bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-term zinc supplementation of zinc-deficient seniors counteracts CREMα - mediated IL-2 suppression
Authors: Baarz Bastian Robinson , Laurentius Thea , Wolf Jana , Wessels Inga , Bollheimer Leo Cornelius , Rink Lothar 
Published: August 2022

AbstractBackgroundAging is accompanied by a dramatic decline in the interleukin (IL)-2 production capacity of human immune cells, thus making seniors more susceptible to a variety of age-related diseases. A common cause of impaired cytokine production in advanced age is a deficiency of the essential micronutrient zinc. Nevertheless, the molecular mechanisms underlying a zinc deficiency-induced decrease in IL-2 production have not yet been satisfactorily elucidated. Recent animal and in vitro data suggested that the transcription factor cAMP-responsive element modulator (CREM)$$\alpha$$αplays a critical role in T cells´ disturbed IL-2 production in suboptimal zinc conditions. However, its role in the human aging process and the possibility of influencing this detrimental process by short-term zinc supplementation have not yet been evaluated.ResultsComparing peripheral lymphocytes of 23 young and 31 elderly subjects with either high, intermediate, or deficient zinc status, we observed zinc-dependent regulation of the IL-2 production mediated by the transcription factor CREM$$\alpha$$α. For the first time in humans, we report a mutual relationship between low zinc levels, high CREM$$\alpha$$αexpression, subsequent impaired IL-2 production, and vice versa. Remarkably, an average of only 6 days of in vivo zinc supplementation to zinc-deficient seniors was sufficient to rapidly improve zinc status, reverse CREM$$\alpha$$αoverexpression, and counteract subsequent low IL-2 production rates.ConclusionsOur ex vivo and in vivo data identify zinc deficiency-mediated CREM$$\alpha$$αoverexpression as a key cellular mechanism underlying impaired IL-2 production in the elderly and point toward the use of zinc as a rapidly immune-enhancing add-on nutraceutical in geriatric therapy.Graphical abstractDuring the aging process, there is a progressive decrease in zinc status, which in turn leads to overexpression of the transcription factor CREM$$\mathrm{\alpha }$$αin peripheral lymphocytes. CREMα is a negative regulator of the IL-2 gene, the overexpression of which dramatically limits adequate IL-2 production. This deleterious mechanism can be counteracted by short-term oral zinc administration, which can adjust IL-2 production in old, zinc-deficient individuals to a level similar to that of young adults.
Unified primal-dual active set method for dynamic frictional contact problems
Authors: Abide Stéphane , Barboteu Mikaël , Cherkaoui Soufiane , Dumont Serge 
Published: August 2022

AbstractIn this paper, we propose a semi-smooth Newton method and a primal-dual active set strategy to solve dynamical contact problems with friction. The conditions of contact with Coulomb’s friction can be formulated in the form of a fixed point problem related to a quasi-optimization one thanks to the semi-smooth Newton method. This method is based on the use of the primal-dual active set (PDAS) strategy. The main idea here is to find the correct subset $\mathcal{A}$
A
of nodes that are in contact (active) opposed to those which are not in contact (inactive). For each case, the nonlinear boundary condition is replaced by a suitable linear one. Numerical experiments on both hyper-elastic problems and rigid granular materials are presented to show the efficiency of the proposed method.
The dietary risk assessment of perfluorooctanoic acid (PFOA) and perfluorosulfonic acid (PFOS) in the root crops from the survey of the residue in agricultural soil and the crops
Authors: Choi Geun-Hyoung , Lee Deuk-Yeong , Song A-Reum , Moon Bo-Yeon , Kim Jin-Hyo 
Published: August 2022

AbstractPerfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are persistent organic pollutants (POPs) that are prohibited from being produced and used. However, they remain in the agricultural environment and are transferred to crops. In addition, PFOA is classified as possibly carcinogenic to humans. To fully understand the exposure and risk of PFOA and PFOS for human in crops, a residue survey and estimation of dietary exposure assessment are needed. Therefore, we investigated the residues of PFOA and PFOS in upland soil and cultivated root crops. The average residues of PFOA and PFOS in the soil were < 0.054–0.541 μg kg–1 and 0.024–0.111 μg kg–1, and 0.067–0.193 μg kg–1 and < 0.02 μg kg–1 in the crops, respectively. The average PFOA residues were higher than PFOS in the soil and crops. The estimated daily intakes of PFOA and PFOS in the crops were 0.284 ng kgbw–1 day–1 and 0.023 ng kgbw–1 day–1, and the estimated hazard quotients were 0.355 and 0.013, respectively. In addition, the excess cancer risk of PFOA was calculated to be 1.99 × 10–8. Thus, the non–carcinogenic and carcinogenic risks of PFOA and PFOS were not notable from the surveyed residues in the crops. However, the risks may be higher when the residues in other food crops are considered.
Advances in molecular biomarkers research and clinical application progress for gastric cancer immunotherapy
Authors: Cai Hongzhen , Li Man , Deng Ruiyi , Wang Mopei , Shi Yanyan 
Published: August 2022

