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Background: The global increase in type 2 diabetes (T2D) poses a significant public health challenge worldwide. Due to the chronic and complex nature of the disease, management does not depend on pharmacotherapy alone; rather, a comprehensive medical and self-management plan is required. Diabetes Self-Management Education programs should address diabetes-specific behaviors and be grounded in patients' perceptions of their disease and its consequences. Aim: The study aims to understand perceptions of diabetes self-management (DSM) among persons of different nationalities with T2D living in Qatar. Method: A phenomenological qualitative study was implemented using four focus group interviews using Triandis Interpersonal Behavior Model to understand factors influencing DSM perceptions and behaviors. Therefore, deductive content analysis was used, also inductive content analysis used to find new emerging themes. Twenty-nine participants with T2D of 12 different nationalities were recruited. Results: Content analyses revealed that participants were mainly motivated to manage their diabetes by fear of future health complications--and the resulting impact on their families--triggered by witnessing these complications on other family members and friends. Factors that influenced DSM included cultural factors such as food content and holidays' customs, weather conditions, psychological distress, and social factors such as lack of family support. Furthermore, access to healthy food, number of working hours and time, and cost of DSM supplies were found to be among the barriers to DSM. Conclusion: Understanding and considering patients' perspectives is a core component of culturally competent and evidence-based DSM programs, and it should be considered in any DSM program.

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 Pjoint

Abstract Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

Abstract Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of key genes in bone biology, particularly to intramembranous ossification, not captured at other skeletal sites. We perform a genome-wide association meta-analysis (n ~ 43,800) of SK-BMD, identifying 59 loci, collectively explaining 12.5% of the trait variance. Association signals cluster within gene-sets involved in skeletal development and osteoporosis. Among the four novel loci (ZIC1, PRKAR1A, AZIN1/ATP6V1C1, GLRX3), there are factors implicated in intramembranous ossification and as we show, inherent to craniosynostosis processes. Functional follow-up in zebrafish confirms the importance of ZIC1 on cranial suture patterning. Likewise, we observe abnormal cranial bone initiation that culminates in ectopic sutures and reduced BMD in mosaic atp6v1c1 knockouts. Mosaic prkar1a knockouts present asymmetric bone growth and, conversely, elevated BMD. In light of this evidence linking SK-BMD loci to craniofacial abnormalities, our study provides new insight into the pathophysiology, diagnosis and treatment of skeletal diseases.

Abstract Background In the field of neuroscience, neural modules and circuits that control biological functions have been found throughout entire neural networks. Correlations in neural activity can be used to identify such neural modules. Recent technological advances enable us to measure whole-brain neural activity with single-cell resolution in several species including $$Caenorhabditis\ elegans$$ C a e n o r h a b d i t i s e l e g a n s . Because current neural activity data in C. elegans contain many missing data points, it is necessary to merge results from as many animals as possible to obtain more reliable functional modules. Results In this work, we developed a new time-series clustering method, WormTensor, to identify functional modules using whole-brain activity data from C. elegans. WormTensor uses a distance measure, modified shape-based distance to account for the lags and the mutual inhibition of cell–cell interactions and applies the tensor decomposition algorithm multi-view clustering based on matrix integration using the higher orthogonal iteration of tensors (HOOI) algorithm (MC-MI-HOOI), which can estimate both the weight to account for the reliability of data from each animal and the clusters that are common across animals. Conclusion We applied the method to 24 individual C. elegans and successfully found some known functional modules. Compared with a widely used consensus clustering method to aggregate multiple clustering results, WormTensor showed higher silhouette coefficients. Our simulation also showed that WormTensor is robust to contamination from noisy data. WormTensor is freely available as an R/CRAN package https://cran.r-project.org/web/packages/WormTensor .

