bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiotensin-(1–7) infusion in COVID-19 patients admitted to the ICU: a seamless phase 1–2 randomized clinical trial
Authors: Martins Ana Luiza Valle , Annoni Filippo , da Silva Filipe Alex , Bolais-Ramos Lucas , de Oliveira Gisele Capanema , Ribeiro Renata Cunha , Diniz Mirella Monique Lana , Silva Thuanny Granato Fonseca , Pinheiro Beatriz Dias , Rodrigues Natália Abdo , dos Santos Matos Alana Helen , Motta-Santos Daisy , Campagnole-Santos Maria José , Verano-Braga Thiago , Taccone Fabio Silvio , Santos Robson Augusto Souza 
Published: September 2024

Abstract
Background
The coronavirus-related disease (COVID-19) is mainly characterized by a respiratory involvement. The renin-angiotensin system (RAS) has a relevant role in the pathogenesis of COVID-19, as the virus enters host’s cells via the angiotensin-converting enzyme 2 (ACE2).

Methods
This investigator-initiated, seamless phase 1–2 randomized clinical trial was conceived to test the safety and efficacy of continuous short-term (up to 7 days) intravenous administration of Angiotensin-(1–7) in COVID-19 patients admitted to two intensive care units (ICU). In addition to standard of care, intravenous administration of Angiotensin-(1–7) was started at 5 mcg/Kg day and increased to 10 mcg/Kg day after 24 h (Phase 1; open label trial) or given at 10 mcg/Kg day and continued for a maximum of 7 days or until ICU discharge (Phase 2; double-blind randomized controlled trial). The rate of serious adverse events (SAEs) served as the primary outcome of the study for Phase 1, and the number of oxygen free days (OFDs) by day 28 for Phase 2.

Results
Between August 2020 and July 2021, when the study was prematurely stopped due to low recruitment rate, 28 patients were included in Phase 1 and 79 patients in Phase 2. Of those, 78 were included in the intention to treat analysis, and the primary outcome was available for 77 patients. During Phase 1, one SAE (i.e., bradycardia) was considered possibly related to the infusion, justifying its discontinuation. In Phase 2, OFDs did not differ between groups (median 19 [0–21] vs. 14 [0–18] days; p = 0.15). When patients from both phases were analyzed in a pooled intention to treat approach (Phase 1–2 trial), OFDs were significantly higher in treated patients, when compared to controls (19 [0–21] vs. 14 [0–18] days; absolute difference −5 days, 95% CI [0–7] p = 0.04).

Conclusions
The main findings of our study indicate that continuous intravenous infusion of Angiotensin-(1–7) at 10 mcg/Kg day in COVID-19 patients admitted to the ICU with severe pneumonia is safe. In Phase II intention to treat analysis, there was no significant difference in OFD between groups.
Trial Registration ClinicalTrials.gov Identifier: NCT04633772—Registro Brasileiro de Ensaios Clínicos, UTN number: U1111-1255-7167.
Chromosomal instability: a key driver in glioma pathogenesis and progression
Authors: Mazzoleni Adele , Awuah Wireko Andrew , Sanker Vivek , Bharadwaj Hareesha Rishab , Aderinto Nicholas , Tan Joecelyn Kirani , Huang Helen Ye Rim , Poornaselvan Jeisun , Shah Muhammad Hamza , Atallah Oday , Tawfik Aya , Elmanzalawi Mohamed Elsayed Abdelmeguid Elsayed , Ghozlan Sama Hesham , Abdul-Rahman Toufik , Moyondafoluwa Jeremiah Adepoju , Alexiou Athanasios , Papadakis Marios 
Published: September 2024

AbstractChromosomal instability (CIN) is a pivotal factor in gliomas, contributing to their complexity, progression, and therapeutic challenges. CIN, characterized by frequent genomic alterations during mitosis, leads to genetic abnormalities and impacts cellular functions. This instability results from various factors, including replication errors and toxic compounds. While CIN’s role is well documented in cancers like ovarian cancer, its implications for gliomas are increasingly recognized. CIN influences glioma progression by affecting key oncological pathways, such as tumor suppressor genes (e.g., TP53), oncogenes (e.g., EGFR), and DNA repair mechanisms. It drives tumor evolution, promotes inflammatory signaling, and affects immune interactions, potentially leading to poor clinical outcomes and treatment resistance. This review examines CIN’s impact on gliomas through a narrative approach, analyzing data from PubMed/Medline, EMBASE, the Cochrane Library, and Scopus. It highlights CIN’s role across glioma subtypes, from adult glioblastomas and astrocytomas to pediatric oligodendrogliomas and astrocytomas. Key findings include CIN’s effect on tumor heterogeneity and its potential as a biomarker for early detection and monitoring. Emerging therapies targeting CIN, such as those modulating tumor mutation burden and DNA damage response pathways, show promise but face challenges. The review underscores the need for integrated therapeutic strategies and improved bioinformatics tools like CINdex to advance understanding and treatment of gliomas. Future research should focus on combining CIN-targeted therapies with immune modulation and personalized medicine to enhance patient outcomes.
Vehicle-to-Grid: quantification of its contribution to security of supply through the F-Factor methodology
Authors: Giannelos Spyros , Borozan Stefan , Strbac Goran , Zhang Tai , Kong Wangwei 
Published: September 2024

