bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconciling differences pertaining to the origin of SARS-CoV-2
Authors: Muhammad Yasin Ali 
Published: February 2022

Abstract
Background
At the time of this writing, SARS-CoV-2 has reportedly claimed the lives of millions of people worldwide. However, there is still disagreement concerning the origin of SARS-CoV-2, its true nature, and the extent of its pathogenicity. Thus, the purpose of this manuscript is to highlight and critically analyze these differences so that research efforts can be geared toward addressing these concerns.

Main Body
For this purpose, the author studied the perspectives of both conventional and non-conventional scientists, physicians, and researchers in an attempt to understand the points of contention and the reasons for the vast gulf in perspective.

Conclusion
After reviewing the varying but divergent perspective pertaining to the origin of SARS-CoV-2 and the premises used to justify them, it has become clear that if the scientific community is to put a halt to the spread of misinformation pertaining to the origin of SARS-CoV-2 and COVID-19, the predominant scientific community (particularly the microbiologist/immunologist) must carry out the requisite scientific procedures and encourage governmental/academic transparency.
Hand sanitizers as a preventive measure in COVID-19 pandemic, its characteristics, and harmful effects: a review
Authors: Prajapati Parixit , Desai Heli , Chandarana Chandni 
Published: February 2022

Abstract
Background
In the global health emergency caused by COVID-19, multiple experts have mandated the use of hand sanitizers as a safety measure from COVID-19. The sale of hand sanitizers has increased many folds. Therefore, when there is such large use of hand sanitizers, it becomes extremely important to study and understand hand sanitizers in a comprehensive manner.

Main body of the abstract
This article starts with the importance of sanitizers as a defence mechanism that is employed by the hand to fight against the coronavirus. This article provides information about history, types, composition, various dosage forms, and marketed formulations of hand sanitizers. The article sheds a detailed light on industrial production techniques for hand sanitizers and also outlines new innovative techniques that were employed by the industry to mass produce hand sanitizers in the wake of the pandemic. The article further dives into a comparison between hand sanitizers and soaps so as to give pros and cons of the use of soap against the use of hand sanitizers. One of the aims of the article is to study the side effects of sanitizers so as to develop a cautious approach while using hand sanitizers and therefore a comprehensive list of side effects of the use of hand sanitizers is given.

Conclusion
The review article finds that hand sanitizers are extremely efficient in fight the virus but along with it, it brings along arrange of risks which are outlined in the article.
COVID-19 and vaccination induced changes in hospital activity in Malta, Q1 2020 to Q1 2021: a population-based study
Authors: Cuschieri Sarah , Borg David , Agius Steve , Scherb Hagen , Grech Victor 
Published: February 2022

Abstract
Background
COVID-19 has severely impacted global healthcare services. Malta has only one acute state hospital, Mater Dei Hospital (MDH), and at the time of writing is the most vaccinated country in Europe. Malta thus provides an ideal setting to assess the impact of COVID-19 on healthcare services at population level, including the impact of vaccination on hospital admissions.

Methods
Hospital data was obtained as anonymised totals from MDH’s Clinical Performance Unit and the European Centre for Disease Prevention and Control. COVID-19-related data was obtained from the Ministry of Health dashboard. Comparative assessments were performed to explore associations between the COVID-19 situation, vaccination, and hospital activity. Poisson regression was used to model the counts of monthly accident and emergency (A&E), outpatient clinics attendances and hospital admissions.

Results
A&E, hospital admissions, and outpatient clinics attendances declined (31.88%; 23.89%; 29.57%; p < 0.01 respectively) with onset of COVID-19 till April 2021 when compared to pre-COVID years (2017–2019). Admissions due to COVID-19 initially increased in parallel to the population’s COVID positivity. Vaccination rollout led to a decline in COVID-19 admissions.

