bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of severe acute respiratory syndrome corona virus 2 in cervico-vaginal secretion of COVID-19-affected female: A prospective observational study from India
Authors: Agarwal Mukta , Basumatary Swmkwr , Bhusan Divendu , Pati Binod Kumar 
Published: June 2021

Background: The novel severe acute respiratory syndrome corona virus 2 (also known as 2019-nCoV) is a highly infectious agent and is declared as a global public health emergency by the World Health Organisation. The main known transmission route of severe acute respiratory syndrome corona virus 2 is through respiratory air droplets. Although recent studies have revealed that the virus is detectable in the throat, blood, urine, anal swabs, tears and even faeces; however, modes of transmission other than respiratory droplets has not been studied much. Knowledge on the presence of the virus in the female genital tract may help determine the risk of sexual transmission as well as the risk of mother-to-child transmission. However, not much data are available yet regarding the presence of the virus in the female genital system. Hence, to explore the presence of the virus in the female genital system and possibility of sexual transmission, a study was conducted where in we tried to detect severe acute respiratory syndrome corona virus 2 in cervico-vaginal secretions. Methods: From July 2020 to September 2020, 35 COVID-19-positive female patients admitted to tertiary care teaching institute of Eastern India, which is now declared dedicated Corona Hospital and Centre of Excellence for COVID-19 care, who consented for the research were enrolled in this prospective observational study. Proper gynaecological history, clinical records along with laboratory findings of the patient was recorded. The possibility of the sexual transmission of the virus from female to her male partner was to be ascertained by testing the presence of severe acute respiratory syndrome corona virus 2 in the vaginal, cervical secretions by reverse transcriptase polymerase chain reaction. Results: All 35 COVID-19-positive female patients were tested for severe acute respiratory syndrome corona virus 2 in their vaginal and cervical secretions by reverse transcriptase polymerase chain reaction. All the samples were tested negative for the virus. Conclusion: Findings from this study reveals that severe acute respiratory syndrome corona virus 2 is not present in the cervical and vaginal secretions, and the possibility of transmission from female to her male partner by vaginal sexual intercourse is unlikely.
A factor VIIIa–mimetic bispecific antibody, Mim8, ameliorates bleeding upon severe vascular challenge in hemophilia A mice
Authors: Østergaard Henrik , Lund Jacob , Greisen Per J. , Kjellev Stine , Henriksen Anette , Lorenzen Nikolai , Johansson Eva , Røder Gustav , Rasch Morten G. , Johnsen Laust B. , Egebjerg Thomas , Lund Søren , Rahbek-Nielsen Henrik , Gandhi Prafull S. , Lamberth Kasper , Loftager Mette , Andersen Lisbeth M. , Bonde Amalie C. , Stavenuiter Fabian , Madsen Daniel E. , Li Xun , Holm Thomas L. , Ley Carsten D. , Thygesen Peter , Zhu Haisun , Zhou Rong , Thorn Karina , Yang Zhiru , Hermit Mette B. , Bjelke Jais R. , Hansen Bjarne G. , Hilden Ida 
Published: June 2021

Abstract
Hemophilia A is a bleeding disorder resulting from deficient factor VIII (FVIII), which normally functions as a cofactor to activated factor IX (FIXa) that facilitates activation of factor X (FX). To mimic this property in a bispecific antibody format, a screening was conducted to identify functional pairs of anti-FIXa and anti-FX antibodies, followed by optimization of functional and biophysical properties. The resulting bispecific antibody (Mim8) assembled efficiently with FIXa and FX on membranes, and supported activation with an apparent equilibrium dissociation constant of 16 nM. Binding affinity with FIXa and FX in solution was much lower, with equilibrium dissociation constant values for FIXa and FX of 2.3 and 1.5 µM, respectively. In addition, the activity of Mim8 was dependent on stimulatory activity contributed by the anti-FIXa arm, which enhanced the proteolytic activity of FIXa by 4 orders of magnitude. In hemophilia A plasma and whole blood, Mim8 normalized thrombin generation and clot formation, with potencies 13 and 18 times higher than a sequence-identical analogue of emicizumab. A similar potency difference was observed in a tail vein transection model in hemophilia A mice, whereas reduction of bleeding in a severe tail-clip model was observed only for Mim8. Furthermore, the pharmacokinetic parameters of Mim8 were investigated and a half-life of 14 days shown in cynomolgus monkeys. In conclusion, Mim8 is an activated FVIII mimetic with a potent and efficacious hemostatic effect based on preclinical data.
Specific targeting of the KRAS mutational landscape in myeloma as a tool to unveil the elicited antitumor activity
Authors: Sacco Antonio , Federico Cinzia , Todoerti Katia , Ziccheddu Bachisio , Palermo Valentina , Giacomini Arianna , Ravelli Cosetta , Maccarinelli Federica , Bianchi Giada , Belotti Angelo , Ribolla Rossella , Favasuli Vanessa , Revenko Alexey S. , Macleod A. Robert , Willis Brandon , Cai Hongbo , Hauser Joana , Rooney Claire , Willis Sophie E. , Martin Philip Lloyd , Staniszewska Anna , Ambrose Helen , Hanson Lyndsey , Cattaneo Chiara , Tucci Alessandra , Rossi Giuseppe , Ronca Roberto , Neri Antonino , Mitola Stefania , Bolli Niccolò , Presta Marco , Moschetta Michele , Ross Sarah , Roccaro Aldo M. 
Published: June 2021

