bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyroptosis‐related molecular classification and immune microenvironment infiltration in breast cancer: A novel therapeutic target
Authors: Luo Jiayue , Lai Jianguo 
Published: March 2022

AbstractThe underlying role of pyroptosis in breast cancer (BC) remains unknown. Herein, we investigated the correlations of 33 pyroptosis‐related genes (PRGs) with immune checkpoints and immune cell infiltrations in BC patients based on The Cancer Genome Atlas cohort (n = 996) and Gene Expression Omnibus cohort (n = 3,262). Enrichment analysis revealed that these PRGs mainly functioned in pyroptosis, inflammasomes and regulation of autophagy pathway. Four prognostic independent PRGs (CASP9, TIRAP, GSDMC and IL18) were identified. Then, cluster 1/2 was recognized using consensus clustering for these four PRGs. Patients from cluster 1 had a favourable prognosis and diverse immune cell infiltrations. A nomogram was developed based on age, TNM stage, tumour subtype and pyroptosis score. Patients with the high‐risk group exhibited worse 5‐year OS, and the result was consistent in the external cohort. Additionally, high‐risk group patients were associated with downregulated immune checkpoint expression. Further analysis suggested that the high‐risk group patients were associated with a higher IC50 of paclitaxel, doxorubicin, cisplatin, methotrexate and vinorelbine. In summarizing, the pyroptosis score‐based nomogram might serve as an independent prognostic predictor and could guide medication for chemotherapy. Additionally, it may bring novel insight into the regulation of tumour immune microenvironment in BC and help to achieve precision immunotherapy.
Conducting a good ward round: How do leaders do it?
Authors: Merriman Clair , Freeth Della 
Published: February 2022

AbstractRationale, Aims and ObjectivesWard rounds (WRs) are complex social processes. Done well, WR discussions and decisions contribute to timely, safe, effective progression of care. However, literature highlights medical dominance; marginalisation or absence of other perspectives, safety risks and suboptimal resource use. This study examined leadership behaviours and what supported good interprofessional WRs, defined as enabling interprofessional collaboration and decision making which progresses patient care in a safe and timely manner. Deepening appreciation of this art should support learning and improvements.MethodMixed‐method appreciative inquiry (AI) into how WRs go well and could go well more often. Context: daily interprofessional consultant‐led WRs in a large adult critical care unit. Data: ethnographic and structured observations (73 h, 348 patient reviews); AI conversations and interviews (71 participants). Inductive iterative analysis shaped by Activity Theory. Participants: 256 qualified healthcare professionals working in the unit.ResultsLeadership of good WRs supported (and minimized contradictions to): making good use of expertise and time, and effective communication. These three key activities required careful and skilled orchestration of contributions to each patient review, which was achieved through four distinct phases (a broadly predictable script), ensuring opportunity to contribute while maintaining focus and a productive pace. This expertise is largely tacit knowledge, learnt informally, which is difficult to analyse and articulate oneself, or explain to others. To make this easier, and thus support learning, we developed the metaphor of a conductor leading musicians.ConclusionsWhilst everyone contributes to the joint effort of delivering a good WR, WR leadership is key. It ensures effective use of time and diverse expertise, and coordinates contributions rather like a conductor working with musicians. Although WR needs and approaches vary across contexts, the key leadership activities we identified are likely to transfer to other settings.
Mucosal interleukin‐8 expression as a predictor of subsequent relapse in ulcerative colitis patients with Mayo endoscopic subscore 0
Authors: Uchiyama Kazuhiko , Takagi Tomohisa , Mizushima Katsura , Asaeda Kohei , Kajiwara Mariko , Kashiwagi Saori , Toyokawa Yuki , Hotta Yuma , Tanaka Makoto , Inoue Ken , Dohi Osamu , Okayama Tetsuya , Yoshida Naohisa , Katada Kazuhiro , Kamada Kazuhiro , Ishikawa Takeshi , Yasuda Hiroaki , Konishi Hideyuki , Kishimoto Mitsuo , Naito Yuji , Itoh Yoshito 
Published: March 2022

