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The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

Abstract Urban heritage is a vital resource that connects communities to their local identity. Unplanned developments and rapid urbanisation often harm the authenticity of historic areas, disrupting the cultural fabric and altering their character. This study introduces the Relative Positive Impact Index (RPII), a novel technique for assessing the socio-cultural impacts of urban revitalisation. The significance of RPII lies in its ability to quantitatively evaluate the impacts on the cultural fabric and integrity of historic urban areas, which is crucial for sustainable urban development. The study’s objective is to apply RPII in evaluating qualitative socio-cultural characteristics in historic urban areas, with a focus on four main criteria and 16 sub-criteria, in the case of the Kuttichira precinct. The methodology integrates the analysis of published literature, a quantitative survey mapping the stakeholders’ perception, and qualitative insights. This approach facilitates an in-depth understanding of how urban revitalisation affects local socio-cultural dynamics, preserving the authenticity and character of historic areas. The study reveals that the revitalisation project in Kuttichira positively impacts the socio-cultural fabric of the area, maintaining cultural integrity and addressing social challenges. These findings offer valuable insights for sustainable urban development and policymaking in historic areas. The study recommends the application of RPII in other urban precincts for comparative analysis and further development of urban development practices, contributing to informed urban policy and planning decisions.

Cybersecurity is een randvoorwaarde voor organisaties en de samenleving om cyberrisico’s te beheersen. Deze cyberrisico’s kunnen zowel lokaal als wereldwijd stabiliteit en veiligheid in gevaar brengen. Het groeiend aantal cyberaanvallen, de toenemende complexiteit en de inzet van steeds meer geavanceerde digitale middelen zijn een punt van grote zorg voor alle belanghebbenden. De publieke transparantie omtrent de wijze waarop de steeds ernstiger wordende cyberrisico’s worden beheerst, is dan ook van groot belang en ook steeds vaker een vereiste. Dit komt onder andere tot uiting in de risicoparagraaf van het bestuursverslag en de ontwikkelende regelgeving, zoals die van de Cybersecurity Act en de SEC over cyber disclosures.

Background The neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic inflammation has been associated with worse prognosis in several chronic disease states, including heart failure. However, few data exist on the prognostic impact of elevated baseline NLR or change in NLR levels during follow-up in patients undergoing transcatheter or surgical aortic valve replacement (TAVR or SAVR) for aortic stenosis. Methods and Results NLR was available in 5881 patients with severe aortic stenosis receiving TAVR or SAVR in PARTNER (Placement of Aortic Transcatheter Valves) I, II, and S3 trials/registries (median [Q1, Q3] NLR, 3.30 [2.40, 4.90]); mean NLR, 4.10; range, 0.5-24.9) and was evaluated as continuous variable and categorical tertiles (low: NLR ≤2.70, n=1963; intermediate: NLR 2.70-4.20, n=1958; high: NLR ≥4.20, n=1960). No patients had known baseline infection. High baseline NLR was associated with increased risk of death or rehospitalization at 3 years (58.4% versus 41.0%; adjusted hazard ratio [aHR], 1.39; 95% CI, 1.18-1.63; P

Background: Recognizing the scarcity of data on caffeine consumption among university students in Malaysia, this study was designed to first characterize the habitual caffeine intake within this group. This study further investigated the potential association between these caffeine consumption patterns and sleep quality and mental health status. Methodology: The study employed an online self-administered questionnaire to assess habitual caffeine intake from various products. Sleep quality and mental health were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and the Depression, Anxiety, and Stress Scale-21 (DASS-21), respectively. Results: 78% of the respondents consumed caffeinated products daily within the safe level recommended by the European Food Safety Authority (£400mg/day). Only 2.6% of the students consumed caffeine exceeding the recommended limit. The median total daily caffeine intake was 100mg/day. Most students had poor sleep quality (77.3%), with 43.5%, 49.5%, and 33.0% reporting varying levels of depression, anxiety, and stress, respectively. Odds ratio calculations revealed respondents consuming less than or more than 400 mg/day of caffeine did not show significantly different odds of poor sleep quality, depression, anxiety, or stress compared to non-consumers. Conclusions: This study highlights the need for further localized research on caffeine's effects among Malaysian university students regarding caffeine consumption, sleep, and mental health.

