bluuebunny/crossref_metadata_2025_split huggingface dataset:
Home medication management problems and associated factors among psychiatric patients using home care pharmacy services at government hospitals in western Malaysia
Authors: Lau Christine Li Ling , Hor Cheah Yen , Ong Siew Ting , Roslan Muhammad Fadhlullah , Beh Xin Yi , Permal Dashnilatha , Rama Shamini 
Published: June 2022

AbstractBackgroundProper home medication management plays a role in improving medication adherence, preserving drug efficacy and ensuring safe medication practices, which is crucial to establish positive treatment outcomes. However, no published studies are available on home medication management among psychiatric patients. The study aimed to identify home medication management problems among psychiatric patients in Malaysia and to examine the associations of inappropriate medication storage and lack of a medication administration schedule with sociodemographic factors, disease insight, number of medications and type of home care pharmacy services (HCPS).MethodsThis multicentre cross-sectional study was conducted among psychiatric patients using HCPS in six government hospitals in western Malaysia. Data were extracted from the HCPS form used for each visit as per the protocol published by the Pharmaceutical Services Division, Ministry of Health Malaysia. A minimum sample size of 169 was needed. Proportional random sampling was applied. The associations of inappropriate medication storage and lack of medication administration schedule with study parameters were analysed using multiple logistic regressions.ResultsA total of 205 home visits were conducted with 229 home medication management problems identified; inappropriate medication storage and lack of medication administration schedule topped the list. Inappropriate medication storage was significantly associated with low income [AOR = 4.34 (95% CI 1.17:15.98),p = 0.027], alcohol consumption [AOR = 14.26 (95% CI 1.82:111.38),p = 0.011], poor insight [AOR = 2.34 (95% CI 1.08:5.06),p = 0.030] and part-time HCPS [AOR = 2.60 (95% CI 1.20:5.67),p = 0.016]. Lack of administration schedule was significantly associated with low income [AOR = 6.90 (95% CI 1.46:32.48),p = 0.014], smoking [AOR = 2.43 (95% CI 1.20:4.92),p = 0.013], poor insight [AOR = 5.32 (95% CI 2.45:11.56),p < 0.05] and part-time HCPS [AOR = 2.96 (95% CI 1.42:6.15),p = 0.004].ConclusionsInappropriate medication storage and a lack of a medication administration schedule are common among psychiatric patients. The study also highlighted the potential of HCPS to improve disease insight and home medication management among psychiatric patients if the service is utilized fully.
Phospholipid scramblase 1: a protein with multiple functions via multiple molecular interactors
Authors: Dal Col Jessica , Lamberti Marìa Julia , Nigro Annunziata , Casolaro Vincenzo , Fratta Elisabetta , Steffan Agostino , Montico Barbara 
Published: June 2022

AbstractPhospholipid scramblase 1 (PLSCR1) is the most studied protein of the scramblase family. Originally, it was identified as a membrane protein involved in maintaining plasma membrane asymmetry. However, studies conducted over the past few years have shown the involvement of PLSCR1 in several other cellular pathways. Indeed, PLSCR1 is not only embedded in the plasma membrane but is also expressed in several intracellular compartments where it interacts with a diverse repertoire of effectors, mediators, and regulators contributing to distinct cellular processes. Although most PLSCR1 interactors are thought to be cell-type specific, PLSCR1 often exerts its regulatory functions through shared mechanisms, including the trafficking of different molecules within intracellular vesicles such as endosomes, liposomes, and phagosomes. Intriguingly, besides endogenous proteins, PLSCR1 was also reported to interact with exogenous viral proteins, thereby regulating viral uptake and spread. This review aims to summarize the current knowledge about the multiple roles of PLSCR1 in distinct cellular pathways.
Application of blood brain barrier models in pre-clinical assessment of glioblastoma-targeting CAR-T based immunotherapies
Authors: Huang Jez , Li Ying Betty , Charlebois Claudie , Nguyen Tina , Liu Ziying , Bloemberg Darin , Zafer Ahmed , Baumann Ewa , Sodja Caroline , Leclerc Sonia , Fewell Gwen , Liu Qing , Prabhakarpandian Balabhaskar , McComb Scott , Stanimirovic Danica B. , Jezierski Anna 
Published: June 2022

