bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Glioma-IRE project − Molecular profiling in patients with glioma: steps toward an individualized diagnostic and therapeutic approach
Authors: Villani Veronica , Casini Beatrice , Tanzilli Antonio , Lecce Mario , Rasile Fabrizio , Telera Stefano , Pace Andrea , Piludu Francesca , Terrenato Irene , Rollo Francesca , De Nicola Francesca , Fanciulli Maurizio , Pallocca Matteo , Ciliberto Gennaro , Carosi Mariantonia 
Published: March 2023

Abstract
Background
This study aimed to characterize the genetic profile of patients with glioma and discuss the impact of next-generation sequencing in glioma diagnosis and treatment.

Methods
Between 2019 and 2022, we analyzed the genetic profile of 99 patients with glioma through the Oncomine Focus Assay. The assay enables the detection of mutations in 52 driver genes, including single nucleotide variants (SNVs), copy number variants (CNVs), and gene fusions. We also collected and analyzed patients’ clinic characteristics and treatment outcomes.

Results
Over a period of 35 months, 700 patients with glioma followed by our neuro-oncology unit were screened, and 99 were enrolled in the study; most of the patients were excluded for inadequate non-morphological MRI or lack/inadequacy of the tissue samples. Based on our findings, most patients with glioma present mutations, such as SNVs, CNVs or gene fusions. Our data were similar to those reported by The Cancer Genome Atlas Program in terms of frequency of SNVs and CNVs, while we observed more cases of gene fusions. Median overall survival, progression-free survival, and time to progression were significantly lower for patients with grade VI glioblastoma than those with other gliomas. Only four patients were offered a targeted treatment based on the mutation detected; however, only one received treatment, the others could not receive the selected treatment because of worsening clinical status.

Conclusion
Routine timely molecular profiling in patients with glioma should be implemented to offer patients an individualized diagnostic approach and provide them with advanced targeted therapy options if available.
Dynamics of factors associated with rates of COVID-19 cases and deaths in African countries
Authors: Obasanjo Iyabo O. , Ahmad Zain , Akkaladevi Somasheker , Adekoya Adeyemi , Abass Olayide 
Published: March 2023

Abstract
Background
African countries have not had the high case and death rates from COVID-19 as was predicted early in the pandemic. It is not well understood what factors modulated the rate of COVID-19 cases and death on the continent.

Methods
We collated data from the World Bank data site, Our World in Data and Freedom House for African for 54 African countries who are members of the African Union. We used them as explanatory variables in two general linear model regression analyses. COVID cases and deaths per 100,000 obtained from WHO COVID-19 dashboard on August 12, 2021, as outcome variables in two prediction models.

Results
GDP, percentage of population under 14 years of age, Maternal Mortality Ratio, number of international tourists visiting per year and public transportation closures were not significant in predicting COVID-19 cases. Higher percentage of unemployed adults in the population, lower percentage of the population over 25 years of age with secondary education, internal travel restrictions increased spread of COVID-19 while international travel restrictions were associated with lower COVID-19 cases per 100,000 population. Higher levels of democratization results in higher cases of COVID-19. Unemployment, education and democratization were still significant for COVID-19 death in the same direction as they were for COVID-19 cases. Number of tourism visitors per year was also associated with higher COVID-19 death rates but not with case rates.

Conclusion
In African countries, internal movement restrictions enacted to inhibit COVID-19, had the opposite effect and enabled COVID-19 spread. Low Education levels and high unemployment were associated with having higher death rates from COVID-19. More studies are needed to understand the impact of tourism on COVID-19 and other infectious diseases arising from other regions on African countries, in order to put in place adequate control protocols.
Role of age in dynamics of autoantibodies in pediatric Celiac disease
Authors: Trovato Chiara Maria , Montuori Monica , Leter Beatrice , Laudadio Ilaria , Russo Giusy , Oliva Salvatore 
Published: March 2023

Abstract
Background
Celiac disease (CD) is characterized by elevated serum titers of autoantibodies IgA anti-tissue transglutaminase 2 (TGA-IgA) and IgA anti-endomysial (EMA), with small bowel mucosa atrophy. We evaluated age differences between CD children exhibiting variable antibody titers at diagnosis.

Methods
CD children diagnosed between January 2014 and June 2019, according to 2012 ESPGHAN guidelines were studied. All had EMA and TGA-IgA measurements, while a proportion of them underwent esophagogastroduodenoscopy (EGD). Patients were grouped based on serum TGA-IgA titers normalized to the upper limit of normal (ULN) and differences in median age (years) assessed by analysis of variance (ANOVA) and creation of orthogonal contrasts.

