bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of pharmacokinetic drug interaction between clesacostat and DGAT2 inhibitor ervogastat in healthy adult participants
Authors: Sawant‐Basak Aarti , Bergman Arthur J. , Mancuso Jessica , Tripathy Sakambari , Gosset James R. , Mendes da Costa Laure , Esler William P. , Calle Roberto A. 
Published: February 2024

AbstractCo‐administration of clesacostat (acetyl‐CoA carboxylase inhibitor, PF‐05221304) and ervogastat (diacylglycerol O‐acyltransferase inhibitor, PF‐06865571) in laboratory models improved non‐alcoholic fatty liver disease (NAFLD)/non‐alcoholic steatohepatitis (NASH) end points and mitigated clesacostat‐induced elevations in circulating triglycerides. Clesacostat is cleared via organic anion‐transporting polypeptide‐mediated hepatic uptake and cytochrome P450 family 3A (CYP3A); in vitro clesacostat is identified as a potential CYP3A time‐dependent inactivator. In vitro ervogastat is identified as a substrate and potential inducer of CYP3A. Prior to longer‐term efficacy trials in participants with NAFLD, safety and pharmacokinetics (PK) were evaluated in a phase I, non‐randomized, open‐label, fixed‐sequence trial in healthy participants. In Cohort 1, participants (n = 7) received clesacostat 15 mg twice daily (b.i.d.) alone (Days 1–7) and co‐administered with ervogastat 300 mg b.i.d. (Days 8–14). Mean systemic clesacostat exposures, when co‐administered with ervogastat, decreased by 12% and 19%, based on maximum plasma drug concentration and area under the plasma drug concentration–time curve during the dosing interval, respectively. In Cohort 2, participants (n = 9) received ervogastat 300 mg b.i.d. alone (Days 1–7) and co‐administered with clesacostat 15 mg b.i.d. (Days 8–14). There were no meaningful differences in systemic ervogastat exposures when administered alone or with clesacostat. Clesacostat 15 mg b.i.d. and ervogastat 300 mg b.i.d. co‐administration was overall safe and well tolerated in healthy participants. Cumulative safety and no clinically meaningful PK drug interactions observed in this study supported co‐administration of these two novel agents in additional studies exploring efficacy and safety in the management of NAFLD.
Comparative analysis of hospitalization risk for incident heart failure in non‐Hispanic Black versus non‐Hispanic White individuals with type 2 diabetes on empagliflozin (Empa‐AA): Insights from real‐world data
Authors: Mishriky Basem M. , Cummings Doyle M. , Fu Yuanyuan , Halladay Jacqueline R. , Jones Schuyler , Boan Andrea D. , Jones Sara , Patil Shivajirao P. , Powell James R. , Adams Alyssa , Irish William 
Published: February 2024

AbstractAimThere are limited data to evaluate hospitalization for heart failure (hHF) in non‐Hispanic Black (hereafter Black) or non‐Hispanic White (hereafter White) individuals without previous hHF. Our goal was to evaluate the risk of hHF among Black versus White patients with type 2 diabetes (T2DM) who were initially prescribed empagliflozin using real‐world data.MethodsThis multicentre retrospective cohort study included participants aged ≥18 years who had T2DM, were either Black or White, had no previous hHF, and were prescribed empagliflozin between August 2014 and December 2019. Our primary outcome was time to first hHF after the initial prescription of empagliflozin. A propensity‐score (PS)‐weighted analysis was performed to balance characteristics by race. The inverse probability treatment weighting method based on PS was used to make treatment comparisons. To compare Black with White, a PS‐weighted Cox's cause‐specific hazards model was used.ResultsIn total, 8789 participants were eligible for inclusion (Black = 3216 vs. White = 5573). The Black cohort was significantly younger, had a higher proportion of females, and had a higher prevalence of chronic kidney disease, hypertension and diabetic retinopathy, while the White cohort had a higher prevalence of coronary artery disease. After adjustment for confounding factors such as age, gender, coronary artery disease, hypertension and diabetic retinopathy, the hazard ratio for first‐time hHF was not significantly different between the two racial groups [hazard ratio (95% confidence interval) = 1.09 (0.84‐1.42), p = .52].ConclusionThis study showed no significant difference in incident hHF among Black versus White individuals with T2DM following a prescription for empagliflozin.
Synergetic impact of lipoprotein(a) and fibrinogen on stroke in coronary artery disease patients
Authors: Yang Cheng , Zhu Cheng‐Gang , Sui Yong‐Gang , Guo Yuan‐Lin , Wu Na‐Qiong , Dong Qian , Xu Rui‐Xia , Qian Jie , Li Jian‐Jun 
Published: February 2024

