bluuebunny/crossref_metadata_2025_split huggingface dataset:
Donor-derived Cell-free DNA in Infections in Kidney Transplant Recipients: Case Series
Authors: Goussous Naeem , Xie Wen , Dawany Noor , Scalea Joseph R. , Bartosic Amanda , Haririan Abdolreza , Kalil Roberto , Drachenberg Cinthia , Costa Nadiesda , Weir Matthew R. , Bromberg Jonathan S. 
Published: July 2020

Background.
Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive plasma biomarker to evaluate for transplant allograft rejection. The relationship between infectious complications in kidney allografts and dd-cfDNA has received cursory attention in prior publications.

Methods.
Retrospective review of all renal transplant recipients who underwent dd-cfDNA testing between November 2017 and August 2019.

Results.
We report on 7 cases in whom infections affecting the transplanted kidney were associated with elevation in dd-cfDNA without concomitant rejection or elevation in serum creatinine. Five patients had BK viremia, and 2 patients had urinary tract infection associated with elevated dd-cfDNA levels.

Conclusions.
These observations suggest that elevations in dd-cfDNA are not specific to kidney allograft rejection and can be associated with infections affecting the transplanted kidney. This biomarker may be valuable in evaluating infectious complications of kidney allografts.
Educational Animations to Inform Transplant Candidates About Deceased Donor Kidney Options: An Efficacy Randomized Trial
Authors: Kayler Liise K. , Dolph Beth A. , Cleveland Chelsea N. , Keller Maria M. , Feeley Thomas H. 
Published: July 2020

Background.
Transplant candidates struggle making decisions about accepting kidneys with variable kidney donor profile index (KDPI) and increased risk donor (IRD) status.

Methods.
This single site, pilot randomized controlled trial evaluated the efficacy of 2 animations to improve KDPI/IRD knowledge, decisional self-efficacy, and willingness. Kidney candidates were randomly assigned to animation viewing plus standard nurse discussion (intervention) or standard nurse discussion alone (control). Linear regression was used to test the significance of animation exposure after controlling for covariates (α < 0.1).

Results.
Mean age was 60 years, and 27% were African American. Both intervention (n = 42) and control (n = 38) groups received similar education at similar duration (12.8 versus 11.8 min, respectively), usually by the same dedicated nurse educator (85% versus 75%, respectively). On multivariate analysis, the intervention group (versus control) exhibited significantly increased knowledge (β = 0.23; 95% confidence interval, 0.66-1.77) and IRD willingness (β = 0.22; 95% confidence interval, 0.05-0.86). There were no between-group differences in KDPI >85% willingness or distribution of KDPI/IRD decisional self-efficacy. Over 90% of participants provided positive ratings on each of 11 acceptability items.

Conclusions.
Supporting conventional IRD and KDPI education with educational animations can improve knowledge and IRD willingness compared with standard methods.
Evaluation of Malnutrition Risk in Lung Transplant Candidates Using the Nutritional Risk Index
Authors: Chohan Karan , Park Jeff , Dales Sarah , Varughese Rhea , Wickerson Lisa , Singer Lianne G. , Stewart Brooke , Rozenberg Dmitry 
Published: July 2020

Background.
Malnutrition in lung transplant (LTx) candidates is an important risk factor for adverse outcomes. We sought to evaluate the Nutritional Risk Index (NRI) in LTx candidates, a validated measure of malnutrition risk in chronic disease. We aimed to characterize malnutrition risk using NRI, evaluate change in body weight between nutritional risk groups, and assess association of malnutrition risk with pretransplant and posttransplant outcomes.

Methods.
Retrospective, single-center cohort study of LTx candidates (2014–2015) evaluated by a dietitian before listing. Nutritional parameters, weight change pretransplant and posttransplant, and clinical outcomes were abstracted up to 1-year posttransplant. NRI was calculated as follows: (1.519 × albumin) + (41.7 × current weight/ideal weight) with high malnutrition risk defined as the lowest quartile of NRI for cystic fibrosis (CF) and non-CF patients.

Results.
The cohort comprises 247 LTx candidates (57% male; median age 59 y; non-CF 88%). Non-CF candidates had a greater mean NRI compared with CF patients (109 ± 11 versus 95 ± 12; P < 0.0001). 86% with high malnutrition risk maintained/gained weight (≥5%) pretransplant. In 196 LTx recipients, malnutrition risk was not associated with hospital stay, discharge disposition, or 1-year mortality. The median percent weight gain for LTx recipients in the first year was 10.5% (4.0–20.1), with high malnutrition risk recipients having comparable or greater weight gain to the low-risk group (mean difference for non CF: 6.8%; P = 0.02 and CF: −3.8%; P = 0.65).

