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Aminath Afaa Mohamed,1,2 Juen Kiem Tan,1,2 Michelle Maryanne Tan,3 Ching Soong Khoo,1,2 Wan Nur Nafisah Wan Yahya,1,2 Muhammad Samir Haziq Abd Rahman,2 Rosnah Sutan,2,4 Hui Jan Tan1,2 1Department of Medicine, Faculty of Medicine, National University of Malaysia, Kuala Lumpur, 56000, Malaysia; 2Department of Medicine, Hospital Canselor Tuanku Muhriz, Cheras, Kuala Lumpur, 56000, Malaysia; 3Department of Medicine, Hospital Tengku Ampuan Rahimah, Klang, 41200, Malaysia; 4Department of Community Health, Faculty of Medicine, National University of Malaysia, Kuala Lumpur, 56000, MalaysiaCorrespondence: Hui Jan Tan, Department of Medicine, Faculty of Medicine, National University of Malaysia, Kuala Lumpur, Malaysia, Email tanhuijan@gmail.com; tanhuijan@ukm.edu.myPurpose: Stroke is the second leading cause of global deaths. Post-stroke seizures (PSS) can lead to lasting complications, such as prolonged hospitalizations, increased disability rates, and higher mortality. Our study investigates the associated factors that contribute to post-stroke seizures in patients at a local tertiary hospital.Patients and Methods: We designed a case–control study where patients admitted with PSS were recruited with consent. Controls admitted for stroke without seizure were then included. Suitability based on exclusion criteria was ensured before recording their sociodemographic and clinical data. An EEG was performed and read by two certified neurologists before the data was analyzed.Results: We recruited 180 participants, 90 cases and 90 matched controls. Gender (p=0.013), race (p=0.015), dyslipidemia (p< 0.001), prior stroke (p< 0.031), large artery atherosclerosis (p< 0.001), small vessel occlusions (p< 0.001), blood pressure on presentation (p< 0.028) and thrombolysis administration (p< 0.029) were significantly associated with the occurrence of PSS. An increase in odds of PSS was observed in the male gender (1.974), dyslipidemia (3.480), small vessel occlusions (4.578), and in participants with epileptiform changes on EEG (3.630). Conversely, lower odds of PSS were seen in participants with high blood pressure on presentation (0.505), large artery atherosclerosis (0.266), and those who underwent thrombolysis (0.319).Conclusion: This study emphasized that identifying post-stroke seizures may be aided by EEGs and recognizing at-risk groups, which include males of Chinese descent in Asia, dyslipidemia, small vessel occlusions, those with low to normal blood pressure on presentation, and epileptiform changes in EEGs.Plain Language Summary: The research aims to establish the risk factors associated with post-stroke seizures in an Asian population and their similarity to the Western literature. Our findings highlight the critical risk factors to identify in at-risk patients, which may prompt changes in guidelines in future to enhance patient outcomes and improve the quality of care.Keywords: seizures, stroke, post-stroke epilepsy, epilepsy, electroencephalogram

Background Differential diagnosis of single-nodule pulmonary metastasis (SNPM) and second primary lung cancer (SPLC) in patients with colorectal cancer (CRC) prior to lung surgery is relatively complex. Radiomics is an emerging technique for image information analysis, while it has not yet been applied to construct a differential diagnostic model between SNPM and SPLC in patients with CRC. In the present study, we aimed to extract radiomics signatures from thin-section computed tomography (CT) images of the chest. These radiomics signatures were combined with clinical features to construct a composite differential diagnostic model. Method A total of 91 patients with CRC, including 66 patients with SNPM and 25 patients with SPLC, were enrolled in this study. Patients were randomly assigned to the training cohort (n = 63) and validation cohort (n = 28) at a ratio of 7 to 3. Moreover, 107 radiomics features were extracted from the chest thin-section CT images. The least absolute shrinkage and selection operator (LASSO) regression was used to filter these features, and clinical features were screened by univariate analysis. The screened radiomics and clinical features were combined to construct a multifactorial logistic regression composite model. The receiver operating characteristic (ROC) curves were adopted to evaluate the models, and the corresponding nomograms were created. Results A series of 6 radiomics characteristics was screened by LASSO. After univariate logistic regression analysis, the composite model finally included 4 radiomics features and 4 clinical features. In the training cohort, the area under the curve scores of ROC curves were 0.912 (95% confidence interval [CI]: 0.813-0.969), 0.884 (95% CI: 0.778-0.951), and 0.939 (95% CI: 0.848-0.984) for models derived from radiomics, clinical, and combined features, respectively. Similarly, these values were 0.756 (95% CI: 0.558-0.897), 0.888 (95% CI: 0.711-0.975), and 0.950 (95% CI: 0.795-0.997) in the validation cohort, respectively. Conclusions We constructed a model for differential diagnosis of SNPM and SPLC in patients with CRC using radiomics and clinical features. Moreover, our findings provided a new assessment tool for patients with CRC in the future.

With the improvement in survival of patients with tumors, and continuous advancement of diagnostic technology and treatment modalities, instances of multiple primary malignancies (MPMs) are becoming an increasingly common phenomenon. The occurrence of esophageal-relevant MPMs increases the difficulty of diagnosis and treatment, and the overall prognosis is poor. Esophageal cancer related-MPMs tend to occur in areas such as the head, neck, stomach, and lungs. “Field cancerization” is one theoretical basis for the disease, and chemoradiotherapy, environmental life factors, and gene polymorphism are etiological factors. However, the influence of new therapeutic methods on MPM is still unclear, and the relationship between gene polymorphism and MPMs related to esophageal cancer needs further elucidation. Additionally, there is a lack of unified standards for diagnosis and treatment. Therefore, this study aimed to review the causes, clinical features, and prognostic factors of MPMs related to esophageal cancer.

Objective: It was initially reported that a novel coronavirus (COVID-19) had been identified in Wuhan, China, in December 2019.To date, COVID-19 is still threatening all humanity and has affected the public healthcare system and the world economic situation. Neutrophil-to-lymphocyte ratio (NLR) has also been demonstrated that associated with severity of COVID-19, but little is known about systemic immune-inflammation index (SII) relation with COVID-19. Methods: One hundred and twenty-five patients with diagnosed COVID-19 including non-severe cases (n = 77) and severe cases (n = 48) were enrolled in this study. Each patient of clinical characteristic information, blood routine parameters, and the haemogram-derived ratios were collected, calculated, and retrospectively analyzed. Receiver operating characteristics (ROC) was performed to investigate whether these parameters could be used to the predictive value of patients with severe COVID-19. Results: White blood cell count (WBC), neutrophil count (NEU), red cell volume distribution width (RDW), NLR, Platelet to lymphocyte ratio (PLR), neutrophil-to-platelet ratio (NPR), and SII were significantly higher in the severe groups than in the non-severe group (p

Objective: To explore the effect and the related mechanism of STAT3 inhibitor AG-490 on inhibiting the proliferation of prostate cancer cells. Methods: PC3 cells and DU145 cells were cultured stably and treated with AG-490 to detect the changes in the activity of PC3 cells and DU145 cells. Thirty 6-8 weeks male BALB/c nude mouse were randomly divided into a control group, a DMSO group, and an AG-490 group to detect differences in various indexes . Results: The overexpression of miR-503-5p depends on the activation of STAT3. After treatment with AG-490, The proliferation and invasion of PC3 cells and DU145 cells and the expression of miR-503-5p were all reduced. Luciferase reporter assay demonstrated that the target proteins of miR-503-5p include PDCD4, TIMP-3, and PTEN. After treatment with AG-490, the expression of PDCD4, TIMP-3, and PTEN in cells was significantly up-regulated. IL-6-induced overexpression of miR-503-5p and restored the expression of STAT3, demonstrating the correlation between STAT3 and miR-503-5p. AG-490 can inhibit tumor growth and induce tumor cell apoptosis in the PC3 BALB/c nude mouse xenograft model. Western blotting and immunohistochemical staining showed that the expression levels of STAT3, Ki67, Bcl-2 and MMP-2 in the AG-490 group were significantly reduced, and the expression of PDCD4, TIMP-3 and PTEN increased. Conclusion: AG-490 can inhibit the growth of prostate cancer cells in a miR-503-5p-dependent manner by targeting STAT3. AG-490 is expected to become a new candidate drug for the treatment of prostate cancer.

