South Central Asia Research Articles

The impact of the QBO vertical structure on June extreme high temperatures in South Asia

Using observation data and numerical simulations, we have demonstrated that the stratospheric Quasi-Biennial Oscillation (QBO) can predict extreme high temperatures (EHTs) in South Asia in June. The vertical structure of the QBO plays a crucial role in this prediction. When the QBO in June shows easterlies (westerlies) at 50 hPa and westerlies (easterlies) at 70 hPa, more (fewer) EHT events occur. This likely results from the QBO’s vertical structure causing positive (negative) temperature anomalies in the lower stratosphere and negative (positive) static stability anomalies near the tropical tropopause. These anomalies enhance (weaken) convective activity over the equatorial Indian Ocean, leading to anomalous circulation with ascending (descending) air over the equatorial Indian Ocean and descending (ascending) air over northern and central South Asia. This suppresses (promotes) convection over northern and central South Asia, affecting cloud formation and precipitation. Consequently, more (less) solar radiation reaches the region, along with weaker (stronger) evaporative cooling effects, warming (cooling) the surface and creating a background state conducive to (against) EHT events. Additionally, the opposite zonal winds at 30 hPa and 50 hPa in April may serve as a reference factor for predicting the probability of EHT events in northern and central South Asia. This study provides a potential approach for forecasting tropospheric extreme weather events based on stratospheric signals.

Global burden of oral cancer in 2022 attributable to smokeless tobacco and areca nut consumption: a population attributable fraction analysis

Consuming products that contain smokeless tobacco or areca nut increases the risk of oral cancer. We aimed to estimate the burden of oral cancer attributable to smokeless tobacco or areca nut consumption globally and by type of smokeless tobacco or areca nut product in four major consuming countries. We calculated population attributable fractions (PAFs) using prevalence of current use of smokeless tobacco or areca nut products from national surveys and corresponding risks of oral cancer from the literature. We applied PAFs to national estimates of oral cancer incidence in 2022 from the Global Cancer Observatory's Cancer Today database to obtain cases attributable to smokeless tobacco or areca nut consumption. We modelled 95% uncertainty intervals (UIs) using Monte Carlo simulations. Globally, an estimated 120 200 (95% UI 115 300-124 300) cases of oral cancer diagnosed in 2022 were attributable to smokeless tobacco or areca nut consumption, accounting for 30·8% (95% UI 29·6-31·9) of all oral cancer cases (120 200 of 389 800). An estimated 77% of attributable cases were among male patients (92 600 cases, 95% UI 88 000-96 500) and 23% were among female patients (27 600 cases, 26 000-29 000). Regions with the highest PAFs were Melanesia, Micronesia, and Polynesia (78·6%, 95% UI 74·4-80·5), southcentral Asia (57·5%, 54·8-59·5), and southeastern Asia (19·8%, 19·0-20·6). Lower-middle-income countries represented 90·2% of the world total attributable cases (108 400 cases, 95% UI 103 400-112 200). Our findings suggest that one in three cases of oral cancer globally are attributable to smokeless tobacco or areca nut consumption, and could be prevented through smokeless tobacco and areca nut control. Global cancer control efforts must incorporate further measures to reduce smokeless tobacco and areca nut consumption in populations with the largest attributable burden. French National Cancer Institute.

Concurrent droughts across Major River Basins of the World modulated by El Niño–Southern Oscillation

Droughts are among the costliest natural disasters with far-reaching impacts. Focusing on the influence of El Niño–Southern Oscillation (ENSO) on worldwide droughts, this paper presents a formulation of the complex network of concurrent droughts across the Major River Basins (MRBs) of the World. Specifically, concurrent droughts are measured by event synchronization and interconnections of concurrent droughts are determined by significance test. Event coincidence analysis is incorporated into interconnections to quantify the effects of El Niño and La Niña events. A case study is devised for the 3-monthly standardized precipitation index (SPI) of Global Drought and Flood Catalogue during the period from 1950 to 2016. The results highlight that owing to the synchronization of droughts, there exist nine communities of the MRBs, each covering MRBs across different continents. While the correlation between SPI and ENSO exhibits mixed patterns for MRBs grouped by continent, there exist distinct patterns of correlation for MRBs grouped by community. Overall, 28.88% of concurrent droughts tend to be modulated by El Niño events, especially over MRBs in South-West Pacific, South Africa, northern South America and South Asia. In the meantime, 23.51% of concurrent droughts tend to be modulated by La Niña events, especially over MRBs in the United States, southwestern South America, northern China and Central Asia. The modulation of El Niño and La Niña is confirmed by composite analysis of SPI and detailed analysis of the Yangtze River Basin. Overall, the complex network provides useful information for drought forecasting and disaster mitigation.

