bluuebunny/crossref_metadata_2025_split huggingface dataset:
18F-FDG PET/CT Imaging of Idiopathic Granulomatous Mastitis
Authors: Muthuswamy Keerthini , Subesinghe Manil 
Published: November 2023

Abstract
A 43-year-old woman, who presented with a suspected left breast abscess, underwent serial ultrasounds, which demonstrated inflammatory changes that were nonresponsive to antibiotics and which spread to the contralateral breast. 18F-FDG PET/CT demonstrated diffuse heterogeneous intense FDG uptake in both breasts with reactive axillary nodes. Breast biopsy confirmed granulomatous inflammation, and overall findings were consistent with idiopathic granulomatous mastitis. In the absence of histological analysis, idiopathic granulomatous mastitis is an important differential diagnosis to consider for bilateral abnormal breast uptake, and early recognition can facilitate prompt commencement of treatment.
The antiviral potential of the antiandrogen enzalutamide and the viral-androgen interplay in seasonal coronaviruses
Authors: Ogunjinmi Oluwadamilola D , Abdullahi Tukur , Somji Riaz-Ali , Bevan Charlotte L , Barclay Wendy S , Temperton Nigel , Brooke Greg N , Giotis Efstathios S 
Published: November 2023

AbstractThe sex disparity in COVID-19 outcomes with males generally faring worse than females has been associated with the androgen-regulated expression of the protease TMPRSS2 and the cell receptor ACE2 in the lung and fueled interest in antiandrogens as potential antivirals. In this study, we explored enzalutamide, an antiandrogen used commonly against prostate cancer, as a potential antiviral against the human coronaviruses which cause seasonal respiratory infections (HCoV-NL63, -229E, and -OC43). Using lentivirus-pseudotyped and authentic HCoV, we report that enzalutamide reduced 229E and NL63 entry and replication in both TMPRSS2- and non-expressing immortalised cells, suggesting a TMPRSS2-independent mechanism. However, no effect was observed against OC43. To decipher this distinction, we performed RNA-sequencing analysis on 229E-and OC43- infected primary human airway cells. Our results show a significant induction of androgen-responsive genes by 229E compared to OC43 at 24 and 72h post-infection. The virus-mediated effect to AR signaling was further confirmed with a consensus androgen response element (ARE)-driven luciferase assay in androgen-depleted MRC-5 cells. Specifically, 229E induced luciferase reporter activity in the presence and absence of the synthetic androgen mibolerone, while OC43 inhibited induction. These findings highlight a complex interplay between viral infections and androgen signaling, offering insights for potential antiviral interventions.
Trapping the exotic weevilCnestus mutilatuswith Isopropanol
Authors: Justice Teresa C. , Justice Michael J. 
Published: November 2023

ABSTRACTThe ambrosia beetle Cnestus mutilatus Blandford, 1894 (Coleoptera: Curculionidae: Scolytinae: Xyleborini) is native to Asia and is currently an exotic species in North America. This study tested whether this species can be trapped with isopropanol as bait. Lindgren multiple-funnel traps were deployed in the piedmont of south-central Virginia, USA. The experimental traps had isopropanol in the collection cups. For comparison, other traps had ethanol or soapy water. Both alcohols were effective for trapping C. mutilatus. More specimens were captured using ethanol. Isopropanol and ethanol may play similar roles in the chemical ecology of ambrosia beetles.
SJPedPanel: A pan-cancer gene panel for childhood malignancies
Authors: Kolekar Pandurang , Balagopal Vidya , Dong Li , Liu Yanling , Foy Scott , Tran Quang , Mulder Heather , Huskey Anna LW , Plyler Emily , Liang Zhikai , Ma Jingqun , Nakitandwe Joy , Gu Jiali , Namwanje Maria , Maciaszek Jamie , Payne-Turner Debbie , Mallampati Saradhi , Wang Lu , Easton John , Klco Jeffery M. , Ma Xiaotu 
Published: November 2023

