bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of Rosuvastatin plus Colchicine, Emtricitabine/Tenofovir and a combination of them in Hospitalized Patients with SARS Covid-19
Authors: Gaitán-Duarte Hernando Guillermo , Álvarez-Moreno Carlos , Rincón-Rodríguez Carlos Javier , Yomayusa-González Nancy , Cortés Jorge Alberto , Villar Juan Carlos , Bravo-Ojeda Juan Sebastián , García-Peña Ángel , Adarme-Jaimes Wilson , Rodríguez-Romero Viviana Alejandra , Villate-Soto Steffany Lorena , Buitrago Giancarlo , Chacón-Sarmiento Julio , Macías-Quintero Martín , Vaca Claudia Patricia , Gómez-Restrepo Carlos , Rodríguez-Malagón Nelcy 
Published: July 2021

ABSTRACTBACKGROUNDThe effectiveness of rosuvastatin plus colchicine, emtricitabine/tenofovir, and of their combined use in hospitalized patients with coronavirus disease 2019 (Covid-19) pneumonia is unclear.METHODSIn each hospital, hospitalized adults with Covid-19 pneumonia, were randomly assigned, in a 1:1 ratio, to receive: a) standard of care; or b) emtricitabine/tenofovir; or c) colchicine + rosuvastatin; or d) emtricitabine/tenofovir + colchicine + rosuvastatin. The primary outcome was all-cause mortality within the first 28 days after randomization. Severe adverse events (SAE) were those with a high probability of being treatment-related.RESULTS633 patients were randomized in 6 hospitals in Bogota, Colombia. Overall, 98% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death through day 28 was 10.7% in the emtricitabine/tenofovir + colchicine + rosuvastatin arm, 14.4% in the colchicine + rosuvastatin arm, 13.8% in the emtricitabine/tenofovir arm, and 17.4% in the standard of care arm, with adjusted risk differences (aRD) against the standard treatment of -0.07 (95% confidence interval [CI], -0.17 to 0.04), aRD -0.03 (95%CI: -0.11 to 0.05) and aRD: -0.05 (95%CI: -0.15 to 0.05), respectively. Need for invasive mechanical ventilation was lower in the emtricitabine/tenofovir + colchicine + rosuvastatin arm compared to the standard treatment arm, aRD: -0.06 (95%CI: -0.11 to -0,01), but no differences were found between the other comparisons. SAE occurred in 3 patients distributed in the 3 treatment arms.CONCLUSIONSAmong patients hospitalized with moderate and severe SARS Covid-19, the use of the emtricitabine/tenofovir + colchicine + rosuvastatin combination emerges as a treatment alternative.ClinicalTrials.gov number:NCT04359095
Aorta-on-a-chip reveals impaired mitochondrial dynamics as a therapeutic target for aortic aneurysm in bicuspid aortic valve disease
Authors: Abudupataer Mieradilijiang , Zhu Shichao , Yan Shiqiang , Xu Kehua , Zhang Jingjing , Luo Shaman , Ma Wenrui , Alam Md. Fazle , Tang Yuyi , Huang Hui , Chen Nan , Wang Li , Yan Guoquan , Li Jun , Lai Hao , Wang Chunsheng , Zhu Kai , Zhang Weijia 
Published: July 2021