Background: Pancreatic cancer is an aggressive type of cancer with poor prognosis, short survival rate, and high mortality. Drug resistance is a major cause of treatment failure in the disease. MiR-331-3p has been reported to play an important role in several cancers. We previously showed that miR-331-3p is upregulated in pancreatic cancer and promotes pancreatic cancer cell proliferation and epithelial-to-mesenchymal transition–mediated metastasis by targeting ST7L. However, it is uncertain whether miR-331-3p is involved in drug resistance. Methods: We investigated the relationship between miR-331-3p and pancreatic cancer drug resistance. As part of this, microRNA mimics or inhibitors were transfected into pancreatic cancer cells. Quantitative polymerase chain reaction was used to detect miR-331-3p expression, and flow cytometry was used to detect cell apoptosis. The Cell Counting Kit-8 assay was used to measure the IC50 values of gemcitabine in pancreatic cancer cells. The expression of multidrug resistance protein 1, multidrug resistance-related protein 1, breast cancer resistance protein, β-Catenin, c-Myc, Cyclin D1, Bcl-2, and Caspase-3 was evaluated by Western blotting. Results: We confirmed that miR-331-3p is upregulated in gemcitabine-treated pancreatic cancer cells and plasma from chemotherapy patients. We also confirmed that miR-331-3p inhibition decreased drug resistance by regulating cell apoptosis and multidrug resistance protein 1, multidrug resistance-related protein 1, and breast cancer resistance protein expression in pancreatic cancer cells, whereas miR-331-3p overexpression had the opposite effect. We further demonstrated that miR-331-3p effects in drug resistance were partially reversed by ST7L overexpression. In addition, overexpression of miR-331-3p activated Wnt/β-catenin signaling in pancreatic cancer cells, and ST7L overexpression restored activation of Wnt/β-catenin signaling. Conclusions: Taken together, our data demonstrate that miR-331-3p contributes to drug resistance by activating Wnt/β-catenin signaling via ST7L in pancreatic cancer cells. These data provide a theoretical basis for new targeted therapies in the future.

Osteosarcoma is the most common primary malignant bone tumor in the clinic. It is more common in children and adolescents. It has high malignancy, early metastasis rate, rapid disease progression, and high mortality. Although past years have witnessed the great improvement in the treatments of osteosarcoma, there remains a long way to go. MicroRNAs affect the malignant biological behaviors such as tumor proliferation and metastasis by regulating their target genes. In this study, we investigated the role and mechanism of miR-384 in osteosarcoma. Quantitative real-time polymerase chain reaction assay was performed to detect the expression of miR-384 and insulin-like growth factor binding protein 3 in osteosarcoma tissues and cell lines and established its correlation with osteosarcoma tumor progression and metastasis. To probe whether miR-384 played a tumor suppression role in osteosarcoma, we carried out gain-of-function and loss-of-function assays. Cell Counting Kit-8, cell colony formation, and transwell assays were carried out to determine the cells proliferation and invasion, respectively. Western blot was used to detect the changes of epithelial–mesenchymal transition marker proteins and insulin-like growth factor binding protein 3. MiR-384 was downregulated in osteosarcoma tissues and cell lines. MiR-384 was overexpressed in G292 cells transfected with miR-384 mimics and knocked down in Saos-2 cells with small hairpin RNA targeting miR-384. Ectopic expression of miR-384 inhibited osteosarcoma cell proliferation, colony formation, and invasion. E-cadherin was brought to a decrease whereas N-cadherin and Snail to an increase under the silent expression of miR-384, while overexpression of miR-384 led to an opposite result. MiR-384 could regulate insulin-like growth factor binding protein 3 expression in osteosarcoma. Quantitative polymerase chain reaction and Western blotting results validated that miR-384 knockdown downgrades both messenger RNA and protein levels of insulin-like growth factor binding protein 3 in G292 cells, while miR-384 upregulation exerted an opposite effect in Saos-2 cells. Insulin-like growth factor binding protein 3 was upregulated in osteosarcoma tissues and osteosarcoma cell lines compared with normal ones. Through the bioinformatics database found that the upstream transcriptional regulator of insulin-like growth factor binding protein 3 is MECP2. So miR-384 can directly inhibit MECP2 and then promote the expression of insulin-like growth factor binding protein 3. These results suggested that miR-384 might be a potential therapeutic targets and biomarker in osteosarcoma.

Low-intensity extracorporeal shockwave therapy (Li-ESWT) has been reported as a useful and noninvasive treatment for erectile dysfunction (ED). Systematic review and meta-analysis are utilized to evaluate the efficacy of Li-ESWT by comparing the changes in the International Index of Erectile Function erectile function domain (IIEF-EF) and the Erection Hardness Score (EHS) versus sham therapy in men with ED. A systematic search of the MEDLINE, EMBASE, ClinicalTrials.gov, CBM, CNKI, WANGFANG, and VIP was conducted to obtain randomized controlled trials (RCTs) published in peer-reviewed journals or presented in abstract forms of Li-ESWT for ED treatment from January 2010 to June 2018. If RCTs are published in peer-reviewed literature and IIEF-EF scores and EHS are used to assess erectile function outcomes, they are eligible for inclusion. A meta-analysis was used to summarize the estimates. The meta-analysis included seven RCTs involving 522 participants. The data revealed that men treated with Li-ESWT showed significant improvement in pooled mean IIEF-EF scores from baseline to follow-up compared with sham therapy (MD: 1.99 points; 95% CI [1.35, 2.63]; p < .00001). Changes in the IIEF-EF score increased significantly in the treatment group (MD: 3.62; 95% CI [2.99, 4.25]; p < .00001). The EHS increased significantly in the treatment group in four studies (OR: 16.02; 95% CI [7.93, 32.37]; p < .00001). Patients with moderate and/or severe ED reported better results in mean IIEF scores (MD: 3.95; 95% CI [2.44, 5.46]; p < .00001). In meta-analysis of seven RCTs with men who received Li-ESWT for ED, there was evidence that the IIEF-EF and EHS experienced improvements following Li-ESWT.

Background:. A total of 42 cases of moderate and severe breast ptosis were treated with sequential liposuction modified double ring areola incision surgery (experimental group), and 45 cases were treated with traditional double ring areola incision alone surgery (control group). Methods:. They were followed up for 6 months after the operation. The scar formation and breast ptosis repair were observed, and postoperative complications and patient satisfaction were monitored. Results:. Better results such as improved postoperative breast appearance were achieved in the sequential liposuction modified double ring areola incision group compared with the double ring areola incision alone group. After treatment, the distance between the midpoint of the inframammary fold and the nipple, the distance between the suprasternal fossa, and the nipple of the two groups were lower than those before treatment. The distance between the midpoint of the inframammary fold and the nipple showed no difference between the two experimental groups. The distance between the suprasternal fossa and the nipple of the experimental group were lower compared with the control group. Lower complication rates and higher satisfaction rates were observed in patients treated with sequential liposuction modified double ring areola incision. The patients in the experimental group were more satisfied with breast symmetry, breast shape, and breast size than those in the control group. Conclusions:. The treatment with sequential liposuction modified double ring areola incision was effective and safe compared with double ring areola incision alone. It could improve the breast shape of patients, improve the satisfaction of patients, and reduce the occurrence of complications.

Background: Healthcare workers face burnout from high job demands and prolonged working conditions. While mental health services are available, barriers to access persist. Evidence suggests digital platforms can enhance accessibility. However, there is a lack of systematic reviews on the effectiveness of digital mental health interventions (DMHIs) for healthcare professionals. This review aims to synthesize evidence on DMHIs' effectiveness in reducing burnout, their acceptability by users, and implementation lessons learned., Method: This Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA)-guided review included 12 RCTs on DMHIs for healthcare professionals, published before 31 May 2024. The primary focus was on burnout, with secondary outcomes related to mental health and occupation. Quality appraisal used Cochrane risk of bias tools. A narrative synthesis explored DMHIs' effectiveness, acceptability, utilization, and implementation lessons., Results: Significant improvements in mental health outcomes were observed in 10 out of 16 RCTs. Burnout and its constructs showed significant improvement in five RCTs. Studies that measured the acceptability of the interventions reported good acceptability. Factors such as attrition, intervention design and duration, cultural sensitivities, flexibility and ease of use, and support availability were identified as key implementation considerations., Conclusions: Web-based DMHIs positively impact burnout, mental health, and occupational outcomes among healthcare professionals, as shown in most RCTs. Future research should enhance DMHIs' effectiveness and acceptability by addressing identified factors. Increasing awareness of DMHIs' benefits will foster acceptance and positive attitudes. Lessons indicate that improving user engagement and effectiveness requires a multifaceted approach., (© The Author(s) 2024.)