AbstractGastric cancer is characterized by high morbidity and mortality worldwide. Early-stage gastric cancer is mainly treated with surgery, while for advanced gastric cancer, the current treatment options remain insufficient. In the 2022 NCCN Guidelines for Gastric Cancer, immunotherapy is listed as a first-line option for certain conditions. Immunotherapy for gastric cancer mainly targets the PD-1 molecule and achieves therapeutic effects by activating T cells. In addition, therapeutic strategies targeting other molecules, such as CTLA4, LAG3, Tim3, TIGIT, and OX40, have also been developed to improve the treatment efficacy of gastric cancer immunotherapy. This review summarizes the molecular biomarkers of gastric cancer immunotherapy and their clinical trials.
Using the English GSAT for placement into EFL classes: accuracy and validity concerns
Authors: Liao Yen-Fen 
Published: August 2022

AbstractThe English General Scholastic Ability Test (GSAT), a nationwide high-stakes college entrance exam in Taiwan, has commonly served as a placement test for streaming college freshmen into EFL classes. There has, however, been scant research reported on the feasibility of using an admission test for EFL placement. This study aims to investigate the accuracy and validity of placement decisions being made using the English GSAT scores, with a focus on its relations with the General English Proficiency Test (GEPT) and students’ subsequent performance in class. Quantitative data, including the English GSAT scores, the GEPT High-Intermediate Listening and Reading scores, and the English final course grades, were collected and statistically analyzed from four EFL classes with a total of 100 students at a university in Taiwan. The English GSAT was found to function well to place students into distinctively lower or higher level of EFL classes but did not discriminate well for the borderline cohort. A three-level placement using the English GSAT appeared to be a better differentiation between each proficiency cluster. High achievers in the English GSAT appeared to perform better on the GEPT listening and reading tests than did low achievers. Yet, apart from the GEPT reading test, the English GSAT yielded weak predictive power of student course attainment, which seemingly varied across classes, hinging on course designs and grading policies. Implications drawn from the results of the investigation were further discussed.
Feasibility of a peer-led, after-school physical activity intervention for disadvantaged adolescent females during the COVID-19 pandemic: results from the Girls Active Project (GAP)
Authors: McQuinn Sara , Belton Sarahjane , Staines Anthony , Sweeney Mary Rose 
Published: August 2022

Abstract
Introduction
There is a critical need for interventions that can be feasibly implemented and are effective in successfully engaging adolescent females in physical activity (PA). A theory-based, peer-led, after-school PA intervention, the Girls Active Project (GAP), was codesigned with adolescent females. This study aimed to assess the feasibility of implementing and evaluating the GAP programme.

Setting
One single-sex, female-only, designated disadvantaged postprimary school (students aged 12–18) in Dublin, Ireland.

Methods
Mixed methods were applied with multiple stakeholders over a 12-week trial (March to May 2021). A single-arm study design was used to examine intervention: reach, dose, fidelity, acceptability, compatibility and context. Feasibility of using proposed self-reported outcome measures (moderate-to-vigorous PA levels, self-rated health, life satisfaction, PA self-efficacy and PA enjoyment) was also explored. Due to school closure resulting from the COVID-19 pandemic, the intervention was delivered both online and in person in the school setting.

Results
Eight exercise classes were peer delivered by project leaders (n = 6, students aged 15–17) to intervention recipients (students aged 13-14). Recruitment was low (n = 8, 10% of eligible students, mean age: 13.3 SD: 0.46), yet retention was high (n = 7/8, 88%). Attendance rates were satisfactory (68%), and the intervention was implemented with high fidelity (87%). Data completion rates suggested proposed self-reported outcome measures were deemed appropriate (≥ 95%), except for weight (50%) and height data (80%). Despite COVID-19 hindering intervention implementation, both quantitative and qualitative data suggested that stakeholders were satisfied and perceived the in-person delivered intervention to be compatible with the school setting. Recommended refinements included extending class duration, introducing different rewards, and boosting programme awareness.