AbstractBackground and AimComplete endoscopic mucosal healing is defined as a Mayo endoscopic subscore of 0. Some patients diagnosed with a Mayo endoscopic subscore 0 may present with subsequent clinical relapse. Here, we aimed to demonstrate mucosal cytokine profile as a predictor of clinical relapse in ulcerative colitis patients with a Mayo endoscopic subscore of 0 as a marker of mucosal healing.MethodsWe conducted prospective observational pilot study to examine the relationship between mucosal cytokine expression and subsequent relapse of UC patients diagnosed with a Mayo endoscopic subscore of 0. We enrolled 55 patients, and expression of cytokines tumor necrosis factor‐α, interferon γ, interleukin‐1β, interleukin‐2, interleukin‐4, interleukin‐5, interleukin‐6, interleukin‐7, interleukin‐8, interleukin‐9, interleukin‐10, interleukin‐12, interleukin‐13, interleukin‐15, interleukin‐17A, interleukin‐17F, interleukin‐18, interleukin‐21, interleukin‐22, interleukin‐23, interleukin‐27, and interleukin‐33 was measured by quantitative real‐time PCR using rectal mucosa biopsy materials. Cytokine expression levels were compared between patients who relapsed between March 1, 2016, and March 30, 2020, of the study period and those who remained in remission.ResultsTen cytokines, including interleukin‐2, interleukin‐4, interleukin‐8, interleukin‐10, interleukin‐12, interleukin‐15, interleukin‐17A, interleukin‐21, interleukin‐23, and interleukin‐33, were significantly elevated in patients with subsequent relapse compared with those who remained in remission. Interleukin‐8 expression was the most useful predictor.ConclusionsIn the rectal mucosa of ulcerative colitis patients with Mayo endoscopic subscore 0, levels of several cytokines were elevated in cases of subsequent relapse. Among these, interleukin‐8 expression was the most useful for predicting relapse.
Modulation of autophagy by an innovative phytocosmetic preparation (Myrothamnus flabelifolia and Coffea arabica) in human fibroblasts and its effects in a clinical randomized placebo‐controlled trial
Authors: Biscaro Rafael C. , Mussi Lilian , Sufi Bianca , Padovani Giovana , Camargo Junior Flavio B. , Magalhães Wagner V. , Di Stasi Luiz C. 
Published: February 2022

AbstractBackgroundAutophagy is a natural and evolutionary mechanism that reduces cell toxic components and reutilizes metabolites to provide energy and renew cell function, which is linked to a wide range of age‐related diseases, including those that affect the skin. Positive modulation of autophagy is useful to treat skin disorders and new active herbal products are potential candidates as autophagy modulators.AimsThe present study aimed to evaluate the effects of a phytocosmetic formulation containing Myrothamnus flabellifolia leaf and Coffea arabica seed plant extracts (MflCas) on the ubiquitin‐proteasome and autophagy markers in human dermal fibroblasts, and investigate its topical skin effects in a randomized, simple‐blind, and placebo‐controlled trial.MethodsHuman dermal fibroblasts were used to determine proteasome activity, protein carbonylation, LC3B protein, and lipofuscin production by luminescence and immune‐enzymatic assays, and to determinate gene expression of autophagy biomarkers (Atg5, Atg7, EI24, EIF2A, Park2, foxo1, and mTOR) by RT‐PCR. A clinical trial was conducted to evaluate the effects of MflCas on the hand, face, and forearms skin features after treatment by 56 days.ResultsTopical treatment with MflCas improved several skin features of volunteers, mainly skin aging and pigmentation signals. On the hand skin, MflCas 2% after 56 days of treatment, reduced the spots length (30.8%), skin contrast (42.2%), and increased skin homogeneity (63.2%) and skin lightening effect (1.4%). On the face skin, topical treatment after 56 days reduced the spots length (21.5%), wrinkles area (8.1%), and wrinkles volume (5.6%) with an increment in face skin homogeneity (59.5%). These effects were related to the ability of MflCas to reduce proteasome activity protein carbonylation, and lipofuscin level, increase LC3B production, downregulate Atg7 and mTOR genes, and upregulate Park2 gene expressions.ConclusionsThe phytocosmetic preparation containing Myrothamnus flabellifolia leaf and Coffea arabica seed modulated ubiquitin‐proteasome and autophagy process, representing an innovative and safe herbal preparation to improve skin features, mainly acting as skin anti‐aging and lightening agent.
Effect of rifaximin on infections, acute‐on‐chronic liver failure and mortality in alcoholic hepatitis: A pilot study (RIFA‐AH)
Authors: Jiménez César , Ventura‐Cots Meritxell , Sala Margarita , Calafat Margalida , Garcia‐Retortillo Montserrat , Cirera Isabel , Cañete Nuria , Soriano Germán , Poca María , Simón‐Talero Macarena , Altamirano José , Lucey Michael , Garcia‐Tsao Guadalupe , Brown Robert S. , Schwabe Robert F. , Verna Elizabeth C. , Schnabl Bernd , Bosques‐Padilla Francisco , Mathurin Philippe , Caballería Juan , Louvet Alexandre , Shawcross Debbie L. , Abraldes Juan G. , Genescà Joan , Bataller Ramon , Vargas Víctor 
Published: February 2022

