bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alteration of pro-carcinogenic gut microbiota is associated with clear cell renal cell carcinoma tumorigenesis
Authors: Yang Bo-Yu , Zhao Fang-Zhou , Li Xuan-Hao , Zhao Mei-Shan , Lv Jing-Cheng , Shi Ming-Jun , Li Jun , Zhou Zhi-Yuan , Wang Jing-Jing , Song Jian 
Published: December 2022

ABSTRACTIncreasing evidence suggests that gut microbiota is involved in the occurrence and progression of urinary system diseases such as clear cell renal cell carcinoma (ccRCC). However, the mechanism of how alteration of gut metagenome promotes ccRCC remains unclear. Here we aim to elucidate the association of specific gut bacteria and their metabolites with ccRCC. In a pilot case-control study among 30 ccRCC patients and 30 healthy controls, 16S ribosomal RNA (rRNA) gene sequencing were analyzed from fecal samples collected prior to surgery or hospitalization. Alpha diversity and beta diversity analysis of the gut microbiota were performed, and differential taxa were identified by multivariate statistics. Meanwhile, serum metabolism was measured by UHPLC-MS, and differential genes were identified based on theTCGAdatabase. Random Forests revealed the relative abundances of 20 species differed significantly between the RCC group and the Control group, among which 9 species, such asDesulfovibrionaceae,were enriched in the RCC group, and 11 species, such as four kinds ofLactobacillus,were less abundant. Concomitantly, serum level of taurine, which was considered to be consumed byDesulfovibrionaceaeand released byLactobacillus, has decreased in the RCC group. In addition, macrophage-related genes such asGabbr1was upregulated in ccRCC patients from our results.IMPORTANCETo our knowledge, few studies investigate the correlation of gut microbiota and ccRCC tumorigenesis. Overall, our sequencing data suggest that changes in the composition of specific gut microbiota, especiallyLactobacillusandDesulfovibrionaceae,may be involved in ccRCC. Numerous serum metabolites, for example, taurine, which were modified in concert with dysregulation of gut microbiota, were associated with metabolic status during ccRCC development. Furthermore, through comparative analysis of clinical indicators, we found that gut dysbiosis could potentially reshape systemic inflammation, which participated in ccRCC tumorigenesis and we performed bioinformatics analysis to draw this conclusion. In Summary, it could be concluded from our study that the reduction of protective bacteriaLactobacillus, proliferation of sulfide-degrading bacteriaDesulfovibrionaceae, reduction of taurine, and enrichment of macrophage related genes might be the risk predictors of ccRCC.
Multiple sites on glycoprotein H (gH) functionally interact with the gB fusion protein to promote fusion during herpes simplex virus (HSV) entry
Authors: Fan Qing , Hippler Daniel P. , Yang Yueqi , Longnecker Richard , Connolly Sarah A. 
Published: December 2022

ABSTRACTEnveloped virus entry requires fusion of the viral envelope with a host cell membrane. Herpes simplex virus type 1 (HSV-1) entry is mediated by a set of glycoproteins that interact to trigger the viral fusion protein glycoprotein B (gB). In the current model, receptor-binding by gD signals a gH/gL heterodimer to trigger a refolding event in gB that fuses the membranes. To explore functional interactions between gB and gH/gL, we used a bacterial artificial chromosome (BAC) to generate two HSV-1 mutants that show a small plaque phenotype due to changes in gB. We passaged the viruses to select for restoration of plaque size and analyzed second-site mutations that arose in gH. HSV-1 gB was replaced either by gB from saimiriine herpesvirus type 1 (SaHV-1) or by a mutant form of HSV-1 gB with three alanine substitutions in domain V (gB3A). To shift the selective pressure away from gB, the gB3A virus was passaged in cells expressing gB3A. Sequencing of passaged viruses identified two interesting mutations in gH, including gH-H789 in domain IV and gH-S830N in the cytoplasmic tail (CT). Characterization of these gH mutations indicated they are responsible for the enhanced plaque size. Rather than being globally hyperfusogenic, both gH mutations partially rescued function of the specific gB version present during their selection. These sites may represent functional interaction sites on gH/gL for gB. gH-H789 may alter the positioning of a membrane-proximal flap in the gH ectodomain, whereas gH-S830 may contribute to an interaction between the gB and gH CTs.IMPORTANCEEnveloped viruses enter cells by fusing their envelope with the host cell membrane. Herpes simplex virus type 1 (HSV-1) entry requires the coordinated interaction of several viral glycoproteins, including gH/gL and gB. gH/gL and gB are essential for virus replication and both proteins are targets of neutralizing antibodies. gB fuses the membranes after being activated by gH/gL, but the details of how gH/gL activates gB are not known. This study examined the gH/gL-gB interaction using HSV-1 mutants that displayed reduced virus entry due to changes in gB. The mutant viruses were grown over time to select for additional mutations that could partially restore entry. Two mutations in gH (H789Y and S830N) were identified. The positions of the mutations in gH/gL may represent sites that contribute to gB activation during virus entry.
Capillary angiopathy and aquaporin-4 after Aβ immunisation in Alzheimer’s disease – potential relevance to Amyloid-Related Imaging Abnormalities
Authors: Harrison Charlotte H. , Sakai Kenji , Johnston David A. , Holmes Clive , Boche Delphine , Nicoll James AR 
Published: December 2022

