bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is facultative sex is the best of both worlds in the parasitoid waspLysiphlebus fabarum?
Authors: Boulton Rebecca A 
Published: February 2024

AbstractThe prevalence of sexual reproduction has long puzzled evolutionary biologists. This is because asexual reproduction is a far more efficient way to transmit copies of one’s own genome to the next generation, and, all-else-being-equal, should predominate over sex. Asexual reproduction is not without its disadvantages though, the lack of genetic recombination can render parthenogenetic lineages vulnerable to extinction under environmental change, or compromise fitness due to the buildup of deleterious recessive mutations. Facultative sex, where individuals retain the ability to reproduce sexually and asexually, has been touted as ‘the best of both worlds’, providing the long-term genetic benefits of sex without the short-term costs. In this study I tested whether sex is facultative in the aphid parasitoidLysiphlebus fabarum, and if so whether facultative sex is ‘the best of both worlds’. I found that females from asexual populations mate with males produced by females from an obligately sexual population, and produced offspring with paternal genetic contributions, confirming facultative sex in this species. I then assayed the fitness of these facultatively sexual wasps and found, contrary to predictions that they actually had significantly lower fitness than asexual or obligately sexual females, as their daughters were up to 40% more likely to fail to reproduce entirely. In contrast, obligately sexual females were not at a disadvantage compared to asexual females in this species; they had increased fecundity compared to asexual females which compensated for the costs of sex. InL. fabarumit seems that all is not equal; the fecundity advantage that obligate sex provides, along with the costs of occasional facultative sex by asexuals may balance the scales and allow stable coexistence of the different reproductive modes in nature.
Sample preparation methods for volume electron microscopy in molluscBerghia stephanieae
Authors: Drescher Brandon , Sant Harshada H. , Schalek Richard L. , Lichtman Jeff W. , Katz Paul S. 
Published: February 2024

AbstractCreating a high-resolution brain atlas in diverse species offers crucial insights into general principles underlying brain function and development. A volume electron microscopy approach to generate such neural maps has been gaining importance due to advances in imaging, data storage capabilities, and data analysis protocols. Sample preparation remains challenging and is a crucial step to accelerate the imaging and data processing pipeline. Here, we introduce several replicable methods for processing the brains of the gastropod mollusc,Berghia stephanieaefor volume electron microscopy. Although high-pressure freezing is the most reliable method, the depth of cryopreservation is a severe limitation for large tissue samples. We introduce a BROPA-based method using pyrogallol and methods to rapidly process samples that can save hours at the bench. This is the first report on sample preparation and imaging pipeline for volume electron microscopy in a gastropod mollusc, opening up the potential for connectomic analysis and comparisons with other phyla.
Food-associated calls in disc-winged bats
Authors: Chaverri Gloriana , Page Rachel A. 
Published: February 2024

ABSTRACTAnimals that engage in social foraging can produce food-associated calls that elicit two main responses in receivers: the recruitment of other individuals to a foraging site, and an increase in feeding-related behaviors in conspecifics. Spix’s disc-winged bat,Thyroptera tricolor, is a highly gregarious species that lives in stable social groups and relies on group call-and-response vocalizations to find ephemeral roosting sites. Because this bat also is known to feed on resources that are abundant but ephemeral – for example insect swarms – we hypothesized that it likewise emits vocalizations that serve to recruit conspecifics to a foraging site and elicit food consumption. We found that indeed, feeding bats emitted distinct vocalizations exclusively while consuming an abundant prey item, a call type that has not been previously described in the acoustic repertoire of any bat to date. We also observed that these “food calls” prompted responses typically associated with food-calling: they increased both feeding-related behaviors and social recruitment. Specifically, we observed that the onset of the consumption of novel prey items was strongly associated with the emission of food calls but not with other types of sounds. In addition, individuals approached a speaker broadcasting food calls, especially when food calls had not been broadcast before, while other types of sounds did not consistently prompt inspection. Taken together, these results suggest thatT. tricolorcoordinates foraging behavior through the emission of food-associated communication calls.SUMMARY STATEMENTThis study provides evidence of food-associated calling in Spix’s disc-winged bats (Thyroptera tricolor), revealing its association with feeding contexts and its potential role in prompting social recruitment and feeding-related behaviors.
Machine Learning for COVID-19 Patient Management: Predictive Analytics and Decision Support
Authors: El Hadi Christopher , Saliba Rindala , Maalouly Georges , Riachy Moussa , Sleilaty Ghassan 
Published: February 2024