AbstractBackgroundBicuspid aortic valve (BAV) is the most common congenital cardiovascular disease in general population and is frequently associated with the development of thoracic aortic aneurysm (TAA). There is no effective strategy to intervene with TAA progression due to an incomplete understanding of the pathogenesis. Insufficiency of NOTCH1 expression is highly related to BAV-TAA, but the underlying mechanism remains to be clarified.MethodsA comparative proteomics analysis was used to explore the biological differences between non-diseased and BAV-TAA aortic tissues. A microfluidics-based aorta-on-a-chip model was constructed to evaluate the effect of NOTCH1 deficiency on contractile phenotype and mitochondrial dynamics of human aortic smooth muscle cells (HAoSMCs).ResultsProtein analyses of human aortic tissues showed the insufficient expression of NOTCH1 and impaired mitochondrial dynamics in BAV-TAA. HAoSMCs with NOTCH1-knockdown exhibited reduced contractile phenotype and were accompanied by attenuated mitochondrial fusion. Furthermore, we identified that mitochondrial fusion activators (leflunomide and teriflunomide) or mitochondrial fission inhibitor (Mdivi-1) partially rescued the disorders of mitochondrial dynamics in HAoSMCs derived from BAV-TAA patients.ConclusionsThe aorta-on-a-chip model simulates the human pathophysiological parameters of aorta biomechanics and provides a platform for molecular mechanism studies of aortic disease and related drug screening. This aorta-on-a-chip model and human tissue proteomic analysis revealed that impaired mitochondrial dynamics could be a potential therapeutic target for BAV-TAA.FundingNational Key R&D Program of China, National Natural Science Foundation of China, Shanghai Municipal Science and Technology Major Project, Shanghai Science and Technology Commission, and Shanghai Municipal Education Commission.
A case of autosomal dominant osteopetrosis type II with a severe bone phenotype but no amino acid converting mutation in the CLCN7 gene
Authors: Hofstaetter Jochen G. , Atkins Gerald J. , Kogawa Masakazu , Blouin Stéphane , Misof Barbara M. , Roschger Paul , Evdokiou Andreas , Solomon L. Bogdan , Findlay David M. , Ito Nobuaki 
Published: July 2021

ABSTRACTAutosomal Dominant Osteopetrosis type II (ADOII), also known as Albers-Schönberg disease, is caused by mutation of the CLCN7 chloride channel gene and is characterized by reduced bone resorption. Here we report on an individual with the classic features of ADOII, who had a history of fractures from childhood, displayed high bone mass and characteristic “sandwich vertebrae” on x-ray. Our genetic analyses showed no amino acid converting mutation in the patient’s DNA but we did find evidence of haploinsufficiency of CLCN7 mRNA. An iliac crest bone sample from the patient revealed bone tissue and material abnormalities relative to normal controls based on quantitative backscattered electron imaging and histomorphometric analyses. Additionally to lamellar bone, we observed significant amounts of woven bone and mineralised cartilage, as well as an increased frequency and thickness (up to 15 microns) of cement lines. Giant osteoclasts with numerous nuclei were present. The bone mineralisation density distribution (BMDD) of the entire bone area revealed markedly increased average mineral content of the dense bone (CaMean T-score +10.1) and frequency of bone with highest mineral content (CaHigh T-score +19.6), suggesting continued mineral accumulation and lack of bone remodelling. Osteocyte lacunae sections (OLS) characteristics were unremarkable except the OLS shape which was unusually circular. Together, our findings suggest that the reduced expression of CLCN7 mRNA in osteoclasts, and possibly also osteocytes, causes poorly remodelled bone with abnormal bone matrix with high mineral content. This together with the lack of adequate bone repair mechanisms makes the material brittle and prone to fracture.
Efficacy and safety of Andrographis paniculata extract in patients with mild COVID-19: A randomized controlled trial
Authors: Wanaratna Kulthanit , Leethong Pornvimol , Inchai Nitapha , Chueawiang Wararath , Sriraksa Pantitra , Tabmee Anutida , Sirinavin Sayomporn 
Published: July 2021

ABSTRACTObjectivesTo assess the efficacy and safety of Andrographis paniculata extract (APE) in adults with mild COVID-19.MethodsSixty-three adults aged 18-60 years, without co-morbidity, with laboratory-confirmed mild COVID-19, were randomized 1:1 to receive APE (60 mg andrographolide, t.i.d, for 5 days) or placebo within 24 hours after admission, plus standard supportive care. The outcomes were clinical recovery rates by Day 5 using self-assessment scores, pneumonia by chest X-rays, nasopharyngeal SARS-CoV-2 detection by rRT-PCR on Day 5, changes of serum CRP levels, and adverse drug reactions. Chest X-rays and blood tests for CRP, liver and renal function, were performed on Days 1, 3, and 5.ResultsBaseline characteristics of patients in the APE-treatment (n=29) and placebo-control (n=28) groups were comparable. None had self-assessment scores showing complete clinical recovery by Day 5. Pneumonia occurred in 0/29 (0%) versus 3/28 (10.7%), (p=0.112). On Day 5, patients with SARS-CoV-2 detection were 10/29 (34.5%) versus 16/28 (57.1%), (p=0.086); patients with CRP >10 mg/L were 0/29 (0%) versus 5/28 (17.9%), (p=0.023), for APE-treatment and placebo-control groups, respectively. All three patients with pneumonia had substantially rising serum CRP; and high CRP levels on Day 5. None had evidence of hematologic, hepatic or renal impairment.ConclusionEven though the study was limited by small sample size, our findings suggested promising efficacy and safety of the APE-treatment regimen in adults with mild COVID-19. Further studies, with adequate power to assure these findings, are required.
Hepatoprotective effects of Aureobasidium pullulans derived Beta 1,3-1,6 biological response modifier glucans in a STAM- animal model of non-alcoholic steatohepatitis
Authors: Ikewaki Nobunao , Kurosawa Gene , Iwasaki Masaru , Preethy Senthilkumar , Dedeepiya Vidyasagar Devaprasad , Vaddi Suryaprakash , Senthilkumar Rajappa , Levy Gary A , Abraham Samuel JK 
Published: July 2021

AbstractBackgroundNon-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are highly prevalent conditions characterized by inflammation and fibrosis of the liver which can progress to cirrhosis and hepatocellular carcinoma if left untreated. Lifestyle disorders such as obesity, diabetes and dyslipidaemia predispose to and are associated with the disease progression. Conventional modalities are mainly symptomatic, with no definite solution. Beta glucan-based biological response modifiers are a potential strategy in lieu of their beneficial metabolic effects.Aureobasidium pullulansstrains AFO-202 and N-163 beta glucans were evaluated for anti-fibrotic and anti-inflammatory hepatoprotective potentials in a NASH animal model in this study.MethodsIn the STAM™ murine model of NASH, five groups were studied for eight weeks— (1) vehicle (RO water), (2) AFO-202 beta glucan; (3) N-163 beta glucan, (4) AFO-202+N-163 beta glucan, and (5) telmisartan (standard pharmacological intervention). Evaluation of biochemical parameters in plasma and hepatic histology including Sirius red staining and F4/80 immunostaining were performed.ResultsAFO-202 beta glucan significantly decreased inflammation-associated hepatic cell ballooning and steatosis. N-163 beta glucan decreased fibrosis and inflammation significantly (p value<0.05). The combination of AFO-202 with N-163 significantly decreased the NAFLD Activity Score (NAS) compared with other groups.ConclusionThis preclinical study supports the potential of N-163 and AFO-202 beta glucans alone or in combination as potential preventive and therapeutic agent(s), for NASH.Graphical abstract
Multi-environment QTL analysis delineates a major locus associated with homoeologous exchanges for water-use efficiency and seed yield in allopolyploidBrassica napus
Authors: Raman Harsh , Raman Rosy , Pirathiban Ramethaa , McVittie Brett , Sharma Niharika , Liu Shengyi , Qiu Yu , Zhu Anyu , Killian Andrzej , Cullis Brian , Farquhar Graham D. , Williams Hilary S. , White Rosemary , Tabah David , Easton Andrew , Zhang Yuanyuan 
Published: July 2021

SummaryCanola varieties exhibit discernible variation in drought avoidance and drought escape traits, suggesting its adaptation to water-deficit environments. However, the underlying mechanisms are poorly understood.A doubled haploid (DH) population was analysed to identify QTL associated with water use efficiency (WUE) related traits. Based on the resequenced parental genome data, we developed sequence-capture based markers for fine mapping. mRNA-Seq was performed to determine the expression of candidate genes underlying QTL for carbon isotope discrimination (Δ13C).QTL contributing to main and QTL × Environment interaction effects for Δ13C and for agronomic WUE were identified. One multi-trait QTL for Δ13C, days to flower, plant height and seed yield was identified on chromosome A09, in the vicinity ofERECTA. Interestingly, this QTL region was overlapped with a homoeologous exchange event (HE), suggesting its association with the major QTL. Transcriptome analysis revealed several differentially expressed genes between parental lines, including in HE regions.This study provides insights into the complexity of WUE related genes in the context of canola adaptation to water-deficit conditions. Our results suggest that alleles for high Δ13C contribute positively to canola yield. Genetic and genomic resources developed herein could be utilised to make genetic gains for improving canola WUE.
COVID-19 and Herpes Simplex Virus Infection: A Cross-Sectional Study
Authors: Shanshal Mohammed , Ahmed Hayder Saad 
Published: July 2021