AbstractBackgroundEmerging data suggested that lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease. Previous studies indicated fibrinogen (Fib) had synergetic effect on Lp(a)‐induced events. However, combined impact of Fib and Lp(a) on ischemic stroke has not been elucidated.MethodsIn this prospective study, we consecutively enrolled 8263 patients with stable coronary artery diseases (CAD) from 2011 to 2017. Patients were categorized into three groups according to tertiles of Lp(a) levels [Lp(a)‐low, Lp(a)‐medium, and Lp(a)‐high] and further divided into nine groups by Lp(a) and Fib levels. All subjects were followed up for the occurrence of ischemic stroke.ResultsDuring a median follow‐up of 37.7 months, 157 (1.9%) ischemic strokes occurred. Stroke incidence increased by Lp(a) (1.1 vs. 2.1 vs. 2.5%, Cochran‐Armitage p < .001) and Fib (1.1 vs. 2.0 vs. 2.6%, Cochran‐Armitage p < .001) categories. When further classified into nine groups by Lp(a) and Fib levels, the incidence of ischemic stroke in group 9 [Lp(a)‐high and Fib‐high] was significantly higher than that in group 1 [Lp(a)‐low and Fib‐low] (3.1 vs. 6%, p < .001). The group 9 was associated with a highest risk for ischemic stroke (adjusted HR 4.907, 95% CI: 2.154–11.18, p < .001), compared with individuals in the Lp(a)‐high (adjusted HR 2.290, 95% CI: 1.483–3.537, p < .001) or Fib‐high (adjusted HR 1.184, 95% CI: 1.399–3.410, p = .001). Furthermore, combining Lp(a) with Fib increased C‐statistics by .045 (p = .004).ConclusionsCurrent study first demonstrated that elevated Lp(a) combining with Fib evaluation enhanced the risk of ischemic stroke in patients with CAD beyond Lp(a) or Fib alone.
Sodium nitroprusside enhances stepping test performance and increases medium spiny neurons responsiveness to cortical inputs in a rat model of Levodopa‐induced dyskinesias
Authors: Ribeiro Danilo Leandro , Guimarães Rayanne Poletti , Bariotto‐dos‐Santos Keila , Del Bel Elaine , Padovan‐Neto Fernando E. 
Published: February 2024

AbstractLevodopa (L‐DOPA) is the classical gold standard treatment for Parkinson's disease. However, its chronic administration can lead to the development of L‐DOPA‐induced dyskinesias (LIDs). Dysregulation of the nitric oxide–cyclic guanosine monophosphate pathway in striatal networks has been linked to deficits in corticostriatal transmission in LIDs. This study investigated the effects of the nitric oxide (NO) donor sodium nitroprusside (SNP) on behavioural and electrophysiological outcomes in sham‐operated and 6‐hydroxydopamine‐lesioned rats chronically treated with vehicle or L‐DOPA, respectively. In sham‐operated animals, systemic administration of SNP increased the spike probability of putative striatal medium spiny neurons (MSNs) in response to electrical stimulation of the primary motor cortex. In 6‐hydroxydopamine‐lesioned animals, SNP improved the stepping test performance without exacerbating abnormal involuntary movements. Additionally, SNP significantly increased the responsiveness of putative striatal MSNs in the dyskinetic striatum. These findings highlight the critical role of the NO signalling pathway in facilitating the responsiveness of striatal MSNs in both the intact and dyskinetic striata. The study suggests that SNP has the potential to enhance L‐DOPA's effects in the stepping test without exacerbating abnormal involuntary movements, thereby offering new possibilities for optimizing Parkinson's disease therapy. In conclusion, this study highlights the involvement of the NO signalling pathway in the pathophysiology of LIDs.
Fatigue life reinforcement of carbon black filled natural rubber under non‐relaxing torsion loadings and comparison with non‐relaxing tension loadings
Authors: Mouslih Yasser , Le Cam Jean‐Benoît , Ruellan Benoît , Jeanneau Isabelle , Canévet Frédéric 
Published: February 2024