Objectives: Influenza virus infection (IVI) occasionally causes lower respiratory tract infection (LRTI) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Although the progression to LRTI entails a high mortality, the role of early antiviral therapy for its prevention has not been fully elucidated. Methods: This was a multicenter retrospective study using an additional questionnaire. Allo-HSCT recipients who developed IVI between 2012 and 2020 were included. Results: A total of 278 cases of IVI after allo-HSCT were identified from 15 institutions. The median patient age was 49 years, and the median time from allo-HSCT to IVI was 918 days. Neuraminidase inhibitors were administered within 48 hours of symptom onset (early neuraminidase inhibitor [NAI]) in 199 (76.9%) patients. Subsequently, 36 (12.3%) patients developed LRTI. On the multivariate analysis, age ≥50 years (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.02-4.58) and moderate to severe chronic graft-versus-host disease (HR, 2.28; 95% CI, 1.14-4.58) were significantly associated with progression to LRTI, whereas early NAI suppressed the progression (HR, 0.17; 95% CI, 0.06-0.46). The IVI-related mortality rate was 2.2%. Conclusion: To reduce the risk of LRTI development after IVI, early NAI therapy should be considered in allo-HSCT recipients, especially with older patients and those with chronic graft-versus-host disease.

BackgroundDiversiPrEP is a culturally-tailored PrEP program for LMSM offered in South Florida. DiversiPrEP navigates LMSM through their PrEP journey, including education, deciding if PrEP is relevant for them, payment, and accessing/maintaining PrEP use. DiversiPrEP includes five ERIC strategies (Increase Demand, Promote Adaptability, Alter Client Fees, Intervene with Clients to Enhance Uptake and Adherence, and Tailor Strategies).DescriptionPhotovoice was used to conduct five two-part focus groups with LMSM (n = 12) and Non-LMSM (n = 12). In the first session, trainers provided guidance on selecting and contextualizing photos to generate CFIR themes. Then, participants captured photos that embodied their lived experiences accessing PrEP. In the second session, using SHOWeD, participants discussed photos, identifiedhow photos relate to culturally relevant issues. Triangulation approaches compared/contrasted themes between LMSM and Non-LMSM.ResultsFive central themes emerged around barriers and facilitators to PrEP services: 1) the need for normalizing PrEP messages within the MSM community, 2) the need for normalizing PrEP messages outside the MSM community, 3) the need for expanding PrEP knowledge, 4) different motivations for using PrEP, and 5) the presence of structural barriers that limit PrEP access. This study compared similarities and differences of barriers and facilitators to PrEP use between Latino/a and non-Latino/a MSM. Similarities included the built environment (outer setting) as a barrier, the need for normalizing PrEP messaging within and outside of the MSM community, and the need to expand PrEP knowledge. Differences between Latino/a and non-Latino/a MSM were found in assessing the motivation and personal drivers (inner setting) for initiating PrEP associated with how participants viewed their responsibilities to self or others.ConclusionsPhotovoice with focus groups identified CFIR constructs that can guide the large-scale implementation of a client-centered PrEP service model with telehealth for both Latino/a and non-Latino/a MSM. Implementing client-centered accessible PrEP programs is an essential step to promoting sexual-health equity.

Abstract Objective: This study aimed to investigate and contain a cluster of invasive candidiasis cases caused by fluconazole-resistant Candida parapsilosis (FRC) in a neonatal intensive care unit. Methods: Active surveillance was initiated. Direct observations of hand-hygiene compliance (HHC) among staff were conducted before and after the implementation of hand-hygiene (HH) education. Thirty-five environmental cultures were obtained. Phylogenetic analysis of FRC was performed using Fourier-transform infrared spectroscopy and microsatellite genotyping. Results: A total of 14 patients (mean birth weight = 860 g, gestational age = 25 weeks) infected with FRC were identified using the fully automated analyzer, including 5 with clinical infection (three with catheter-related bloodstream infection, one with cutaneous infection, and one with fatal peritonitis) and 9 with colonization. The HHC rate in nurses before performing a sterile or aseptic procedure significantly improved after the HH education (P < .05). Sinks near the patients were contaminated with FRC. All FRC strains were confirmed to be susceptible to fluconazole using the CLSI method, and the microdilution procedure indicated a trailing effect. Phylogenetic analysis showed that all the fluconazole-trailing isolates from patients were clustered together and had the same genotype. Sinks were successfully decontaminated using accelerated hydrogen peroxide and drainage pipes were replaced. Ultraviolet-C decontamination was applied in the milk preparation room. No new cases were detected after the education and disinfection interventions. Conclusions: Sinks are an important reservoir of C. parapsilosis. Active surveillance, environmental hygiene, and constant staff education on maintaining a high level of HHC are necessary to limit the spread of C. parapsilosis.