Results
CD was diagnosed in 295 subjects (median age: 4.4 [IQR: 2.60–8.52]) with a biopsy sparing protocol (high titer: ≥ 10xULN) and in 204 by EGD biopsy. Of the latter, 142 (median age: 8.5 [IQR: 5.81–11.06]) and 62 (median age: 9.5 [IQR: 6.26–12.76]) had a low (< 5xULN) and a moderate (≥ 5 < 10xULN) TGA-IgA titer, respectively. Potential CD was diagnosed in 20 patients (median age: 3.6 [IQR: 2.47–6.91]). The median age was significantly lower in the no-biopsy group (ANOVA: F(3, 516) = 25.98, p < .001) than in low- and moderate titer groups (p < 0.0001), while there was no statistical difference between biopsy-sparing and potential CD groups.

Conclusion
CD patients with greatly elevated antibody titers (≥ 10xULN) were diagnosed at an earlier age than those with lower titers. This may indicate that an increase in TGA-IgA is independent of age and suggests a polarization of autoimmunity in younger individuals with higher serum antibody levels.
Vitamin E-induced coagulopathy in a young patient: a case report
Authors: Abrol Ritika , Kaushik Reshma , Goel Deepak , Sama Sonu , Kaushik Rajeev Mohan , Kala Mansi 
Published: March 2023

Abstract
Background
High-dose vitamin E intake is known to inhibit vitamin K-derived coagulation factor synthesis, which can cause serious bleeding events such as gastrointestinal bleeding and intracranial hemorrhage. We report a case of coagulopathy induced by marginally increased levels of vitamin E.

Case presentation
A 31-year-old Indian man presented with oral bleeding, black tarry stools, and bruising over his back. He had been taking non-steroidal anti-inflammatory drugs for low backache and vitamin E for hair loss. He had mild anemia with normal platelet count, thrombin time, and prolonged bleeding time, activated partial thromboplastin time, and prothrombin time. Serum fibrinogen was slightly raised. Mixing studies with pooled normal plasma, aged plasma, and adsorbed plasma were suggestive of deficiency of multiple coagulation factors due to acquired vitamin K deficiency. Serum phylloquinone was normal, while prothrombin induced by vitamin K absence-II level was increased. Serum alpha-tocopherol was slightly raised. Upper gastrointestinal endoscopy showed multiple gastroduodenal erosions. A final diagnosis of vitamin E toxicity-related coagulopathy was made. The patient responded well to pantoprazole, vitamin K supplementation, multiple fresh frozen plasma transfusions, and other supportive treatments besides the discontinuation of vitamin E supplementation. The coagulation parameters normalized, and the patient was discharged with complete resolution of symptoms and remained asymptomatic during the follow-up for 6 months.

Conclusions
Vitamin E-related inhibition of vitamin K-dependent factors with coagulopathy may occur even at marginally increased levels of serum vitamin E. This risk becomes significant in patients receiving other drugs that may increase the risk of bleeding.
Pharmacy students’ attitudes and intentions of pursuing postgraduate studies and training in pharmacogenomics and personalised medicine
Authors: Makrygianni Dimitra , Koufaki Margarita-Ioanna , Patrinos George P. , Vasileiou Konstantinos Z. 
Published: March 2023

Abstract
Background
Pharmacists’ contribution to pharmacogenomics (PGx) implementation in clinical practice is vital, but a great proportion of them are not aware of PGx and its applications. This highlights the university education’s crucial role to prepare pharmacists to face future challenges in such a constantly evolving and demanding environment.

Objectives
Our study aims to examine pharmacy students’ training satisfaction, knowledge, self-confidence and attitudes towards PGx on their intentions for postgraduate training in PGx and personalised medicine (PM).

Methods
An initial model on students’ intention to pursue postgraduate training in PGx and PM and its predicting factors, based on the Theory of Planned Behaviour (TPB), was proposed. Based on it, a questionnaire was developed and distributed to 346 pharmacy students of all study years, capturing the selected factors influencing students’ intentions to postgraduate training in PGx and PM, as well as their demographics. Structural equation modelling (SEM) analysis was employed to determine the effects of both the examined factors and demographics on students’ intentions.