Conclusions
Further thought must be given on how to increase recruitment. Overall, the in-person delivered after-school PA programme was well-received by stakeholders and shows promise as an intervention that can be feasibly implemented and evaluated. Suggested improvements to the GAP intervention programme are recommended, before continuing to a more robust evaluation.

Trial registration
10.17605/OSF.IO/75HWJ (prospectively registered, date of registration: 9th December 2020)
Slow recruitment in the HIMALAIA study: lessons for future clinical trials in patients with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage based on feasibility data
Authors: Gathier Celine S. , van der Jagt Mathieu , van den Bergh Walter M. , Dankbaar Jan Willem , Rinkel Gabriel J. E. , Slooter Arjen J. C. ,   for the HIMALAIA Study Group, Algra Ale , Dankbaar Jan-Willem , Gathier Celine S. , Kesecioglu Jozef , Rinkel Gabriel J. E. , van der Schaaf Irene C. , Slooter Arjen J. C. , Verweij Bon H. , Dammers Ruben , Dippel Diederik W. J. , Dirven Clemens M. F. , van der Jagt Mathieu , van Kooten Fop , van der Lugt Aad , van den Bergh Walter M. , Coert Bert A. , Müller Marcella C. , Vandertop W. Peter , Beute Guus N. , Oldenbeuving Annemarie W. , van der Pol Bram , Roks Gerwin , van Rooij Willem Jan J. , Sluzewski Menno 
Published: August 2022

AbstractBackgroundOur randomized clinical trial on induced hypertension in patients with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) was halted prematurely due to unexpected slow recruitment rates. This raised new questions regarding recruitment feasibility. As our trial can therefore be seen as a feasibility trial, we assessed the reasons for the slow recruitment, aiming to facilitate the design of future randomized trials in aSAH patients with DCI or other critically ill patient categories.MethodsEfficiency of recruitment and factors influencing recruitment were evaluated, based on the patient flow in the two centers that admitted most patients during the study period. We collected numbers of patients who were screened for eligibility, provided informed consent, and developed DCI and who eventually were randomized.ResultsOf the 862 aSAH patients admitted in the two centers during the course of the trial, 479 (56%) were eligible for trial participation of whom 404 (84%) were asked for informed consent. Of these, 188 (47%) provided informed consent, of whom 50 (27%) developed DCI. Of these 50 patients, 12 (24%) could not be randomized due to a logistic problem or a contraindication for induced hypertension emerging at the time of randomization, and four (8%) were missed for randomization. Eventually, 34 patients were randomized and received intervention or control treatment.ConclusionsEnrolling patients in a randomized trial on a treatment strategy for DCI proved unfeasible: only 1 out of 25 admitted and 1 out of 14 eligible patients could eventually be randomized. These rates, caused by a large proportion of ineligible patients, a small proportion of patients providing informed consent, and a large proportion of patients with contraindications for treatment, can be used to make sample size calculations for future randomized trials in DCI or otherwise critically ill patients. Facilitating informed consent through improved provision of information on risks, possible benefits, and study procedures may result in improved enrolment.Trial registrationThe original trial was prospectively registered withClinicalTrials.gov(NCT01613235), date of registration 07-06-2012.
Primary pilocytic astrocytoma of the cerebellopontine angle in pediatric patient with neurofibromatosis type 1: a case report
Authors: Zakaria Zaitun , Raja Mohd Rasi Raja Zubaidah , Rahman Noor Azman A. 
Published: August 2022

Abstract
Background
Cerebellopontine angle tumor (CPA) in pediatrics is rare as compared to adults. We describe a case of pediatric pilocytic astrocytoma presented as a right CPA mass with a concurrent clinical diagnosis of neurofibromatosis type 1 (NF1).

Case presentation
A 14-year-old boy with a newly diagnosed hypertension presented with a short history of headache and blurring vision. Neurological examination revealed bilateral papilloedema, partial right third nerve palsy and mild sensorineuronal hearing deficits. Skin examination identified multiple café au lait spots with cutaneous neurofibromas. Preoperative neuroimaging suggested the diagnosis of an extraaxial CPA mass consistent with meningioma, with obstructive hydrocephalus. A left ventriculoperitoneal shunt was inserted and the child was subjected for a suboccipital retrosigmoid approach for tumor resection. The histopathological features, however, were typical for pilocytic astrocytoma.

