bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative analyses of genes about venous thromboembolism: An umbrella review of systematic reviews and meta-analyses
Authors: Lee Sangyeob , Lee Chang Han , Seo Min Seok , Yoo Jun-Il 
Published: October 2022

Background:
In recent years, many studies have found possible links between gene polymorphisms and venous thromboembolism (VTE). By identifying genetic risk factors before facing environmental risk factors such as surgical interventions and COVID-19 vaccination, we could rapidly respond to the risk of VTE. The aim of this study was to perform an umbrella review of genetic variants related to VTE. Integrative gene analysis of VTE was performed to identify critical genetic variations.

Methods:
This study conducted an umbrella review of systematic reviews and meta-analyses. All included studies were selected from the PubMed/MEDLINE database. To select eligible studies, the following variables were extracted: first author name; effect size of each study genetic variant; year of publication; the number of studies included in each article; ethnicity, sample size, P values, and heterogeneity estimates. To assess cumulative evidence in genetic epidemiology about effects of gene polymorphisms on VTE, Human Genome Epidemiology Network’s Venice criteria were used. Methodological quality assessment was conducted with JBI Critical Appraisal Checklist for Systematic Reviews and Research Syntheses.

Results:
Genes provided in the present study with genetic variants associated with VTE were FVL (G1691A), Prothrombin (G20210A), MTHFR (C677T, A1298C), PAI-1 (4G/5G), factor VII activating protease (1601G > A), and endothelial protein C receptor (g.6936A_G, c.4600A_G). Among them, variants in FVL, Prothrombin, MTHFR, and PAI-1 showed high significance. Particularly, variants in Prothrombin (G20210A), MTHFR (C677T), and PAI-1 (4G/5G) had more than 2 types of model significance.

Conclusion:
The present study performed a systematic review of genetic variants associated with VTE. Our results could lead to a more comprehensive understanding of VTE etiology. These results could give a strategy of prediagnosis about evaluating individual risks of VTE who might be exposed to environmental risk factors.
Anti-glomerular basement membrane disease with rupture of the newly formed bilateral corpus luteum cysts: A case report
Authors: Luo Pei-Yi , Chen Xia , Cheng Lu , Ma Liang , Gou Shen-Ju 
Published: October 2022

Rationale:Anti-glomerular basement membrane (anti-GBM) disease during gestation is sparse and even rarer when combined with bilateral large corpus luteum cysts. In this case, we report a case of anti-GBM disease in the early stage of pregnancy with ruptured newly formed bilateral large corpus luteum cysts.Patient concerns:A 24-year-old female was initially diagnosed with anti-GBM disease. During treatment, abdominal distention and vaginal bleeding successively staged. The results of the first gynecological ultrasound and abdominal CT were negative.Diagnosis:Based on the dynamic imaging change of the ovaries, the elevated human chorionic gonadotropin (hCG) and sex hormones, and the pathological findings, a diagnosis of anti-GBM disease with rupture of the newly formed bilateral corpus luteum cysts during early pregnancy was considered.Interventions:The patient was treated with corticosteroids, plasma-exchange along with intensive hemodialysis. Then, to confirm the diagnosis, laparoscopic debulking of bilateral ovarian cysts and curettage were performed.Outcomes:After treatment, the anti-GBM antibody titer declined and the condition of the patient was still stable 2 months following discharge.Lessons:As clinicians, we should be aware that even if the first imaging tests are negative, the relevant indicators should be reviewed dynamically based on the condition of the patients. Additionally, this case raised the question of whether anti-GBM disease was associated with pregnancy and giant corpus luteum cysts, which needs further investigations.
Genomic epidemiology of SARS-CoV-2 within households in coastal Kenya: a case ascertained cohort study
Authors: Agoti Charles N. , Gallagher Katherine E. , Nyiro Joyce , Lambisia Arnold W. , Murunga Nickson , Mohammed Khadija Said , Ndwiga Leonard , Morobe John M. , Mburu Maureen W. , Ongera Edidah M. , Makori Timothy O. , Phan My V.T. , Cotten Matthew , Ochola-Oyier Lynette Isabella , Dellicour Simon , Bejon Philip , Githinji George , Nokes D. James 
Published: October 2022

AbstractAnalysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences from household infections may provide useful epidemiological information for future control measures. Between December 2020 and July 2022, we conducted a case-ascertained household cohort study whereby households were recruited if a member was either a SARS-CoV-2 case or contact of a confirmed case. A total of 765 members of 214 households were prospectively monitored for SARS-CoV-2 infection and transmission. Follow-up visits collected a nasopharyngeal/oropharyngeal (NP/OP) swab on days 1, 4 and 7 for RT-PCR diagnosis. If any of these were positive, further swabs were collected on days 10, 14, 21 and 28. Of 2,780 NP/OP swabs collected, 540 (19.4%) tested SARS-CoV-2 positive and viral genome sequences were recovered for 288 (53.3%) positive samples. The genomes belonged to 23 different Pango lineages. Phylogenetic analysis including contemporaneous Coastal Kenya data estimated 233 putative transmission events involving 162 members of the 89 households, of which 60 (25%) were intra-household transmission events while 173 (75%) were infections that likely occurred outside the households. In 34 (38%) households, multiple virus introductions were observed (up to six) within the one-month follow-up period, in contrast to high-income settings, where a single introduction seemed to occur during epidemic waves. Our findings suggests that in this setting control of respiratory virus spread by household member isolation will be ineffective.
Increased lipid peroxidation and lowered antioxidant defenses predict methamphetamine induced psychosis
Authors: Al-Hakeim Hussein Kadhem , Altufaili Mazin Fadhil , Almulla Abbas F. , Moustafa Shatha Rouf , Maes Michael 
Published: October 2022

AbstractBackgroundA significant percentage of methamphetamine (MA) dependent patients develop psychosis. However, the associations between oxidative pathways and MA-induced psychosis (MIP) are not well delineated.ObjectiveThe aim of this study is to delineate whether acute MA intoxication in MA dependent patients is accompanied by increased nitro-oxidative stress and whether the latter is associated with MIP.MethodWe recruited 30 healthy males and 60 acutely intoxicated MA males with MA dependence and assessed severity of MA use and dependence and psychotic symptoms during intoxication and measured serum oxidative toxicity (OSTOX) biomarkers including oxidized high (oxHDL) and low (oxLDL)-density lipoprotein, myeloperoxidase (MPO), malondialdehyde (MDA), and nitric oxide (NO), and antioxidant defenses (ANTIOX) including HDL-cholesterol, zinc, glutathione peroxidase (GPx), total antioxidant capacity (TAC), and catalase-1.ResultsA large part (50%, n=30) of patients with MA dependence could be allocated to a cluster characterized by high psychosis ratings including delusions, suspiciousness, conceptual disorganization and difficulties abstract thinking and an increased OSTOX/ANTIOX ratio. Partial Least Squares analysis showed that 29.9% of the variance in MIP severity (a first factor extracted from psychosis, hostility, excitation, mannerism, and formal thought disorder scores) was explained by HDL, TAC and zinc (all inversely) and oxLDL (positively). MA dependence and dosing explained together 44.7% of the variance in the OSTOX/ANTIOX ratio.ConclusionMA dependence and intoxication are associated with increased oxidative stress and lowered antioxidant defenses, which both increase risk of MIP during acute intoxication. MA dependence is accompanied by increased atherogenicity due to lowered HDL and increased oxLDL and oxHDL.
Activation of an injury-associated transient progenitor state in the epicardium is required for zebrafish heart regeneration
Authors: Xia Yu , Duca Sierra , Perder Björn , Dündar Friederike , Zumbo Paul , Qiu Miaoyan , Yao Jun , Cao Yingxi , Harrison Michael R. , Zangi Lior , Betel Doron , Cao Jingli 
Published: October 2022

