bluuebunny/crossref_metadata_2025_split huggingface dataset:
End‐of‐life impact of concurrent diabetes mellitus and adrenal insufficiency as immune‐related adverse events in an advanced non‐small cell lung cancer patient
Authors: Nakamura Tomoaki , Takeyasu Yuki , Yoshida Tatsuya , Ohashi Ken , Ohe Yuichiro 
Published: October 2022

AbstractA 49‐year‐old man diagnosed with metastatic non‐small cell lung cancer was treated with immune checkpoint inhibitor (ICI) combination therapy (nivolumab + ipilimumab) as first‐line therapy. During the treatment course, the patient developed ICI‐associated diabetes mellitus and adrenal insufficiency, and insulin and hydrocortisone replacement therapy (10 mg/day) were initiated for endocrine toxicity. Despite systemic treatment, the disease progressed. Near the end of the patient's life, he was repeatedly hospitalized for diabetic ketoacidosis and adrenal crisis because he could not physically administer insulin subcutaneously or self‐administer oral hydrocortisone due to the deterioration of his general condition as a result of disease progression. This case report demonstrates that it is necessary to evaluate not only the impact of immune‐related adverse events on short‐term quality of life during ICI treatment but also on the patient's end‐of‐life care.
Geographical dispersion of ragweed leaf beetle (Ophraella communa) based on climatic and biological characters in the Palearctic habitats
Authors: Keszthelyi Sándor , Kazinczi Gabriella , Somfalvi‐Tóth Katalin 
Published: October 2022

Abstract
The accidentally introduced ragweed leaf beetle (Ophraella communa) is a most promising biological control agent for common ragweed (Ambrosia artemisiifolia), which herbivore has already emerged in several areas of the Palearctic region.
The aim of our study was to model the expansion of O. communa and the number of generations in the various Palearctic regions. Furthermore, our objective was to determine the effect of the prevailing wind on the direction of its spread and to ascertain the relationship between the green biomass production of ragweed and individual numbers of this leaf beetle.
According to our meta‐analytical findings, the advancement of O. communa is continuous in the Palearctic areas. This phytophagous insect invades new habitats, which are occupied by A. artemisiifolia, and spreads quickly. The stable populations of O. communa seem to be strictly linked to the presence of its primary host, A. artemisiifolia.
We show that the rapid spread of this insect is due to the combination of wind direction and topography features, which was reinforced by our analysis. O. communa possesses uniformly multivoltine populations in its Palearctic habitats. So, insects possessing facultative diapause are able to colonize northern areas depending on the presence of their host, which statement is based on the processing of 143 East‐ and 68 West‐Palearctic records
According to our investigations, the mass appearance of this phytophagous insect coincided with the assimilation peak of its main host, common ragweed.
“Who is not an agent here?”: The Collateral Damage of Anti‐Trafficking in Nepal
Authors: Bhagat Ayushman 
Published: October 2022

AbstractIn this paper, I explore how the diverse labour migration practices of people who challenge their state’s restrictive policies produce a form of stigma that extends from people to the places where they reside. Drawing on the findings of Participatory Action Research (PAR) conducted in Nepal, I demonstrate how people residing in one such place attempt to undo stigma by adopting diverse practices amidst restrictive anti‐trafficking and migration policies. I reveal a novel practice of prospective labour migrants negotiating and receiving money from their choicest mobility facilitators to assist their unauthorised labour migration. This exchange of money potentially criminalises prospective labour migrants, their family members, unlicensed and licensed recruitment agents, community leaders, anti‐traffickers, government officials, hotel owners, transport service providers, and airport immigration officials as traffickers. Underscoring the collateral damage of anti‐trafficking in Nepal, I assert that the exchange of money to facilitate unauthorised migration expands the remit of criminalisation of citizens as “traffickers”.
The inexorable increase of biologic exposure in paediatric inflammatory bowel disease: a Scottish, population‐based, longitudinal study
Authors: Burgess Christopher J. , Jackson Rebecca , Chalmers Iain , Russell Richard K. , Hansen Richard , Scott Gregor , Henderson Paul , Wilson David C. 
Published: October 2022