AbstractBackgroundLarge scale genomics projects have identified driver alterations for most childhood cancers that provide reliable biomarkers for clinical diagnosis and disease monitoring using targeted sequencing. However, there is lack of a comprehensive panel that matches the list of known driver genes. Here we fill this gap by developing SJPedPanel for childhood cancers.ResultsSJPedPanel covers 5,275 coding exons of 357 driver genes, 297 introns frequently involved in rearrangements that generate fusion oncoproteins, commonly amplified/deleted regions (e.g.,MYCNfor neuroblastoma,CDKN2AandPAX5for B-/T-ALL, andSMARCB1for AT/RT), and 7,590 polymorphism sites for interrogating tumors with aneuploidy, such as hyperdiploid and hypodiploid B-ALL or 17q gain neuroblastoma. We used driver alterations reported from an established real-time clinical genomics cohort (n=253) to validate this gene panel. Among the 485 pathogenic variants reported, our panel covered 417 variants (86%). For 90 rearrangements responsible for oncogenic fusions, our panel covered 74 events (82%). We re-sequenced 113 previously characterized clinical specimens at an average depth of 2,500X using SJPedPanel and recovered 354 (91%) of the 389 reported pathogenic variants. We then investigated the power of this panel in detecting mutations from specimens with low tumor purity (as low as 0.1%) using cell line-based dilution experiments and discovered that this gene panel enabled us to detect ∼80% variants with allele fraction of 0.2%, while the detection rate decreases to ∼50% when the allele fraction is 0.1%. We finally demonstrate its utility in disease monitoring on clinical specimens collected from AML patients in morphologic remission.ConclusionsSJPedPanel enables the detection of clinically relevant genetic alterations including rearrangements responsible for subtype-defining fusions for childhood cancers by targeted sequencing of ∼0.15% of human genome. It will enhance the analysis of specimens with low tumor burdens for cancer monitoring and early detection.
Prevalence of Methicillin-ResistantStaphylococcus aureusin Diabetic Patients Visiting the 37-MilitaryHospital in the Accra Metropolis
Authors: Boaitey-Biko Akosua Serwaa , Bukari Ishmael , Ogbe Isaac , Debrah Michael Acheampong 
Published: November 2023

AbstractMisuse of antibiotics contributes to the worldwide rise in antibiotic resistance. However, it is equally important to consider inevitable situations that may contribute to a rise in antibiotic resistance and implement best practices to ensure the minimality of their resulting adverse effects. A case in point is the increasing prevalence of methicillin-resistantStaphylococcus aureus(MRSA), a strain of bacterium that has developed resistance to the antibiotic methicillin and other lactams among long-term diabetic patients as observed in this study. Diabetes is associated with immunosuppression and foot ulcers, which require the constant use of antibiotics as prophylactics, as such, persons with this condition would hold bacterial populations subject to immense selective pressure and are therefore at increased risk for MRSA colonization. Furthermore, these individuals may serve as reservoirs and disseminate these highly drug-resistant strains on return to the general populace. This warranted an investigation into the prevalence of MRSA among diabetic patients at the 37-Military Hospital. A total of 50 samples were taken from the sampled Military Hospital by swabbing the participants’ skin, nose, and wounds aseptically, and 20 samples were acquired from non-diabetics to serve as controls. To culture the samples, blood, and mannitol salt agar were used. Bacteria were isolated and identified using Gram staining and other biochemical testing. The Kirby-Bauer disc diffusion method was used with Muller-Hinton agar to test for antimicrobial susceptibility. According to the study’s findings, antibiotic resistance was much higher among diabetic patients than among non-diabetic patients at the 37-Military Hospital in the Accra Metropolis, Ghana.
Elevated Cardiac Biomarkers in Relatively Healthy U.S. Adults
Authors: Claudel Sophie E. , Schmidt Insa M. , Gopal Deepa M. , Verma Ashish 
Published: November 2023

