bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between CYP3A4/CYP3A5 genetic polymorphisms and treatment outcomes of atorvastatin worldwide: is there enough research on the Egyptian population?
Authors: Maslub Mohammed G. , Radwan Mahasen A. , Daud Nur Aizati Athirah , Sha’aban Abubakar 
Published: September 2023

Abstract
Introduction
Atorvastatin is regarded as the most frequently prescribed statin worldwide for dyslipidemia. However, clinical response and risk of adverse effects to statin therapy are associated with genetic variations. Numerous research linked statins pharmacokinetics (PK) variations to genetic polymorphisms in cytochromes P450 (CYPs) metabolic enzymes.

Objective
This article reviews the association between CYP3A4/5 genetic variations and response to atorvastatin therapy globally, which includes atorvastatin PK, and the risk for adverse reactions, with a hint to the Egyptians.

Methods
Up to March 30, 2022, electronic medical databases like PubMed, Web of Science, MEDLINE, and Egyptian Knowledge Bank (EKB) were searched. All articles that highlighted the relationship between CYP3A4/5 genetic polymorphisms and atorvastatin efficacy/safety profile were included in this review.

Results
Initially, 492 articles were retrieved after an exhaustive search. There were 24 articles included according to the inclusion criteria. Findings of association studies of CYP3A4/5 genetic polymorphisms with response to atorvastatin varied among different ethnicities. CYP3A4*1B was associated with better therapeutic outcomes after atorvastatin therapy in Chileans and vice versa in Americans. Caucasians with myalgia while using atorvastatin were at significant risk of suffering severe muscle damage if they were carriers of CYP3A5*3/*3. As far as we can report for the Egyptian population, the impact of CYP3A4/5 genetic variations on the response to atorvastatin therapy was understudied.

Conclusion
More pharmacogenetic studies amongst diverse populations worldwide, like the Egyptian population, are necessary to detect further atorvastatin-gene interactions.

Graphical Abstract
The risk factors of the 72-h unscheduled return visit admission to emergency department in adults below 50 years old
Authors: Kao Chia-Lung , Chuang Chia-Chang , Hwang Chi-Yuan , Lee Chung-Hsun , Huang Po-Chang , Hong Ming-Yuan , Chi Chih-Hsien 
Published: September 2023

Abstract
Background
An unscheduled return visit (URV) to the emergency department (ED) within 72-h is an indicator of ED performance. An unscheduled return revisit (URV) within 72-h was used to monitor adverse events and medical errors in a hospital quality improvement program. The study explores the potential factors that contribute to URV to the ED within 72-h and the unscheduled return revisit admission (URVA) in adults below 50 years old.

Methods
The case–control study enrolled 9483 URV patients during 2015–2020 in National Cheng-Kung University Hospital. URVA and URV non-admission (URVNA) patients were analyzed. The Gini impurity index was calculated by decision tree (DT) to split the variables capable of partitioning the groups into URVA and URVNA. Logistic regression is applied to calculate the odds ratio (OR) of candidate variables. The α level was set at 0.05.

Results
Among patients under the age of 50, the percentage of females in URVNA was 55.05%, while in URVA it was 53.25%. Furthermore, the average age of URVA patients was 38.20 ± 8.10, which is higher than the average age of 35.19 ± 8.65 observed in URVNA. The Charlson Comorbidity Index (CCI) of the URVA patients (1.59 ± 1.00) was significantly higher than that of the URVNA patients (1.22 ± 0.64). The diastolic blood pressure (DBP) of the URVA patients was 85.29 ± 16.22, which was lower than that of the URVNA (82.89 ± 17.29). Severe triage of URVA patients is 21.1%, which is higher than the 9.7% of URVNA patients. The decision tree suggests that the factors associated with URVA are “severe triage,” “CCI higher than 2,” “DBP less than 86.5 mmHg,” and “age older than 34 years”. These risk factors were verified by logistic regression and the OR of CCI was 2.42 (1.50–3.90), the OR of age was 1.84 (1.50–2.27), the OR of DBP less than 86.5 was 0.71 (0.58–0.86), and the OR of severe triage was 2.35 (1.83–3.03).