AbstractThe increasing adoption of electric vehicles is expected to substantially raise electricity demand. This could require significant grid investment to maintain secure electricity supply, which has traditionally been provided through infrastructure upgrades. The potential of smart technologies like Vehicle-to-Grid (V2G) to contribute to security of supply has prompted the need to quantify their impact. We hypothesize that the F-Factor methodology can effectively quantify V2G’s security of supply contribution. Applying F-Factor analysis to V2G through optimization modeling and sensitivity studies, we find that key parameters like V2G charger ratings, EV battery capacities, and load profile peakiness significantly influence the results. We conclude that the F-Factor provides a valuable tool for assessing V2G’s potential to enhance security of supply, with implications for more efficient grid planning in the context of transport electrification.
A serological survey of COVID-19 among predominantly aboriginal residents of a tourist island in southern Thailand
Authors: Sripaew Supakorn , Yasharad Kameelah , Rahari Dzerlina S. , Feng Weiyan , Qian Zhenzhu , Thanh Huynh Ngoc , Li Pei , Fitriangga Agus , Purwanto Satiti Palupi , Phyu Aye Nyein , Xianyu Fangming , Phadungvitvatthana Sombat , Wichaidit Wit , Kumwichar Ponlagrit , Chongsuvivatwong Virasakdi 
Published: September 2024

Abstract
Background
The current survey describes the seroprevalence, history of coronavirus disease 2019 (COVID-19), and vaccination status among predominantly aboriginal residents on a tourist island in southern Thailand. This information can be translated into COVID-19 vaccination and control plans for this population.

Methods
We implemented questionnaire interviews and collected blood samples from 249 residents of Lipe Island, Satun Province, in January 2022. We measured the anti-nucleocapsid protein and anti-spike (anti-S) receptor-binding protein levels of immunoglobulin (Ig) M and IgG. The differences in antibody levels among participants with different histories of vaccination and infection were analyzed using one-way analysis of variance with multiple comparisons.

Results
During the 2-year pandemic period, no island residents with COVID-19 required hospitalization despite the high prevalence of hypertension (33.3%) and diabetes mellitus (21.7%). Approximately 18.8% of the participants reported a history of COVID-19 diagnosis. In total, 95.1% of the participants had a history of complete vaccination, of which 93.5% were seropositive. The anti-S IgG geometric means (geometric standard deviation) were 3945.8 (2.0), 829.8 (9.7) AU/mL, 789.9 (5.3) AU/mL, and 22.7 (7.1) AU/mL, respectively, in participants with a history of both COVID-19 diagnosis and complete vaccination (group 1), incomplete vaccination and subsequent COVID-19 diagnosis (group 2), complete vaccination but no previous infection (group 3), or neither previous COVID-19 and complete vaccination (group 4). Significant pairwise differences in anti-S IgG levels were found between certain groups (1 vs 3, 1 vs 4, 2 vs 4, and 3 vs 4).

Conclusions
The high coverage of vaccination, high levels of population antibody titers, variable antibody levels among completely vaccinated non-infected residents, and high prevalence of non-communicable diseases (NCDs) suggested that the local health systems could control the pandemic. However, continuing surveillance, booster vaccinations, and NCD prevention programs were still required.
Antibiotic resistance challenge: evaluating anthraquinones as rifampicin monooxygenase inhibitors through integrated bioinformatics analysis
Authors: Arabestani Mohammad Reza , Saadat Masoumeh , Taherkhani Amir 
Published: September 2024

Abstract
Objective
Antibiotic resistance poses a pressing and crucial global public health challenge, leading to significant clinical and health-related consequences. Substantial evidence highlights the pivotal involvement of rifampicin monooxygenase (RIFMO) in the context of antibiotic resistance. Hence, inhibiting RIFMO could offer potential in the treatment of various infections. Anthraquinones, a group of organic compounds, have shown promise in addressing tuberculosis. This study employed integrated bioinformatics approaches to evaluate the potential inhibitory effects of a selection of anthraquinones on RIFMO. The findings were subsequently compared with those of rifampicin (RIF), serving as a positive control inhibitor.

