Population Studies Research Articles

Investigation of the psychometric properties of "exercise Benefits/Barriers scale" in Turkish patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic disease accompanied by several symptoms and functional disabilities. Physical activity (PA) is crucial for disease management and patients' perception of exercise is essential for a rehabilitation plan. This study aims to examine the psychometric properties of the Exercise Benefits/Barriers Scale (EBBS) that is frequently used in previous studies in the RA population. We included a total of 104 patients in our study. Test-retest reliability was assessed using intraclass correlation coefficient (ICC 2,k). The International Physical Activity Questionnaire (IPAQ) and the Bristol Rheumatoid Arthritis Fatigue Scale (BRAFS) were used for the convergent validity of the scale. For discriminant validity analysis, the total barriers and benefits scores were examined according to exercise status (yes/no), PA level (high/low), and fatigue severity (high/low). Additionally, standard error of measurement (SEM) and minimal detectable change with 95% confidence (MDC95) are calculated. EBBS subscores showed moderate to excellent reliability (ICC: 0.71 to 0.98) and correlated PA (r = 0.453 and 0.515, EBBS-barriers and benefits subscores, respectively) and fatigue (r=-0.261 and -0.393, EBBS-barriers and benefits subscores, respectively). The SEM and MDC95 values were calculated as 2.03 and 7.96 for EBBS-benefits subscores and 0.93 and 3.65 for EBBS-barriers subscores. The EBBS-Benefits and Barriers subscores differed according to exercise status (p = .08), PA level (p < .01), and fatigue (p = .08). The results highlighted that the EBBS is a reliable and valid instrument to assess exercise benefits and barriers in patients with RA.

Characteristics of forensic psychiatric patients with a neurocognitive disorder.

Emotional and behavioural disturbances accompanying neurocognitive disorders may sometimes lead to a criminal offence. Our knowledge of this specific forensic subpopulation is lagging behind the knowledge on, and attention for, 'classic' psychiatric disorders in forensic populations. To gain knowledge on the prevalence and characteristics of individuals with neurocognitive disorders in the forensic population. This retrospective database study uses an anonymised data-set of the National Database of penitentiary psychiatric centres (PPC) (N = 8391), which collects data on all patients admitted to one of the four PPCs (mental health clinics within the prison system) in The Netherlands since May 2013. Inclusion criterion for this study was the presence of a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) or Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnostic code belonging to the category of neurocognitive disorders. A DSM-IV-TR or DSM-5 diagnostic code of a neurocognitive disorder was classified in 254 out of 8391 unique individuals, resulting in a prevalence of 3.0% in the total PPC population. The most prevalent diagnosis was unspecified neurocognitive disorder (59.1%). The neurocognitive disorder group significantly differed from a random control group from the database (n = 762) on demographic, clinical and criminological variables. The prevalence of neurocognitive disorders in this real-world clinical sample is remarkably lower than in two earlier studies in similar populations. Also remarkable is the relatively high prevalence of an unspecified neurocognitive disorder. These findings lead us to hypothesise that neurocognitive disorders may be underdiagnosed in this population. Forensic psychiatric settings should evaluate whether they have sufficient expertise available in neuropsychological assessment.

A novel radiomics-based technique for identifying vulnerable coronary plaques: a follow-up study.

Previous reports have suggested that coronary computed tomography angiography (CCTA)-based radiomics analysis is a potentially helpful tool for assessing vulnerable plaques. We aimed to investigate whether coronary radiomic analysis of CCTA images could identify vulnerable plaques in patients with stable angina pectoris. This retrospective study included patients initially diagnosed with stable angina pectoris. Patients were randomly divided into either the training or test dataset at an 8 : 2 ratio. Radiomics features were extracted from CCTA images. Radiomics models for predicting vulnerable plaques were developed using the support vector machine (SVM) algorithm. The model performance was assessed using the area under the curve (AUC); the accuracy, sensitivity, and specificity were calculated to compare the diagnostic performance using the two cohorts. A total of 158 patients were included in the analysis. The SVM radiomics model performed well in predicting vulnerable plaques, with AUC values of 0.977 and 0.875 for the training and test cohorts, respectively. With optimal cutoff values, the radiomics model showed accuracies of 0.91 and 0.882 in the training and test cohorts, respectively. Although further larger population studies are necessary, this novel CCTA radiomics model may identify vulnerable plaques in patients with stable angina pectoris.