Conclusions
The results provide physicians with a reference for discharging patients and could help ED physicians reduce the cognitive burden associated with the diagnostic errors and stress.
Identifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysis
Authors: Zhou Donglin , Zhu Yimin , Jiang Peng , Zhang Tongfu , Zhuang Jianfeng , Li Tao , Qi Linzeng , Wang Yunyan 
Published: September 2023

Abstract
Background
Intracranial aneurysm (IA) is the most common cerebrovascular disease, and subarachnoid hemorrhage caused by its rupture can seriously impede nerve function. Pyroptosis is an inflammatory mode of cell death whose underlying mechanisms involving the occurrence and rupture of IAs remain unclear. In this study, using bioinformatics analysis, we identified the potential pyroptosis-related genes (PRGs) and performed their inflammatory response mechanisms in IAs.

Methods
The mRNA expression matrix of the IA tissue was obtained from the Gene Expression Omnibus database, and 51 PRGs were obtained from previous articles collected from PubMed. The differentially expressed PRGs (DEPRGs) were performed using R software. Subsequently, we performed enrichment analysis, constructed a protein–protein interaction network, performed weighted gene coexpression network analysis (WGCNA) and external validation using another dataset, and identified a correlation between hub genes and immune cell infiltration. Finally, the expression and tissue distribution of these hub genes in IA tissues were detected using Western blotting and immunohistochemical (IHC) staining.

Results
In total, 12 DEPRGs associated with IA were identified in our analysis, which included 11 up-regulated and one down-regulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the DEPRGs were mostly enriched in the NOD-like receptor signaling pathway, interleukin-1 beta production, and the inflammasome complex. Three hub genes, NLRP3, IL1B and IL18, were identified using Cytoscape software and the WGCNA correlation module, and external validation revealed statistically significant differences between the expression of these hub genes in the ruptured and unruptured aneurysm groups (p < 0.05). Furthermore, all AUC values were > 0.75. Immune cell infiltration analysis suggested that the hub genes are related to CD8 T cell, macrophages and mast cells. Finally, IHC staining revealed that the protein levels of these hub genes were higher in ruptured and unruptured IA tissues than in normal tissues (p < 0.05).

Conclusion
The results of bioinformatics analysis showed that pyroptosis is closely related to the formation and rupture of IA, and identified three potential hub genes involved in the pyroptosis and infiltration ofcells. Our findings may improve the understanding of the mechanisms underlying pyroptosis in IA.
Development of an item pool for a patient reported outcome measure of resilience for people living with dementia
Authors: Roberts Jennifer Rhiannon , MacLeod Catherine Anne , Hoare Zoe , Sullivan Mary Pat , Brotherhood Emilie , Stott Joshua , Windle Gill 
Published: September 2023

Abstract
Background and objectives
Policies to support people living with dementia increasingly focus on strengths-based approaches, highlighting the importance of building resilience. This research responds to the lack of a suitable resilience measure for people with dementia. It develops a pool of items to inform a new measure of resilience for this population.

Methods
A conceptual model and associated data informed the item generation of the draft resilience measure. Regular meetings with professionals (n = 7) discussed response-scale formatting, content and face validity, leading to refinement and item reduction. Cognitive interviews with people living with dementia (n = 11) then examined the face and content validity of items and the suitability of response-scale formatting. These two phases informed subsequent revision and further item reduction of the resilience measure.

Results
The first item generation exercise led to 140 items. These were independently assessed by the professionals and this refinement reduced the measure to 63 items across 7 domains of the conceptual model (psychological strengths; practical approaches for adapting to life with dementia; continuing with hobbies, interests and activities; strong relationships with family and friends; peer support and education; participating in community activities; the role of professional support services). Cognitive interviews explored the 63 items with people living with dementia. Detailed feedback led to items removed due to difficulty with (a) understanding (N = 7); (b) answering (n = 11); (c) low preference for that item (n = 6); and (d) presence of a preferred item within a cluster of similar questions (n = 4). Items were amended to enhance clarity/conciseness (n = 19) leading to a final 37-item pool.

