bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acidosis and alkali therapy in patients with kidney transplant is associated with transcriptional changes and altered abundance of genes involved in cell metabolism and acid–base balance
Authors: Imenez Silva Pedro H , Wiegand Anna , Daryadel Arezoo , Russo Giancarlo , Ritter Alexander , Gaspert Ariana , Wüthrich Rudolf P , Wagner Carsten A , Mohebbi Nilufar 
Published: July 2021

Abstract

Background
Metabolic acidosis occurs frequently in patients with kidney transplant and is associated with a higher risk for and accelerated loss of graft function. To date, it is not known whether alkali therapy in these patients improves kidney function and whether acidosis and its therapy are associated with altered expression of proteins involved in renal acid–base metabolism.

Methods
We retrospectively collected kidney biopsies from 22 patients. Of these patients, nine had no acidosis, nine had metabolic acidosis [plasma bicarbonate (HCO3− &lt;22 mmol/L) and four had acidosis and received alkali therapy. We performed transcriptome analysis and immunohistochemistry for proteins involved in renal acid–base handling.

Results
We found that the expression of 40 transcripts significantly changed between kidneys from non-acidotic and acidotic patients. These genes are mostly involved in proximal tubule (PT) amino acid and lipid metabolism and energy homoeostasis. Three transcripts were fully recovered by alkali therapy: the Kir4.2 potassium channel, an important regulator of PT HCO3− metabolism and transport, acyl-CoA dehydrogenase short/branched chain and serine hydroxymethyltransferase 1, genes involved in beta oxidation and methionine metabolism. Immunohistochemistry showed reduced staining for the PT NBCe1 HCO3− transporter in kidneys from acidotic patients who recovered with alkali therapy. In addition, the HCO3− exchanger pendrin was affected by acidosis and alkali therapy.

Conclusions
Metabolic acidosis in kidney transplant recipients is associated with alterations in the renal transcriptome that are partly restored by alkali therapy. Acid–base transport proteins mostly from PT were also affected by acidosis and alkali therapy, suggesting that the downregulation of critical players contributes to metabolic acidosis in these patients.
Protease inhibitor plasma concentrations associate with COVID-19 infection
Authors: Medjeral-Thomas Nicholas R , Troldborg Anne , Hansen Annette G , Pihl Rasmus , Clarke Candice L , Peters James E , Thomas David C , Willicombe Michelle , Palarasah Yaseelan , Botto Marina , Pickering Matthew C , Thiel Steffen 
Published: July 2021

Abstract
Protease inhibitors influence a range of innate immunity and inflammatory pathways. We quantified plasma concentrations of key anti-inflammatory protease inhibitors in chronic haemodialysis patients with coronavirus disease 2019 (COVID-19). The samples were collected early in the disease course to determine whether plasma protease inhibitor levels associated with the presence and severity of COVID-19. We used antibody-based immunoassays to measure plasma concentrations of C1 esterase inhibitor, alpha2-macroglobulin, antithrombin and inter-alpha-inhibitor heavy chain 4 (ITIH4) in 100 serial samples from 27 haemodialysis patients with COVID-19. ITIH4 was tested in two assays, one measuring intact ITIH4 and another also detecting any fragmented ITIH4 (total ITIH4). Control cohorts were 32 haemodialysis patients without COVID-19 and 32 healthy controls. We compared protease inhibitor concentration based on current and future COVID-19 severity and with C-reactive protein. Results were adjusted for repeated measures and multiple comparisons. Analysis of all available samples demonstrated lower plasma C1 esterase inhibitor and α2M and higher total ITIH4 in COVID-19 compared with dialysis controls. These differences were also seen in the first sample collected after COVID-19 diagnosis, a median of 4 days from diagnostic swab. Plasma ITIH4 levels were higher in severe than the non-severe COVID-19. Serum C-reactive protein correlated positively with plasma levels of antithrombin, intact ITIH4 and total ITIH4. In conclusion, plasma protease inhibitor concentrations are altered in COVID-19.
Can we predict if patients with SLE will require more than one cycle of rituximab?
Authors: Fernández González Raquel , Abida Rym , Gisca Eugeniu , Duarte Leila , Isenberg David A 
Published: July 2021