ABSTRACTThe epicardium, a mesothelial cell tissue that encompasses vertebrate hearts, supports heart regeneration after injury through paracrine effects and as a source of multipotent progenitors. However, the progenitor state in the adult epicardium has yet to be defined. Through single-cell RNA-sequencing of isolated epicardial cells from uninjured and regenerating adult zebrafish hearts, we defined the epithelial and mesenchymal subsets of the epicardium. We further identified a transiently activated epicardial progenitor cell (aEPC) subpopulation marked byptx3aandcol12a1bexpression. Upon cardiac injury, aEPCs emerge from the epithelial epicardium, migrate to enclose the wound, undergo epithelial-mesenchymal transition (EMT), and differentiate into mural cells andpdgfra+hapln1a+mesenchymal epicardial cells. These EMT and differentiation processes are regulated by the Tgfβ pathway. Conditional ablation of aEPCs blocked heart regeneration through reduced Nrg1 expression and mesenchymal cell number. Our findings identify a transient progenitor population of the adult epicardium that is indispensable for heart regeneration and highlight it as a potential target for enhancing cardiac repair.
Influenza-associated hospitalisation and mortality rates among global Indigenous populations; a systematic review and meta-analysis
Authors: Betts Juliana M. , Weinman Aaron L. , Oliver Jane , Braddick Maxwell , Huang Siyu , Nguyen Matthew , Miller Adrian , Tong Steven Y.C. , Gibney Katherine B. 
Published: October 2022

AbstractBackgroundMore than 50 million influenza infections and over 100,000 deaths from influenza occur annually. While Indigenous populations experience an inequitable influenza burden, the magnitude of this inequity has not previously been estimated on a global scale. This study compared rates of influenza-associated hospitalisation and mortality between Indigenous and non-Indigenous populations globally.MethodsA systematic review and meta-analysis was conducted including literature published prior to 13 July 2021. Eligible articles either reported a rate ratio (RR) comparing laboratory-confirmed influenza-associated hospitalisation and/or mortality between an Indigenous population and a corresponding benchmark population, or reported sufficient information for this to be calculated using publicly available data. Findings were reported by country/region and pooled by country and period (pandemic/seasonal) when multiple studies were available using a random-effects model. The I2statistic assessed variability between studies.ResultsThirty-six studies (moderate/high quality) were included; all from high or high-middle income countries. The pooled influenza-associated hospitalisation RR (HRR) for indigenous compared to benchmark populations was 5·7 (95% CI: 2·7–12·0) for Canada, 5·2 (2.9–9.3) for New Zealand, and 5.2 (4.2–6.4) for Australia. Of the Australian studies, the pooled HRR for seasonal influenza was 3.1 (2·7–3·5) and for pandemic influenza was 6·2 (5·1–7·5). Heterogeneity was slightly higher among studies of pandemic influenza than seasonal influenza. The pooled mortality RR was 4.1 (3·0–5.7) in Australia and 3·3 (2.7–4.1) in the United States.ConclusionsEthnic inequities in severe influenza persist and must be addressed by reducing disparities in the underlying determinants of health. Influenza surveillance systems worldwide should include Indigenous status to determine the extent of the disease burden among Indigenous populations. Ethnic inequities in pandemic influenza illustrate the need to prioritise Indigenous populations in pandemic response plans.
Comparison of Simulated Outcomes Between Stool- and Blood-Based Colorectal Cancer Screening Tests
Authors: Fendrick A. Mark , Vahdat Vahab , Chen Jing Voon , Lieberman David , Karlitz Jordan J. , Limburg Paul J. , Ozbay A. Burak , Kisiel John B. 
Published: October 2022

AbstractObjectivesThe Centers for Medicare & Medicaid Services (CMS) recommends covering blood-based tests meeting proposed minimum performance thresholds for colorectal cancer (CRC) screening. Outcomes were compared between currently available stool-based screening tests and a hypothetical blood-based test meeting CMS minimum thresholds.MethodsUsing the CRC-AIM model, outcomes were simulated for average-risk individuals screened between ages 45-75 years with triennial multi-target stool DNA (mt-sDNA), annual fecal immunochemical test (FIT), and annual fecal occult blood test (FOBT). Per CMS guidance, blood-based CRC screening was modeled triennially, with 74% CRC sensitivity and 90% specificity. Although not specified by CMS, adenoma sensitivity was set between 10-20%. Published adenoma and CRC sensitivity and specificity were used for stool-based tests. Adherence was set at (a) 100%, (b) 30-70%, in 10% increments, and (c) real-world rates for stool-based tests (mt-sDNA=65.6%; FIT=42.6%; FOBT=34.4%).ResultsAssuming perfect adherence, a blood-based test produced ≥19 lower LYG than stool-based strategies. At the best-case scenario for blood-based tests (100% adherence and 20% adenoma sensitivity), mt-sDNA at real-world adherence achieved more LYG (287.2 vs 297.1, respectively) with 14% fewer colonoscopies. At 100% blood-based test adherence and real-world mt-sDNA and FIT adherence, the blood-based test would require advanced adenoma sensitivity of 30% to reach the LYG of mt-sDNA (297.1) and approximately 15% sensitivity to reach the LYG of FIT (258.9).ConclusionsThis model suggests that blood-based tests with CMS minimally-acceptable CRC sensitivity and low advanced adenoma sensitivity will frequently yield inferior outcomes to stool-based testing across a wide range of adherence assumptions.
A cold-blooded vertebrate shows integration of antimicrobial defenses and tissue repair through fever
Authors: Haddad Farah , Soliman Amro M. , Wong Michael E. , Albers Emilie H. , Semple Shawna L. , Torrealba Débora , Heimroth Ryan D. , Nashiry Asif , Tierney Keith B. , Barreda Daniel R. 
Published: October 2022