SummaryBackgroundThe use of biologics in paediatric‐onset inflammatory bowel disease (PIBD) is rapidly changing.AimsTo identify the incidence and prevalence of biologic use within Scottish PIBD services, and to describe patient demographics and outcomes for those patients who required escalation of therapy beyond anti‐tumour necrosis factor alpha (anti‐TNFα) agentsMethodsWe captured a nationwide cohort of prospectively identified patients less than 18 years of age with PIBD (A1 phenotype; diagnosed <17 years of age) within paediatric services over a 4.5‐year period (1 January 2015–30 June 2019). All patients who received infliximab, adalimumab, vedolizumab or ustekinumab during the study period and/or received their first dose of these biologics were audited retrospectively.ResultsScotland‐wide PIBD‐prevalence cases increased from 554 to 644 over the study period. A total of 495 incident new‐start biological therapies were commenced on 403 PIBD patients: 295 infliximab (60%), 161 adalimumab (32%), 24 vedolizumab (5%) and 15 ustekunumab (3%). The proportion of new‐start biologics changed with infliximab initiation rates decreasing (87%–54%) while adalimumab (13%–31%), vedolizumab (0%–9%) and ustekinumab (0%–6%) all increased. The incidence rate (first dose of new biologic not including biosimilar switch) increased from 6.9% to 8.1% over the study period and point prevalence rates (any biologic use) increased from 20.2% to 43.5% ‐ an average annual percentage increase of 20%. Biosimilar penetration of new‐start anti‐TNFα agents increased from 3% to 91%. Demographics and outcomes of those patients receiving vedolizumab and ustekinumab were similar.ConclusionsComplete accrual of Scottish nationwide biologic usage within paediatric services demonstrates a rapidly changing, inexorably increasing PIBD biologics landscape.
Extracorporeal life support in cardiotoxicant poisoning—A narrative review
Authors: Voicu Sebastian , M'Rad Aymen , Malissin Isabelle , Deye Nicolas , Mégarbane Bruno 
Published: October 2022

AbstractExtracorporeal life support (ECLS) improves circulation in life‐threatening cardiac dysfunction or arrest patients. Its benefits in drug‐induced cardiovascular complications are debated. Indications and outcomes are poorly established. We performed a narrative review discussing ECLS indications, timing and results in cardiotoxicant‐poisoned patients. The review was focused on antiarrhythmic drugs and aluminium phosphide. Literature analysis was limited to the past 30 years in adults. Most reports were single cases and retrospective except one prospective case series of limited size, two of them controlled. ECLS indications and timing were at the discretion of physicians in charge but mostly included persistent cardiovascular failure despite elevated doses of inotropic/vasopressor support associated with elevated blood lactate concentrations (usually, >5 mmol/L) and collapsed left ventricular ejection fraction (LVEF; usually, ≤40%). Survival improved using ECLS versus standard care in one study. Survival was ~80% if ECLS was implemented in refractory cardiovascular failure and 25%–66% if implemented in cardiac arrest. In two controlled studies, survival of ECLS‐treated aluminium phosphide‐poisoned patients was improved versus standard care, if implemented in the presence of systolic blood pressure ≤80 mmHg despite inotropic/vasopressor treatment, arterial pH ≤ 7.0 and LVEF ≤ 40%. Despite low‐to‐moderate level of evidence, ECLS seems effective to improve survival in selected cardiotoxicant‐poisoned patients. Selection criteria need clarification.
Targeting cluster of differentiation 26 / dipeptidyl peptidase 4 (CD26/DPP4) in organ fibrosis
Authors: Ohm Birte , Moneke Isabelle , Jungraithmayr Wolfgang 
Published: October 2022

Cluster of differentiation 26 (CD26)/dipeptidyl peptidase 4 (DPP4) is an exopeptidase that is expressed as a transmembrane protein in many organs but also present in a circulating soluble form. Beyond its enzymatic and costimulatory activity, CD26/DPP4 is involved in the pathogenesis of chronic fibrotic diseases across many organ types, such as liver cirrhosis, kidney fibrosis and lung fibrosis. Organ fibrosis is associated with a high morbidity and mortality, and there are no causative therapies that can effectively attenuate the progress of the disease. Growing evidence suggests that inhibiting CD26/DPP4 can modulate the profibrotic tissue microenvironment and thus reduce fibrotic changes within affected organs. This review summarizes the role of CD26/DPP4 in fibroproliferative disorders and highlights new opportunities for an antifibrotic treatment by CD26/DPP4 inhibition. As a major advantage, CD26/DPP4 inhibitors have been in safe and routine clinical use in type 2 diabetes for many years and thus qualify for repurposing to repurpose as a promising therapeutic against fibrosis.LINKED ARTICLESThis article is part of a themed issue on Translational Advances in Fibrosis as a Therapeutic Target. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc
Mesozoic–Cenozoic multistage tectonic evolution of the Pamir: Detrital fission‐track constraints from the Tajik Basin
Authors: Li Lin , Najman Yani , Dupont‐Nivet Guillaume , Parra Mauricio , Roperch Pierrick , Kaya Mustafa , Meijer Niels , O'Sullivan Paul , Jepson Gilby , Aminov Jovid 
Published: October 2022

