bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a rabies virus-based retrograde tracer with high trans-monosynaptic efficiency by reshuffling glycoprotein
Authors: Jia Fan , Li Li , Liu Haizhou , Lv Pei , Shi Xiangwei , Wu Yang , Ling Chen , Xu Fuqiang 
Published: July 2021

AbstractRabies virus (RV) is the most widely used vector for mapping neural circuits. Previous studies have shown that the RV glycoprotein can be a target to improve the retrograde transsynaptic tracing efficiency. However, the current versions still label only a small portion of all presynaptic neurons. Here, we reshuffled the oG sequence, a chimeric glycoprotein, with positive codon pair bias score (CPBS) based on bioinformatic analysis of mouse codon pair bias, generating ooG, a further optimized glycoprotein. Our experimental data reveal that the ooG has a higher expression level than the oG in vivo, which significantly increases the tracing efficiency by up to 12.6 and 62.1-fold compared to oG and B19G, respectively. The new tool can be used for labeling neural circuits Therefore, the approach reported here provides a convenient, efficient and universal strategy to improve protein expression for various application scenarios such as trans-synaptic tracing efficiency, cell engineering, and vaccine and oncolytic virus designs.
MiR-585-3p suppresses tumor proliferation and migration by directly targeting CAPN9 in high grade serous ovarian cancer
Authors: Lu Xiaoyuan , Li Guilin , Liu Sicong , Wang Haihong , Chen Buze 
Published: July 2021

Abstract
Background
Aberrant expression of microRNAs (miRNAs) contributes to the development of high grade serous ovarian cancer (HGSOC). However, the molecular mechanism by which miRNA-585-3p mediates high-grade serous ovarian carcinogenesis is unclear. This study aims to investigate the specific mechanism of action of miR-585-3p in HGSOC.

Methods
Expression of miR-585-3p in HGSOC tissues and cell lines was detected by qRT-PCR. Cell viability and migration were detected using MTT and transwell system. The expression of target genes and target proteins of miR-585-3p was detected by dual luciferase reporter assay and western blot.

Results
The expression of miR-585-3p was significantly lower in HGSOC tissues and cells than in normal ovarian tissues and cell lines. In HGSOC tissues, CAPN9 expression was inversely correlated with miR-585-3p expression. MiR-585-3p inhibited the proliferation and migration of HGSOC cells. MiR-585-3p bound to the 3'-untranslated region (UTR) of CAPN9 and inhibits CAPN9 expression. Overexpression of CAPN9 reduced the inhibitory effect of miR-585-3p in HGSOC cells.

Conclusions
miR-585-3p is significantly down-regulated in HGSOC tissues and cell lines. MiR-585-3p inhibits the proliferation and migration of HGSOC cells by targeting CAPN9.
Diagnostic yield of routine daily blood culture in patients on veno-arterial extracorporeal membrane oxygenation
Authors: de Roux Quentin , Renaudier Marie , Bougouin Wulfran , Boccara Johanna , Fihman Vincent , Lepeule Raphaël , Cherait Chamsedine , Fiore Antonio , Hemery François , Decousser Jean-Winoc , Langeron Olivier , Mongardon Nicolas 
Published: July 2021

AbstractBackgroundBloodstream infections (BSIs) are frequent on veno-arterial extracorporeal membrane oxygenation (V-A ECMO). Performing routine blood cultures (BCs) may identify early paucisymptomatic BSIs. We investigated the contribution of systematic daily BCs to detect BSIs on V-A ECMO.MethodsThis was a retrospective study including all adult patients requiring V-A ECMO and surviving more than 24 h. Our protocol included routine daily BCs, from V-A ECMO insertion up to 5 days after withdrawal; other BCs were performed on-demand.ResultsOn the 150 V-A ECMO included, 2146 BCs were performed (1162 routine and 984 on-demand BCs); 190 (9%) were positive, including 68 contaminants. Fifty-one (4%) routine BCs revealed BSIs; meanwhile, 71 (7%) on-demand BCs revealed BSIs (p = 0.005). Performing routine BCs was negatively associated with BSIs diagnosis (OR 0.55, 95% CI [0.38; 0.81],p = 0.002). However, 16 (31%) BSIs diagnosed by routine BCs would have been missed by on-demand BCs. Independent variables for BSIs diagnosis after routine BCs were: V-A ECMO for cardiac graft failure (OR 2.43, 95% CI [1.20; 4.92],p = 0.013) and sampling with on-going antimicrobial therapy (OR 2.15, 95% CI [1.08; 4.27],p = 0.029) or renal replacement therapy (OR 2.05, 95% CI [1.10; 3.81],p = 0.008). Without these three conditions, only two BSIs diagnosed with routine BCs would have been missed by on-demand BCs sampling.ConclusionsAlthough routine daily BCs are less effective than on-demand BCs and expose to contamination and inappropriate antimicrobial therapy, a policy restricted to on-demand BCs would omit a significant proportion of BSIs. This argues for a tailored approach to routine daily BCs on V-A ECMO, based on risk factors for positivity.
Estimating the wave 1 and wave 2 infection fatality rates from SARS-CoV-2 in India
Authors: Purkayastha Soumik , Kundu Ritoban , Bhaduri Ritwik , Barker Daniel , Kleinsasser Michael , Ray Debashree , Mukherjee Bhramar 
Published: July 2021

