Judith M.A. , Herfst Sander , Smith Derek J. , Fouchier Ron A.M. , Richard Mathilde 
Published: August 2024

AbstractHighly pathogenic avian influenza A(H5) viruses globally impact wild and domestic birds, and mammals, including humans, underscoring their pandemic potential. The antigenic evolution of the A(H5) hemagglutinin (HA) poses challenges for pandemic preparedness and vaccine design. Here, the global antigenic evolution of the A(H5) HA was captured in a high-resolution antigenic map. The map was used to engineer immunogenic and antigenically central vaccine HA antigens, eliciting antibody responses that broadly cover the A(H5) antigenic space. In ferrets, a central antigen protected as well as homologous vaccines against heterologous infection with two antigenically distinct viruses. This work showcases the rational design of subtype-wide influenza A(H5) pre-pandemic vaccines and demonstrates the value of antigenic maps for the evaluation of vaccine-induced immune responses through antibody profiles.
Autophagosomes coordinate an AKAP11-dependent regulatory checkpoint that shapes neuronal PKA signaling
Authors: Segura-Roman Ashley , Citron Y. Rose , Shin Myungsun , Sindoni Nicole , Maya-Romero Alex , Rapp Simon , Goul Claire , Mancias Joseph D. , Zoncu Roberto 
Published: August 2024

AbstractProtein Kinase A (PKA) is regulated spatially and temporally via scaffolding of its catalytic (Cα/β) and regulatory (RI/RII) subunits by the A-kinase-anchoring proteins (AKAP). PKA engages in poorly understood interactions with autophagy, a key degradation pathway for neuronal cell homeostasis, partly via its AKAP11 scaffold. Mutations in AKAP11 drive schizophrenia and bipolar disorders (SZ-BP) through unknown mechanisms. Through proteomic-based analysis of immunopurified lysosomes, we identify the Cα−RIα-AKAP11 holocomplex as a prominent autophagy-associated protein kinase complex. AKAP11 scaffolds Cα−RIα to the autophagic machinery via its LC3-interacting region (LIR), enabling both PKA regulation by upstream signals, and its autophagy-dependent degradation. We identify Ser83 on the RIα linker-hinge region as an AKAP11-dependent phospho-residue that modulates RIα-Cα binding and cAMP-induced PKA activation. Decoupling AKAP11-PKA from autophagy alters Ser83 phosphorylation, supporting an autophagy-dependent checkpoint for PKA signaling. Ablating AKAP11 in induced pluripotent stem cell-derived neurons reveals dysregulation of multiple pathways for neuronal homeostasis. Thus, the autophagosome is a novel platform that modulate PKA signaling, providing a possible mechanistic link to SZ/BP pathophysiology.
Novel replication-competent reporter-expressing Rift Valley Fever Viruses for molecular studies
Authors: Nogales Aitor , Alonso Celia , Moreno Sandra , Lorenzo Gema , Borrego Belén , Martinez-Sobrido Luis , Brun Alejandro 
Published: August 2024

