bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiologically based pharmacokinetic and pharmacodynamic modelling of alprazolam: Implications for anxiety and addiction
Authors: Burkat Paul M. 
Published: March 2023

AimsAlprazolam is an anxiolytic compound that can lead to psychological and physiological dependence especially with prolonged use. This study utilized physiologically based pharmacokinetic (PK) and pharmacodynamic (PD) modelling to further examine the underlying mechanisms of anxiety treatment and addiction.MethodsData and parameter values for this study were obtained from PubMed and DrugBank literature searches. The physiologically based PK models for alprazolam were developed using PK‐Sim software and PD models were implemented with the MonolixSuite 2021R platform.ResultsAfter single administrations, peak unbound interstitial brain concentrations range from 4 to 33 nM for 0.25–2 mg‐doses of the immediate‐release form and 3–54 nM for 0.5–10‐mg doses of the extended‐release form. With repetitive administrations, peak concentration is 59 nM for a 2‐mg alprazolam immediate‐release dose and 122 nM for a 10‐mg extended‐release dose. Potentiation of EC10 GABA‐gated currents from recombinant GABAARs composed of α1β2γ2, α2β3γ2 and α5β3γ2 subunit combinations is 92, 150 and 75%, respectively, for an alprazolam concentration of 59 nM. The 10–90% rise times for the brain concentration–time profile following a single 1‐mg immediate‐release administration is 22.8 min and 3.8 h for a 3‐mg extended‐release administration.ConclusionUnbound interstitial brain concentration–time profiles of alprazolam corresponded to changes in β rhythm activity, peak saccade velocity, mood improvement, cognitive speed slowing and digit symbol substitution test scores. PD models for these endpoints suggest that alprazolam immediate‐release maximal effects on cognitive slowing, cognitive impairment, sedation and mood improvement occur sequentially following the brain concentration–time profile.
Ureteropelvic junction obstruction (UPJ) due to congenital crossing of the renal vessels (CRV): Comparison of the pre‐ and postoperative features of UPJO with and without CRV
Authors: Çelebi Süleyman 
Published: March 2023

AbstractWe evaluated the differences in demographic characteristics of patients with and without underlying crossing renal vessels (CRVs) operated for unilateral symptomatic ureteropelvic junction obstruction (UPJO). We identified the features of patients who had undergone open, laparoscopic and robotically assisted laparoscopic pyeloplasty at our institution from July 2000 to January 2021. The ratio of renal parenchymal thickness (RPT; ratio between the kidney with UPJO and the healthy kidney), pelvic diameter and kidney functions were recorded. A total of 641 patients were operated for UPJO; 448 were male (69.8%) and 193 (30.1%) were female; 257 had right‐side (40%) and 384 (60%) left‐side disease. Fifty‐eight patients (9%) were found to have CRV (operated on to treat CRV). The age at diagnosis was 6.51 ± 5.09 years in the CRV (+) group and 1.82 ± 1.37 years in the CRV (−) (p < 0.001). The age at surgery was 8.00 ± 4.71 and 4.27 ± 3.54 years, respectively (p < 0.001). At the time of diagnosis, the RPT measurement was significantly better in CRV (+) compared to CRV (−) group (0.71 ± 0.2 vs. 0.64 ± 0.23, p = 0.043) and initial renal functions were 45.53 ± 8.99% and 42.99 ± 11.65% in CRV (+) and (−) groups respectively. At the time of surgery, the RPTs were 0.60 ± 0.24 and 0.63 ± 0.21 in CRV (+) and (−) groups and these values were also correlated with split renal functions (36.28 ± 15.81% and 41.80 ± 14.26%, respectively). Renal functions were significantly decreased in CRV (+) group (p = 0.027). Significant parenchymal improvements were noted during the first postoperative year. The RPTs were 0.71 ± 0.2 and 0.77 ± 0.19 in the CRV (+) and CRV (−) groups, respectively (p = 0.27) in that time; the improvements continued to increase to postoperative third year (0.74 ± 0.20 and 0.78 ± 0.19 respectively; p = 0.939). In patients with CRVs, renal functions seemed to be preserved in the early stages, however it should be kept in mind that sudden obstruction and loss of kidney function might develop in the follow up period.
Clinical course and management of adverse events after endoscopic resection of superficial duodenal epithelial tumors: Multicenter retrospective study
Authors: Dohi Osamu , Kato Motohiko , Takeuchi Yoji , Hoteya Shu , Oyama Tsuneo , Nonaka Satoru , Yoshimizu Shoichi , Yoshida Masao , Ohata Ken , Miura Yoshimasa , Hara Yuko , Tsuji Shigetsugu , Yamasaki Yasushi , Ueyama Hiroya , Kurahara Koichi , Tashima Tomoaki , Abe Nobutsugu , Nakayama Atsushi , Oda Ichiro , Yahagi Naohisa 
Published: March 2023