Methods
The AutoDock 4.0 tool assessed the binding free energy between 21 anthraquinones and the RIFMO catalytic cleft. The ligands were ranked based on the most favorable scores derived from ΔGbinding. The docking analyses for the highest-ranked anthraquinone and RIF underwent a cross-validation process. This validation procedure utilized the SwissDock server and the Schrödinger Maestro docking software. Molecular dynamics simulations were conducted to scrutinize the stability of the backbone atoms in free RIFMO, RIFMO-RIF, and RIFMO complexed with the top-ranked anthraquinone throughout a 100-ns computer simulation. The Discovery Studio Visualizer tool visualized interactions between RIFMO residues and ligands. An evaluation of the pharmacokinetics and toxicity profiles of the tested compounds was also conducted.

Results
Five anthraquinones were indicated with ΔGbinding scores less than − 10 kcal/mol. Hypericin emerged as the most potent RIFMO inhibitor, boasting a ΔGbinding score and inhibition constant value of − 12.11 kcal/mol and 798.99 pM, respectively. The agreement across AutoDock 4.0, SwissDock, and Schrödinger Maestro results highlighted hypericin’s notable binding affinity to the RIFMO catalytic cleft. The RIFMO-hypericin complex achieved stability after a 70-ns computer simulation, exhibiting a root-mean-square deviation of 0.55 nm. Oral bioavailability analysis revealed that all anthraquinones except hypericin, sennidin A, and sennidin B may be suitable for oral administration. Furthermore, the carcinogenicity prediction analysis indicated a favorable safety profile for all examined anthraquinones.

Conclusion
Inhibiting RIFMO, particularly with anthraquinones such as hypericin, holds promise as a potential therapeutic strategy for infectious diseases.
The Value of Robust Assortment Optimization Under Ranking-Based Choice Models
Authors: Sturt Bradley 
Published: September 2024

We study a class of robust assortment optimization problems that was proposed by Farias et al. [Farias VF, Jagabathula S, Shah D (2013) A nonparametric approach to modeling choice with limited data. Management Sci. 59(2):305–322]. The goal in these problems is to find an assortment that maximizes a firm’s worst-case expected revenue under all ranking-based choice models that are consistent with the historical sales data generated by the firm’s past assortments. We establish for various settings that these robust optimization problems can either be solved in polynomial time or can be reformulated as compact mixed-integer optimization problems. To establish our results, we prove that optimal assortments for these robust optimization problems have a simple structure that is closely related to the structure of revenue-ordered assortments. We use our results to show how robust optimization can be used to overcome the risks of estimate-then-optimize and the need for experimentation with ranking-based choice models in the overparameterized regime. This paper was accepted by Omar Besbes, revenue management and market analytics. Supplemental Material: The online appendices and data files are available at https://doi.org/10.1287/mnsc.2021.04059 .
Pheochromocytoma and thyroid storm presenting as ST elevation myocardial infarction in a patient with non-obstructive coronary arteries
Authors: Shehzad Mustafa , Shehzad Dawood , Ahmad Muhammad , Younis Humna , Wassey Abdul , Fatima Rida 
Published: September 2024

Introduction: Pheochromocytomas can present as a diagnostic challenge, given their diverse clinical manifestations. Though classically taught as presenting with headaches, palpitations and paroxysmal hypertension, only 1 in 4 present with such a triad. Catecholamines affect the myocardium in various ways, ranging from beta-adrenergic receptor-mediated myofibril dysfunction to direct myocardial injury by catecholamine oxidation products. Case description: We report the case of a 41-year-old female with no significant past medical history, who presented with acute coronary syndrome. She was found to have myocardial infarction with non-obstructive coronary arteries (MINOCA), and her clinical course was complicated by erratic blood pressure management. Laboratory findings and imaging findings confirmed the diagnosis of pheochromocytoma. Post-cardiac catheterisation, she developed a thyroid storm and fatal cardiac arrest. Conclusions: The combination of hyperthyroidism with pheochromocytoma is rare but often fatal; iodinated angiography contrast likely precipitated her thyroid storm. This case underscores the importance of considering pheochromocytoma early in patients with MINOCA, particularly in those with erratic blood pressure. Pheochromocytomas have been reported to be associated with MINOCA in rare cases and have significant mortality. Current guidelines do not include pheochromocytoma as a possible differential diagnosis; recognition and early diagnosis are crucial for improved outcomes.
Efficacy and safety of tranexamic acid on blood loss and seizures in patients undergoing meningioma resection: A systematic review and meta-analysis
Authors: Liu Xiaoyuan , Liu Minying , Li Shu , Ren Yue , Zheng Maoyao , Zeng Min , Peng Yuming 
Published: September 2024

Introduction
It is unclear how tranexamic acid (TXA) affects blood loss and seizures in meningioma resections. We performed a systematic review and meta-analysis and tried to evaluate the effectiveness and safety of TXA use for patients undergoing meningioma resections.

