bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Subclinical and Clinical Kidney Allograft Rejection Within 1 Year Posttransplantation Among Compatible Transplant With Steroid Withdrawal Protocol
Authors: Owoyemi Itunu , Tandukar Srijan , Jorgensen Dana R. , Wu Christine M. , Sood Puneet , Puttarajappa Chethan , Sharma Akhil , Shah Nirav A. , Randhawa Parmjeet , Molinari Michele , Tevar Amit D. , Mehta Rajil B. , Hariharan Sundaram 
Published: June 2021

Background.
Early acute kidney rejection remains an important clinical issue.

Methods.
The current study included 552 recipients who had 1–2 surveillance or indication biopsy within the 1 y posttransplant. We evaluated the impact of type of allograft inflammation on allograft outcome. They were divided into 5 groups: no inflammation (NI: 95), subclinical inflammation (SCI: 244), subclinical T cell–mediated rejection (TCMR) (SC-TCMR: 110), clinical TCMR (C-TCMR: 83), and antibody-mediated rejection (AMR: 20). Estimated glomerular filtration rate (eGFR) over time using linear mixed model, cumulative chronic allograft scores/interstitial fibrosis and tubular atrophy (IFTA) ≥2 at 12 mo, and survival estimates were compared between groups.

Results.
The common types of rejections were C-TCMR (15%), SC-TCMR (19.9%), and AMR (3.6%) of patients. Eighteen of 20 patients with AMR had mixed rejection with TCMR. Key findings were as follows: (i) posttransplant renal function: eGFR was lower for patients with C-TCMR and AMR (P < 0.0001) compared with NI, SCI, and SC-TCMR groups. There was an increase in delta-creatinine from 3 to 12 mo and cumulative allograft chronicity scores at 12 mo (P < 0.001) according to the type of allograft inflammation. (ii) Allograft histology: the odds of IFTA ≥2 was higher for SC-TCMR (3.7 [1.3-10.4]; P = 0.04) but was not significant for C-TCMR (3.1 [1.0-9.4]; P = 0.26), and AMR (2.5 [0.5-12.8]; P = 0.84) compared with NI group, and (iii) graft loss: C-TCMR accounted for the largest number of graft losses and impending graft losses on long-term follow-up. Graft loss among patient with AMR was numerically higher but was not statistically significant.

Conclusions.
The type of kidney allograft inflammation predicted posttransplant eGFR, cumulative chronic allograft score/IFTA ≥2 at 12 mo, and graft loss.
Causes and Circumstances of Death in Portopulmonary Hypertension
Authors: Sahay Sandeep , Al Abdi Sami , Melillo Celia , Newman Jennie , Dweik Raed A. , Heresi Gustavo A. , Tonelli Adriano R. 
Published: June 2021

Background.
The causes and circumstances surrounding death are poorly studied in patients with portopulmonary hypertension (PoPH). We sought to determine the specific reasons for dying and characteristics surrounding this process in patients with PoPH.

Methods.
All deaths of patients with PoPH followed in the Cleveland Clinic Pulmonary Vascular Program were prospectively reviewed by the pulmonary hypertension team between 1996 and 2020.

Results.
A total of 69 patients with PoPH (age 56.0 ± 8.9 y), with 49% females, were included. Causes of death were available in 52 (75%) patients, of these PoPH either directly or indirectly contributed to death in 13 of 52 (25%) of patients, meanwhile 39 of 52 (75%) of the patients died because of progressive liver disease and its related complications. Decompensated liver disease was the leading cause of death in this cohort 20 of 52 (38%), whereas 19 of 52 (37%) died because of conditions associated with liver disease. About half, 36 of 69 (52%) of patients died in a healthcare environment and 23 of 36 (64%) during a hospitalization at Cleveland Clinic. A total of 59 of 69 (74%) of patients received pulmonary arterial hypertension (PAH)-specific therapies. Six patients died after liver transplantation (in 3 death was related to PAH-related complications). Most of the patients in this cohort of PoPH patients were considered unsuitable for liver transplantation for a variety of reasons. Advanced healthcare directives were available in only 28% of patients.