Abstract
Objective
There has been much discussion and debate around the underreporting of COVID-19 infections and deaths in India. In this short report we first estimate the underreporting factor for infections from publicly available data released by the Indian Council of Medical Research on reported number of cases and national seroprevalence surveys. We then use a compartmental epidemiologic model to estimate the undetected number of infections and deaths, yielding estimates of the corresponding underreporting factors. We compare the serosurvey based ad hoc estimate of the infection fatality rate (IFR) with the model-based estimate. Since the first and second waves in India are intrinsically different in nature, we carry out this exercise in two periods: the first wave (April 1, 2020–January 31, 2021) and part of the second wave (February 1, 2021–May 15, 2021). The latest national seroprevalence estimate is from January 2021, and thus only relevant to our wave 1 calculations.

Results
Both wave 1 and wave 2 estimates qualitatively show that there is a large degree of “covert infections” in India, with model-based estimated underreporting factor for infections as 11.11 (95% credible interval (CrI) 10.71–11.47) and for deaths as 3.56 (95% CrI 3.48–3.64) for wave 1. For wave 2, underreporting factor for infections escalate to 26.77 (95% CrI 24.26–28.81) and to 5.77 (95% CrI 5.34–6.15) for deaths. If we rely on only reported deaths, the IFR estimate is 0.13% for wave 1 and 0.03% for part of wave 2. Taking underreporting of deaths into account, the IFR estimate is 0.46% for wave 1 and 0.18% for wave 2 (till May 15). Combining waves 1 and 2, as of May 15, while India reported a total of nearly 25 million cases and 270 thousand deaths, the estimated number of infections and deaths stand at 491 million (36% of the population) and 1.21 million respectively, yielding an estimated (combined) infection fatality rate of 0.25%. There is considerable variation in these estimates across Indian states. Up to date seroprevalence studies and mortality data are needed to validate these model-based estimates.
Pharmacokinetic evaluation of Chalcone derivatives with antimalarial activity in New Zealand White Rabbits
Authors: Sinha Shweta , Prakash Ajay , Medhi Bikash , Sehgal Alka , Batovska Daniela I. , Sehgal Rakesh 
Published: July 2021

Abstract
Objective
Malaria is a major global health concern with the urgent need for new treatment alternatives due to the alarming increase of drug-resistant Plasmodium strains. Chalcones and its derivatives are important pharmacophores showing antimalarial activity. Determination of the pharmacokinetic variables at the preliminary step of drug development for any drug candidates is an essential component of in vivo antimalarial efficacy tests. Substandard pharmacokinetic variables are often responsible for insufficient therapeutic effect. Therefore, three chalcone derivatives, 1, 2, and 3, having antimalarial potency were studied further for potential therapeutic efficacy.

Results
In vivo pharmacokinetic studies of these three derivatives were performed on New Zealand White rabbits. The three derivatives were administered intra-peritoneally or orally at effective dose concentration and blood samples at different time points were collected. The determination of drug concentration was done through reverse phase-high performance liquid chromatography. The peak plasma concentration of derivative 1, 2, and 3 were 1.96 ± 0.46 µg/mL (intraperitoneal route), 69.89 ± 5.49 µg/mL (oral route), and 3.74 ± 1.64 µg/mL (oral route). The results indicate a very low bioavailability of these derivatives. The present study gives a benchmark to advance the investigation of more derivatives in order to revamp the pharmacokinetic variables while maintaining both potency and metabolic constancy.
Lewy Body Dementia Association’s Industry Advisory Council: proceedings of the second annual meeting
Authors: Goldman Jennifer G. , Boeve Bradley F. , Armstrong Melissa J. , Galasko Doug R. , Galvin James E. , Irwin David J. , Leverenz James B. , Marder Karen , Abler Victor , Biglan Kevin , Irizarry Michael C. , Keller Bill , Lai Robert , Munsie Leanne , Belleville Michael , Chaney Ondrea , Richard Ian , Taylor Angela , Graham Todd 
Published: July 2021