Echocardiographic Measurements in Normal Chinese Adults (EMINCA) II focusing on left ventricular and left atrial size and function by three-dimensional echocardiography.

Current guidelines encourage large studies in a diverse population to establish normal reference ranges for three-dimensional (3D) echocardiography for different ethnic groups. This study was designed to establish the normal values of 3D-left ventricular (LV) and left atrial (LA) volume and function in a nationwide, population-based cohort of healthy Han Chinese adults. A total of 1117 healthy volunteers aged 18-89 years were enrolled from 28 collaborating laboratories in China. Two sets of 3D echocardiographic instruments were used, and full-volume echocardiographic images were recorded and transmitted to a core laboratory for image analysis with a vendor-independent off-line workstation. Finally, 866 volunteers (mean age of 48.4 years, 402 men) were qualified for final analysis. Most parameters exhibited substantial differences between different sex and age groups, even after indexation by body surface area. The normal ranges of 3D-LV and 3D-LA volume and function differed from those recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines, presented by the World Alliance Societies of Echocardiography (WASE) study, and from the 2D values in the EMINCA study. The normal reference values of 3D echocardiography-derived LV and LA volume and function were established for the first time in healthy Han Chinese adults. Normal ranges of 3D-LV and 3D-LA echocardiographic measurements stratified with sex, age, and race should be recommended for clinical applications.

The landscape of etiological patterns of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in Thailand.

Thailand is among countries with the highest global incidence and mortality rates of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). While viral hepatitis and liver fluke infections have been associated with HCC and iCCA, respectively, other environmental risk factors, overall risk factor commonality and combinatorial roles, and effects on survival have not been systematically examined. We conducted a TIGER-LC consortium-based population study covering all high-incidence areas of both malignancies across Thailand: 837 HCC, 1474 iCCA, and 1112 controls (2011-2019) were comprehensively queried on lifelong environmental exposures, lifestyle, and medical history. Multivariate logistic regression and Cox proportional hazards analyses were used to evaluate risk factors and associated survival patterns. Our models identified shared risk factors between HCC and iCCA, such as viral hepatitis infection, liver fluke infection, and diabetes, including novel and shared associations of agricultural pesticide exposure (OR range of 1.50; 95% CI: 1.06-2.11 to 2.91; 95% CI: 1.82-4.63) along with vulnerable sources of drinking water. Most patients had multiple risk factors, magnifying their risk considerably. Patients with lower risk levels had better survival in both HCC (HR 0.78; 95% CI: 0.64-0.96) and iCCA (HR 0.84; 95% CI: 0.70-0.99). Risk factor co-exposures and their common associations with HCC and iCCA in Thailand emphasize the importance for future prevention and control measures, especially in its large agricultural sector. The observed mortality patterns suggest ways to stratify patients for anticipated survivorship and develop plans to support medical care of longer-term survivors, including behavioral changes to reduce exposures.

Risk analysis of noise-induced hearing loss of workers in the automobile manufacturing industries based on back-propagation neural network model: a cross-sectional study in Han Chinese population.

This study aims to predict the risk of noise-induced hearing loss (NIHL) through a back-propagation neural network (BPNN) model. It provides an early, simple and accurate prediction method for NIHL. Population based, a cross sectional study. Han, China. This study selected 3266 Han male workers from three automobile manufacturing industries. Information including personal life habits, occupational health test information and occupational exposure history were collected and predictive factors of NIHL were screened from these workers. BPNN and logistic regression models were constructed using these predictors. The input variables of BPNN model were 20, 16 and 21 important factors screened by univariate, stepwise and lasso-logistic regression. When the BPNN model was applied to the test set, it was found to have a sensitivity (TPR) of 83.33%, a specificity (TNR) of 85.92%, an accuracy (ACC) of 85.51%, a positive predictive value (PPV) of 52.85%, a negative predictive value of 96.46% and area under the receiver operating curve (AUC) is: 0.926 (95% CI: 0.891 to 0.961), which demonstrated the better overall properties than univariate-logistic regression modelling (AUC: 0.715) (95% CI: 0.652 to 0.777). The BPNN model has better predictive performance against NIHL than the stepwise-logistic and lasso-logistic regression model in terms of TPR, TNR, ACC, PPV and NPV (p<0.05); the area under the receiver operating characteristics curve of NIHL is also higher than that of the stepwise and lasso-logistic regression model (p<0.05). It was a relatively important factor in NIHL to find cumulative noise exposure, auditory system symptoms, age, listening to music or watching video with headphones, exposure to high temperature and noise exposure time in the trained BPNN model. The BPNN model was a valuable tool in dealing with the occupational risk prediction problem of NIHL. It can be used to predict the risk of an individual NIHL.