Results
Students did not consider themselves adequately prepared for using PGx in clinical practice. Their attitudes towards PGx implementation were the most important factor influencing their intentions to pursue postgraduate training in PGx and PM. Other factors such as self-confidence and training satisfaction also affected students’ intentions, but to a lower extent. Students of the last two study years (40% of the whole sample) and male (36%) students stated to be less willing to pursue PGx-related studies in the future. Only 10% of the participants claimed to have undergone a recent PGx or genetic test, but this did not affect their intentions.

Conclusion
There is an important gap in pharmacy school curriculum regarding PGx and PM training which coupled with the slow rate of PGx and PM implementation into clinical practice seems to restrain students’ aspiration to further expand their knowledge and horizons in terms of PGx and PM.
Circular RNA circHMCU promotes breast tumorigenesis through miR-4458/PGK1 regulatory cascade
Authors: Qiu Shubian , Zou Lele , Qiu Ruimin , Wang Xin 
Published: March 2023

Abstract
Background
Circular RNAs (circRNAs) are abnormally expressed in breast cancer (BC). However, the biological function and mechanism of circHMCU still need to be further explored.

Methods
The expression levels of circHMCU, miR-4458 and phosphoglycerate kinase 1 (PGK1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The glucose uptake, lactate production and ATP level were assayed by related commercial kits. Cell Counting Kit-8 (CCK8), 5’-ethynyl-2’-deoxyuridine (EdU) and flow cytometry assays were used to test cell proliferation and apoptosis, respectively. The migratory and invasive abilities were detected by transwell and wound-healing assays. The relationships among circHMCU, miR-4458 and PGK1 were verified by dual-luciferase reporter assay. The function of circHMCU in tumor growth was evaluated by animal studies.

Results
CircHMCU was upregulated in BC tissues and cell lines, whereas miR-4458 was downregulated. For biological experiments, circHMCU knockdown inhibited cell proliferation, migration, glycolysis, while promoted cell apoptosis. CircHMCU bound miR-4458, and miR-4458 targeted PGK1. MiR-4458 inhibition reversed circHMCM knockdown-mediated effects on BC cell malignant behaviors. MiR-4458 overexpression suppressed cell glycolysis, proliferation, and metastasis and promoted apoptosis in BC cells through PGK1 upregulation. Additionally, circHMCU suppressed tumor growth in vivo.

Conclusion
CircHMCU acted as an oncogenic factor by regulating the miR-4458/PGK1 axis in BC.
Zolbetuximab + CAPOX in 1L claudin-18.2+ (CLDN18.2+)/HER2− locally advanced (LA) or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Primary phase 3 results from GLOW.
Authors: Xu Rui-hua , Shitara Kohei , Ajani Jaffer A. , Bang Yung-Jue , Enzinger Peter C. , Ilson David H. , Lordick Florian , Van Cutsem Eric , Gallego Plazas Javier , Huang Jing , Shen Lin , Oh Sang Cheul , Sunpaweravong Patrapim , Soo Hoo Hwoei Fen , Turk Haci M. , Park Jung Wook , Moran Diarmuid Martin , Bhattacharya Pranob P. , Arozullah Ahsan , Shah Manish A. 
Published: March 2023