Conclusions.
Malnutrition risk assessed with NRI was not prognostic of posttransplant outcomes in this retrospective cohort. LTx candidates with high malnutrition risk were able to maintain their weight pretransplant and demonstrated considerable weight gain in the first-year posttransplant.
Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid
Authors: Bernaola Nikolas , Mena Raquel , Bernaola Ander , Carballo Cesar , Lara Antonio , Bielza Concha , Larrañaga Pedro 
Published: July 2020

AbstractBackgroundMany different treatments were heavily administered to patients with COVID-19 during the peak of the pandemic in Madrid without robust evidence supporting them.MethodsWe examined the association between sixteen treatments in four groups (steroids, antivirals, antibiotics and immunomodulators) and intubation or death. Data were obtained from patients that were admitted to an HM hospital with suspicion of COVID-19 until 24/04/2020, excluding unconfirmed diagnosis, those who were admitted before the epidemic started in Madrid, had an outcome that was not discharge or death or died within 24 hours of presentation. We compared outcomes between treated and untreated patients using propensity-score caliper matching.ResultsOf 2,307 patients in the dataset, 679 were excluded. Of the remaining 1,645 patients, 263 (16%) died and 311 (18.9%) died or were intubated. Except for hydroxychloroquine and prednisone, patients that were treated with any of the medications were more likely to go through an outcome of death or intubation at baseline. After propensity matching we found an association between treatment with hydroxychloroquine and prednisone and better outcomes (hazard ratios with 95% CI of 0.83 ± 0.06 and 0.85 ± 0.03). Results were similar in multiple sensitivity analyses.ConclusionsIn this multicenter study of patients admitted with COVID-19 hydroxychloroquine and prednisone administration was found to be associated with improved outcomes. Other treatments were associated with no effect or worse outcomes. Randomized, controlled trials of these medications in patients with COVID-19 are needed to avoid heavy administration of treatments with no strong evidence to support them.
Adaptive short term COVID-19 prediction for India
Authors: Jana Shuvrangshu , Ghose Debasish 
Published: July 2020

AbstractIn this paper, a data-driven adaptive model for infection of COVID-19 is formulated to predict the confirmed total cases and active cases of an area over 4 weeks. The parameter of the model is always updated based on daily observations. It is found that the short term prediction of up to 3-4 weeks can be possible with good accuracy. Detailed analysis of predicted value and the actual value of confirmed total cases and active cases for India from 1st June to 3rd July is provided. Prediction over 7, 14, 21, 28 days has the accuracy about 0.73% ± 1.97%, 1.92% ± 2.95%, 4.34% ± 3.91%, 6.40% ± 9.26% of the actual value of confirmed total cases. Similarly, the 7, 14, 21, 28 days prediction has the accuracy about 1.24% ± 6.57%, 3.04% ± 10.00%, 6.33% ± 16.12%, 10.20% ± 24.14% of the actual value of confirmed active cases.
Neutralizing and binding antibody kinetics of COVID-19 patients during hospital and convalescent phases
Authors: Yao Xiang-Yang , Liu Wei , Li Zhi-Yong , Xiong Hua-Long , Su Ying-Ying , Li Ting-Dong , Zhang Shi-Yin , Zhang Xue-Jie , Bi Zhao-Feng , Deng Chen-Xi , Li Cai-Yu , Yuan Quan , Zhang Jun , Zhang Tian-Ying , Wang Zhan-Xiang , Ge Sheng-Xiang , Xia Ning-Shao 
Published: July 2020