AbstractBackgroundThe global impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has profoundly affected economies and healthcare systems around the world, including Lebanon. While numerous meta-analyses have explored the systemic manifestations of COVID-19, few have linked them to patient history. Our study aims to fill this gap by using cluster analysis to identify distinct clinical patterns among patients, which could aid prognosis and guide tailored treatments.MethodsWe conducted a retrospective cohort study at Beirut’s largest teaching hospital on 556 patients with SARS-CoV-2. We performed cluster analyses using K-prototypes, KAMILA and LCM algorithms based on 26 variables, including laboratory results, demographics and imaging findings. Silhouette scores, concordance index and signature variables helped determine the optimal number of clusters. Subsequent comparisons and regression analyses assessed survival rates and treatment efficacy according to clusters.ResultsOur analysis revealed three distinct clusters: “resilient recoverees” with varying disease severity and low mortality rates, “vulnerable veterans” with severe to critical disease and high mortality rates, and “paradoxical patients” with a late presentation but eventual recovery.ConclusionsThese clusters offer insights for prognosis and treatment selection. Future studies should include vaccination data and various COVID-19 strains for a comprehensive understanding of the disease’s dynamics.
CXCL14 suppresses the progression of colon cancer by regulating tumor epithelial-mesenchymal transition and tumor microenvironment
Authors: Zhang Yinjie , Jin Yue , Wang Siyi , Niu Yuchen , Ma Buyong , Li Jingjing 
Published: February 2024

AbstractBackgroundThe widespread silencing of CXCL14 in advanced colon cancer underscores the association between CXCL14 and the development of colon cancer. Some studies have demonstratedin vitrothat CXCL14 can inhibit the growth and metastasis of colon cancer cell, and it has also been studied in other disease models for its regulation of immune cell infiltration.AimsThe aim of this study is to clarify the transcriptional regulation of colon cancer cells mediated by CXCL14 and its regulatory role in the tumor microenvironment.MethodWe analyzed the expression characteristics of CXCL14 in clinical databases of colon cancer. CXCL14 overexpression cell lines were established to study its functions on gene transcriptional regulation and cell physiology. Through subcutaneous tumor models, we investigated the effects of CXCL14 on the immune microenvironment.ResultFirstly, the clinical data revealed that CXCL14 is silenced during cancer progression, and negatively associated with EMT and cell proliferation markers, and positively associated with the abundance of T cells and NK cells in colon tissue. Secondly, RNA-seq reveals that CXCL14 overexpression is negatively associated with cell EMT, and inhibits tumor migration and invasion. Western blot (WB) assay confirmed that CXCL14 inhibits the Erk/MAPK and Akt signaling pathways. Finally, subcutaneous tumor models demonstrate that CXCL14 overexpression inhibited tumor growth, increased the infiltration of tumor-associated T cells and DC cells, activated the anti-tumor immune response, antigen processing and presentation, and T helper differentiation in the tumor microenvironment.ConclusionCXCL14 becomes silenced in late-stage colon cancer samples.In vivoandin vitroexperiments demonstrate that CXCL14 inhibits tumor EMT, proliferation, and metastasis through autocrine signaling. It also enhances the infiltration of T and NK lymphocytes through paracrine signaling and inhibits the proliferation of subcutaneous tumors.
Antiandrogen Flutamide-Induced Restoration of miR-449 Expression Mitigates Functional Biomarkers Associated with Ovarian Cancer Risk
Authors: Wang Xia , Woo Ho-Hyung , Wei Michele , Gibson Steven , Miranda Mitzi , Rush Demaretta , Cragun Janiel , Zheng Wenxin , Yao Guang , Chambers Setsuko K 
Published: February 2024