AbstractHuman blood brain barrier (BBB) models derived from induced pluripotent stem cells (iPSCs) have become an important tool for the discovery and preclinical evaluation of central nervous system (CNS) targeting cell and gene-based therapies. Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary form of gene-modified cell-based immunotherapy with potential for targeting solid tumors, such as glioblastomas. Crossing the BBB is an important step in the systemic application of CAR-T therapy for the treatment of glioblastomas and other CNS malignancies. In addition, even CAR-T therapies targeting non-CNS antigens, such as the well-known CD19-CAR-T therapies, are known to trigger CNS side-effects including brain swelling due to BBB disruption. In this study, we used iPSC-derived brain endothelial-like cell (iBEC) transwell co-culture model to assess BBB extravasation of CAR-T based immunotherapies targeting U87MG human glioblastoma (GBM) cells overexpressing the tumor-specific mutated protein EGFRvIII (U87vIII). Two types of anti-EGFRvIII targeting CAR-T cells, with varying tonic signaling profiles (CAR-F263 and CAR-F269), and control Mock T cells were applied on the luminal side of BBB model in vitro. CAR-F263 and CAR-F269 T cells triggered a decrease in transendothelial electrical resistance (TEER) and an increase in BBB permeability. CAR-T cell extravasation and U87vIII cytotoxicity were assessed from the abluminal compartment using flow cytometry and Incucyte real-time viability imaging, respectively. A significant decrease in U87vIII cell viability was observed over 48 h, with the most robust cytotoxicity response observed for the constitutively activated CAR-F263. CAR-F269 T cells showed a similar cytotoxic profile but were approximately four fold less efficient at killing the U87vIII cells compared to CAR-F263, despite similar transmigration rates. Visualization of CAR-T cell extravasation across the BBB was further confirmed using BBTB-on-CHIP models. The described BBB assay was able to discriminate the cytotoxic efficacies of different EGFRvIII-CARs and provide a measure of potential alterations to BBB integrity. Collectively, we illustrate how BBB models in vitro can be a valuable tool in deciphering the mechanisms of CAR-T–induced BBB disruption, accompanying toxicity and effector function on post-barrier target cells.
Racial disparities in triple negative breast cancer: toward a causal architecture approach
Authors: Siegel Scott D. , Brooks Madeline M. , Lynch Shannon M. , Sims-Mourtada Jennifer , Schug Zachary T. , Curriero Frank C. 
Published: June 2022

AbstractBackgroundTriple negative breast cancer (TNBC) is an aggressive subtype of invasive breast cancer that disproportionately affects Black women and contributes to racial disparities in breast cancer mortality. Prior research has suggested that neighborhood effects may contribute to this disparity beyond individual risk factors.MethodsThe sample included a cohort of 3316 breast cancer cases diagnosed between 2012 and 2020 in New Castle County, Delaware, a geographic region of the US with elevated rates of TNBC. Multilevel methods and geospatial mapping evaluated whether the race, income, and race/income versions of the neighborhood Index of Concentration at the Extremes (ICE) metric could efficiently identify census tracts (CT) with higher odds of TNBC relative to other forms of invasive breast cancer. Odds ratios (OR) and 95% confidence intervals (CI) were reported;p-values < 0.05 were significant. Additional analyses examined area-level differences in exposure to metabolic risk factors, including unhealthy alcohol use and obesity.ResultsThe ICE-Race, -Income-, and Race/Income metrics were each associated with greater census tract odds of TNBC on a bivariate basis. However, only ICE-Race was significantly associated with higher odds of TNBC after adjustment for patient-level age and race (most disadvantaged CT: OR = 2.09; 95% CI 1.40–3.13), providing support for neighborhood effects. Higher counts of alcohol and fast-food retailers, and correspondingly higher rates of unhealthy alcohol use and obesity, were observed in CTs that were classified into the most disadvantaged ICE-Race quintile and had the highest odds of TNBC.ConclusionThe use of ICE can facilitate the monitoring of cancer inequities and advance the study of racial disparities in breast cancer.
Efficacy and safety of Gyejibokryeong-hwan (GBH) in major depressive disorder: study protocol for multicentre randomised controlled trial
Authors: Choi Yujin , Jung In Chul , Kim Ju Yeon , Cho Seung-Hun , Kim Yunna , Chung Sun-Yong , Kwak Hui-Yong , Lee Doo Suk , Lee Wonwoo , Nam In-Jeong , Yang Changsop , Lee Mi Young 
Published: June 2022

Abstract
Background
Gyejibokryeong-hwan (GBH) is an herbal medicine composed of five herbs. It has been widely used to treat gynaecological diseases in traditional East Asian medicine. Recent animal studies suggest antidepressant effects of GBH. In this trial, we explore the efficacy and safety of GBH in patients with major depressive disorder and to identify the optimal dose for the next phase III trial.