Conclusion
Established methods for measurement development included the expertise of people with dementia and led to the generation of a set of items for a new resilience measure that were understandable and acceptable to this target population. This 37-item pool reflects the conceptual understanding of resilience in dementia as being derived across individual, community and societal level resources.
Comprehensive evaluation of the Infinium human MethylationEPIC v2 BeadChip
Authors: Kaur Diljeet , Lee Sol Moe , Goldberg David , Spix Nathan J. , Hinoue Toshinori , Li Hong-Tao , Dwaraka Varun B. , Smith Ryan , Shen Hui , Liang Gangning , Renke Nicole , Laird Peter W. , Zhou Wanding 
Published: September 2023

AbstractInfinium Methylation BeadChips are widely used to profile DNA cytosine modifications in large cohort studies for reasons of cost-effectiveness, accurate quantification, and user-friendly data analysis in characterizing these canonical epigenetic marks. In this work, we conducted a comprehensive evaluation of the updated Infinium MethylationEPIC v2 BeadChip (EPICv2). Our evaluation revealed that EPICv2 offers significant improvements over its predecessors, including expanded enhancer coverage, applicability to diverse ancestry groups, support for low-input DNA down to one nanogram, coverage of existing epigenetic clocks, cell type deconvolution panels, and human trait associations, while maintaining accuracy and reproducibility. Using EPICv2, we were able to identify epigenome and sequence signatures in cell line models of DNMT and SETD2 loss and/or hypomorphism. Furthermore, we provided probe-wise evaluation and annotation to facilitate the use of new features on this array for studying the interplay between somatic mutations and epigenetic landscape in cancer genomics. In conclusion, EPICv2 provides researchers with a valuable tool for studying epigenetic modifications and their role in development and disease.
Coherence dynamics in Simon's quantum algorithm
Authors: Ye Linlin , Wu Zhaoqi , Fei Shao-Ming 
Published: September 2023

Abstract
Quantum coherence plays a pivotal role in quantum algorithms. We study the coherence dynamics of the evolved states in Simon's quantum algorithm based on Tsallis relative α entropy and

norm. We prove that the coherence of the first register and the second register both rely on the dimension N of the state spaces of the n qubit systems, and increase with the increase of N. We show that the oracle operator O does not change the coherence. Moreover, we study the coherence dynamics in Simon's quantum algorithm and prove that overall the coherence is in production when

and in depletion when

.
Community detection from fuzzy and higher-order perspectives
Authors: Xiao Jing , Xu Xiao-Ke 
Published: September 2023

Abstract
Our ability to observe the mesoscale topology of complex networks through community detection has significantly advanced in the past decades. This progress has opened up new frontiers in discovering more sophisticated and meaningful community structures that possess fuzzy and higher-order characteristics. This review provides an overview of two emerging research directions, which are fuzzy and higher-order community detection. It includes related concepts and practical scenarios, mathematical descriptions and latest advancements, as well as current challenges and future directions. Therefore, it will facilitate researchers in swiftly grasping the two emerging fields, offering valuable insights for future development of community detection studies.
SIRT1 and miR-34a-5p Expression in PBMCs as Potential Biomarkers for Patients With Type 2 Diabetes With Cognitive Impairments
Authors: Liu Xiaofeng , Zhao Zhipei , Chen Dengbin , Zhang Zeqin , Lin Xiaozhen , Shen Zhanbo , Lin Qingwen , Fan Kengna , Wang Qi , Zhang Weiqing , Ou Qishui 
Published: September 2023

Abstract

Context
Patients with type 2 diabetes mellitus (T2DM) are at significantly increased risk of Alzheimer disease (AD). However, no biomarkers are available for early identification of patients with T2DM with cognitive impairment (T2DM-CI). Mitochondrial dysfunction is linked to AD. Silent Information Regulator 1 (SIRT1), which is responsible for regulating mitochondrial biogenesis, and its related miRNAs were also altered in AD.

Objective
This study aimed to determine whether mitochondrial function in peripheral blood mononuclear cells (PBMCs) of patients with T2DM-CI was altered and if these alterations could be used as biomarkers.

Methods
A total of 374 subjects were enrolled, including AD, T2DM-CI, T2DM-nCI (T2DM without cognitive impairment), and healthy controls. The mitochondrial function was determined using a commercial assay kit. The mitochondrial DNA (mtDNA) content, the expression of SIRT1, and selected miRNAs in PBMCs were measured by quantitative polymerase chain reaction. The correlations and diagnostic accuracy were assessed using the Spearman correlation coefficient or receiver operating characteristics analysis, respectively.

