bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANALYSIS OF FOUR DIFFERENT TRANSPORT AND PRESERVATION MEDIUM KITS FOR SARS-COV-2 DIAGNOSIS FROM NASOPHARYNGEAL SWAB BY REAL-TIME PCR: ADAPTING TO THE CONSTANTLY INCREASING DEMAND OF SAMPLING PROCESSING AND STOCK-OUTS DURING THE PANDEMIC
Authors: Barrera-Avalos Carlos , Luraschi Roberto , Vallejos-Vidal Eva , Figueroa Maximiliano , Arenillas Esteban , Barría Daniela , Hernández Felipe , Mateluna Carlos , Mena Javier , Rioseco Claudia , Torrent Claudia , Vergara Claudio , Gutiérrez Gaby , Quiroz Javiera , Alarcón Javiera , Cartagena Julio , Cayunao Javiera , Mella Andrea , Santibañez Álvaro , Tapia Sebastián , Undurraga Alejandro , Vargas Deborah , Wong Valentina , Inostroza Ailen , Valdés Daniel , Imarai Mónica , Acuña-Castillo Claudio , Reyes-López Felipe E. , María Sandino Ana 
Published: July 2021

ABSTRACTThe high demand for supplies during the COVID19-pandemic has generated several stock-out of material and essential reagents needed to meet the current high demand for diagnosis in the worldwide population. In this way, there is limited information regarding the performance of different virus transport medium (VTM) for nasopharyngeal swab sampling (NPS) aimed for SARS-CoV-2 detection. We compared the RT-qPCR amplification profile of four different commercial transport medium kits, including DNA/RNA Shield™, NAT™, VTM, and Phosphate-buffered saline (PBS) transport medium, for NPSs samples from Central Metropolitan Health Service, Santiago, Chile. The RT-qPCR showed a slight lower RNase P Cq value of the samples preserved and transported in DNA/RNA Shield™ compared to NAT medium. By contrast, a marked increase in the RNase P Cq value was registered in the samples transported with VTM compared to DNA/RNA Shield™ medium. For PBS-preserved NPS, the performance of two strategies were assessed due to the potential presence of any remaining active virus in the sample: (1) thermal inactivation; and (2) thermal inactivation treatment followed by RNA extraction. The heat inactivation showed a significantly lower Cq value for RNase P and viral ORF1ab Cq compared to the followed by RNA extraction. This study indicates that new medium alternatives could be used if supplies run out to diagnose COVID19.
The Association of Stay-at-Home Orders and the Spread of COVID-19 in Rural and Urban United States
Authors: Jiang David H. , Roy Darius J. , Pollock Benjamin D. , Shah Nilay D. , McCoy Rozalina G. 
Published: July 2021

AbstractBackgroundThroughout the spring of 2020, stay-at-home orders were imposed to curb the spread of COVID-19. There is limited data on the effectiveness of stay-at-home orders, particularly in rural as compared to urban areas.ObjectiveTo examine the association between stay-at-home order implementation and the incidence of COVID-19 in rural vs. urban counties.DesignInterrupted time series analysis using a mixed effects zero-inflated Poisson model.Participants3,142 U.S. counties.InterventionsStay-at-home orders.Main MeasuresCOVID-19 daily incidence (primary) and mobility (secondary and intermediate measure of stay-at-home effectiveness)Key ResultsStay-at-home orders were implemented later (median March 30 vs. March 28) and were shorter (median 35 vs. 54 days) in rural than urban counties. Indoor mobility was, on average, 2.6-6.9% higher in rural than urban counties both during and after stay-at-home orders. Compared to the baseline (pre-stay-at-home) period, the number of new COVID-19 cases increased under stay-at-home by IRR 1.60 (95% CI, 1.57-1.64) in rural and 1.36 (95% CI, 1.30-1.42) in urban counties. For each day under stay-at-home orders, the number of new cases changed by a factor of 0.982 (95% CI 0.981-0.982) in rural and 0.952 (95% CI, 0.951-0.953) in urban counties compared to prior to stay-at-home. Each day after stay-at-home orders expired, the number of new cases changed by a factor of 0.995 (95% CI, 0.994-0.995) in rural and 0.997 (95% CI, 0.995-0.999) in urban counties compared to prior to stay-at-home.ConclusionStay-at-home orders decreased mobility and slowed the spread of COVID-19, but less effectively in rural than in urban counties. This necessitates a critical reevaluation of how stay-at-home orders are designed, communicated, and implemented in rural areas.
Optimising Early Management of Acute Severe Ulcerative Colitis in the Biologics Era: Admission Model for Intensification of Therapy in Acute Severe Colitis (ADMIT–ASC)
Authors: Adams Alex , Gupta Vipin , Mohsen Waled , Chapman Thomas P , Subhaharan Deloshaan , Ramaswamy Pradeep Kakkadasam , Vuyyuru Sudheer Kumar , Kedia Saurabh , McGregor Colleen GC , Ambrose Tim , George Bruce D , Palmer Rebecca , Brain Oliver , Walsh Alissa , Ahuja Vineet , Travis Simon , Satsangi Jack 
Published: July 2021