AbstractBackgroundDespite the importance of early cardiovascular disease (CVD) intervention, little data exists for evaluating cardiovascular risk in adults without traditional CVD risk factors (e.g., diabetes, hypertension).MethodsWe included 4,544 adults from the 1999-2004 National Health and Nutrition Examination Survey without prevalent diabetes, hypertension, chronic kidney disease, or CVD. We used multi-variable adjusted Cox proportional hazards regression modeling to assess the relationship between logarithmically transformed cardiac biomarkers (high sensitivity cardiac troponin T (hs-cTnT), hs-cTnI (Abbott, Ortho, and Siemens assays), and NT-proBNP) and CVD mortality among a nationally representative cohort of relatively healthy adults.ResultsThe mean age was 38.2 years (SD 12.8) and 53.9% were women. 8.7% had elevated levels of hs-cTnT or NT-proBNP above previously established thresholds for subclinical CVD. In multivariable adjusted models, each doubling of hs-cTnT was associated with a 49% increased risk of CVD mortality (Hazard Ratio (HR) 1.49, 95%CI 1.02-2.17,p=0.04). Only two of the hs-cTnI assays (Abbott and Ortho) were significantly associated with CVD mortality (Abbott HR 1.48, 95%CI 1.06-2.07,p=0.02; Ortho HR 1.47, 95%CI 1.23-1.77,p=0.0001). Each doubling of NT-proBNP was associated with a 41% increased risk of CVD mortality (HR 1.38, 95%CI 1.09-1.74,p=0.008).ConclusionYounger patients who maintain relatively good health may still carry occult CVD risk. Efforts to reduce population-wide CVD should consider novel methods for risk stratification, as standard CVD risk factors may overlook subpopulations at risk.Clinical SignificanceAmong relatively healthy adults without significant CVD risk factors, elevated cardiac troponins and NT-proBNP are associated with cardiovascular and all-cause mortality.Subclinical cardiovascular disease poses higher cardiovascular risk among relatively healthy adults than previously appreciated.Efforts to reduce population-wide CVD should consider novel methods for risk stratification and early intervention to mitigate preventable CVD.
Transcription-coupled changes in higher-order genomic structure and transcription hub viscosity prolong enhancer-promoter connectivity
Authors: Ohishi Hiroaki , Shinkai Soya , Owada Hitoshi , Fujii Takeru , Hosoda Kazufumi , Onami Shuichi , Yamamoto Takashi , Ohkawa Yasuyuki , Ochiai Hiroshi 
Published: November 2023

AbstractThe orchestration of our genes heavily relies on a coordinated communication between enhancers and promoters, yet how this dynamic interplay remains elusive while transcription is active. Here, we investigated enhancer-promoter (E-P) interactions and relative to transcriptional bursting in mouse embryonic stem cells using sequential DNA/RNA/immunofluorescence (IF)-FISH analyses and computational simulations. Our data reveal that the active state of specific genes is characterized by higher-order genomic structures and local condensates of transcriptional regulatory factors, leading to an elevation in local viscosity that highly stabilizes the duration of E-P interactions. Our study underscores the pivotal role of viscosity in transcriptional dynamics and paves the way for a more nuanced understanding of gene-specific regulatory mechanisms.
Polygraph: A Software Framework for the Systematic Assessment of Synthetic Regulatory DNA Elements
Authors: Lal Avantika , Gunsalus Laura , Gupta Anay , Biancalani Tommaso , Eraslan Gokcen 
Published: November 2023

AbstractThe design of regulatory elements is pivotal in gene and cell therapy, where DNA sequences are engineered to drive elevated and cell-type specific expression. However, the systematic assessment of synthetic DNA sequences without robust metrics and easy-to-use software remains challenging. Here, we introduce Polygraph, a Python framework that evaluates synthetic DNA elements, based on features like diversity, motif and k-mer composition, similarity to endogenous sequences, and screening with predictive and foundational models. Polygraph is the first instrument for assessing synthetic regulatory sequences, enabling faster progress in therapeutic interventions and improving our understanding of gene regulatory mechanisms.
SOX2 and NR2F1 coordinate the gene expression program of the early postnatal visual thalamus
Authors: Serra Linda , Nordin Anna , Jonasson Mattias , Marenco Carolina , Gullo Francesca , Ottolenghi Sergio , Zambelli Federico , Studer Michèle , Pavesi Giulio , Cantù Claudio , Nicolis Silvia K. , Mercurio Sara 
Published: November 2023