Background: Delirium is a prevalent yet underdiagnosed disorder characterized by acute cognitive impairment. Various screening tools are available, including the Confusion Assessment Method (CAM) and 4 A's test (4AT). However, the results of these assessments may vary among raters. Therefore, we investigated the objective use of electroencephalography (EEG) in delirium and its clinical associations and predictive value., Method: This cross-sectional observational study was conducted at Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan, Malaysia, from April 2021 to April 2023. This study included patients aged ≥18 years with a preliminary diagnosis of delirium. Demographic and clinical data were collected along with EEG recordings evaluated by certified neurologists to classify abnormalities and compare the associated factors between patients with delirium with or without EEG abnormalities., Results: One hundred and twenty patients were recruited, with 80.0% displaying EEG abnormalities, mostly generalized slowing (moderate to severe) and primarily generalized slowing (mild to severe), and were characterized by theta activity. Age was significantly associated with EEG abnormalities, with patients aged 75 and older demonstrating the highest incidence (88.2%). The CAM scores were strongly correlated with EEG abnormalities (r = 0.639, P < 0.001) and was a predictor of EEG abnormalities ( P < 0.012), indicating that EEG can complement clinical assessments for delirium. The Richmond Agitation and Sedation Scale (RASS) scores (r = -0.452, P < 0.001) and Barthel index (BI) (r = -0.582, P < 0.001) were negatively correlated with EEG abnormalities. Additionally, a longer hospitalization duration was associated with EEG abnormalities (r = 0.250, P = 0.006) and emerged as a predictor of such changes ( P = 0.030)., Conclusion: EEG abnormalities are prevalent in patients with delirium, particularly in elderly patients. CAM scores and the duration of hospitalization are valuable predictors of EEG abnormalities. EEG can be an objective tool for enhancing delirium diagnosis and prognosis, thereby facilitating timely interventions., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background and Objectives: The role of body mass index (BMI) in Parkinson disease (PD) is unclear. Based on the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in PD (Courage-PD) consortium, we used 2-sample Mendelian randomization (MR) to replicate a previously reported inverse association of genetically predicted BMI with PD and investigated whether findings were robust in analyses addressing the potential for survival and incidence-prevalence biases. We also examined whether the BMI-PD relation is bidirectional by performing a reverse MR., Methods: We used summary statistics from a genome-wide association study (GWAS) to extract the association of 501 single-nucleotide polymorphisms (SNPs) with BMI and from the Courage-PD and international Parkinson Disease Genomics Consortium (iPDGC) to estimate their association with PD. Analyses are based on participants of European ancestry. We used the inverse-weighted method to compute odds ratios (OR IVW per 4.8 kg/m 2 [95% CI]) of PD and additional pleiotropy robust methods. We performed analyses stratified by age, disease duration, and sex. For reverse MR, we used SNPs associated with PD from 2 iPDGC GWAS to assess the effect of genetic liability toward PD on BMI., Results: Summary statistics for BMI are based on 806,834 participants (54% women). Summary statistics for PD are based on 8,919 (40% women) cases and 7,600 (55% women) controls from Courage-PD, and 19,438 (38% women) cases and 24,388 (51% women) controls from iPDGC. In Courage-PD, we found an inverse association between genetically predicted BMI and PD (OR IVW 0.82 [0.70-0.97], p = 0.012) without evidence for pleiotropy. This association tended to be stronger in younger participants (≤67 years, OR IVW 0.71 [0.55-0.92]) and cases with shorter disease duration (≤7 years, OR IVW 0.75 [0.62-0.91]). In pooled Courage-PD + iPDGC analyses, the association was stronger in women (OR IVW 0.85 [0.74-0.99], p = 0.032) than men (OR IVW 0.92 [0.80-1.04], p = 0.18), but the interaction was not statistically significant ( p -interaction = 0.48). In reverse MR, there was evidence for pleiotropy, but pleiotropy robust methods showed a significant inverse association., Discussion: Using an independent data set (Courage-PD), we replicate an inverse association of genetically predicted BMI with PD, not explained by survival or incidence-prevalence biases. Moreover, reverse MR analyses support an inverse association between genetic liability toward PD and BMI, in favor of a bidirectional relation.

Background: The impact of adverse childhood experiences (ACE, e.g., abuse, neglect, and/or household dysfunction experienced before the age of 18) and resilience on risk for cardiovascular disease (CVD) has not previously been investigated in adult survivors of childhood cancer., Methods: We conducted a nested case-control study among long-term, adult-aged survivors of childhood cancer from the Childhood Cancer Survivor Study. Self-report questionnaires ascertained ACEs and resilience, and scores were compared between cases with serious/life-threatening CVD and controls without CVD matched on demographic and cardiotoxic treatment factors., Results: Among 95 cases and 261 controls, the mean ACE score was 1.4 for both groups; 53.4% of survivors endorsed ≥1 ACE. No association was observed between ACEs or resilience and CVD in adjusted models., Conclusions: ACEs and resilience do not appear to contribute to CVD risk for adult survivors of childhood cancer with cardiotoxic treatment exposures., Impact: Although not associated with CVD in this population, ACEs are associated with serious health issues in other populations. Therefore, future studies could investigate the effects of ACEs on other health outcomes affecting childhood cancer survivors., (©2024 American Association for Cancer Research.)

Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10 -12 , OR = 1.27) and APOE (rs6857; p = 1.31 × 10 -12 , OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10 -8 , OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex., Competing Interests: Declaration of interests O.A.A. has received speakers’ honoraria from Janssen, Lundbeck, and Sunovion and is a consultant to Cortechs.ai. C.C. received research support from GSK and EISAI. The funders of the study had no role in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. C.C. is a member of the advisory board of Vivid Genomics and Circular Genomics. M.A.N. and H.L.L. hold part of a competitive contract awarded to Data Tecnica International LLC by the National Institutes of Health to support open science research. M.A.N. currently serves on the scientific advisory board for Character Bio Inc. and Neuron23 Inc. I.R.M. receives license royalties for patent related to PGRN therapy and is a member of the scientific advisory committee for Prevail Therapeutics. H.R.M. is employed by UCL. In the last 12 months he reports paid consultancy from Roche, Aprinoia, AI Therapeutics, and Amylyx; lecture fees/honoraria from BMJ, Kyowa Kirin, and Movement Disorders Society; and research grants from Parkinson’s UK, Cure Parkinson’s Trust, PSP Association, Medical Research Council, and the Michael J. Fox Foundation. H.R.M. is a co-applicant on a patent application related to C9ORF72—Method for diagnosing a neurodegenerative disease (PCT/GB2012/052140). R.P. has received honoraria for advisory boards and speaker engagements from Roche, EISAI, Eli Lilly, Biogen, Janssen-Cilag, Astra Zeneca, Schwabe, Grifols, Novo Nordisk, and Tabuk. R.S.-V. served in advisory board meetings for Wave Life Sciences, Ionis, and Novo Nordisk; has received personal fees for participating in educational activities from Janssen, Roche Diagnostics, and Neuraxpharm; and has received funding to her institution for research projects from Biogen and Sage Pharmaceuticals. S.W.S. received research support from Cerevel Therapeutics and is a member of the scientific advisory board of the Lewy Body Dementia Association and the Multiple System Atrophy Coalition. J.S.Y. serves on the scientific advisory board for the Epstein Family Alzheimer’s Research Collaboration. J.H. does consulting and gives talks for Eli-Lilly, Roche, and Eisai and is on the Ceracuity advisory board., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Addressing the challenge of understanding how cellular interfaces dictate the mechanical resilience and adhesion of archaeal cells, this study demonstrates the role of the surface layer (S-layer) in methanogenic archaea. Using a combination of atomic force microscopy and single-cell force spectroscopy, we quantified the impact of S-layer disruption on cell morphology, mechanical properties, and adhesion capabilities. We demonstrate that the S-layer is crucial for maintaining cell morphology, where its removal induces significant cellular enlargement and deformation. Mechanical stability of the cell surface is substantially compromised upon S-layer disruption, as evidenced by decreased Young's modulus values. Adhesion experiments revealed that the S-layer primarily facilitates hydrophobic interactions, which are significantly reduced after its removal, affecting both cell-cell and cell-bubble interactions. Our findings illuminate the S-layer's fundamental role in methanogen architecture and provide a chemical understanding of archaeal cell surfaces, with implications for enhancing methane production in biotechnological applications.