Methods
Regards to this systematic review and meta-analysis (registered with CRD42023416693), we searched PubMed, Embase (Ovid), EBSCO, and Cochrane central library up to and including Oct 2023. Patients undergoing meningioma resections treated with TXA and placebo or no treatment were eligible for this study. This would allow delineation of the impact of TXA on blood loss, postoperative seizure, and other complication incidences.

Results
Four prospective cohort studies with 781 patients (390 patients in the TXA group and 391 patients in the control group) were conducted via a systematic review and meta-analysis. The results suggested that the application of TXA for patients undergoing meningioma resections reduced mean blood loss of 252 mL with 95% confidence interval (CI) -469.26 to -34.67 (P = 0.02) and I2 of 94% but did not increase postoperative seizure (risk ratio: 1.08; 95%CI: 0.54 to 2.15; P = 0.84) and other complication rates.

Conclusions
This systematic review and meta-analysis suggests that the administration of TXA could reduce blood loss in patients undergoing intracerebral meningioma resection.

Registry information
The systematic review protocol has been registered at PROSPERO (Registration No. CRD42023416693) on April 23, 2023.
Polypharmacy in primary care: A population-based retrospective cohort study of electronic health records
Authors: Woodcock Thomas , Lovett Derryn , Ihenetu Gloria , Novov Vesselin , Beaney Thomas , Armani Keivan , Quilley Angela , Majeed Azeem , Aylin Paul 
Published: September 2024

Background
Polypharmacy, prescription of multiple medications to a patient, is a major challenge for health systems. There have been no peer-reviewed studies of polypharmacy prevalence and medication cost at a population level in England.

Aims
To determine prevalence and medication cost of polypharmacy, by patient characteristics.
Design and setting: Retrospective cohort study of North West London electronic health records

Method
We quantified prevalence and direct cost of polypharmacy (five or more regular medications), stratified by demographics and frailty. We fitted a mixed-effects logistic regression for polypharmacy.

Results
Of 1.7 million adults, 167,665 (9.4%) were on polypharmacy. Age and socio-economic deprivation were associated with polypharmacy (OR 9.24 95% CI 8.99 to 9.50, age 65–74 compared with 18–44; OR 0.68 95% CI 0.65 to 0.71, least deprived compared with most). Polypharmacy prevalence increased with frailty (OR 1.53 95% CI 1.53 to 1.54 per frailty component, for White women). Men had higher odds of polypharmacy than women at average frailty (OR 1.26 95% CI 1.24 to 1.28) and with additional frailty components (OR 1.10 95% CI 1.09 to 1.10). Black people had lower odds of polypharmacy at average frailty (OR 0.82 95% CI 0.79 to 0.85, compared with White), but along with other ethnicities, saw greater odds increases with increasing frailty (OR 1.02 95% CI 1.01 to 1.03). Annual medication cost 8.2 times more for those on polypharmacy compared with not (£370.89 and £45.31).

Conclusion
Demographic characteristics are associated with polypharmacy, after adjusting for frailty. Further research should explore why, to reduce health inequities and optimise cost associated with polypharmacy.
Consumption patterns and factors associated with inappropriate prescribing of benzodiazepines in Primary Health Care settings
Authors: Barboza Zanetti Maria Olívia , dos Santos Iara , Durante Júlia Casanova , Varallo Fabiana Rossi , Pereira Leonardo Régis Leira , Miasso Adriana Inocenti 
Published: September 2024

Background
Benzodiazepines are frequently prescribed to treat anxiety and insomnia, but long-term use has been associated with the development of dependence, tolerance, and cognitive decline, especially among older adults. This study aimed to investigate the pattern of consumption and factors associated with inappropriate prescribing of benzodiazepines in primary health care.