AbstractKnowledge of the host immune response after natural SARS-CoV-2 infection is essential for informing directions of vaccination and epidemiological control strategies against COVID-19. In this study, thirty-four COVID-19 patients were enrolled with 244 serial blood specimens (38.1% after hospital discharge) collected to explore the chronological evolution of neutralizing (NAb), total (TAb), IgM, IgG and IgA antibody in parallel. IgG titers reached a peak later (approximately 35 days postonset) than those of Nab, Ab, IgM and IgA (20∼25 days postonset). After peaking, IgM levels declined with an estimated average half-life of 10.36 days, which was more rapid than those of IgA (51.25 days) and IgG (177.39 days). Based on these half-life data, we estimate that the median times for IgM, IgA and IgG to become seronegative are 4.59 (IQR 4.12-5.03), 7.78 (IQR 6.71-9.16) and 42.72 (IQR 33.75-47.96) months post disease onset. The relative contribution of IgM to NAb was higher than that of IgG (standardized β regression coefficient: 0.53 vs 0.48), so the rapid decline in NAb may be attributed to the rapid decay of IgM in acute phase. However, the relative contribution of IgG to NAb increased and that of IgM further decreased after 6 weeks postonset. It’s assumed that the decline rate of NAb might slow down to the same level as that of IgG over time. This study suggests that SARS-CoV-2 infection induces robust neutralizing and binding antibody responses in patients and that humoral immunity against SARS-CoV-2 acquired by infection may persist for a relatively long time.
Adjunctive Corticosteroids for COVID-19: A Retrospective Cohort Study
Authors: Tat Ooi Say , Parthasarathy Purnima , Yi Lin , D/O Nallakaruppan Valliammai , Jia Huey Shereen Ng , Choon Tan Teck , Serena Low , Terence Tang 
Published: July 2020

ABSTRACTBackgroundCoronavirus disease 2019 (COVID-19) is associated with severe pneumonia, respiratory failure and death. We aim to evaluate the efficacy of adjunctive corticosteroids in the management of COVID-19.MethodsThis is a retrospective cohort study of hospitalized adults (≥18 years) who were diagnosed with COVID-19 and were given treatment. Treatment included hydroxycholoroquine and lopinavir-ritonavir. Corticosteroids were included as adjunctive therapy in mid-April, 2020. We compared composite outcomes of clinical progression and invasive mechanical ventilation (MV) or death between group that received treatment only (Group A) versus group that received adjunctive corticosteroids (Group B). Entropy balancing was used to generate stabilized weight for covariates between treatment groups. Unweighted Kaplan-Meir curves, weighted and adjusted Cox regression analysis were used to estimate effect of adjunctive corticosteroids on composite outcomes. Subgroup analysis was performed on those with pneumonia.ResultsOf 1046 patients with COVID-19, 57 received treatment alone (Group A) and 35 received adjunctive corticosteroids in addition to treatment (Group B). Median day of illness at treatment initiation was 5 day. There were 44 patients with pneumonia; 68.9% of them were not requiring supplemental oxygen at treatment initiation. Overall, 17 (18.5%) of 92 patients had clinical progression including 13 (22.8%) of 57 patients in Group A versus 4 (11.4%) of 35 patients in Group B (p=0.172). Unweighted Kaplan-Meier estimates showed no significant difference in the proportion of patients who had clinical progression or invasive MV or death between the 2 treatment groups. However in those with pneumonia, there were lower proportions of patients in Group B with clinical progression (11.1%, 95% CI 0.0 - 22.2 versus 58.8%, 95% CI 27.3 - 76.7, log rank p<0.001); and invasive MV or death (11.3%, 95% CI 0.0 - 22.5 versus 41.2%, 95% CI 12.4. - 60.5, log rank p=0.016). In weighted and adjusted cox regression analysis, patients in Group B were less likely to have clinical progression, (adjusted HR [aHR] 0.08, 95% CI 0.01-0.99, p=0.049) but there was no statistical significant difference in risk of requiring invasive MV or death (aHR 0.22, 95%CI 0.02 - 2.54, p=0.22). In subgroup with pneumonia, patients in Group B were significantly at lower risk of clinical progression (aHR 0.15, 95% CI 0.06 - 0.39, p<0.001) and requiring invasive MV compared to Group A (aHR 0.30, 0.10-0.87, p=0.029).ConclusionsUse of adjunctive corticosteroids is associated with lower risk of clinical progression and invasive MV or death, especially in those with pneumonia. Concurrent use of antivirals and corticosteroids should be considered in the management of COVID-19 related pneumonia.
Population genetic analysis of Indian SARS-CoV-2 isolates reveals a unique phylogenetic cluster
Authors: Das Dhruv , Akkipeddi V.S.S.N.R 
Published: July 2020