Results
We found significant changes in mitochondrial function in PBMCs of patients with AD compared with controls (all P &lt; .05), which were not found in T2DM-CI. However, mtDNA content and SIRT1 mRNA expression were lower in PBMCs of patients with T2DM-CI, while miR-34a-5p expression was higher than in patients with T2DM-nCI (all P &lt; .05). A combination of SIRT1 and miR-34a-5p demonstrated excellent discrimination between T2DM-CI and T2DM-nCI (area under the curve = 0.793; sensitivity: 80.01%; specificity: 78.46%). Furthermore, correlation analysis revealed a link between miR-34a-5p expression and hyperglycemia in T2DM-CI.

Conclusion
Our findings revealed that there was an alteration of mitochondria at the peripheral level in patients with T2DM-CI. SIRT1 combined with miR-34a-5p in PBMCs performed well in identifying patients with T2DM-CI and may be a promising biomarker.
New Treatments for Acromegaly in Development
Authors: Gadelha Mônica R , Gadelha Ana Carolina , Kasuki Leandro 
Published: September 2023

Abstract
Acromegaly treatment has greatly evolved in recent decades, but there are still patients whose acromegaly is not controlled with currently available treatments, and there is a need to improve the treatment burden. Fortunately, there are new treatments under development that may increase treatment efficacy and convenience.
The Frequency of Differentiated Thyroid Cancer Recurrence in 2302 Patients With Excellent Response to Primary Therapy
Authors: Pałyga Iwona , Rumian Maciej , Kosel Alicja , Albrzykowski Maciej , Krawczyk Paulina , Kalwat Agata , Gąsior-Perczak Danuta , Walczyk Agnieszka , Kuchareczko Artur , Kopczyński Janusz , Chrapek Magdalena , Góźdź Stanisław , Kowalska Aldona 
Published: September 2023

Abstract

Context
Discrepant data on the recurrence rate of differentiated thyroid cancer (DTC) are reported.

Objective
To evaluate the frequency and risk factors of true recurrence in DTC patients with excellent responses (ExR) to initial therapy.

Methods
A retrospective analysis of the 2302 consecutive DTC patients with ExR to primary therapy, treated during 24 years at single center. The percentage of recurrence and cumulative recurrence rate (CRR) were analyzed. Risk factors for recurrence for patients with papillary thyroid cancer (PTC) were investigated and methods for establishing a diagnosis of recurrence were evaluated.

Results
Of DTC patients, 32 (1.4%) experienced recurrence. PTC patients with recurrence were more likely to have younger age (P = .0182), larger tumor size (P = .0013), lymph node metastases (P = .0013), incomplete resection (P = .0446), higher ATA risk (P = .0002), and had more frequently been treated with 131I (P = .0203). CRRs at 5, 10, 15, 20, and 24 years after surgery were 1.2%, 1.9%, 2.5%, 2.9%, and 2.9%, respectively. The CRRs according to histological type were highest for poorly differentiated thyroid cancer (PDTC), lower for oncocytic (OTC) and follicular thyroid cancer (FTC), and lowest for PTC. Most recurrences occurred within the first 5 years of observation. The most effective method for detecting local recurrence was ultrasonography with fine needle aspiration cytology, and for distant metastases, 18F-FDG PET.

Conclusion
True recurrence is rare in DTC patients. PTC patients with ExR to primary therapy and N0/Nx can be dismissed from oncological follow-up. Despite ExR to primary therapy, DTC patients with N1, and PDTC, OTC, FTC should remain under oncological follow-up.
Spectrum of Adrenal Dysfunction in Hemoglobin E/Beta Thalassemia
Authors: Singha Arijit , Mukhopadhyay Pradip , Ghosh Sujoy 
Published: September 2023

Abstract

Background
Adrenal insufficiency (AI) in hemoglobin E (HbE)/beta thalassemia, including evaluation of mineralocorticoid axis, had not been studied.

Aims and Objectives
In this study, we attempted to evaluate the prevalence of AI in HbE/beta thalassemia and wanted to determine if the prevalence of AI varied according to severity of HbE/beta thalassemia and transfusion requirements.

Methods
In this observational, cross-sectional study, 104 patients with HbE/beta thalassemia were evaluated. Among them, 57 and 47 were transfusion dependent and non-transfusion dependent. According to Mahidol criteria, patients were classified into mild (n = 39), moderate (n = 39), and severe (n = 26) disease. Early morning (8 Am) serum cortisol, plasma ACTH, and plasma aldosterone, renin were measured. Patients with baseline cortisol of 5 to 18 μg/dL underwent both 1 μg and 250 μg short Synacthen test. According to these results, patients were classified as having either normal, subclinical, or overt (primary/secondary) adrenal dysfunction.