Conclusions
A careful evaluation of the clinical presentation and radiological images of CPA lesions is necessary prior to surgical embarkment. To the best of our knowledge, this case is the first report of pilocytic astrocytoma in the CPA in pediatric with NF1.
Development and evaluation of novel rodent model of PCOS mimicking clinical phenotype in human disease
Authors: Kumar G. Santhana , Tirgar Pravin , Dalal Mittal 
Published: August 2022

Abstract
Background
Polycystic ovary syndrome is a most common female reproductive disorder, involving endocrine and metabolic disorders with unclear etiology. Androgen-based rodent animal models like DHEA and DHT are most suitable for PCOS induction, but still, these models fail to produce non-lean PCOS phenotypes such as hyperandrogenism, hyperinsulinemia, elevated estrogen levels, and ovary weight. Excess fructose consumption leads to hyperandrogenism, hyperinsulinemia, and insulin resistance. The purpose of this study is to investigate, whether fructose consumption along with androgens in rats, could develop all metabolic and endocrine phenotypes of non-lean human PCOS disease.

Methods
Prepubertal SD rats were administered with DHT (83ug, s.c.) and fructose (20%, p.o.) for 90 days whereas DHEA (7 mg/kg, s.c) and fructose (20%, p.o.) for 30 days. During study duration, the blood glucose level for oral glucose tolerance test, estrus cyclicity, and ultrasonography was observed. Reproductive hormones LH, FSH, insulin, testosterone, and estradiol levels were assessed using ELISA. The ovary, uterus, abdominal fat, and subcutaneous fat were collected and weighed, and histopathology was done for any anomaly’s findings.

Results
DHT + fructose-treated rats showed significant (p < 0.05) increase in serum testosterone, LH, estradiol, decreased FSH levels, and caused multiple cystic follicles. Abdominal fat, subcutaneous fat, ovary, and uterine weight were higher in DHT + F and DHEA + F when compared to control groups. OGTT reveals impaired insulin sensitivity and glucose tolerance in both model groups. Ovarian histopathology of DHT + F shows more cysts than the DHEA + F groups. No significant changes in uterine histology of DHT + F and DHEA + F-treated rats.

Conclusion
DHT + F-treated rats mimic all clinical phenotypes and could be used as novel rodent model for non-lean type PCOS.
Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer
Authors: Hoimes Christopher J. , Flaig Thomas W. , Milowsky Matthew I. , Friedlander Terence W. , Bilen Mehmet Asim , Gupta Shilpa , Srinivas Sandy , Merchan Jaime R. , McKay Rana R. , Petrylak Daniel P. , Sasse Carolyn , Moreno Blanca Homet , Yu Yao , Carret Anne-Sophie , Rosenberg Jonathan E. 
Published: August 2022

PURPOSE Cisplatin-based combination chemotherapy remains the standard of care for locally advanced or metastatic urothelial cancer (la/mUC); however, toxicity is substantial, responses are rarely durable, and many patients with la/mUC are ineligible. Each enfortumab vedotin and pembrolizumab have shown a survival benefit versus chemotherapy in UC, are not restricted by cisplatin eligibility, and warrant investigation as a first-line (1L) combination therapy in patients ineligible for cisplatin. METHODS In this ongoing phase Ib/II, multicenter, open-label study, 1L cisplatin-ineligible patients with la/mUC received enfortumab vedotin 1.25 mg/kg once daily on days 1 and 8 and pembrolizumab 200 mg (day 1) intravenously once daily in 3-week cycles. The primary end point was safety. Key secondary end points included confirmed objective response rate, duration of response (DOR), and overall survival (OS). RESULTS Forty-five patients received enfortumab vedotin plus pembrolizumab. The most common treatment-related adverse events (TRAEs) were peripheral sensory neuropathy (55.6%), fatigue (51.1%), and alopecia (48.9%). Twenty-nine patients (64.4%) had grade 3 or higher TRAEs; the most common were increased lipase (17.8%), maculopapular rash (11.1%), and fatigue (11.1%). One death (2.2%) was classified as a TRAE. The confirmed objective response rate after a median of nine cycles was 73.3% with a complete response rate of 15.6%. The median DOR and median OS were 25.6 months and 26.1 months, respectively. CONCLUSION Enfortumab vedotin plus pembrolizumab showed a manageable safety profile. Most patients experienced tumor shrinkage. The median DOR and median OS exceeding 2 years in a cisplatin-ineligible patient population make this a promising combination currently under investigation in a phase III study (ClinicalTrials.gov identifier: NCT04223856 ).
Subgenomic sequence analysis reveals emergence of new circulating recombinant forms of HIV-1 in Pakistan
Authors: Zahid Maria , Khan Saeed , Muhammad Asif Qureshi  , Yasir Raza  
Published: August 2022