AbstractObjectiveTo identify clinical and serological features that distinguish patients with SLE who require single as opposed to repeated rituximab (RTX) cycles.MethodsAll 175 SLE patients followed up at University College Hospital from 2000 onwards were retrospectively reviewed. They were divided into a one-RTX-cycle group and a multiple-cycle group (2 or more cycles). Patients included had a follow-up of at least 3 years after their first RTX cycle, unless they needed a second infusion sooner.ResultsA total of 131 patients were included; 44 (33.6%) received one cycle of RTX and 87 (66.4%) received two or more. The former were older at diagnosis (31.4 vs 21 years, P &lt; 0.001) and at first RTX infusion (39.9 vs 29 years, P &lt; 0.001). This group of patients had more organs/systems involved (P = 0.044), more leukopenia, lymphopenia and thrombocytopenia (P = 0.001, P &lt; 0.0001 and P = 0.003, respectively) and lower C3 levels (P = 0.035). They also had fewer immunosuppressive drugs before RTX therapy compared with those who required multiple RTX cycles (P = 0.003). There was no statistical difference in either the clinical or serological response after the first RTX cycle between both groups. Furthermore, patients who had received more immunosuppressive treatments were more likely to require more than one cycle of RTX infusions (P = 0.007).ConclusionsRTX is an effective option for SLE patients with severe flares. Patients who received more immunosuppressive drugs were more likely to receive more than one set of RTX infusions. This suggests that RTX is best used for SLE patients with no history of refractory disease.
QRISK3 relation to carotid plaque is higer than that of score in patients with systemic lupus erythematosus
Authors: Quevedo-Abeledo Juan Carlos , Caceres Laura , Palazuelos Camilo , Llorca Javier , González-Gay Miguel Á , Ferraz-Amaro Iván 
Published: July 2021

Abstract

Introduction
SLE has been described as an independent risk factor for the development of cardiovascular (CV) disease. Recently, the QRESEARCH risk estimator version 3 (QRISK3) calculator has been launched for CV risk assessment in the general population. QRISK3 now includes the presence of SLE as one of its variables for calculating CV risk. Our objective was to compare the predictive capacity between QRISK3 and the Systematic Coronary Risk Evaluation (SCORE) for the presence of subclinical carotid atherosclerosis in patients with SLE.

Methods
Two hundred and ninety-six patients with SLE were recruited. The presence of subclinical atherosclerosis was evaluated by carotid ultrasound to identify carotid plaque and the thickness of the carotid intima–media (cIMT). QRISK3 and SCORE were calculated. The relationship of QRISK3 and SCORE with each other and with the presence of subclinical carotid atherosclerosis (both carotid plaque and cIMT) was studied.

Results
There was no correlation between SCORE and QRISK3 in patients with SLE (Spearman’s rho = −0.008, P = 0.90). Although QRISK3 showed a statistically significant correlation with cIMT (Spearman’s rho = 0.420, P = 0.000), this relationship was not found between SCORE and cIMT (Spearman’s rho = −0.005, P = 0.93). The discrimination capacity of QRISK3 for the presence of carotid plaque was statistically significant and superior to that of SCORE (AUC 0.765 [95% CI: 0.711, 0.820] vs 0.561 [95% CI: 0.494, 0.629], P = 0.000).

Conclusion
QRISK3 discrimination for subclinical atherosclerosis is higher than that of SCORE. QRISK3, and not SCORE, should be used for the calculation of CV risk in patients with SLE.
Biallelic Editing of the LOB1 Promoter via CRISPR/Cas9 Creates Canker-Resistant ‘Duncan’ Grapefruit
Authors: Jia Hongge , Omar Ahmad A. , Orbović Vladimir , Wang Nian 
Published: July 2021

Citrus canker caused by Xanthomonas citri subsp. citri is one of the most devastating citrus diseases worldwide. Generating disease-resistant citrus varieties is considered one of the most efficient and environmentally friendly measures for controlling canker. X. citri subsp. citri causes canker symptoms by inducing the expression of canker susceptibility gene LOB1 via PthA4, a transcription activator-like (TAL) effector, by binding to the effector binding element (EBE) in the promoter region. In previous studies, canker-resistant plants were generated by mutating the coding region or the EBE of LOB1. However, homozygous or biallelic canker-resistant plants have not been generated for commercial citrus varieties, such as grapefruit (Citrus paradisi), which usually contain two alleles of LOB1 and thus, have two types of LOB1 promoter sequences: TI LOBP and TII LOBP. Two different sgRNAs were used to target both EBE types. Both 35S promoter and Yao promoter were used to drive the expression of SpCas9p to modify EBEPthA4-LOBP in grapefruit. Using ‘Duncan’ grapefruit epicotyls as explants, 19 genome-edited grapefruit plants were generated with one biallelic mutant line (#DunYao7). X. citri subsp. citri caused canker symptoms on wild-type and nonbiallelic mutant plants but not on #DunYao7. XccPthA4 mutant containing the designer TAL effector dLOB1.5, which recognizes a conserved sequence in both wild-type and #DunYao7, caused canker symptoms on both wild-type and #DunYao7. No off-target mutations were detected in #DunYao7. This study represents the first time that CRISPR-mediated genome editing has been successfully used to generate disease-resistant plants for ‘Duncan’ grapefruit, paving the way for using disease-resistant varieties to control canker.
Plasmodiophora brassicae CBM18 Proteins Bind Chitin and Suppress Chitin-Triggered Immunity
Authors: Muirhead Kevin , Pérez-López Edel 
Published: July 2021