AbstractKnowledge of the tectonic history of the Pamir contributes to our understanding of both the evolution of collisional orogenic belts as well as factors controlling Central Asian aridification. It is, however, not easy to decipher the Mesozoic–Cenozoic tectonics of the Pamir due to extensive Neogene deformation in an orogen that remains largely understudied. This study reports detrital apatite and zircon fission‐track (FT) ages from both the eastern Tajik Basin sedimentary rocks and Pamir modern river sands. These FT data, supported by vitrinite reflectance and zircon and apatite U–Pb double dating, suggest that the majority of the FT ages are unreset and record exhumation stages of the Pamir, which has served as the source terrane of the Tajik Basin since the Cretaceous. Furthermore, we combine the new data with a compilation of published detrital apatite and zircon FT data from both the Tajik Basin sedimentary rocks and Pamir modern river sands, to explore the Mesozoic–Cenozoic tectonic history of Pamir. Deconvolved FT Peak Ages document two major Mesozoic exhumation events associated with the Late Triassic–Early Jurassic Cimmerian orogeny that reflects accretion of the Pamir terranes, as well as the Early–early Late Cretaceous deformation associated with the northward subduction of the Neo‐Tethys Ocean beneath Pamir. The compiled data also show significant Late Eocene–Neogene exhumation associated with the ongoing formation of the Pamir, which peaks at ca. 36, 25, 14 and 7 Ma.
Does paid family leave save infant lives? Evidence from California's paid family leave program
Authors: Chen Feng 
Published: October 2022

AbstractPaid family leave (PFL) aims to help working parents balance their careers and family responsibilities while also improving the well‐being of infants. Using linked U.S. birth and infant death data with a difference‐in‐differences framework, I find that a 6‐week PFL in California reduced the post‐neonatal mortality rate by 0.135‐ that is, it saved approximately 339 infant lives. There were fewer deaths from health‐related causes and larger effects for infants with married mothers and for infant boys. Additional checks and placebo examinations indicate that the observed effect is not due to contemporaneous shocks but rather is causal.
Aligning conservation and public health goals to tackle unsustainable trade of mammals
Authors: Cronin Melissa R. , de Wit Luz A. , Martínez‐Estévez Lourdes 
Published: October 2022

AbstractUnsustainable wildlife trade is a major driver of biodiversity loss and an important public health threat. Yet, effective wildlife trade regulation is currently at odds with food security and economic incentives provided by this global, multibillion‐dollar industry. Given such limitations, public health and conservation resources can be aligned to target species for which trade both increases risk of extinction and threatens public health. Here, we developed a simple conservation and health trade risk (CHT) index (range: 2–50) using a case study of traded mammals based on species' extinction and zoonotic risks, weighed by the extent of their trade. We applied this index to 1161 International Union for the Conservation of Nature‐listed terrestrial mammals involved in the wildlife trade to identify 284 high‐priority species that scored high in the CHT index (CHT ≥ 18). Species ranking high for conservation, public health, and trade risks include those belonging to the orders Primates, Cetartiodactyla (even‐toed ungulates), Rodentia (rodents), Chiroptera (bats), and Carnivora (carnivores). Of the high‐priority species, 33% (n = 95) are country‐endemics and may be good candidates for trade regulations and enforcement at national scales. Our study provides a preliminary step in prioritizing species, taxonomic groups, and countries for focused wildlife trade regulation to meet both conservation and public health goals.
An evaluation of a supratherapeutic dose of inclisiran on cardiac repolarization in healthy volunteers: A phase I, randomized study
Authors: Kallend David , Mason Jay , Smith Patrick F. , Koren Michael J. , Stoekenbroek Robert , He YanLing , Wijngaard Peter 
Published: October 2022