Abstract Aims Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with cardiovascular (CV) and non‐CV events, but long‐term risk is poorly studied. We assessed incidence and predictors of the long‐term CV and non‐CV events. Methods and results Patients presenting with acute HF, EF ≥ 45%, and N‐terminal pro‐brain natriuretic peptide > 300 ng/L were enrolled in the Karolinska‐Rennes study in 2007–11 and were reassessed after 4–8 weeks in a stable state. Long‐term follow‐up was conducted in 2018. The Fine–Gray sub‐distribution hazard regression was used to detect predictors of CV and non‐CV deaths, investigated separately from baseline acute presentation (demographic data only) and from the 4–8 week outpatient visit (including echocardiographic data). Of 539 patients enrolled [median age 78 (interquartile range: 72–84) years; 52% female], 397 patients were available for the long‐term follow‐up. Over a median follow‐up time from acute presentation of 5.4 (2.1–7.9) years, 269 (68%) patients died, 128 (47%) from CV and 120 (45%) from non‐CV causes. Incidence rates per 1000 patient‐years were 62 [95% confidence interval (CI) 52–74] for CV and 58 (95% CI 48–69) for non‐CV death. Higher age and coronary artery disease (CAD) were independent predictors of CV death, and anaemia, stroke, kidney disease, and lower body mass index (BMI) and sodium concentrations of non‐CV death. From the stable 4–8 week visit, anaemia, CAD, and tricuspid regurgitation (>3.1 m/s) were independent predictors of CV death, and higher age of non‐CV death. Conclusions In patients with acute decompensated HFpEF, over 5 years of follow‐up, nearly two‐thirds of patients died, half from CV and the other half from non‐CV causes. CAD and tricuspid regurgitation were associated with CV death. Stroke, kidney disease, lower BMI, and lower sodium were associated with non‐CV death. Anaemia and higher age were associated with both outcomes. [Correction added on 24 March 2023, after first online publication: In the first sentence of the Conclusions, ‘two‐thirds’ has been inserted before ‘of patients died...’ in this version.]

The gut microbiome, hosting a diverse microbial community, plays a pivotal role in metabolism, immunity, and digestion. While the potential of exercise to influence this microbiome has been increasingly recognized, findings remain incongruous. This systematic review examined the effects of exercise on the gut microbiome of human and animal models. Databases (i.e., PubMed, Cochrane Library, Scopus, and Web of Science) were searched up to June 2022. Thirty-two exercise studies, i.e., 19 human studies, and 13 animal studies with a minimum of two groups that discussed microbiome outcomes, such as diversity, taxonomic composition, or microbial metabolites, over the intervention period, were included in the systematic review (PROSPERO registration numbers for human review: CRD42023394223). Results indicated that over 50% of studies found no significant exercise effect on human microbial diversity. When evident, exercise often augmented the Shannon index, reflecting enhanced microbial richness and evenness, irrespective of disease status. Changes in beta-diversity metrics were also documented with exercise but without clear directionality. A larger percentage of animal studies demonstrated shifts in diversity compared to human studies, but without any distinct patterns, mainly due to the varied effects of predominantly aerobic exercise on diversity metrics. In terms of taxonomic composition, in humans, exercise usually led to a decrease in the Firmicutes/Bacteroidetes ratio, and consistent increases with Bacteroides and Roseburia genera. In animal models, Coprococcus, another short chain fatty acid (SCFA) producer, consistently rose with exercise. Generally, SCFA producers were found to increase with exercise in animal models. With regard to metabolites, SCFAs emerged as the most frequently measured metabolite. However, due to limited human and animal studies examining exercise effects on microbial-produced metabolites, including SCFAs, clear patterns did not emerge. The overall risk of bias was deemed neutral. In conclusion, this comprehensive systematic review underscores that exercise can potentially impact the gut microbiome with indications of changes in taxonomic composition. The significant variability in study designs and intervention protocols demands more standardized methodologies and robust statistical models. A nuanced understanding of the exercise-microbiome relationship could guide individualized exercise programs to optimize health.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=394223, identifier CRD42023394223.