Methods
This trial will enrol 126 patients diagnosed with major depressive disorder and not treated with antidepressants. Participants will be randomised to receive a high or a low dose of GBH or placebo granules. The study drugs will be administered three times a day, for 8 weeks. The 17-item Hamilton Depression Rating Scale (HDRS) will be used to measure the severity of depressive symptoms at weeks 2, 4, 6, 8, and 12. The primary efficacy endpoint is the change from baseline in HDRS-17 total score post-treatment at week 8. Analysis of covariance will be based on the baseline HDRS-17 total score and site as the covariates. Safety assessment will be based on the frequency of adverse events. The severity and causality of the study drug will be assessed.

Discussion
This study is designed to evaluate the efficacy and safety of GBH granules compared with placebo in patients with major depressive disorder.

Trial registration
Clinical Research Information Service KCT0004417. Registered on November 1, 2019 (prospective registration)
Open chromatin analysis in Trypanosoma cruzi life forms highlights critical differences in genomic compartments and developmental regulation at tDNA loci
Authors: Lima Alex Ranieri Jerônimo , Silva Herbert Guimarães de Sousa , Poubel Saloe , Rosón Juliana Nunes , de Lima Loyze Paola Oliveira , Costa-Silva Héllida Marina , Gonçalves Camila Silva , Galante Pedro A. F. , Holetz Fabiola , Motta Maria Cristina Machado , Silber Ariel M. , Elias M. Carolina , da Cunha Julia Pinheiro Chagas 
Published: June 2022

Abstract
Background
Genomic organization and gene expression regulation in trypanosomes are remarkable because protein-coding genes are organized into codirectional gene clusters with unrelated functions. Moreover, there is no dedicated promoter for each gene, resulting in polycistronic gene transcription, with posttranscriptional control playing a major role. Nonetheless, these parasites harbor epigenetic modifications at critical regulatory genome features that dynamically change among parasite stages, which are not fully understood.

Results
Here, we investigated the impact of chromatin changes in a scenario commanded by posttranscriptional control exploring the parasite Trypanosoma cruzi and its differentiation program using FAIRE-seq approach supported by transmission electron microscopy. We identified differences in T. cruzi genome compartments, putative transcriptional start regions, and virulence factors. In addition, we also detected a developmental chromatin regulation at tRNA loci (tDNA), which could be linked to the intense chromatin remodeling and/or the translation regulatory mechanism required for parasite differentiation. We further integrated the open chromatin profile with public transcriptomic and MNase-seq datasets. Strikingly, a positive correlation was observed between active chromatin and steady-state transcription levels.

Conclusion
Taken together, our results indicate that chromatin changes reflect the unusual gene expression regulation of trypanosomes and the differences among parasite developmental stages, even in the context of a lack of canonical transcriptional control of protein-coding genes.
Zibotentan in systemic sclerosis-associated chronic kidney disease: a phase II randomised placebo-controlled trial
Authors: Stern Edward P. , Host Lauren V. , Wanjiku Ivy , Escott K. Jane , Gilmour Peter S. , Ochiel Rachel , Unwin Robert , Burns Aine , Ong Voon H. , Cadiou Helen , O’Keeffe Aidan G. , Denton Christopher P. 
Published: June 2022

Abstract
Background
We report results from a phase II randomised placebo-controlled trial assessing zibotentan, a highly selective endothelin receptor antagonist (ERA), in chronic kidney disease (CKD) secondary to systemic sclerosis (SSc).

Methods
This trial included three sub-studies: ZEBRA 1—a randomised placebo-controlled, double-blind trial of zibotentan in SSc patients with CKD2 or CKD3 (and glomerular filtration rate (GFR) >45 ml/min) over 26 weeks; ZEBRA 2A—a 26-week placebo-controlled, single-blind trial of zibotentan in scleroderma renal crisis patients not requiring dialysis; and ZEBRA 2B—an open label pharmacokinetic study of zibotentan in patients on haemodialysis.