Background: Although socio-environmental factors are known to contribute to the maintenance of smoking behavior, few studies have examined the impact of family functioning on smoking during pregnancy., Objective: The current study examined the relationship between perceptions of family functioning and smoking during pregnancy., Methods: Pregnant women ( N  = 345, 59% ethnic/racial minority) completed the Family Assessment Device, a gold-standard assessment examining perceptions of family functioning in seven domains. Multinomial logistic regressions analyzed associations between clinically determined suboptimal levels of family functioning by domain and smoking status during pregnancy (smoking, ≥28 continuous days quit, nonsmoking), with stratified analyses exploring ethnic/racial differences (non-Hispanic/White vs. racial/ethnic minority)., Results: Participants who reported suboptimal levels of family functioning in domains of Affective Involvement , Affective Responsiveness , Behavioral Control , and Roles were significantly more likely to have been smoking than nonsmoking during pregnancy. Stratified analyses revealed differing effects by ethnic/racial identity, with perceptions of Roles remaining the only significant effect on smoking outcomes for both groups. No significant effects were found regarding the impact of family functioning on whether participants were smoking vs. quit during pregnancy., Conclusions: Suboptimal family functioning may contribute to smoking during pregnancy, but effects may differ based on domain of family functioning and by ethnic/racial identity.

Background and Objectives: Self-perception of aging is an important psychosocial factor that can influence quality of life in older age. This review aimed to synthesize findings on the association between self-perception of aging and quality of life among older adults aged 60 and above., Research Design and Methods: A systematic search was conducted in 4 electronic databases (Ovid Medline, PsycInfo, CINAHL, and Web of Science). Studies conducted in English and including measures on the perception of aging and quality of life were included in this review. A total of 32 observational studies (21 cross-sectional, 8 longitudinal, 2 mixed-method, and 1 qualitative) met the inclusion criteria. Outcomes reported in the included studies were quality of life, physical health and functioning, psychological health, mental health, and general well-being., Results: Overall, 20 quantitative studies indicated a strong association between positive perception of aging and increased quality of life. Similarly, 9 quantitative studies demonstrated that negative perception of aging is associated with lower quality of life. Results of the mixed-method and qualitative studies indicated that older adults with higher morale and good physical capability had more positive perceptions of health., Discussion and Implications: These results suggest that promoting a positive perception of aging and a self-care attitude would help to enhance older adults' quality of life and should be incorporated into future health promotions and interventions., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objective: Half of the patients with acute large artery occlusion (LAO) have poor outcomes after endovascular treatment (EVT). Early complications such as cerebral edema and symptomatic intracranial hemorrhage (sICH) can lead to early neurological deterioration (END), which correlates with hemodynamics. This study aimed to identify the hemodynamic predictors of END and outcomes in LAO patients after EVT., Methods: A total of 76 patients with anterior circulation LAO who underwent EVT and received transcranial Doppler (TCD) monitoring were included. Bilateral middle cerebral artery (MCA) blood flow velocities (BFVs) were measured repeatedly within 1 week. Mean flow velocities (MFV) and MFV index (ipsilateral MFV/contralateral MFV) were calculated. The primary outcome was the incidence of END within 72 h. The secondary outcome was the functional outcome at 90 days-a good outcome was defined as a modified Rankin scale (mRS) score of 0-2, while a poor outcome was defined as an mRS score of 3-6., Results: A total of 13 patients (17.1 %) experienced END within 72 h, including 5 (38.5 %) with cerebral edema, 5 (38.5 %) with sICH, and 3 (23.0 %) with infarct progression. Multivariable logistic regression analysis showed that a higher 24 h MFV index was independently associated with END (aOR 10.5; 95 % CI 2.28-48.30, p = 0.003) and a poor 90-day outcome (aOR 5.10; 95 % CI 1.38-18.78, p = 0.014). The area under the receiver operating characteristic (ROC) curve (AUC) of the 24 h MFV index for predicting END was 0.807 (95 % CI 0.700-0.915, p = 0.0005), the sensitivity was 84.6 %, and the specificity was 66.7 %. At the 1-week TCD follow-up, patients who had poor 90-day outcomes showed significantly higher 1-week iMFV [73.5 (58.4-99.0) vs. 57.7 (45.3-76.3), p = 0.004] and MFV index [1.24 (0.98-1.57) vs.1.0 (0.87-1.15) p = 0.007]. A persistent high MFV index (PHMI) was independently associated with a poor outcome (aOR 7.77, 95 % CI 1.81-33.3, p = 0.006)., Conclusion: TCD monitoring within 24 h after EVT in LAO patients can help predict END, while dynamic follow-up within 1 week is valuable in predicting clinical outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Breast cancer (BC) screening uptake in Malaysia is low and a high number of cases present at a late stage. Community navigation and mobile health (mHealth) may increase screening attendance, particularly by women from rural communities. This randomized controlled study evaluated an intervention that used mHealth and community health workers to educate women about BC screening and navigate them to clinical breast examination (CBE) services in the context of the COVID-19 pandemic., Methods: Women aged 40-74 years, from Segamat, Malaysia, with a mobile phone number, who participated in the South East Asian Community Observatory health survey, (2018) were randomized to an intervention (IG) or comparison group (CG). The IG received a multi-component mHealth intervention, i.e. information about BC was provided through a website, and telephone calls and text messages from community health workers (CHWs) were used to raise BC awareness and navigate women to CBE services. The CG received no intervention other than the usual option to access opportunistic screening. Regression analyses were conducted to investigate between-group differences over time in uptake of screening and variable influences on CBE screening participation., Results: We recruited 483 women in total; 122/225 from the IG and 144/258 from the CG completed the baseline and follow-up survey. Uptake of CBE by the IG was 45.8% (103/225) whilst 3.5% (5/144) of women from the CG who completed the follow-up survey reported that they attended a CBE during the study period (adjusted OR 37.21, 95% CI 14.13; 98.00, p<0.001). All IG women with a positive CBE attended a follow-up mammogram (11/11). Attendance by IG women was lower among women with a household income ≥RM 4,850 (adjusted OR 0.48, 95% CI 0.20; 0.95, p = 0.038) compared to participants with a household income