ABSTRACTRift Valley fever virus (RVFV) is a mosquito-borne zoonotic disease that causes severe disease in both domestic and wild ungulates and humans, making it a significant threat to livestock and public health. The RVFV genome consists of three single-stranded, negative-sense RNA segments differing in size: Small (S), Medium (M) and Large (L). Segment S encodes the virus nucleoprotein N and the virulence-associated factor non-structural (NSs) protein in opposite orientations, separated by an intergenic region (IGR). To overcome the current need of using secondary techniques to detect the presence of RVFV in infected cells, we used T7-driven polymerase plasmid-based reverse genetics to generate replication-competent recombinant (r)RVFV expressing Nanoluciferase (Nluc) or Venus fluorescent proteins. These reporter genes were used as valid surrogates to track the presence of RVFV in mammalian and insect cells. Notably, we explored the genome plasticity of RVFV and compared four different strategies by modifying the viral segment S in order to introduce the reporter gene foreign sequences. The reporter-expressing rRVFV were stable and able to replicate in cultured mammalian and insect cells, although to a lesser extent than the recombinant wild-type (WT) counterpart. Moreover, rRVFV expressing reporter genes were validated to identify neutralizing antibodies or compounds with antiviral activity.In vivo, all mice infected with the reporter-expressing rRVFV displayed an attenuated phenotype, although at different levels. These rRVFV expressing reporter genes provide a novel approach to better understand the biology and pathogenesis of RVFV, and represent an excellent biotechnological tool for developing new therapeutics against RVFV infections.IMPORTANCERift Valley fever virus (RVFV) is a mosquito-borne virus and zoonotic agent threat that can be deadly to domestic or wild ungulates, and humans. In this work, we used reverse genetics approaches to explore the genome plasticity of RVFV by generating a set of recombinant rRVFV that express fluorescent or luminescent proteins to track viral infection. All the generated reporter-expressing rRVFV were able to propagate in mammalian or insect cells, and in a mouse model of infection. Our studies may contribute to advances in research on RVFV and other bunyaviruses and pave the way for the development of novel vaccines and the identification of new antivirals for the prophylactic and therapeutic treatment, respectively, of RVFV infections.
Relative Distribution of DnaA and DNA inEscherichia coliCells as a Factor of Their Phenotypic Variability
Authors: Namboodiri Sharanya K. , Aranovich Alexander , Hadad Uzi , Gheber Levi A. , Feingold Mario , Fishov Itzhak 
Published: August 2024

AbstractPhenotypic variability in isogenic bacterial populations is a remarkable feature that helps them cope with external stresses, yet it is incompletely understood. This variability can stem from gene expression noise and/or unequal partitioning of low-copy-number freely diffusing proteins during cell division. Some high-copy-number components are transiently associated with almost immobile large assemblies (hyperstructures) and may be unequally distributed, contributing to bacterial phenotypic variability. We focus on the nucleoid hyperstructure containing numerous DNA-associated proteins, including the replication initiator DnaA. Previously we found an increasing asynchrony in the nucleoid segregation dynamics in growingE. colicell lineages and suggested that variable replication initiation timing may be the main cause of this phenomenon. Here we support this hypothesis revealing that DnaA/DNA variability represents a key factor leading to the enhanced asynchrony inE. coli. We followed the intra- and intercellular distribution of fluorescently tagged DnaA and histone-like HU chromosomally encoded under their native promoters. The diffusion rate of DnaA is low, corresponding to a diffusion-binding mode of mobility, but still one order faster than that of HU. The intracellular distribution of DnaA concentration is homogeneous in contrast to the significant asymmetry in the distribution of HU to the cell halves, leading to unequal DNA content of nucleoids and DnaA/DNA ratios in future daughter compartments. Accordingly, the intercellular variabilities of HU concentration (CV=26%) and DnaA/DNA ratio (CV=18%) are high. The variable DnaA/DNA may cause a variable replication initiation time (initiation noise). Asynchronous initiation at different replication origins may, in turn, be the mechanism leading to the observed asymmetric intracellular DNA distribution. Our findings indicate that the feature determining the variability of initiation time inE. coliis the DnaA/DNA ratio rather than separately each of them. We provide a likely mechanism for the ‘loss of segregation synchrony’ phenomenon.
WITHDRAWN: Interspecies recombination between cassava brown streak disease-causing viruses
Authors: Astacio-Berrios Keryan , Duffy Siobain 
Published: August 2024

Withdrawal StatementThe authors have withdrawn this manuscript because the putative interspecific recombinant sequences (MW961179.1, MW961204.1, MW961211.1 and MW961191.1), upon further scrutiny by the researchers who generated the data, have been revealed to be artifacts of assembly from illumina sequencing of plants with mixed CBSV/UCBSV infection. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Allele ages provide limited information about the strength of negative selection
Authors: Shastry Vivaswat , Berg Jeremy J. 
Published: August 2024