ObjectivesThis study aimed to elucidate the clinical course and management of adverse events (AEs) after endoscopic resection (ER) for superficial duodenal epithelial tumors (SDETs).MethodsConsecutive patients who underwent ER of SDETs between January 2008 and July 2018 at 18 Japanese institutions were retrospectively enrolled. The study outcomes included the clinical course, management, and risk of surgical conversion with perioperative AEs after ER for SDETs.ResultsOf the 226 patients with AEs, the surgical conversion rate was 8.0% (18/226), including 3.7% (4/108), 1.0% (1/99), and 50.0% (12/24) of patients with intraoperative perforation, delayed bleeding, or delayed perforation, respectively. In the multivariate logistic analysis, involvement of the major papilla (odds ratio [OR] 12.788; 95% confidence interval [CI] 2.098–77.961, P = 0.006) and delayed perforation (OR 37.054; 95% CI 10.219–134.366, P < 0.001) were significant risk factors for surgical conversion after AEs. Delayed bleeding occurred from postoperative days 1–14 or more, whereas delayed perforation occurred within 3 days in all cases.ConclusionsThe surgical conversion rate was higher for delayed perforation than those for other AEs after ER of SDETs. Involvement of the major papilla and delayed perforation were significant risk factors for surgical conversion following AEs. In addition, reliable prevention of delayed perforation is required for 3 days after duodenal ER to prevent the need for surgical interventions.
The post‐9/11 novel revisited: Reading three perspectives in contemporary American fiction
Authors: Altwaiji Mubarak 
Published: March 2023

AbstractThis essay on the Ground Zero novel offers three perspectives on one of the most exciting current debates in humanities by approaching the effects of the most notable 21st century event on the American novel. It presents a scholarly analysis of the American novel of the past 20 years and provides a discussion for readers who are divided by geography, ideology, and religion to understand how the 9/11 novel reflects both geopolitical relations and conflicts of our collective present. It sets two necessary provisos for the analysis of post‐9/11 American narrative: terrorism and counter‐terrorism. This analysis approaches the post‐9/11 novel from two opposing perspectives/voices—neutral narratives and political narratives—to provide a neutral cultural territory divorced from geopolitical strategy to understand this new version of American literature and explore the common beliefs and values in it. A third focus, on the literature of immigrants, is emerging in American literary studies and offers a bridge to those interested in exploring the cultural contributions of Muslim immigrants to American culture. It would be a mistake to conclude without referring to the contributions of Arab American writers because the concepts of culture and coexistence are interlinked.
Relationships between T‐lymphocytes and physical function in adults with chronic lymphocytic leukemia: Results from the HEALTH4CLL pilot study
Authors: Crane Justin C. , Gordon Max J. , Basen‐Engquist Karen , Ferrajoli Alessandra , Markofski Melissa M. , Lee Che Young , Fares Sara , Simpson Richard J. , LaVoy Emily C. 
Published: March 2023