Background: Vitamin D deficiency among adult people with epilepsy (PWE) is scarcely studied, despite its essential role in bone health and maintaining homeostasis. Several studies have studied the relationship between factors related to epilepsy and vitamin D metabolism. We aim to investigate this in our multi-ethnic society., Methods: This was a single-center cross-sectional study. We recruited 159 participants diagnosed with epilepsy on antiseizure medications (ASMs). We included those aged 18 years and above, excluding patients with long-term medical conditions that would affect vitamin D metabolism. Sociodemographic data and details of epilepsy were collated. Venous sampling was performed to analyze the levels of albumin-corrected calcium, phosphate, alkaline phosphatase, and 25-hydroxyvitamin D3 [25(OH)D]. Serum 25(OH)D level is defined as deficient (<20 ng/ml), insufficient (20-29 ng/ml), and sufficient (≥30 ng/ml)., Results: The study reported that 73 (45.9%) participants had vitamin D deficiency, 38 (23.9%) had vitamin D insufficiency, and 48 (30.2%) patients had sufficient vitamin D levels. The predictors identified were PWE aged 18 to 44 years old (p = 0.001), female gender (OR 3.396, p = 0.002), and ethnicity (p < 0.001), specifically Malay and Chinese. However, no significant association was identified between types of ASMs, serum calcium, or the prevalence of vitamin D deficiency., Conclusion: Vitamin D deficiency among PWE is prevalent in our local population, suggesting that regular screening should be considered for those at risk. Early identification would allow intervention to reduce the risk of future complications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have seemed to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose of Review: This review aims to elucidate the limitations of diagnosing metabolic syndrome in adolescents as well as challenges and opportunities in the identification and reduction of cardiometabolic risk in this population., Recent Findings: There are multiple criticisms of how we define and approach obesity in clinical practice and scientific research, and weight stigma further complicates the process of making and communicating weight-related diagnoses. While the goal of diagnosing and managing metabolic syndrome in adolescents would be to identify individuals at elevated future cardiometabolic risk and intervene to reduce the modifiable component of this risk, there is evidence that identifying cardiometabolic risk factor clustering may be more useful in adolescents than establishing a cutoff-based diagnosis of metabolic syndrome. It has also become clear that many heritable factors and social and structural determinants of health contribute more to weight and body mass index than do individual behavioral choices about nutrition and physical activity. Promoting cardiometabolic health equity requires that we intervene on the obesogenic environment and mitigate the compounding effects of weight stigma and systemic racism. The existing options to diagnose and manage future cardiometabolic risk in children and adolescents are flawed and limited. While striving to improve population health through policy and societal interventions, there are opportunities to intervene at all levels of the socioecological model in order to decrease future morbidity and mortality from the chronic cardiometabolic diseases associated with central adiposity in both children and adults. More research is needed to identify the most effective interventions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Many upper-middle-income countries (UMICs), including Malaysia, continue to face low breast cancer (BC) screening rates and patients with delayed presentation of BC. This study investigated the role of beliefs about BC and use of screening (e.g. beliefs about whether or not screening reduced the possibility of dying from BC)., Methods: A nationwide cross-sectional study was conducted in which a total of 813 women (aged ≥ 40 years old) were randomly selected and surveyed using the validated Awareness and Beliefs about Cancer (ABC) measure. The association between BC screening use, sociodemographic characteristics, and negative beliefs about BC screening were analysed using stepwise Poisson regressions., Results: Seven out of ten Malaysian women believed that BC screening was necessary only when experiencing cancer symptoms. Women > 50 years and from households with more than one car or motorcycle were 1.6 times more likely to attend a mammogram or a clinical breast examination (mammogram: Prevalence Ratio (PR) = 1.60, 95% Confidence Interval (CI) = 1.19-2.14, Clinical Breast Examination (CBE): PR = 1.61, 95% CI = 1.29-1.99). About 23% of women expected to feel anxious about attending BC screening, leading them to avoid the procedure. Women who held negative beliefs about BC screening were 37% less likely to attend a mammogram (PR = 0.63, 95% CI = 0.42-0.94) and 24% less likely to seek a CBE (PR = 0.75, 95% CI = 0.60-0.95)., Conclusions: Public health strategies or behaviour interventions targeting negative beliefs about BC screening among Malaysian women may increase uptake and reduce late presentation and advanced-stage cancer. Insights from the study suggest that women under 50 years, in the lower income group without a car or motorcycle ownership, and of Malay or Indian ethnicity (compared to Chinese-Malay) are more likely to hold beliefs inhibiting BC screening., (© 2023. Crown.)

Individuals from communities with a low socioeconomic status have the highest rates of tobacco use but are less likely to receive assistance with quitting. Community health workers (CHWs) are well-positioned to engage these communities; however, CHWs face barriers in receiving relevant tobacco cessation training. The objective of this study was to conduct a mixed methods needs assessment to describe tobacco practices and the desire for training among CHWs. After incorporating CHW feedback, we developed a needs assessment survey to understand knowledge, practices, and attitudes about tobacco cessation in Chicago, IL. CHWs (N = 23) recruited from local community-based organizations completed the survey online or in-person. We then conducted a focus group with CHWs (N = 6) to expand upon the survey and used the Framework Method to analyze the qualitative data. CHWs reported that their clients had low incomes, low literacy levels, and high smoking rates (e.g., "99%" of patients). About 73.3% reported discussing tobacco use during visits, but fewer reported that they had provided cessation advice (43%) or intervened directly (9%). CHWs described high variability in their work environments (e.g., location, duration, content of visits, etc.) and greater continuity of care. CHWs discussed that existing training on how to conduct tobacco interventions is ineffective, because of its stand-alone design. Our findings illustrate how CHWs adapt to their clients' needs, and that the currently available "gold-standard" cessation curricula are incompatible with the training needs and flexible care delivery model of CHWs. A curriculum tailored to the CHW experience is needed to maximize the strengths of the CHW care model by training CHWs to adaptively intervene regarding tobacco use in their highly burdened patients.

Childhood and adolescent and young adult (AYA) cancer survivors experience poor health outcomes in adulthood. Adverse childhood experiences (ACEs) also portend poor health outcomes for the general population. Resilience can mitigate effects of ACEs. We examined the feasibility of assessing ACEs and resilience in childhood and AYA cancer patients. We also described occurrences of ACEs, resilience, and poor health outcomes. Of 52 participants, most rated their study experience favorably, with privacy in answering sensitive questions. Half reported ACEs, and those with ACEs had lower resilience; X 2 (3, N = 52) = 9.4, p = .02. Further investigations of ACEs and resilience in larger cohorts are warranted to delineate associations with long-term health outcomes., (© 2022 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: Despite the importance of advance care planning (ACP), a process that optimizes future medical treatment and end-of-life care, for at-risk populations, rates of patient-provider ACP conversations are extremely low among Black women with breast cancer. Community health workers (CHWs) are well-positioned to support patients in engaging in ACP conversations with their providers; yet research on integrating CHWs to promote ACP is scant. The current study examined multilevel facilitators and barriers to successful ACP conversations among Black women from the perspective of providers and CHWs who serve this community., Methods: Providers and CHWs were recruited from an academic medical center in a large urban city. Retrospective qualitative data on barriers and facilitators to ACP conversations, as well as CHWs' training needs, were collected from two focus groups (N = 5 providers, N = 5 CHWs) and one individual interview (N = 1 provider), and transcribed and coded for themes., Results: All providers reported working primarily with Black patients, and identified stigma and time constraints as major barriers to ACP discussions; they also identified the structural barriers and injustices that their patients face during medical care. CHWs reported having a trusted relationship with their patients and flexibility in their care that would allow for ongoing ACP conversations, discussing their ability to serve as a bridge between the patient and provider. However, CHWs discussed that they lacked the tools and skills to have ACP conversations, largely because existing formal trainings in ACP are cost prohibitive., Discussion: Competing priorities of the provider to discuss/treat the patient's disease and medical mistrust were major barriers to successful ACP conversations among Black women with breast cancer, leading to ACP completion occurring late in treatment. CHWs are uniquely qualified to overcome multilevel barriers to ACP and establish trusting relationships with patients in order to facilitate earlier and ongoing communication between patients and providers.

Objective: To determine the proportion of adults with hypertension who reported: (i) having been previously diagnosed with hypertension; (ii) taking blood pressure-lowering medication; and (iii) having achieved hypertension control, in five health and demographic surveillance system sites across five countries in Asia., Methods: Data were collected during household surveys conducted between 2016 and 2020 in the five surveillance sites in Bangladesh, India, Indonesia, Malaysia and Viet Nam. We defined hypertension as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg or taking blood pressure-lowering medication. We defined hypertension control as systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg. We disaggregated hypertension awareness, treatment and control by surveillance site, and within each site by sex, age group, education, body mass index and smoking status., Findings: Of 22 142 participants, 11 137 had hypertension (Bangladesh: 211; India: 487; Indonesia: 1641; Malaysia: 8164; and Viet Nam: 634). The mean age of participants with hypertension was 60 years (range: 19-101 years). Only in the Malaysian site were more than half of individuals with hypertension aware of their condition. Hypertension treatment ranged from 20.8% (341/1641; 95% CI: 18.8-22.8%) in the Indonesian site to 44.7% (3649/8164; 95% CI: 43.6-45.8%) in the Malaysian site. Less than one in four participants with hypertension had achieved hypertension control in any site. Hypertension awareness, treatment and control were generally higher among women and older adults., Conclusion: While hypertension awareness and treatment varied widely across surveillance sites, hypertension control was low in all sites., ((c) 2022 The authors; licensee World Health Organization.)

Hypertension might be a contributing factor of mental illness. The aim of this study was to investigate the association between different levels of hypertension care and mental distress among hypertensive individuals in Malaysia. We constructed a hypertension care cascade using data of 6531 hypertensive individuals aged ≥ 35 years that were collected as part of the community health survey conducted in 2013 in the South East Asia Community Observatory. We examined the association between the status of hypertension care and mental distress using multiple logistic regressions. Respondents who had not been screened for hypertension and those who had uncontrolled blood pressure (BP) had higher odds of depression, anxiety and, stress compared to those who had been screened and those who had controlled BP, respectively. Respondents who were not taking antihypertensive medication had lower odds of depression and anxiety compared to those who were on medication. There was an association between different levels of hypertension care and mental distress. The application of a hypertension care cascade may help improve the provision of mental health support in primary care clinics. Specific mental health interventions could be provided for patients with particular needs along the cascade., (© 2022. The Author(s).)