Conclusions
The drastic drop in admissions and outpatient attendees was expected but not for A&E attendees as acutely ill patients should still have attended. This is of public health concern since delayed or deferred medical management increases population morbidity, mortality and increases the eventual burden on the healthcare system. Mass vaccination saw the return to normality with an increase in A&E burden.
Accelerating CFD simulation with high order finite difference method on curvilinear coordinates for modern GPU clusters
Authors: Ye Chuang-Chao , Zhang Peng-Jun-Yi , Wan Zhen-Hua , Yan Rui , Sun De-Jun 
Published: February 2022

AbstractA high fidelity flow simulation for complex geometries for high Reynolds number (Re) flow is still very challenging, requiring a more powerful HPC system. However, the development of HPC with traditional CPU architecture suffers bottlenecks due to its high power consumption and technical difficulties. Heterogeneous architecture computation is raised to be a promising solution to the challenges of HPC development. GPU accelerating technology has been utilized in low order scheme CFD solvers on the structured grid and high order scheme solvers on unstructured meshes. The high-order finite difference methods on structured grids possess many advantages, e.g., high efficiency, robustness, and low storage. However, the strong dependence among points for a high-order finite difference scheme still limits its application on the GPU platform. In the present work, we propose a set of hardware-aware technology to optimize data transfer efficiency between CPU and GPU, as well as communication efficiency among GPUs. An in-house multi-block structured CFD solver with high order finite difference methods on curvilinear coordinates is ported onto the GPU platform and obtains satisfying performance with a speedup maximum of around 2000x over a single CPU core. This work provides an efficient solution to apply GPU computing in CFD simulation with specific high order finite difference methods on current GPU heterogeneous computers. The test shows that significant accelerating effects can be achieved for different GPUs.
Varus stress MRI in diagnosis of medial meniscal posterior root tear
Authors: Qardash Ashgan Ali Abdo , Hassan Afaf A. , El kady Hesham A. , Mohammed Hosam El-Deen G. , Abdel-Tawab Mohamed , Mohammed Nisreen A. A. 
Published: February 2022

Abstract
Background
Early and accurate diagnosis of medial meniscal posterior root tear (MMPRT) via magnetic resonance imaging (MRI) is crucial to prevent the development of medial meniscus extrusion (MME) and subsequent osteoarthritic changes. The study aims to assess the role of MRI in diagnosing the medial meniscal posterior root tear (MMPRT) as well as to investigate the additive value of a new MRI technique (varus stress position technique) in measuring the accurate degree of a truly extruded meniscus, during normal daily activities like standing or walking. This prospective study included 70 patients who had an episode of posteromedial knee pain. All patients underwent conventional MRI, whereas only 35 of them underwent MRI with varus stress loading position.

Results
The study included 70 patients, of which 56 were female (80.0%), with a mean age of 49.1 ± 8.5 years. According to duration onset of MMPRT, 39 patients were in the chronic stage (4–12 months), 16 patients were in the acute stage (early < 1 month), and 15 patients were in the subacute stage (1–3 months). It was found that varus stress position could detect 100% of the patients (35/35) with positive medial meniscus extrusion (MME) (≥ 3 mm), whereas the MRI with the traditional position could detect only 62.9% of the cases (22/35) (P < 0.000). Regarding the chronicity of MMPRT, a significant increase was observed in the amount of MME in post-varus MRI compared with that in pre-varus MRI for each stage (acute, subacute, and chronic) (P < 0.000).

Conclusion
MRI is considered a superior imaging modality in diagnosing MMPRT through several characteristic MRI findings. The varus stress position showed a valuable role in assessing the presence and degree of severity of true extruded meniscus using positional varus stress load.
A self-guided and monitored digital problem-solving intervention for patients with symptoms of depression or anxiety on the waiting list for treatment in routine psychiatric care: feasibility study
Authors: Hentati Amira , Forsell Erik , Ljótsson Brjánn , Lindefors Nils , Kraepelien Martin 
Published: February 2022