AbstractFor many problems in population genetics, it is useful to characterize the distribution of fitness effects (DFE) ofde novomutations among a certain class of sites. A DFE is typically estimated by fitting an observed site frequency spectrum (SFS) to an expected SFS given a hypothesized distribution of selection coefficients and demographic history. The development of tools to infer gene trees from haplotype alignments, along with ancient DNA resources, provides us with additional information about the frequency trajectories of segregating mutations. Here, we ask how useful this additional information is for learning about the DFE, using the joint distribution on allele frequency and age to summarize information about the trajectory. To this end, we introduce an accurate and efficient numerical method for computing the density on the age of a segregating variant found at a given sample frequency, given the strength of selection and an arbitrarily complex population size history. We then use this framework to show that the unconditional age distribution of negatively selected alleles is very closely approximated by re-weighting the neutral age distribution in terms of the negatively selected SFS, suggesting that allele ages provide very little information about the DFE beyond that already contained in the present day frequency. To confirm this prediction, we extended the standard Poisson Random Field (PRF) method to incorporate the joint distribution of frequency and age in estimating selection coefficients, and test its performance using simulations. We find that when the full SFS is observed and the true allele ages are known, including ages in the estimation provides only small increases in the accuracy of estimated selection coefficients. However, if only sites with frequencies above a certain threshold are observed, then the true ages can provide substantial information about the selection coefficients, especially when the selection coefficient is large. When ages are estimated from haplotype data using state-of-the-art tools, uncertainty about the age abrogates most of the additional information in the fully observed SFS case, while the neutral prior assumed in these tools when estimating ages induces a downward bias in the case of the thresholded SFS.
PTEN neddylation aggravates CDK4/6 inhibitor resistance in breast cancer
Authors: Liu Fan , Liu Weixiao , Tan Yawen , Shang Yaxin , Ling Sihui , Jiang Xiaokun , Zhang Zhen , Sun Shiyao , Xie Ping 
Published: August 2024

AbstractBackgroundThe gradual emergence of a novel therapeutic approach lies in the restoration of tumor suppressive machinery. PTEN is a crucial negative regulator of the PI3K/Akt signaling pathway. Protein neddylation modification contributes to PTEN inactivation and fuels breast cancer progression.MethodsIn this study, well-established CDK4/6 inhibitor resistance models were used to detect the levels of PTEN neddylation. Co-immunoprecipitation,in vivoandin vitromodification assays and transcriptome data were integrated to delve into the mechanism. Following this, a PTEN CDK4/6 inhibitors in bothin situtumor models and breast cancer cells. Furthermore, in patient-derived organoids (PDOs), we combined the PTEN neddylation inhibitor with CDK4/6 inhibitors to confirm their inhibitory effect on breast cancer progression.ResultsWe highlight that an elevated level of PTEN neddylation is markedly associated with resistance to palbociclib, a CDK4/6 inhibitor used in luminal subtype breast cancer patients. Mechanistically, PTEN neddylation activates the PI3K/Akt signaling pathway, and more notably, upregulates the activity of the AP-1 transcription factor. Our data showed that PTEN neddylation stabilizes JUND, a transcription factor involved in the AP-1, by disrupting its interaction with the E3 ubiquitin ligase ITCH. Consequently, activated JUND leads to the release of cytokines and chemokines, such as G-CSF, GM-CSF, IL-1RA, IL-1β, which in turn may drive an inflammatory tumor microenvironment, potentially contributing to drug resistance. Then, we identified Echinacoside as a potent inhibitor of PTEN neddylation bothin vivoandin vitroby disrupting its interaction with XIAP, the E3 ligase responsible for PTEN neddylation. Combination of Echinacoside could effectively overcome resistance to palbociclib in breast cancer treatment.ConclusionsThis novel insight underscores the potential of targeting PTEN neddylation as a promising strategy for restoring the activity of key tumor suppressor and overcoming resistance in breast cancer therapy.
Extensive Surveillance of Mosquitoes and molecular investigation of Arboviruses in central Iran; First Record of Molecular Identification ofCulex tarsalisin Qom Province
Authors: Abedi-Astaneh Fatemeh , Rad Hedaiatollah Raoofi , Pouriayevali Mohammad Hassan , Jalali Tahmineh , Izanlou Hassan , Hosseinalipour Seied Abbas , Hamta Amir , Es’haghieh Mohammad , Ebrahimi Mahdi , Ansari-Cheshmeh Mohammad Ali , Salehi-Vaziri Mostafa , Talbalaghi Asghar , Abbasi Ebrahim 
Published: August 2024