Abstract
Alterations in KRAS have been identified as the most recurring somatic variants in the multiple myeloma (MM) mutational landscape. Combining DNA and RNA sequencing, we studied 756 patients and observed KRAS as the most frequently mutated gene in patients at diagnosis; in addition, we demonstrated the persistence or de novo occurrence of the KRAS aberration at disease relapse. Small-molecule inhibitors targeting KRAS have been developed; however, they are selective for tumors carrying the KRASG12C mutation. Therefore, there is still a need to develop novel therapeutic approaches to target the KRAS mutational events found in other tumor types, including MM. We used AZD4785, a potent and selective antisense oligonucleotide that selectively targets and downregulates all KRAS isoforms, as a tool to dissect the functional sequelae secondary to KRAS silencing in MM within the context of the bone marrow niche and demonstrated its ability to significantly silence KRAS, leading to inhibition of MM tumor growth, both in vitro and in vivo, and confirming KRAS as a driver and therapeutic target in MM.
Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis
Authors: Vukmirovic Milica , Yan Xiting , Gibson Kevin F. , Gulati Mridu , Schupp Jonas C. , DeIuliis Giuseppe , Adams Taylor S. , Hu Buqu , Mihaljinec Antun , Woolard Tony N. , Lynn Heather , Emeagwali Nkiruka , Herzog Erica L. , Chen Edward S. , Morris Alison , Leader Joseph K. , Zhang Yingze , Garcia Joe G.N. , Maier Lisa A. , Collman Ronald G. , Drake Wonder P. , Becich Michael J. , Hochheiser Harry , Wisniewski Steven R. , Benos Panayiotis V. , Moller David R. , Prasse Antje , Koth Laura L. , Kaminski Naftali 
Published: June 2021

BackgroundSarcoidosis is a multisystem granulomatous disease of unknown origin with a variable and often unpredictable course and pattern of organ involvement. In this study we sought to identify specific bronchoalveolar lavage (BAL) cell gene expression patterns indicative of distinct disease phenotypic traits.MethodsRNA sequencing by Ion Torrent Proton was performed on BAL cells obtained from 215 well-characterised patients with pulmonary sarcoidosis enrolled in the multicentre Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Weighted gene co-expression network analysis and nonparametric statistics were used to analyse genome-wide BAL transcriptome. Validation of results was performed using a microarray expression dataset of an independent sarcoidosis cohort (Freiburg, Germany; n=50).ResultsOur supervised analysis found associations between distinct transcriptional programmes and major pulmonary phenotypic manifestations of sarcoidosis including T-helper type 1 (Th1) and Th17 pathways associated with hilar lymphadenopathy, transforming growth factor-β1 (TGFB1) and mechanistic target of rapamycin (MTOR) signalling with parenchymal involvement, and interleukin (IL)-7 and IL-2 with airway involvement. Our unsupervised analysis revealed gene modules that uncovered four potential sarcoidosis endotypes including hilar lymphadenopathy with increased acute T-cell immune response; extraocular organ involvement with PI3K activation pathways; chronic and multiorgan disease with increased immune response pathways; and multiorgan involvement, with increased IL-1 and IL-18 immune and inflammatory responses. We validated the occurrence of these endotypes using gene expression, pulmonary function tests and cell differentials from Freiburg.ConclusionTaken together, our results identify BAL gene expression programmes that characterise major pulmonary sarcoidosis phenotypes and suggest the presence of distinct disease molecular endotypes.
MULTI-PHACET: multidimensional clinical phenotyping of hospitalised acute COPD exacerbations
Authors: MacDonald Martin I. , Osadnik Christian R. , Bulfin Lauren , Leahy Elizabeth , Leong Paul , Shafuddin Eskandarain , Hamza Kais , King Paul T. , Bardin Philip G. 
Published: June 2021