AbstractInclisiran is a small interfering RNA molecule that has been shown to provide an effective and sustained reduction in low‐density lipoprotein cholesterol levels. This study aimed to determine whether a supratherapeutic dose of inclisiran affects cardiac repolarization and conduction in healthy volunteers. A phase I, randomized, double‐blind, double‐dummy, placebo‐ and positive‐controlled, three‐way crossover study was performed in 48 healthy volunteers. Volunteers were assigned to three treatments in a randomized sequence: a supratherapeutic dose of inclisiran sodium (900 mg), placebo, or moxifloxacin 400 mg as a positive control, with a minimum 7‐day washout period between treatments. Continuous electrocardiogram monitoring was performed from >60 min before dosing until 48 h after dosing. Pharmacokinetics, pharmacodynamics, and safety were also assessed. Inclisiran, at a supratherapeutic dose, did not show a clinically significant effect on the QT interval (Fridericia correction formula [QTcF]; maximal placebo‐ and baseline‐corrected change: 2.5 ms [90% confidence interval: 0.6, 4.5]) near the maximal plasma concentrations at 4 h. In addition, inclisiran did not show any effects on other electrocardiogram intervals or ST‐ and T‐wave morphology. The positive control, moxifloxacin, demonstrated the expected changes in QTcF interval, validating the adequate sensitivity of the study. A supratherapeutic dose of inclisiran sodium (900 mg) had no effect on the QTcF interval or other electrocardiogram parameters, providing additional insight and reassurance regarding the safety profile of inclisiran.
Improving risk prediction for death, stroke and bleeding in Asian patients with atrial fibrillation
Authors: Krittayaphong Rungroj , Kanjanarutjawiwat Wiwat , Wisaratapong Treechada , Lip Gregory Y. H. 
Published: October 2022

AbstractBackgroundThe objectives of this study were to compare the GARFIELD Refitted model and CHA2DS2‐VASc/HAS‐BLED risk scores with the new model from the COOL‐AF registry for all‐cause death, ischaemic stroke/systemic embolism (SSE) and major bleeding in Asian patients with atrial fibrillation (AF).MethodsPatients with non‐valvular AF in the nationwide COOL‐AF registry were studied. Patients were enrolled from 27 hospitals in Thailand during 2014–2017. Main outcomes were all‐cause mortality, SSE and major bleeding. Predictive models of the three outcomes were developed from the variables in the multivariable Cox‐proportional Hazard model. Predictive values of the models were evaluated by C‐statistics, calibration plots and decision curve analysis (DCA). The new COOL‐AF models were compared with the GARFIELD Refitted models and CHA2DS2‐VASc model for all‐cause mortality, SSE/HAS‐BLED model for major bleeding.ResultsA total of 3405 patients were enrolled. The C‐statistics for the COOL‐AF models were 0.727 (0.712–0.742), 0.708 (0.693–0.724) and 0.706 (0.690–0.721) for all‐cause mortality, SSE and major bleeding, respectively. Calibration plots showed good agreement between predicted probability the observed outcomes for the COOL‐AF models with a calibration slope of 0.94–0.99. The predictive ability remains preserved after the internal validation with bootstraps and optimism (bias) correction. The COOL‐AF predictive models tended to be superior to the GARFIELD Refitted, CHA2DS2‐VASc and HAS‐BLED models.ConclusionThe COOL‐AF predictive models for all‐cause mortality, SSE and major bleeding in Asian patients with AF had a good predictive ability. The COOL‐AF model for all‐cause mortality was superior to the GARFIELD Refitted and CHA2DS2‐VASc model.
Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox–Gastaut syndrome: Interim analysis of an open‐label extension study
Authors: Knupp Kelly G. , Scheffer Ingrid E. , Ceulemans Berten , Sullivan Joseph , Nickels Katherine C. , Lagae Lieven , Guerrini Renzo , Zuberi Sameer M. , Nabbout Rima , Riney Kate , Agarwal Anupam , Lock Michael , Dai David , Farfel Gail M. , Galer Bradley S. , Gammaitoni Arnold R. , Polega Shikha , Davis Ronald , Gil‐Nagel Antonio 
Published: October 2022