AbstractBackgroundArboviruses are one of the greatest threats to animal and public health.Culicidaefamily is one of the most important vectors for the transmission of Arboviruses in the world. According to the geographical, demographic and climatic features of Qom city in Iran, it can be a suitable region for vectors and therefore transmission of Arboviruses.MethodsIn this study, which was conducted between 2019 and 2020 in different parts of Qom city, 83,414 mosquitoes were collected and after evaluating the species of mosquitoes based on morphological and molecular detection, the presence of alphaviruses, flaviviruses and phleboviruses were evaluated using genus specific RT-PCR assays.ResultsIn this study,Culex tarsalis, Culex theilerivoucher, Culex quinquefasciatusand most importantly for the first time in IranCulex tarsaliswere detected. No alphavirus, flavivirus and phlebovirus infection was identified in collected mosquitoes.ConclusionClimatic and weather changes are the basis for the growth and spread of vectors and consequently the spread of arboviral diseases, and this issue seems to be very important on the necessity of increasing and continuing entomological and virological studies.Author SummaryArboviruses pose significant threats to animal and public health globally, with mosquitoes from the Culicidae family serving as key vectors in their transmission. This study focuses on Qom city, Iran, which, due to its unique geographical, demographic, and climatic characteristics, provides a potentially suitable environment for these vectors. Over the course of 2019 to 2020, researchers collected 83,414 mosquitoes across various locations within Qom. Through morphological and molecular analysis, they identified species such asCulex tarsalis, Culex theileri, andCulex quinquefasciatus, notably reportingCulex tarsalisin Iran for the first time. Using genus-specific RT-PCR assays, the study evaluated the presence ofalphaviruses, flaviviruses, andphlebovirusesin the collected samples but found no evidence of infection. These findings underscore the importance of ongoing entomological and virological research, particularly given the potential for climatic changes to influence vector growth and the spread of arboviral diseases.
Predicting onward care needs at admission to reduce discharge delay using machine learning
Authors: Duckworth Chris , Burns Dan , Lamas Fernandez Carlos , Wright Mark , Leyland Rachael , Stammers Matthew , George Michael , Boniface Michael 
Published: August 2024

AbstractEarly identification of patients who require onward referral for social care can prevent delays to discharge from hospital. We introduce a machine learning (ML) model to identify potential social care needs at the first point of admission. The model performance is comparable to clinician’s predictions of discharge care needs, despite working with only a subset of the information available to the clinician. We find that ML and clinician perform better for identifying different types of care needs, highlighting the added value of a potential system supporting decision making. We also demonstrate the ability for ML to provide automated initial discharge need assessments, in the instance where initial clinical assessment is delayed. Finally, we demonstrate that combining clinician and machine predictions, in a hybrid model, provides even more accurate early predictions of onward social care requirements and demonstrates the potential for human-in-the-loop decision support systems in clinical practice.
From Goals to Gains: Results Based Management Revolutionizes NCD Care in Rural Egypt
Authors: Utterman Sonia , Hussein Muhammad , ElKady Mona , Awad Walaa , Marrison Amanda 
Published: August 2024

AbstractThis paper examines the application of Results Based Management (RBM) in a health program aimed at combating noncommunicable diseases (NCDs) in rural Egypt. The study focuses on a three-year initiative implemented from 2019 to 2022 across five governorates, targeting diabetes, hypertension, and cardiovascular diseases. Using a mixed-methods approach, we analyze the program’s design, implementation, and outcomes through the lens of RBM principles.Our findings indicate that the adoption of RBM led to improved goal clarity, enhanced monitoring and evaluation processes, and increased accountability among stakeholders. The program achieved a 15% reduction in NCD-related mortality and a 22% increase in early detection rates. However, challenges were encountered in data collection and local capacity building.This case study contributes to the growing body of literature on RBM in public health contexts, particularly in resource-limited settings. We conclude by offering recommendations for policymakers and program managers on effectively integrating RBM into health initiatives targeting NCDs in similar environments.