Results
Sixteen patients were screened for ZEBRA 1. Of these, 6 patients were randomised to zibotentan and 7 to placebo. In ZEBRA 1, there were 47 non-serious adverse events (AE) during the trial. Twenty-seven occurred in the placebo group and 20 in the zibotentan group. One serious adverse event (SAE) occurred during ZEBRA1, in the placebo arm. Descriptive statistics did not suggest an effect of study drug on serum sVCAM1. Estimated GFR numerically declined in patients treated with placebo at 26 weeks and 52 weeks. In contrast, average eGFR increased in zibotentan-treated cases.
The 4 patients in ZEBRA 2A experienced 8 non-serious AEs, distributed equally between placebo and zibotentan. There was one SAE each in placebo and zibotentan groups, both unrelated to study medication.
ZEBRA 2B recruited 8 patients, 6 completed first dosing, and 2 completed a second dosing visit. Pharmacokinetic analysis confirmed zibotentan levels within the therapeutic range. Three patients experienced 3 non-serious AEs. One SAE occurred and was unrelated to study drug.

Conclusions
Zibotentan was generally well-tolerated. ZEBRA 1 did not show any effect of zibotentan on serum sVCAM-1 but was associated with numerical improvement in eGFR at 26 weeks that was more marked at 52 weeks. ZEBRA 2B suggested a feasible dose regimen for haemodialysis patients.

Trial registration
EudraCT no: 2013-003200-39 (first posted January 28, 2014)
ClinicalTrials.gov Identifier: NCT02047708
Sponsor protocol number: 13/0077
Clinical course of patients with rheumatoid arthritis who continue or discontinue biologic therapy after hospitalization for infection: a retrospective observational study
Authors: Kashiwado Yusuke , Kiyohara Chikako , Kimoto Yasutaka , Nagano Shuji , Sawabe Takuya , Oryoji Kensuke , Mizuki Shinichi , Nishizaka Hiroaki , Yoshizawa Seiji , Yoshizawa Shigeru , Tsuru Tomomi , Inoue Yasushi , Ueda Naoyasu , Ota Shun-ichiro , Suenaga Yasuo , Miyamura Tomoya , Tada Yoshifumi , Niiro Hiroaki , Akashi Koichi , Horiuchi Takahiko 
Published: June 2022

Abstract
Background
To analyse the subsequent clinical course of patients with rheumatoid arthritis (RA) who either continued or discontinued biologic agents after hospitalization for infections.

Methods
We retrospectively reviewed the clinical records of 230 RA patients with 307 hospitalizations for infections under biologic therapy between September 2008 and May 2014 in 15 institutions for up to 18 months after discharge. The risks of RA flares and subsequent hospitalizations for infections from 61 days to 18 months after discharge were evaluated.

Results
Survival analyses indicated that patients who continued biologic therapy had a significantly lower risk of RA flares (31.4% vs. 60.6%, P < 0.01) and a slightly lower risk of subsequent infections (28.7% vs. 34.5%, P = 0.37). Multivariate analysis showed that discontinuation of biologic therapy, diabetes, and a history of hospitalization for infection under biologic therapy were associated with RA flares. Oral steroid therapy equivalent to prednisolone 5 mg/day or more and chronic renal dysfunction were independent risk factors for subsequent hospitalizations for infections.

Conclusions
Discontinuation of biologic therapy after hospitalization for infections may result in RA flares. Continuation of biologic therapy is preferable, particularly in patients without immunodeficiency.
Well-differentiated cerebellum in an ovarian mature cystic teratoma: a case report and review of the literature
Authors: AlEssa Ahmed , AlAhmadi Hassan H. , Ahmed Ayesha , AlMousa Abdulatif , Hamadeh Nasreen G. , Farah Yasir A. Hassan 
Published: June 2022

Abstract
Background
Mature teratoma is the most common germ cell tumor as it represents 95% of germ cell tumors. Although common in children and young adults, ovarian teratoma can occur at any age. Mature teratomas are composed of mature tissues representing elements derived from more than one embryonic germ layer (ectoderm, mesoderm, and endoderm), with ectodermal derivatives being the usual predominant component; however, the finding of a well-differentiated cerebellum is extremely rare.