AbstractAimsAmyloid-related imaging abnormalities (ARIA) have hampered clinical trials and therapeutic use of amyloid-β (Aβ) immunotherapy for Alzheimer’s disease (AD), with the cause of the white matter oedema (ARIA-E) unknown. Aquaporin 4 (AQP4), present in astrocyte endfeet, controls water flow across the blood-brain barrier. Experimental studies suggest that as Aβ plaques are cleared following immunotherapy, capillary angiopathy (capCAA) increases, displacing astrocyte endfeet allowing influx of extracellular water (oedema). We sought neuropathological evidence for this mechanism in immunised AD patients.MethodsBrains of 16 Alzheimer’s patients immunised against Aβ42 (iAD, AN1792, Elan Pharmaceuticals) and 28 unimmunized Alzheimer’s (cAD) cases were immunolabelled and quantified for Aβ42 and AQP4.ResultsCapCAA was 3.5 times higher in iAD (p=0.009). No difference between the groups was identified in the proportion of capillaries wrapped by AQP4 or AQP4 protein load. However, capCAA in iAD negatively correlated with AQP4 load (r = -0.498, p<0.001), suggesting disturbance of AQP4 in presence of capCAA.ConclusionsAfter Aβ immunotherapy, capCAA was increased, likely reflecting the drainage of soluble Aβ towards the vasculature and providing a potential mechanism to disrupt AQP4-containing astrocyte endfeet, resulting in ARIA-E. We did not identify alterations in AQP4, potentially because of limitations in the timing of the post-mortem analysis. Given the recent licencing of Aβ immunotherapy, the field must prioritise obtaining neuropathological correlates of ARIA to explore its mechanisms further.
Th17.1 cell driven sarcoidosis-like inflammation after anti-BCMA CAR T cells in multiple myeloma
Authors: Leipold Alexander M. , Werner Rudolf A. , Düll Johannes , Jung Pius , John Mara , Stanojkovska Emilia , Zhou Xiang , Hornburger Hannah , Ruckdeschel Anna , Dietrich Oliver , Imdahl Fabian , Krammer Tobias , Knop Stefan , Rosenwald Andreas , Buck Andreas , Sander Leif Erik , Einsele Hermann , Kortüm K. Martin , Saliba Antoine-Emmanuel , Rasche Leo 
Published: December 2022

ABSTRACTPseudo-progression and flare-up phenomena constitute a novel diagnostic challenge in the follow-up of patients treated with immune-oncology drugs. We present a case study on pulmonary flare-up after Idecabtagen Vicleucel (Ide-cel), a BCMA targeting CAR T-cell therapy, and used single-cell RNA-seq (scRNA-seq) to identify a Th17.1 driven autoimmune mechanism as the biological underpinning of this phenomenon. By integrating datasets of various lung pathological conditions, we revealed transcriptomic similarities between post CAR T pulmonary lesions and sarcoidosis. Furthermore, we explored a noninvasive PET based diagnostic approach and showed that tracers binding to CXCR4 complement FDG PET imaging in this setting, allowing discrimination between immune-mediated changes and true relapse after CAR T-cell treatment. In conclusion, our study highlights a Th17.1 driven autoimmune phenomenon after CAR T, which may be misinterpreted as disease relapse, and that imaging with multiple PET tracers and scRNA-seq could help in this diagnostic dilemma.
Comparable Efficacy of Curcumin and Proton Pump Inhibitor for Functional Dyspepsia: A Randomized Double-blind Controlled Trial
Authors: Kongkam Pradermchai , Khongkha Wichittra , Lopimpisuth Chawin , Chumsri Chisanucha , Kosarussawadee Prach , Phutrakool Phanupong , Khamsai Sittichai , Sawanyawisuth Kittisak , Sura Thanyachai , Phisalprapa Pochamana , Buamahakul Thanwa , Siwamogsatham Sarawut , Angsusing Jaenjira , Poonniam Pratchayanan , Wanaratna Kulthanit , Teerachaisakul Monthaka , Pongpirul Krit 
Published: December 2022