Background and Objective: Pakistan has witnessed a dramatic change in the increasing prevalence and emergence of HIV subtypes for more than two decades. Pakistani population is increasingly engaged in high-risk practices, and the prescribed drugs are potentially causing resistance. There are chances that these resistant strains are beginning to circulate from high-risk to the general population.
Methods: The study was conducted at the section of Molecular Pathology Lab of Dow Diagnostic and Research Laboratory, Dow University of Health Sciences (DUHS) Karachi. In this study, we analyzed gene sequences of HIV for drug resistance and molecular epidemiology., along with amino acid sequence variability. Furthermore, we undertook phylogenetic analysis for possible geographic linkages of Pakistani HIV strains.
Results: Our results demonstrate that A1 is the leading HIV subtype circulating in the country, whereas other emerging subtypes and recombinant forms, including subtype B, CRF02_AG, CRF10_CD CRF35_AD, and CRF11_cpx were also observed. Our sequences cluster with the Middle East, African, and a few European sequences according to geographical distribution. These sequences showed high-level resistance per drug resistance pattern, with 62.5% of patients exhibiting resistance to NNRTI drugs and 60% mutation at E138A and K103N, respectively, against NNRTI drugs. About 75% sequences showed resistance mutation at M184V against NRTI drugs. The antiretroviral drugs are now causing H-LR to the patients with no effect. Our results also revealed that certain regions of RT exhibited high sequence variability, especially at Amino Acids positions p.119, p.130, p.157, p.164.
Conclusion: We hereby report major novel mutations and several minor mutations that may have a drastic change in the drug resistance pattern.
doi: https://doi.org/10.12669/pjms.38.7.5591
How to cite this:Zahid M, Khan S, Qureshi MA, Raza Y. Subgenomic sequence analysis reveals emergence of new circulating recombinant forms of HIV-1 in Pakistan. Pak J Med Sci. 2022;38(7):1857-1863. doi: https://doi.org/10.12669/pjms.38.7.5591
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Parental spiritual and religious beliefs and behaviour data collected from the Avon Longitudinal Study of Parents and Children, 2020
Authors: Iles-Caven Yasmin , Gregory Steven , Bickerstaffe Iain , Northstone Kate , Golding Jean 
Published: August 2022

There are few studies that chart the ways in which the religious beliefs and practices of parents and their offspring vary over time. Even fewer can relate this to aspects of their physical and mental health or distinguish the different facets of the environment that may have influenced the development or loss of religious/spiritual belief and behaviours over time. This paper describes the recent data collection in the Avon Longitudinal Study of Parents and Children (ALSPAC) on the beliefs and behaviours of the study parents some 27-28 years after the first measures were collected. Questions that were previously administered to the mother and her partner on religion, spirituality, behaviours, and beliefs (RSBB) were repeated for the fourth time, together with enhanced data on RSBB. The new data are described and compared with previous responses. The most notable difference between the 9 year and the 2020 sweep was the increase of professed non-believers in both the mothers (17.5% vs 29.8%) and partners (31.9% vs. 45.3%). As expected, on each occasion study partners were less likely to acknowledge RSBB compared to the study mothers. In the latest sweep, respondents were less likely to be unsure if they believed and more likely to not believe. Responses to “Do you believe in God or a divine power?” in mothers ranged from 49.9% stating ‘yes’ antenatally to 43.5% doing so in 2020; 14.9% vs 29.8% for ‘no’ and 35.2% to 26.6% for ‘not sure’. For partners, the corresponding figures are: ‘yes’ 37.0% vs. 30.0%; ‘no’ 28.6% vs. 45.3% and ‘not sure’ 34.5% vs. 24.6%. We plan to undertake detailed analyses of the antecedents and consequences of RBSS. All data are available for use by interested researchers.