ABSTRACTBackground & aimsWe aimed to determine whether changes in ulcerative colitis management have translated to improved outcomes, in order to develop a simple model to predict steroid non-response on admission.MethodsOutcomes of 131 adult ASC admissions (117 patients) in Oxford, UK between 2015-19 were compared with prospectively collected data from 1992-3. All patients received standard treatment with intravenous corticosteroids and endoscopic disease activity scoring (UCEIS). Steroid non-response was defined as receiving rescue medical therapy or surgery. A predictive model created in the Oxford cohort was validated in Australia and India (110 hospitalised patients Gold Coast University Hospital 2015-20; 62 hospitalised patients AIIMS, New Delhi 2018-20).ResultsIn the 2015-19 Oxford cohort, 71 (54%) patients received medical rescue therapy (27% ciclosporin, 27% anti-TNF), compared to 27% ciclosporin in 1992-3, p=0.0015. Only 15% required colectomy during admission vs 29% in 1992-3 (p=0.033). Admission CRP, albumin, and UCEIS scores predicted steroid non-response (FDR p=0.00066, 0.0066 and 0.015). A four-point model was developed involving CRP ≥100mg/L (1 point), albumin ≤25g/L (1 point), UCEIS ≥4 (1 point) or ≥7 (2 points). Scoring 0 or 4 was 100% predictive of steroid response and non-response, respectively, in all three cohorts. Patients scoring 3-4 had 83% risk of steroid non-response in Oxford and 84% (0.70-0.98) in the validation cohorts – OR 11.9 (10.8-13).ConclusionColectomy rates for ASC have halved in 25 years, while use of rescue medical therapy has doubled. Patients who are highly unlikely to respond to parenteral steroid treatment alone may be readily identified on admission, to be prioritised for early intensification of therapy.WHAT YOU NEED TO KNOWBackground and contextAcute severe colitis (ASC) requires hospitalisation and, frequently, colectomy. The accepted management of ASC is three-five days of intravenous steroids followed by protocolised response assessment.New findingsMedical rescue therapy has doubled and the colectomy rate halved in 25 years. A predictive index identifying steroid non-response was derived and validated in three independent centres in three countries.LimitationsA need remains to demonstrate that earlier rescue medical therapy for patients predicted to be steroid non-responders will further improve outcomes.ImpactThe outcome of ASC has substantially improved in the past 25 years, with the potential for further improvement by identifying patients on admission for early escalation of therapy.
Effects of a 33-ion sequential beam galactic cosmic ray analog on male mouse behavior and evaluation of CDDO-EA as a radiation countermeasure
Authors: Kiffer Frederico C , Luitel Krishna , Tran Fionya H , Patel Riya A , Guzman Catalina S , Soler Ivan , Xiao Rui , Shay Jerry W , Yun Sanghee , Eisch Amelia J 
Published: July 2021