ABSTRACTObjectivesCurcumin has been claimed to have gastrointestinal benefits, including dyspepsia, a common disorder that could be managed in a primary care setting with behavioral and dietary modifications as well as over-the-counter medications. This study aimed to compare the efficacy of curcumin versus omeprazole in improving patient-reported outcomes.DesignPatients with functional dyspepsia were randomized to curcumin alone (C), omeprazole alone (O), or curcumin plus omeprazole (C+O). Patients in the combination group received 2 capsules of 250 mg curcumin 4 times daily and 1 capsule of 20 mg omeprazole once daily for 28 days. The primary outcomes were functional dyspepsia symptoms on days 28 and 56 assessed using the Severity of Dyspepsia Assessment (SODA) scores. Secondary outcomes were the occurrence of adverse events (AEs) and serious adverse events (SAEs).ResultsA total of 206 enrolled patients were randomly assigned to the three groups, of which 151 completed the study. Demographic data (age 49.7±11.9 years; female 73.4%), clinical characteristics, and baseline dyspepsia scores were comparable between the three groups. SODA scores in each group showed significant improvement on day 28 and day 56 in the pain, non-pain, and satisfaction categories. No significant differences were observed among the three groups and no serious adverse events occurred.ConclusionCurcumin and omeprazole have comparable efficacy for functional dyspepsia with no obvious synergistic effect.Key MessagesWhat is already knownDyspepsia is one of the most common disorders in which patients usually try behavioral and diet modifications, and over-the-counter drugs before seeing a physician.Proton pump inhibitors have been established as an effective treatment for functional dyspepsia.Curcumin, an active ingredient in turmeric, is currently used for the treatment of dyspepsia in countries in Southeast Asia.However, there is no clinical trial evidence to support the use of curcumin as a first-line treatment.What this study addsBased on this double-blind, placebo-controlled clinical trial, oral curcumin is safe and well tolerated.Patients with functional dyspepsia were treated with curcumin, curcumin plus omeprazole, and omeprazole, which showed a similar significant symptomatic improvement.There was no synergistic effect detected between omeprazole and curcumin.How this study might affect research, practice, or policyThis study provides a possible additional drug option for patients with functional dyspepsia.More clinical trials are required to assess long-term outcomes and adverse events.
Statistical Assessment of Biomarker Replicability using MAJAR Method
Authors: Xie Yuhan , Zhai Song , Jiang Wei , Zhao Hongyu , Mehrotra Devan V. , Shen Judong 
Published: December 2022

AbstractIn the era of precision medicine, many biomarkers have been discovered to be associated with drug efficacy and safety responses, which can be used for patient stratification and drug response prediction. Due to small sample size and limited power of randomized clinical studies, meta-analysis is usually conducted to aggregate all available studies to maximize the power for identifying prognostic and predictive biomarkers. Since all available data are already aggregated, it is often challenging to find an independent study to replicate the discoveries from the meta-analysis (e.g., in meta-analysis of pharmacogenomics genome-wide association studies (PGx GWAS)), which seriously limits the potential impacts of the discovered biomarkers. To overcome this challenge, we develop a novel statistical framework, MAJAR (Meta-Analysis of Joint effect Associations for biomarker Replicability assessment), to jointly test prognostic and predictive effects and assess the replicability of identified biomarkers by implementing an enhanced Expectation–Maximization algorithm and calculating their posterior-probability-of-replicabilities (PPR) and Bayesian false discovery rates (Fdr). Extensive simulation studies were conducted to compare the performance of MAJAR and existing methods in terms of Fdr, power, and computational efficiency. The simulation results showed improved statistical power with well-controlled Fdr of MAJAR over existing methods and robustness to outliers under different data generation processes while considering both prognostic and predictive effects in the model. We further demonstrated the advantages of MAJAR over existing methods by applying MAJAR to the PGx GWAS summary statistics data from a large cardiovascular randomized clinical trial (IMPROVE-IT). Compared to testing main effects only, MAJAR identified 12 novel variants associated with the treatment-related LDL cholesterol (LDL-C) reduction from baseline.
Liver disease is a significant risk factor for cardiovascular outcomes - a UK Biobank study
Authors: Roca-Fernandez Adriana , Banerjee Rajarshi , Thomaides-Brears Helena , Telford Alison , Sanyal Arun , Neubauer Stefan , Nichols Thomas E , Raman Betty , McCracken Celeste , Petersen Steffen E , Ntusi Ntobeko AB , Cuthbertson Daniel J , Lai Michele , Dennis Andrea , Banerjee Amitava 
Published: December 2022

