bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parkin is not required to sustain OXPHOS function in adult mammalian tissues
Authors: Filograna Roberta , Gerlach Jule , Choi Hae-Na , Rigoni Giovanni , Barbaro Michela , Oscarson Mikael , Lee Seungmin , Tiklova Katarina , Ringnér Markus , Koolmeister Camilla , Wibom Rolf , Riggare Sara , Nennesmo Inger , Perlmann Thomas , Wredenberg Anna , Wedell Anna , Motori Elisa , Svenningsson Per , Larsson Nils-Göran 
Published: September 2023

AbstractLoss-of-function variants in thePRKNgene encoding the ubiquitin E3 ligase PARKIN cause autosomal recessive early-onset Parkinson’s disease (PD). Extensivein vitroandin vivostudies have reported that PARKIN is involved in multiple pathways of mitochondrial quality control, including mitochondrial degradation and biogenesis. However, these findings are surrounded by substantial controversy due to conflicting experimental data. In addition, the existing PARKIN-deficient mouse models have failed to faithfully recapitulate PD phenotypes. Therefore, we have investigated the mitochondrial role of PARKIN during ageing and in response to stress by employing a series of conditionalParkinknockout mice. We report that PARKIN loss does not affect oxidative phosphorylation (OXPHOS) capacity and mitochondrial DNA (mtDNA) levels in the brain, heart, and skeletal muscle of aged mice. We also demonstrate that PARKIN deficiency does not exacerbate the brain defects and the pro-inflammatory phenotype observed in mice carrying high levels of mtDNA mutations. To rule out compensatory mechanisms activated during embryonic development ofParkin-deficient mice, we generated a mouse model where loss of PARKIN was induced in adult dopaminergic (DA) neurons. Surprisingly, also these mice did not show motor impairment or neurodegeneration, and no major transcriptional changes were found in isolated midbrain DA neurons. Finally, we report a patient with compound heterozygousPRKNpathogenic variants that lacks PARKIN and has developed PD. The PARKIN deficiency did not impair OXPHOS activities or induce mitochondrial pathology in skeletal muscle from the patient. Altogether, our results argue that PARKIN is dispensable for OXPHOS function in adult mammalian tissues.
HCN channels sense temperature and determine heart rate responses to heat
Authors: Wu Yuejin , Wang Qinchuan , Granger Jonathan , Gaido Oscar Reyes , Aguilar Eric Nunez , Ludwig Andreas , Moroni Anna , Bianchet Mario A. , Anderson Mark E. 
Published: September 2023

AbstractHeart rate increases with heat, [1–3] constituting a fundamental physiological relationship in vertebrates. Each normal heartbeat is initiated by an action potential generated in a sinoatrial nodal pacemaker cell. Pacemaker cells are enriched with hyperpolarization activated cyclic nucleotide-gated ion channels (HCN) that deliver cell membrane depolarizing inward current that triggers action potentials. HCN channel current increases due to cAMP binding, a mechanism coupling adrenergic tone to physiological ‘fight or flight’ heart rate acceleration. However, the mechanism(s) for heart rate response to thermal energy is unknown. We used thermodynamical and homology computational modeling, site-directed mutagenesis and mouse models to identify a concise motif on the S4-S5 linker of the cardiac pacemaker HCN4 channels (M407/Y409) that determines HCN4 current (If) and cardiac pacemaker cell responses to heat. This motif is required for heat sensing in cardiac pacemaker cells and in isolated hearts. In contrast, the cyclic nucleotide binding domain is not required for heat induced HCN4 current increases. However, a loss of function M407/Y409 motif mutation prevented normal heat and cAMP responses, suggesting that heat sensing machinery is essential for operating the cAMP allosteric pathway and is central to HCN4 modulation. The M407/Y409 motif is conserved across all HCN family members suggesting that HCN channels participate broadly in coupling heat to changes in cell membrane excitability.
Determinants of Load capacity factor in BRICS countries: A panel data analysis
Authors: Yang Minjing , Magazzino Cosimo , Awosusi Abraham Ayobamiji , Abdulloev Navzodbek 
Published: September 2023