AbstractObjectiveExamine physical function and T‐cell phenotype in patients with chronic lymphocytic leukemia (CLL) before and after a physical activity (PA) intervention.MethodsPhysical function measures and blood samples were collected from CLL patients (Rai stage 0–4, 50% receiving targeted therapy, N = 24) enrolled in a 16‐week intervention of at‐home aerobic and/or resistance exercise. Flow cytometry characterized T‐cells in cryopreserved peripheral blood cells. Wilcoxon signed‐rank test compared physical function and T‐cell phenotype at baseline and 16‐weeks; Kendall's Tau assessed associations between variables.ResultsGodin leisure‐time PA score increased from baseline to 16‐weeks (mean difference: 14.61, p < .01) and fatigue decreased (mean difference: 6.71, p < .001). At baseline, lower fatigue correlated with a lower proportion of CD8+ T‐cells (τ = 0.32, p = .03) and cardiorespiratory fitness (CRF) inversely correlated with the percentage of PD‐1+CD8+ T‐cells (τ −0.31, p = .03). At 16‐weeks, CRF inversely correlated with the proportion of PD‐1+CD4+ T‐cells (τ −0.34, p = .02). Reduced fatigue at 16‐weeks correlated with an increased CD4:CD8 ratio (τ = 0.36, p = .02) and lower percentage of HLA‐DR+PD‐1+CD4+ T‐cells (τ = −0.37, p = .01).ConclusionsThis intervention increased leisure‐time PA and decreased fatigue in CLL patients. These changes correlated with an increased CD4:CD8 T‐cell ratio and reduced proportion of T‐cells subsets previously associated with poor outcomes in CLL patients.Trial registrationClinicalTrials.gov Identifier: NCT02194387.
Widespread latitudinal asymmetry in the performance of marginal populations: A meta‐analysis
Authors: Pulido Fernando , Castagneyrol Bastien , Rodríguez‐Sánchez Francisco , Cáceres Yónatan , Pardo Adara , Moracho Eva , Kollmann Johannes , Valladares Fernando , Ehrlén Johan , Jump Alistair S. , Svenning Jens‐Christian , Hampe Arndt 
Published: March 2023

AbstractAimRange shifts are expected to occur when populations at one range margin perform better than those at the other margin, yet no global trend in population performances at range margins has been demonstrated empirically across a wide range of taxa and biomes. Here we test the prediction that, if impacts of ongoing climate change on performance in marginal populations are widespread, then populations from the high‐latitude margin (HLM) should perform as well as or better than central populations, whereas low‐latitude margin (LLM) populations should perform worse.LocationGlobal.Time period1995–2019.Major taxa studiedPlants and animals.MethodsTo test our prediction, we used a meta‐analysis to quantify empirical support for asymmetry in the performance of high‐ and low‐latitude margin populations compared to central populations. Performance estimates (survival, reproduction, or lifetime fitness) for populations occurring in their natural environment were derived from 51 papers involving 113 margin‐centre comparisons from 54 species and 705 populations from the Americas, Europe, Africa and Australia. We then related these performance differences to climatic differences among populations. We also tested whether patterns are consistent across taxonomic kingdoms (plants vs animals) and across realms (marine vs terrestrial).ResultsPopulations at margins performed significantly worse than central populations, and this trend was primarily driven by the low‐latitude margin. Although the difference was of small magnitude, it was largely consistent across biological kingdoms and realms. Differences in performance were weakly (p = .08) related to the difference in average temperatures between central and marginal populations.Main conclusionsThe observed asymmetry in performance in marginal populations is consistent with predictions about the effects of global climate change, though further research is needed to confirm the effect of climate. It indicates that changes in demographic rates in marginal populations can serve as early‐warning signals of impending range shifts.
Nocturnal blood pressure surge in seconds is associated with arterial stiffness independently of conventional nocturnal blood pressure variability in suspected obstructive sleep apnea patients
Authors: Kokubo Ayako , Kuwabara Mitsuo , Tomitani Naoko , Yamashita Shingo , Shiga Toshikazu , Kario Kazuomi 
Published: March 2023

AbstractNocturnal blood pressure (BP) surge in seconds (sec‐surge), which is characterized as acute transient BP elevation over several tens of seconds is induced by obstructive sleep apnea (OSA) and OSA‐related sympathetic hyperactivity. The authors assessed the relationship between sec‐surge and arterial stiffness in 34 nocturnal hypertensive patients with suspected OSA (mean age 63.9 ± 12.6 years, 32.4% female). During the night, they had beat‐by‐beat (BbB) BP and cuff‐oscillometric BP measurements, and brachial‐ankle pulse wave velocity (baPWV) was assessed as an arterial stiffness index. Multiple linear regression analysis revealed that the upward duration (UD) of sec‐surge was significantly associated with baPWV independently of nocturnal oscillometric systolic BP variability (β = .365, p = .046). This study suggests that the UD of sec‐surge, which can only be measured using a BbB BP monitoring device, may be worth monitoring in addition to nocturnal BP level.
PRMT5 inhibition induces pro‐inflammatory macrophage polarization and increased hepatic triglyceride levels without affecting atherosclerosis in mice
Authors: Zhang Yiheng , Verwilligen Robin A. F. , Van Eck Miranda , Hoekstra Menno 
Published: March 2023