ABSTRACTMultiple lines of evidence support the value of moderate fever to host survival, but the mechanisms involved remain unclear. This is difficult to establish in warm-blooded animal models, given the strict programs controlling core body temperature and the physiological stress that results from their disruption. Thus, we took advantage of a cold-blooded teleost fish that offered natural kinetics for the induction and regulation of fever and a broad range of tolerated temperatures. A custom swim chamber, coupled to high-fidelity quantitative positional tracking, showed remarkable consistency in fish behaviours and defined the febrile window. Animals exerting fever engaged pyrogenic cytokine gene programs in the CNS, increased efficiency of leukocyte recruitment into the immune challenge site, and markedly improved pathogen clearancein vivo, even when an infecting bacterium grew better at higher temperatures. Contrary to earlier speculations for global upregulation of immunity, we identified selectivity in the protective immune mechanisms activated through fever. Fever then inhibited inflammation and markedly improved wound repair. Artificial mechanical hyperthermia, often used as a model of fever, recapitulated some but not all benefits achieved through natural host-driven dynamic thermoregulation. Together, our results define fever as an integrative host response that regulates induction and resolution of acute inflammation, and demonstrate that this integrative strategy emerged prior to endothermy during evolution.
The nucleolar protein GNL3 prevents resection of stalled replication forks
Authors: Lebdy Rana , Canut Marine , Patouillard Julie , Cadoret Jean-Charles , Letessier Anne , Ammar Josiane , Basbous Jihane , Urbach Serge , Miotto Benoit , Constantinou Angelos , Abou Merhi Raghida , Ribeyre Cyril 
Published: October 2022

SummaryDNA replication requires specific proteins that protect replication forks and so prevent the formation of DNA lesions that may damage the genome. Identification of new proteins involved in these processes is essential to understand how cancer cells tolerate DNA lesions. Here we show that human GNL3/nucleostemin, a GTP-binding protein localized mostly in the nucleolus and highly expressed in cancer cells, prevents nuclease-dependent resection of nascent DNA in response to exogenous replication stress. We demonstrate that inhibition of origin firing decreases this resection, indicating that the increased replication origin firing seen upon GNL3 depletion mainly accounts for the observed DNA resection. We show that GNL3 and DNA replication initiation factor ORC2 interact in the nucleolus and that the concentration of GNL3 in the nucleolus is required to limit DNA resection in response to replicative stress. We propose that the accurate control of origin firing by GNL3, possibly through the regulation of ORC2 sub-nuclear localization, is critical to prevent nascent DNA resection in response to replication stress.
Biogeographic Distribution of Five Antarctic Cyanobacteria Using Large-Scale k-mer Searching with sourmash branchwater
Authors: Lumian Jessica , Sumner Dawn , Grettenberger Christen , Jungblut Anne D. , Irber Luiz , Pierce-Ward N. Tessa , Brown C. Titus 
Published: October 2022