Background: Cancer screening provision in resource-constrained settings tends to be opportunistic, and uptake tends to be low, leading to delayed presentation and treatment and poor survival., Objective: The aim of this study was to identify, review, map, and summarize findings from different types of literature reviews on the use of mobile health (mHealth) technologies to improve the uptake of cancer screening., Methods: The review methodology was guided by the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). Ovid MEDLINE, PyscINFO, and Embase were searched from inception to May 2021. The eligible criteria included reviews that focused on studies of interventions that used mobile phone devices to promote and deliver cancer screening and described the effectiveness or implementation of mHealth intervention outcomes. Key data fields such as study aims, types of cancer, mHealth formats, and outcomes were extracted, and the data were analyzed to address the objective of the review., Results: Our initial search identified 1981 titles, of which 12 (0.61%) reviews met the inclusion criteria (systematic reviews: n=6, 50%; scoping reviews: n=4, 33%; rapid reviews: n=1, 8%; narrative reviews: n=1, 8%). Most (57/67, 85%) of the interventions targeted breast and cervical cancer awareness and screening uptake. The most commonly used mHealth technologies for increasing cancer screening uptake were SMS text messages and telephone calls. Overall, mHealth interventions increased knowledge about screening and had high acceptance among participants. The likelihood of achieving improved uptake-related outcomes increased when interventions used >1 mode of communication (telephone reminders, physical invitation letters, and educational pamphlets) together with mHealth., Conclusions: mHealth interventions increase cancer screening uptake, although multiple modes used in combination seem to be more effective., (©Désirée Schliemann, Min Min Tan, Wilfred Mok Kok Hoe, Devi Mohan, Nur Aishah Taib, Michael Donnelly, Tin Tin Su. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 15.08.2022.)

Background: The rising prevalence of food allergy reported in the United States, UK, and Australia may be attributable to the rise in peanut allergy prevalence. The food allergy prevalence in other parts of the world such as Asia is, however, less well documented., Objective: This study aimed to evaluate the prevalence of cow's milk, egg, and peanut allergies in a general population of Singaporean children below 30 months of age., Methods: A total of 4,115 children from the general population who attended well-baby visits between 2011 and 2015 completed standardized questionnaires to elicit a convincing history of food allergy to estimate the population prevalence of food allergies., Results: The prevalence of a convincing history of cow's milk allergy was 0.51% (95% confidence interval [CI], 0.3-0.7), hen's egg allergy 1.43% (95% CI, 1.1-1.8), and peanut allergy 0.27% (95% CI, 0.12-0.42). Of the 15 of 59 children with a convincing history of hen's egg allergy who consented, 12 (80%) had corroborative positive skin prick tests., Conclusion: The prevalence of food allergy, in particular peanut allergy, in children below 2 years of age is lower in this South East Asian population than reported in Western cohorts. Further research should focus on deciphering differential risk factors for food allergy across different geographical locations., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2022. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Effective containment of the COVID-19 pandemic requires rapid and accurate detection of the pathogen. Polymerase chain reaction (PCR) remains the gold standard for COVID-19 confirmation. In this article, we report the performance of a cost-effective modular microfluidic reverse transcription (RT)-PCR and RT-loop mediated isothermal amplification (RT-LAMP) platform, Epidax®, for the point-of-care testing and confirmation of SARS-CoV-2. This platform is versatile and can be reconfigured either for screening using endpoint RT-PCR or RT-LAMP tests or for confirmatory tests using real-time RT-PCR. Epidax® is highly sensitive and detects as little as 1 RNA copy per µL for real-time and endpoint RT-PCR, while using only half of the reagents. We achieved comparable results with those of a commercial platform when detecting SARS-CoV-2 viruses from 81 clinical RNA extracts. Epidax® can also detect SARS-CoV-2 from 44 nasopharyngeal samples without RNA extraction by using a direct RT-PCR assay, which shortens the sample-to-answer time to an hour with minimal user steps. Furthermore, we validated the technology using an RT-LAMP assay on 54 clinical RNA extracts. Overall, our platform provides a sensitive, cost-effective, and accurate diagnostic solution for low-resource settings., Competing Interests: Conflict of interestC.T.L., P.Q.M.N., M.W., A.Y.L., G.M.X., and A.A.S.B., along with others, have filed a patent application on the technology described here., (© The Author(s) 2022.)

Smoking cessation is associated with decreases in C-reactive protein (CRP), a biomarker of systemic inflammation and cancer risk; yet CRP levels remain higher long-term in individuals who quit vs. those who never smoked. While non-Hispanic, Black/African American (NHB) have higher levels of CRP vs. non-Hispanic, White/Caucasian (NHW) adults, the association between CRP and race has not been examined in individuals with smoking history. Utilizing longitudinal data from the Health and Retirement Study (HRS), the current study examined the effects of race and smoking history on CRP in older adults. NHB (n = 242) and NHW (n = 1529) participants completed HRS assessments in 2006, 2010, and 2014. Dried blood spots collected at each wave were assayed for CRP. Linear mixed models were used to examine the effect of race and smoking history on CRP across waves - controlling for sociodemographics, physical activity, body mass index (BMI), and current smoking. Overall, results showed no significant effects of race or current smoking on CRP; rather age, sex, education, BMI, physical activity, smoking history, and time × race predicted CRP ( p s<.04). However, while age, sex, education, BMI, physical activity, and smoking history were also predictive of CRP in NHWs ( p s<.04) in race-stratified models, only BMI was a significant predictor of CRP in NHBs ( p =.012). BMI may be important in explaining inflammation-related disease risk in NHBs with a history of smoking. NHBs may not experience the same reductions in CRP with smoking cessation as NHWs - potentially contributing to tobacco-related health disparities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Health care organizations have struggled to establish par levels of risk management personnel needed to effectively accomplish risk management functions. This study set out to determine whether a par level staffing model could be established utilizing a nonclinical role to enable the clinical risk manager to focus on key risk management core functions, therefore enhancing risk management department efficacy. Utilizing a model published by Howard and Felton, Trinity Health Insurance and Risk Management Services (IRMS) evaluated risk management staffing according to our core functions and workload and determined recommended risk management staffing levels for our organization. Eighteen Risk Managers from 13 acute care hospitals participated in a 2-week time study documenting time spent and estimated time needed to complete core risk management functions. By quantifying the time needed to complete risk management core functions and evaluating which activity could best be completed by specific roles, we have established both a recommended baseline staffing level of one risk manager FTE per 6650 monthly average adjusted patient days (APD), as well as a work distribution model of 70% clinical and 30% nonclinical split of risk management FTEs for our hospitals. Organizations can similarly evaluate their staffing according to their core functions and workload., (© 2022 American Society for Healthcare Risk Management of the American Hospital Association.)