BackgroundThe generic term “exacerbation” does not reflect the heterogeneity of acute exacerbations of COPD (AECOPD). We utilised a novel algorithmic strategy to profile exacerbation phenotypes based on underlying aetiologies.MethodsPatients hospitalised for AECOPD (n=146) were investigated for aetiological contributors summarised in a mnemonic acronym ABCDEFGX (A: airway virus; B: bacterial; C: co-infection; D: depression/anxiety; E: eosinophils; F: failure (cardiac); G: general environment; X: unknown). Results from clinical investigations were combined to construct AECOPD phenotypes. Relationships to clinical outcomes were examined for both composite phenotypes and their specific aetiological components. Aetiologies identified at exacerbation were reassessed at outpatient follow-up.ResultsHospitalised AECOPDs were remarkably diverse, with 26 distinct phenotypes identified. Multiple aetiologies were common (70%) and unidentifiable aetiology rare (4.1%). If viruses were detected (29.5%), patients had longer hospitalisation (7.7±5.6versus6.0±3.9 days, p=0.03) despite fewer “frequent exacerbators” (9.3%versus37%, p=0.001) and lower mortality at 1 year (p=0.03). If bacterial infection was found (40.4%), patients were commonly “frequent exacerbators” (44%versus18.4%, p=0.001). Eosinophilic exacerbations (28%) were associated with lower pH (7.32±0.06versus7.36±0.09, p=0.04), higher venous carbon dioxide tension (PvCO2) (53.7±10.5versus48.8±12.8, p=0.04), greater noninvasive ventilation (NIV) usage (34.1%versus18.1%) but shorter hospitalisation (4 (3–5)versus6 (4–9) days, p<0.001) and lower infection rates (41.4%versus80.9%, p<0.0001). Cardiac dysfunction and severe anxiety/depression were common in both infective and non-infective exacerbations. Characteristics identified at exacerbation often persisted after recovery.ConclusionsHospitalised AECOPDs have numerous causes, often in combination, that converge in complex, multi-faceted phenotypes. Clinically important differences in outcomes suggest that a phenotyping strategy based on aetiologies can enhance AECOPD management.
Targeting dynamic hyperinflation in moderate-to-severe asthma: a randomised controlled trial
Authors: van der Meer Akke-Nynke , de Jong Kim , Hoekstra-Kuik Aranka , Bel Elisabeth H. , ten Brinke Anneke 
Published: June 2021

BackgroundDynamic hyperinflation is highly prevalent in moderate-to-severe asthma, which may significantly impede activities of daily life. We hypothesised that dynamic hyperinflation in asthma is due to inflammation of large and small airways and can be reduced by systemic anti-inflammatory treatment. Therefore, we investigated the effect of systemic glucocorticoids on dynamic hyperinflation in moderate-to-severe asthma patients and explored the relationships between inflammatory markers and changes in dynamic hyperinflation.MethodsIn this randomised placebo-controlled trial we included 32 asthma patients on inhaled glucocorticoid therapy showing dynamic hyperinflation, defined by a ≥10% reduction in inspiratory capacity measured by standardised metronome-paced tachypnea test. Patients received either triamcinolone (80 mg) or placebo intramuscularly. Before and 2 weeks after treatment, patients completed respiratory health questionnaires, had blood eosinophils and exhaled nitric oxide levels measured, and underwent lung function and dynamic hyperinflation testing.ResultsAfter adjustment for potential confounders, dynamic hyperinflation was significantly reduced by 28.1% in the triamcinolone group and increased by 9.4% in the placebo group (p=0.027). In the triamcinolone-treated patients, the reduction in dynamic hyperinflation was greater in patients with higher blood eosinophils at baseline (r=−0.592, p=0.020) and tended to be associated with a reduction in blood eosinophils (r=0.412, p=0.127) and exhaled nitric oxide (r=0.442, p=0.099).ConclusionsThis exploratory study suggests that dynamic hyperinflation in asthma can be reduced by systemic anti-inflammatory treatment, particularly in patients with elevated blood eosinophils. This supports the hypothesis that dynamic hyperinflation in asthma is due to airway inflammation and should be considered an important target for treatment.
Prospective association between use of electronic cigarettes and use of conventional cigarettes: a systematic review and meta-analysis
Authors: Adermark Louise , Galanti Maria Rosaria , Ryk Charlotta , Gilljam Hans , Hedman Linnea 
Published: June 2021