AbstractSeveral developing markets, such as Brazil, Russia, India, China, and South Africa (BRICS), are facing challenges in attaining the targets set with regard to the Sustainable Development Goals (SDGs). While previous studies have extensively examined the Environmental Kuznets Curve in BRICS nations, focusing on other proxy of environmental degradation like CO2 emissions and ecological footprint, little attention has been given to the Load Capacity Curve (LCC) hypothesis specifically in relation to emerging economies. Consequently, there exists a gap in the literature regarding the validation of the LCC hypothesis for these economies. To bridge this gap, our research intends to assess the validity of the LCC hypothesis in the context of the BRICS countries. Specifically, we investigate the impact of biomass energy and social globalization on the load capacity factor (a proxy for ecological quality) in the BRICS countries from 1990 to 2018, while considering the roles of economic growth and natural resources. Additionally, we explore the development of an SDG framework tailored for the BRICS nations, which can serve as a blueprint for other emerging economies. To analyze the data, we employ the Method of Moments‐Quantile‐Regression (MMQR) approach along with long‐run estimators. The findings of the MMQR analysis reveal that natural resources, social globalization, and gross domestic product have adverse effects on ecological quality, while biomass energy exhibits a positive influence on ecological quality. Furthermore, our research validates the LCC hypothesis for the BRICS economies. We also observe evidence of causality between the load capacity factor and its determinants. Based on our investigation, we recommend a transition in energy policies from hydrocarbon energy to sustainable energy options by implementing innovative approaches to biomass technology that can enhance conversion efficiency. Implementing these policy changes will not only enhance ecological quality but also align the SDG targets.
Letter: non‐steroidal anti‐inflammatory drugs reduce the risk of post‐colonoscopy colorectal cancer—authors' reply
Authors: Cheung Ka Shing , Leung Wai K. 
Published: September 2023

LINKED CONTENT
This article is linked to Cheung et al and TanTai et al papers. To view these articles, visit https://doi.org/10.1111/apt.15693 and https://doi.org/10.1111/apt.16105
The risk of later surgery at the anastomotic site following right hemicolectomy for Crohn's disease in a national cohort of 12 230 patients
Authors: King Dominic , Coupland Benjamin , Dosanjh Amandeep , Cole Andrew , Adderley Nicola J. , Reulen Raoul C. , Patel Prashant , Trudgill Nigel J. 
Published: September 2023

SummaryBackgroundCrohn's disease (CD) has a high‐risk of bowel resection and later surgery for recurrent disease. Recent guidelines recommend colonoscopy 6‐12 months following surgery to reduce further surgical intervention through medical therapy intensification.AimsTo investigate the risk of further surgery at the anastomosis following right hemicolectomy for CD.MethodsHospital Episode Statistics were used to identify patients with CD and a right hemicolectomy between 2007 and 2016. Adherence to post‐resection colonoscopy guidance timing and risk of further surgery at the anastomosis were examined. Cox proportional hazards models assessed risk factors for further surgery.Results12 230 patients were identified: 45% male; median age 36 (IQR 26‐49) years. Median follow‐up was 5.9 (IQR 3.6‐8.6) years: totalling 74 960 person‐years. Median time to further surgery was 2.9 (IQR 1.2‐5.3) years. By 5 years 9% and by 10 years 16.9% of those with sufficient follow‐up had at least one further surgery involving the anastomotic site. Older, less deprived patients and those whose index surgery took place on an elective admission had a reduced risk of further surgery. The annual number of right hemicolectomies increased over the study from 1063 to 1317, driven by the increasing prevalence of CD. Overall, 78% of patients did not have a colonoscopy, as recommended, within 6‐12 months following index resection.ConclusionsFurther surgery involving the anastomotic site remains common following index right hemicolectomy for CD. Post‐surgical colonoscopy was only undertaken in 22% of patients within suggested timeframes. Increased colonoscopy may lead to a reduced need for surgery if early optimisation of medical therapy is undertaken for recurrence.
Letter: TIPSS improves muscle mass indices in patients with cirrhosis and severe portal hypertension
Authors: Debnath Prasanta , Rathi Pravin 
Published: September 2023