Abstract Background and Aim Mental status such as anxiety and depression in patients with non‐esophageal eosinophilic gastrointestinal diseases (non‐EoE EGIDs) has not been studied. The aim of this study was to evaluate whether patients with non‐EoE EGIDs had mental disorders and decreased mental‐health‐related quality of life (QOL) similar to those in patients with disorders of gut–brain interaction (DGBI). Methods We enrolled patients with non‐EoE EGIDs and DGBI visiting the Osaka Metropolitan University Hospital, and the measures listed below were compared between the groups. We collected data using the following questionnaires: hospital anxiety and depression scale, and short form (SF)‐8 including mental component summary (MCS)‐8. Results We evaluated 21 and 17 patients with non‐EoE EGIDs and DGBI, respectively. The anxiety score was not significantly different between the groups. The proportion of patients with possible anxiety was not significantly different between the groups (19.0% vs 33.3%). These results show that patients with non‐EoE EGIDs had anxiety that might be equivalent to that of patients with DGBI. The depression score and proportion of patients with possible depression in the non‐EoE EGID group tended to be lower than those in the DGBI group. MCS‐8 scores were not significantly different between the non‐EoE EGID and DGBI groups, which might imply an equivalent decrease in mental‐health‐related QOL in both groups of patients. In patients with non‐EoE EGIDs, the anxiety score had a significant inverse association with the MCS‐8 score. Conclusions Patients with non‐EoE EGIDs may have anxiety that correlates with decreased mental‐health‐related QOL.

BackgroundResearch has found a COVID-19 pandemic–related impact on HIV medical services, including clinic visits, testing, and antiviral therapy initiation in countries including Japan. However, the change in trend for HIV/AIDS testing during the COVID-19 pandemic has not been explored extensively in the Japanese population. ObjectiveThis infodemiology study examines the web-based search interest for two types of HIV tests, self-test kits and facility-based tests, before and during the COVID-19 pandemic in Japan. MethodsThe monthly search volume of queried search terms was obtained from Yahoo! JAPAN. Search volumes for the following terms were collected from November 2017 to October 2018: “HIV test,” “HIV test kit,” and “HIV test health center.” The search term “Corona PCR” and the number of new COVID-19 cases by month were used as a control for the search trends. The number of new HIV cases in the corresponding study period was obtained from the AIDS Trend Committee Quarterly Report from the AIDS Prevention Foundation. ResultsCompared to the search volume of “corona-PCR,” which roughly fluctuated corresponding to the number of new COVID-19 cases in Japan, the search volume of “HIV test” was relatively stable from 2019 to 2022. When we further stratified by the type of HIV test, the respective web-based search interest in HIV self-testing and facility-based testing showed distinct patterns from 2018 to 2022. While the search volume of “HIV test kit” remained stable, that of “HIV test health center” displayed a decreasing trend starting in 2018 and has remained low since the beginning of the COVID-19 pandemic. Around 66%-71% of the search volume of “HIV test kits” was attributable to searches made by male internet users from 2018 to 2022, and the top three contributing age groups were those aged 30-39 (27%-32%), 20-29 (19%-32%), and 40-49 (19%-25%) years. On the other hand, the search volume of “HIV test health centers” by male users decreased from more than 500 from 2018 to 2019 to fewer than 300 from 2020 to 2022. ConclusionsOur study found a notable decrease in the search volume of “HIV test health center” during the pandemic, while the search volume for HIV self-testing kits remained stable before and during the COVID-19 crisis in Japan. This suggests that the previously reported COVID-19–related decrease in the number of HIV tests mostly likely referred to facility-based testing. This sheds light on the change in HIV-testing preferences in Japan, calling for a more comprehensive application and regulatory acceptance of HIV self-instructed tests.