Gardnerella diversity and ecology in pregnancy and preterm birth.

The vaginal microbiome has been linked to negative health outcomes including preterm birth. Specific taxa, including Gardnerella spp., have been identified as risk factors for these conditions. Historically, microbiome analysis methods have treated all Gardnerella spp. as one species, but the broad diversity of Gardnerella has become more apparent. We explore the diversity of Gardnerella clades and genomic species in the vaginal microbiome of pregnant women and their associations with microbiome composition and preterm birth. Relative abundance of Gardnerella clades and genomic species and other taxa was quantified in shotgun metagenomic sequencing data from three distinct cohorts of pregnant women. We also assessed the diversity and abundance of Gardnerella variants in 16S rRNA gene amplicon sequencing data from seven previously conducted studies in differing populations. Individual microbiomes often contained multiple Gardnerella variants, and the number of clades was associated with increased microbial load, or the ratio of non-human reads to human reads. Taxon co-occurrence patterns were largely consistent across Gardnerella clades and among cohorts. Some variants previously described as rare were prevalent in other cohorts, highlighting the importance of surveying a diverse set of populations to fully capture the diversity of Gardnerella. The diversity of Gardnerella both across populations and within individual vaginal microbiomes has long been unappreciated, as has been the intra-species diversity of many other members of the vaginal microbiome. The broad genomic diversity of Gardnerella has led to its reclassification as multiple species; here we demonstrate the diversity of Gardnerella found within and between vaginal microbiomes.IMPORTANCEThe present study shows that single microbiomes can contain all currently known species of Gardnerella and that multiple similar species can exist within the same environment. Furthermore, surveys of demographically distinct populations suggest that some species appear more commonly in certain populations. Further studies in broad and diverse populations will be necessary to fully understand the ecological roles of each Gardnerella sp., how they can co-exist, and their distinct impacts on microbial communities, preterm birth, and other health outcomes.

DNA methylation and type 2 diabetes: a systematic review.

DNA methylation influences gene expression and function in the pathophysiology of type 2 diabetes mellitus (T2DM). Mapping of T2DM-associated DNA methylation could aid early detection and/or therapeutic treatment options for diabetics. A systematic literature search for associations between T2DM and DNA methylation was performed. Prospero registration ID: CRD42020140436. PubMed and ScienceDirect databases were searched (till October 19, 2023). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and New Castle Ottawa scale were used for reporting the selection and quality of the studies, respectively. Thirty-two articles were selected. Four of 130 differentially methylated genes in blood, adipose, liver or pancreatic islets (TXNIP, ABCG1, PPARGC1A, PTPRN2) were reported in > 1 study. TXNIP was hypomethylated in diabetic blood across ethnicities. Gene enrichment analysis of the differentially methylated genes highlighted relevant disease pathways (T2DM, type 1 diabetes and adipocytokine signaling). Three prospective studies reported association of methylation in IGFBP2, MSI2, FTO, TXNIP, SREBF1, PHOSPHO1, SOCS3 and ABCG1 in blood at baseline with incident T2DM/hyperglycemia. Sex-specific differential methylation was reported only for HOOK2 in visceral adipose tissue (female diabetics: hypermethylated, male diabetics: hypomethylated). Gene expression was inversely associated with methylation status in 8 studies, in genes including ABCG1 (blood), S100A4 (adipose tissue), PER2 (pancreatic islets), PDGFA (liver) and PPARGC1A (skeletal muscle). This review summarizes available evidence for using DNA methylation patterns to unravel T2DM pathophysiology. Further validation studies in diverse populations will set the stage for utilizing this knowledge for identifying early diagnostic markers and novel druggable pathways.

Validation and Application of a Dried Blood Spot Amoxicillin Assay

AbstractDried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK) investigations in situations where venous blood sampling is logistically and/or ethically challenging. The aim of this study was to establish, validate and demonstrate the application of a DBS amoxicillin assay for PK studies in vulnerable populations. The matrix effect, process efficiency (84–104%) and recovery (85–110%) of the liquid chromatography–mass spectrometry (LC–MS/MS) assay for amoxicillin in DBS was determined at 1, 10 and 100 µg/mL, and three different haematocrits. Thermal stability studies of amoxicillin in DBS were performed and a bridging study comprising 26 paired plasma and DBS samples was conducted in four healthy individuals. The limits of detection and quantification were 0.02 and 0.05 µg/mL for plasma and DBS amoxicillin assays, respectively. Accuracy and interday precision of amoxicillin in DBS (0.1–100 µg/mL) were 88–103% and 4.5–9.2%, respectively. At room temperature (22 °C) and 4 °C, amoxicillin was stable in DBS for ≈4 and 26 h, respectively. There was no degradation of amoxicillin in DBS at −20 °C for &gt; 6 months. When comparing DBS and plasma collected from healthy volunteers, the slope of the Deming regression was 0.74. Amoxicillin CL/F estimates from DBS and plasma concentration data were 40.8 and 30.7 L/h/70 kg, respectively; V/F was 43.2 and 37.4 L/70 kg, respectively. In conclusion, amoxicillin can be reliably assayed from DBS in research studies but may have limited application in therapeutic drug monitoring. Due to poor stability at room temperature, amoxicillin DBS samples should be promptly dried and placed in frozen storage.

Comprehensive examination of support needs and mental well-being: a mixed-method study of the Austrian general population in times of crisis

IntroductionIn the recent years, the Austrian general population has faced a confluence of multiple crises. This study investigates the support wishes and mental health parameters of the Austrian general population aiming to comprehending the unmet needs and providing guidance for future psychosocial interventions and research endeavors.Methods1,031 participants attended the online survey and one third (n = 332) wished for further support to improve mental well-being in April 2022. A total of 280 participants accompanied their support wish with written accounts. Participants’ mental health status was evaluated using the PHQ-9 (depression), GAD-7 (anxiety), ISI (insomnia), PSS-10 (perceived stress), CAGE (alcohol abuse), WHO-5 (well-being), and the SCOFF (eating disorder) questionnaires. Data analysis employed a mixed-methods approach.ResultsThe preeminent support wish identified was the need for professional mental support (29.3%), followed by communication (21.6%), other professional support except mental and medical support (13.9%). In line with these findings, participants expressing a support wish experienced increased mental health distress across all assessed parameters.ConclusionThe findings indicate the presence of a vulnerable population within the Austrian general population, which may benefit from targeted support interventions. Consequently, this study contributes to the identification of unmet support needs among the Austrian populace during times of crisis, facilitating the development and enhancement of precisely tailored intervention strategies.

Sex difference in the associations among risk factors with gastroesophageal reflux disease in a large Taiwanese population study