Objectives: To explore the genetics of four Parkinson's disease (PD) subtypes that have been previously described in two large cohorts of patients with recently diagnosed PD. These subtypes came from a data-driven cluster analysis of phenotypic variables., Methods: We looked at the frequency of genetic mutations in glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 against our subtypes. Then we calculated Genetic Risk Scores (GRS) for PD, multiple system atrophy, progressive supranuclear palsy, Lewy body dementia, and Alzheimer's disease. These GRSs were regressed against the probability of belonging to a subtype in the two independent cohorts and we calculated q-values as an adjustment for multiple testing across four subtypes. We also carried out a Genome-Wide Association Study (GWAS) of belonging to a subtype., Results: A severe disease subtype had the highest rates of patients carrying GBA mutations while the mild disease subtype had the lowest rates (p=0.009). Using the GRS, we found a severe disease subtype had a reduced genetic risk of PD (p=0.004 and q=0.015). In our GWAS no individual variants met genome wide significance (<5×10e-8) although four variants require further follow-up, meeting a threshold of <1×10e-6., Conclusions: We have found that four previously defined PD subtypes have different genetic determinants which will help to inform future studies looking at underlying disease mechanisms and pathogenesis in these different subtypes of disease., Competing Interests: Competing interests: ML: received fees for advising on a secondary analysis of an RCT sponsored by North Bristol NHS trust. MMXT: reports no disclosures. YB-S: reports no disclosures. FB: reports no disclosures. TB: reports no disclosures. JCK: reports no disclosures. SGE: reports no disclosures. SM: reports no disclosures. NM: reports no disclosures. KG: reports no disclosures. RAB: received grants from Parkinson’s UK, NIHR, Cure Parkinson’s Trust, Evelyn Trust, Rosetrees Trust, MRC and EU along with payment for advisory board attendance from Oxford Biomedica, Aspen Neuroscience, UCB, BlueRock Therapeutics, Novo Nordisk and LCT, and honoraria from Wiley and Springer. NW: reports no disclosures. DJB: received grants from NIHR, Wellcome Trust, GlaxoSmithKline, Parkinson’s UK, and Michael J Fox Foundation. TF: grants from National Institute of Health Research, Michael J Fox Foundation, John Black Charitable Foundation, Cure Parkinson’s Trust, Innovate UK, Janet Owens Research Fellowship, Van Andel Research Institute and Defeat MSA. Advisory Boards for Peptron, Voyager Therapeutics, Handl therapeutics, Living Cell Technologies, Bial grants from Welsh Assembly Government, personal fees from Teva, personal fees from Abbvie, personal fees from Teva, personal fees from UCB, personal fees from Boehringer-Ingelheim, personal fees from GSK, non-financial support from Teva, grants from Ipsen Fund, non-financial support from Medtronic, grants from MNDA, grants from PSP Association, grants from CBD Solutions, grants from Drake Foundation, personal fees from Acorda, outside the submitted work; In addition, HRM has a patent. HRM is a coapplicant on a patent application related to C9ORF72 - Method for diagnosing a neurodegenerative disease (PCT/GB2012/052140) pending. NW: reports Funding from Aligning science against Parkinsons (ASAP). He has also received consultancy fees from GSK. DGG: received payment for advisory board attendance from Merz Pharma, Vectura plc, and consultancy fees from the GM clinic. Grant support from Parkinson’s UK, the Neurosciences Foundation, and Michael’s Movers. MT-MH: received payment for Advisory Board attendance/consultancy for Biogen, Roche, CuraSen Therapeutics, Evidera, Manus Neurodynamica. She received funding/grant support from Parkinson’s UK, Oxford NIHR BRC, University of Oxford, CPT, Lab10X, NIHR, Michael J Fox Foundation, H2020 European Union, GE Healthcare and the PSP Association. MT-MH is a coapplicant on a patent application related to smartphone predictions in Parkinson’s (PCT/GB2019/052522) pending., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Breast cancer patients in low- and middle-income countries often present at an advanced stage. This qualitative study elicited views regarding the challenges and opportunities for breast cancer screening and early detection among women in a low-income semi-rural community in Segamat district, Malaysia., Methods: Individual semi-structured interviews with 22 people (health professionals, cancer survivors, community volunteers and member from a non-governmental organization) and four focus group discussions (n = 22 participants) with women from a local community were conducted. All participants were purposively sampled and female residents registered with the South East Asia Community Observatory aged ≥40 years were eligible to participate in the focus group discussions. Data were transcribed verbatim and analyzed using thematic analysis., Results: The thematic analysis illuminated barriers, challenges and opportunities across six domains: (i) personal experiences and barriers to help-seeking as well as financial and travel access barriers; (ii) primary care challenges (related to delivering clinical breast examination and teaching breast-self-examination); (iii) secondary care challenges (related to mammogram services); (iv) disconnection between secondary and primary care breast cancer screening pathways; and (v) opportunities to improve breast cancer early detection relating to community civil service society activities (i.e. awareness raising, support groups, addressing stigma/embarrassment and encouraging husbands to support women) and vi) links between public healthcare personnel and community (i.e. improving breast self-examination education, clinical breast examination provision and subsidised mammograms)., Conclusion: The results point to a variety of reasons for low uptake and, therefore, to the complex nature of improving breast cancer screening and early detection. There is a need to adopt a systems approach to address this complexity and to take account of the socio-cultural context of communities in order, in turn, to strengthen cancer control policy and practices in Malaysia., Competing Interests: The authors have declared that no competing interests exist.

Research has shown that religion is associated with a better quality of life (QoL). This study aims to examine ethnic differences in the association between religion and the QoL of older adults in a predominantly Muslim population within a multicultural setting. Two-wave data of 3,810 participants consisting of mostly Muslims and older adults aged ≥ 55 years were collected as part of the community health surveys conducted in 2013 and 2018 in the South East Asia Community Observatory (SEACO). Both cross-sectional analyses of baseline data and prospective analyses of longitudinal data were conducted. The associations between religiosity and quality of life were mainly positive in the cross-sectional analysis. In the two-wave analysis, religious importance was negatively associated with QoL among the Malays (B = - 1.103, SE B = 0.029, p < .001) and the Chinese (B = - 0.160, SE B = 0.043, p < .001), and a belief in a higher power control was associated with better QoL among the Malays (B = 0.051, SE B = 0.022, p < .005) and poorer QoL domains among the Indians (physical health: B = - 5.412, SE B = 1.382, p < .001; psychological: B = - 3.325, SE B = 1.42, p < .001; social relationship: B = - 5.548, SE B = 1.616, p < .001; environment: B = - 2.586, SE B = 1.288; p < .05). Our study's mixed results suggest that religiosity is positively associated with quality of life in cross-sectional analyses. However, in longitudinal analyses, the results are different. Conclusions with regard to causality based on cross-sectional analyses may be misleading. Health promotion programs should continue to examine the effect of religiousness on health outcomes over time among aging populations across different ethnic groups., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Social distancing is crucial in breaking the cycle of transmission of COVID-19. However, many religions require the faithful to congregate. In Malaysia, the number of COVID-19 cases spiked up from below 30 in February 2020 to more than a thousand a month later. The sudden increase was mostly linked to a large Islamic gathering attended by 16,000 near the capital, Kuala Lumpur. Another large COVID-19 cluster was from a church gathering in Kuching, Sarawak. Within a few weeks, Malaysia became the worst hit country by COVID-19 in Southeast Asia. While religious leaders have advised social distancing among their congregants, the belief that "God is our shield" is often cited for gathering. There is a need to promote sound decision-making among religious adherents so that they will not prioritize their loyalty to the subjective interpretation of religion over evidence-based medicine. Malaysia, a multi-cultural and multi-faith country, is an example of how religious beliefs could strongly influence health behaviours at individual and community levels. In this article, we detail the religious aspects of COVID-19 prevention and control in Malaysia and discuss the possible role of religious organizations in encouraging sound decision-making among religious adherents in mitigating this crisis. We make recommendations on how to promote a partnership between the healthcare system and religious organizations, and how religion and faith could be integrated into health promotion channels and resources in the response of COVID-19 and future communicable diseases., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To conduct a needs assessment for lay health workers and non-physician healthcare professionals [i.e., community health workers (CHW) and lung health professionals who spend more time face-to-face with tobacco-related disparity populations] to describe current gaps in tobacco cessation practices and knowledge., Methods: A 46-item needs assessment survey was developed to understand knowledge, practices, and confidence about tobacco cessation among non-physician health professionals in a large, urban city in the U.S. Participants, recruited from local community-based organizations and email listservs, completed the online or paper survey, which included a 10-item investigator-initiated tobacco knowledge questionnaire., Results: About 61.5% of participants (N = 53) asked each client/patient about tobacco use at initial visit, 41.8% reported extreme likelihood of discussing tobacco during a visit, and 43.1% reported addressing tobacco use directly. Despite assisting with cessation, tobacco-related knowledge and confidence was low, with respondents scoring an average of 4.08 out of 10 (SD = 2.21) on the tobacco knowledge questionnaire., Conclusion: There was a clear lack of knowledge about tobacco cessation in the U.S. among non-physician healthcare professionals. These professionals could benefit from trainings that are relevant to their model of care and better equip them to assist the disparity populations that they serve.