Epidemiological Profile of Oral Cancer Patients Attending at B.P. Koirala Memorial Cancer Hospital, Chitwan, Nepal

Background: Oral cancer is one of the most prevalent and leading causes of mortality in certain regions, like South-Central Asia. The incidence of oral cancer in Nepal is also increasing. Oral cancer is preventable and treatable if diagnosed in an early stage. The study conducted at B.P. Koirala Memorial Cancer Hospital (BPKMCH) in Bharatpur, Nepal, was aimed at assessing the epidemiological profile of oral cancer patients attending BPKMCH. Methods: A descriptive cross-sectional study design was used to assess the epidemiological profile of oral cancer, and 50 patients were included in this study during January to July 2023. A semi-structured interview schedule was developed, which has 3 parts, viz., i. socio-demographic variables, ii. Lifestyle-related factors and iii. Clinical profile of oral cancer, to obtain the information from the respondents. Results: The study findings revealed that out of 50 majorities of respondents (88%) were male. According to the religion, most of them (84%) were Hindu, and likewise, according to ethnicity, about half of them (40%) belong to Madeshi, followed by 30% Brahmin/Chhetri. Similarly, most of the respondents (90%) were married. Regarding the exposure to risk factors, half of the respondents (50%) had habits of smoking consumption, More than half (68%) had the habit of tobacco consumption, near to half (40%) had the habit of Gudka consumption, and 68% had the habit of alcohol consumption. None of the respondents had the habits of oral sex or a family history of oral cancer. Similarly, about one-third (30%) of respondents had stage IV, followed by 28% stage II, 26% stage I, and only a few (14%) stages in III disease; all the oral cancer was OSCC. Concerning the treatment modalities, 36% of respondents had surgery, near to one quarter (20%) received chemotherapy, 10% received radiation therapy, and 30% of respondents had surgery with adjuvant therapy. Conclusion: The study found that the majority of oral cancer patients attending BPKMCH were between the ages of 30 and 45 and were predominantly male. Smoking, tobacco, and Gudka consumption are the main risk factors for oral cancer. The risk assessment approach and screening program should be focused on preventing oral cancer.

A global analysis of the burden of ischemic heart disease attributable to diet low in fiber between 1990 and 2019

AimIschemic heart disease (IHD) represents a major cardiovascular condition heavily influenced by dietary factors. This study endeavors to assess the global, regional, and temporal impact of low-fiber diets on the burden of IHD.MethodLeveraging data from the Global Burden of Disease (GBD) 2019 study, we analyzed the worldwide burden of IHD resulting from diet low in fiber using indices including death and disability-adjusted life years (DALY). This burden was further segmented based on variables including regions and countries. To track the evolution from 1990 to 2019, we utilized the Joinpoint regression model to estimate the temporal trend of IHD burden stemming from low-fiber diets.ResultsIn 2019, a total of 348.85 thousand (95%UI: 147.57, 568.31) deaths and 7942.96 thousand (95%UI: 3373.58,12978.29) DALY (95% UI: 707.88, 1818) of IHD were attributed to diet low in fiber globally. These figures correspond to 3.82% of all IHD deaths and 4.36% of total IHD DALYs. The age-standardized death and DALY rates per 100,000 individuals were 4.48 (95% UI: 1.90,7.27) and 97.4(95%UI: 41.44, 158.88) respectively. However, significant regional disparities emerged in these age-standardized rates, with South Asia and Central Asia experiencing the highest rates. Between 1990 and 2019, we observed that most regions displayed a downward trend of the age-standardized DALY and death rate of IHD resulting from low-fiber diets, except for Central Sub-Saharan Africa and Southern Sub-Saharan Africa.ConclusionOur analysis underscores the substantial toll of IHD associated with low-fiber diets, particularly considering the significant regional variations. Therefore, it is imperative to sustain efforts to implement effective measures aimed at enhancing fiber intake worldwide, particularly in countries with lower socio-demographic indices.

Serum mRNA levels of cytokeratin-19 and vascular endothelial growth factor in oral squamous cell carcinoma and oral potentially malignant disorders using RT-PCR