Plants have a sophisticated and multilayered immune system. However, plant pathogens, helped by effector proteins, have found several strategies to evade plant immunity. For instance, the clubroot pathogen Plasmodiophora brassicae is able to turn the roots of susceptible hosts into nutrient-sink galls suppressing pattern-triggered immunity (PTI) and effector-triggered immunity. Chitin, the main component of P. brassicae spore cell walls and a well-known pathogen-associated molecular pattern, can elicit PTI but is also the target of plant chitinases and chitin deacetylases. The fact that P. brassicae does not trigger PTI during infection of susceptible hosts motivated a genome-wide search of genes coding for secreted proteins with domains previously associated with chitin binding. We found that the P. brassicae genome encodes a repertoire of candidate-secreted effectors containing the chitin-binding domain carbohydrate-binding module family 18 (CBM18), chitinase, and chitin deacetylase domains. The role of these proteins in the pathogenicity of the clubroot pathogen is unknown. Here, we characterized two CBM18 proteins, PbChiB2 and PbChiB4, which are transcriptionally activated during infection. Through coprecipitation, we found that recombinant PbChiB2 and PbChiB4 bind to spores and to chitin oligomers. We also showed that both proteins suppress chitin-triggered activation of the map kinase proteins MPK3 and MPK6 in the host Brassica napus. These findings suggest that P. brassicae CBM18 proteins act as effectors for protecting the clubroot pathogen and for suppressing chitin-triggered immunity during infection. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Real-time RT-PCR Allelic Discrimination Assay for Detection of N501Y Mutation in the Spike Protein of SARS-CoV-2 Associated with Variants of Concern
Authors: Abdulnoor Mariana , Eshaghi AliReza , Perusini Stephen J. , Corbeil Antoine , Cronin Kirby , Fittipaldi Nahuel , Forbes Jessica D. , Guthrie Jennifer L. , Kus Julianne V. , Majury Anna , Mazzulli Tony , Melano Roberto G. , Olsha Romy , Sullivan Ashleigh , Tran Vanessa , Patel Samir N. , Allen Vanessa G. , Gubbay Jonathan B. 
Published: July 2021

AbstractThe N501Y amino acid mutation caused by a single point substitution A23063T in the spike gene of SARS-CoV2 is possessed by the three most common variants of concern - B.1.1.7, B.1.351, and P.1. A rapid screening tool using this mutation is important for surveillance during the COVID-19 pandemic.We developed and validated a single nucleotide polymorphism real-time reverse transcription polymerase chain reaction assay using allelic discrimination of the spike gene N501Ymutation to screen for potential variants of concern and differentiate them from wild-type SARS-CoV-2. A total of 160 clinical specimens positive for SARS-CoV-2 were characterized as mutant (N501Y) or wild-type by Sanger sequencing and were subsequently tested with the N501Y single nucleotide polymorphism real time reverse transcriptase polymerase chain reaction assay. Our assay compared to sequencing, the gold standard for SNP detection and lineage identification, demonstrated clinical sensitivity of 100% for all 57 specimens displaying N501Y mutant, which were confirmed by Sanger sequencing to be typed as A23063T, including one specimen with mixed signal for wildtype and mutant. Clinical specificity was 100% in all 103 specimens typed as wild-type, with A23063 identified as wild-type by Sanger sequencing. The identification of circulating SARS-CoV-2 lineages carrying an N501Y mutation is critical for surveillance purposes. Current identification methods rely primarily on Sanger sequencing or whole genome sequencing which are time-consuming, labor-intensive and costly. The assay described herein is an efficient tool for high-volume specimen screening for SARS-CoV-2 VOCs and for selecting specimens for confirmatory Sanger or whole genome sequencing.
Heterogeneity of hypoxemia severity according to oxygenation index in COVID-19 pneumonia
Authors: Núñez Isaac , Soto-Mota Adrian 
Published: July 2021

ABSTRACTObjectiveTo compare hypoxemia severity of patients with COVID-19 pneumonia that arrive at an emergency department as classified by three oxygenation indexes.DesignRetrospective analysis of pulse oximeter saturation and arterial blood gas analysis obtained at arrival.SettingTertiary referral hospital in Mexico City converted early in the pandemic to a COVID-19 center.Patients and measurementsA total of 2,960 patients with suspected COVID-19 pneumonia were admitted to the emergency department from April 2020 until March 2021. Pulse oximeter saturation and arterial blood gas analysis was obtained in all of them. Pulse oximeter saturation (SpO2) to inspired oxygen fraction ratio (FiO2), oxygen saturation in arterial blood (SatO2) to FiO2 ratio, and oxygen pressure in arterial blood to FiO2 ratio were calculated for every patient.InterventionsNone.Main ResultsA strong correlation was seen between PaO2/FiO2 & SpO2/FiO2 (rho = 0.6, p < 0.001), and SatO2/FiO2 & SpO2/FiO2 (rho = 0.65, p < 0.001), while a very strong correlation was seen between PaO2/FiO2 & SatO2/FiO2 (rho = 0.88, p < 0.001). When classifying severity by quantiles, considerable cross-over was observed when comparing oxygenation indexes, as only 785 (26.5%) patients were in the same quintile across the three indexes.ConclusionsHypoxemia severity is heterogeneous according to the oxygenation index utilized. This limits their usefulness as sole markers of severity, as inter-observer variability, especially on FiO2 estimation, and different practices limit consistent follow up and treatment decisions.
Change in disease dynamics and health care utilisation in children during COVID 19 in a tertiary care hospital of Eastern India
Authors: Sahoo Bandya , Kanyari S Suneeti , Pradhan Deepti Damayanty , Patnaik Sibabratta , Behera Manas Ranjan 
Published: July 2021

AbstractThis retrospective, observational study was conducted by collecting data from medical records during COVID 19 pandemic from March 2020 till August 2020. This was compared with the data of 2019 during similar months. The impact of COVID 19 on use of preventive and curative paediatric health care service units like outpatient department, casualty, intensive care and immunization clinic were assessed. Data from 2019 to 2020 were compared using standard parametric and nonparametric tests. There was a significant decline in routine OPD (68%) attendance during the COVID 19 period as compared to pre-COVID period. Paediatric ward admissions and PICU admissions were decreased by 55% and 42% respectively. We also observed a significant 43% decline in the number of children attending immunization clinic in the year 2020. The fear of COVID 19 pandemic and the measures taken to control the pandemic has affected the health seeking behaviour of patients. This evaluation of trends in healthcare use may help in planning the delivery of healthcare service delivery in future.
Joint estimation of relaxation and diffusion tissue parameters for prostate cancer grading with relaxation-VERDICT MRI
Authors: Palombo Marco , Valindria Vanya , Singh Saurabh , Chiou Eleni , Giganti Francesco , Pye Hayley , Whitaker Hayley C. , Atkinson David , Punwani Shonit , Alexander Daniel C. , Panagiotaki Eleftheria 
Published: July 2021

AbstractPurposeThe Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumours (VERDICT) technique has shown promise discriminating normal from prostate cancer (PCa) tissue and Gleason grade 3+3 from 3+4. However, VERDICT currently doesn’t account for the inherent relaxation properties of the tissue that could add complementary information and potentially enhance its diagnostic power. The aim of this work is to introduce relaxation-VERDICT (rVERDICT) for prostate, a model for the joint estimation of diffusion and relaxation parameters.Methods72 men with suspected PCa underwent multiparametric MRI (mp-MRI) and VERDICT MRI. Among these, 44 underwent targeted biopsy and were analysed with rVERDICT using deep neural networks for fast fitting (∼60 times faster than non-linear least squares minimisation approach). A convolutional neural network classifier assessed the rVERDICT parameters in differentiating Gleason grades measured with accuracy, F1-score and Cohen’s kappa. To assess repeatability, five men were imaged twice.ResultsThere were 37 cancer lesions: 6 Gleason 3+3, 18 Gleason 3+4, and 13 Gleason ≥4+3. The rVERDICT intracellular volume fraction fic discriminated between Gleason 3+3 and 3+4 (p=0.003); Gleason 3+4 and ≥4+3 (p=0.040); and between 5-class Gleason grades with (accuracy, F1-score,kappa)=(8,7,3) percentage points higher than classic VERDICT, and (12,13,24) percentage points higher than the ADC from mp-MRI. Repeatability of rVERDICT parameters was high (R2=0.79–0.98,CV=1%–7%,ICC=92%-98%). T2 values estimated with rVERDICT were not significantly different from those estimated with an independent multi-TE acquisition (p>0.05).ConclusionrVERDICT allows for accurate, fast and repeatable estimation of diffusion and relaxation properties of PCa and enables discriminating Gleason grade groups.
Communicating about COVID-19 vaccine development and safety
Authors: Thorpe Alistair , Fagerlin Angela , Butler Jorie , Stevens Vanessa , Drews Frank A. , Shoemaker Holly , Riddoch Marian , Scherer Laura D. 
Published: July 2021