AbstractProtein arginine methyltransferase 5 (PRMT5) controls inflammation and metabolism through modulation of histone methylation and gene transcription. Given the important role of inflammation and metabolism in atherosclerotic cardiovascular disease, here we examined the role of PRMT5 in atherosclerosis using the specific PRMT5 inhibitor GSK3326595. Cultured thioglycollate‐elicited peritoneal macrophages were exposed to GSK3326595 or DMSO control and stimulated with either 1 ng/mL LPS or 100 ng/mL interferon‐gamma for 24 h. Furthermore, male low‐density lipoprotein (LDL) receptor knockout mice were fed an atherogenic Western‐type diet and injected intraperitoneally 3×/week with a low dose of 5 mg/kg GSK3326595 or solvent control for 9 weeks. In vitro, GSK3326595 primed peritoneal macrophages to interferon‐gamma‐induced M1 polarization, as evidenced by an increased M1/M2 gene marker ratio. In contrast, no difference was found in the protein expression of iNOS (M1 marker) and ARG1 (M2 marker) in peritoneal macrophages of GSK3326595‐treated mice. Also no change in the T cell activation state or the susceptibility to atherosclerosis was detected. However, chronic GSK3326595 treatment did activate genes involved in hepatic fatty acid acquisition, i.e. SREBF1, FASN, and CD36 (+59%, +124%, and +67%, respectively; p < 0.05) and significantly increased hepatic triglyceride levels (+50%; p < 0.05). PRMT5 inhibition by low‐dose GSK3326595 treatment does not affect the inflammatory state or atherosclerosis susceptibility of Western‐type diet‐fed LDL receptor knockout mice, while it induces hepatic triglyceride accumulation. Severe side effects in liver, i.e. development of non‐alcoholic fatty liver disease, should thus be taken into account upon chronic treatment with this PRMT5 inhibitor.
How nursing care is expressed among nurse anaesthetists in the perioperative context: A meta‐ethnographic synthesis
Authors: Lekens Aina L. Bjerkeli , Drageset Sigrunn , Hansen Britt Sætre 
Published: March 2023

AbstractAimTo develop a conceptual framework describing nursing care from the anaesthesia nurse's perspective in the perioperative context.BackgroundSurgical patients find themselves in a vulnerable situation in need of advanced treatment and care. Nurse anaesthetists have a central role in reducing harm and enhance patient safety, in which person‐centred care has been identified as a key component. However, they are challenged by productivity and efficiency demands leading to a potential risk to patient safety.DesignNoblit and Hare's interpretative meta‐ethnography, directed by the eMERGe reporting guidance.MethodsA comprehensive systematic search of nine databases without year limitation. Fifteen studies published between 2002 and 2021 were found eligible for inclusion. Quality appraisal was performed using the Joanna Briggs Institute Qualitative Assessment and Review Instrument.ResultsFour themes were identified: being vigilant to keep safe from harm, strengthening patients' confidence, expressing courage to act and speak up, and endorsing team collaboration to achieve best practice. The themes were synthesised into the metaphor, ‘Continuously assessing and acting according to the patients' needs in a holistic perspective’. A conceptual framework was developed, illustrating the interconnection between the different nursing expressions, as the nurse anaesthetists seek to care for the patient as a whole person.ConclusionsNurse anaesthetists aim to deliver holistic nursing care. Nursing care is expressed at two levels, foregrounding and backgrounding anaesthetic nursing, in line with the philosophy of person‐centred care. Nursing care in anaesthesia is a matter of how and why it is performed, expressed in attitudes toward the recipients of care.Relevance to clinical practiceThe framework may be used to inform educational programs and clinical practice in nurse anaesthesia and to promote person‐centred care as a shared value across all levels involved in perioperative patient care.No patient or public contributionData were retrieved from already published literature.
Fusion genes aiding the diagnosis of soft tissue tumours of the oral cavity: From bench to bedside
Authors: Gomes Isadora Pereira , Guimarães Letícia Martins , Gomez Ricardo Santiago , Gomes Carolina Cavalieri 
Published: March 2023