Mature gametes are transported externally for fertilization. In vertebrates, the gonads are located within the coelom. Consequently, each species has specific organs for export, which often vary according to sex. In most vertebrates, sperm ducts and oviducts develop from the Wolffian and Müllerian ducts, respectively. However, exceptions exist. Both sexes of cyclostomes, as well as females of basal teleosts, lack genital ducts but possess genital pores. In teleosts of both sexes, genital ducts are formed through the posterior extensions of gonads. These structures appear to be independent of both Wolffian and Müllerian ducts. Furthermore, the development of Wolffian and Müllerian ducts differs significantly among various vertebrates. Are these gamete-exporting organs homologous or not? A question extensively debated around the turn of the 20th century but now largely overlooked. Recent research has revealed the indispensable role of Wnt4a in genital duct development in both sexes of teleosts: zebrafish and medaka. wnt4a is an ortholog of mammalian Wnt4, which has functions in Müllerian duct formation. These results suggest a potential homology between the mammalian Müllerian ducts and genital ducts in teleosts. To investigate the homology of gamete-exporting organs in vertebrates, more detailed descriptions of their development across vertebrates, using modern cellular and genetic tools, are needed. Therefore, this review summarizes existing knowledge and unresolved questions on the structure and development of gamete-exporting organs in diverse vertebrate groups. This also underscores the need for comprehensive studies, particularly on cyclostomes, cartilaginous fishes, basal ray-finned fishes, and teleosts.

Summary: Ribosomes polymerize nascent peptides through repeated inter-subunit rearrangements between the classic and hybrid states. The peptidyl-tRNA, the intermediate species during translation elongation, stabilizes the translating ribosome to ensure robust continuity of elongation. However, the translation of acidic residue-rich sequences destabilizes the ribosome, leading to a stochastic premature translation cessation termed intrinsic ribosome destabilization (IRD), which is still ill-defined. Here, we dissect the molecular mechanisms underlying IRD in Escherichia coli. Reconstitution of the IRD event reveals that (1) the prolonged ribosome stalling enhances IRD-mediated translation discontinuation, (2) IRD depends on temperature, (3) the destabilized 70S ribosome complex is not necessarily split, and (4) the destabilized ribosome is subjected to peptidyl-tRNA hydrolase-mediated hydrolysis of the peptidyl-tRNA without subunit splitting or recycling factors-mediated subunit splitting. Collectively, our data indicate that the translation of acidic-rich sequences alters the conformation of the 70S ribosome to an aberrant state that allows the noncanonical premature termination.

Backgrounds Few paediatric and perinatal quality indicators (QIs) have been developed in the Japanese setting, and the quality of care is not assured or validated. The aim of this study was to develop QIs in paediatric and perinatal care in Japan using an administrative database and confirm the feasibility and applicability of the indicators using a single-site practice test.Methods We used a RAND-modified Delphi method that integrates evidence review with expert consensus development. QI candidates were generated from clinical practice guidelines (CPGs) available in English or Japanese and existing QIs in nine selected paediatric or perinatal conditions. Consensus building was based on independent panel ratings. The performance of QIs was retrospectively assessed using data from an administrative database at the National Children’s Hospital. Data between April 2018 and March 2019 were used, while data between April 2019 and March 2021 were also used for selected condition, considering the small number of patients. Each QI was calculated as follows: number of times the indicator was met/number of participants×100.Results From the literature review conducted between 2010 and 2020, 124 CPGs and 193 existing indicators were identified to generate QI candidates. Through the consensus-building process, 133 QI candidates were assessed and 79 QIs were accepted. The practice test revealed wide variations in the process-level performance of QIs in four categories: patient safety: median 43.9% (IQR 16.7%–85.6%), general paediatrics: median 98.8% (IQR 84.2%–100%), advanced paediatrics: median 94.4% (IQR 46.0%–100%) and advanced obstetrics: median 80.3% (IQR 59.6%–100%).Conclusions We established 79 QIs for paediatric and perinatal care in Japan using an administrative database that can be applied to hospitals nationwide. The practice test confirmed the measurability of the developed QIs. Benchmarking these QIs will be an attractive approach to improving the quality of care.

Unintended pregnancy (UP) can negatively impact the health of mothers, children, and families. While Adverse Childhood Experiences (ACEs) are increasingly known to affect sexual health, the influence on pregnancy intention is not fully understood. This study examines the relationship between ACEs and UP and explores other related factors, using 5049 pregnant and postpartum women data from the Japan COVID-19 and Society Internet Survey (JACSIS). We measured participants’ pregnancy intentions, ACEs, family functioning, and social network size. Logistic regression analysis provided odds ratios and 95% confidence intervals (CI). The prevalence of UP was approximately 16.5% (n = 893). Cumulative ACEs were consistently associated with UP, even after adjusting for intermediate variables in adulthood. The odds ratio for UP with a single ACE was 1.00 (CI: 0.82–1.21) but rose significantly with multiple ACEs: 1.39 (CI: 1.10–1.76) with double, 1.38 (CI: 1.02–2.86) with triple, and 1.81 (CI: 1.37–2.39) with more. Additionally, bad family functioning and lack of social networks emerged as contributors to UP. In conclusion, this study showed that ACEs are potentially correlated with UP. A deeper understanding of the transition from childhood experiences to UP is important for health interventions, necessitating further investigation.