BackgroundGastroesophageal reflux disease (GERD) is a common global health issue. Previous studies have revealed a higher prevalence of GERD in females than in males, however few studies have investigated sex differences in the risk factors associated with GERD. Therefore, the aim of this population-based study was to examine sex differences in the risk factors for GERD in a large cohort of over 120,000 Taiwanese participants.MethodsWe enrolled 121,583 participants (male: 43,698; female: 77,885; mean age 49.9 ± 11.0 years) from the Taiwan Biobank. The presence of GERD was ascertained using self-reported questionnaires. Sex differences in the risk factors associated with GERD were examined using multivariable logistic regression analysis.ResultsThe overall prevalence of GERD was 13.7%, including 13.0% in the male participants and 14.1% in the female participants (p < 0.001). Multivariable analysis showed that older age, hypertension, smoking history, alcohol history, low fasting glucose, and low uric acid were significantly associated with GERD in the male participants. In the female participants, older age, diabetes, hypertension, smoking history, alcohol history, low systolic blood pressure, low fasting glucose, high hemoglobin, high total cholesterol, low high-density lipoprotein cholesterol (HDL-C), low low-density lipoprotein cholesterol, and low uric acid were significantly associated with GERD. Significant interactions were found between sex and age (p < 0.001), diabetes (p < 0.001), smoking history (p < 0.001), fasting glucose (p = 0.002), triglycerides (p = 0.001), HDL-C (p = 0.001), and estimated glomerular filtration rate (p = 0.002) on GERD.ConclusionsOur results showed a higher prevalence of GERD among females compared to males. Furthermore, sex differences were identified in the risk factors associated with GERD, and older age, diabetes, smoking history, and low HDL-C were more closely related to GERD in females than in males.

High-throughput DNA extraction strategy for fecal microbiome studies.

Next-generation sequencing (NGS) is a widely used method for determining the composition of the gut microbiota. Due to the differences in the gut microbiota composition between individuals, microbiome studies have expanded into large population studies to maximize detection of small effects on microbe-host interactions. Thus, the demand for a rapid and reliable microbial profiling is continuously increasing, making the optimization of high-throughput 96-format DNA extraction integral for NGS-based downstream applications. However, experimental protocols are prone to bias and errors from sample collection and storage, to DNA extraction, primer selection and sequencing, and bioinformatics analyses. Methodological bias can contribute to differences in microbiome profiles, causing variability across studies and laboratories using different protocols. To improve consistency and confidence of the measurements, the standardization of microbiome analysis methods has been recognized in many fields.

Validation of a prediction model for early reconnection after cryoballoon ablation.

We previously developed an early reconnection/dormant conduction (ERC) prediction model for cryoballoon ablation to avoid a 30-min waiting period with adenosine infusion. We now aimed to validate this model based on time to isolation, number of unsuccessful cryo-applications, and nadir balloon temperature. Consecutive atrial fibrillation patients who underwent their first cryoballoon ablation in 2018-2019 at the Leiden University Medical Center were included. Model performance at the previous and at a new optimal cutoff value was determined. A total of 201 patients were included (85.57% paroxysmal AF, 139 male, median age 61years (IQR 53-69)). ERC was found in 35 of 201 included patients (17.41%) and in 41 of 774 veins (5.30%). In the present study population, the previous cutoff value of - 6.7 provided a sensitivity of 37.84% (previously 70%) and a specificity of 89.07% (previously 86%). Shifting the cutoff value to - 7.2 in both study populations resulted in a sensitivity of 72.50% and 72.97% and a specificity of 78.22% and 78.63% in data from the previous and present study respectively. Negative predictive values were 96.55% and 98.11%. Applying the model on the 101 patients of the present study with all necessary data for all veins resulted in 43 out of 101 patients (43%) not requiring a 30-min waiting period with adenosine testing. Two patients (2%) with ERC would have been missed when applying the model. The previously established ERC prediction model performs well, recommending its use for centers routinely using adenosine testing following PVI.

DORA: an interactive map for the visualization and analysis of ancient human DNA and associated data.

The ability to sequence ancient genomes has revolutionized the way we study evolutionary history by providing access to the most important aspect of evolution-time. Until recently, studying human demography, ecology, biology, and history using population genomic inference relied on contemporary genomic datasets. Over the past decade, the availability of human ancient DNA (aDNA) has increased rapidly, almost doubling every year, opening the way for spatiotemporal studies of ancient human populations. However, the multidimensionality of aDNA, with genotypes having temporal, spatial and genomic coordinates, and integrating multiple sources of data, poses a challenge for developing meta-analyses pipelines. To address this challenge, we developed a publicly-available interactive tool, DORA, which integrates multiple data types, genomic and non-genomic, in a unified interface. This web-based tool enables browsing sample metadata alongside additional layers of information, such as population structure, climatic data, and unpublished samples. Users can perform analyses on genotypes of these samples, or export sample subsets for external analyses. DORA integrates analyses and visualizations in a single intuitive interface, resolving the technical issues of combining datasets from different sources and formats, and allowing researchers to focus on the scientific questions that can be addressed through analysis of aDNA datasets.