Parkinson's disease (PD) is a complex neurodegenerative disorder in which both rare and common genetic variants contribute to disease risk. Multiple genes have been reported to be linked to monogenic PD but these only explain a fraction of the observed familial aggregation. Rare variants in RIC3 have been suggested to be associated with PD in the Indian population. However, replication studies yielded inconsistent results. We further investigate the role of RIC3 variants in PD in European cohorts using individual-level genotyping data from 14,671 PD patients and 17,667 controls, as well as whole-genome sequencing data from 1,615 patients and 961 controls. We also investigated RIC3 using summary statistics from a Latin American cohort of 1,481 individuals, and from a cohort of 31,575 individuals of East Asian ancestry. We did not identify any association between RIC3 and PD in any of the cohorts. However, more studies of rare variants in non-European ancestry populations, in particular South Asian populations, are necessary to further evaluate the world-wide role of RIC3 in PD etiology., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Breast cancer (BC) is the commonest cancer in Malaysia. Delayed diagnosis is a significant cause of BC mortality in the country. Early diagnosis and screening are vital strategies in mortality reduction. This study assessed the level of utilisation and barriers for breast self-examination (BSE), clinical breast examination (CBE) and mammogram in a semi-rural population in Malaysia and compared these across the different ethnic groups. This cross-sectional study was conducted among women aged 40 years and above, embedded within a health and demographic surveillance site (HDSS) in Segamat, Malaysia. Trained data collectors collected data on screening and barriers during home visits. Study participants ( n = 250) were aged 59.4 ± 10.9 years and represented Malaysia's three major ethnic groups. Practice of regular BSE, CBE uptake (ever) and mammogram (ever) was 23.2%, 36% and 22.4%, respectively. Regular BSE practice was highest in the Malay ethnic group and least among the Chinese. Regular CBE was very low in all ethnic groups (<5%). Mammogram uptake was highest among Chinese (34.4%), followed by Indians (30.4%) and Malays (16.6%). After adjusting for other socio-demographic variables, Malay ethnicity was positively associated with regular BSE (adjusted OR = 5.26, 95% CI 2.05, 13.50) and negatively associated with having had a mammogram (adjusted OR = 0.3, 95% CI 0.15, 0.57). Lower education was negatively associated (adjusted OR = 0.36, 95% CI 0.17, 0.74) with mammogram attendance (ever). Emotional and financial barriers were the most reported types of barriers, specifically, fear of diagnosis (74.8%), cost of diagnosis (69.6%) and fear of losing a breast (66.4%). Malay women more commonly reported most barriers compared to other ethnic groups. Screening uptake was low among semi-rural women in Malaysia. Implementing culturally appropriate interventions that consider ethnic differences is crucial to empowering women to engage in BC screening initiatives in these communities.

Objectives: Religion and spirituality gain importance as a person ages. Research has shown that religion has a salutary effect on mental health, and it is associated with health differently across ethnic groups. The current study examined ethnic differences in the association between religion and mental health among older adults in a predominantly Muslim population and multicultural setting., Methods: Data of 7068 participants (4418 Malays, 2080 Chinese and 570 Indians) aged ≥55 years that were collected as part of the community health survey conducted in 2013 in the South East Asia Community Observatory (SEACO) were analyzed using bivariate and multiple regressions. Analyses were stratified by ethnicity., Results: The importance of having an enriched religious/spiritual life was associated with higher scores of depression, anxiety and stress among Chinese and higher score of depression among Malays, while belief in a higher power was associated with better mental health among Malays, Chinese and Indians., Conclusion: The current study showed that there were ethnic variations in the associations between religion and mental health, and the associations depended on the religious variable included in the analysis. The findings of this study showed that religion could be another potential channel to improve mental health among older adults by accommodating and understanding their religious beliefs.

Cancer is a leading cause of death, affecting people in both developed and developing countries. It is a challenging disease due to its complicated pathophysiological mechanism. Many anti-cancer drugs are used to treat cancer and reduce mortality rates, but their toxicity limits their administration. Drugs made from natural products, which act as multi-targeted therapy, have the ability to target critical signaling proteins in different pathways. Natural compounds possess pharmacological activities such as anti-cancer activity, low toxicity, and minimum side effects. Panax notoginseng is a medicinal plant whose extracts and phytochemicals are used to treat cancer, cardiovascular disorders, blood stasis, easing inflammation, edema, and pain. P. notoginseng 's secondary metabolites target cancer's dysregulated pathways, causing cancer cell death. In this review, we focused on several ginsenosides extracted from P. notoginseng that have been evaluated against various cancer cell lines, with the aim of cancer treatment. Furthermore, an in vivo investigation of these ginsenosides should be conducted to gain insight into the dysregulation of several pathways, followed by clinical trials for the potential and effective treatment of cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tan, Chen, Han, Wang and Tu.)

Background: Since December 2019, there have been many new cases of coronavirus pneumonia in Wuhan, Hubei Province, which has gradually spread throughout the country., Aim: To explore our hospital's innovative management system to ensure the efficient operation of fever clinics during the epidemic, since controlling the spread of disease is an important way to prevent and control the epidemic., Methods: In total, 200 outpatients with fever at our hospital between November 2019 and July 2020 were selected and allocated into two groups., Results: The fever clinic in our hospital operated smoothly, and infection with the novel coronavirus disease (COVID-19) has not been reported in our hospital. Additionally, we did not have any cases of missed diagnosis. The awareness regarding COVID-19 infection sources, transmission routes, early symptoms, and preventive measures was significantly higher in our fever clinic than in those of the pre-management group., Conclusion: "An integrated system, three separate responsibilities" ensured the efficient functioning of our fever outpatient clinic and early screening of COVID-19 cases, which effectively curbed the transmission of COVID-19 and hence prevented COVID-19 pneumonia epidemic in our hospital, ultimately achieving the maximum effect of epidemic prevention and control., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Many psychological researchers have proven the deteriorating effects of the coronavirus disease 2019 (Covid-19) pandemic on public mental health. In Malaysia, various Covid-19 clusters were associated with religious gatherings. From a cultural psychology perspective, how ethno-religious groups respond to this crisis originating from their unique rationality and ecological systems. Therefore, this study aimed to explore the illness perceptions of major religious groups (Christian, Muslim, and Buddhist) in Malaysia toward the Covid-19 pandemic, their stress levels, and the relationship between illness perception, stress, and forms of religious expression during the lockdown period. Through an online survey method, 608 Malaysian religious believers were included in this mixed-method empirical study, which adapted standardized instruments [Duke University Religion Index (DUREL), Brief Illness Perception Questionnaire (BIPQ), and Perceived Stress Scale (PSS)]. Statistical analysis showed that all three groups reported moderate levels of stress in average without any significant difference after controlling for age. Both internal and external forms of religious expression had a significant negative relationship with stress levels. Personal control, comprehension, and emotions domains of illness perception accounted for a significant variance in the stress level. Furthermore, religious expression significantly moderated the relationship between some illness perception domains and stress. Qualitative coding revealed that most participants perceived human behavior and attitudes, sociopolitical, and sociological factors as causal factors to the current pandemic. These findings confirmed the relationship between religious expression, illness belief, and stress regulation during the pandemic lockdown. Incidental findings of age as a potential protective factor for Malaysian believers warrants further study. In the conclusion, implications for public health policymakers and religious communities on pandemic prevention and well-being promotion were discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ting, Aw Yong, Tan and Yap.)

African Americans have disproportionate rates of post-cessation weight gain compared to non-Hispanic whites, but few studies have examined this weight gain in a multiracial sample of smokers receiving evidence-based treatment in a community setting. We examined race differences in short-term weight gain during an intervention to foster smoking cessation plus weight management. Data were drawn from the Best Quit Study, a randomized controlled trial conducted via telephone quitlines across the U.S. from 2013 to 2017. The trial tested the effects on cessation and weight gain prevention of adding a weight control intervention either simultaneously with or sequentially after smoking cessation treatment. African Americans (n = 665) and whites (n = 1723) self-reported smoking status and weight during ten intervention calls. Random effects longitudinal modeling was used to examine predictors of weight change over the intervention period (average 16 weeks). There was a significant race × treatment effect; in the simultaneous group, weight increased for African Americans at a faster rate compared to whites (b = 0.302, SE = 0.129, p  < 0.05), independent of smoking status, age, baseline obesity, and education. After stratifying the sample, the effect of treatment group differed by race. Education level attenuated the rate of weight gain for African Americans in the simultaneous group, but not for whites. African Americans receiving smoking and weight content simultaneously gained weight faster than whites in the same group; however, the weight gain was slower for African Americans with higher educational attainment. Future studies are needed to understand social factors associated with treatment receptivity that may influence weight among African American smokers., Competing Interests: The authors at Alere Wellbeing (TB, AJT, and KW) declare that they are employed by Alere Wellbeing (a subsidiary of Optum) which provides tobacco cessation and weight management services to states and commercial clients. They have no other competing interests. MT, JCL, HJ, and BS have no conflicts to disclose. No financial disclosures were reported by the authors of this paper., (© 2020 The Authors.)

Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia.