bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 Compromises in the Medical Practice and the Consequential Effect on Endometriosis Patients
Authors: Ashkenazi Shaked , Huseby Ole Linvåg , Kroken Gard , Soto-Mota Adrian , Pents Marius , Loschiavo Alessandra , Lewandowska Roksana , Tran Grace , Kwiatkowski Sebastian 
Published: May 2021

ABSTRACTBackground and purposeIn response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, self-isolation practices aimed to curb the spread of COVID-19 have severely complicated the medical management of patients suffering from endometriosis and their physical and mental well- being. Endometriosis, the main cause for chronic pelvic pain (CPP), is a highly prevalent disease characterized by the presence of endometrial tissue in locations outside the uterine cavity that affects up to 10% of women in their reproductive age. This study aimed to explore the effects of the global COVID-19 pandemic on patients suffering from endometriosis across multiple countries, and to investigate the different approaches to the medical management of these patients based on their self-reported experiences.MethodsA cross-sectional survey, partially based on validated quality of life questionnaires for endometriosis patients, was initially created in English, which was then reviewed by experts. Through the process of assessing face and content validity, the questionnaire was then translated to fifteen different languages following the WHO recommendations for medical translation. After evaluation, the questionnaire was converted into a web form and distributed across different platforms. An analysis of 2964 responses of participants from 59 countries suffering from self-reported endometriosis was then conducted.ResultsThe data shows an association between COVID-19 imposed compromises with the reported worsening of the mental state of the participants, as well as with the aggravation of their symptoms. For the 1174 participants who had their medical appointments cancelled, 43.7% (n=513) reported that their symptoms had been aggravated, and 49.3% (n=579) reported that their mental state had worsened. In comparison, of the 1180 participants who kept their appointments, only 29.4% (n=347) stated that their symptoms had been aggravated, and 27.5% (n=325) stated their mental health had worsened. 610 participants did not have medical appointments scheduled, and these participants follow a similar pattern as the participants who kept their appointments, with 29.0% (n=177) reporting aggravation of symptoms and 28.2% (n=172) reporting that their mental state had worsened.ConclusionsThese findings suggest that COVID-19 pandemic has had a clinically significant negative effect on the mental and physical well-being of participants suffering from endometriosis based on their self-reported experiences. Thus, they show the importance of further assessment and reevaluation of the current and future management of this condition in medical practices worldwide.
Oral Vitamin D supplementation induces transcriptomic changes in rectal mucosa that are consistent with anti-tumour effects
Authors: Vaughan-Shaw P.G. , Grimes G. , Blackmur JP , Timofeeva M. , Walker M , Ooi L.Y , Svinti Victoria , Donnelly Kevin , Din FVN , Farrington S.M. , Dunlop M.G. 
Published: May 2021

AbstractBackgroundRisk for several common cancers is influenced by the transcriptomic landscape of the respective tissue-of-origin. Vitamin D influences in-vitro gene expression and cancer cell growth. We sought to determine whether oral vitamin D induces beneficial gene expression effects in human rectal epithelium and identify biomarkers of response.MethodsBlood and rectal mucosa was sampled from 191 human subjects and mucosa gene expression (HT12) correlated with plasma vitamin D (25-OHD) to identify differentially expressed genes. Fifty subjects were then administered 3200IU/day oral vitamin D3 and matched blood/mucosa resampled after 12 weeks’. Transcriptomic changes (HT12/RNAseq) after supplementation were tested against the prioritised genes for gene-set and GO-process enrichment. To identify blood biomarkers of mucosal response, we derived receiver-operator curves and C-statistic (AUC) and tested biomarker reproducibility in an independent Supplementation Trial (BEST-D).Results629 genes were associated with 25-OHD level (P<0.01), highlighting 453 GO-term processes (FDR<0.05). In the whole intervention cohort, vitamin D supplementation enriched the prioritised mucosal gene-set (upregulated gene-set P<1.0E-07; downregulated gene-set P<2.6E-05) and corresponding GO terms (P=2.90E-02), highlighting gene expression patterns consistent with anti-tumour effects. However, only 9 individual participants (18%) showed a significant response (NM gene-set enrichment P<0.001) to supplementation. Expression changes in HIPK2 and PPP1CC expression served as blood biomarkers of mucosal transcriptomic response (AUC=0.84 [95%CI:0.66-1.00]), and replicated in BEST-D trial subjects (HIPK2 AUC=0.83 [95%CI:0.77-0.89]; PPP1CC AUC=0.91 [95%CI:0.86-0.95]).ConclusionsHigher plasma 25-OHD correlates with rectal mucosa gene expression patterns consistent with anti-tumour effects and this beneficial signature is induced by short-term vitamin D supplementation. Heterogenous gene expression responses to vitamin D may limit the ability of randomised trials to identify beneficial effects of supplementation on CRC risk. However, in the current study blood expression changes in HIPK2 and PPP1CC identify those participants with significant anti-tumor transcriptomic responses to supplementation in the rectum. These data provide compelling rationale for a trial of vitamin D and CRC prevention using easily assayed blood gene expression signatures as intermediate biomarkers of response.
Saudi Arabian SARS-CoV-2 genomes implicate a mutant Nucleocapsid protein in modulating host interactions and increased viral load in COVID-19 patients
Authors: Mourier Tobias , Shuaib Muhammad , Hala Sharif , Mfarrej Sara , Alofi Fadwa , Naeem Raeece , Alsomali Afrah , Jorgensen David , Subudhi Amit Kumar , Rached Fathia Ben , Guan Qingtian , Salunke Rahul P , Ooi Amanda , Esau Luke , Douvropoulou Olga , Nugmanova Raushan , Perumal Sadhasivam , Zhang Huoming , Rajan Issaac , Al-Omari Awad , Salih Samer , Shamsan Abbas , Mutair Abbas Al , Taha Jumana , Alahmadi Abdulaziz , Khotani Nashwa , Alhamss Abdelrahman , Mahmoud Ahmed , Alquthami Khaled , Dageeg Abdullah , Khogeer Asim , Hashem Anwar M. , Moraga Paula , Volz Eric , Almontashiri Naif , Pain Arnab 
Published: May 2021

SummaryMonitoring SARS-CoV-2 spread and evolution through genome sequencing is essential in handling the COVID-19 pandemic. The availability of patient hospital records is crucial for linking the genomic sequence information to virus function during the course of infections. Here, we sequenced 892 SARS-CoV-2 genomes collected from patients in Saudi Arabia from March to August 2020. From the assembled sequences, we estimate the SARS-CoV-2 effective population size and infection rate and outline the epidemiological dynamics of import and transmission events during this period in Saudi Arabia. We show that two consecutive mutations (R203K/G204R) in the SARS-CoV-2 nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. Our comparative biochemical analysis reveals that the mutant N protein displays enhanced viral RNA binding and differential interaction with key host proteins. We found hyper-phosphorylation of the adjacent serine site (S206) in the mutant N protein by mass-spectrometry analysis. Furthermore, analysis of the host cell transcriptome suggests that the mutant N protein results in dysregulated interferon response genes. We provide crucial information in linking the R203K/G204R mutations in the N protein as a major modulator of host-virus interactions and increased viral load and underline the potential of the nucleocapsid protein as a drug target during infection.
Identification of a novel FUS/ETV4 fusion and comparative analysis with other Ewing sarcoma fusion proteins
Authors: Boone Megann A. , Taslim Cenny , Crow Jesse C. , Selich-Anderson Julia , Watson Mike , Heppner Peter , Hamill James , Wood Andrew C. , Lessnick Stephen L. , Winstanley Mark 
Published: May 2021

AbstractEwing sarcoma is an aggressive pediatric bone cancer defined by a chromosomal translocation fusing one of the FET family members to a member of the ETS transcription factor family. To date, there have been seven reported translocations, with the most recent translocation reported over a decade ago. We now report the first identification of a novel translocation occurring between the FUS gene and ETS family member ETV4 detected in a neonatal patient with Ewing sarcoma. Given its apparent rarity, we conducted an initial characterization of FUS/ETV4 function by performing genomic localization and transcriptional regulatory studies. We knocked down endogenous EWS/FLI in the A673 cell line, and expressed FUS/ETV4 in its stead, and performed CUT&Tag and RNA-sequencing analyses. We compared these data to similar “knock-down/rescue” analyses of other rare (non-EWS/FLI) Ewing sarcoma-associated translocation products. Through this comparative analysis in the same genetic background, we demonstrate significant similarities across these fusions, and in doing so, validate this novel FUS/ETV4 translocation as a bona fide Ewing sarcoma translocation. This study presents the first genomic comparisons of the rare Ewing sarcoma-associated translocation products, and reveals that the FET/ETS fusions share highly similar, but not identical, genomic localization and transcriptional regulation patterns. These data provide insights into the roles of both the FET and ETS sides of these fusions, and provide a generic strategy to provide further strength to the notion that FET/ETS fusions are key drivers of, and thus pathognomonic for, Ewing sarcoma.SignificanceIdentification and initial characterization of the novel Ewing sarcoma fusion, FUS/ETV4, expands the family of Ewing-fusions and extends the diagnostic possibilities for this aggressive tumor of adolescents and young adults.
The Association Between Threatened Miscarriage And Development Of Gestational Hypertension/Pre-Eclampsia
Authors: Gunarathna S.M.S.G. , Ratnayake Naleen , Pallemulla Lakshman , Rasanjana D.P. Lanka , Abeysundara P.K. , Nishad A.A. Nilanga 
Published: May 2021

AbstractIntroductionGestational hypertension (GH)/Pre-eclampsia (PEC) is an important cause of direct maternal deaths in Sri Lanka. GH/PEC and threatened miscarriage (TM) share common pathophysiological mechanisms. This study was conducted to determine the association between TM and development of GH/PEC.MethodologyA case control study was conducted at Castle Street Hospital for Women, Sri Lanka from April 2015 to October 2015. Cases consisted of patients with GH/PEC and compared with age and parity matched controls. A systematic random sampling method was used. Similar number of cases and controls were compared while each group consisted of 245 subjects. Data was obtained from medical records. It’s also important to note that mothers aged 20-35 years were included and medical disorders other than GH/PEC was excluded.ResultsThere were 245 subjects in each group of the study. Among the cases, 56% had GH and the rest had PEC. There were 25 patients with TM in the study population and 64% of them subsequently developed GH or PEC. There is also a significant risk of developing PEC in a patient who had a history of threatened miscarriage (OR 3.31, 95% CI 1.35-8.11). Moreover the patients who had a history of TM tend to develop GH or PEC early, within 20-32 weeks of gestation (OR 11.49, 95% CI 3.88-33.99). As we identified, 62% of patients who had TM developed GH/PEC early (from 20 to 32 weeks) but among the cases who had no history of TM, only 12% developed GH/PEC between 20 to 32 weeks of gestation (O.R. 20.7 (5.66 to 91.96). There is a significant risk of developing severe GH/PEC in the group of patients who had a history of TM (OR 8.59, 95% CI 2.87-25.66). Eighty one percent (81%) of the cases, who had a history of TM, developed severe and moderate GH/PEC rather than mild. But the majority (63%) of the cases, who had no history of TM, developed mild GH/PEC (O.R. 7.6 (2.00 to 42.55).ConclusionsShared pathophysiological mechanisms of GH/PEC and TM may explain the observed association between these obstetric complications. Early onset, severe GH/PEC in cases with TM suggests temporality and a biological gradient which favors causality.
Respiratory cryptosporidiosis in Malawian children with diarrheal disease
Authors: Tam Pui-Ying Iroh , Chisala Mphatso , Nyangulu Wongani , Thole Herbert , Nyirenda James 
Published: May 2021