ObjectiveThe aim of this systematic review and meta-analysis was to assess the association between e-cigarette use and subsequent initiation or recurrence of cigarette smoking.Data sourcesA systematic literature search was finalised on 11 November 2019 using PubMed (including MEDLINE), EMBASE, Cochrane Library, Scopus, PubMed Health, NICE Evidence Search, PROSPERO, CRD and PsycInfo.Study selectionStudies were included if meeting the following criteria: reporting empirical results; longitudinal observational design with a minimum of 3 months of follow-up; including general population samples; allowing for the comparison between users and nonusers of e-cigarettes. Studies rated as having high risk of bias were excluded. Studies were independently assessed by at least two authors. The procedures described by PRISMA were followed, and the quality of evidence was rated using GRADE.Data synthesis30 longitudinal studies from 22 different cohorts assessing e-cigarette use among nonsmokers or never-smokers at baseline, and subsequent use of cigarette smoking at follow-up, were included in this review. A random-effects meta-analysis based on 89 076 participants showed a pooled unadjusted odds ratio (OR) of cigarette smoking among baseline nonsmoker e-cigarette users compared with nonusers of 4.68 (CI 3.64–6.02), while the adjusted OR was 3.37 (CI 2.68–4.24). These results were consistent irrespective of whether the outcome was measured as ever-smoking or as past 30-day smoking. The evidence was graded as moderate.ConclusionsUse of e-cigarettes may predict the initiation or recurrence of cigarette smoking.
Designs of InGaN Micro-LED Structure for Improving Quantum Efficiency at Low Current Density
Authors: Lu Shiqiang , Li Jinchai , Huang Kai , Liu Guozhen , Zhou Yinghui , Cai Duanjun , Zhang Rong , Kang Junyong 
Published: June 2021

AbstractHere we report a comprehensive numerical study for the operating behavior and physical mechanism of nitride micro-light-emitting-diode (micro-LED) at low current density. Analysis for the polarization effect shows that micro-LED suffers a severer quantum-confined Stark effect at low current density, which poses challenges for improving efficiency and realizing stable full-color emission. Carrier transport and matching are analyzed to determine the best operating conditions and optimize the structure design of micro-LED at low current density. It is shown that less quantum well number in the active region enhances carrier matching and radiative recombination rate, leading to higher quantum efficiency and output power. Effectiveness of the electron blocking layer (EBL) for micro-LED is discussed. By removing the EBL, the electron confinement and hole injection are found to be improved simultaneously, hence the emission of micro-LED is enhanced significantly at low current density. The recombination processes regarding Auger and Shockley–Read–Hall are investigated, and the sensitivity to defect is highlighted for micro-LED at low current density.Synopsis: The polarization-induced QCSE, the carrier transport and matching, and recombination processes of InGaN micro-LEDs operating at low current density are numerically investigated. Based on the understanding of these device behaviors and mechanisms, specifically designed epitaxial structures including two QWs, highly doped or without EBL and p-GaN with high hole concentration for the efficient micro-LED emissive display are proposed. The sensitivity to defect density is also highlighted for micro-LED.
RNAdetector: a free user-friendly stand-alone and cloud-based system for RNA-Seq data analysis
Authors: La Ferlita Alessandro , Alaimo Salvatore , Di Bella Sebastiano , Martorana Emanuele , Laliotis Georgios I. , Bertoni Francesco , Cascione Luciano , Tsichlis Philip N. , Ferro Alfredo , Bosotti Roberta , Pulvirenti Alfredo 
Published: June 2021

Abstract
Background
RNA-Seq is a well-established technology extensively used for transcriptome profiling, allowing the analysis of coding and non-coding RNA molecules. However, this technology produces a vast amount of data requiring sophisticated computational approaches for their analysis than other traditional technologies such as Real-Time PCR or microarrays, strongly discouraging non-expert users. For this reason, dozens of pipelines have been deployed for the analysis of RNA-Seq data. Although interesting, these present several limitations and their usage require a technical background, which may be uncommon in small research laboratories. Therefore, the application of these technologies in such contexts is still limited and causes a clear bottleneck in knowledge advancement.