Quick recipes for gravitational-wave selection effects

Accurate modeling of selection effects is a key ingredient to the success of gravitational-wave astronomy. The detection probability plays a crucial role in both statistical population studies, where it enters the hierarchical Bayesian likelihood, and astrophysical modeling, where it is used to convert predictions from population-synthesis codes into observable distributions. We review the most commonly used approximations, extend them, and present some recipes for a straightforward implementation. These include a closed-form expression capturing both multiple detectors and noise realizations written in terms of the so-called Marcum Q-function and a ready-to-use mapping between signal-to-noise ratio (SNR) thresholds and false-alarm rates from state-of-the-art detection pipelines. The bias introduced by approximating the matched filter SNR with the optimal SNR is not symmetric: sources that are nominally below threshold are more likely to be detected than sources above threshold are to be missed. Using both analytical considerations and software injections in detection pipelines, we confirm that including noise realizations when estimating the selection function introduces an average variation of a few %. This effect is most relevant for large catalogs and specific subpopulations of sources at the edge of detectability (e.g. high redshifts).

Clinical implementation of first trimester screening for congenital heart defects.

To examine the feasibility and performance of implementing a standardized fetal cardiac scan at the time of a routine first-trimester ultrasound scan. A retrospective, single-center study in an unselected population between March 2021 and July 2022. A standardized cardiac scan protocol consisting of a four-chamber and 3-vessel trachea view with color Doppler was implemented as part of the routine first-trimester scan. Sonographers were asked to categorize the fetal heart anatomy. Data were stratified into two groups based on the possibility of evaluating the fetal heart. The influence of maternal and fetal characteristics and the detection of major congenital heart disease were investigated. A total of 5083 fetuses were included. The fetal heart evaluation was completed in 84.9%. The proportion of successful scans increased throughout the study period from 76% in the first month to 92% in the last month. High maternal body mass index and early gestational age at scan significantly decreased the feasibility. The first-trimester detection of major congenital heart defects was 7/16, of which four cases were identified by the cardiac scan protocol with no false-positive cases. First-trimester evaluation of the fetal heart by a standardized scan protocol is feasible to implement in daily practice. It can contribute to the earlier detection of congenital heart defects at a very low false positive rate.

Authority Over Investigation Decisions in Child Welfare Services: How is it Distributed Among Social Workers, Managers and Citizen Representatives?

ABSTRACTThis study examined the distribution of authority over decisions made during investigations within child welfare services (CWS). The distribution between various actors, such as social workers, citizen representatives and managers, was examined regarding 19 key decisions that frequently occur during investigations. The study also examined how the municipal socio‐economic status and the internal organizational conditions of CWS impact the overall hierarchical level of authority using linear regression analysis. The study was a full population study of Swedish municipalities and districts in larger cities (n = 309, response rate of 62%). The study indicates that the head of the unit holds authority over most decision types, followed by the social worker. However, the study also indicates that there are significant variations between municipalities and decision types. In the municipality delegating authority to the lowest hierarchical level, social workers hold authority over 15 decision types compared with two decision types in the municipality delegating authority to the highest hierarchical level. This variation concerns most decision types except two, where authority is almost exclusively delegated to the same actor in all municipalities. The regression analysis indicated that the educational level of the municipal inhabitants and the size of the CWS budget were the strongest predictors of the hierarchical level of authority in a municipality. High educational levels in municipalities are associated with delegating authority to low hierarchical levels, such as social workers, whereas large CWS budgets (spending as SEK per inhabitant) are associated with delegating authority to high hierarchical levels, such as top‐level managers. The implications of these results for social work research and practice are discussed.

Trends in the survival of patients with trisomy 13 from 1995 to 2021: A population study in Japan.