AbstractBackgroundThe involvement of the androgen and androgen receptor (AR) pathway in the development of epithelial ovarian cancer is increasingly recognized. However, the specific mechanisms by which anti-androgen agents, such as flutamide, may prevent ovarian cancer and their efficacy remain unknown. We examined the effects of flutamide on the miRNA expression profile found in women at high risk (HR) for ovarian cancer.MethodsOvarian and tubal tissues, free from ovarian, tubal, peritoneal cancers, and serous tubal intraepithelial carcinoma (STIC), were collected from untreated and flutamide-treated HR women. Low-risk (LR) women served as controls. Transcriptomic miRNA sequencing was performed on these 3 sample cohorts. The miRNAs that showed the most notable differential expression were subjected to functional assays in primary ovarian epithelial cells and ovarian cancer cells.ResultsFlutamide treatment demonstrated a normalization effect on diminished miRNA levels in HR tissues compared to LR tissues. Particularly, the miR-449 family was significantly upregulated in HR ovarian tissues following flutamide treatment, reaching levels comparable to those in LR tissues. MiR-449a and miR-449b-5p, members of the miR-449 family, were computationally predicted to target the mRNAs of AR and colony-stimulating factor 1 receptor (CSF1R, also known asc-fms), both of which are known contributors to ovarian cancer progression, with emerging evidence also supporting their roles in ovarian cancer initiation. These findings were experimentally validated in primary ovarian epithelial cells and ovarian cancer cell lines (SKOV3 and Hey): flutamide treatment resulted in elevated levels of miR-449a and miR-449b-5p, and introducing mimics of these miRNAs reduced the mRNA and protein levels of CSF1R and AR. Furthermore, introducing miR-449a and miR-449b-5p mimics showed inhibitory effects on the migration and proliferation of ovarian cancer cells.ConclusionFlutamide treatment restored the reduced expression of miR-449a and miR-449b-5p in HR tissues, thereby decreasing the expression of CSF1R and AR, functional biomarkers associated with an increased risk of ovarian cancer. In addition to the known direct binding of flutamide to the AR, we found that flutamide also suppresses AR expression via miR-449a and miR-449b-5p upregulation, revealing a novel dual-inhibitory mechanism on the AR pathway. Taken together, our study highlights mechanisms supporting the chemopreventive potential of flutamide in ovarian cancer, particularly in HR patients with reduced miR-449 expression.
A pilot study to investigate the safety and feasibility of antiretroviral therapy for Alzheimer’s disease (ART-AD)
Authors: Sullivan A. Campbell , Zuniga Gabrielle , Ramirez Paulino , Fernandez Roman , Wang Chen-Pin , Li Ji , Davila Lisa , Pelton Kristine , Gomez Sandra , Sohn Claira , Gonzalez Elias , Lopez-Cruzan Marisa , Gonzalez David A. , Parker Alicia , Zilli Eduardo , de Erausquin Gabriel A. , Seshadri Sudha , Espinoza Sara , Musi Nicolas , Frost Bess 
Published: February 2024

