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Integrating digital twin (DT) technologies with Geographic Information Systems (GIS) marks a transformative shift in geospatial analysis, enabling continuous synchronization for an accurate representation of the physical landscape, offering decision-makers dynamic and context-specific insights for informed decision-making. Geospatial data, crucial across various domains, has historically faced challenges in integration, visualization, and interpretation due to its vast and fragmented nature. The emergence of the DT concept has the potential to address these constraints by creating virtual replicas of real-world objects in a digital environment. The seamless integration of DT technologies with existing GIS (integrated DT-GIS) enables multiple stakeholders to make collaborative decisions through interactive processes. This review aims to investigate the state of the art of the use of integrated DT-GIS across domains such as urban planning, disaster management, and water resource and environmental management, challenges that hinder the full potential of integrated DT-GIS, and some improvements that can be made to enhance the capabilities of integrated DT-GIS for geospatial analysis to enhance the decision-making process.

Abstract Canine vector-borne infections (CVBIs) are a global health problem. The military working dogs of Sri Lanka die at an early age, and CVBIs have been a leading speculated cause. We examined CVBIs in the working dogs of the Sri Lanka air force (SLAF) and free-roaming dogs (FRDs) and privately owned dogs (PODs) country-wide. Giemsa-stained smears were prepared and conventional PCR-positive DNA was subjected to sequencing and phylogeny. Of the 668 dogs sampled, 212 (31.7%) had one or more CVBIs. The prevalence of infections among the FRDs (40.0%) was significantly higher than SLAF working dogs (30.0%; χ2 = 10.5216; p = 0.0012) and PODs (26.2%; χ2 = 5.3414, p = 0.0208) but not between SLAF dogs and PODs (χ2 = 1.7655, p = 0.1838). Many infected dogs were asymptomatic (57.4%), which was higher among the FRDs. Seven infectious agents were identified: Babesia gibsoni, B. canis, Ehrlichia canis, Anaplasma platys, Leishmania sp., Hepatozoon canis, and filaria worms. The most common infection was B. gibsoni (13.8%), followed by E. canis (9.9%). Three tick species: Rhipicephalus linneai, Rhipicephalus haemaphysaloides and Haemophysalis bispinosa were found infesting the dogs. The SLAF dogs were thoroughly quarantined upon arrival, but the infection prevalence was similar to PODs.

Abstract Suicide is the second leading cause of death in youth, and depression is a strong proximal predictor of adolescent suicide. It is important to identify psychological factors that may protect against suicide ideation in depressed adolescents. Self-compassion may be such a factor. Converging evidence indicates the inverse association between self-compassion and suicide ideation, but the neural mechanisms underlying their link remain unknown. Because self-referential caudate activity is associated with both self-compassion and suicide ideation, its functional connectivity might explain their relationship. In this study, we examined the relationship between self-compassion and caudate functional connectivity during self-appraisals, a typical self-referential paradigm, and their associations with suicide ideation in both depressed and healthy youth. In the scanner, 79 depressed youth and 36 healthy controls evaluated, from various perspectives, whether phrases they heard were self-descriptive. Self-compassion and suicide ideation were rated with self-report and interview-based measures. We found that self-compassion was associated with stronger left caudate functional connectivity with bilateral posterior superior temporal sulcus/temporoparietal junction, the left middle temporal gyrus (MTG), and the left middle occipital gyrus during positive versus negative self-appraisals. Stronger left caudate connectivity with the left MTG explained the association between higher self-compassion and lower suicide ideation, even controlling for non-suicide ideation depression severity, anxiety severity, and non-suicidal self-injurious behavior. The findings suggest that the left caudate to MTG connectivity during positive versus negative self-referential processing could be a biomarker to be targeted by neural stimulation interventions for reducing suicide ideation in depressed youth, combined with self-compassion interventions.

Abstract ALG1‐CDG is a rare, clinically variable metabolic disease, caused by the defect of adding the first mannose (Man) to N‐acetylglucosamine (GlcNAc2)‐pyrophosphate (PP)‐dolichol to the growing oligosaccharide chain, resulting in impaired N‐glycosylation of proteins. N‐glycosylation has a key role in functionality, stability, and half‐life of most proteins. Therefore, congenital defects of glycosylation typically are multisystem disorders. Here we report a 3‐year‐old patient with severe neurological, cardiovascular, respiratory, musculoskeletal and gastrointestinal symptoms. ALG1‐CDG was suggested based on exome sequencing and Western blot analysis. Despite her severe clinical manifestations and genetic diagnosis, serum transferrin glycoform analysis was normal. Western blot analysis of highly glycosylated proteins in fibroblasts revealed decreased intercellular adhesion molecule 1 (ICAM1), but normal lysosomal associated membrane protein 1 and 2 (LAMP1 and LAMP2) expression levels. Glycoproteomics in fibroblasts showed the presence of the abnormal tetrasacharide. Reviewing the literature, we found 86 reported ALG1‐CDG patients, but only one with normal transferrin analysis. Based on our results we would like to highlight the importance of multiple approaches in diagnosing ALG1‐CDG, as normal serum transferrin glycosylation or other biomarkers with normal expression levels can occur.

AimsAlthough highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS.Methods and resultsA genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10-8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2-SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26-1.35; P = 2.7 × 10-51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08-1.37; P = 1.4 × 10-3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90-5.12; P = 2.1 × 10-20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17-1.23; P = 4.8 × 10-73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05-1.9; P = 1.9 × 10-12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS.ConclusionDyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.

Wawekale Rainforest Reserve (WRR) is a primary lowland tropical rainforest area in the Western Province of Sri Lanka, established with diversity, but disturbed by human activities such as rubber cultivation, logging, poaching, chemical release, and the collection of firewood. Visual Encounter Surveys (VES) were conducted for 100 hours in the year 2022, which covered wide habitat distribution. The herpetofaunal diversity was measured in the WRR which can indicate broader ecological shifts, environmental changes, or habitat degradation. Water quality was measured in the WRR area to determine the ecosystem health and human impact. The study reports 171 species in 73 families, including two Critically Endangered (1.17%), six Endangered (3.51%), 16 Vulnerable (9.36%), and 14 Near Threatened (8.19%) species according to the IUCN Red List. The study area showed 51 endemic faunal species in Sri Lanka, which represented 29.83% of endemism. Based on the observations conducted on the herpetofauna diversity, the Shannon-Wiener diversity index (H) was calculated and the overall herpetofauna (H’H) showed high diversity within the forest premises. The water quality of the forest fragment had an influence from anthropogenic activities such as removing forest cover, bathing, washing vehicles, and releasing agro-chemical compounds resulting in high water temperature, basic pH level, high electrical conductivity, and high total dissolved solid conditions. The WRR, designated under protection, exhibits the need for immediate remedial actions to mitigate human-induced pollution and deforestation, emphasizing the critical importance of implementing proactive conservation measures to sustain ecological integrity and preserve biodiversity.