LINKED CONTENT
This article is linked to Artru et al papers. To view these articles, visit https://doi.org/10.1111/apt.16080 and https://doi.org/10.1111/apt.16154
Letter: TIPSS is a promising therapy for sarcopenia in cirrhosis
Authors: Hey Penelope , Sinclair Marie , Testro Adam , Gow Paul 
Published: September 2023

LINKED CONTENT
This article is linked to Artru et al and Kumar & Dixit papers. To view these articles, visit https://doi.org/10.1111/apt.16080, https://doi.org/10.1111/apt.16129 and https://doi.org/10.1111/apt.16152
Letter: TIPSS and reversal of sarcopenia
Authors: Kumar Karan , Dixit Indresh 
Published: September 2023

LINKED CONTENT
This article is linked to Artru et al and Hey et al papers. To view these articles, visit https://doi.org/10.1111/apt.16080, https://doi.org/10.1111/apt.16128 and https://doi.org/10.1111/apt.16152
Targeted versus universal tuberculosis chemoprophylaxis in 1968 patients with inflammatory bowel disease receiving anti‐TNF therapy in a tuberculosis endemic region
Authors: Ye Lingna , Chapman Thomas P. , Wen Zhenzhen , Lin Lang , Qiu Yun , Liu Zhanju , Ran Zhihua , Qian Jiaming , Wu Kaichun , Gao Xiang , Hu Pinjin , Chen Minhu , Travis Simon P. L. , Cao Qian ,   The Chinese IBD Elite Union
Published: September 2023

SummaryBackgroundAnti‐tumour necrosis factor (anti‐TNF) therapy increases the risk of tuberculosis (TB). Given limitations of screening techniques, it remains uncertain if patients receiving anti‐TNF in TB endemic regions should be screened for latent infection with chemoprophylaxis restricted to those with proven infection, or if all patients should receive chemoprophylaxis.AimsTo compare the incidence of active TB with infliximab (IFX) following targeted and universal TB chemoprophylaxis, and to determine the rates of adverse events (AE) related to TB chemoprophylaxisMethodsA multi‐centre retrospective cohort study was performed at 18 hospitals in China of 1968 adult patients with IBD receiving IFX from 2009 to 2017. TB screening prior to IFX was performed with chest X‐ray and/or computed tomography [CT] and immune reactivity testing (interferon‐γ release assay and/or tuberculin skin test). Patients were followed‐up for a minimum of 3 months after IFX discontinuation, or until last hospital visit if IFX therapy was ongoing. Targeted strategy was defined as TB chemoprophylaxis only for patients with a positive latent TB screen, with universal strategy defined as TB chemoprophylaxis for all patients.ResultsMean follow‐up was 1.07 ± 0.87 years with a total follow‐up of 2102 patient‐years. There were 1433 patients in the targeted and 483 patients in the universal TB chemoprophylaxis groups, with no significant difference in the incidence rates of active TB between groups (673.3 per 100 000 population per year vs 891.5 per 100 000 population per year, P = 0.60). In the targeted group, 55/1433 patients received TB chemoprophylaxis compared with 483/483 in the universal group, with significantly fewer AEs related to TB chemoprophylaxis in the targeted compared to the universal group (0.35% (5/1433) vs 6.8% (33/483), P < 0.05).ConclusionsIn this study of patients receiving IFX in a TB endemic area, universal chemoprophylaxis was not associated with a reduced risk of active TB when compared to a targeted chemoprophylaxis strategy, and AEs were more common. This supports the use of targeted TB chemoprophylaxis when anti‐TNF therapy is initiated in TB endemic regions.
Letter: no‐biopsy pathway for diagnosing adult coeliac disease
Authors: Paul Siba Prosad , Lau Wing‐Yu Siobhan , Khan Zubair Hanif , Heaton Paul Anthony 
Published: September 2023