ABSTRACTRetrotransposons are viral-like DNA sequences that constitute approximately 41% of the human genome. Studies inDrosophila,mice, cultured cells, and human brain indicate that retrotransposons are activated in settings of tauopathy, including Alzheimer’s disease, and causally drive neurodegeneration. The anti-retroviral medication 3TC (lamivudine), a nucleoside analog reverse transcriptase inhibitor, limits retrotransposon activation and suppresses neurodegeneration in tau transgenicDrosophila,two mouse models of tauopathy, and in brain assembloids derived from patients with sporadic Alzheimer’s disease. We performed a 24-week phase 2a open-label clinical trial of 300 mg daily oral 3TC (NCT04552795) in 12 participants aged 52-83 years with a diagnosis of mild cognitive impairment due to suspected Alzheimer’s disease. Primary outcomes included feasibility, blood brain barrier penetration, effects of 3TC on reverse transcriptase activity in the periphery, and safety. Secondary outcomes included changes in cognition and fluid-based biomarkers of neurodegeneration and neuroinflammation. All participants completed the six-month trial; one event of gastrointestinal bleeding due to a peptic ulcer was reported. 3TC was detected in blood and cerebrospinal fluid (CSF) of all participants, suggestive of adherence to study drug and effective brain penetration. Cognitive measures remained stable throughout the study. Glial fibrillary acidic protein (GFAP) (P=0.03) and Flt1 (P=0.05) were significantly reduced in CSF over the treatment period; Aβ42/40 (P=0.009) and IL-15 (P=0.006) were significantly elevated in plasma. While this is an open label study of small sample size, the significant decrease of some neurodegeneration- and neuroinflammation-related biomarkers in CSF, significantly elevated levels of plasma Aβ42/40, and a trending decrease of CSF NfL after six months of 3TC exposure suggest a beneficial effect on subjects with mild cognitive impairment due to suspected Alzheimer’s disease. Feasibility, safety, tolerability, and central nervous system (CNS) penetration assessments further support clinical evaluation of 3TC in a larger placebo-controlled, multi-dose clinical trial.
Curating genomic disease-gene relationships with Gene2Phenotype
Authors: Yates T Michael , Ansari Morad , Thompson Louise , Hunt Sarah E , Uhalte Elena Cibrian , Hobson Rachel J , Marsh Joseph A , Wright Caroline F , Firth Helen V 
Published: February 2024

AbstractGenetically determined disorders are highly heterogenous in clinical presentation and underlying molecular mechanism. The evidence underpinning these conditions in the peer-reviewed literature is variable and requires robust critical evaluation for diagnostic use. Here, we present a structured curation process for the Gene2Phenotype (G2P) project. This draws on multiple lines of clinical, bioinformatic and functional evidence. The process utilises and extends existing terminologies, allows for precise definition of the molecular basis of disease, and confidence levels to be attributed to a given gene-disease assertion. In-depth disease curation using this process will prove useful in applications including in diagnostics, research and the development of targeted therapeutics.
Multidimensional vulnerability and financial risk protection in health in contexts of protracted conflict: Evidence from the Occupied Palestinian Territory
Authors: Hatamyar Julia , Shayeb Sally , Hussain Akseer , Hammoudeh Weeam , Mazumdar Sumit , Moreno-Serra Rodrigo 
Published: February 2024

ABSTRACTThis paper proposes a multidimensional vulnerability index for a setting of protracted conflict, which is applied to study the relationship between financial vulnerability and catastrophic healthcare expenditure (CHE) incidence in the Occupied Palestinian Territory in 2018. We find that our index better captures the extent of financial risk protection (FRP) compared to conventional measures of financial welfare. Results indicate that the most vulnerable groups experience a significantly higher likelihood of incurring CHE, and this likelihood is increased for those living in the West Bank compared to the Gaza Strip. We also find a lack of protection from existing insurance types against the risk of CHE. Our analysis provides valuable insights about key aspects, such as health financing and insurance bottlenecks, that will deserve careful policy attention in efforts to rebuild the Palestinian health system, following the Israel-Hamas war.KEY MESSAGESWhat is already known on this topic•In settings of protracted conflict, conventional welfare measures, such as household consumption expenditure, may not adequately capture the multifaceted nature of financial risk protection (FRP) in health.•There is a need for more comprehensive approaches to assess household vulnerability and FRP in such settings.What this study adds•We propose a novel multidimensional index of household vulnerability for populations in protracted conflict areas, applied to 2018 data from the Occupied Palestinian Territory.•Assessing FRP through this multidimensional lens reveals different patterns of exposure to financially catastrophic health expenditure (CHE) across sub-populations, which are not evident through traditional measures.•We find a positive association between CHE risk and greater vulnerability in both the West Bank and the Gaza Strip, with the most vulnerable groups likely to incur CHE regardless of insurance status.How this study might affect research, practice, or policy•Our vulnerability index predicts the risk of CHE across population sub-groups in a protracted conflict setting more effectively than traditional metrics, thereby offering better insights for health policy.•The analysis highlights particular policy aspects, such as health insurance arrangements, that will require addressing to “build back better” the Palestinian heath system following escalation of violent conflicts, damages caused to critical health service and social infrastructure, and different constraints on available policy options.
Incidence, prevalence, and survival of lung cancer in the United Kingdom from 2000-2021: a population-based cohort study
Authors: Corby George , Barclay Nicola L , Tan Eng Hooi , Burn Edward , Delmestri Antonella , Duarte-Salles Talita , Golozar Asieh , Man Wai Yi , Tietzova Ilona ,   OPTIMA Consortium, Prieto-Alhambra Daniel , Newby Danielle 
Published: February 2024

