bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicentre study and systematic review: Allopurinol exposure during pregnancy
Authors: Crouwel Femke , Simsek Melek , de Boer Marjon A. , van Asseldonk Dirk P. , Bhalla Abha , Weusthuis Angelique L. M. , Gilissen Lennard P. L. , Verburg Robert J. , Mares Wout G. N. , Jharap Bindia , Kuijvenhoven Johan P. , Oldenburg Bas , Buiter Hans J. C. , Julsgaard Mette , de Boer Nanne K. 
Published: July 2024

SummaryBackgroundData about the safety of allopurinol in pregnant women are sparsely reported.AimsTo investigate the risk of adverse pregnancy outcome and congenital abnormalities after in utero exposure to allopurinol in inflammatory bowel disease (IBD) pregnancies and in general.MethodsWe collected safety data of patients with IBD who were treated with allopurinol during pregnancy between January 2013 and March 2022. Additionally, we performed a systematic review about the teratogenic potential of allopurinol.ResultsWe collected data from 42 allopurinol‐exposed pregnancies, including one twin pregnancy; in all women, allopurinol was combined with a thiopurine. Six pregnancies (14.3%) resulted in miscarriage and one in stillbirth at 32 weeks. A congenital anomaly was observed in one newborn (coarctation of the aorta discovered postpartum). Three pregnancies, including the twin pregnancy, ended in moderate preterm delivery and one in very preterm delivery. Five neonates (15.2%) were small for gestational age. From our literature search, we identified an additional 102 allopurinol‐exposed pregnancies resulting in 129 live births, including 36 infants from our cohort. Ten infants (7.8%) were born with a congenital anomaly. Two (1.6%) had a comparable pattern of multiple anomalies. The systematic review sub‐analysis including only infants born to mothers with IBD (n = 76) revealed that 2.6% of infants had congenital anomalies after in utero exposure to a low dose of allopurinol.ConclusionsOverall, the teratogenicity of allopurinol remains inconclusive. Children conceived by mothers treated for IBD with allopurinol/thiopurine co‐therapy do not seem to have an increased risk of congenital anomalies.
Inflammation‐mediated drug interactions of olokizumab and cytochrome P450 activities in patients with rheumatoid arthritis
Authors: Agachi Svetlana , Beloukhova Marina , Mould Diane , Lemak Maria , Grishin Sergey , Samsonov Mikhail 
Published: July 2024

AbstractAimsIn patients with rheumatoid arthritis (RA), interleukin (IL)‐6 affects the activity of cytochrome P450 (CYP) enzymes. Treatment with anti‐IL‐6 therapy can reverse the IL‐6‐mediated downregulation of CYP enzymes, resulting in changes in plasma levels of CYP substrates. The primary objective of this study was to evaluate the impact of the IL‐6 inhibitor olokizumab on the pharmacokinetics of CYP probe substrates in subjects with active RA.MethodsSeventeen patients with active RA were orally administered a phenotyping cocktail of midazolam (CYP3A4 substrate), omeprazole (CYP2C19 substrate), warfarin (CYP2C9 substrate) and caffeine (CYP1A2 substrate) alone and 2 weeks after a single subcutaneous injection of 128 mg olokizumab. The pharmacokinetic parameters of each substrate were calculated using noncompartmental analysis.ResultsSixteen of 17 enrolled patients received the complete doses of the cocktail drugs and olokizumab and were eligible for the pharmacokinetic evaluations. After single‐dose administration of olokizumab, the exposure of midazolam and omeprazole decreased by 30‐33% and 26‐32%, respectively, compared to when the substrates were administered along via cocktail. In the presence of olokizumab, caffeine exposure increased by 19‐23% compared to caffeine administration alone. There were no significant changes in S‐warfarin exposure.ConclusionIn patients with active RA, olokizumab potentially reverses the IL‐6‐mediated suppression of CYP3A4 and CYP2C19. According to FDA guidance, olokizumab is considered a weak inducer of CYP3A4 and CYP2C19.
Impact of homologous recombination repair/BReast CAncer (BRCA) gene alterations on survival in a real‐world setting of metastatic prostate cancer
Authors: Wenzel Mike , Hoeh Benedikt , Koll Florestan , Humke Clara , Fassl Anne , Reis Henning , Wild Peter , Steuber Thomas , Graefen Markus , Tilki Derya , Traumann Miriam , Banek Severine , Chun Felix K.H. , Mandel Philipp 
Published: July 2024