LINKED CONTENT
This article is linked to Fuchs et al and Kurppa et al papers. To view these articles, visit https://doi.org/10.1111/apt.15109 and https://doi.org/10.1111/apt.16195
Validating the positivity thresholds of drug‐tolerant anti‐infliximab and anti‐adalimumab antibody assays
Authors: Nice Rachel , Chanchlani Neil , Green Harry , Bewshea Claire , Ahmad Tariq , Goodhand James R. , McDonald Timothy J. , Perry Mandy H. , Kennedy Nicholas A. 
Published: September 2023

SummaryBackgroundWhen used proactively, drug‐tolerant anti‐tumour necrosis factor (TNF) antibody assays provide early opportunity to suppress immunogenicity.AimTo validate positivity thresholds of IDKmonitor drug‐tolerant anti‐infliximab and ‐adalimumab antibody assays.MethodsWe applied positivity thresholds, defined by testing sera from 498 anti‐TNF naive healthy adults, from the Exeter Ten Thousand study to data from our therapeutic drug monitoring (TDM) service and Personalised Anti‐TNF Therapy in Crohn's disease (PANTS) cohort to explore associations with drug level and treatment outcomes.ResultsThe 80% one‐sided lower confidence interval of the 99th centile concentration for anti‐infliximab and –adalimumab antibodies were lower than the manufacturers threshold of 10 arbitrary units (AU)/mL; 9 and 6 AU/mL, respectively. Using these new thresholds in the TDM cohort, more adalimumab‐ than infliximab‐ (11.2% [814/7272] vs 3.1% [390/12 683] P < 0.0001) treated patients were reclassified as antibody‐positive. Adalimumab drug concentrations in this reclassified group (median 8.1, interquartile range [IQR] 5.5‐11.0 mg/L) were lower than those below the new threshold (<5AU/mL) (median 9.9, IQR 7.1‐13.0 mg/L; P < 0.0001), but higher than at the manufacturer's threshold (10‐29 AU/mL) (median 5.9 mg/L, IQR 3.5‐8.7; P < 0.0001). No difference in infliximab drug concentration was observed using the new or manufacturer's positivity threshold (P = 0.11). In the PANTS cohort, patients with anti‐adalimumab antibody concentrations at or above the new threshold were more likely to be in primary non‐response (25/68 [37%] vs. 64/332 [19%], P = 0.0035), and non‐remission at week 54 (51/62 [82%] vs. 168/279 [60%], P = 0.0011), than patients with anti‐drug antibody concentrations in the group below the new threshold (0‐5 AU/mL); this was not seen for anti‐infliximab antibodies.ConclusionLaboratories should derive antibody positivity thresholds for assays they use. For adalimumab, low‐concentration anti‐drug antibodies were associated with lower drug levels and treatment failure.
Editorial: acid suppression with potassium‐competitive acid blockers dismissing genotype concerns
Authors: Scarpignato Carmelo , Hunt Richard H. 
Published: September 2023

LINKED CONTENT
This article is linked to Hwang et al and Hwang & Lee papers. To view these articles, visit https://doi.org/10.1111/apt.16131 and https://doi.org/10.1111/apt.16158
Editorial: pharmacodynamics of potassium‐competitive acid blockers: comparing apples with apples—and with oranges
Authors: Howden Colin W. 
Published: September 2023

LINKED CONTENT
This article is linked to Sunwoo et al papers. To view these articles, visit https://doi.org/10.1111/apt.16121 and https://doi.org/10.1111/apt.16165
The significance of histological activity measurements in immune checkpoint inhibitor colitis
Authors: Pai Rish K. , Pai Reetesh K. , Brown Ian , Choi Won‐Tak , Schaeffer David F. , Farnell David , Kumarasinghe M. Priyanthi , Gunawardena Dilini , Kim Baek Hui , Friedman Mark , Ghayouri Masoumeh , Lauwers Gregory Y. 
Published: September 2023