ABSTRACTBackgroundChronic liver disease (CLD) and cardiovascular diseases (CVD) share common risk factors; the former is associated with a two-fold greater incidence of CVD. With most CLD being preventable/modifiable, early identification of at high-risk individuals is crucial. Using data from the UK Biobank imaging sub-study, we tested the hypothesis that early signs of liver disease (measured by iron corrected T1-mapping (cT1)) is associated with an increased risk of major cardiovascular events.MethodsLiver disease activity (cT1) and fat (PDFF) were measured using LiverMultiScan® from images acquired between January-2016 and February-2020 in the UK Biobank imaging sub-study. Multivariable Cox regression was used to explore associations between liver cT1 (MRI) andprimary CVD outcomes(coronary artery disease, atrial fibrillation, embolism/vascular events, heart failure and stroke), as well as CVDhospitalisationandall-cause mortality. Other liver blood biomarkers (AST, ALT, AST/ALT ratio, FIB4), general metabolism biomarkers (CRP, HbA1c, systolic blood pressure (SBP), total cholesterol), and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (MetS= at least 3 of these traits: a large waist, high triglycerides, low HDL cholesterol, increased SBP, or elevated HbA1c)Results33,616 participants in the UK Biobank imaging sub-study (65 years, mean BMI 26kg/m2, mean HbA1c 35mmol/mol) had complete MRI liver data with linked clinical outcomes [median time to major CVD event onset: 1.4 years (range:0.002-5.1); follow-up: 2.5 years (range:1.1-5.2)]. Liver disease activity (cT1), but not liver fat (PDFF), was associated with a higher risk of any major CVD event [HR(CI) 1.14(1.03-1.26), p=0.008], AF [1.30 (1.12-1.5), p<0.001]; HF [1.30 (1.08 - 1.58), p=0.004]; CVD hospitalisation [1.27(1.18-1.387, p<0.001] and all-cause mortality [1.19(1.02-1.38), p=0.026]. FIB4 index, was associated with HF [1.06 (1.01 - 1.10)), p=0.007]. The risk of CVD hospitalisation was also independently associated with cT1 in individuals without MetS [1.26(1.13-1.4), p<0.001].ConclusionLiver disease activity, as measured with MRI-derived biomarker cT1, was independently associated with a higher risk of new onset CVD events and all-cause mortality. This association occurred even without pre-existing impairment of metabolic health and was independent of FIB4 or liver fat content. cT1 was identified as a major predictor of adverse CVD outcomes.
The effect of free school fruit on academic performance: a nationwide quasi-experiment
Authors: Halkjelsvik Torleif , Bere Elling 
Published: December 2022