AbstractBackground & AimsAlcoholic hepatitis (AH) is associated with a high incidence of infection and mortality. Rifaximin reduces bacterial overgrowth and translocation. We aimed to study whether the administration of rifaximin as an adjuvant treatment to corticosteroids decreases the number of bacterial infections at 90 days in patients with severe AH compared to a control cohort.MethodsThis was a multicentre, open, comparative pilot study of the addition of rifaximin (1200 mg/day/90 days) to the standard treatment for severe AH. The results were compared with a carefully matched historical cohort of patients treated with standard therapy and matching by age and model of end‐stage liver disease (MELD). We evaluated bacterial infections, liver‐related complications, mortality and liver function tests after 90 days.ResultsTwenty‐one and 42 patients were included in the rifaximin and control groups respectively. No significant baseline differences were found between groups. The mean number of infections per patient was 0.29 and 0.62 in the rifaximin and control groups, respectively (p = .049), with a lower incidence of acute‐on‐chronic liver failure (ACLF) linked to infections within the treatment group. Liver‐related complications were lower within the rifaximin group (0.43 vs. 1.26 complications/patient respectively) (p = .01). Mortality was lower in the treated versus the control groups (14.2% vs. 30.9, p = .15) without significant differences. No serious adverse events were associated with rifaximin treatment.ConclusionsRifaximin is safe in severe AH with a significant reduction in clinical complications. A lower number of infections and a trend towards a lower ACLF and mortality favours its use in these patients.
Knowledge of liver fibrosis stage among adults with NAFLD/NASH improves adherence to lifestyle changes
Authors: Carrieri Patrizia , Mourad Abbas , Marcellin Fabienne , Trylesinski Aldo , Calleja José Luis , Protopopescu Camelia , Lazarus Jeffrey V. 
Published: February 2022

AbstractBackground & AimsThough lifestyle interventions can reverse disease progression in people with non‐alcoholic fatty liver disease/non‐alcoholic steatohepatitis (NAFLD/NASH), unawareness about disease severity might compromise behavioural changes. Data from this first international cross‐sectional survey of individuals with NAFLD/NASH were used to identify correlates of both unawareness about fibrosis stage and its association with adherence to lifestyle adjustments.MethodsAdults with NAFLD/NASH registered on the platform Carenity were invited to participate in an online 20‐min, six‐section survey in Canada, France, Germany, Italy, Spain and the United Kingdom to describe their experience with NAFLD/NASH and its care (N = 1411). Weighted binary and multinomial logistic regressions were performed to estimate the effect of explanatory variables on unawareness of fibrosis stage and poor adherence to lifestyle changes respectively.ResultsIn the study group, 15.5% had obesity and 59.2% did not know their fibrosis stage. After multiple adjustments, individuals with a body mass index (BMI) ≥35 were over twice as likely to not know their fibrosis stage. People with a BMI >30 had a threefold higher risk of having poor adherence to lifestyle changes. Unawareness about fibrosis stage was also significantly associated with poor adherence to lifestyle adjustments.ConclusionsAs fibrosis stage is becoming the main predictor of NAFLD progression, improving patient–provider communication—especially for people with obesity—about liver fibrosis stage, its associated risks and how to mitigate them, is needed. Training for healthcare professionals and promoting patient educational programmes to support behaviour changes should also be included in the liver health agenda.
Screening and surveillance of oesophageal varices in patients with HCV‐positive liver cirrhosis successfully treated by direct‐acting antiviral agents
Authors: Ciancio Alessia , Ribaldone Davide Giuseppe , Salamone Rossella , Bruno Mauro , Caronna Stefania , Debernardi Venon Wilma , Giordanino Chiara , Mondardini Alessandra , Musso Alessandro , Pennazio Marco , Rolle Emanuela , Sacco Marco , Sprujevnik Tatiana , De Angelis Claudio , Saracco Giorgio Maria 
Published: February 2022