405736 Background: There is an unmet need for novel targeted therapies that improve outcomes for pts with HER2− LA unresectable or mG/GEJ adenocarcinoma. CLDN18.2 is expressed in normal gastric mucosa cells and retained in most G/GEJ adenocarcinomas. In the phase 3 SPOTLIGHT study, zolbetuximab, a CLDN18.2-targeted chimeric monoclonal antibody, significantly prolonged PFS and OS in pts with CLDN18.2+/HER2− LA unresectable or mG/GEJ adenocarcinoma when combined with mFOLFOX6. GLOW (NCT03653507) is a phase 3 global, double-blind study comparing zolbetuximab or PBO with capecitabine and oxaliplatin (CAPOX) as 1L treatment for this pt population. Methods: Pts with CLDN18.2+ (moderate-to-strong membranous CLDN18 staining in ≥75% tumor cells by IHC)/HER2− LA unresectable or mG/GEJ adenocarcinoma were randomized 1:1 to zolbetuximab IV 800 mg/m2 (cycle 1, day [D] 1) followed by 600 mg/m2 (D1 in subsequent cycles) + CAPOX (oral capecitabine 1000 mg/m2 BID on D1−14 of each cycle; oxaliplatin IV 130 mg/m2 on D1 of each cycle) for eight 21-day cycles vs PBO + CAPOX; pts continued for >8 cycles with zolbetuximab or PBO, plus capecitabine (investigator decision), until PD or a discontinuation criterium was met. The primary endpoint (EP) was PFS per RECIST v1.1 by IRC. OS was a key secondary EP; other secondary EPs included ORR and safety. Differences between treatment arms in PFS and OS were tested by stratified log-rank tests; OS was tested if PFS was significant. Results: 507 pts were randomized 1:1 to zolbetuximab + CAPOX (N = 254) or PBO + CAPOX (N = 253). Both PFS (median 8.21 vs 6.80 mo, HR 0.687, P=0.0007) and OS (median 14.39 vs 12.16 mo, HR 0.771, P=0.0118) were significantly prolonged with zolbetuximab + CAPOX (Table); in pts with measurable disease, ORR (95% CI) was 53.8% (46.58−60.99) vs 48.8% (41.76−55.84) in zolbetuximab vs PBO arm. The most common TEAEs with zolbetuximab + CAPOX were nausea (68.5% vs 50.2% in zolbetuximab vs PBO arm), vomiting (66.1% vs 30.9%), and decreased appetite (41.3% vs 33.7%); serious TEAEs (47.2% vs 49.8%), grade ≥3 TEAEs (72.8% vs 69.9%), and drug-related TEAEs leading to death (2.4% vs 2.8%) were similar in both arms. Conclusions: Targeting CLDN18.2 with zolbetuximab combined with CAPOX significantly prolonged PFS and OS in 1L pts with CLDN18.2+/HER2− LA unresectable or mG/GEJ adenocarcinoma. These results align with those observed in SPOTLIGHT and establish zolbetuximab + chemotherapy as a potential new standard-of-care option for these pts. Clinical trial information: NCT03653507 . [Table: see text]
Micronutrient Supplementation and Bone Health After Prophylactic Total Gastrectomy in Patients With CDH1 Variants
Authors: Gamble Lauren A , Lopez Rachael , Rajasimhan Suraj , Samaranayake Sarah G , Bowden Cassidy , Famiglietti Amber L , Blakely Andrew M , Jha Smita , Ahlman Mark A , Davis Jeremy L 
Published: March 2023

Abstract

Introduction
Patients with germline variants in CDH1 who undergo prophylactic total gastrectomy (TG) are at risk of altered nutrient and drug absorption due to modified gastrointestinal anatomy. Bone mineral density loss and micronutrient deficiencies have not been described previously in this patient population.

Methods
In this study we included 94 patients with germline CDH1 variants who underwent prophylactic TG between October 2017 and February 2022. We examined pre- and post-gastrectomy bone mineral density (BMD); serum biomarkers including calcium, phosphorus, alkaline phosphatase, and 25 (OH)-vitamin D; and postoperative adherence to calcium and multivitamin supplementation.

Results
Almost all patients (92/94, 98%) lost a substantial amount of weight post-TG, with an average weight loss of 26.5% at 12 months post-surgery. Serum biomarkers of mineral metabolism, namely calcium and phosphorus, did not change significantly after TG. However, average BMD was decreased in all patients at 12 months post-TG. Nonadherence to calcium supplementation was associated with a decrease in BMD. Nonadherence to multivitamin supplementation was associated with greater percent BMD loss in the femoral neck and total hip.

Conclusions
Appropriate micronutrient supplementation and nutritional counseling pre- and postoperatively in patients undergoing prophylactic TG are important to mitigate the long-term effects of gastrectomy on bone health.
COVID-19 as a Trigger for Type 1 Diabetes
Authors: Wang Yichen , Guo Hui , Wang Gongquan , Zhai Jiawei , Du Bing 
Published: March 2023

Abstract
Type 1 diabetes (T1D) is usually caused by immune-mediated destruction of islet β cells, and genetic and environmental factors are thought to trigger autoimmunity. Convincing evidence indicates that viruses are associated with T1D development and progression. During the COVID-19 pandemic, cases of hyperglycemia, diabetic ketoacidosis, and new diabetes increased, suggesting that SARS-CoV-2 may be a trigger for or unmask T1D. Possible mechanisms of β-cell damage include virus-triggered cell death, immune-mediated loss of pancreatic β cells, and damage to β cells because of infection of surrounding cells. This article examines the potential pathways by which SARS-CoV-2 affects islet β cells in these 3 aspects. Specifically, we emphasize that T1D can be triggered by SARS-CoV-2 through several autoimmune mechanisms, including epitope spread, molecular mimicry, and bystander activation. Given that the development of T1D is often a chronic, long-term process, it is difficult to currently draw firm conclusions as to whether SARS-CoV-2 causes T1D. This area needs to be focused on in terms of the long-term outcomes. More in-depth and comprehensive studies with larger cohorts of patients and long-term clinical follow-ups are required.
The Problem of Developing Scientific and Methodological Support of Subjects of Interdepartmental Cooperation in the Implementation of the Strategy for the Development of Education of the Russian Federation
Authors: Yakovlev Sergey 
Published: March 2023