SummaryBackgroundColitis is a significant complication of immune checkpoint inhibitors (ICI). Currently, clinical and endoscopic severity are used to guide therapy.AimsTo investigate associations between clinical, endoscopic, and histological features with outcomesMethodsWe identified 149 patients from seven institutions with biopsy‐proven ICI colitis. Biopsies were evaluated for histological features including the Geboes score, and the Robarts histopathological index (RHI) was calculated. Clinical, endoscopic, and histological data were tested for associations with biological use and adverse colitis outcomes (biological‐refractory colitis, colectomy or death from colitis).ResultsThree mutually exclusive histological patterns were identified: acute colitis, chronic active colitis and microscopic colitis. Microscopic colitis was associated with older age (68.5 vs 61 years for acute colitis pattern, P = 0.02) and longer time to colitis (5.5 vs 3 months for the other patterns, P = 0.05). Biological use was associated with earlier time to colitis (2 vs 3 months, P = 0.04) and higher RHI (18 vs 12, P = 0.007). On multivariate analysis, RHI ≥14 was associated with biological use with an odds ratio of 4.5 (95% CI 1.4‐13.8; P = 0.01). Adverse colitis outcomes were associated with shorter time to colitis (2 vs 3 months, P = 0.008) and higher RHI (24 vs 14, P = 0.001). On multivariate analysis, RHI ≥24 was associated with adverse colitis outcomes with an odds ratio 9.5 (95% CI 2.1‐42.3 P = 0.003).ConclusionHistological activity as measured by RHI is the only factor independently associated with biological use and adverse colitis outcomes. Prospective studies are needed to validate these findings to determine if histological activity should be incorporated into therapeutic algorithms.
Systematic review with meta‐analysis: the appropriateness of colonoscopy increases the probability of relevant findings and cancer while reducing unnecessary exams
Authors: Frazzoni Leonardo , La Marca Marina , Radaelli Franco , Spada Cristiano , Laterza Liboria , Zagari Rocco Maurizio , Bazzoli Franco , Hassan Cesare , Frazzoni Marzio , Dinis‐Ribeiro Mario , Fuccio Lorenzo 
Published: September 2023

SummaryBackgroundColonoscopy is frequently performed in industrialised countries. Inappropriate colonoscopies might lead to unnecessary exams, increasing risks and costs.AimTo estimate the impact of colonoscopy appropriateness in terms of gain in additional diagnoses and sparing of unnecessary exams.MethodsSystematic review including studies reporting the prevalence of relevant findings, colorectal cancer (CRC) and inflammatory bowel disease (IBD) according to colonoscopy appropriateness as defined by the American Society for Gastrointestinal Endoscopy and European Panel on Appropriateness of Gastrointestinal Endoscopy.ResultsTwenty‐one studies with 19,822 patients were included. Colonoscopy was appropriate in 15,162 (71%, CI 64%‐78%). Appropriateness significantly increased the probability of relevant findings (34% vs. 18%; RR 1.81, CI 1.53‐2.14), CRC (7% vs. 2%; RR 3.62, CI 2.44‐5.37) and IBD (6% vs. 4%; RR 1.86, CI 1.09‐3.19). Appropriateness had sensitivity 88% (CI 85%‐91%), 97% (CI 93%‐98%) and 89% (CI 80%‐94%), and specificity 24% (CI 20%‐29%), 22% (CI 18%‐26%) and 24% (CI 20%‐28%) for relevant findings, CRC and IBD, respectively. On average, performing colonoscopy with appropriate indication would find 15 (CI 10‐21) more relevant findings, five (CI 3‐9) more CRCs and three (CI 1‐9) more diagnoses of IBD per 100 patients, and save 24 (CI 20‐29), 22 (CI 18‐26) and 24 (CI 20‐28) examinations per 100 patients for relevant findings, CRC and IBD, respectively.ConclusionsAppropriateness affects the diagnostic yield of colonoscopy for CRC, IBD and relevant findings. Appropriateness criteria are useful, although integrated with clinical evaluation of the patient.
Fatigue in inflammatory bowel disease and its impact on daily activities
Authors: Schreiner Philipp , Rossel Jean‐Benoît , Biedermann Luc , Valko Philipp O. , Baumann Christian R. , Greuter Thomas , Scharl Michael , Vavricka Stephan R. , Pittet Valérie , Juillerat Pascal , Rogler Gerhard , von Känel Roland , Misselwitz Benjamin ,   the Swiss IBD Cohort Study Group
Published: September 2023