AIMS: Contemporary 2nd-generation thin-strut drug-eluting stents (DES) are considered standard of care for revascularization of patients undergoing percutaneous coronary intervention. A previous meta-analysis of 10 randomized controlled trials (RCTs) with 11 658 patients demonstrated a 16% reduction in the 1-year risk of target lesion failure (TLF) with ultrathin-strut DES compared with conventional 2nd-generation thin-strut DES. Whether this benefit is sustained longer term is not known, and newer trial data may inform these relative outcomes. We therefore sought to perform an updated systematic review and meta-analysis of RCTs comparing clinical outcomes with ultrathin-strut DES (≤70 µm strut thickness) with conventional 2nd-generation thin-strut DES. METHODS AND RESULTS: We performed a random-effects meta-analysis of all RCTs comparing ultrathin-strut DES to conventional 2nd-generation thin-strut DES. The pre-specified primary endpoint was long-term TLF, a composite of cardiac death, myocardial infarction (MI), or clinically driven target lesion revascularization (CD-TLR). Secondary endpoints included the components of TLF, stent thrombosis (ST), and all-cause death. There were 16 eligible trials in which 20 701 patients were randomized. The weighted mean follow-up duration was 2.5 years. Ultrathin-strut DES were associated with a 15% reduction in long-term TLF compared with conventional 2nd-generation thin-strut DES [relative risk (RR) 0.85, 95% confidence interval (CI) 0.76-0.96, P = 0.008] driven by a 25% reduction in CD-TLR (RR 0.75, 95% CI 0.62-0.92, P = 0.005). There were no significant differences between stent types in the risks of MI, ST, cardiac death, or all-cause mortality. CONCLUSIONS: At a mean follow-up of 2.5 years, ultrathin-strut DES reduced the risk of TLF, driven by less CD-TLR compared with conventional 2nd-generation thin-strut DES, with similar risks of MI, ST, cardiac death, and all-cause mortality.

Heart failure (HF) is a global pandemic affecting 64 million people worldwide. HF with preserved ejection fraction (HFpEF) has traditionally received less attention than its main counterpart, HF with reduced ejection fraction (HFrEF). The incidence and prevalence of HFpEF show geographic variation and are increasing over time, soon expected to surpass those of HFrEF. Morbidity and mortality rates of HFpEF are considerable, albeit lower than those of HFrEF. This review focuses on the burden of HFpEF, providing contemporary data on epidemiology, clinical characteristics and comorbidities, cause-specific outcomes, costs and pharmacotherapy.

In biology and biomedicine, relating phenotypic outcomes with genetic variation and environmental factors remains a challenge: patient phenotypes may not match known diseases, candidate variants may be in genes that haven't been characterized, research organisms may not recapitulate human or veterinary diseases, environmental factors affecting disease outcomes are unknown or undocumented, and many resources must be queried to find potentially significant phenotypic associations. The Monarch Initiative (https://monarchinitiative.org) integrates information on genes, variants, genotypes, phenotypes and diseases in a variety of species, and allows powerful ontology-based search. We develop many widely adopted ontologies that together enable sophisticated computational analysis, mechanistic discovery and diagnostics of Mendelian diseases. Our algorithms and tools are widely used to identify animal models of human disease through phenotypic similarity, for differential diagnostics and to facilitate translational research. Launched in 2015, Monarch has grown with regards to data (new organisms, more sources, better modeling); new API and standards; ontologies (new Mondo unified disease ontology, improvements to ontologies such as HPO and uPheno); user interface (a redesigned website); and community development. Monarch data, algorithms and tools are being used and extended by resources such as GA4GH and NCATS Translator, among others, to aid mechanistic discovery and diagnostics.

Urban revitalization is a viable approach to revive historic temple precincts which imbibe physical, social and cultural aspects of not only bygone times but the present, woven seamlessly into the precinct's functioning, offering a rich cultural milieu. This paper discusses the case of one such revitalization project of the 'Tali Temple Tank Precinct' in Calicut City, Kerala; to demonstrate the value added to society through such initiatives. A mixed-methods approach was adopted to gauge socio-cultural factors contributing to perceptions of success and failure of the project. A semi-structured interview was conducted with 20 key stakeholders within the temple tank precinct. Thematic analysis of responses suggests that a relatively high percentage of respondents appreciate the revitalization, as it contributes to maintaining the cultural character and integrity of the temple heritage precinct while solving societal challenges and issues. The study underscores the need for community stakeholder participation during developmental stages of the project, and to carry out subsequent community perception assessments. This will allow successes or failures to be monitored and measured for sustainable development or remedial interventions and improvements. Such a cyclic process of management for the urban revitalization of sacred precincts will enable it to be genuinely appreciated and successful.