AbstractIn this paper, the effect of non‐relaxing torsion loadings on the fatigue lifetime reinforcement of carbon black filled natural rubber is fully addressed. Torsion fatigue tests with different loading ratios have been performed with highly notched axisymmetric‐shaped specimens. Finite element analysis is used to predict the mechanical state at any point in the specimens. The prediction is significantly improved by taking into account the heterogeneous accommodation. The first Haigh diagram under fatigue torsion is built and analyzed by calculating the minimum loading in terms of the Cauchy stress as the normal stress to the crack for the minimum angle prescribed during the cycle. A strong lifetime reinforcement has been observed, which is found to be of the same amplitude to the one obtained under uniaxial tension with the same material. This has been confirmed by specific tests that combined non‐relaxing torsion and non‐relaxing tension loadings. Post‐mortem analysis carried out at the macroscopic and the microscopic scales enabled us to identify damage mechanisms, especially in the cases where the lifetime reinforcement was observed.
Nutrient conditions influence allelopathic capabilities of Ludwigia adscendens and other tropical macrophytes against Microcystis aeruginosa
Authors: Sim Darren Z. H. , Mowe Maxine A. D. , Mitrovic Simon M. , Tulsian Nikhil K. , Anand Ganesh S. , Yeo Darren C. J. 
Published: February 2024

Abstract

Macrophytes may release allelochemicals that suppress competing phytoplankton, although it is unclear how their effectiveness could be influenced by environmental nutrient conditions. To approach this, we conducted a series of bioassays against the bloom‐forming cyanobacterium Microcystis aeruginosa using extracts and exudates from potentially allelopathic macrophytes under varying nutrient conditions.

We screened six different tropical macrophytes and identified antialgal effects in both extracts and exudates of Ludwigia adscendens, Persicaria barbata, Pontederia crassipes and Vallisneria spiralis. Growth assays indicated that extract inhibitory effectiveness decreased as nutrient concentration increased from 5% to 50% strength.

Focusing on the potent antialgal extract of L. adscendens, we determined that its inhibitory effects were enhanced by specifically reducing the availability of either micronutrient or bicarbonate availability, indicating a role of these nutrients in protecting algal cells from allelochemicals.

Bioactivity‐guided fractionation and ultra‐performance liquid chromatography – mass spectrometry analyses of L. adscendens extract indicated that ellagitannins were the major constituent of bioactive extract fractions, suggesting an antialgal mechanism common to other tannic compounds. Novel allelopathic alkaloids and terpenoid compounds also were described, although their mechanisms of action are unknown.

Our findings provide evidence that the availability of carbon and micronutrients to cyanobacteria could influence the effects of macrophyte allelochemicals. This interaction between the nutrient environment and allelochemical sensitivity of cyanobacteria can be substantial, and studies or applications involving allelopathic interactions between macrophytes and phytoplankton should consider this.
Community views on the secondary use of general practice data: Findings from a mixed‐methods study
Authors: Braunack‐Mayer Annette J. , Adams Carolyn , Nettel‐Aguirre Alberto , Fabrianesi Belinda , Carolan Lucy , Beilby Justin , Flack Felicity 
Published: February 2024