Genetic substudies of randomized controlled trials demonstrate that high coronary heart disease (CHD) polygenic risk score modifies statin CHD relative risk reduction; it is unknown if the association extends to statin users undergoing routine care. We sought to determine how statin effectiveness is modified by CHD polygenic risk score in a real-world cohort of participants without previous myocardial infarction. We determined CHD polygenic risk scores in participants of the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Covariate-adjusted Cox regression models were used to compare the risk of cardiovascular outcomes between statin users and matched nonusers. Statin effectiveness on incident myocardial infarction showed no gradient with increasing 10-year Pooled Cohort Equations atherosclerotic cardiovascular disease (ASCVD) risk across low, borderline, intermediate, and high ASCVD risk score groups. In contrast, statin effectiveness by polygenic risk was largest in the high polygenic risk score group (hazard ratio (HR) 0.41, 95% confidence interval (CI), 0.31-0.53; P = 1.5E-11), intermediate in the intermediate polygenic risk score group (HR 0.56, 95% CI, 0.47-0.66; P = 8.4E-12), and smallest in the low polygenic risk score group (HR 0.67, 95% CI, 0.47-0.97; P = 0.03; P for high vs. low = 0.01). ASCVD risk and statin low-density lipoprotein cholesterol (LDL-C) lowering did not differ across polygenic risk score groups. In patients undergoing routine care, CHD polygenic risk modified statin relative risk reduction of incident myocardial infarction independent of LDL-C lowering. Our findings extend prior work by identifying a subset (i.e., self-identified White individuals with low CHD polygenic risk scores) with attenuated clinical benefit from statins.

This report outlines the case of a child affected by a type of congenital disorder of glycosylation (CDG) known as ALG2-CDG (OMIM 607906), presenting as a congenital myasthenic syndrome (CMS) caused by variants identified in ALG2, which encodes an α1,3-mannosyltransferase (EC 2.4.1.132) involved in the early steps of N-glycosylation. To date, fourteen cases of ALG2-CDG have been documented worldwide. From birth, the child experienced perinatal asphyxia, muscular weakness, feeding difficulties linked to an absence of the sucking reflex, congenital hip dislocation, and hypotonia. Over time, additional complications emerged, such as inspiratory stridor, gastroesophageal reflux, low intake, recurrent seizures, respiratory infections, an inability to maintain the head upright, and a global developmental delay. Whole genome sequencing (WGS) revealed the presence of two ALG2 variants in compound heterozygosity: a novel variant c.1055_1056delinsTGA p.(Ser352Leufs*3) and a variant of uncertain significance (VUS) c.964C>A p.(Pro322Thr). Additional studies, including determination of carbohydrate-deficient transferrin (CDT) revealed a mild type I CDG pattern and the presence of an abnormal transferrin glycoform containing a linear heptasaccharide consisting of one sialic acid, one galactose, one N-acetyl-glucosamine, two mannoses and two N-acetylglucosamines (NeuAc-Gal-GlcNAc-Man2-GlcNAc2), ALG2-CDG diagnostic biomarker, confirming the pathogenicity of these variants.

Abstract The donor–acceptor (D-A) type of conjugated polymers has emerged as the paradigm of the third generation of electronically conducting polymers demonstrating improved infrared activity and intrinsic electronic conductivity. Judicious selection of donor (D) and acceptor (A) monomers for copolymerization can further fine-tune these properties. Notably, for such refinement, natural compounds provide many conjugated molecules with various functional groups. Berberine cation (Ber+) found in Coscinium fenestratum has extensive conjugation and contains both an electron deficient isoquinolium A moiety and electron-rich D-type methylenedioxy and methoxy groups. The incorporation of natural products in electronic materials is a novel area of research which opens a wide scope for future electronic and optoelectronic devices. Investigation of their fundamental properties via computer simulations is therefore important. In this study, quantum chemical calculations are performed using density functional theory (DFT) to investigate the electronic and optical properties of oligomers of Ber+ and 3,4-ethylenedioxythiophene (EDOT) and to explore the possibilities for homo-polymerization of Ber+ and its copolymerization with EDOT. It has been revealed that homo-polymerization is not favoured but copolymerization with EDOT is possible. As such, Ber+ was copolymerized with EDOT and the copolymers formed by electro-polymerization are extensively characterised and the D-A behaviour of the copolymers verified. Furthermore, the theoretical predictions have been compared with the experimental data.