ObjectiveTo investigate alterations of homologous recombination repair (HRR) and especially BReast CAncer 1/2 (BRCA1/2) gene on overall survival (OS). Moreover, to explore the effect of inhibition of poly(ADP‐ribose)‐polymerase (PARPi) as systemic therapy for metastatic castration‐resistant prostate cancer (mCRPC).Patients and methodsOf all HRR‐screened patients with metastatic prostate cancer, baseline characteristics were sampled. Kaplan–Meier estimates and multivariable Cox regression models predicted the effect of HRR/BRCA1/2 alterations on OS.ResultsOf 196 eligible patients, 61 (31%) harboured any HRR and 40 (20%) BRCA1/2 alterations. Of HRR alterations, 40 (66%) vs six (10%) vs five (8.2%) vs four (6.6%) vs two (3.3%) vs four (6.6%) were BRCA1/2 vs Ataxia‐telangiectasia mutated kinase (ATM) vs checkpoint kinase 2 (CHEK2) vs cyclin‐dependent kinase 12 (CDK12) vs Fanconi anaemia complementation Group A (FANCA) vs positive for other mutations. Of these, 30% received a PARPi. OS differed significantly between HRR‐positive vs ‐negative patients. Specifically in hormone‐sensitive prostate cancer, the median OS was 63 (HRR positive) vs 57 (BRCA1/2 positive) vs 113 months (HRR negative) (P ≤ 0.01). In mCRPC, OS was 42 (HRR positive) vs 41 (BRCA1/2 positive) vs 70 months (HRR negative) (P ≤ 0.01). HRR and BRCA1/2 alterations were associated with worse OS after multivariable adjustment. Finally, patients with mCRPC with BRCA1/2 mutation treated without PARPi harboured worse OS than patients with BRCA1/2 mutation and PARPi therapy (median OS: 33 vs 48 months, P < 0.03).ConclusionIncidence of HRR alteration in a clinical real‐world setting is high when using blood‐ and tissue‐based tests. Patients with HRR/BRCA alterations have worse outcomes resulting in significant OS differences between HRR/BRCA‐positive patients with mCRPC with and without PARPi usage vs HRR/BRCA‐negative patients.
Visualizing alpha‐synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo
Authors: Straumann Nadja , Combes Benjamin F. , Dean Ben Xose Luis , Sternke‐Hoffmann Rebecca , Gerez Juan A. , Dias Ines , Chen Zhenyue , Watts Benjamin , Rostami Iman , Shi Kuangyu , Rominger Axel , Baumann Christian R. , Luo Jinghui , Noain Daniela , Nitsch Roger M. , Okamura Nobuyuki , Razansky Daniel , Ni Ruiqing 
Published: July 2024

AbstractAbnormal alpha‐synuclein (αSyn) and iron accumulation in the brain play an important role in Parkinson's disease (PD). Herein, we aim to visualize αSyn inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. The fluorescent pyrimidoindole derivative THK‐565 probe was characterized by means of recombinant fibrils and brains from 10‐ to 11‐month‐old M83 mice. Concurrent wide‐field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging were subsequently performed in vivo. Structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 T as well as scanning transmission x‐ray microscopy (STXM) were performed to characterize the iron deposits in the perfused brains. Immunofluorescence and Prussian blue staining were further performed on brain slices to validate the detection of αSyn inclusions and iron deposition. THK‐565 showed increased fluorescence upon binding to recombinant αSyn fibrils and αSyn inclusions in post‐mortem brain slices from patients with PD and M83 mice. Administration of THK‐565 in M83 mice showed higher cerebral retention at 20 and 40 min post‐intravenous injection by wide‐field fluorescence compared to nontransgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe3+ form, as evinced by the STXM results. In conclusion, we demonstrated in vivo mapping of αSyn by means of noninvasive epifluorescence and vMSOT imaging and validated the results by targeting the THK‐565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo.
Evolution of parasites in the Anthropocene: new pressures, new adaptive directions
Authors: Poulin Robert , Salloum Priscila M. , Bennett Jerusha 
Published: July 2024