AbstractBackgroundRespiratory cryptosporidiosis has been documented in children with diarrhea. We sought to describe the dynamics of respiratory involvement in children hospitalized with gastrointestinal (GI) diarrheal disease.MethodsWe conducted a prospective, observational longitudinal study of Malawian children 2-24 months hospitalized with diarrhea. Nasopharyngeal (NP) swabs, induced sputum and stool specimens were collected. Participants that were positive by cryptosporidium PCR in any of the three compartments were followed up with fortnightly visits up to 8 weeks post-enrollment.ResultsOf the 162 children recruited, participants had mild-moderate malnutrition, 36 (22%) were PCR-positive for cryptosporidium at enrollment (34 stool, 11 sputum, and 4 NP) and 27 completed the majority of follow-up visits (75%). Cryptosporidium was detected in all compartments over the 4 post-enrollment visits, most commonly in stool (94% at enrollment with mean cycle thresholds (Ct) of 28.8±4.3 to 44% at 8 weeks with Ct 29.9±4.1), followed by sputum (31% at enrollment with mean Ct 31.1±4.4 to 20% at 8 weeks with Ct 35.7±2.6), then NP (11% with mean Ct 33.5±1.0 to 8% with Ct 36.6±0.7). Participants with cryptosporidium detection in both the respiratory and GI tract over the study period reported respiratory and GI symptoms in 81% and 62% of study visits, respectively, compared to 68% and 27%, respectively, for those with only GI detection, and had longer GI shedding (17.5±6.6 v. 15.9±2.9 days).ConclusionCryptosporidium was detected in both respiratory and GI tracts throughout the 8 weeks post-enrollment. The development of therapeutics for cryptosporidium in children should target the respiratory as well as GI tract. (255)Author summaryWe conducted a prospective, observational longitudinal study of Malawian children 2-24 months hospitalized with diarrhea. Nasopharyngeal (NP) swabs, induced sputum and stool specimens were collected. Participants that were positive by cryptosporidium PCR in any of the three compartments were followed up with fortnightly visits up to 8 weeks post-enrollment. Cryptosporidium was detected by PCR in 21%, 7% and 3% in stool, sputum and nasopharynx of children hospitalized with diarrhea. Of those positive at enrollment, detection was noted in 44%, 20%, and 8%, respectively, by 8 weeks post-enrollment. (87)
THE COST-EFFECTIVENESS OF DEPRESSION SCREENING FOR THE GENERAL ADULT POPULATION
Authors: Yildirim Melike , Gaynes Bradley N , Keskinocak Pinar , Pence Brian W , Swann Julie 
Published: May 2021

ABSTRACTBackgroundDepression is a treatable disease, and untreated depression can lead to serious health complications and decrease the quality of life. Therefore, prevention, early identification, and treatment efforts are essential. Screening has an essential role in preventive medicine in the general population. Ideally, screening tools detect patients early enough to manage the disease and reduce symptoms. We aimed to determine the cost-effectiveness of routine screening schedules.MethodsWe used a discrete-time nonstationary Markov model to simulate the progression of depression. We used Monte Carlo techniques to simulate the stochastic model for 20 years or during the lifetime of individuals. Baseline and screening scenario models with screening frequencies of annual, 2-year, and 5-year strategies were compared based on incremental cost-effectiveness ratios (ICER). Monte Carlo (MC) simulation and one-way sensitivity analysis were conducted to manage uncertainties.ResultsIn the general population, all screening strategies were cost-effective compared to the baseline. However, male and female populations differed based on cost over quality-adjusted life years (QALY). Females had lower ICERs, and annual screening had the highest ICER for females, with 11,134$/QALY gained. In contrast, males had around three times higher ICER, with annual screening costs of 34,065$/QALY gained.LimitationsWe assumed that the screening frequency was not changing at any time during the screening scenario. In our calculations, false-positive cases were not taking into account.ConclusionsConsidering the high lifetime prevalence and recurrence rates of depression, detection and prevention efforts can be one critical cornerstone to support required care. Our analysis combined the expected benefits and costs of screening and assessed the effectiveness of screening scenarios. We conclude that routine screening is cost-effective for all age groups of females and young, middle-aged males.
Elevated nest temperature has opposing effects on host species infested with parasitic nest flies
Authors: Albert Lauren , Rumschlag Samantha , Parker Alexandra , Vaziri Grace , Knutie Sarah A. 
Published: May 2021

ABSTRACTEnvironmental factors, such as elevated temperature, can have varying effects on hosts and their parasites, which can have consequences for disease outcomes. The individual direct effects of temperature must be disentangled to determine the net-effect in host-parasite relationships, yet few studies have determined the net-effects in a multi-host system. To address this gap, we experimentally manipulated temperature and parasite presence in the nests of two host species infested by parasitic blowflies (Protocalliphora sialia). We conducted a factorial experiment by increasing temperature (or not) and removing all parasites (or not) in the nests of eastern bluebirds (Sialia sialis) and tree swallows (Tachycineta bicolor). We then measured nestling morphometrics, blood loss, and survival and quantified parasite abundance. We predicted that if temperature had a direct effect on parasite fitness, then elevated temperature would cause similar directional effects on parasite abundance across host species. If temperature had a direct effect on hosts, and therefore an indirect effect on the parasite, parasite abundance would differ across host species. Heated swallow nests had fewer parasites compared to non-heated nests. In contrast, heated bluebird nests had more parasites compared to non-heated nests. The results of our study demonstrate that elevated temperature can have differential effects on host species, which can impact infestation susceptibility. Furthermore, changing climates could have complex net-effects on parasite fitness and host health across multi-host-parasite interactions.
Acorde: unraveling functionally-interpretable networks of isoform co-usage from single cell data
Authors: Arzalluz-Luque Angeles , Salguero Pedro , Tarazona Sonia , Conesa Ana 
Published: May 2021