AbstractThe SARS-CoV-2 pandemic originated from Wuhan, China in December 2019 raised an alarming situation all over the globe. Sequencing of this novel virus provides an opportunity to evaluate the genetic polymorphism present in the viral population. Herein, we analysed 173 sequences isolated from Indian patients and performed SNP linkage, clustering and phylogenetic analysis to understand the local genetic diversity. We found that the SNP linkages that lead to the identification of some global clades, do not hold true for the local clade classification. In addition to the unique cluster, established by another Indian study, we identified a new cluster (I-20D) that encompasses 28% of the analysed sequences. This cluster is defined by two linked variations – C22444T and C28854T. A detailed study of such polymorphisms can be useful for drug and vaccine development.
Exploration of endogenous miRNA-200b/c activity and regulation through a functional dual fluorescence reporter
Authors: Gollavilli Paradesi , Parma Beatrice , Siddiqui Aarif , Yang Hai , Ramesh Vignesh , Napoli Francesca , Schwab Annemarie , Natesan Ramakrishnan , Asangani Irfan Ahmed , Brabletz Thomas , Pilarsky Christian , Ceppi Paolo 
Published: July 2020

ABSTRACTSince their discovery, microRNAs (miRNA)s have been widely studied in almost every aspect of biology and medicine, leading to the identification of important gene regulation circuits and cellular mechanisms. However, investigations are generally focused on the analysis of their downstream targets and biological functions in overexpression and knockdown approaches, while miRNAs endogenous levels and activity remain poorly understood. Here, we used the cellular plasticity-regulating process of epithelial-to-mesenchymal transition (EMT) as a model to show the efficacy of a fluorescent sensor to separate cells with distinct EMT signatures, based on miR-200b/c activity. The system was further combined with a CRISPR-Cas9 screening platform to unbiasedly identify miR-200b/c upstream regulating genes. The sensor allows to infer miRNAs fundamental biological properties, as profiling of sorted cells indicated miR-200b/c as a molecular switch between EMT differentiation and proliferation, and suggested a role for metabolic enzymes in miR-200/EMT regulation. Analysis of miRNAs’ endogenous levels and activity could lead to a better understanding of their biological role in physiology and disease.
Probing the dynamic structure-function and structure-free energy relationships of the corona virus main protease with Biodynamics theory
Authors: Wan Hongbin , Aravamuthan Vibhas , Pearlstein Robert A. 
Published: July 2020

AbstractThe SARS-CoV-2 Main protease (Mpro) is of major interest as an anti-viral drug target. Structure-based virtual screening efforts, fueled by a growing list of apo and inhibitor-bound SARS-CoV/CoV-2 Mprocrystal structures, are underway in many labs. However, little is known about the dynamic enzyme mechanism, which is needed to inform both structure-based design and assay development. Here, we apply Biodynamics theory to characterize the structural dynamics of substrate-induced Mproactivation, and explore the implications thereof for efficacious inhibition under non-equilibrium conditions. The catalytic cycle (including tetrahedral intermediate formation and hydrolysis) is governed byconcerteddynamic structural rearrangements of domain 3 and the m-shaped loop (residues 132-147) on which Cys145 (comprising the thiolate nucleophile and one-half of the oxyanion hole) and Gly143 reside (comprising the other half of the oxyanion hole). In particular:Domain 3 undergoes dynamic rigid-body rotations about the domain 2-3 linker, alternately visiting two conformational states (denoted as).The Gly143-containing crest of the m-shaped loop (denoted as crest B) undergoes up and down translations in concert with the domain 3 rotations (denoted as, whereas the Cys145-containing crest (denoted as crest A) remains statically in the up position. The crest B translations are driven by conformational transitions within the rising leg of the loop (Lys137-Asn142).We propose that substrates associate to thestate, which promotes thestate, dimerization (denoted as-substrate), and catalysis. The structure resets to the dynamic monomeric form upon dissociation of the N-terminal product. We describe the energetics of the aforementioned state transitions, and address the implications of our proposed mechanism for efficacious Mproinhibition under native-like conditions.
Unique contributions of sensory discrimination and gamma synchronization deficits to cognitive, clinical, and psychosocial functional impairments in schizophrenia
Authors: Koshiyama Daisuke , Miyakoshi Makoto , Thomas Michael L. , Joshi Yash B. , Molina Juan L. , Tanaka-Koshiyama Kumiko , Sprock Joyce , Braff David L. , Swerdlow Neal R. , Light Gregory A. 
Published: July 2020