ABSTRACTThe Anthropocene is seeing the human footprint rapidly spreading to all of Earth's ecosystems. The fast‐changing biotic and abiotic conditions experienced by all organisms are exerting new and strong selective pressures, and there is a growing list of examples of human‐induced evolution in response to anthropogenic impacts. No organism is exempt from these novel selective pressures. Here, we synthesise current knowledge on human‐induced evolution in eukaryotic parasites of animals, and present a multidisciplinary framework for its study and monitoring. Parasites generally have short generation times and huge fecundity, features that predispose them for rapid evolution. We begin by reviewing evidence that parasites often have substantial standing genetic variation, and examples of their rapid evolution both under conditions of livestock production and in serial passage experiments. We then present a two‐step conceptual overview of the causal chain linking anthropogenic impacts to parasite evolution. First, we review the major anthropogenic factors impacting parasites, and identify the selective pressures they exert on parasites through increased mortality of either infective stages or adult parasites, or through changes in host density, quality or immunity. Second, we discuss what new phenotypic traits are likely to be favoured by the new selective pressures resulting from altered parasite mortality or host changes; we focus mostly on parasite virulence and basic life‐history traits, as these most directly influence the transmission success of parasites and the pathology they induce. To illustrate the kinds of evolutionary changes in parasites anticipated in the Anthropocene, we present a few scenarios, either already documented or hypothetical but plausible, involving parasite taxa in livestock, aquaculture and natural systems. Finally, we offer several approaches for investigations and real‐time monitoring of rapid, human‐induced evolution in parasites, ranging from controlled experiments to the use of state‐of‐the‐art genomic tools. The implications of fast‐evolving parasites in the Anthropocene for disease emergence and the dynamics of infections in domestic animals and wildlife are concerning. Broader recognition that it is not only the conditions for parasite transmission that are changing, but the parasites themselves, is needed to meet better the challenges ahead.
Bilateralism vs. multilateralism: Role of political economy for the prospect of multilateral free trade
Authors: Conglin Chi Eric , Murat Yildiz Halis 
Published: July 2024

AbstractIn this paper, we use a unified framework of competing exporters and competing importers models where political biases in both exporting and import‐competing sectors influence governments' decisions in trade agreement formation and external tariff setting. Using an endogenous trade agreement formation model, we show that the relative strength of political biases in import‐competing and exporting sectors are pivotal in determining the free‐riding incentives, exclusion incentives and whether the ability to form free trade areas acts as building or stumbling blocks towards multilateral free trade. When the political biases toward exporting and import‐competing sectors are sufficiently weak, the ability to form free trade agreements acts as strong building blocks toward free trade. However, when the political bias towards exporting sectors is at the intermediate range and political bias towards import‐competing sectors is sufficiently strong, the ability to form free trade agreements acts as strong stumbling blocks.
Adaptive spatiotemporal management to reduce shark bycatch in tuna fisheries
Authors: Crespo Guillermo Ortuño , Griffiths Shane , Murua Hilario , Österblom Henrik , Lopez Jon 
Published: July 2024

AbstractPurse‐seine tropical tuna fishing in the eastern tropical Pacific Ocean (EPO) results in the bycatch of several sensitive species groups, including elasmobranchs. Effective ecosystem management balances conservation and resource use and requires considering trade‐offs and synergies. Seasonal and adaptive spatial measures can reduce fisheries impacts on nontarget species while maintaining or increasing target catches. Identifying persistently high‐risk areas in the open ocean, where dynamic environmental conditions drive changes in species’ distributions, is essential for exploring the impact of fisheries closures. We used fisheries observer data collected from 1995 to 2021 to explore the spatiotemporal persistence of areas of high bycatch risk for 2 species of oceanic sharks, silky shark (Carcharhinus falciformis) and oceanic whitetip shark (Carcharhinus longimanus), and of low tuna catch rates. We analyzed data collected by fisheries scientific observers onboard approximately 200 large purse‐seine vessels operating in the EPO under 10 different flags. Fishing effort, catch, and bycatch data were aggregated spatially and temporally at 1° × 1° cells and monthly, respectively. When areas of high fishing inefficiency were closed the entire study period and effort was reallocated proportionally to reflect historical effort patterns, yearly tuna catch appeared to increase by 1–11%, whereas bycatch of silky and oceanic whitetip sharks decreased by 10–19% and 9%, respectively. Prior to fishing effort redistribution, bycatch reductions accrued to 21–41% and 14% for silky and oceanic whitetip sharks, respectively. Our results are consistent with previous findings and demonstrate the high potential for reducing elasmobranch bycatch in the EPO without compromising catch rates of target tuna species. They also highlight the need to consider new dynamic and adaptive management measures to more efficiently fulfill conservation and sustainability objectives for exploited resources in the EPO.
Impact of CD151 overexpression on prognosis and therapy in non‐small cell lung cancer patients lacking EGFR mutations
Authors: Wong Amanda Huee‐Ping , Nga Min En , Chin Chin Yein , Tai Yee Kit , Wong Hung Chew , Soo Ross , An Omer , Yang Henry , Seet Ju Ee , Lim Yaw Chyn , Tam John Kit Chung , Tran Thai 
Published: July 2024