Heart failure (HF) is a rapidly growing public health issue with an estimated prevalence of 64 million people globally. Although the incidence of HF has stabilised worldwide and seems to be declining in developed countries, the prevalence is increasing due to the ageing of the population, improved survival after MI and improved treatment and survival of patients with HF. Yet, HF remains associated with high mortality and morbidity, poor quality of life and functional capacity, and confers a substantial burden to the healthcare system. The prevalence, incidence, mortality and morbidity rates reported show geographical variations, depending on the different aetiologies and clinical characteristics observed among patients with HF. In this review, we provide an overview of the global epidemiology of HF with updated data on prevalence, incidence, mortality and morbidity worldwide.

Objectives: This study aimed to evaluate the relationship of diabetes mellitus (DM) and trigeminal neuralgia (TN) in order to provide new insight for TN pathogenesis. Materials and Methods: This retrospective cross-sectional study compared the prevalence of DM in patients with TN and healthy controls without TN during 2007-2018. Totally, 193 participants were enrolled in the patient and control groups. These participants were selected among patients referred to the Oral and Maxillofacial Medicine Department of Dental School of Shiraz University of Medical Sciences. The age and gender of patients were matched in the two groups. DM (types 1 and 2) was diagnosed based on patient reports and routinely requested lab tests (fasting blood sugar, 2-hour post-prandial). The odds ratio (OR) and Chi-square test were used to compare the mean values. Results: The prevalence of DM in TN patients and control group was 11.4% and 9.8%, respectively. The mean age of the participants was 56.96±13.66 and 56.46±13.47 years in the TN and control groups, respectively. The difference in TN prevalence between the two groups was not significant (P=0.62). Conclusion: Although the prevalence of DM in patients with TN was higher than the control group, this difference was not significant (P>0.05). Women with TN showed DM 25% more than men with TN.

Background Peripheral artery disease (PAD) and heart failure (HF) often coexist. Whether PAD influences outcomes of transcatheter mitral valve repair (TMVr) in patients with HF and severe secondary mitral regurgitation is unknown. The objectives are to assess the impact of PAD on outcomes of TMVr plus guideline‐directed medical therapy (GDMT) versus GDMT alone in patients with HF and secondary mitral regurgitation. Methods and Results The COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) randomized patients with HF with ≥moderate‐to‐severe secondary mitral regurgitation to TMVr with MitraClip implant plus GDMT versus GDMT alone. We evaluated the relationship between PAD and 2‐year outcomes in the COAPT trial and examined whether PAD modified the benefits of TMVr. Among 614 patients enrolled, 109 (17.8%) had PAD. By multivariable analysis, PAD was independently associated with 2‐year mortality (adjusted hazard ratio [adjHR], 1.51 [95% CI, 1.07–2.15]) but not HF hospitalizations. Compared with GDMT alone, TMVr reduced the 2‐year risk of death in patients without PAD (adjHR, 0.42 [95% CI, 0.30–0.60]) but not those with PAD (adjHR, 1.27 [95% CI, 0.72–2.27]; Pinteraction=0.001). In contrast, TMVr reduced HF hospitalizations consistently in patients with (adjHR, 0.65 [95% CI, 0.35–1.23]) and without (adjHR, 0.42 [95% CI, 0.31–0.57]) PAD (Pinteraction=0.22). Improvements in health status and exercise capacity at 2 years with TMVr compared with GDMT alone were similar in degree, irrespective of PAD status (Pinteraction=0.76 and 0.64, respectively). Conclusions In patients with HF and severe secondary mitral regurgitation, the reduced mortality with TMVr in the overall COAPT study population was not observed in the subgroup of patients with PAD. However, TMVr reduced HF hospitalizations and improved health status and exercise capacity consistently in patients with and without PAD. Registration Clinical Trial Name: Cardiovascular Outocmes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (The COAPT Trial); URL: https://www.clinicaltrials.gov/; Unique identifier: NCT01626079. https://clinicaltrials.gov/ct2/show/NCT01626079