SummaryBackgroundFatigue is a common symptom of chronic inflammation, including inflammatory bowel disease (IBD), resulting in significant impairment in quality of life.AimsTo identify the prevalence of fatigue in a large IBD cohort compared to the general population, address risk factors, and evaluate its impact on daily life.MethodsWe evaluated 1208 IBD patients from the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS) and 414 healthy controls. Significant fatigue was defined as a visual analogue scale (VAS‐F, range 0‐10) score ≥ 4. Secondary endpoints were severity of fatigue and its impact on daily activities with the Fatigue Severity Scale (FSS), with a score ≥ 4 indicative of fatigue. Demographic, IBD‐related and psychiatric symptoms were assessed with a multivariate analysis of variance (MANOVA) model optimised for prediction of VAS‐F (primary outcome) and FSS scores.ResultsOverall, 672 IBD patients (55.6%) reported significant fatigue compared to 145 (35%) controls (OR 2.71; 95% CI 2.08‐3.54; P < 0.001). In IBD, fatigue also significantly affected daily activities (FSS ≥ 4; 405 (33.5%) IBD patients vs 81 (19.6%) controls, P < 0.001). In the MANOVA model, fatigue levels were associated with female gender (coefficient 0.839; 0.556 ‐ 1.123; P < 0.001), younger age at diagnosis (−0.031 per year; −0.042– −0.019; P < 0.001), shorter disease duration (−0.036 per year; −0.050– −0.022; P < 0.001), nocturnal diarrhoea (0.718; 0.295‐1.141; P = 0.001), low educational level (P = 0.034) and symptoms of depression and anxiety.ConclusionsFatigue is both more frequent and more severe in patients with IBD than in the general population.
Letter: accuracy of magnetic resonance index of activity score to predict response to biologics in Crohn’s disease
Authors: Debnath Prasanta , Rathi Pravin 
Published: September 2023

LINKED CONTENT
This article is linked to Rimola et al papers. To view these articles, visit https://doi.org/10.1111/apt.16069 and https://doi.org/10.1111/apt.16163
Systematic review: the global incidence of faecal microbiota transplantation‐related adverse events from 2000 to 2020
Authors: Marcella Cicilia , Cui Bota , Kelly Colleen R. , Ianiro Gianluca , Cammarota Giovanni , Zhang Faming 
Published: September 2023

SummaryBackgroundFaecal microbiota transplantation (FMT) is an effective treatment in C. difficile infection (CDI) and is currently being investigated in other diseases. There is concern around the safety of FMT and that side effects or complications may be under‐reported in the medical literature.AimTo evaluate the safety of FMT by summarising the overall reported Adverse Events (AEs) over a 20‐year periodMethodsWe searched EMBASE, MEDLINE, and Cochrane Library databases, and CNKI and Wanfang Data from January 2000 to April 2020. All original studies reporting FMT‐related AEs were considered for inclusion. FMT‐related AEs were further classified as delivery‐related or microbiota‐related.ResultsBased on the inclusion criteria, 129 studies, which included 4241 patients (5688 FMT courses), were finally eligible. The most common indication for FMT was CDI. Overall, FMT‐related AEs were observed in 19% of FMT procedures. The most frequently reported FMT‐related AEs were diarrhoea (10%) and abdominal discomfort/pain/cramping (7%). FMT‐related serious adverse events (SAEs), including infections and deaths, have been reported in 1.4% of patients who underwent FMT (0.99% microbiota‐related SAEs). Four of five FMT‐related deaths were reported in patients receiving FMT via the upper gastrointestinal route. Importantly, all reported FMT‐related SAEs were in patients with mucosal barrier injury.ConclusionMost FMT‐related AEs were mild or moderate and self‐limiting. Although FMT appears to be highly safe, its methodology should be improved to reduce both delivery‐related AEs and, microbiota‐related AEs.