AbstractIntroductionGeneral practice data, particularly when combined with hospital and other health service data through data linkage, are increasingly being used for quality assurance, evaluation, health service planning and research. In this study, we explored community views on sharing general practice data for secondary purposes, including research, to establish what concerns and conditions need to be addressed in the process of developing a social licence to support such use.MethodsWe used a mixed‐methods approach with focus groups (November–December 2021), followed by a cross‐sectional survey (March–April 2022).ResultsThe participants in this study strongly supported sharing general practice data with the clinicians responsible for their care, and where there were direct benefits for individual patients. Over 90% of survey participants (N = 2604) were willing to share their general practice information to directly support their health care, that is, for the primary purpose of collection. There was less support for sharing data for secondary purposes such as research and health service planning (36% and 45% respectively in broad agreement) or for linking general practice data to data in the education, social services and criminal justice systems (30%–36%). A substantial minority of participants were unsure or could not see how benefits would arise from sharing data for secondary purposes. Participants were concerned about the potential for privacy breaches, discrimination and data misuse and they wanted greater transparency and an opportunity to consent to data release.ConclusionThe findings of this study suggest that the public may be more concerned about sharing general practice data for secondary purposes than they are about sharing data collected in other settings. Sharing general practice data more broadly will require careful attention to patient and public concerns, including focusing on the factors that will sustain trust and legitimacy in general practice and GPs.Patient and Public ContributionMembers of the public were participants in the study. Data produced from their participation generated study findings.Clinical Trial RegistrationNot applicable.
Differences in integrated assessment and management of non‐communicable diseases (NCDs) for people with HIV across the WHO European region
Authors: Kraef Christian , Singh Sabine , Fursa Olga , Abutidze Akaki , Rukhadze Nino , Mulabdic Velida , Yancheva Nina , Mehmeti Murat , Balayan Tatevik , Harxhi Arjan , Trajanovska Jasmina , Mackintosh Claire , Duvivier Claudine , Beniowski Marek , Jilich David , Reikvam Dag Henrik , Tau Luba , Podlekareva Daria , Ryom Lene , Peters Lars , Kowalska Justyna , Kirk Ole ,   for the EuroSIDA Study Group
Published: February 2024

AbstractObjectivesWe aimed to assess the extent of integration of non‐communicable disease (NCD) assessment and management in HIV clinics across Europe.MethodsA structured electronic questionnaire with 41 multiple‐choice and rating‐scale questions assessing NCD assessment and management was sent to 88 HIV clinics across the WHO European Region during March–May 2023. One response per clinic was collected.ResultsIn all, 51 clinics from 34 countries with >100 000 people with HIV under regular follow‐up responded. Thirty‐seven clinics (72.6%) reported shared NCD care responsibility with the general practitioner. Systematic assessment for NCDs and integration of NCD management were common overall [median agreement 80%, interquartile range (IQR): 55–95%; and 70%, IQR: 50–88%, respectively] but were lowest in central eastern and eastern Europe. Chronic kidney disease (median agreement 96%, IQR: 85–100%) and metabolic disorders (90%, IQR: 75–100%) were regularly assessed, while mental health (72%, IQR: 63–85%) and pulmonary diseases (52%, IQR: 40–75%) were less systematically assessed. Some essential diagnostic tests such as glycated haemoglobin (HbA1c) for diabetes (n = 38/51, 74.5%), proteinuria for kidney disease (n = 30/51, 58.8%) and spirometry for lung disease (n = 11/51, 21.6%) were only employed by a proportion of clinics. The most frequent barriers for integrating NCD care were the lack of healthcare workers (n = 17/51, 33.3%) and lack of time during outpatient visits (n = 12/51, 23.5%).ConclusionMost HIV clinics in Europe systematically assess and manage NCDs. People with HIV appear to be screened more frequently than the general population at the same age. There are, however, larger gaps among eastern European clinics in general and for clinics in all regions related to mental health, pulmonary diseases and the employment of some essential diagnostic tests.
Living on the edge—Genomic and ecological delineation of cryptic lineages in the high‐elevation specialist Erebia nivalis
Authors: Augustijnen Hannah , Patsiou Theofania , Schmitt Thomas , Lucek Kay 
Published: February 2024

Abstract
Cold‐adapted species at high elevations may be especially impacted by global warming since they may be limited in their capacity to adapt to changing conditions or may be prevented from shifting their distributions upwards if no suitable habitats are available.
The latter may be true for Erebia nivalis, a high‐elevation specialist that mainly occurs in the Austrian Alps and on few mountaintops in Switzerland, where its taxonomic and conservation status remains unclear.
We aimed to clarify the relationships among geographically isolated populations of E. nivalis using whole‐genome resequencing data to reconstruct population connectivity and phylogenetic relationships. We inferred current and historical effective population sizes and combined these with tests for ecological differentiation based on available occurrence data to re‐evaluate the conservation status of E. nivalis.
Our results confirm that Swiss and Austrian E. nivalis should be considered different evolutionarily significant units for conservation purposes, as they are marked by moderate genomic differentiation, distinct demographic histories and a difference in the abiotic conditions of their habitats.
In both Austria and Switzerland, we found rapid uphill range shifts over the last decades, little population connectivity, low current effective population sizes and low genetic diversity. The above, combined with the low dispersal capacity of this 2‐year lifecycle species and its need to overwinter under snow, which is rapidly retreating from several regions of the Alps, leads us to suggest that the status of E. nivalis should be updated to ‘Vulnerable’ or ‘Endangered’ in the European, Swiss and Austrian Red Lists.
Prognostic significance of bone marrow fibrosis in diffuse large B‐cell lymphoma
Authors: Cetintepe Tugba , Ozkan Gamze , Kucukzeybek Betul Polat , Cetintepe Lutfi , Unal Demet Kiper , Solmaz Serife , Aygun Kemal , Acar Alev Garip , Bener Sadi , Çallı Aylin Orgen , Payzın Kadriye Bahriye 
Published: February 2024