AbstractThis study investigates CD151, a protein linked to cancer progression, in non‐small cell lung cancer (NSCLC) patients without epidermal growth factor receptor (EGFR) mutations. These patients often have limited treatment options. The study used retrospective analysis to examine 157 adenocarcinoma biopsy specimens and 199 patient cases from The Cancer Genome Atlas, correlating CD151 expression with patient survival. Cellular studies revealed that CD151 interacts with EGFR, influencing epidermal growth factor (EGF)‐induced cell proliferation and the effectiveness of the EGFR inhibitor, erlotinib. A strong association was found between CD151 expression and EGFR mutation status. High CD151 expression in the absence of EGFR mutations is correlated with poorer survival outcomes. Biological assays showed that CD151 colocalizes and associates with EGFR, playing a crucial role in regulating EGF‐induced cell proliferation via the AKT and ERK1/2 pathways. Importantly, CD151 expression was found to influence the anti‐proliferative effects of the EGFR tyrosine kinase inhibitor, erlotinib. High CD151 expression, in the absence of EGFR mutations, was associated with poorer survival outcomes. It could serve as a potential prognostic marker and influence cellular responses to EGFR‐targeted treatments. This study highlights CD151 as a potential novel target for therapeutic intervention in NSCLC, especially in populations lacking EGFR mutations.
More dads at home, more girls in maths‐intensive studies? Evidence from a parental leave reform
Authors: Mikkelsen Sara , Peter Noemi 
Published: July 2024

AbstractEvidence suggests that separate spheres gender norms discourage girls from maths. We therefore examine a policy that counteracts such norms among parents, and investigate whether it increases girls' participation in maths‐intensive studies. Specifically, we examine a parental leave reform that reserved one month of leave for fathers, and estimate its effect on children's study choices. We find that the reform increases the probability of doing a maths‐intensive programme in upper secondary education among girls whose father was otherwise reluctant to take leave. There is no effect on boys. We also conduct heterogeneity analyses to investigate whether the results can be explained by human capital transmission or the gender norms mechanism. The results of our analyses suggest that the gender norms mechanism is at play.
The effect of an evidence‐based practice course on students' lifelong learning skills and problem‐solving skills: An educational intervention study
Authors: Gönderen Çakmak Huri Seval , Ayhan Başer Duygu 
Published: July 2024

AbstractIn this study, the aim was to investigate the effect of an evidence‐based practice course on the lifelong learning skills and problem‐solving skills of health science students. A prospective one‐group pre‐test–post‐test design. The universe of the study consisted of 189 students from Cankiri Karatekin University. Student information form, Jefferson lifelong learning skill scale, Problem‐solving inventory (PSI) were used as data collection instruments. The sample of the study consisted of 156 students who completed the 14‐week course and fully completed the pre‐test and post‐test. For data analysis, IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp. package program was used. While 84% of the students said that they had never heard of the term EBP before, 91.7% of those who knew the term said they had heard it in their field courses. The lifelong learning skill scale total score change of the students, the PSI total score change of the students after the 26‐h EBP course were statistically significant. EBP is very important for health science students to increase their problem‐solving success and lifelong learning skills, and it should be integrated into the curriculum.
A case of frontal lobe seizures with ‘dancing‐like’ semiology
Authors: Atanasio Giorgia , Germanò Antonio , Granata Francesca , Tomaiuolo Francesco , Labate Angelo 
Published: July 2024