Evidence synthesis serves an important role to promote informed decision-making in healthcare practice. A key issue of evidence synthesis is the approach to deal with rare adverse events and the methods to address bias of harm effects. Empirical data is essential to help methodologists and statisticians to solve the issues in evidence synthesis of adverse events. For this reason, we have established SMART Safety dataset, the largest empirical dataset of meta-analyses of adverse events. The dataset contains 151 systematic reviews with 629 meta-analyses on safety outcomes, which covers more than 2,300 randomized controlled trials and 362 harm outcomes, with 10,069 rows and 45 columns of trial level information. All information was double- or even quadra-checked and further verified by referring the original source (e.g., the full-text of the included randomized trials) to ensure high validity of the data.

Background: The choice of operative method for lumbar spinal stenosis with Meyerding grade I degenerative spondylolisthesis remains controversial. The purpose of this study was to identify the preoperative factors affecting the 2-year postoperative patient-reported outcome in Meyerding grade I degenerative spondylolisthesis. Methods: Seventy-two consecutive patients who had minimally invasive decompression alone (D group; 28) or with fusion (DF group; 44) were enrolled. The parameters investigated were the Japanese Orthopaedic Association back pain evaluation questionnaire as patient-reported assessment, and L4 slippage (L4S), lumbar lordosis (LL), and lumbar axis sacral distance (LASD) as an index of sagittal alignment for radiological evaluation. Data collected prospectively at 2 years postoperatively were examined by statistical analysis. Results: Sixty-two cases (D group; 25, DF group; 37) were finally evaluated. In multiple logistic regression analysis, preoperative L4S and LASD were extracted as significant preoperative factors affecting the 2-year postoperative outcome. Patients with preoperative L4S of 6 mm or more have a lower rate of improvement in lumbar spine dysfunction due to low back pain (risk ratio=0.188, p=.043). Patients with a preoperative LASD of 30 mm or more have a higher rate of improvement in lumbar dysfunction due to low back pain (risk ratio=11.48, p=.021). The results of multiple logistic analysis by operative method showed that there was a higher rate of improvement in lumbar spine dysfunction due to low back pain in patients with preoperative LASD of 30 mm or more in DF group (risk ratio=172.028, p=.01). Conclusions: Preoperative L4S and LASD were extracted as significant preoperative factors affecting patient-reported outcomes at 2 years postoperatively. Multiple logistic analyses by the operative method suggested that DF may be advantageous in improving lumbar dysfunction due to low back pain in patients with preoperative LASD of 30 mm or more.

ABSTRACTObjectives and Methods This single-center retrospective study was performed to evaluate the safety and efficacy of FMS-like tyrosine kinase 3 (FLT3) inhibitors before and after allogeneic hematopoietic cell transplantation (HCT) in relapsed/refractory patients with FLT3-mutation positive acute myeloid leukemia (AML).Results Ten patients who met the eligibility criteria were included. Eight of them achieved hematological remission at HCT, within a median span of 79 days (range: 43–197). In post-HCT, patients started maintenance therapy (MT; median time-to-start 79 days, range: 43–197), and the median duration of MT was 390 days (range: 67–815). Grade 3 hematological adverse events (AEs) were found in two patients, and non-hematological AEs were found in five patients. Nine patients underwent either dose reduction, discontinuation of therapy, or a switch to another FLT3 inhibitor due to AEs. Disease relapse occurred in one patient during MT. At the time of the last follow-up, seven patients are alive and disease-free, while three have died due to infection or transplant complications.Conclusion In relapsed/refractory FLT3 mutation-positive AML, the use of FLT3 inhibitors can lead to high response rates and provide a safe bridge from HCT to MT. If sufficient attention is paid to safety, this therapy is expected to prevent disease relapse even with reduced dosages.

BackgroundChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia.MethodsData from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake.ResultsIn a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16-3.07] mg/dL per allele; P