AbstractObjectiveThis study was undertaken to evaluate the long‐term safety and effectiveness of fenfluramine in patients with Lennox–Gastaut syndrome (LGS).MethodsEligible patients with LGS who completed a 14‐week phase 3 randomized clinical trial enrolled in an open‐label extension (OLE; NCT03355209). All patients were initially started on .2 mg/kg/day fenfluramine and after 1 month were titrated by effectiveness and tolerability, which were assessed at 3‐month intervals. The protocol‐specified treatment duration was 12 months, but COVID‐19‐related delays resulted in 142 patients completing their final visit after 12 months.ResultsAs of October 19, 2020, 247 patients were enrolled in the OLE. Mean age was 14.3 ± 7.6 years (79 [32%] adults) and median fenfluramine treatment duration was 364 days; 88.3% of patients received 2–4 concomitant antiseizure medications. Median percentage change in monthly drop seizure frequency was −28.6% over the entire OLE (n = 241) and −50.5% at Month 15 (n = 142,p < .0001); 75 of 241 patients (31.1%) experienced ≥50% reduction in drop seizure frequency. Median percentage change in nondrop seizure frequency was −45.9% (n = 192,p = .0038). Generalized tonic–clonic seizures (GTCS) and tonic seizures were most responsive to treatment, with median reductions over the entire OLE of 48.8% (p < .0001,n = 106) and 35.8% (p < .0001,n = 186), respectively. A total of 37.6% (95% confidence interval [CI] = 31.4%–44.1%,n = 237) of investigators and 35.2% of caregivers (95% CI = 29.1%–41.8%,n = 230) rated patients as Much Improved/Very Much Improved on the Clinical Global Impression of Improvement scale. The most frequent treatment‐emergent adverse events were decreased appetite (16.2%) and fatigue (13.4%). No cases of valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) were observed.SignificancePatients with LGS experienced sustained reductions in drop seizure frequency on fenfluramine treatment, with a particularly robust reduction in frequency of GTCS, the key risk factor for sudden unexpected death in epilepsy. Fenfluramine was generally well tolerated; VHD or PAH was not observed long‐term. Fenfluramine may provide an important long‐term treatment option for LGS.
Presence of TRPV3 in macrophage lysosomes helps in skin wound healing against bacterial infection
Authors: Sahu Ram P. , Goswami Chandan 
Published: October 2022

AbstractTransient Receptor Potential Vanilloid subtype 3 (TRPV3) is a non‐selective cation channel that is known to be activated by physiological temperature and endogenous ligands. Involvement of TRPV3 in different skin functions has been reported. In this work, we demonstrate that activation of TRPV3 by FPP, an endogenous ligand enhances skin wound healing and bacterial clearance there. We report for the first time that TRPV3 is endogenously expressed in macrophages and activation of TRPV3 results in efficient bacterial clearance. At the subcellular level, TRPV3 is present in the lysosome and also in the nucleolus. We demonstrate that pharmacological modulation of TRPV3 protects lysosomal functions at hyperthermic shock conditions. The localization of TRPV3 at the nucleolus is specific, more in case of LPS‐treatment and dynamic with respect to the cell signalling. We demonstrate that at certain conditions, the nucleolar localization of TRPV3 is correlated with the presence of TRPV3 at the lysosome and with the cellular stress in general. We propose that TRPV3 act as a lysosomal regulator and sensor for cellular stress. These findings may have broad implications in understanding the cellular stress and TRPV3‐induced channelopathies and may have clinical relevance to skin infection treatment.
Internalized stigma and caregiver burden among parents of young adults with substance use disorders
Authors: Russell Beth S. , D'Aniello Carissa , Tambling Rachel R. , Stekler Nathaniel 
Published: October 2022

AbstractObjectiveThe present study explores mediation of the link between internalized stigma and caregiver burden by difficulties regulating distress and depression among a sample of family caregivers.BackgroundCaregiver burden is a common experience among parents whose children struggle with substance use. Depression, anxiety, and difficulties regulating distress are significantly related to the strains associated with this family caregiver role; further, stigmatizing attitudes about substance use can further impact family caregivers' mental health, thus heightening caregiver burden.MethodTwo‐hundred and sixty‐four family caregivers completed online, anonymous surveys on their experiences as a parent of a young adult struggling with substance use.ResultsParallel mediation modeling indicates significant effects such that difficulty regulating distress and depression symptoms partially explain the association between internalized stigma and caregiving burden.ConclusionCaregiver experiences occur in a societal context that includes stigmatizing attitudes toward the care recipient for their substance use balanced against their emotion regulation resources to manage psychological distress.ImplicationsFamily‐centered interventions to build caregiver emotion regulation resources are recommended, as these skills buffer against negative outcomes by reducing self‐critical judgments and encouraging nonreactive responses to perceived social threats like rejection, or shame.