ABSTRACTIn long-term spaceflight, astronauts will face unique cognitive loads and social challenges which will be complicated by communication delays with Earth. It is important to understand the central nervous system (CNS) effects of deep spaceflight and the associated unavoidable exposure to galactic cosmic radiation (GCR). Rodent studies show single- or simple-particle combination exposure alters CNS endpoints, including hippocampal-dependent behavior. An even better Earth-based simulation of GCR is now available, consisting of a 33-beam (33-GCR) exposure. However, the effect of whole-body 33-GCR exposure on rodent behavior is unknown, and no 33-GCR CNS countermeasures have been tested. Here astronaut-age-equivalent (6mo-old) C57BL/6J male mice were exposed to 33-GCR (75cGy, a Mars mission dose). Pre-/during/post-Sham or 33-GCR exposure, mice received a diet containing a ‘vehicle’ formulation alone or with the antioxidant/anti-inflammatory compound CDDO‐EA as a potential countermeasure. Behavioral testing beginning 4mo post-irradiation suggested radiation and diet did not affect measures of exploration/anxiety-like behaviors (open field, elevated plus maze) or recognition of a novel object. However, in 3-Chamber Social Interaction (3-CSI), CDDO-EA/33-GCR mice failed to spend more time exploring a holder containing a novel mouse vs. a novel object (empty holder), suggesting sociability deficits. Also, Vehicle/33-GCR and CDDO-EA/Sham mice failed to discriminate between a novel stranger vs. familiarized stranger mouse, suggesting blunted preference for social novelty. CDDO-EA given pre-/during/post-irradiation did not attenuate the 33-GCR-induced blunting of preference for social novelty. Future elucidation of the mechanisms underlying 33-GCR-induced blunting of preference for social novelty will improve risk analysis for astronauts which may in-turn improve countermeasures.
c-Jun N-terminal kinase (JNK) signaling contributes to cystic burden in polycystic kidney disease
Authors: Smith Abigail O. , Jonassen Julie A. , Preval Kenley M. , Davis Roger J. , Pazour Gregory J. 
Published: July 2021

AbstractPolycystic kidney disease is an inherited degenerative disease in which the uriniferous tubules are replaced by expanding fluid-filled cysts that ultimately destroy organ function. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form, afflicting approximately 1 in 1,000 people. It primarily is caused by mutations in the transmembrane proteins polycystin-1 (Pkd1) and polycystin-2 (Pkd2). The most proximal effects of Pkd mutations leading to cyst formation are not known, but pro-proliferative signaling must be involved for the tubule epithelial cells to increase in number over time. The c-Jun N-terminal kinase (JNK) pathway promotes proliferation and is activated in acute and chronic kidney diseases. Using a mouse model of cystic kidney disease caused by Pkd2 loss, we observe JNK activation in cystic kidneys and observe increased nuclear phospho c-Jun in cystic epithelium. Genetic removal of Jnk1 and Jnk2 suppresses the nuclear accumulation of phospho c-Jun, reduces proliferation and reduces the severity of cystic disease. While Jnk1 and Jnk2 are thought to have largely overlapping functions, we find that Jnk1 loss is nearly as effective as the double loss of Jnk1 and Jnk2. Jnk pathway inhibitors are in development for neurodegeneration, cancer, and fibrotic diseases. Our work suggests that the JNK pathway should be explored as a therapeutic target for ADPKD.Author SummaryAutosomal dominant polycystic kidney disease is a leading cause of end stage renal disease requiring dialysis or kidney transplant. During disease development, the cells lining the kidney tubules proliferate. This proliferation transforms normally small diameter tubules into fluid-filled cysts that enlarge with time, eventually destroying all kidney function. Despite decades of research, polycystic kidney disease remains incurable. Furthermore, the precise signaling events involved in cyst initiation and growth remain unclear. The c-Jun N-terminal kinase (JNK), is a major pathway regulating cellular proliferation and differentiation but its importance to polycystic kidney disease was not known. We show that JNK activity is elevated in cystic kidneys and that reducing JNK activity decreases cyst growth pointing to JNK inhibition as a therapeutic strategy for treating polycystic kidney disease.
BAZ2A-RNA mediated association with TOP2A and KDM1A represses genes implicated in prostate cancer
Authors: Roganowicz Marcin , Bär Dominik , Bersaglieri Cristiana , Aprigliano Rossana , Santoro Raffaella 
Published: July 2021