The paper discloses the structure of scientific and methodological support for interagency cooperation in the implementation of the Strategy for the Development of Upbringing in the Russian Federation that includes the coordination of work of legislative authorities and public administration bodies of the education system, scientific institutions of the Russian Academy of Education system, institutions of secondary professional and higher education system and the system of advanced training of education workers, educational institutions and additional images. The content and structure of scientific and methodological support of interdepartmental cooperation in the implementation of the Strategy for the Development of Upbringing in the Russian Federation are proposed.
An Oblivious Ellipsoid Algorithm for Solving a System of (In)Feasible Linear Inequalities
Authors: Lamperski Jourdain , Freund Robert M. , Todd Michael J. 
Published: March 2023

The ellipsoid algorithm is a fundamental algorithm for computing a solution to the system of m linear inequalities in n variables [Formula: see text] when its set of solutions has positive volume. However, when [Formula: see text] is infeasible, the ellipsoid algorithm has no mechanism for proving that (P) is infeasible. This is in contrast to the other two fundamental algorithms for tackling [Formula: see text], namely, the simplex and interior-point methods, each of which can be easily implemented in a way that either produces a solution of [Formula: see text] or proves that [Formula: see text] is infeasible by producing a solution to the alternative system [Formula: see text]. This paper develops an oblivious ellipsoid algorithm (OEA) that either produces a solution of [Formula: see text] or produces a solution of [Formula: see text]. Depending on the dimensions and other condition measures, the computational complexity of the basic OEA may be worse than, the same as, or better than that of the standard ellipsoid algorithm. We also present two modified versions of OEA, whose computational complexity is superior to that of OEA when [Formula: see text]. This is achieved in the first modified version by proving infeasibility without producing a solution of [Formula: see text], and in the second version by using more memory. Funding: J. Lamperski and R. M. Freund were supported by the Air Force Office of Scientific Research [Grant FA9550-19-1-0240].
Protocol for a randomized controlled trial to assess the effect of Self-Management for Amputee Rehabilitation using Technology (SMART): An online self-management program for individuals with lower limb loss
Authors: Esfandiari Elham , Miller WC , King Sheena , Payne Michael , Mortenson W. Ben , Underwood Heather , MacKay Crystal , Ashe Maureen C. 
Published: March 2023

Background
Lower limb loss (LLL) is a distressing experience with psychological, physical, and social challenges. Education is needed to enhance the coping skills and confidence of patients to improve LLL outcomes. However, access to rehabilitation services and education is limited outside of urban centers. To address this service gap, we co-created an eHealth platform, called Self-Management for Amputee Rehabilitation using Technology (SMART).

Objectives
First, we will test the effect of SMART and usual care compared with usual care only on walking capacity and confidence among individuals with LLL. Second, we will describe key implementation factors for program delivery and adoption at the person- and provider-level.

Methods
This is a Type 1 Effectiveness-Implementation Hybrid Design, mixed-methods, multi-site (British Columbia and Ontario, Canada), parallel, assessor-blinded randomized controlled trial. Participants will include adults with unilateral LLL, during early prosthetic fitting (<2 years after casting for initial prosthesis). Participants in both groups will receive usual care. The experimental group will receive SMART with weekly support sessions from a trained peer mentor for goal setting and action planning for six weeks. Participants will be encouraged to continue using SMART for an additional four weeks. The control group will receive usual care, and weekly social contacts for six weeks. The primary outcome measure is walking capacity operationalized as the performance based Timed Up and Go test. The secondary outcome is walking confidence using the Ambulatory Self-Confidence Questionnaire. Outcome measures will be assessed at baseline, immediately post-intervention, and four weeks follow-up. We will describe key implementation factors (such as, participant experience, intervention adoption, fidelity) throughout the study using questionnaires, semi-structured interviews, and direct observation.

Results
No participants have been enrolled.

Conclusions
SMART has the potential to provide knowledge and skill development to augment rehabilitation outcomes for adults with LLL.

Trial registration
NCT04953364 in Clinical Trial Registry (https://clinicaltrials.gov/).