AbstractBackgroundDespite being variable and poorly characterized, the reported cutaneous manifestations of COVID-19 are of increasing concern.Aim of the StudyThis study aimed to assess the prevalence and possible association between COVID-19 and herpes simplex virus (HSV) infection.Patients and methodsA 9-item questionnaire was sent to 120 PCR-confirmed COVID-19 patients with a response rate of 66.67%. This cross-sectional observational study included 80 patients with mild to moderate COVID-19 infection who did not require hospitalization or steroid therapy.ResultsOne or more HSV infections were observed in 28 patients (35%) with COVID-19 infection, including 10 males (35.7%) and 18 females (64.29%). Of the 28 patients, fever was reported in 17 patients (75%) during COVID-19. Most of the respondents (78%) described a single HSV reactivation, 14.29% had 2 attacks, and 7.14% experienced 3 attacks. Compared to previous non-COVID-19 related HSV reactivation, the COVID-19 related attacks were more severe in 12 patients (42.85%), equally severe in 5 patients (17.85%) and less severe in 1 patient (3.57%). Interestingly, 10 patients (35.71%) developed an initial symptomatic HSV attack during COVID-19 infection.ConclusionsThis study demonstrated a possible association between COVID-19 infection and primary HSV infection and/or reactivation. The COVID-19 direct neuronal effect in addition to COVID-19 related psychological stress, fever and immunological dysregulation could play a potential role.
A connectome-based neuromarker of the non-verbal number acuity and arithmetic skills
Authors: Zhang Dai , Zhou Liqin , Yang Anmin , Li Shanshan , Chang Chunqi , Zhou Ke , Liu Jia 
Published: July 2021

AbstractThe approximate number system (ANS) is vital for survival and reproduction in animals and crucial in constructing abstract mathematical abilities in humans. Most previous neuroimaging studies focused on identifying discrete brain regions responsible for the ANS and characterizing their functions in numerosity perception. However, there lacks a neuromarker to characterize an individual’s ANS acuity, especially one based on the whole-brain functional connectivity (FC). Here, we identified a distributed brain network (i.e., numerosity network) using a connectome-based predictive modeling (CPM) analysis on the resting-state functional magnetic resonance imaging (rs-fMRI) data based on a large sample size. The summed strength of all FCs within the numerosity network could reliably predict individual differences of the ANS acuity in behavior. Furthermore, in an independent dataset from the Human Connectome Project (HCP), we found that the summed FC strength within the numerosity network could also predict individual differences in arithmetic skills. Our findings illustrate that the numerosity network we identified could be an applicable neuromarker of the non-verbal number acuity and might serve as the neural basis underlying the known link between the non-verbal number acuity and mathematical abilities.
The organization of the gravity-sensing system in zebrafish
Authors: Liu Zhikai , Hildebrand David G. C. , Morgan Joshua L. , Jia Yizhen , Slimmon Nicholas , Bagnall Martha W. 
Published: July 2021

AbstractMotor circuits develop in sequence from those governing fast movements to those governing slow. Here we examine whether upstream sensory circuits are organized by similar principles. Using serial-section electron microscopy in larval zebrafish, we generated a complete map of the gravity-sensing (utricular) system spanning from the inner ear to the brainstem. We find that both sensory tuning and developmental sequence are organizing principles of vestibular topography. Patterned rostrocaudal innervation from hair cells to afferents creates an anatomically inferred directional tuning map in the utricular ganglion, forming segregated pathways for rostral and caudal tilt. Furthermore, the mediolateral axis of the ganglion is linked to both developmental sequence and neuronal temporal dynamics. Early-born pathways carrying phasic information preferentially excite fast escape circuits, whereas later-born pathways carrying tonic signals excite slower postural and oculomotor circuits. These results demonstrate that vestibular circuits are organized by tuning direction and dynamics, aligning them with downstream motor circuits and behaviors.
Tracking neural markers of template formation and implementation in attentional inhibition under different distractor consistency
Authors: Wen Wen , Huang Zhibang , Hou Yin , Li Sheng 
Published: July 2021