AbstractIn 2019, the Lewy Body Dementia Association formed an Industry Advisory Council to bring together a collaborative group of stakeholders with the goal of accelerating clinical research into Lewy body dementia treatments. At the second annual meeting of the Industry Advisory Council, held virtually on June 18, 2020, the key members presented ongoing and planned efforts toward the council’s goals. The meeting also featured a discussion about the effects of the COVID-19 pandemic on Lewy body dementia clinical research, lessons learned from that experience, and how those lessons can be applied to the design and conduct of future clinical trials. This report provides a brief summary of the meeting proceedings with a focus on efforts to improve and adapt future Lewy body dementia clinical research.
Pre-existing asthma as a comorbidity does not modify cytokine responses and severity of COVID-19
Authors: Luo Jian , Chen Yi-Ling , Chen Wentao , Duncan David A. , Mentzer Alexander , Knight Julian C. , Ogg Graham , Klenerman Paul , Pavord Ian D. , Xue Luzheng 
Published: July 2021

Abstract
Background
A significant portion of COVID-19 sufferers have asthma. The impacts of asthma on COVID-19 progression are still unclear but a modifying effect is plausible as respiratory viruses are acknowledged to be an important trigger for asthma exacerbations and a different, potentially type-2 biased, immune response might occur. In this study, we compared the blood circulating cytokine response to COVID-19 infection in patients with and without asthma.

Methods
Plasma samples and clinical information were collected from 80 patients with mild (25), severe (36) or critical (19) COVID-19 and 29 healthy subjects at the John Radcliffe Hospital, Oxford, UK. The concentrations of 51 circulating proteins in the plasma samples were measured with Luminex and compared between groups.

Results
Total 16 pre-existing asthma patients were found (3 in mild, 10 in severe, and 3 in critical COVID-19). The prevalence of asthma in COVID-19 severity groups did not suggest a clear correlation between asthma and COVID-19 severity. Within the same COVID-19 severity group, no differences were observed between patients with or without asthma on oxygen saturation, CRP, neutrophil counts, and length of hospital stay. The mortality in the COVID-19 patients with asthma (12.5%) was not higher than that in patients without asthma (17.2%). No significant difference was found between asthmatic and non-asthmatic in circulating cytokine response in different COVID-19 severity groups, including the cytokines strongly implicated in COVID-19 such as CXCL10, IL-6, CCL2, and IL-8.

Conclusions
Pre-existing asthma was not associated with an enhanced cytokine response after COVID-19 infection, disease severity or mortality.
Quantitative ultrasound shear wave elastography (USWE)-measured tissue stiffness correlates with PIRADS scoring of MRI and Gleason score on whole-mount histopathology of prostate cancer: implications for ultrasound image-guided targeting approach
Authors: Ageeli Wael , Wei Cheng , Zhang Xinyu , Szewcyk-Bieda Magdalena , Wilson Jennifer , Li Chunhui , Nabi Ghulam 
Published: July 2021

Abstract
Objective
To correlate quantitative tissue stiffness measurements obtained by transrectal ultrasound shear wave elastography (USWE) with PI-RADS scoring of multiparametric magnetic imaging resonance (mpMRI) using Gleason scores of radical prostatectomy as a reference standard.

Patients and methods
196 men with localised prostate cancer were prospectively recruited into the study and had quantitative prostate tissue stiffness measurements in kilopascals (kPa) using transrectal USWE prior to radical prostatectomy. PI-RADS scores of mpMRI were also obtained in all the men. Imaging and histopathology of radical prostatectomy specimen were oriented to each other using patient specific customised 3D moulds to guide histopathology grossing of radical prostatectomy specimens. All included patients had confirmed PCa on TRUS-guided biopsies, had both USWE and mpMRI imaging data, and underwent radical prostatectomy. Chi-square test with 95% confidence interval was used to assess the difference between Gleason score (GS) of radical prostatectomy and PI-RADS classification, as well as GS of radical prostatectomy and stiffness (in Kpa) using USWE. The correlation coefficient (r) was calculated in order to investigate relation between PI-RADS classification and tissue stiffness in kPa.