AbstractBAZ2A is the repressor of rRNA genes that are transcribed by RNA Polymerase I. In prostate cancer (PCa), however, BAZ2A function goes beyond this role since it can also repress other genes that are frequently silenced in metastatic disease. However, the mechanisms of BAZ2A-mediated repression in PCa remain elusive. Here we show that BAZ2A represses genes implicated in PCa through its RNA-binding TAM domain using mechanisms differing from rRNA gene silencing. While TAM domain mediates BAZ2A recruitment to rRNA genes, in PCa cells this is not required for BAZ2A association with target genes. Instead, BAZ2A-TAM domain in association with RNA mediates the interaction with topoisomerase 2A (TOP2A) and histone demethylase KDM1A, whose expression positively correlates with BAZ2A levels in both localized and aggressive PCa. Pharmacological inhibition of TOP2A and KDM1A activities upregulates the expression of BAZ2A-repressed genes that are regulated by a class of inactive enhancers bound by BAZ2A whereas rRNA genes are not affected. Our findings showed a novel RNA-based mechanism of gene regulation in PCa. Further, the data indicate that RNA-mediated interactions between BAZ2A and TOP2A and KDM1A repress genes critical to PCa and may prove to be useful to stratify prostate cancer risk and treatment in patients.
Monitoring the spread of SARS-CoV-2 variants in Moscow and the Moscow region using targeted high-throughput sequencing
Authors: Borisova N.I. , Kotov I.A. , Kolesnikov A.A. , Kaptelova V.V. , Speranskaya A.S. , Kondrasheva L.Yu. , Tivanova E.V. , Khafizov K.F. , Akimkin V. G. 
Published: July 2021

AbstractSince the outbreak of the COVID-19 pandemic caused by the SARS-CoV-2 coronavirus, the international community has been concerned about the emergence of mutations that alter the biological properties of the pathogen, for example, increasing its infectivity or virulence. In particular, since the end of 2020, several variants of concern have been identified around the world, including variants “alpha” (B.1.1.7, “British”), “beta” (B.1.351, “South African”), “gamma” (P.1, “Brazilian”) and “delta” (B.1.617.2, “Indian”). However, the existing mechanism for searching for important mutations and identifying strains may not be effective enough, since only a relatively small fraction of all identified pathogen samples can be examined for genetic changes by whole genome sequencing due to its high cost. In this study, we used the method of targeted high-throughput sequencing of the most significant regions of the gene encoding the S-glycoprotein of the SARS-CoV-2 virus, for which a primer panel was developed. Using this technique, we examined 579 random samples obtained from patients in Moscow and the Moscow region with coronavirus infection from February to June 2021. The study demonstrated the dynamics of the representation in the Moscow region of a number of SARS-CoV-2 strains and its most significant individual mutations in the period from February to June 2021. It was found that the strain B.1.617.2 began to spread rapidly in Moscow and the Moscow region in May, and in June it became dominant, partially displacing other varieties of the virus. The results obtained make it possible to accurately determine the belonging of the samples to the abovementioned and some other strains. The approach can be used to standardize the procedure for searching for new and existing epidemiologically significant mutations in certain regions of the SARS-CoV-2 genome, which allows studying a large number of samples in a short time and to get a more detailed picture of the epidemiological situation in the region.
Latent neural dynamics encode temporal context in speech
Authors: Stephen Emily P , Li Yuanning , Metzger Sean , Oganian Yulia , Chang Edward F 
Published: July 2021

AbstractDirect neural recordings from human auditory cortex have demonstrated encoding for acoustic-phonetic features of consonants and vowels. Neural responses also encode distinct acoustic amplitude cues related to timing, such as those that occur at the onset of a sentence after a silent period or the onset of the vowel in each syllable. Here, we used a group reduced rank regression model to show that distributed cortical responses support a low-dimensional latent state representation of temporal context in speech. The timing cues each capture more unique variance than all other phonetic features and exhibit rotational or cyclical dynamics in latent space from activity that is widespread over the superior temporal gyrus. We propose that these spatially distributed timing signals could serve to provide temporal context for, and possibly bind across time, the concurrent processing of individual phonetic features, to compose higher-order phonological (e.g. word-level) representations.
Engineering functional human gastrointestinal organoid tissues using the three primary germ layers separately derived from pluripotent stem cells
Authors: Eicher Alexandra K. , Kechele Daniel O. , Sundaram Nambirajan , Berns H. Matthew , Poling Holly M. , Haines Lauren E. , Sanchez J. Guillermo , Kishimoto Keishi , Krishnamurthy Mansa , Han Lu , Zorn Aaron M. , Helmrath Michael A. , Wells James M. 
Published: July 2021