ABSTRACTCyanobacteria form diverse communities and are important primary producers in Antarctic freshwater environments, but their geographic distribution patterns in Antarctica and globally are still unresolved. There are however few genomes of cultured cyanobacteria from Antarctica available and therefore metagenome-assembled genomes (MAGs) from Antarctic cyanobacteria microbial mats provide an opportunity to explore distribution of uncultured taxa. These MAGs also allow comparison with metagenomes of cyanobacteria enriched communities from a range of habitats, geographic locations, and climates. However, most MAGs do not contain 16S rRNA gene sequences, making a 16S rRNA gene-based biogeography comparison difficult. An alternative technique is to use large-scale k-mer searching to find genomes of interest in public metagenomes.This paper presents the results of k-mer based searches for 5 Antarctic cyanobacteria MAGs from Lakes Fryxell and Lake Vanda, assigned the namesPhormidium pseudopriestleyi, aMicrocoleus, aLeptolyngbya, aPseudanabaena, and aNeosynechococcus(Lumian et al., 2021, Lumian et al., 2022, in prep.) in 498,942 unassembled metagenomes from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA). TheMicrocoleusMAG was found in a wide variety of environments,P. pseudopriestleyiwas found in environments with challenging conditions, theNeosynechococcuswas only found in Antarctica, and theLeptolyngbyaandPseudanabaenaMAGs were found in Antarctic and other cold environments. The findings based on metagenome matches and global comparisons suggest that these Antarctic cyanobacteria have distinct distribution patterns ranging from locally restricted to global distribution across the cold biosphere and other climatic zones.
The E2F4/p130 repressor complex cooperates with oncogenic ΔNp73α to promote cell survival in human papillomavirus 38 E6/E7-transformed keratinocytes and in cancer cells
Authors: Taverniti Valerio , Krynska Hanna , Venuti Assunta , Straub Marie-Laure , Sirand Cécilia , Lohmann Eugenie , Romero-Medina Maria Carmen , Moro Stefano , Robitaille Alexis , Negroni Luc , Martinez-Zapien Denise , Masson Murielle , Tommasino Massimo , Zanier Katia 
Published: October 2022

ABSTRACTTumor suppressor p53 and its related proteins, p63 and p73, can be synthesized as multiple isoforms lacking part of the N- or C-terminal regions. Specifically, high expression of the ΔNp73α isoform is notoriously associated with various human malignancies characterized by poor prognosis. This isoform is also accumulated by oncogenic viruses such as Epstein–Barr virus (EBV), as well as genus beta human papillomaviruses (HPV) that appear to be involved in carcinogenesis. To gain additional insight into ΔNp73α mechanisms, we have performed proteomics analyses using human keratinocytes transformed by the E6 and E7 proteins of the beta-HPV type 38 virus as an experimental model (38HK). We find that ΔNp73α associates with the E2F4/p130 repressor complex through a direct interaction with E2F4. This interaction is favored by the N-terminal truncation of p73 characteristic of ΔNp73 isoforms. Moreover, it is independent of the C-terminal splicing status, suggesting that it could represent a general feature of ΔNp73 isoforms (α, β, γ, δ, ε, ζ, θ, η, and η1). We also show that the ΔNp73α- E2F4/p130 complex inhibits the expression of specific genes, including genes encoding for negative regulators of proliferation, both in 38HK and in HPV-negative cancer-derived cell lines. Consistently, silencing of E2F4 in 38HK and in cancer cells results in induction of senescence. In conclusion, we have identified and characterized a novel transcriptional regulatory complex that exerts pro-survival functions in transformed cells.IMPORTANCEThe TP53 gene is mutated in about 50% of human cancers. In contrast, the TP63 and TP73 genes are rarely mutated but rather expressed as ΔNp63 and ΔNp73 isoforms in a wide range of malignancies, where they act as p53 antagonists. Accumulation of ΔNp63 and ΔNp73, which is associated with chemoresistance, can result from infection by oncogenic viruses such as EBV or HPV. Our study focuses on the highly carcinogenic ΔNp73α isoform and uses a viral model of cellular transformation. We unveil a physical interaction between ΔNp73α and the E2F4/p130 complex involved in cell cycle control, which rewires the E2F4/p130 transcriptional program. Consistently, we find that E2F4 gains pro-survival functions in transformed cells expressing ΔNp73α. This report shows, for the first time, that ΔNp73 isoforms acquire novel protein-protein interactions with respect to the TAp73 tumor suppressor. This situation is analogous to the gain-of-function interactions of p53 mutants supporting cellular proliferation.