bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transformation of the HIV treatment cascade for people who inject drugs in Ukraine
Authors: Bromberg Daniel J. , Rhoades Delaney , Madden Lynn M. , Ivasiy Roman , Meteliuk Anna , Pykalo Iryna , Filippovych Myroslava , Nikitin Benjamin M. , Farnum Scott O. , Fomenko Tetiana , Dvoriak Sergii , Altice Frederick L. ,   the ExMAT Consortium
Published: November 2024

Background:
Ukraine's HIV epidemic, the second-largest in Europe, is concentrated among people who inject drugs (PWID), primarily opioids. Between 2014 and 2021, Ukraine has scaled up opioid agonist therapies (OAT) considerably.

Methods:
We conducted a large cross-sectional biobehavioral survey of PWID in 2020–2021 to compare to an equivalent survey from 2014 to 2015 using representative sampling approaches including random sampling and RDS of PWID with opioid dependence, recruiting those who were: currently on OAT; previously on OAT; and never on OAT. Only PWID who tested positive for HIV were assessed for the proportion linked to care, prescribed antiretroviral therapy (ART), and adherent to ART.

Results:
Comparing samples from 2021 (N = 2027) to 2014 (N = 1613), there were differences in HIV diagnosis (92.6 vs. 90%), linkage to care (86.5 vs. 85.3%), prescription of ART (95.8 vs. 78.9%), and adherence to ART (93.6 vs. 85.7%), for those patients who had previously been on OAT. In a subanalysis from the 2020 to 2021 sample, having ever touched the OAT treatment system (currently or previously on OAT) had significantly better outcomes at each step of the cascade relative to those who had never been on OAT.

Interpretation:
Although OAT had previously been demonstrated to improve HIV treatment outcomes along the HIV care cascade, findings here suggest that OAT has scaled-up along with higher levels of engagement in the HIV care cascade over time. Importantly, but not previously described, is the finding that touching the OAT treatment system, irrespective of retention on treatment contributes to improved HIV treatment outcomes for each step of the cascade.
Impact of Specimen Extraction Site and Gallstone Size on Early Postoperative Pain Following Laparoscopic Cholecystectomy: A Prospective Randomized Controlled Study
Authors: Akgul Nedim , Turan Mehmet I. , Dincer Aydin , Ozyurt Erhan 
Published: November 2024

Background:
Laparoscopic cholecystectomy (LC) is widely performed with generally favorable outcomes, but postoperative pain remains a significant issue, influenced by various factors including the specimen extraction site and gallstone size.

Methods:
A prospective randomized controlled study was conducted on 100 patients undergoing LC. Participants were randomized to have the specimen removed through either the epigastric or umbilical trocar. Postoperative pain was assessed using the visual analog scale (VAS) on postoperative days 1, 3, and 7. Statistical analyses were performed to evaluate the impact of trocar site and gallstone size on pain levels.

Results:
Patients whose specimens were extracted through the umbilical trocar experienced significantly less pain on postoperative days 1 and 3 (P=0.006 and 0.014, respectively) than those with epigastric trocar extraction. In addition, patients with gallstones larger than 10 mm reported higher pain levels on day 3 (P=0.001) irrespective of the extraction site.

Conclusions:
The umbilical trocar site for specimen extraction and smaller gallstone size is associated with reduced early postoperative pain following LC. These findings suggest the importance of considering extraction site and gallstone size in managing postoperative pain in LC patients.
Leaving Slings and Other Transfer Devices Under Patients
Authors: Bradley Sarah E. , Chavez Margeaux , Barrett Blake , Lind Jason , Cowan Linda , Broderick Vianna , Bulat Tatjana 
Published: November 2024

PURPOSE:
The purpose of this quality improvement project was to develop guidance for safe patient handling and mobility efforts to prevent pressure injuries (PIs) within the Veterans Health Administration (VHA) when slings and other transfer devices are left under patients.

PARTICIPANTS AND SETTING:
Health care staff (n = 112) in patient safety and nursing at 77 unique VHA facilities responded to surveys between November and December 2019. Interviews (n = 24) were conducted using purposive sampling with VHA staff at facilities with highest and lowest PI rates (n = 9) between January and March 2021.

APPROACH:
Feedback on practices and perceptions related to leaving slings and other transfer devices were evaluated using online cross-sectional surveys and interviews with VHA staff. Secondary data for VHA inpatient rates of PIs were used to examine associations with staff-reported sling and other transfer device practices.