Case presentation
A 20-year-old Saudi female presented to the emergency department with severe abdominal pain of 1-day duration. Pelvic ultrasound showed a large ovoid- to bilobed-shaped cystic pelvic structure extending to the lower abdomen. The patient underwent left ovarian cystectomy. Microscopic examination showed a cyst wall with skin tissue, including adnexal structures (sebaceous glands), a well-differentiated cerebellum, and mature glial tissue. After extensive sampling, no immature component was identified. Thus, the final diagnosis of a mature cystic teratoma with well-differentiated cerebellum was established. The patient was well postoperatively and was discharged in a stable condition.

Conclusion
We report this case of well-differentiated cerebellum within ovarian teratoma to expand the pool of cases reported in literature of this extremely rare entity, as only 22 cases with such findings have been reported in literature to the best of our knowledge. This finding poses a diagnostic challenge to the pathologist due to its rarity and its similarity to immature teratoma. We thus emphasize that thorough sampling of ovarian teratoma is of paramount importance and to keep the aforementioned diagnosis in mind and not confuse it with immature elements, especially in intraoperative consultation and frozen sections.
Covid-19 and female migrants: policy challenges and multiple vulnerabilities
Authors: Nhengu Dudziro 
Published: June 2022

AbstractTo what extent has Covid-19 policy responses exacerbated the already existing multiple vulnerabilities of female migrants in Southern Africa? Using strategic conversations, the paper explores personal experiences of key conversants, to explore how gender blind policy responses to the pandemic have heightened female migrants’ socio-economic challenges. The paper recommends gender sensitive and context specific policy responses to mitigate the existing socio-economic challenges.
A new two-degree of freedom combined PID controller for automatic generation control of a wind integrated interconnected power system
Authors: Karanam Appala Naidu , Shaw Binod 
Published: June 2022

AbstractFrequency control of an interconnected power system in the presence of wind integration is complex since wind speed/power variations also affect system frequency in addition to load perturbations. Therefore, improving existing control schemes is necessary to maintain a stable frequency in such complex power system scenarios. In this paper, a new 2-degree of freedom combined proportional-integral and derivative control scheme is applied to a wind integrated interconnected power system. In designing the controller, several inputs used for a secondary frequency control loop are considered along with the merits of the existing controllers. The combined controller provides better control action than existing controllers in the presence of wind as is evidenced by the wide variety of results presented. For tuning of the controller gains, a crow search optimization algorithm (CRSOA) is used. Results are obtained via the MATLAB/Simulink software.
Sphingolipids in plant immunity
Authors: Zeng Hong-Yun , Yao Nan 
Published: June 2022

AbstractSphingolipids (lipids with a sphingoid base backbone) are important components of eukaryotic membrane systems and key signaling molecules that are essential for controlling cellular homeostasis, acclimating to stress, and regulating plant immunity. Studies using sphingolipid treatments, measuring sphingolipids in infected plants, and functionally studying sphingolipid biosynthetic mutants demonstrated that sphingolipids participate in plant cell death and defense responses. In this review, we present an updated map of sphingolipid signaling and review recent progress in understanding the functions of sphingolipids in plant immunity as structural components of biological membranes, and as mediators of defense signaling. Moreover, several pressing questions, such as how sphingolipids in the plasma membrane, particularly microdomains, act to perceive pathogens and transduce signals during plant–pathogen interactions, remain to be further explored in future research.
Assessing aerodynamic loads on low-rise buildings considering Reynolds number and turbulence effects: a review
Authors: Khaled Md Faiaz , Aly Aly Mousaad 
Published: June 2022

AbstractThis paper presents an extensive review of existing techniques used in estimating design wind pressures considering Reynolds number and turbulence effects, as well as a case study of a reference building investigated experimentally. We shed light on the limitations of current aerodynamic testing techniques, provisions in design standards, and computational fluid dynamics (CFD) methods to predict wind-induced pressures. The paper highlights the reasons for obstructing the standardization of the wind tunnel method. Moreover, we introduce improved experimental and CFD techniques to tackle the identified challenges. CFD provides superior and efficient performance by employing wall-modeled large-eddy simulation (WMLES) and hybrid RANS-LES models. In addition, we tested a large-scale building model and compared the results with published small-scale data. The findings reinforce our hypothesis concerning the scaling issues and Reynolds number effects in aerodynamic testing.