AbstractPurposeBeliefs that the risks from the vaccine outweigh the risks from getting COVID-19 and concerns that the vaccine development process was rushed and lacking rigor have been identified as important drivers of hesitancy and refusal to get a COVID-19 vaccine. We tested whether messages designed to address these beliefs and concerns might promote intentions to get a COVID-19 vaccine.MethodAn online survey fielded between March 8-March 23, 2021 with US Veteran (n=688) and non-Veteran (n=387) respondents. In a between-subjects experiment, respondents were randomly assigned to a control group (with no message) or to read one of two intervention messages: 1. a fact-box styled message comparing the risks of getting COVID-19 compared to the vaccine, and 2. a timeline styled message describing the development process of the COVID-19 mRNA vaccines.ResultsMost respondents (60%) wanted a COVID-19 vaccine. However, 17% expressed hesitancy and 23% did not want to get a COVID-19 vaccine. The fact-box styled message and the timeline message did not significantly improve vaccination intentions, F(2,358)=0.86, p=.425, , or reduce the time respondents wanted to wait before getting vaccinated, F(2,306)=0.79, p=.453, , compared to no messages.DiscussionWe did not find an impact on vaccine intention based on providing information about vaccine risks and development. Further research is needed to identify how to effectively address concerns about the risks associated with COVID-19 vaccines and the development process and to understand additional factors that influence vaccine intentions.
Clinical management and impact of scarlet fever in the modern era: findings from a cross-sectional study of cases in London, 2018-2019
Authors: Herdman M. Trent , Cordery Rebecca , Karo Basel , Purba Amrit Kaur , Begum Lipi , Lamagni Theresa , Kee Chuin , Balasegaram Sooria , Sriskandan Shiranee 
Published: July 2021

AbstractBackgroundScarlet fever incidence has risen steeply in recent years, and is associated with wider outbreaks of severe Group A Streptococcal infections. Yet, few studies of its epidemiology, clinical features, and management have been undertaken in the antibiotic era.AimTo characterize symptomatology, management, and consequences of scarlet fever and identify associations with delayed diagnosis.Design/SettingCross-sectional study of children with scarlet fever in London, 2018-2019.Methodsonline survey of parents/guardians of children with scarlet fever identified by Health Protection Teams, recording demographics, symptoms, care-seeking, and management; logistic regression for factors associated with delayed diagnosis; Cox’s regression for consequences of delayed diagnosis.ResultsResponses represented 412 cases in a period with 6828 notifications for children 0-14 years old, and 410 school/nursery outbreaks. 70% first sought care from general practice, and 31% had multiple consultations. For 28%, scarlet fever was not considered at first consultation: in these cases, symptoms were frequently attributed to viral infection (60%, 64/106). Delay in diagnosis beyond first consultation occurred more frequently among children aged 5+ who presented with sore throat (odds ratio 2.8 vs. 5+ without sore throat; 95%CI 1.3-5.8; P=0.006). On average, cases with delayed diagnosis took one day longer to return to baseline activities, and required one additional day off school versus those diagnosed at first consultation.ConclusionsIn assessing children with fever, rash, and sore throat, practitioners should be alert to the possibility of scarlet fever: it is frequently missed at first consultation, and prompt recognition speeds clinical recovery and public health management.How this fits in [4 sentences summarising key messages of background and findings]-In the five years leading up to the pandemic lockdown of 2020, scarlet fever incidence rose markedly in England and Wales, prompting this investigation of cases in London 2018-2019.-Prompt recognition of the disease by carers and clinicians can direct timely antibiotic therapy, limit transmission in the household and community, and direct the identification and control of outbreaks.-In this study, delayed diagnosis was more likely to occur among older children presenting with sore throat—perhaps reflecting a lower index of suspicion in this age group.-Cases with delayed diagnosis took longer to return to normal activities, and required more time off from school than those diagnosed at the first consultation.