ABSTRACTBackgroundLung cancer is the leading cause of cancer-associated mortality worldwide. In the UK, there has been a major reduction in smoking, the leading risk factor for lung cancer, as well as the introduction of the new screening in 2023. Therefore, an up-to-date assessment of the trends of lung cancer is required in the UK.MethodsWe performed a population-based cohort study using the UK primary care Clinical Practice Research Datalink (CPRD) GOLD database, compared with CPRD Aurum. Participants aged 18+ years, with one-year of prior data availability, were included. We estimated lung cancer incidence rates (IR), period prevalence (PP), and survival at one-, five– and ten years after diagnosis using the Kaplan-Meier method.ResultsOverall, 11,388,117 participants, with 45,563 lung cancer cases were studied. The incidence rate of lung cancer was 52.0 (95% CI 51.5 to 52.5) per 100,000 person-years, with incidence increasing from 2000 to 2021, especially in females aged over 50, and males aged over 80, with the highest incidence rate in people aged 80-89. Period prevalence in 2021 was 0.18%, with the largest rise seen in participants aged over 60. Median survival post-diagnosis increased from 6.6 months in those diagnosed between 2000-2004 to 10 months between 2015-2019. Both short and long-term survival was higher in younger cohorts, with 82.7% one-year survival in those aged 18-29, versus 24.2% in the age 90+ cohort. Throughout the study period, survival was longer in females, with a larger increase in survival over time than in males.ConclusionThe incidence and prevalence of lung cancer diagnoses in the UK have increased, especially in female and older populations, with a small increase in median survival. With the introduction of the UK lung cancer screening programme, this study will enable future comparisons of overall disease burden, so the overall impact may be seen.
AI Derived Therapeutic Development for the Treatment of Opioid Use Disorder
Authors: Lallai Valeria , Martin A.C. , Fowler J.P. , Bautista Malia , Mogul Allison S. , Cheepluesak Jinjutha E. , Mirzaei Saman , Jenkins Ian , Lakey Jonathan R.T. , Tinder Robert , Fowler Christie D. 
Published: February 2024

AbstractThe opioid epidemic has led to a devastating loss of life nationwide. Of those dependent on opioids, many individuals desire to quit or reduce use, but their efforts are often unsuccessful given the powerful reinforcing properties associated with opioid drugs, especially fentanyl given its high potency and speed of onset. Here, we developed a novel theraputic based on a newly developed artificial intelligence (AI)-based platform, which was rationally designed to identify markers of dysregulation from human drug user postmortem brain tissue. The GATC-021 compound was synthesized and validated within vitroscreening for target specificity. Thereafter, GATC-021 was examined for its effectiveness in modulating opioid dependence with an animal model of addiction. We found that GATC-021 substantially reduced fentanyl intake in both male and female rats, as assessed with intravenous self-administration. However, given drug soluability challenges, additional studies are needed to better develop drug formulations to permit translation into clinical populations more effectively. Taken together, these findings validate our AI-based platform for novel therapeutic development with a polypharmacy approach and further support the effectiveness of such target modulation as a promising therapeutic approach for those suffering from opioid use disorder.