Conclusions.
Most patients with PoPH died because of complications of their liver disease. PAH directly or indirectly contributed to death in a third of them. A quarter of them did not receive PAH-specific therapy before their death.
Karnofsky Performance Score—Failure to Thrive as a Frailty Proxy?
Authors: Stedman Margaret R. , Watford Daniel J. , Chertow Glenn M. , Tan Jane C. 
Published: June 2021

Background.
Among patients listed for kidney transplantation, the Karnofsky Performance Status (KPS) Scale has been used as a proxy for frailty and proposed as a predictor of long-term posttransplant outcomes. The KPS is required by the Organ Procurement and Transplantation Network for all transplants; however, the interrater reliability of KPS reporting in kidney transplant candidates has not been well investigated, and there is concern regarding limitations of using KPS that may influence transplant eligibility.

Methods.
We performed an observational study using existing Scientific Registry of Transplant Recipients data from 2006 to 2020 to examine the variability, reliability, and trends in the KPS among patients on the kidney transplant waitlist.

Results.
Our analysis included 8197 kidney transplant candidates with >1 KPS in a 3-mo period. We observed 2–7 scores per patient with an average score of 78.9 (SD = 12, 95% confidence interval, 78.8-79.1). We found substantial variability in KPS reporting, in which 27% of the patients had scores that varied widely with 20–80 points in difference. Interrater reliability in the 10-point scale was poor (30%). When using a condensed 4-category scale (disabled, requires assistance, capable of self-care, normal activity), 38% of patients experienced at least a 1-category shift in their score.

Conclusions.
The lack of reliability in KPS reporting raises concerns when applying the KPS as a proxy for frailty and a metric to be considered when evaluating candidacy for kidney transplantation.
Namilumab or infliximab compared to standard of care in hospitalised patients with COVID-19 (CATALYST): a phase 2 randomised adaptive trial
Authors: Fisher Benjamin A. , Veenith Tonny , Slade Daniel , Gaskell Charlotte , Rowland Matthew , Whitehouse Tony , Scriven James , Parekh Dhruv , Balasubramaniam Madhu S. , Cooke Graham , Morley Nick , Gabriel Zoe , Wise Matthew P. , Porter Joanna , McShane Helen , Ho Ling-Pei , Newsome Philip N. , Rowe Anna , Sharpe Rowena , Thickett David R. , Bion Julian , Gates Simon , Richards Duncan , Kearns Pamela 
Published: June 2021

SummaryBackgroundDysregulated inflammation is associated with poor outcomes in Coronavirus disease 2019 (COVID-19). We assessed the efficacy of namilumab, a granulocyte-macrophage colony-stimulating factor inhibitor and infliximab, a tumour necrosis factor inhibitor in hospitalised patients with COVID-19 in order to prioritise agents for phase 3 trials.MethodsIn this randomised, multi-arm, parallel group, open label, adaptive phase 2 proof-of-concept trial (CATALYST) we recruited hospitalised patients ≥ 16 years with COVID-19 pneumonia and C-reactive protein (CRP) ≥ 40mg/L in nine UK hospitals. Participants were randomly allocated with equal probability to usual care, or usual care plus a single 150mg intravenous dose of namilumab (150mg) or infliximab (5mg/kg). Randomisation was stratified for ward versus ICU. The primary endpoint was improvement in inflammation in intervention arms compared to control as measured by CRP over time, analysed using Bayesian multi-level models. ISRCTN registry number 40580903.FindingsBetween 15thJune 2020 and 18thFebruary 2021 we randomised 146 participants: 54 to usual care, 57 to namilumab and 35 to infliximab. The probabilities that namilumab and infliximab were superior to usual care in reducing CRP over time were 97% and 15% respectively. Consistent effects were seen in ward and ICU patients and aligned with clinical outcomes, such that the probability of discharge (WHO levels 1-3) at day 28 was 47% and 64% for ICU and ward patients on usual care, versus 66% and 77% for patients treated with namilumab. 134 adverse events occurred in 30/55 (54.5%) namilumab patients compared to 145 in 29/54 (53.7%) usual care patients. 102 events occurred in 20/29 (69.0%) infliximab patients versus 112 events in 17/34 (50.0%) usual care patients.InterpretationNamilumab, but not infliximab, demonstrated proof-of-concept evidence for reduction in inflammation in hospitalised patients with COVID-19 pneumonia which was consistent with secondary clinical outcomes. Namilumab should be prioritised for further investigation in COVID-19.FundingMedical Research Council.
A Chinese host genetic study discovered type I interferons and causality of cholesterol levels and WBC counts on COVID-19 severity
Authors: Zhu Huanhuan , Zheng Fang , Li Linxuan , Jin Yan , Luo Yuxue , Li Zhen , Zeng JingYu , Tang Ling , Li Zilong , Xia Ningyu , Liu Panhong , Han Dan , Shan Ying , Zhu Xiaoying , Liu Siyang , Xie Rong , Chen Yilin , Liu Wen , Liu Longqi , Xu Xun , Wang Jian , Yang Huanming , Shen Xia , Jin Xin , Cheng Fanjun 
Published: June 2021