BackgroundThere is often a waiting period for people who seek psychiatric treatment for depression or anxiety. As this delay risks worsening symptoms, an alternative could be to provide an intervention that requires minimal resources during the waiting period.AimsThe aim was to investigate if a digital problem-solving intervention delivered in a self-guided format with automated features is feasible to provide for patients on the waiting list in routine psychiatric care.MethodA total of 12 patients with symptoms of depression or anxiety on the waiting list for treatment in routine psychiatric care were given access to a self-guided and monitored digital problem-solving intervention over 4 weeks. Primary outcome measures were treatment credibility and usability. Secondary outcome measures were behavioural engagement, symptoms of depression and anxiety, and negative effects.ResultsA majority of participants rated the intervention as both credible and usable. The intervention was used at least once by nine out of 12 individuals, with an average of 11 logins. The participants did, on average, initiate 2.8 problem-solving attempts and 10.1 solutions. A few participants reached a clinically relevant symptom improvement of depression and anxiety. No serious negative effects were reported.ConclusionsThe credibility and usability of the intervention was perceived as good, and the behavioural engagement with the intervention was deemed sufficient compared with similar self-guided interventions. A self-guided and monitored digital problem-solving intervention may be a beneficial option for patients waiting for or receiving treatment in routine psychiatric care, and should be further evaluated.
Phase II Study of Copanlisib in Patients With Tumors With PIK3CA Mutations: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1F
Authors: Damodaran Senthil , Zhao Fengmin , Deming Dustin A. , Mitchell Edith P. , Wright John J. , Gray Robert J. , Wang Victoria , McShane Lisa M. , Rubinstein Larry V. , Patton David R. , Williams P. Mickey , Hamilton Stanley R. , Suga Jennifer M. , Conley Barbara A. , Arteaga Carlos L. , Harris Lyndsay N. , O'Dwyer Peter J. , Chen Alice P. , Flaherty Keith T. 
Published: February 2022

PURPOSE Activating mutations in PIK3CA are observed across multiple tumor types. The NCI-MATCH (EAY131) is a tumor-agnostic platform trial that enrolls patients to targeted therapies on the basis of matching genomic alterations. Arm Z1F evaluated copanlisib, an α and δ isoform–specific phosphoinositide 3-kinase (PI3K) inhibitor, in patients with PIK3CA mutations (with or without PTEN loss). PATIENTS AND METHODS Patients received copanlisib (60 mg intravenous) once weekly on days 1, 8, and 15 in 28-day cycles until progression or toxicity. Patients with KRAS mutations, human epidermal growth factor receptor 2–positive breast cancers, and lymphomas were excluded. The primary end point was centrally assessed objective response rate (ORR); secondary end points included progression-free survival, 6-month progression-free survival, and overall survival. RESULTS Thirty-five patients were enrolled, and 25 patients were included in the primary efficacy analysis as prespecified in the Protocol. Multiple histologies were enrolled, with gynecologic (n = 6) and gastrointestinal (n = 6) being the most common. Sixty-eight percent of patients had ≥ 3 lines of prior therapy. The ORR was 16% (4 of 25, 90% CI, 6 to 33) with P = .0341 against a null rate of 5%. The most common reason for protocol discontinuation was disease progression (n = 17, 68%). Grade 3/4 toxicities observed were consistent with reported toxicities for PI3K pathway inhibition. Sixteen patients (53%) had grade 3 toxicities, and one patient (3%) had grade 4 toxicity (CTCAE v5.0). Most common toxicities include hyperglycemia (n = 19), fatigue (n = 12), diarrhea (n = 11), hypertension (n = 10), and nausea (n = 10). CONCLUSION The study met its primary end point with an ORR of 16% ( P = .0341) with copanlisib showing clinical activity in select tumors with PIK3CA mutation in the refractory setting.
Effects of Dapagliflozin and Combination Therapy With Exenatide on Food-Cue Induced Brain Activation in Patients With Type 2 Diabetes
Authors: van Ruiten Charlotte C , Veltman Dick J , Schrantee Anouk , van Bloemendaal Liselotte , Barkhof Frederik , Kramer Mark H H , Nieuwdorp Max , IJzerman Richard G 
Published: February 2022

Abstract

Context
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) cause less weight loss than expected based on urinary calorie excretion. This may be explained by SGLT2i-induced alterations in central reward and satiety circuits, leading to increased appetite and food intake. Glucagon-like peptide-1 receptor agonists are associated with reduced appetite and body weight, mediated by direct and indirect central nervous system (CNS) effects.

Objective
We investigated the separate and combined effects of dapagliflozin and exenatide on the CNS in participants with obesity and type 2 diabetes.

Methods
This was a 16-week, double-blind, randomized, placebo-controlled trial. Obese participants with type 2 diabetes (n = 64, age 63.5 ± 0.9 years, BMI 31.7 ± 0.6 kg/m2) were randomized (1:1:1:1) to dapagliflozin 10 mg with exenatide-matched placebo, exenatide twice daily 10 µg with dapagliflozin-matched placebo, dapagliflozin and exenatide, or double placebo. Using functional MRI, the effects of treatments on CNS responses to viewing food pictures were assessed after 10 days and 16 weeks of treatment.