BackgroundReports about the magnitude of co-existence of under- and over-nutrition is limited in Afghanistan. This study aimed to assess the prevalence of double burden of malnutrition (DBM) at individual and household level in Afghanistan.MethodsThis study was done based on the Afghanistan National Nutrition Survey 2013, which included a representative sample of 126,890 individuals (including more than 18,000 households) throughout Afghanistan. Intra-individual DBM was defined as the co-existence of "overweight/obese" and "stunting or micronutrient deficiencies" (including anemia, vitamin A deficiency, vitamin D deficiency and iodine deficiency). At the household level, DBM was considered as having at least one household member as overweight/obese and at least one another member of that household as undernourished (stunted, wasted, underweight or any micronutrient deficiency). SPSS and Stata software were used in the current analysis. Cross-tabulations was used to estimate the prevalence and its 95% confidence interval(CI). This study was ethically approved at Tehran University of Medical sciences.ResultsThe overall prevalence of intra-individual DBM was 12.5% (95% CI: 12.1; 12.9). Among the whole study participants at individual level of DBM, 11.7% (11.3; 12.1) of individuals had overweight along with stunting simultaneously and 20.5% (18.8; 22.4) had overweight and micronutrient deficiencies at the same time at individual level. The household level of DBM was found among 28.6% (95% CI: 27.9; 29.4) of households; such that 27.3% (26.6; 28.1) of households had at least one member with overweight and another member with stunting or wasting or underweight. Co-existence of overweight and micronutrient deficiencies at the same household was seen in 38.3% (35.5; 41.2).ConclusionThis study demonstrated a high prevalence of DBM at individual and household level in Afghanistan. Therefore, developing appropriate national macro-policies and strategies and designing appropriate programs such as public awareness programs, subsidization, food assistance programs, food fortification and dietary supplementation should be implemented by the ministry of public health, inter- related organs and international health agencies to reduce the burden of this problem in this country.

Background Diabetes mellitus and high platelet reactivity (HPR) on clopidogrel are both associated with increased risk of ischemic events after percutaneous coronary intervention, but whether the HPR‐associated risk of adverse ischemic events differs by diabetes mellitus status is unknown. Methods and Results ADAPT‐DES (Assessment of Dual Antiplatelet Therapy With Drug‐Eluting Stents) was a prospective, multicenter registry of patients treated with coronary drug‐eluting stents. HPR was defined as P2Y12 reaction units >208 by the VerifyNow point‐of‐care assay. Cox multivariable analysis was used to assess whether HPR‐associated risk of major adverse cardiac events (MACE; cardiac death, myocardial infarction, or stent thrombosis) varied for patients with insulin‐treated diabetes mellitus (ITDM), non–ITDM, and no diabetes mellitus. Diabetes mellitus and HPR were included in an interaction analysis. Of 8582 patients enrolled, 2429 (28.3%) had diabetes mellitus, of whom 998 (41.1%) had ITDM. Mean P2Y12 reaction units were higher in patients with diabetes mellitus versus without diabetes mellitus, and HPR was more frequent in patients with diabetes mellitus. HPR was associated with consistently increased 2‐year rates of MACE in patients with and without diabetes mellitus (Pinteraction=0.36). A significant interaction was present between HPR and non–insulin‐treated diabetes mellitus versus ITDM for 2‐year MACE (adjusted hazard ratio [HR] for non–ITDM, 2.28 [95% CI, 1.39–3.73] versus adjusted HR for ITDM, 1.02 [95% CI, 0.70–1.50]; Pinteraction=0.01). Conclusions HPR was more common in patients with diabetes mellitus and was associated with an increased risk of MACE in both patients with and without diabetes mellitus. In patients with diabetes mellitus, a more pronounced effect of HPR on MACE was present in lower‐risk non–ITDM patients than in higher‐risk patients with ITDM. Registration URL: https://clinicaltrials.gov/ct2/show/NCT00638794; Unique identifier: NCT00638794. ADAPT‐DES (Assessment of Dual Antiplatelet Therapy With Drug‐Eluting Stents).