Results
There was a statistically significant correlation between USWE-measured tissue stiffness and GS (χ2 (2, N = 196) = 23.577, p < 0.001). Also, there was a statistically significant correlation between Gleason score and PI-RADS score (χ2 (2, N = 196) = 12.838, p = 0.002). High PIRADS on MRI and high stiffness on USWE (> 100 kPa) detected more than 80% and 90% high risk prostate cancer disease. However, a weak correlation coefficient of 0.231 was observed between PI-RADS score and level of tissue stiffness measured in kPa.

Conclusion
Quantitative USWE and mpMRI using PI-RADS classification provide a good degree of prediction for Gleason score of clinically significant prostate cancer (csPCa). Stiffer lesions on ultrasound showed a weak correlation with PI-RADS scoring system. USWE could be used to target suspected prostate cancer.
mRNP granule proteins Fmrp and Dcp1a differentially regulate mRNP complexes to contribute to control of muscle stem cell quiescence and activation
Authors: Roy Nainita , Sundar Swetha , Pillai Malini , Patell-Socha Farah , Ganesh Sravya , Aloysius Ajoy , Rumman Mohammed , Gala Hardik , Hughes Simon M. , Zammit Peter S. , Dhawan Jyotsna 
Published: July 2021

Abstract
Background
During skeletal muscle regeneration, satellite stem cells use distinct pathways to repair damaged myofibers or to self-renew by returning to quiescence. Cellular/mitotic quiescence employs mechanisms that promote a poised or primed state, including altered RNA turnover and translational repression. Here, we investigate the role of mRNP granule proteins Fragile X Mental Retardation Protein (Fmrp) and Decapping protein 1a (Dcp1a) in muscle stem cell quiescence and differentiation.

Methods
Using isolated single muscle fibers from adult mice, we established differential enrichment of mRNP granule proteins including Fmrp and Dcp1a in muscle stem cells vs. myofibers. We investigated muscle tissue homeostasis in adult Fmr1-/- mice, analyzing myofiber cross-sectional area in vivo and satellite cell proliferation ex vivo. We explored the molecular mechanisms of Dcp1a and Fmrp function in quiescence, proliferation and differentiation in a C2C12 culture model. Here, we used polysome profiling, imaging and RNA/protein expression analysis to establish the abundance and assembly status of mRNP granule proteins in different cellular states, and the phenotype of knockdown cells.

Results
Quiescent muscle satellite cells are enriched for puncta containing the translational repressor Fmrp, but not the mRNA decay factor Dcp1a. MuSC isolated from Fmr1-/- mice exhibit defective proliferation, and mature myofibers show reduced cross-sectional area, suggesting a role for Fmrp in muscle homeostasis. Expression and organization of Fmrp and Dcp1a varies during primary MuSC activation on myofibers, with Fmrp puncta prominent in quiescence, but Dcp1a puncta appearing during activation/proliferation. This reciprocal expression of Fmrp and Dcp1a puncta is recapitulated in a C2C12 culture model of quiescence and activation: consistent with its role as a translational repressor, Fmrp is enriched in non-translating mRNP complexes abundant in quiescent myoblasts; Dcp1a puncta are lost in quiescence, suggesting stabilized and repressed transcripts. The function of each protein differs during proliferation; whereas Fmrp knockdown led to decreased proliferation and lower cyclin expression, Dcp1a knockdown led to increased cell proliferation and higher cyclin expression. However, knockdown of either Fmrp or Dcp1a led to compromised differentiation. We also observed cross-regulation of decay versus storage mRNP granules; knockdown of Fmrp enhances accumulation of Dcp1a puncta, whereas knockdown of Dcp1a leads to increased Fmrp in puncta.

Conclusions
Taken together, our results provide evidence that the balance of mRNA turnover versus utilization is specific for distinct cellular states.
Transcriptomic analysis of equine chorioallantois reveals immune networks and molecular mechanisms involved in nocardioform placentitis
Authors: El-Sheikh Ali Hossam , Loux Shavahn C. , Kennedy Laura , Scoggin Kirsten E. , Dini Pouya , Fedorka Carleigh E. , Kalbfleisch Theodore S. , Esteller-Vico Alejandro , Horohov David W. , Erol Erdal , Carter Craig N. , Smith Jackie L. , Ball Barry A. 
Published: July 2021