AbstractIntroductionDiffuse large B‐cell lymphoma (DLBCL) is the most common subtype of non‐Hodgkin lymphomas. The aim of this study is to determine the relationship between the increase in the degree of fibrosis in the bone marrow and prognosis and mortality in newly diagnosed DLBCL.MethodsBone marrow biopsy of 153 newly diagnosed DLBCL patients was determined by staining with reticulin, Masson's trichrome histochemical stain, and the degree of fibrosis was determined.ResultsIn the bone marrow biopsy performed at the time of diagnosis, bone marrow fibrosis (BMF) was observed in 70 patients. While BMF‐1 was detected in 42 patients (60%), BMF‐2 was detected in 25 patients (35%) and BMF‐3 was detected in 3 patients (4%). As the degree of BMF increased, the median overall survival and median progression‐free survival times were significantly shorter (p: 0.008), (p < 0.001). In patients with an increased degree of BMF, a significant decrease in leukocyte and neutrophil counts was observed after chemotherapy (p: 0.004).According to the results of the multivariate Cox regression model, it was determined that high NCCN‐IPI risk (HR: 8.25; %95 CI: 1.09–62.52; p = 0.041) and being BMF ≥ 2 (HR: 3.75; %95 CI: 1.65–8.51; p = 0.002), increased the risk of death (p = 0.002, −2 loglikelihood = 392,553).ConclusionWhen the literature was reviewed, it was seen that this study was the first to define that bone marrow fibrosis grade 2 and above in DLBCL is a prognostic marker associated with worse survival. In the bone marrow pathology, which is examined to detect advanced disease in DLBCL, besides lymphomatous involvement, the detection of fibrosis grade is very important.
A relational analysis of migration in old age: How transnational ties affect migration decisions
Authors: Tomás Livia , Molina José Luis 
Published: February 2024

AbstractRecently, the role of personal ties in migration decisions has received considerable attention. However, this aspect has seldom been studied in the context of retirement. This paper addresses this gap by shedding light on the composition of personal networks, types of mobility patterns and retirement locations for four groups of older adults. To this end, two methodological approaches are employed: (1) a qualitative Social Network Analysis to examine the composition of older adults' personal networks and (2) thematic coding to analyse the relational aspects of migration decisions. This paper draws on 29 semi‐structured interviews conducted in Spain and Switzerland in 2020 and 2021. The findings demonstrate that pre‐retirement migration trajectories shape personal network composition. Moreover, personal ties play a critical role in older adults' mobility patterns and choices of retirement location. Overall, this study provides valuable insights into the impact of personal networks on migration decisions of older adults.
Refugees as perceived threat: College students' attitudes towards refugees in South Korea
Authors: Yuk Joowon , Shin Hyoung‐jin 
Published: February 2024

AbstractIn 2018, the influx of Yemeni asylum seekers generated the unprecedented politicization of the refugee issue in South Korea. This paper explored South Korean attitudes towards refugees by collecting data from Korean college students. In doing so, we looked into what led to negative attitudes towards refugees and the role perceived threats play as a mediator. Following previous studies on intergroup threat theory, we noted that threat perception was a useful tool in understanding intergroup prejudice and anxiety as perceived threats and their antecedents were found to explain a significant amount of the attitudes towards refugees. We also found strong interconnections between prejudices towards different minority groups, including Islamophobia, homophobia and anti‐refugee attitudes. This finding supported the idea that such prejudices are part of a larger intolerant belief system towards minority groups in general.