AbstractBackgroundSchizophrenia patients show widespread deficits in neurocognitive, clinical and psychosocial functioning. Mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are robust biomarkers for domains of neuropsychiatric disorders that are impaired in schizophrenia patients and are separately associated with cognitive dysfunction, negative symptom severity and psychosocial disability. Although these measures of early auditory information processing are conceptually linked, it is unclear, whether these measures are redundant or account for unique variance in important outcome measures. In this study, we aimed to determine whether MMN and gamma-band ASSR are associated with cognitive, clinical, and functional variables and, if so, whether they account for shared vs. non-shared variance in those important domains.MethodsMultiple regression analyses with MMN, gamma-band ASSR and clinical measures were performed in large cohorts of schizophrenia outpatients (N=428) and healthy comparison subjects (N=283).ResultsReduced MMN (d= 0.67), gamma-band ASSR (d= –0.40), and lower cognitive function were confirmed in schizophrenia patients compared to healthy comparison subjects. Regression analyses revealed that both MMN and gamma-band ASSR have significant unique associations with tasks measuring of working memory, and daily functioning in schizophrenia patients.ConclusionThese findings suggest that MMN and ASSR measures are non-redundant and complementary measures. Studies are needed to clarify the neural substrates of MMN and gamma-band ASSR in order to improve our understanding of pathophysiology of schizophrenia and accelerate their use in the development of novel therapeutic interventions.
The association between stigmatizing attitudes towards depression and help seeking attitudes in college students
Authors: da Conceição Virgínia , Rothes Inês , Gusmão Ricardo 
Published: July 2020

AbstractObjectiveDepression stigma has been considered a significant barrier to treatment and rehabilitation. This study aimed to understand the effects of gender, previous health care use, and symptomatology on depression stigma and analyze the impact of depression stigma on help-seeking attitudes.MethodsA total of 969 students with a mean age of 18.87 (SD=1.49) were included in this study and completed the Depression Stigma Scale, the Attitude Toward Seeking Professional Psychological Help, the Patient Health Questionnaire-4 questionnaire, and a socio-demographic questionnaire. We analyzed data using SPSS 24.0, with a 95% confidence interval. We performed an analysis of variance using One-Way ANOVA and analyzed possible interactions between gender and previous mental healthcare groups on depression stigma and help-seeking attitudes using a Two-Way ANOVA. T-tests were used to study differences between the gender, symptomatology groups, and previous access to mental healthcare. We also executed a hierarchical linear regression to evaluate the effects of individual characteristics on Depression Stigma and Help-seeking attitudes scores.ResultsParticipants came from all University schools, and 64.6% were women. Stigma and help-seeking attitudes are positively affected by gender and previous access to mental healthcare services. Higher personal stigma weakened help-seeking attitudes. Depressive and anxiety symptoms influenced personal depression stigma and perceived stigma; however, we detected no direct symptomatology effect on help-seeking attitudes.ConclusionsPersonal depression stigma has an essential effect on help-seeking attitudes, and depressive and anxiety symptoms do not. The promotion of literacy may decrease personal depression stigma and increase professional help-seeking intentions.
SARS-CoV2 spike protein displays biologically significant similarities with paramyxovirus surface proteins; a bioinformatics study
Authors: Ahmadi Ehsan , Zabihi Mohammad Reza , Hosseinzadeh Ramin , Noorbakhsh Farshid 
Published: July 2020

AbstractRecent emergence of SARS-CoV2 and associated COVID-19 pandemic has posed a great challenge for the scientific community. Understanding various aspects of SARS-CoV2 biology, virulence and pathogenesis as well as determinants of immune response have become a global research priority. In this study, we performed bioinformatic analyses on SAR-CoV2 protein sequences, trying to unravel biologically important similarities between this newly emerged virus with other RNA viruses. Comparing the proteome of SARS-CoV2 with major positive and negative strand ssRNA viruses showed significant homologies between SARS-CoV2 spike protein with pathogenic paramyxovirus fusion proteins. This ‘spike-fusion’ homology was not limited to SARS-CoV2 and it existed for some other pathogenic coronaviruses; nonetheless, SARS-CoV2 spike-fusion homology was orders of magnitude stronger than homologies observed for other known coronaviruses. Moreover, this homology did not seem to be a consequence of general ssRNA virus phylogenetic relations. We also explored potential immunological significance of this spike-fusion homology. Spike protein epitope analysis using experimentally verified data deposited in Immune Epitope Database (IEDB) revealed that the majority of spike’s T cell epitopes as well as many B cell and MHC binding epitopes map within the spike-fusion homology region. Overall, our data indicate that there might be a relation between SARS-CoV2 and paramyxoviruses at the level of their surface proteins and this relation could be of crucial immunological importance.