AbstractBackground and purpose‘Dancing‐like’ semiology is extremely rare and described in few case reports. It is characterized by rhythmic, oscillatory movements of the pelvis and/or limbs during which the subject appears to be dancing. It has been associated with both the frontal and temporal epileptic zone; however, the possible network involved in these fascinating seizures is unclear.MethodsThe case of a 45‐year‐old woman suffering from drug‐resistant focal epilepsy with multi‐day seizures of bizarre semiology is described. A structural and perfusion magnetic resonance imaging study (interictal and peri‐ictal) and video‐electroencephalograms were carried out, and several home videos were employed. A vagal stimulator was implanted.ResultsHome videos documented the ‘dancing’ semiology of seizures better than video‐ electroencephalogram recordings. The imaging study revealed a focal frontal polymicrogyria with a peri‐ictal cerebral blood flow increase at the perisylvian lesion foci. The combination of add‐on cenobamate and vagal nerve stimulation resulted in complete seizure freedom.ConclusionThe unusual and complex dancing‐like semiology observed during our patient's seizures adds to the repertoire of fascinating complex motor manifestations of frontal lobe epilepsy.
Fathers' experiences with supportive parenting interventions: A qualitative systematic review
Authors: Shorey Shefaly , Chee Cornelia , Sambhi Sharan Kaur , Chong Shang Chee , Choolani Mahesh 
Published: July 2024

AbstractDespite proven efficacy, fatherhood interventions face challenges in attracting and retaining participants. This qualitative systematic review aims to inform the future design of fatherhood interventions by consolidating and synthesizing the evidence around fathers' experiences with interventions aimed at enhancing their involvement and relationships with their children. Following PRISMA guidelines, we analyzed 10 studies from a search of six electronic databases. Our analysis coalesced into three pivotal themes: (a) creating a sense of belonging: facilitating participation; (b) transformative takeaways; and (c) challenges of negotiating expectations of masculinity. Our findings indicate that group‐based, culturally sensitive programs are advantageous but also reveal that fathers grapple with reconciling evolving fatherhood roles with societally entrenched expectations of masculinity. This review offers actionable insights for the future development, evaluation, and implementation of fatherhood interventions, particularly those utilizing qualitative research methodologies.
6‐Phosphogluconolactonase is critical for the efficient functioning of the pentose phosphate pathway
Authors: Phégnon Léa , Pérochon Julien , Uttenweiler‐Joseph Sandrine , Cahoreau Edern , Millard Pierre , Létisse Fabien 
Published: July 2024

The metabolic networks of microorganisms are remarkably robust to genetic and environmental perturbations. This robustness stems from redundancies such as gene duplications, isoenzymes, alternative metabolic pathways, and also from non‐enzymatic reactions. In the oxidative branch of the pentose phosphate pathway (oxPPP), 6‐phosphogluconolactone hydrolysis into 6‐phosphogluconate is catalysed by 6‐phosphogluconolactonase (Pgl) but in the absence of the latter, the oxPPP flux is thought to be maintained by spontaneous hydrolysis. However, in Δpgl Escherichia coli, an extracellular pathway can also contribute to pentose phosphate synthesis. This raises question as to whether the intracellular non‐enzymatic reaction can compensate for the absence of 6‐phosphogluconolactonase and, ultimately, on the role of 6‐phosphogluconolactonase in central metabolism. Our results validate that the bypass pathway is active in the absence of Pgl, specifically involving the extracellular spontaneous hydrolysis of gluconolactones to gluconate. Under these conditions, metabolic flux analysis reveals that this bypass pathway accounts for the entire flux into the oxPPP. This alternative metabolic route—partially extracellular—sustains the flux through the oxPPP necessary for cell growth, albeit at a reduced rate in the absence of Pgl. Importantly, these findings imply that intracellular non‐enzymatic hydrolysis of 6‐phosphogluconolactone does not compensate for the absence of Pgl. This underscores the crucial role of Pgl in ensuring the efficient functioning of the oxPPP.
The effect of fiber bridging on mode I fatigue delamination propagation—Part II: Cohesive zone model
Authors: Ben Gur Hila , Banks‐Sills Leslie 
Published: July 2024

AbstractThis is Part II of a series of two papers in which the effect of fiber bridging on fatigue delamination propagation is assessed. In Part I, unidirectional double cantilever beam specimens composed of the carbon fiber‐reinforced polymer prepreg AS4/8552 were tested by means of fatigue cycling. Fiber bridging in beam specimens composed of unidirectional plies causes the apparent fatigue delamination curves to exhibit growth which is slower than that for the case when fiber bridging does not occur. Generally, fiber bridging does not occur in laminate structures. In Part II of this study, a cohesive zone model (CZM) is developed and used to carry out finite element analyses to simulate the experiments. The CZM is employed to quantify and eliminate the contribution of fiber bridging to the fatigue delamination growth curves. In this way, more realistic results are obtained. These results are compared to an upper bound curve determined in Part I.