Results
After 10 days, dapagliflozin increased, whereas exenatide decreased CNS activation in the left putamen. Combination therapy had no effect on responses to food pictures. After 16 weeks, no changes in CNS activation were observed with dapagliflozin, but CNS activation was reduced with dapagliflozin-exenatide in right amygdala.

Conclusion
The early increase in CNS activation with dapagliflozin may contribute to the discrepancy between observed and expected weight loss. In combination therapy, exenatide blunted the increased CNS activation observed with dapagliflozin. These findings provide further insights into the weight-lowering mechanisms of SGLT2i and GLP-1 receptor agonists.
Causal Associations Between Circulating Adipokines and Cardiovascular Disease: A Mendelian Randomization Study
Authors: Chen Delong , Zhang Yuxuan , Yidilisi Abuduwufuer , Xu Yi , Dong Qichao , Jiang Jun 
Published: February 2022

Abstract

Context
Observational studies have suggested associations between adipokines and cardiovascular disease (CVD), but the roles of certain adipokines remain controversial, and these associations have not yet been ascertained causally.

Objective
To investigate whether circulating adipokines causally affect the risk of CVD using 2-sample Mendelian randomization (MR).

Methods
Independent genetic variants strongly associated with adiponectin, resistin, chemerin, and retinol binding protein 4 (RBP4) were selected from public genome-wide association studies. Summary-level statistics for CVD, including coronary artery disease (CAD), myocardial infarction, atrial fibrillation (AF), heart failure (HF), and stroke and its subtypes were collected. The inverse-variance weighted and Wald ratio methods were used for the MR estimates. The MR pleiotropy residual sum and outlier, weighted median, MR-Egger, leave-one-out analysis, MR Steiger, and colocalization analyses were used in the sensitivity analysis.

Results
Genetically predicted resistin levels were positively associated with AF risk (odds ratio [OR] 1.09; 95% confidence interval [CI], 1.04-1.13; P = 4.1 × 10-5), which was attenuated to null after adjusting for blood pressure. We observed suggestive associations between higher genetically predicted chemerin levels and an increased risk of CAD (OR 1.27; 95% CI, 1.01-1.60; P = 0.040), higher genetically predicted RBP4 levels and an increased risk of HF (OR 1.14; 95% CI, 1.02-1.27; P = 0.024). There was no causal association between genetically predicted adiponectin levels and CVD risk.

Conclusions
Our findings reveal the causal association between resistin and AF, probably acting through blood pressure, and suggest potential causal associations between chemerin and CAD, RBP4, and HF.
Contribution of Clinical and Genetic Approaches for Diagnosing 209 Index Cases With 46,XY Differences of Sex Development
Authors: Gomes Nathalia Lisboa , Batista Rafael Loch , Nishi Mirian Y , Lerário Antônio Marcondes , Silva Thatiana E , de Moraes Narcizo Amanda , Benedetti Anna Flávia Figueredo , de Assis Funari Mariana Ferreira , Faria Junior José Antônio , Moraes Daniela Rodrigues , Quintão Lia Mesquita Lousada , Montenegro Luciana Ribeiro , Ferrari Maria Teresa Martins , Jorge Alexander A , Arnhold Ivo J P , Costa Elaine Maria Frade , Domenice Sorahia , Mendonca Berenice Bilharinho 
Published: February 2022

Abstract

Context
Massively parallel sequencing (MPS) technologies have emerged as a first-tier approach for diagnosing several pediatric genetic syndromes. However, MPS has not been systematically integrated into the diagnostic workflow along with clinical/biochemical data for diagnosing 46,XY differences of sex development (DSD).

Objective
To analyze the contribution of phenotypic classification either alone or in association with genetic evaluations, mainly MPS, for diagnosing a large cohort of 46,XY DSD patients.

Design/patients
209 nonsyndromic 46,XY DSD index cases from a Brazilian DSD center were included. Patients were initially classified into 3 subgroups according to clinical and biochemical data: gonadal dysgenesis (GD), disorders of androgen secretion/action, and DSD of unknown etiology. Molecular genetic studies were performed by Sanger sequencing and/or MPS.