AbstractSoft tissue tumours (STT) are a heterogeneous group of benign, malignant, and intermediate/borderline mesenchymal tumours. In the oral and maxillofacial region, less than 3% of all lesions correspond to benign STT and <1% are sarcomas. Overlapping microscopic features may lead to quite challenging diagnostic processes. Translocations and fusion genes are frequent, and type‐specific genetic alterations are detected in these tumours. The detection of such alterations by classic cytogenetic, FISH, RT‐PCR or NGS can help to define the diagnosis. This narrative review aims to review fusion genes reported for STT that affect the oral cavity and their use in diagnostic molecular pathology. Basic concepts regarding mechanisms of fusion genes formation are presented to clarify this information for surgical pathologists. The chromosomal rearrangements and fusion genes of adipocytic, fibroblastic and myofibroblastic, vascular, pericytic, smooth muscle, skeletal muscle, chondro‐osseous, and uncertain origin STT are summarised. The advance in molecular pathology techniques has led not only to a better understanding of the molecular pathogenesis of STT, but also to the development of helpful diagnostic tools. Therefore, it is important for the oral and head and neck pathologists to familiarise with the signature rearrangements and fusion genes for each tumour.
Vertebrate genomics and adaptation – Status and prospects in Africa
Authors: Ishengoma Edson 
Published: March 2023

AbstractAfrica is considered the “mother continent” from which the first hominins arose. The diversified wildlife and flora of Africa, which ranges from those in the scorching Sahara and Kalahari deserts to those in the vast Savannas and wet tropical forests, are also the most diverse of any continent. Although the continent's abundance and diversity of living resources have provided critical means of subsistence for its inhabitants, future utilization of this biodiversity will demand a fundamental understanding of genetic variation and its adaptive capabilities in the face of natural and man‐made stressors. Molecular ecological insights have previously been gained from a variety of vertebrate species native to Africa, and some of these discoveries have larger evolutionary and conservation implications. Despite lagging in genomics research, African scientists are increasingly eager to use the increasingly accessible ‐omics technology to routinely sequence more animals and plants native to Africa. This overview, which focuses on Africa's vertebrate biodiversity, aims to provide a continental scale perspective on organismal and ecological adaptations discovered through prior genomics research, as well as what conceptually these findings suggest for future research.
The correlates of regional cooperation: A regional dyadic approach
Authors: Kayaalp Özgür 
Published: March 2023

AbstractUnder what conditions do regional countries engage in cooperation? Regional cooperation arguably matters as an essential factor for the peace and development of nations, yet few quantitative studies have observed only countries. Cooperation nevertheless occurs between countries. This study presents the first global analysis of the correlates of regional cooperation through an analyses of dyads—where cooperation occurs. The independence concerns of interstate dyads are addressed using dyadic clustering robust standard error estimation. The analyses offered here, of memberships in 76 regional organizations from 1945 to 2012, yield several factors as significant forces of regional cooperation. In order of importance, these are: joint democracy, joint language, equal material capability, and trade interdependence. I also explore if weaker countries are more hesitant to cooperate with stronger ones in the regions studied. This is an interesting contribution at the theoretical level, as it seems to privilege a liberal explanation of regional organizations (trade, democracy) over a hegemonic realist explanation (power asymmetry).Related ArticlesBishwakarma, Jham Kumar, and Zongshan Hu. 2021. “Problems and Prospects for the South Asian Association for Regional Cooperation (SAARC).”Politics & Policy50(1): 154–79.https://doi.org/10.1111/polp.12443.Genna, Gaspare M., and David A. Mayer‐Foulkes. 2011. “Beyond Borders: Migration, Security, and Cooperation in North America.”Politics & Policy39(1): 5–9.https://doi.org/10.1111/j.1747‐1346.2010.00280.x.Levine, Steven. 2007. “Asian Values and the Asia Pacific Community: Shared Interests and Common Concerns.”Politics & Policy35(1): 102–35.https://doi.org/10.1111/j.1747‐1346.2007.00050.x.