AbstractThe thalamic dorsolateral geniculate nucleus, (dLGN) receives visual input from the retina via the optic nerve, and projects to the cortical visual area, where eye-derived signals are elaborated. The transcription factors SOX2 and NR2F1 are directly involved in the differentiation of dLGN neurons, based on mouse work and patient mutations leading to vision defects. However, whether they regulate each other, or control common targets is still unclear. By RNA-seq analysis of neonatal dLGN from thalamo-specificSox2andNr2f1mouse mutants, we found a striking overlap of deregulated genes. Among them, VGF, a cytokine transported along thalamic-cortical axons is strongly downregulated in both mutants. CUT&RUN analysis of SOX2 binding in dLGN chromatin identified a binding pattern characteristic of the dLGN. Collectively, the SOX2 and NR2F1- coregulated genes, and cognate SOX2 binding sites, contribute as a basis to understand the gene regulatory network driving the differentiation and connectivity of thalamic neurons.
Parotid glands have a dysregulated immune response following radiation therapy
Authors: Gunning Jordan A. , Gilman Kristy E. , Zúñiga Tiffany M. , Simpson Richard J. , Limesand Kirsten H. 
Published: November 2023

AbstractHead and neck cancer treatment often consists of surgical resection of the tumor followed by ionizing radiation (IR), which can damage surrounding tissues and cause adverse side effects. The underlying mechanisms of radiation-induced salivary gland dysfunction are not fully understood, and treatment options are scarce and ineffective. The wound healing process is a necessary response to tissue injury, and broadly consists of inflammatory, proliferative, and redifferentiation phases with immune cells playing key roles in all three phases. In this study, select immune cells were phenotyped and quantified, and certain cytokine and chemokine concentrations were measured in mouse parotid glands after IR. Further, we used a model where glandular function is restored to assess the immune phenotype in a regenerative response. These data suggest that irradiated parotid tissue does not progress through a typical inflammatory response observed in wounds that heal. Specifically, total immune cells (CD45+) decrease at days 2 and 5 following IR, macrophages (F4/80+CD11b+) decrease at day 2 and 5 and increase at day 30, while neutrophils (Ly6G+CD11b+) significantly increase at day 30 following IR. Additionally, radiation treatment reduces CD3-cells at all time points, significantly increases CD3+/CD4+CD8+ double positive cells, and significantly reduces CD3+/CD4-CD8-double negative cells at day 30 after IR. Previous data indicate that post-IR treatment with IGF-1 restores salivary gland function at day 30, and IGF-1 injections attenuate the increase in macrophages, neutrophils, and CD4+CD8+ T cells observed at day 30 following IR. Taken together, these data indicate that parotid salivary tissue exhibits a dysregulated immune response following radiation treatment which may contribute to chronic loss of function phenotype in head and neck cancer survivors.
Thermal biology diversity of bee pollinators: taxonomic, phylogenetic and plant community-level correlates
Authors: Herrera Carlos M. 
Published: November 2023

AbstractCommunity-wide assembly of plant-pollinator systems depends on an intricate combination of biotic and abiotic factors, including heterogeneity among pollinators in thermal biology and responses to abiotic factors. Studies on the thermal biology of pollinators have mostly considered only one or a few species of plants or pollinators at a time, and the possible driving role of the diversity in thermal biology of pollinator asemblages at the plant community level remains largely unexplored. More specifically, it is unknown whether diversity in the thermal biology of bees, a major pollinator group worldwide, contributes to the assembly and maintenance of diverse bee communities, broadens the spectrum of possibilities available to bee-pollinated plants, facilitate interspecific partitioning of ecological gradients across habitats, seasons and time of day, and/or enhance plant pollination success through complementarity effects. The objectives of this study were to assess the diversity in thermal biology of the bee assemblage that pollinates plants in a Mediterranean montane area, evaluate its taxonomic and phylogenetic underpinnings, and elucidate whether there existed seasonal, daily, between-habitat or floral visitation correlates of bee thermal biology which could contribute to partition ecological gradients among plant and bee species. Thermal biology parameters were obtained in the laboratory (K, intrinsic warming constant) and the field (thoracic and ambient temperature at foraging site,TthandTair) on individual bees of a diverse sample (N= 204 bee species) comprising most bee pollinators of the regional plant community. Species-specific thermal biology parameters were combined with quantitative field data on bee pollinators and flower visitation for the regional community of entomophilous plants (N= 292 plant species). Results revealed that the regional bee assemblage harbored considerable diversity in thermal biology features, that such diversity was mostly taxonomically, phylogenetically and body-size structured, and that the broad interspecific heterogeneity in thermal biology represented in the bee community as a whole eventually translated into daily, seasonal, among-habitat and flower visitation patterns at the plant community level. This lends support to the hypothesis that broad diversity in thermal biology of bees can act enhancing opportunities for bee coexistence, spatio-temporal partitioning of floral resources, and plant pollination success.
Psychological impact of COVID-19 on frontline healthcare workers during the early months of the pandemic and responses to reduce the burden, helping to prepare for Disease X: A systematic review
Authors: Ludski Jarryd S. 
Published: November 2023