AbstractNocardioform placentitis (NP) continues to result in episodic outbreaks of abortion and preterm birth in mares and remains a poorly understood disease. The objective of this study was to characterize the transcriptome of the chorioallantois (CA) of mares with NP. The CA were collected from mares with confirmed NP based upon histopathology, microbiological culture and PCR for Amycolatopsis spp. Samples were collected from the margin of the NP lesion (NPL, n = 4) and grossly normal region (NPN, n = 4). Additionally, CA samples were collected from normal postpartum mares (Control; CRL, n = 4). Transcriptome analysis identified 2892 differentially expressed genes (DEGs) in NPL vs. CRL and 2450 DEGs in NPL vs. NPN. Functional genomics analysis elucidated that inflammatory signaling, toll-like receptor signaling, inflammasome activation, chemotaxis, and apoptosis pathways are involved in NP. The increased leukocytic infiltration in NPL was associated with the upregulation of matrix metalloproteinase (MMP1, MMP3, and MMP8) and apoptosis-related genes, such as caspases (CASP3 and CASP7), which could explain placental separation associated with NP. Also, NP was associated with downregulation of several placenta-regulatory genes (ABCG2, GCM1, EPAS1, and NR3C1), angiogenesis-related genes (VEGFA, FLT1, KDR, and ANGPT2), and glucose transporter coding genes (GLUT1, GLUT10, and GLUT12), as well as upregulation of hypoxia-related genes (HIF1A and EGLN3), which could elucidate placental insufficiency accompanying NP. In conclusion, our findings revealed for the first time, the key regulators and mechanisms underlying placental inflammation, separation, and insufficiency during NP, which might lead to the development of efficacious therapies or diagnostic aids by targeting the key molecular pathways.
Preventive interventions to reduce the burden of rheumatic heart disease in populations at risk: a systematic review protocol
Authors: Shimanda Panduleni Penipawa , Shumba Tonderai Washington , Brunström Mattias , Söderberg Stefan , Lindholm Lars , Iipinge Scholastika Ndatinda , Norström Fredrik 
Published: July 2021

Abstract
Background
Rheumatic heart disease is preventable, yet associated with significant health burden, mostly in low-resourced settings. It is prevalent among children and young adults living in impoverished areas. Primordial, primary, and secondary preventive measures have been recommended through health interventions and comprehensive programmes, although most implemented interventions are the high-resourced settings. The proposed review aims to synthesise the evidence of prevention effectiveness of implemented health interventions for the prevention of rheumatic heart disease.

Methods and design
This article describes a protocol for a systematic review. A predefined search strategy will be used to search for relevant literature published from the year 2000 to present. Electronic databases Medline, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials will be searched for the studies, as well as reference lists of relevant studies included. Risk of bias and quality appraisal will be done for the included studies using ROBINS-I tool and Cochrane tool for assessing risk of bias in randomised control trials. Findings will be analysed in subgroups based on the level of intervention and prevention strategy implemented. We will present the findings in descriptive formats with tables and flow diagrams.

Discussion
This review will provide evidence on the prevention effectiveness of interventions or strategies implemented for the prevention of RHD. The findings of this will be significant for policy, practice, and research in countries planning to implement interventions.

Registration
PROSPERO ID: CRD42020170503.
Co-existence of Alport syndrome and C3 glomerulonephritis in a proband with family history
Authors: Ding Yin , Tang Xuanli , Du Yuanyuan , Chen Hongyu , Yu Dongrong , Zhu Bin , Yuan Bohan 
Published: July 2021

Abstract
Background
Alport syndrome and C3 glomerulonephritis (C3GN) are rare kidney diseases, frequently responsible for familial haematuria, proteinuria, and renal impairment. With the rapid development of molecular genetic testing, Alport syndrome causes have been restricted mostly to variants in the COL4A5 or COL4A3/COL4A4 genes. Moreover, a broad range of genetic contributors in the complement and complement-regulating proteins are definitely implicated in the pathogenesis of C3GN.

Methods
We sought a family with persistent microscopic haematuria associated with renal failure. Clinicopathologic and follow-up data were obtained, and molecular genetic testing was used to screen for pathogenic variants.

Results
We describe a three-generation family with Alport syndrome showing a dominant maternal inheritance. Notably, renal biopsy showed the concurrent histological evidence of C3GN in the proband harbouring an uncommon heterozygous variation in CFHR5, c.508G > A. The alteration leads to replacement of a highly conserved residue at position 170 of the β-strand subunit of CFHR5 (p.Val170Met). In silico analysis showed that the variation was predicted to deregulate complement activation by altering the structural properties and enhancing C3b binding capacity to compete with Complement Factor H (CFH), which was in line with experimental data previously published.

Conclusions
The comorbidity findings between Alport syndrome and C3GN indicate an underlying overlap and require further study.