AbstractBackground & Aimslimited evidence is available to guide hepatologists regarding endoscopic surveillance of oesophageal varices (EV) in Hepatitis C Virus (HCV)‐positive cirrhotic patients achieving a sustained virologic response. To address these issues, we conducted a long‐term prospective study on 427 HCV‐positive cirrhotic patients successfully treated by Direct Antiviral Agents (DAAs).MethodsPatients were divided into two groups according to their baseline Baveno VI status: Group 1 (92, 21.5%, favourable Baveno VI status) and Group 2 (335, 78.5%, unfavourable Baveno VI status). Each patient underwent baseline endoscopy and was endoscopically monitored for a median follow‐up of 65.2 months according to Baveno VI recommendations.ResultsAbout 4.3% of Group 1 patients showed baseline EV compared with 30.1% of Group 2 patients (p < .0001). No patients belonging to Group 1 without baseline EV developed EV at follow‐up endoscopy compared with 6.5% in Group 2 patients (p = .02); 69/107 (64.5%) patients with baseline EV showed small varices. During the endoscopic follow‐up, EV disappeared/improved in 36 (33.6%), were stable in 39 (36.4%) and worsened in 32 (29.9%) patients, all belonging to Group 2 (p = .001). Improvement in Baveno VI status was observed in 118/335 (35.2%, p < .0001) of Group 2 patients and among those without pre‐therapy EV, none developed EV throughout the follow‐up.ConclusionsHCV‐positive cirrhotic patients cured by DAAs showing baseline favourable Baveno VI status and no worsening during follow‐up can safely avoid endoscopic screening and surveillance. Patients having unfavourable Baveno VI status without baseline EV who improve their status may suspend further endoscopic surveillance.
Durability of sustained virological response to glecaprevir/pibrentasvir and resistance development: A long‐term follow‐up study
Authors: Poordad Fred , Felizarta Franco , Yao Betty B. , Overcash J. Scott , Hassanein Tarek , Agarwal Kosh , Gane Edward , Shaw David , Waters Michael , Krishnan Preethi , Topp Andrew , Burroughs Margaret , Nevens Frederik 
Published: February 2022

AbstractBackground and AimsThis study aimed to determine durability of sustained virologic response (SVR) in hepatitis C virus‐infected participants treated with glecaprevir‐ and/or pibrentasvir‐containing regimens.MethodsM13‐576, a rollover study, evaluated the durability of SVR in a follow‐up period of approximately 3 years after hepatitis C virus genotype 1–6‐infected participants received a glecaprevir‐ and/or pibrentasvir‐containing regimen in previous phase 2/3 clinical trials. The primary efficacy endpoint was the percentage of participants maintaining SVR and the percentage of participants experiencing relapse or reinfections. Resistance‐associated substitutions and safety outcomes related to liver progression were also assessed.ResultsOf 384 participants enroled, 377 participants were included in the as‐observed population and 287 participants completed the study. In prior studies, 99.7% (376/377) of participants achieved SVR12; of those, an observed 99.5% (374/376) and 100% (286/286) completing the study, maintained SVR. After non‐responder imputation of missing data, 286/376 participants (76%) maintained SVR. The participant previously not achieving SVR was a treatment‐experienced male with compensated cirrhosis who had NS3 and NS5A substitutions at enrolment, which remained detectable for 12 months. Of the two participants not maintaining SVR, one was re‐infected and one experienced late relapse at post‐treatment week 60. Five participants (all with a fibrosis stage ≥F3) had hepatocellular carcinoma. No events were deemed related to glecaprevir/pibrentasvir.ConclusionsGlecaprevir/pibrentasvir demonstrated long‐term durability of efficacy after SVR12 was achieved. Hepatic‐related decompensation events were not seen. Owing to low incidence of virologic failure, conclusions were not drawn on persistence of resistance‐associated substitutions.
Seroprevalence of hepatitis C virus infection in children: A systematic review and meta‐analysis
Authors: Abdel‐Gawad Muhammad , Abd‐elsalam Sherief , Abdel‐Gawad Ibrahim , Tag‐Adeen Mohammed , El‐Sayed Marwa , Abdel‐Malek Dalia 
Published: February 2022