OUTCOMES:
Leaving slings under patients was associated with higher proportion of patients developing PIs in intensive care units (ICUs, P = .042) and medical-surgical care units (P = .025). In addition, use of sliding boards for seated transfer among short-stay residents in Community Living Centers was associated with higher PI occurrences (P = .017). Qualitative interviews found perceptions and guidance about PI risk related to slings and other transfer devices varied among staff who consider many factors when determining risk.

IMPLICATIONS FOR PRACTICE:
There are perceived benefits and risks of leaving slings and other transfer devices under patients and limited knowledge of PI occurrences associated with this practice. Clinical decision support can help staff determine safe sling use. More work is needed to test the safety of common sling and transfer device practices and define best practices for communicating PI risk related to sling and transfer device use across the care continuum.
Dysregulated airway epithelial antiviral immunity in Down Syndrome impairs type III IFN response and amplifies airway inflammation during RSV infection
Authors: Chorvinsky Elizabeth , Bhattacharya Surajit , Bera Betelehem Solomon , Welham Allison , Ismat Karim , Lawlor Claire M , Preciado Diego , Gomez Jose L , Morizono Hiroki , Pillai Dinesh K , Gutierrez Maria J. , Jaiswal Jyoti K , Nino Gustavo 
Published: November 2024

ABSTRACTTrisomy 21 (TS21), also known as Down syndrome (DS), increases pediatric mortality risk from respiratory syncytial virus (RSV) by nine-fold, yet its underlying immunological basis remains unclear. Here, we investigated RSV-induced immunological responses in TS21 airway epithelial cells (AECs), the primary site of respiratory virus entry and host defense. TS21 AECs exhibit hyperactive interferon (IFN) signaling and reduced RSV infectivity, but they also show impaired type-III IFN responses during viral infection. Furthermore, TS21 AECs demonstrate heightened production of proinflammatory mediators CXCL5 and CXCL10 both before and after RSV exposure. Infants with DS suffering from severe viral bronchiolitis demonstrate dysregulated airway immune responses in vivo, characterized by diminished type-III IFN levels and increased CXCL5/CXCL10 secretion. Our results indicate that RSV severity in DS is not due to impaired viral control but to dysregulated airway proinflammatory responses, offering new therapeutic opportunities to mitigate the severity of RSV infection in children with DS.
Evolvability through segmental duplication follows species-specific dynamics
Authors: Islam Saiful , Aqil Alber , Hach Faraz , Numanagić Ibrahim , Masuda Naoki , Gokcumen Omer 
Published: November 2024

AbstractEvolvability, the capacity of populations to respond to selection, is influenced by genomic structural properties such as segmental duplications. These duplications establish redundancy, creating adaptive potential by co-opting duplicated elements for new functions. Here, we identify segmental duplications in 117 vertebrate species and the starfish outgroup using long-read genome assemblies. We constructed independent segmental duplication networks for each species to represent the landscape of segmental duplications therein. We quantified the duplication landscapes across species using 13 network properties and tested three hypotheses for their evolution: 1) selective constraint, 2) phylogenetic drift, and 3) species-specific dynamics. Our results show that segmental duplication profiles across vertebrates are shaped by fast-evolving, species-specific dynamics, driving unique adaptive potentials. One notable exception of lineage-specific evolution is observed within mammals, where monotremes (platypus and echidna) exhibit distinct genomic structural features, characterized by elevated insertion and deletion rates compared to therian mammals. Analysis of genome size variation in vertebrates revealed no significant correlation with segmental duplication metrics. However, in ray-finned fish, lineage-specific events such as whole-genome duplications in some species (e.g., sterlet sturgeon and brown trout) influence genome size. These findings highlight the role of segmental duplications in species-specific adaptive potential and demonstrate the utility of network-based methods in genomic research. Our dataset and framework provide a valuable resource for understanding genomic evolvability, underscoring the integration of evolutionary biology and network analysis in studying genome evolution.
Fish MicroRNA Responses to Thermal Stress: Insights and Implications for Aquaculture and Conservation Amid Global Warming
Authors: Lin Ting , Meegaskumbura Madhava 
Published: November 2024