AbstractIn past research, higher intake of fruit has been associated with better academic achievement. Can the provision of one piece of fruit every school day improve children’s academic performance? In Norway, the government required all lower secondary schools to provide fruit to their pupils from 2007 to 2014. The policy also covered schools with combined elementary and lower secondary education (1st to 10thgrade), but not ordinary elementary schools (1stto 7thgrade). This differentiation, in combination with administrative data on test scores before, during, and after the law was enforced, created a nationwide quasi-experiment. Population register data on parents’ sociodemographic characteristics allowed for targeted analyses of a subsample with lower grades and lower fruit intake (boys of low socioeconomic status). In pre-registered analyses, we found no evidence that exposure to the free school fruit policy improved academic performance in the subsample or the entire population of Norwegian pupils. The free fruit policy coincided with a slight decline in performance among pupils covered by the policy. In a Western country with low levels of food insecurity, a policy that required schools to provide free fruit to pupils did not improve learning and may even have interfered with learning.Significance StatementThe intake of fruit is believed to be beneficial for children’s concentration, and research has linked a higher intake of fruit to better academic performance. During a national policy that made it mandatory for some types of elementary schools to provide one daily piece of fruit to every pupil, we did not observe any beneficial effects on learning. On the contrary, the policy coincided with a slight performance decline. Even for low-socioeconomic boys, who have lower-than-average grades and a lower intake of fruit, there was no improvement in academic results associated with the policy. We speculate that the policy may have required resources that otherwise would be used for teaching or teaching-related administration.
Determinants for detection of infection with SARS-CoV-2 Omicron variants of concern in health care workers by rapid antigen tests
Authors: Wettengel Jochen M. , Strehle Katharina , von Lucke Catharina , Roggendorf Hedwig , Jeske Samuel D. , Christa Catharina , Zelger Otto , Haller Bernhard , Protzer Ulrike , Knolle Percy A. 
Published: December 2022

IMPORTANCEThe rapid genetic evolution of SARS-CoV-2 and in particular the highly contagious Omicron variant of concern (VoC) may pose problems for rapid and accurate diagnosis of infection.OBJECTIVEDetermine the diagnostic accuracy and robustness of a second generation rapid antigen tests compared to gold-standard, PCR-based diagnostics, for detection of infection with different SARS-CoV-2 Omicron VoC sub lineages in health care workers.DESIGN, SETTING, AND PARTICIPANTSThe study included 428 health care workers from the University Hospital Munich Rechts der Isar of the Technical University of Munich who either reported recent onset of COVID-19 associated symptoms or completed routine diagnostic testing between 24thof May and 22ndof September 2022. All participants gave written informed consent to participate in this study and completed a questionnaire on infection-associated symptoms, prior SARS-CoV-2 infections and vaccination status.INTERVENTIONSDuring the first visit, two nasal swabs and one oropharyngeal swab were taken to perform two rapid antigen tests and a SARS-CoV-2 PCR-assay, respectively. A second set of nasal swabs was taken by the participants themselves two days later to repeat the two rapid antigen tests.MAIN OUTCOMES AND MEASURESThe accuracy for detection of infection with different SARS-CoV-2 Omicron VoCs with two rapid antigen tests (Test IandTest II) was determined and compared to quantitative SARS-CoV-2 RNA levels detected by PCR.RESULTSIn a side-by-side comparison, we found thatTest Idetected viral nucleocapsids from Omicron VoC (BA.5.2.3) at higher dilutions compared toTest II. In the 428 health care workers,Test Iand Test II detected PCR-confirmed SARS-CoV-2 infection with different Omicron VoCs (BA.2, BA.4, BA.5) with a sensitivity of 89.4% (95% CI 81.9% - 94.6%) and 83.7% (95% CI 75.12% - 90.18%), respectively. Increased sensitivity ofTest Iwas also reflected by earlier detection of SARS-CoV-2 infection. The lower test sensitivity ofTest IIcould be compensated for by a repeated test performed two days later.CONCLUSIONS AND RELEVANCEOur study demonstrates that rapid antigen tests are suited to detect infection with the SARS-CoV-2 Omicron VoC and reveal an advantage of a lower detection limit for earlier detection of infection in health care workers.
Mental health self-care during the COVID-19 pandemic: A prospective cohort study in Australia
Authors: Griffiths Daniel , Dhira Pradipta Vinsensia Maharani Kanya , Collie Alex 
Published: December 2022

AbstractPandemic public health measures have affected mental health for many people, resulting in varied approaches to mental health self-care. During 27 April – 26 July 2020, we surveyed a cohort of 1646 Australians, who were in paid employment prior to the pandemic, on changes in work, health, and managing their mental health concerns. Lifestyle changes were most the most frequently reported action to manage mental health concerns (78%), and were more common for women (OR=2.33, 95%CI=[1.82, 3.03]), and people experiencing recent work loss (OR=1.54, 95%CI=[1.04, 2.28]). Mental health self-care was more common for people experiencing psychological distress, or with pre-exisiting mental health conditions. Talking to friends about mental health, exercise and dietary changes, were more common for women and younger adults. Findings highlight potential benefits of reducing barriers to formal mental health services and supports during crises, particularly for people who less commonly seek help, and those experiencing psychological distress.