It remains unclear whether recent changes in the prognosis and management of patients with trisomy 13 impact patient survival. We investigated changes in survival of patients with trisomy 13 in Japan. Data from the Vital Statistics Database in Japan was retrieved to examine the association of sex, surgical history, and years of birth and death with changes in survival patterns in 1164 patients with trisomy 13 between 1995 and 2021. The rates of deaths due to trisomy 13 increased from 9.8% to 23.1% in those over 1 year of age and from 7.3% to 19.2% in those within 24 h of birth between 1995 and 2021. The median survival time was longer in 2009-2021 than in 1996-2008 (40 vs. 84 days, p < 0.001). The median survival time and the rate of patients with surgical history increased from 91 days and 16.0% in 1996-2008 to 179 days and 28.0% in 2009-2021, respectively. Median survival time among patients with trisomy 13 has increased over the last 26 years, with almost 1 in 3 patients currently surviving for more than 1 year. The increased surgical intervention rate might have contributed to this improvement.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) and clinical outcomes in dialysis patients.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), a factor accelerating the degradation of LDL receptors, was associated with a gender-dependent risk for cardiovascular (CV) events in the general population and with all-cause and CV mortality in two relatively small studies in black Africans and South Korean haemodialysis patients. The effect modification by gender was untested in these studies. The study enrolled 1188 dialysis patients from the Prospective Registry of The Working Group of Epidemiology of Dialysis Region Calabria (PROGREDIRE) cohort. PCSK9 was measured by colorimetric enzyme-linked immunosorbent assay. The primary outcomes were all-cause and CV mortality. Statistical analysis included Cox regression analysis and effect modification analysis. During a median 2.9-year follow-up, out of 494 deaths, 278 were CV-related. In unadjusted analyses, PCSK9 levels correlated with increased all-cause (HRfor1ln unit increase: 1.23, 95% CI 1.06-1.43, p =.008) and CV mortality (HRfor1ln unit increase: 1.26, 95% CI 1.03-1.54, p =.03). After multivariate adjustment, these associations were no longer significant (all-cause mortality, HRfor 1 ln unit increase: 1.16, 95% CI .99-1.36, p =.07; CV mortality, HRfor1ln unit increase: 1.18, 95% CI .95-1.46, p =.14). However, in fully adjusted interaction analyses, a doubling in the risk of this outcome in women was registered (Women, HRfor1ln unit increase: 1.88, 95% CI 1.27-2.78, p =.002; Men, HRfor1ln unit increase: 1.07, 95% CI .83-1.38, p =.61; p for effect modification: .02). PCSK9 levels are unrelated to all-cause mortality in haemodialysis patients but, like in studies of the general population, independently of other risk factors, entail a doubling in the risk of CV events in women in this population.

R2R3-MYB transcription factor CsMYB60 controls mature fruit skin color by regulating flavonoid accumulation in cucumber.

Skin color is an important trait that determines the cosmetic appearance and quality of fruits. In cucumber, the skin color ranges from white to brown in mature fruits. However, the genetic basis for this important trait remains unclear. We conducted a genome-wide association study of natural cucumber populations, along with map-based cloning techniques, on an F2 population resulting from a cross between Pepino (with yellow-brown fruit skin) and Zaoer-N (with creamy fruit skin). We identified CsMYB60 as a candidate gene responsible for skin coloration in mature cucumber fruits. In cucumber accessions with white to pale yellow skin color, a premature stop mutation (C to T) was found in the second exon region of CsMYB60, whereas light yellow cucumber accessions exhibited splicing premature termination caused by an intronic mutator-like element insertion in CsMYB60. Transgenic CsMYB60c cucumber plants displayed a yellow-brown skin color by promoting accumulation of flavonoids, especially hyperoside, a yellow-colored flavonol. CsMYB60c encodes a nuclear protein that primarily acts as a transcriptional activator through its C-terminal activation motif. RNA sequencing and DNA affinity purification sequencing assays revealed that CsMYB60c promotes skin coloration by directly binding to the YYTACCTAMYT motif in the promoter regions of flavonoid biosynthetic genes, including CsF3'H, which encodes flavonoid 3'-hydroxylase. The findings of our study not only offer insight into the function of CsMYB60 as dominantly controlling fruit coloration, but also highlight that intronic DNA mutations can have a similar phenotypic impact as exonic mutations, which may be valuable in future cucumber breeding programs.