Leishmania parasites are transmitted to mammalian hosts through the bite of sandflies. These parasites can infect phagocytic cells (macrophages, dendritic cells, and neutrophils) and non-phagocytic cells (B cells and fibroblasts). In mice models, the disease development or resolution is linked to T cell responses involving inflammatory cytokines and the activation of macrophages with the M1/M2 phenotype. However, this mechanism does not apply to human infection where a more complex immunological response occurs. The understanding of interactions between immune cells during Leishmania infection in humans is still limited, as current infection models focus on individual cell types or late infection using controlled human infection models (CHIMs). This study investigated the early parasite infection in freshly isolated peripheral blood-derived (PBD) leukocytes over 24 h. Flow cytometer analysis is used in immunophenotyping to identify different subpopulations. The study found that among the L. aethiopicaGFP-associated leukocytes, most cells were neutrophils (55.87% ± 0.09 at 4 h) and monocytes (23.50% ± 0.05% at 24 h). B cells were 12.43% ± 0.10% at 24 h. Additionally, 10–20% of GFP+ leukocytes did not belong to the aforementioned cell types, and further investigation revealed their identity as CD4+ T cells. Data not only confirm previous findings of Leishmania infection with PBD leukocytes and association with B cells but also suggest that CD4+ T cells might influence the early-stage of infection.

Abstract Hepatocellular carcinoma (HCC) is an aggressive primary malignancy of the liver and is the third most common cause of cancer‐related global mortality. There has been a steady increase in treatment options for HCC in recent years, including innovations in both curative and non‐curative therapies. These advances have brought new challenges and necessary improvements in strategies of disease monitoring, to allow early detection of HCC recurrence. Current serological and radiological strategies for post‐treatment monitoring and prognostication and their limitations will be discussed and evaluated in this review.

Background: In Sri Lanka, consumption of foods high in salt is high. Efforts are underway to tackle this issue, including the reformulation of fast foods to contain less salt. To succeed, understanding the practices in using salt among restaurant owners, cooks, and chefs are important. The objective of this study was to explore the challenges that may prevent the reformulation of foods to contain less salt in selected food premises in Sri Lanka.Methods: In a qualitative study design using semi-structured interviews and focus groups as data gathering tools, food premises from ten districts in Sri Lanka were selected; while owners of food premises, chefs and cooks were the study population.Results: The study recognised several key themes related to the study objective including awareness and practices on salt use, ‘eating outside’ behaviour, dominance of experience when using salt, commercial vs. domestic use of salt and catering to the demand. Findings included both supportive and resistive perceptions and attitudes.Conclusion: Fears of competition and consumer demands may prevent restaurant owners, chefs and cooks from taking decisive steps towards lowering salt use. Training them on ways of lowering salt, while maintaining the appeal for foods and building trust on equitable implementation of salt lowering policies may win industry support. However, such efforts must parallel approaches to changing consumer behavior towards salt containing foods.

Synthetic pyrethroid (SP) insecticides are used extensively around the world in both agricultural and non-agricultural applications. Their toxicity to mammals is low, however, they have a high toxicity to invertebrates, fish and amphibians, including threatened species, affecting the health of the ecosystems and their biodiversity. This paper reviews the current global research on SP toxicity on non-target aquatic organisms and looks at the current biomonitoring approaches to detect their effects on aquatic ecosystems. Over the past decade, the toxicological effects of SPs on aquatic macroinvertebrates have been documented in laboratory, mesocosm and field studies. Toxicity of SPs for aquatic organisms can vary greatly between species and highlights the importance of assessing toxicity in all major aquatic groups. However, little data exist, and more research is needed on how sediment bound SPs affect less studied aquatic groups like zooplankton, amphibians and fish. Detecting stress caused by toxicants in aquatic ecosystems can indicate how SPs are affecting individual organisms and the community. Development of toxicity thresholds for all aquatic groups like invertebrates, fish and amphibians, should assist in assessing the biological risks of SPs to inform regulations and management actions to protect aquatic ecosystems.