AbstractAs of early May 2021, the ongoing pandemic COVID-19 has caused over 160 million of infections and over 3 million deaths worldwide. Many risk factors, such as age, gender, and comorbidities, have been studied to explain the variable symptoms of infected patients. However, these effects may not fully account for the diversity in disease severity. Here, we present a comprehensive analysis of a broad range of patients’ laboratory and clinical assessments to investigate the genetic contributions to COVID-19 severity. By performing GWAS analysis, we discovered several concrete associations for laboratory features. Based on these findings, we performed Mendelian randomization (MR) analysis to investigate the causality of laboratory traits on disease severity. From the MR study, we identified two causal traits, cholesterol levels and WBC counts. The functional gene related to cholesterol levels is ApoE and people with particular ApoE genotype are more likely to have higher cholesterol levels, facilitating the process that SARS-CoV-2 binds on its receptor ACE2 and aggravating COVID-19 disease. The functional gene related to WBC counts is MHC system that plays a central role in the immune system. The host immune response to the SARS-CoV-2 infection greatly affects the patients’ severity status and clinical outcome. Additionally, our gene-based and GSEA analysis revealed interferon pathways, including type I interferon receptor binding, regulation of IFNA signaling, and SARS coronavirus and innate immunity. We hope that our work will make a contribution in studying the genetic mechanisms of disease illness and serve as useful reference for the clinical diagnosis and treatment of COVID-19.
COVID-19 infections in day care centres in Germany: Social and organisational determinants of infections in children and staff in the second and third wave of the pandemic
Authors: Neuberger Franz , Grgic Mariana , Diefenbacher Svenja , Spensberger Florian , Lehfeld Ann-Sophie , Buchholz Udo , Haas Walter , Kalicki Bernhard , Kuger Susanne 
Published: June 2021

AbstractBackgroundDuring the SARS-CoV-2 pandemic, German early childhood education and care (ECEC) centres organised childrens attendance variably (i.e., reduced opening hours, emergency support for few children only or full close-down). Further, protection and hygiene measures like fixed children/staff groups, ventilation and surface disinfection were introduced among ECEC centres. To inform or modify public health measures in ECEC, we investigate the occurrence of SARS-CoV-2 infections among children and staff of ECEC centres in light of social determinants (socioeconomic status of the children) and recommended structural and hygiene measures. We focus on the question if the relevant factors differ between the 2nd (when no variant of concern (VOC) circulated) and the 3rd wave (when VOC B.1.1.7 (Alpha) predominated).MethodsBased on panel data from a weekly online survey of ECEC centre managers (calendar week 36/2020 to 22/2021, ongoing) including approx. 8500 centres, we estimate the number of SARS-CoV-2 infections in children and staff using random-effect-within-between (REWB) panel models for count data in the 2nd and 3rd wave.ResultsCentres with a high proportion of children with low socioeconomic status (SES) have a higher risk of infections in staff and children. Strict contact restrictions between groups like fixed group assignments among children and fixed staff assignments to groups prevent infections. Both effects tend to be stronger in the 3rd wave.ContributionECEC centres with a large proportion of children from a low SES background and lack of using fixed child/staff cohorts experience higher COVID-19 rates. Centres should be supported in maintaining recommended measures over the long run. Preventive measures such as vaccination of staff should be prioritised in centres with large proportions of low SES children.
Inverse planning for radiofrequency ablation in cancer therapy using multiple damage models
Authors: Kulkarni-Thaker Shefali , Aleman Dionne , Fenster Aaron 
Published: June 2021