SUMMARYThe development of human organoid model systems has provided new avenues for patient-specific clinical care and disease modeling. However, all organoid systems are missing important cell types that, in the embryo, get incorporated into organ tissues during development. Based on the concept of how embryonic organs are assembled, we developed an organoid assembly approach starting with cells from the three primary germ layers; enteric neuroglial, mesenchymal, and epithelial precursors, all separately derived from human pluripotent stem cells. From these we generated human gastric tissue containing differentiated glands, surrounded by layers of smooth muscle containing functional enteric neurons that controlled contractions of the engineered tissue. We used this highly tractable system to identify essential roles for the enteric nervous system in the growth and regional identity of the gastric epithelium and mesenchyme and for glandular morphogenesis of the antral stomach. This approach of starting with separately-derived germ layer components was applied to building more complex fundic and esophageal tissue, suggesting this as a new paradigm for tissue engineering.
Integrated transcriptomics identifies β-cell subpopulations and genetic networks associated with obesity and glycemic control in SM/J mice
Authors: Miranda Mario A , Macias-Velasco Juan F , Schmidt Heather , Lawson Heather A 
Published: July 2021

AbstractUnderstanding how heterogeneous β-cell function and stress response impact diabetic etiology is imperative for therapy development. Standard single-cell RNA sequencing analysis illuminates some genetic underpinnings driving heterogeneity, but new strategies are required to capture information lost due to technical limitations. Here, we integrate pancreatic islet single-cell and bulk RNA sequencing data to identify β-cell subpopulations based on gene expression and characterize genetic networks associated with β-cell function in high- and low-fat fed male and female SM/J mice at 20 and 30wks of age. Previous studies have shown that high-fat fed SM/J mice resolve glycemic dysfunction between 20 and 30wks. We identify 4 β-cell subpopulations associated with insulin secretion, hypoxia response, cell polarity, and stress response. Relative proportions of these cells are influenced by age, sex, and diet. Network analysis identifies fatty acid metabolism and β-cell physiology gene expression modules associated with the hyperglycemic-obese state. We identify subtype-specific expression of Pdyn and Fam151a as candidate regulators of genetic pathways associated with β-cell function in obesity. In sum, this study uses a novel data integration method to explore how β-cells respond to obesity and glycemic stress, helping to define the relationship between β-cell heterogeneity and diabetes, and shedding light on novel genetic pathways with therapeutic potential.
LincRNA-Cox2 functions to regulate inflammation in alveolar macrophages during acute lung injury
Authors: Robinson Elektra Kantzari , Worthington Atesh K. , Poscablo Donna M. , Shapleigh Barbara , Salih Mays Mohammed , Halasz Haley , Seninge Lucas , Mosqueira Benny , Smaliy Valeriya , Forsberg E. Camilla , Carpenter Susan 
Published: July 2021

AbstractThe respiratory system exists at the interface between our body and the surrounding non-sterile environment; therefore, it is critical for a state of homeostasis to be maintained through a balance of pro- and anti- inflammatory cues. An appropriate inflammatory response is vital for combating pathogens, while an excessive or uncontrolled inflammatory response can lead to the development of chronic diseases. Recent studies show that actively transcribed noncoding regions of the genome are emerging as key regulators of biological processes, including inflammation. LincRNA-Cox2 is one such example of an inflammatory inducible long noncoding RNA functioning to control immune response genes. Here using bulk and single cell RNA-seq, in addition to florescence activated cell sorting, we show that lincRNA-Cox2 is most highly expressed in the lung, particularly in alveolar macrophages where it functions to control immune gene expression following acute lung injury. Utilizing a newly generated lincRNA-Cox2 transgenic overexpressing mouse, we show that it can function in trans to control genes including Ccl3, 4 and 5. This work greatly expands our understanding of the role for lincRNA-Cox2 in host defense and sets in place a new layer of regulation in RNA-immune-regulation of genes within the lung.