Abstract Few germline genetic variants have been robustly linked with breast cancer outcomes. We conducted trans-ethnic meta genome-wide association study (GWAS) of overall survival (OS) in 3973 breast cancer patients from the Pathways Study, one of the largest prospective breast cancer survivor cohorts. A locus spanning the UACA gene, a key regulator of tumor suppressor Par-4, was associated with OS in patients taking Par-4 dependent chemotherapies, including anthracyclines and anti-HER2 therapy, at a genome-wide significance level ( $$P = 1.27 \times 10^{ - 9}$$ P = 1.27 × 1 0 − 9 ). This association was confirmed in meta-analysis across four independent prospective breast cancer cohorts (combined hazard ratio = 1.84, $$P = 1.28 \times 10^{ - 11}$$ P = 1.28 × 1 0 − 11 ). Transcriptome-wide association study revealed higher UACA gene expression was significantly associated with worse OS ( $$P = 4.68 \times 10^{ - 7}$$ P = 4.68 × 1 0 − 7 ). Our study identified the UACA locus as a genetic predictor of patient outcome following treatment with anthracyclines and/or anti-HER2 therapy, which may have clinical utility in formulating appropriate treatment strategies for breast cancer patients based on their genetic makeup.

Canine vector-borne infections (CVBIs) are a global health problem. The military working dogs of Sri Lanka die at an early age, and CVBIs have been a leading speculated cause. We examined CVBIs in the working dogs of the Sri Lanka air force (SLAF) and free-roaming dogs (FRDs) and privately owned dogs (PODs) country-wide. Giemsa-stained smears were prepared and conventional PCR-positive DNA was subjected to sequencing and phylogeny. Of the 668 dogs sampled, 212 (31.7%) had one or more CVBIs. The prevalence of infections among the FRDs (40.0%) was significantly higher than SLAF working dogs (30.0%; χ2 = 10.5216; p = 0.0012) and PODs (26.2%; χ2 = 5.3414, p = 0.0208) but not between SLAF dogs and PODs (χ2 = 1.7655, p = 0.1838). Many infected dogs were asymptomatic (57.4%), which was higher among the FRDs. Seven infectious agents were identified: Babesia gibsoni, B. canis, Ehrlichia canis, Anaplasma platys, Leishmania sp., Hepatozoon canis, and filaria worms. The most common infection was B. gibsoni (13.8%), followed by E. canis (9.9%). Three tick species: Rhipicephalus linneai, Rhipicephalus haemaphysaloides and Haemophysalis bispinosa were found infesting the dogs. The SLAF dogs were thoroughly quarantined upon arrival, but the infection prevalence was similar to PODs. [ABSTRACT FROM AUTHOR]

Leishmania parasites are transmitted to mammalian hosts through the bite of sandflies. These parasites can infect phagocytic cells (macrophages, dendritic cells, and neutrophils) and non-phagocytic cells (B cells and fibroblasts). In mice models, the disease development or resolution is linked to T cell responses involving inflammatory cytokines and the activation of macrophages with the M1/M2 phenotype. However, this mechanism does not apply to human infection where a more complex immunological response occurs. The understanding of interactions between immune cells during Leishmania infection in humans is still limited, as current infection models focus on individual cell types or late infection using controlled human infection models (CHIMs). This study investigated the early parasite infection in freshly isolated peripheral blood-derived (PBD) leukocytes over 24 h. Flow cytometer analysis is used in immunophenotyping to identify different subpopulations. The study found that among the L. aethiopicaGFP-associated leukocytes, most cells were neutrophils (55.87% ± 0.09 at 4 h) and monocytes (23.50% ± 0.05% at 24 h). B cells were 12.43% ± 0.10% at 24 h. Additionally, 10–20% of GFP+ leukocytes did not belong to the aforementioned cell types, and further investigation revealed their identity as CD4+ T cells. Data not only confirm previous findings of Leishmania infection with PBD leukocytes and association with B cells but also suggest that CD4+ T cells might influence the early-stage of infection. [ABSTRACT FROM AUTHOR]