Results
Motivated by these considerations, we have developed RNAdetector, a new free cross-platform and user-friendly RNA-Seq data analysis software that can be used locally or in cloud environments through an easy-to-use Graphical User Interface allowing the analysis of coding and non-coding RNAs from RNA-Seq datasets of any sequenced biological species.

Conclusions
RNAdetector is a new software that fills an essential gap between the needs of biomedical and research labs to process RNA-Seq data and their common lack of technical background in performing such analysis, which usually relies on outsourcing such steps to third party bioinformatics facilities or using expensive commercial software.
Lactobacillus rhamnosus GG modifies the metabolome of pathobionts in gnotobiotic mice
Authors: Kim Jinhee , Balasubramanian Iyshwarya , Bandyopadhyay Sheila , Nadler Ian , Singh Rajbir , Harlan Danielle , Bumber Amanda , He Yuling , Kerkhof Lee J. , Gao Nan , Su Xiaoyang , Ferraris Ronaldo P. 
Published: June 2021

Abstract
Background
Lactobacillus rhamnosus GG (LGG) is the most widely used probiotic, but the mechanisms underlying its beneficial effects remain unresolved. Previous studies typically inoculated LGG in hosts with established gut microbiota, limiting the understanding of specific impacts of LGG on host due to numerous interactions among LGG, commensal microbes, and the host. There has been a scarcity of studies that used gnotobiotic animals to elucidate LGG-host interaction, in particular for gaining specific insights about how it modifies the metabolome. To evaluate whether LGG affects the metabolite output of pathobionts, we inoculated with LGG gnotobiotic mice containing Propionibacterium acnes, Turicibacter sanguinis, and Staphylococcus aureus (PTS).

Results
16S rRNA sequencing of fecal samples by Ion Torrent and MinION platforms showed colonization of germ-free mice by PTS or by PTS plus LGG (LTS). Although the body weights and feeding rates of mice remained similar between PTS and LTS groups, co-associating LGG with PTS led to a pronounced reduction in abundance of P. acnes in the gut. Addition of LGG or its secretome inhibited P. acnes growth in culture. After optimizing procedures for fecal metabolite extraction and metabolomic liquid chromatography-mass spectrometry analysis, unsupervised and supervised multivariate analyses revealed a distinct separation among fecal metabolites of PTS, LTS, and germ-free groups. Variables-important-in-projection scores showed that LGG colonization robustly diminished guanine, ornitihine, and sorbitol while significantly elevating acetylated amino acids, ribitol, indolelactic acid, and histamine. In addition, carnitine, betaine, and glutamate increased while thymidine, quinic acid and biotin were reduced in both PTS and LTS groups. Furthermore, LGG association reduced intestinal mucosal expression levels of inflammatory cytokines, such as IL-1α, IL-1β and TNF-α.

Conclusions
LGG co-association had a negative impact on colonization of P. acnes, and markedly altered the metabolic output and inflammatory response elicited by pathobionts.
Poplar aquaporin PIP1;1 promotes Arabidopsis growth and development
Authors: Leng Huani , Jiang Cheng , Song Xueqin , Lu Mengzhu , Wan Xianchong 
Published: June 2021

Abstract
Background
Root hydraulic conductance is primarily determined by the conductance of living tissues to radial water flow. Plasma membrane intrinsic proteins (PIPs) in root cortical cells are important for plants to take up water and are believed to be directly involved in cell growth.

Results
In this study, we found that constitutive overexpression of the poplar root-specific gene PtoPIP1;1 in Arabidopsis accelerated bolting and flowering. At the early stage of the developmental process, PtoPIP1;1 OE Arabidopsis exhibited faster cell growth in both leaves and roots. The turgor pressure of plants was correspondingly increased in PtoPIP1;1 OE Arabidopsis, and the water status was changed. At the same time, the expression levels of flowering-related genes (CRY1, CRY2 and FCA) and hub genes in the regulatory networks underlying floral timing (FT and SOC1) were significantly upregulated in OE plants, while the floral repressor FLC gene was significantly downregulated.

Conclusions
Taken together, the results of our study indicate that constitutive overexpression of PtoPIP1;1 in Arabidopsis accelerates bolting and flowering through faster cell growth in both the leaf and root at an early stage of the developmental process. The autonomous pathway of flowering regulation may be executed by monitoring developmental age. The increase in turgor and changes in water status with PtoPIP1;1 overexpression play a role in promoting cell growth.