Methods
This is a cross-sectional analytical study, using dispensing records of diazepam, clonazepam, and nitrazepam from public pharmacies in a Brazilian municipality between 2018 and 2022. Metrics for benzodiazepine consumption were DDD (Defined Daily Dose) and DDD/1000PD (per 1000 population per day). Long-term/prolonged benzodiazepine use was defined as consuming at least 90 DDD and at least 2 dispensations per year. To ascertain associations between long-term use and predictor variables, a multivariate logistic regression model was utilized.

Findings
A total of 40402 participants were included, with an average age of 55 years (SD = 0.30), 38.5% were older aged. Diazepam and nitrazepam exceeded the daily dose recommended. There was a reduction in diazepam consumption during the study period, as calculated by DDD/1.000PD, while the consumption of other benzodiazepines remained stable. However, a significant increase in diazepam consumption is noted when considering the last decade. Prolonged use was observed in 29.1% of participants, with a significant prevalence among the older people (34.8% of them were long-term users) and advancing age was identified as a risk factor for long-term use. Higher PDDs were also associated with long-term use and aging. Participants who used different benzodiazepines during the period had a higher risk of prolonged use.

Conclusions
These results provide insights into the prevalence of problematic utilization of benzodiazepines in primary health care. Authorities and health care providers must take steps to encourage gradual cessation of prolonged benzodiazepine prescriptions and the embrace of suitable strategies for addressing anxiety and insomnia within primary health care settings.
Coping Stress Pada Pelajar Kawruh Jiwa Lansia Duda Pasca Kematian Pasangan
Authors: Himawan Ronan , Prasetya Berta Esti Ari 
Published: September 2024

Becoming a widower after the death of a spouse in the elderly is not an easy matter for men. The event of the death of a life partner is one of life's challenges that cause and increase stress in the elderly. Culture also influences the way individuals cope with stress. This study explores the perspective of individuals living within the wisdom of local culture, as adherents of kawruh jiwa spirituality. The research employs a qualitative phenomenological study method, involving two elderly spiritual adherents who are widowers following the death of their partners. Moustakas' phenomenological data analysis is utilized. The research findings reveal the existence of a spiritual concept of kawruh jiwa knowledge that is utilized as a stress coping strategy. Among these concepts are saiki kene ngene yo gelem, nyawang karep, bungah susah, and sabutuhe saperlune sacukupe sapenake samestine sabenere. This study's findings offer novelty in terms of thematic analysis using the concept of kawruh jiwa spirituality as a source of coping strategies for elderly widowers following the death of their partners.

Menjadi duda pasca kematian pasangan pada lansia bukanlah perkara mudah bagi para pria. Peristiwa kematian pasangan hidup merupakan salah satu tantangan hidup yang mengakibatkan dan meningkatkan stres pada lansia. Kebudayaan juga turut memengaruhi cara individu tersebut dalam menghadapi stres. Dalam penelitian ini peneliti mengeksplorasisudut pandang dari individu yang hidup dalam kearifan budaya lokal, sebagai penghayat kawruh jiwa. Penelitian ini menggunakan metode penelitian studi kualitatif fenomenologi, dengan melibatkan dua orang penghayat kawruh jiwa lansia yang berstatus duda pasca kematian pasangan. Analisis data menggunakan analisis data fenomenologi Moustakas. Hasil penelitian menemukan bahwa terdapat konsep spiritual kawruh jiwa yang dimanfaatkan sebagaistrategi koping stres. Di antaranya adalah konsep saiki kene ngene yo gelem, nyawang karep, bungah susah, dan sabutuhe saperlune sacukupe sapenake samestine sabenere. Temuan studi ini menawarkan kebaharuan dari sisi analisis tema yang menggunakan konsep spiritual kawruh jiwa sebagai sumber strategi pemecahan masalah bagi lansia duda pasca kematian pasangan.
Corrosion behavior of Cu–40Zn alloy in a periodic service between simulating atmospheric and deep sea environment
Authors: Hu Shengbo , Liu Zhong , Yuan Xuwen , Meng Fandi , Liao Luhai , Guo Rui , Yang Wei , Li Fengguang 
Published: September 2024

Abstract
The corrosion behavior of Cu–40Zn alloy in a periodic service between simulating atmospheric and deep sea environment has been systematically studied. Results showed that a layer of protective corrosion products can be formed quickly and become defective over time. During the periodic service, the HP (high hydrostatic pressure) promotes the anodic dissolution of the base and the generation of (Cu, Zn)2(OH)3Cl, which causes expansion of the corrosion products; the AP (alternating pressure) facilitates the wetting process during dry to wet stage, and the alternating force caused by AP leads to the cracks, peeling off of the corrosion products. Severe intergranular corrosion takes place, which initiates at the β phase and is accelerated by the combination of defective corrosion products and the drying stage.