AbstractBackground and AimsEstimates of paediatric hepatitis C virus (HCV) seroprevalence are needed to aid treatment scaling‐up, screening and detection approach in this age range, with the ultimate goal of global HCV eradication. The aim of this study was to gather all of the available information on HCV seroprevalence in children all around the world.MethodsWe searched PubMed, Scopus, Web of Science (WOS), Wiley and EBSCO databases for all studies evaluating HCV seroprevalence in children; however, studies examining seroprevalence in high‐risk children or specific groups were excluded.ResultsOnly 20 articles with 48 963 people met our inclusion criteria, with an overall prevalence of 0.904% and a 95% confidence interval (CI) of 0.543 to 1.355. Seroprevalence was higher in research published prior to 2010 than in those published after 2010 (0.77% vs. 0.53%).ConclusionFew studies were conducted to assess the seroprevalence of HCV in children worldwide. However, the worldwide pooled seroprevalence of HCV in children in these studies is low (less than 1%).
Liver pathology and biochemistry in patients with mutations in TRIM37 gene (Mulibrey nanism)
Authors: Sivunen Johanna , Karlberg Susann , Kivisaari Reetta , Lohi Jouko , Karlberg Niklas , Jokinen Eero , Sarkola Taisto , Jahnukainen Timo , Lipsanen‐Nyman Marita , Jalanko Hannu 
Published: February 2022

AbstractBackground and AimsMulibrey nanism (MUL) is a multiorgan disease caused by recessive mutations in the TRIM37 gene. Chronic heart failure and hepatopathy are major determinants of prognosis in MUL patients, which prompted us to study liver biochemistry and pathology in a national cohort of MUL patients.MethodsClinical, laboratory and imaging data were collected in a cross‐sectional survey and retrospectively from hospital records. Liver histology and immunohistochemistry for 10 biomarkers were assessed.ResultsTwenty‐one MUL patients (age 1–51 years) with tumour suspicion showed moderate congestion, steatosis and fibrosis in liver biopsies and marginally elevated levels of serum GGT, AST, ALT and AST to platelet ratio index (APRI) in 20%–66%. Similarly, GGT, AST, ALT and APRI levels were moderately elevated in 12%–69% of 17 MUL patients prior to pericardiectomy. In a cross‐sectional evaluation of 36 MUL outpatients, GGT, total bilirubin and galactose half‐life (Gal½) correlated with age (r = 0.45, p = .017; r = 0.512, p = .007; r = 0.44, p = .03 respectively). The frequency of clearly abnormal serum values of 15 parameters analysed, however, was low even in patients with signs of restrictive cardiomyopathy. Transient elastography (TE) of the liver revealed elevated levels in 50% of patients with signs of heart failure and TE levels correlated with several biochemistry parameters. Biomarkers of fibrosis, sinusoidal capillarization and hepatocyte metaplasia showed increased expression in autopsy liver samples from 15 MUL patients.ConclusionLiver disease in MUL patients was characterized by sinusoidal dilatation, steatosis and fibrosis with individual progression to cirrhosis and moderate association of histology with cardiac function, liver biochemistry and elastography.
Serum keratin 19 (CYFRA21‐1) is a prognostic biomarker in severe alcoholic hepatitis
Authors: Atkinson Stephen Rahul , Aly Mahmoud , Remih Katharina , Tyson Luke David , Guldiken Nurdan , Goldin Robert , Quaglia Alberto , Thursz Mark , Strnad Pavel 
Published: February 2022

AbstractBackground and AimsUp to 30% of patients with severe alcoholic hepatitis (sAH) die within 3 months of presentation. The degree of ductular reaction, characterized by accumulation of biliary and liver progenitor cells, confers a poor prognosis. Keratin fragments are established serological surrogates of liver injury and keratin 19 (K19) is a histological marker of the ductular reaction. We assessed the relationship between serum K19 levels (viz. CYFRA21‐1), histology and outcome in patients with sAH.MethodsSerum CYFRA21‐1 was quantified in pre‐treatment serum samples from 824 patients enrolled in the STOPAH trial. The cohort was randomly divided into two groups to test mortality associations; histological analyses were performed using the 87 cases with suitable samples.ResultsCYFRA21‐1 levels were elevated in sAH and strongly predicted alcoholic steatohepatitis (ASH) on biopsy (area under the receiver operated characteristic [AUROC] 0.785 [95% Confidence Interval 0.602–0.967]) and 90‐day survival (AUROC 0.684/0.693). The predictive ability of CYFRA21‐1 was comparable with the model of end‐stage liver disease (MELD) score and was independently associated with survival in multivariable analysis. CYFRA21‐1 moderately correlated with hepatocellular injury markers M30/M65 but displayed a more robust predictive ability. A combination of MELD and CYFRA21‐1 conferred a modest improvement in the AUROC value (0.731/0.743).ConclusionsIn sAH serum, CYFRA21‐1 levels associate with the presence of ASH on biopsy and independently predict 90‐day survival. As a single marker performance is comparable to established scoring systems. Therefore, CYFRA21‐1, which is available in many clinical laboratories, may become a useful component of prognostic models.