AbstractObjectiveThe COVID-19 pandemic placed enormous strain on healthcare workers (HCW) and systems. With currently over 766 million cases, a high risk of workplace-acquired infection and a constantly evolving disease trajectory, COVID-19 placed an incredible burden on frontline HCWs. Studies from previous pandemics highlight significant psychological distress in these workers, yet mental health remained a secondary consideration in many hospitals pandemic response. This review explores the psychological impact of COVID-19 on frontline HCWs during the early stages of the pandemic and describes responses implemented by health services to reduce this impact. Additionally, it aims to provide a framework for future evidence-based programs that support the wellbeing of frontline HCWs throughout the ongoing pandemic and into the future, helping to prepare for Disease X.MethodsA systematic review was completed using MEDLINE, CINHAL and Cochrane databases with bibliographic and grey literature searches.Results17 publications were included. Symptoms of psychological distress were reported in up to 70% of frontline HCWs, with as many as 50% suffering depression, 62% reporting anxiety and 45% of those requiring quarantine experiencing insomnia. Mindfulness training, safe rest areas, mental health practitioners and pandemic rostering are responses that have been implemented across health services during the pandemic, but their efficacy in reducing psychological burden has not been fully assessed.ConclusionsThe impact of COVID-19 has been enormous; however, its final toll remains unknown. High rates of psychological distress amongst frontline HCWs means the impact will extend far beyond the virus itself. Health services must implement evidence-based resilience strategies to ensure the safety of their frontline staff now and into the future.
3D electron microscopy of theLeishmania mexicanacell cycle: Patterns of organelle duplication and segregation and their implications for parasite biology
Authors: Hair Molly , Yanase Ryuji , Moreira-Leite Flávia , Wheeler Richard , Sádlová Jovana , Volf Petr , Vaughan Sue , Sunter Jack 
Published: November 2023

AbstractThe unicellular parasiteLeishmaniahas a precisely defined cell architecture that is inherited by each subsequent generation, requiring a highly coordinated pattern of duplication and segregation of organelles and cytoskeletal structures. A framework of nuclear division and morphological changes is known from light microscopy, yet this has limited resolution and the intrinsic organisation of organelles within the cell body and their manner of duplication and inheritance is unknown. Using volume electron microscopy approaches, we have produced three-dimensional reconstructions of different promastigote cell cycle stages to give a spatial and quantitative overview of organelle positioning, division and inheritance. The first morphological indications seen in our dataset that a new cell cycle had begun were the assembly of a new flagellum, the duplication of the contractile vacuole and the increase in volume of the nucleus and kinetoplast. We showed that the progression of the cytokinesis furrow created a specific pattern of membrane indentations and sub-pellicular microtubule organisation indicates that is likely a preferred site of new microtubule insertion. The daughter cells retained these indentations in their cell body for a period post-abscission. By comparing cultured and sand fly derived promastigotes, we found an increase in the number and overall volume of lipid droplets in the promastigotes from the sand fly, reflecting a change in their metabolism to ensure transmissibility to the mammalian host. Our insights into the cell cycle mechanics ofLeishmaniawill be invaluable for future molecular cell biology analyses of these important parasites.