AbstractUnder the backdrop of global warming, heat tolerance emerges as an important physiological trait governing the distribution and survival of fish species worldwide. While knowledge on fish heat tolerance and stress has progressed from behavioral studies to transcriptomic analyses, our understanding at the transcriptomic level remains limited. Recently, the highly conserved nature of microRNAs (miRNAs) has introduced new ways of explaining molecular mechanisms of heat stress in fish. Here, we systematically review current research across three main reference databases to explain the universal responses and mechanisms of fish miRNAs to heat stress. An initial screen of 569 articles yielded 13 target papers for comprehensive analysis. Among these, at least 214 differentially expressed genes (DEGs) were identified, with 15 DEGs recurring in at least two studies (12 upregulated, 13 downregulated). The 15 recurrent DEGs were subjected to DIANA mirPath v.3 utilizing the microT-CDS v5.0 database to identify potential target genes. The results indicate that multiple miRNAs target genes, forming a complex network to regulate glucose and energy balance metabolism, maintain homeostasis, and modulate inflammation and immune disorders. Notably,miR-1,miR-122,let-7a, andmiR-30bare identified as potential biomarkers of heat stress in fish. Due to their high conservation across species, these miRNAs could be used to monitor the health of wild fish populations, improve selective breeding programs in aquaculture, and guide conservation strategies for species that are vulnerable to climate change. This review provides a framework for further investigation into the molecular mechanisms of fish heat tolerance.
Pseudomonas aeruginosa-mediated cardiac dysfunction is driven by extracellular vesicles released during infection
Authors: Kumar Naresh , Mattoo Sameer Salam , Sanghvi Shridhar , Ellendula Maneeth P. , Mahajan Sahil , Planner Clara , Bednash Joseph S. , Khan Mahmood , Ganesan Latha P. , Singh Harpreet , Lafuse William P. , Wozniak Daniel J. , Rajaram Murugesan V.S. 
Published: November 2024

AbstractPseudomonas aeruginosa (P.a.)is a gram-negative, opportunistic bacterium abundantly present in the environment. OftenP.a.infections cause severe pneumonia, if left untreated. Surprisingly, up to 30% of patients admitted to the hospital for community- acquired pneumonia develop adverse cardiovascular complications such as myocardial infarction, arrhythmia, left ventricular dysfunction, and heart failure. However, the underlying mechanism of infection-mediated cardiac dysfunction is not yet known. Recently, we demonstrated thatP.a.infection of the lungs led to severe cardiac electrical abnormalities and left ventricular dysfunction with limitedP.a.dissemination to the heart tissue. To understand the mechanism of cardiac dysfunction duringP.a.infection, we utilized bothin vitroandin vivomodels. Our results revealed that inflammatory cytokines contribute but are not solely responsible for severe contractile dysfunction in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Instead, exposure of hiPSC-CMs with conditioned media fromP.a.infected human monocyte-derived macrophages (hMDMs) was sufficient to cause severe contractile dysfunction and arrhythmia in hiPSC-CMs. Specifically, exosomes released from infected hMDMs and bacterial outer membrane vesicles (OMVs) are the major drivers of cardiomyocyte contractile dysfunction. By using LC-MS/MS, we identified bacterial proteins, including toxins that are packaged in the exosomes and OMVs, which are responsible for contractile dysfunction. Furthermore, we demonstrated that systemic delivery of bacterial OMVs to mice caused severe cardiac dysfunction, mimicking the natural bacterial infection. In summary, we conclude that OMVs released during infection enter circulation and drive cardiac dysfunction.
Diet and trophic niche partitioning of three aerial hawking bat species in the Venezuelan Llanos
Authors: Azofeifa Romero Yara , Nassar Jafet M , Mavárez Jesús 
Published: November 2024