Results
Adrenal insufficiency was found in 41% (n = 43). Among them 83.7% (n = 34) had primary AI and 16.3% (n = 9) had secondary AI. Thirty-three patients (31%) with normal or elevated ACTH and with low or normal aldosterone with high renin were diagnosed as having subclinical AI. There was no difference in prevalence of AI between transfusion dependent and non-transfusion dependent (P = .56) nor was there was any difference in prevalence of AI according to disease severity (P = .52).

Conclusion
Adrenal insufficiency is common in HbE/beta thalassemia and is independent of transfusion dependency and disease severity.
Multiple Fractures in an Infant With Hepatoblastoma and Beckwith-Wiedemann Syndrome
Authors: Eimicke Toni , Swartz Jonathan 
Published: September 2023

Abstract
Children with hepatoblastoma have an increased incidence of fractures, but data are limited. Previous reports document an average of 4 fractures per child with hepatoblastoma. We present a severe case of a premature 4-month-old with multiple fractures in the setting of Beckwith-Wiedemann syndrome and hepatoblastoma. Although prematurity is a known risk for metabolic bone disease, it did not entirely explain the severity. Our patient underwent chemotherapy and surgical resection of his hepatoblastoma. Once deemed stable, he received a dose of zoledronic acid (ZA). One month post treatment with ZA, a skeletal survey revealed healing of the rib and femoral fractures and no new fractures. Five months post ZA, the skeletal survey revealed no new fractures and motor development was appropriate. An extensive search revealed scant literature on the rate or cause of pathologic fractures in patients with newly diagnosed hepatoblastoma. A better understanding of fracture risk in this population may guide prevention strategies, screening, and treatment. In our case, prematurity and substantial chronic illness may have compounded the known fracture risk associated with hepatoblastoma and may provide insight into the pathophysiology and prevention of fractures in this setting.
The Physician Anesthesia Workforce in Canada From 1996 to 2018: A Longitudinal Analysis of Health Administrative Data
Authors: Simkin Sarah , Orser Beverley A. , Wilson C. Ruth , McVicar Jason A. , Crozier Mitchell , Bourgeault Ivy Lynn 
Published: September 2023

BACKGROUND:
A robust anesthesia workforce is essential to the provision of safe surgical, obstetrical, and critical care but information describing the physician anesthesia workforce and volume of clinical services delivered in Canada is limited. This study examines the Canadian physician anesthesia workforce, exploring trends in physician characteristics and activity levels over time. Practice patterns of specialist anesthesiologists and family physician anesthetists (FPAs) working in urban and rural communities were of particular interest.

METHODS:
Physicians who provided anesthesia care between 1996 and 2018 were identified using health administrative data from the Canadian Institute of Health Information (CIHI). In addition, data from the Canadian Post-MD Education Registry (CAPER) were used to characterize physicians pursuing postgraduate anesthesia training (1996–2019). Descriptive analyses of physician demographics, training, location, specialty designations, and volume of clinical services were undertaken.

RESULTS:
Between 1996 and 2018, the anesthesia workforce grew 1.8-fold to 3681 physicians, including 536 FPAs. Over the same time, nerve block services increased 7-fold, and payments for other anesthesia services increased 5-fold. The average age of the anesthesiology workforce increased by 2.3 years and the annual retirement rate was 3%. The workforce has become more gender balanced but remains predominantly male (73% in 2018). The proportion of physicians who were trained internationally (about 30%; 38% in rural areas) remained stable (and higher than that in the overall physician workforce). FPAs provided most anesthesia care in rural Canada and their attrition rate was generally 2- to 3-fold higher than specialists. Physicians in the rural anesthesia workforce provided anesthesia services more intensively over time. Relatively few FPAs who left the anesthesia workforce entered full retirement and they instead contributed other medical services to their communities.

CONCLUSIONS:
This study provides foundational information regarding anesthesia workforce capacity over a 22-year period, including insights into demographics, locations of practice, and clinical volumes. The results do not quantify the gap between service capacity and need; however, they support the need for a national workforce strategy to achieve equitable access to sustainable anesthesia services in Canada, particularly for rural communities.