AbstractPerforming visual search tasks requires optimal attention deployment to promote targets and inhibit distractors. Rejection templates based on the distractor’s feature can be built to constrain the search process. We measured electroencephalography (EEG) of human participants of both sexes when they performed a visual search task in conditions where the distractor cues were constant within a block (fixed-cueing) or changed on a trial-by-trial basis (varied-cueing). In the fixed-cueing condition, sustained decoding of the cued colors could be achieved during the retention interval and the participants with higher decoding accuracy showed larger suppression benefit of the distractor cueing in the search period. In the varied-cueing condition, the cued color could only be transiently decoded after its onset and the higher decoding accuracy was observed from the participants who demonstrated lower suppression benefit. The differential neural representations of the to-be-ignored color in the two cueing conditions as well as their reverse associations with behavioral performance implied that rejection templates were formed in the fixed-cueing condition but not in the varied-cueing condition. Additionally, we observed stronger posterior alpha lateralization and mid-frontal theta/beta power during the retention interval of the varied-cueing condition, indicating the cognitive costs in template formation caused by the trialwise change of distractor colors. Taken together, our findings revealed the neural markers associated with the critical roles of distractor consistency in linking template formation to successful inhibition.
Directional Gaussian Mixture Models of the gut microbiome elucidate microbial spatial structure
Authors: Pasarkar Amey P. , Joseph Tyler A. , Pe’er Itsik 
Published: July 2021

AbstractThe gut microbiome is spatially heterogeneous, with environmental niches contributing to the distribution and composition of microbial populations. A recently developed mapping technology, MaPS-seq, aims to characterize the spatial organization of the gut microbiome by providing data about local microbial populations. However, information about the global arrangement of these populations is lost by MaPS-seq. To address this, we propose a class of Gaussian Mixture Models (GMM) with spatial dependencies between mixture components in order to computationally recover the relative spatial arrangement of microbial communities. We demonstrate on synthetic data that our spatial models can identify global spatial dynamics, accurately cluster data, and improve parameter inference over a naive GMM. We applied our model to three MaPS-Seq datasets taken from varying regions of the mouse intestine. On cecal and distal colon datasets, we find our model accurately recapitulates known spatial behaviors of the gut microbiome, including compositional differences between mucus and lumen-associated populations. Our model also seem to capture the role of a pH gradient on microbial populations in the mouse ileum and proposes new behaviors as well.ImportanceThe spatial arrangement of the microbes in the gut microbiome is a defining characteristic of its behavior. Various experimental studies have attempted to provide glimpses into the mechanisms that contribute to microbial arrangements. However, many of these descriptions are qualitative. We developed a computational method that takes microbial spatial data and learns many of the experimentally validated spatial factors. We can then use our model to propose previously unknown spatial behaviors. Our results demonstrate that the gut microbiome, while exceptionally large, has predictable spatial patterns that can be used to help us understand its role in health and disease.Code availabilitygithub.com/amepas/Spatial_Mbiome
Speech and language impairments in behavioral variant frontotemporal dementia: A systematic review
Authors: Geraudie Amandine , Battista Petronilla , García Adolfo M. , Allen Isabel E. , Miller Zachary A. , Gorno-Tempini Maria Luisa , Montembeault Maxime 
Published: July 2021

AbstractAlthough behavioral variant frontotemporal dementia (bvFTD) is classically defined by behavioral and socio-emotional changes, impairments often extend to other cognitive functions. These include early speech and language deficits related to the disease’s core neural disruptions. Yet, their scope and clinical relevance remains poorly understood. This systematic review characterizes such disturbances in bvFTD, considering clinically, neuroanatomically, genetically, and neuropathologically defined subgroups. We included 181 experimental studies, with at least 5 bvFTD patients diagnosed using accepted criteria, comparing speech and language outcomes between bvFTD patients and healthy controls or between bvFTD subgroups. Results reveal extensive and heterogeneous deficits across cohorts, with (a) consistent lexico-semantic, orthographic, and prosodic impairments; (b) inconsistent deficits in motor speech and grammar; and (c) relative preservation of phonological skills. Also, preliminary findings suggest that the severity of speech and language deficits might be associated with global cognitive impairment, predominantly temporal or fronto-temporal atrophy andMAPTmutations (vsC9orf72). Although under-recognized, these impairments contribute to patient characterization and phenotyping, while potentially informing diagnosis and prognosis.