ABSTRACTSince Neotropical insectivorous bats (IB) share feeding sites and prey, their coexistence must depend on processes promoting divergence at trophic niches. We conducted diet and activity time analyses of three coexisting IB species in Venezuelan paddies,Molossus molossus, Eptesicus furinalis, andMyotis nigricans, to understand their trophic niche partitioning. We used statistical models to understand: (1) the dietary and activity time overlap among IB species, and (2) the relationship of IB species’ morphology and hunting strategies with prey’s hardness and flight speed. We found high prey richness forM. molossus(32 families),M. nigricans(19 families), andE. furinalis(13 families). Bats exhibited differences in prey richness, proportions, types consumed, as well as in their activity periods. As expected from its larger size and fast flight,M. molossusprefers larger, fast-flying, and medium-to-high sclerotized preys such as Coleoptera and Lepidoptera, with hunting activities starting and peaking significantly earlier than the other two bat species. On the other hand, also consistent with its size and flight type,M. nigricansexhibits a significant preference for small, slow-flying, and weekly sclerotized preys such as Diptera, although with relatively high dietary and temporal overlaps withE. furinalis.Thus, in concordance with niche theory predictions, the coexistence between these bats, particularly betweenM. molossusand the other two species, seems enhanced by reduced competition driven by divergence at trophic niche dimensions.
Naturally occurring N-terminal mutations in SARS-CoV-2 nsp1 impact innate immune modulation but do not affect virus virulence
Authors: Rani Ruchi , Nooruzzaman Mohammed , Caserta Leonardo C. , Diel Diego G. 
Published: November 2024

AbstractThe non-structural protein 1 (nsp1) of SARS-CoV-2 plays a key role in host innate immune evasion. We identified two deletion variants (Δ82-85 and Δ83-86) in the N-terminal region of the nsp1 of a SARS-CoV-2 BA.5.2.1 variant recovered from a human patient. Analysis of the sequence databases revealed a frequency of 0.5% of these mutations amongst available SARS-CoV-2 sequences. Structural analysis of the deletion mutant nsp1Δ82-85 and nsp1Δ83-86 revealed a distortion in the protein pocket when compared to the wild-type nsp1 which may affect protein function. To evaluate the functional relevance of these mutations, we cloned the mutant BA.5.2.1 nsp1Δ82-85 and nsp1Δ83-86 and wild-type nsp1 proteins in expression plasmids and performed luciferase reporter-based assays to assess activation of the interferon and nuclear factor kappa B (NF-κB) signalling pathways. Both nsp1Δ82-85 and nsp1Δ83-86 mutants showed marked decreased ability to inhibit the interferon beta (IFN-β) and NF-κB pathway activation. To assess the relevance of these deletions in the context of SARS-CoV-2 infection, we generated recombinant viruses carrying the wild type BA.5.2.1 nsp1 or the BA.5.2.1 nsp1Δ82-85 and nsp1Δ83-86 deletions in the backbone of WA1 strain.In vitrocharacterization of the recombinant SARS-CoV-2 viruses revealed that the recombinant viruses containing the nsp1Δ82-85 and nsp1Δ83-86 deletions presented similar plaque size and morphology to those produced by the wild-type rWA1-BA.5.2.1-nsp1 virus, indicating a similar ability of the mutant viruses to spread from cell to cell. Importantly, pathogenesis studies revealed that these mutations did not affect virus virulence and pathogenesis in a hamster model of SARS-CoV-2 infection.
Residual flexibility in the topologically constrained multivalent complex between the GKAP scaffold and LC8 hub proteins
Authors: Nagy-Kanta Eszter , Kálmán Zsófia E. , Tossavainen Helena , Juhász Tünde , Farkas Fanni , Hegedüs József , Keresztes Melinda , Beke-Somfai Tamás , Gáspári Zoltán , Permi Perttu , Péterfia Bálint 
Published: November 2024

SummaryGuanylate kinase-associated protein (GKAP) is a large postsynaptic scaffold protein bearing two closely spaced noncanonical binding sites for the bivalent dynein light chain LC8 hub protein. This might allow the formation of heterogeneous complexes with different sizes and topologies. Here, we show that a well-defined hexameric complex is formed, composed of 2 GKAP molecules and 2 LC8 dimers. Using NMR spectroscopy, we demonstrate that the LC8-binding segment of GKAP is intrinsically disordered and the flexibility of the linker region is largely retained even in the complex form. Molecular dynamics calculations suggest that besides the tightly bound residues, the hexamer also exhibits several dynamically interchanging interactions. The flanking regions of the two binding sites on GKAP exhibit different interaction patterns, hinting at additional contacts that might explain the fixed stoichiometry of the assembly. Our results demonstrate that constrained stoichiometry can coexist with substantial flexibility in a multivalent system.
CRISPRi Screen Uncovers lncRNA Regulators of Human Monocyte Growth
Authors: Flores-Arena Cristina , Malekos Eric , Covarrubias Sergio , Sudek Lisa , Montano Christy , Dempsey Valory , Hyunh Vuky , Katzman Sol , Carpenter Susan 
Published: November 2024