AbstractAlternative splicing (AS) is a highly-regulated post-transcriptional mechanism known to modulate isoform expression within genes and contribute to cell-type identity. However, the extent to which alternative isoforms establish co-expression networks that may relevant in cellular function has not been explored yet. Here, we presentacorde, a pipeline that successfully leverages bulk long reads and single-cell data to confidently detect alternative isoform co-expression relationships. To achieve this, we developed and validated percentile correlations, a novel approach that overcomes data sparsity and yields accurate co-expression estimates from single-cell data. Next,acordeuses correlations to cluster co-expressed isoforms into a network, unraveling cell type-specific alternative isoform usage patterns. By selecting same-gene isoforms between these clusters, we subsequently detect and characterize genes with co-differential isoform usage (coDIU) across neural cell types. Finally, we predict functional elements from long read-defined isoforms and provide insight into biological processes, motifs and domains potentially controlled by the coordination of post-transcriptional regulation.
A Metric for Quantifying the Resolution of Molecular Assays
Authors: Wilson Brandon D. , Eisenstein Michael , Soh H. Tom 
Published: May 2021

AbstractMany assay developers focus on limit of detection (LOD) as a primary performance metric, and LOD is indeed useful for assays designed to determine the presence or absence of an analyte. However, LOD is less useful for ‘continuous assays’ designed to discriminate between concentrations of an analyte—e.g., glucose monitoring in diabetes, where clinical care is guided by particular concentration ranges and thresholds. In such scenarios, it would be valuable to quantify discriminatory resolution—i.e., whether an assay can differentiate 1 pM from 10 pM— but no such standardized metric currently exists. Here, we propose a useful solution, termed ‘resolution of molecular concentration’ (RMC). RMC offers a simple means for characterizing quantitative resolution and quickly comparing the quantitative performance of assays. By raising awareness of the limitations of current metrics for evaluating assay performance, we hope to empower the molecular diagnostics community to evaluate their methods in a more application-appropriate manner.
RNA toxicity and perturbation ofrRNA processing in spinocerebellar ataxia type 2
Authors: Li Pan P. , Moulick Roumita , Feng Hongxuan , Sun Xin , Arbez Nicolas , Jin Jing , Marque Leonard O. , Hedglen Erin , Chan H.Y. Edwin , Ross Christopher A. , Pulst Stefan M. , Margolis Russell L. , Woodson Sarah , Rudnicki Dobrila D. 
Published: May 2021

AbstractBACKGROUNDSpinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease caused by expansion of a CAG repeat inAtaxin-2(ATXN2) gene. The mutant ATXN2 protein with a polyglutamine tract is known to be toxic and contributes to the SCA2 pathogenesis.OBJECTIVEHere we tested the hypothesis that the mutantATXN2transcript with an expanded CAG repeat (expATXN2) is also toxic and contributes to SCA2 pathogenesis.METHODSThe toxic effect ofexpATXN2transcripts on SK-N-MC neuroblastoma cells and primary mouse cortical neurons was evaluated by caspase 3/7 activity and nuclear condensation assay, respectively. RNA immunoprecipitation assay was performed to identify RNA binding proteins (RBPs) that bind toexpATXN2RNA. Quantitative PCR was used to examine if rRNA processing is disrupted in SCA2 and Huntington disease (HD) human brain tissue.RESULTSexpATXN2RNA induces neuronal cell death, and aberrantly interacts with RBPs involved in RNA metabolism. One of the RBPs, transducin β-like protein 3 (TBL3), involved in rRNA processing, binds to bothexpATXN2and expandedhuntingtin(expHTT) RNAin vitro. rRNA processing is disrupted in both SCA2 and HD human brain tissue.CONCLUSIONThese findings provide the first evidence of a contributory role ofexpATXN2transcripts in SCA2 pathogenesis, and further support the roleexpHTTtranscripts in HD pathogenesis. The disruption of rRNA processing, mediated by aberrant interaction of RBPs withexpATXN2andexpHTTtranscripts, suggest a point of convergence in the pathogeneses of repeat expansion diseases with potential therapeutic implications.