AbstractRadiofrequency ablation (RFA) offers localized and minimally invasive treatment of small-to-medium sized inoperable tumors. In RFA, tissue is ablated with high temperatures obtained from electrodes (needles) inserted percutaneously or via an open surgery into the target. RFA treatments are generally not planned in a systematic way, and do not account for nearby organs-at-risk (OARs), potentially leading to sub-optimal treatments and inconsistent treatment quality. We therefore develop a mathematical framework to design RFA treatment plans that provide complete ablation while minimizing healthy tissue damage. Borrowing techniques from radiosurgery inverse planning, we design a two-stage approach where we first identify needle positions and orientations, called needle orientation optimization, and then compute the treatment time for optimal thermal dose delivery, called thermal dose optimization. Several different damage models are used to determine both target and OAR damage. We present numerical results on three clinical case studies. Our findings indicate a need for high source voltage for short tip length (conducting portion of the needle) or fewer needles, and low source voltage for long tip length or more needles to achieve full coverage. Further, more needles yields a larger ablation volume and consequently more OAR damage. Finally, the choice of damage model impacts the source voltage, tip length, and needle quantity.
A novel RT-LAMP workflow for rapid salivary diagnostics of COVID-19 and effects of age, gender and time from symptom onset
Authors: Kobayashi Gerson Shigeru , Brito Luciano Abreu , de Paula Moreira Danielle , Suzuki Angela May , Hsia Gabriella Shih Ping , Pimentel Lylyan Fragoso , de Paiva Ana Paula Barreto , Dias Carolina Regoli , Lourenço Naila Cristina Vilaça , Oliveira Beatriz Araujo , Manuli Erika Regina , Corral Marcelo Andreetta , Cavaçana Natale , Neto Miguel Mitne , Sales Maria Mirtes , Aquila Luiz Phellipe Dell’ , Filho Alvaro Razuk , Parrillo Eduardo Fagundes , Mendes-Corrêa Maria Cássia , Sabino Ester Cerdeira , Costa Silvia Figueiredo , Leal Fabio Eudes , Sgro Germán Gustavo , Farah Chuck Shaker , Zatz Mayana , Passos-Bueno Maria Rita 
Published: June 2021

ABSTRACTObjectivesRapid diagnostics is pivotal to curb SARS-CoV-2 transmission, and saliva has emerged as a practical alternative to naso/oropharyngeal (NOP) specimens. We aimed to develop a direct RT-LAMP workflow for viral detection in saliva, and to provide more information regarding its potential in COVID-19 diagnostics.MethodsClinical and contrived specimens were used to screen/optimize formulations and sample processing protocols. Salivary viral load was determined in symptomatic patients to evaluate clinical performance (n = 90) and to characterize saliva based on age, gender and time from onset of symptoms (n = 49).ResultsThe devised workflow achieved 93.2% sensitivity, 97% specificity, and 0.895 Kappa for salivas containing >102 copies/μL. Further analyses in saliva showed peak viral load in the first days of symptoms and lower viral loads in females, particularly among young individuals (<38 years). NOP RT-PCR data did not yield relevant associations.ConclusionsThis novel saliva RT-LAMP workflow can be applied to point-of-care testing. This work reinforces that saliva better correlates with transmission dynamics than NOP specimens, and reveals gender differences that may reflect higher transmission by males. To maximize detection, testing should be done immediately after symptom onset, especially in females.HIGHLIGHTS-Development of DGS, a dithiothreitol/guanidine-based solution for stabilization of the viral genome that increases sensitivity for SARS-CoV-2 detection in saliva;-Rapid, cost-effective RT-LAMP assay workflow for viral detection in saliva without need of RNA extraction;-Insights into the differences in viral load between saliva and naso-oropharyngeal specimens, and correlation with age, gender and time from symptom onset;
Percolation across households in mechanistic models of non-pharmaceutical interventions in SARS-CoV-2 disease dynamics
Authors: Franco Caroline , Ferreira Leonardo Souto , Sudbrack Vítor , Borges Marcelo Eduardo , Poloni Silas , Inácio Prado Paulo , White Lisa J , Águas Ricardo , André Kraenkel Roberto , Coutinho Renato Mendes 
Published: June 2021