AbstractLong noncoding RNAs are emerging as critical regulators of biological processes. While there are over 20,000 lncRNAs annotated in the human genome we do not know the function for the majority. Here we performed a high-throughput CRISPRi screen to identify those lncRNAs that are important in viability in human monocytes using the cell line THP1. We identified a total of 38 hits from the screen and validated and characterized two of the top intergenic hits. The first is a lncRNA neighboring the macrophage viability transcription factor IRF8 (RP11-542M13.2hereafter referred to as long noncoding RNA regulator of monocyte proliferation,LNCRMP) and the second is a lncRNA calledOLMALINC(oligodendrocyte maturation-associated long intervening non-coding RNA) that was previously found to be important in oligodendrocyte maturation. Transcriptional repression ofLNCRMP and OLMALINCfrom monocytes severely limited their proliferation capabilities. RNA-seq analysis of knockdown lines showed thatLNCRMPregulated proapoptotic pathways while knockdown ofOLMALINCimpacted genes associated with the cell cycle. Data supports bothLNCRMPandOLMALINCfunctioningin cisto regulate their neighboring proteins that are also essential for THP1 cell growth. This research highlights the importance of high-throughput screening as a powerful tool for quickly discovering functional long non-coding RNAs (lncRNAs) that play a vital role in regulating monocyte viability.
Conspecific sociability is regulated by associative learning circuits
Authors: Lobato-Rios Victor , Lam Thomas Ka Chung , Ramdya Pavan 
Published: November 2024

AbstractSociability, an animal’s ease and propensity to interact with members of its own species, is a prerequisite for many important social interactions including courtship, mating, brood rearing, and collective behavior. Despite its fundamental nature, the manner through which sociability arises—whether it is innate or acquired and its neural mechanisms— remains unknown. Here, we found that the fly,Drosophila melanogaster, produces a constellation of fearful reactions when it encounters another fly for the first time. However, these animals become sociable following several hours of exposure to conspecific (but not heterospecific) odors. Two large-scale neural silencing screens of 188 brain cell types revealed that both initial fearful reactions and learned sociability depend upon overlapping networks including circuits in the mushroom body, the principal center for associative learning and memory in the insect brain. Functional recordings of key mushroom body output neurons (MBONs) from this network over two hours of social interactions support a mechanistic model whereby fly odors modulate social valence by rebalancing MBON population activity, biasing action selection, and thereby driving sociable rather than fearful responses towards other flies. Thus, a center for learning and memory plays a fundamental role in establishing the basis for most social interactions.
A versatile mouse model to advance human microglia transplantation research in neurodegenerative diseases
Authors: Serneels Lutgarde , Sierksma Annerieke , Pasciuto Emanuela , Geric Ivana , Nair Arya , Martinez-Muriana Anna , Snellinx An , Strooper Bart De 
Published: November 2024

AbstractBackgroundRecent studies highlight the critical role of microglia in neurodegenerative disorders, and emphasize the need for humanized models to accurately study microglial responses. Human-mouse microglia xenotransplantation models are a valuable platform for functional studies and for testing therapeutic approaches, yet currently those models are only available for academic research. This hampers their implementation for the development and testing of medication that targets human microglia.MethodsWe developed thehCSF1Bdesmouse line suitable as new transplantation model available to be crossed to any disease model of interest. ThehCSF1Bdesmodel created by CRISPR gene editing is RAG2 deficient and expresses human CSF1. Additional we crossed this model with two humanizedAppKI mice, theAppHuand theAppSAA. Flow cytometry, immunohistochemistry and bulk sequencing was used to study the response of microglia in the context of Alzheimer’s disease.ResultsOur results demonstrate the successful transplantation of iPSC-derived human microglia into the brains of hCSF1Bdesmice without triggering a NK-driven immune response. Furthermore we confirmed the multipronged response of microglia in the context of Alzheimer’s disease. ThehCSF1Bdesand the crosses with the Alzheimer’s disease knock-in modelAppSAAand the humanizedApp knock-incontrol mice,AppHuare deposited with EMMA and fully accessible to the research community.Conclusionthe hCSF1Bdesmouse is available for both non-profit and for-profit organisations, facilitating the use of the xenotransplantation paradigm for human microglia to study complex human disease.