Results
Clinical/biochemical classification into either GD or disorders of hormone secretion/action was obtained in 68.4% of the index cases. Among these, a molecular diagnosis was obtained in 36% and 96.5%, respectively. For the remainder 31.6% classified as DSD of clinically unknown etiology, a molecular diagnosis was achieved in 31.8%. Overall, the molecular diagnosis was achieved in 59.3% of the cohort. The combination of clinical/biochemical and molecular approaches diagnosed 78.9% of the patients. Clinical/biochemical classification matched with the genetic diagnosis in all except 1 case. DHX37 and NR5A1 variants were the most frequent genetic causes among patients with GD and DSD of clinical unknown etiology, respectively.

Conclusions
The combination of clinical/biochemical with genetic approaches significantly improved the diagnosis of 46,XY DSD. MPS potentially decreases the complexity of the diagnostic workup as a first-line approach for diagnosing 46,XY DSD.
Placental sFlt-1 Gene Delivery in Early Primate Pregnancy Suppresses Uterine Spiral Artery Remodeling
Authors: Aberdeen Graham W , Babischkin Jeffery S , Lindner Jonathan R , Pepe Gerald J , Albrecht Eugene D 
Published: February 2022

Abstract
Uterine spiral artery remodeling (SAR) is essential for promoting placental perfusion and fetal development. A defect in SAR results in placental ischemia and increase in placental expression and serum levels of the soluble fms-like tyrosine kinase-1 (sFlt-1) receptor that binds to and suppresses vascular endothelial growth factor (VEGF) bioavailability, thereby leading to maternal vascular dysfunction. We have established a nonhuman primate model of impaired SAR and maternal vascular dysfunction by prematurely elevating estradiol levels in early baboon pregnancy. However, it is unknown whether this primate model of defective SAR involves an increase in placental expression of sFlt-1, which may suppress VEGF bioavailability and thus SAR in the first trimester. Therefore, to establish the role of sFlt-1 in early pregnancy, SAR was quantified in baboons treated on days 25 through 59 of gestation (term = 184 days) with estradiol or with the sFlt-1 gene targeted selectively to the placental basal plate by ultrasound-mediated/microbubble-facilitated gene delivery technology. Placental basal plate sFlt-1 protein expression was 2-fold higher (P &lt; 0.038) and the level of SAR for vessels &gt; 25 µm in diameter was 72% and 63% lower (P &lt; 0.01), respectively, in estradiol-treated and sFlt-1 gene-treated baboons than in untreated animals. In summary, prematurely elevating estradiol levels or sFlt-1 gene delivery increased placental basal plate sFlt-1 protein expression and suppressed SAR in early baboon pregnancy. This study makes the novel discovery that in elevated levels sFlt-1 has a role both in suppressing SAR in early primate pregnancy and maternal vascular endothelial function in late gestation.
Olig2 defines a subset of neural stem cells that produce specific olfactory bulb interneuron subtypes in the subventricular zone of adult mice
Authors: del Águila Ángela , Adam Mike , Ullom Kristy , Shaw Nicholas , Qin Shenyue , Ehrman Jacqueline , Nardini Diana , Salomone Joseph , Gebelein Brian , Lu Q. Richard , Potter Steven S. , Waclaw Ronald , Campbell Kenneth , Nakafuku Masato 
Published: February 2022

ABSTRACT
Distinct neural stem cells (NSCs) reside in different regions of the subventricular zone (SVZ) and generate multiple olfactory bulb (OB) interneuron subtypes in the adult brain. However, the molecular mechanisms underlying such NSC heterogeneity remain largely unknown. Here, we show that the basic helix-loop-helix transcription factor Olig2 defines a subset of NSCs in the early postnatal and adult SVZ. Olig2-expressing NSCs exist broadly but are most enriched in the ventral SVZ along the dorsoventral axis complementary to dorsally enriched Gsx2-expressing NSCs. Comparisons of Olig2-expressing NSCs from early embryonic to adult stages using single cell transcriptomics reveal stepwise developmental changes in their cell cycle and metabolic properties. Genetic studies further show that cross-repression contributes to the mutually exclusive expression of Olig2 and Gsx2 in NSCs/progenitors during embryogenesis, but that their expression is regulated independently from each other in adult NSCs. Finally, lineage-tracing and conditional inactivation studies demonstrate that Olig2 plays an important role in the specification of OB interneuron subtypes. Altogether, our study demonstrates that Olig2 defines a unique subset of adult NSCs enriched in the ventral aspect of the adult SVZ.