AbstractSince the emergence of the novel coronavirus disease, mathematical modelling has become an important tool for planning strategies to combat the pandemic by supporting decision-making and public policies, as well as allowing an assessment of the effect of different intervention scenarios. A proliferation of compartmental models was observed in the mathematical modelling community, aiming to understand and make predictions regarding the spread of COVID-19. Such approach has its own advantages and challenges: while compartmental models are suitable to simulate large populations, the underlying well-mixed population assumption might be problematic when considering non-pharmaceutical interventions (NPIs) which strongly affect the connectivity between individuals in the population. Here we propose a correction to an extended age-structured SEIR framework with dynamic transmission modelled using contact matrices for different settings in Brazil. By assuming that the mitigation strategies for COVID-19 affect the connections between different households, network percolation theory predicts that the connectivity across all households decreases drastically above a certain threshold of removed connections. We incorporated this emergent effect at population level by modulating the home contact matrices through a percolation correction function, with the few remaining parameters fitted to to hospitalisation and mortality data from the city of São Paulo. We found significant support for the model with implemented percolation effect using the Akaike Information Criteria (AIC). Besides better agreement to data, this improvement also allows for a more reliable assessment of the impact of NPIs on the epidemiological dynamics.
Breakthrough infection with SARS-CoV-2 and its predictors among healthcare workers in a medical college and hospital complex in Delhi, India
Authors: Sharma Pragya , Mishra Suruchi , Basu Saurav , Tanwar Neha , Kumar Rajesh 
Published: June 2021

AbstractIntroductionThe study objective was to determine the breakthrough infection rate of Covid-19 (SARS-CoV-2) infection in those vaccinated with either BBV152 or AZD1222 (ChAdOx1-S) vaccine among healthcare workers (HCWs).MethodsA cross-sectional analysis was conducted a medical college and hospital complex in Delhi, India through telephonic interviews among HCWs who had received at-least one dose of a Covid-19 vaccine during January to March’ 2021. Breakthrough infections were operationally defined as occurrence of Covid-19 infection ≥14 days after administration of two doses of either Covid-19 vaccine.ResultsWe enrolled 325 HCWs with mean (SD) age of 29.1 (9.9) years including 211 (64.9%) males. Two seventy nine (85.8%) HCWs were fully vaccinated while 46 (14.2%) were partially vaccinated. There were 168 (51.7%) BBV152 and 157 (48.3%) AZD1222 (ChAdOx1-S) recipients.A total of 37 (11.3%, 95% C.I. 8.3, 15.3) breakthrough infections were observed in the HCWs. The median (IQR) time until incidence of Covid-19 breakthrough infection since receiving second dose of either Covid-19 vaccine was 47 (28.5, 55) days. Additionally, 20 (6.1%) non-breakthrough Covid-19 infections were recorded in the HCWs post vaccination with either a single dose of a Covid-19 vaccine or both doses but prior to a period of 14 days since administration of the second dose.Most breakthrough infection cases (94.4%) were mild and did not require supplemental oxygen therapy. HCWs without a history of natural Covid-19 infection and recovery prior to vaccination were 3.8 times more at risk to contract a Covid-19 infection or reinfection in spite of vaccination with at-least one dose of either Covid-19 vaccine.ConclusionNearly one in nine HCWs experienced a Covid-19 breakthrough infection in the present study.
Whole-exome sequencing of the mummified remains of Cangrande della Scala (1291–1329 CE) indicates the first known case of late-onset Pompe disease
Authors: Iadarola Barbara , Lavezzari Denise , Modi Alessandra , Esposti Chiara Degli , Beltrami Cristina , Rossato Marzia , Zaro Valentina , Napione Ettore , Latella Leonardo , Lari Martina , Caramelli David , Salviati Alessandro , Delledonne Massimo 
Published: June 2021

ABSTRACTMummified remains of relevant historical figures are nowadays an important source of information to retrace data concerning their private life and health, especially when historical archives are not available. Next-generation-sequencing was proved to be a valuable tool to unravel the characteristics of these individuals through their genetic heritage. Using the strictest criteria currently available for the validation of ancient DNA sequences, whole-genome and whole-exome sequencing were generated from the mummy remains of an Italian nobleman died almost 700 years ago, Cangrande della Scala. While its genome sequencing could not yield sufficient coverage for in depth investigation, exome sequencing could overcome the limitations of this approach to achieve significantly high coverage on coding regions, thus allowing to perform the first extensive exome analysis of a mummy genome. Similar to a standard “clinical exome analysis” conducted on modern DNA, an in-depth variant annotation, high-quality filtering and interpretation was performed, leading to the identification of a genotype associated with late-onset Pompe disease (glycogen storage disease type II). This genetic diagnosis was concordant with the limited clinical history available for Cangrande della Scala, who likely represents the earliest known case of this autosomal recessive metabolic disorder.