BackgroundOral cancers, which include tumors of the oral cavity, salivary glands, and pharynx, are becoming increasingly prevalent worldwide. Squamous cell carcinoma accounts for over 90% of malignant oral lesions, with oral squamous cell carcinoma (OSCC) being notably common in the Indian subcontinent and other regions of Asia. This is especially true in South-Central Asia, including Sri Lanka, where it is particularly prevalent among men. This study aims to evaluate the levels of Vascular Endothelial Growth Factor-A (VEGF-A) and Cytokeratin-19 (CK-19) mRNAs in whole blood as a potential method for the early detection of OSCC.MethodsThe study included 40 patients (each from OSCC, Oral Submucous Fibrosis (OSF), Oral Leukoplakia (OLK), Oral Lichen Planus (OLP), and 10 healthy controls. The expression levels of VEGF-A and CK-19 mRNAs were measured from extracellular RNA extracted from whole blood samples using real-time reverse transcription polymerase chain reaction (RT-PCR) with sequence-specific primers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of these biomarkers in detecting OSCC.ResultsThe results demonstrated a significant increase in blood transcripts of the candidate mRNAs CK-19 and VEGF-A in patients with OSCC, OSF, OLK, and OLP. The Wilcoxon signed-rank test revealed a p-value of 0.002 for each specific comparison between diseased patients and healthy controls (i.e., OSCC vs. HC, OSF vs. HC, OLP vs. HC, OLK vs. HC) for both CK-19 and VEGF-A. When these two biomarkers were used together, they provided a 60% predictive probability for patients with OSCC (p = 0.023).ConclusionThis study highlights the efficacy of blood mRNA transcriptome diagnostics in detecting OSCC. This innovative clinical approach has the potential to be a robust, efficient, and reliable tool for early cancer detection. Blood-based transcriptomes could be further explored for their effectiveness in various health contexts and for routine health monitoring.

Epidemiology of travel-associated dengue from 2007 to 2022: A GeoSentinel analysis.

Dengue is a leading cause of febrile illness among international travellers. We aimed to describe the epidemiology and clinical characteristics of imported dengue in returning travellers evaluated at GeoSentinel sites from 2007 to 2022. We retrieved GeoSentinel records of dengue among travellers residing in non-endemic countries. We considered dengue confirmed when diagnosed by a positive dengue virus (DENV)-specific reverse-transcriptase polymerase chain reaction, positive NS-1 antigen and/or anti-DENV IgG seroconversion, and probable when diagnosed by single anti-DENV IgM or high-titre anti-DENV IgG detection. Severe dengue was defined as evidence of clinically significant plasma leakage or bleeding, organ failure, or shock, according to the 2009 World Health Organization guidance. Complicated dengue was defined as either severe dengue or dengue with presence of any warning sign. Analyses were descriptive. This analysis included 5958 travellers with confirmed (n = 4859; 81.6%) or probable (n = 1099; 18.4%) dengue. The median age was 33 years (range: <1-91); 3007 (50.5%) travellers were female. The median travel duration was 21 days (interquartile range [IQR]: 15-32). The median time between illness onset and GeoSentinel site visit was 7 days (IQR: 4-15). The most frequent reasons for travel were tourism (67.3%), visiting friends or relatives (12.2%) and business (11.0%). The most frequent regions of acquisition were South East Asia (50.4%), South Central Asia (14.9%), the Caribbean (10.9%) and South America (9.2%). Ninety-five (1.6%) travellers had complicated dengue, of whom 27 (0.5%) had severe dengue and one died. Of 2710 travellers with data available, 724 (26.7%) were hospitalized. The largest number of cases (n = 835) was reported in 2019. A broad range of international travellers should be aware of the risk of acquiring dengue and receive appropriate pre-travel counselling regarding preventive measures. Prospective cohort studies are needed to further elucidate dengue risk by destination and over time, as well as severe outcomes and prolonged morbidity (long dengue) due to travel-related dengue.

Patient characteristics and antimicrobial susceptibility profiles of Escherichia coli and Klebsiella pneumoniae infections in international travellers: a GeoSentinel analysis.

Antimicrobial resistance (AMR) is a global health crisis, with Enterobacterales including Escherichia coli and Klebsiella pneumoniae playing significant roles. While international travel to low- and middle-income countries is linked to colonisation with AMR Enterobacterales, the clinical implications, particularly the risk of subsequent infection, remain unclear due to limited data. We aimed to characterise E. coli and K. pneumoniae infections in travellers and the antimicrobial susceptibility profiles of their isolates. We analysed data on E. coli and K. pneumoniae infections in travellers collected at GeoSentinel sites between 2015 and 2022, focusing on epidemiological, clinical and microbiological characteristics. We defined multi-drug resistance (MDR) as non-susceptibility to agents from at least three drug classes. Over the 8-year period, we included 655 patients (median age 41years; 74% female) from 57 sites in 27 countries, with 584 E. coli and 72K. pneumoniae infections. Common travel regions included Sub-Saharan Africa, Southeast Asia, and South-Central Asia. Urinary tract infections predominated. Almost half (45%) were hospitalised. Among infections with antimicrobial susceptibility data across three or more drug classes, 203/544 (37%) E. coli and 19/67 (28%) K. pneumoniae demonstrated MDR. Over one-third of E. coli and K. pneumoniae isolates were non-susceptible to third-generation cephalosporins and cotrimoxazole, with 38% and 28% non-susceptible to fluoroquinolones, respectively. Travellers to South-Central Asia most frequently had isolates non-susceptible to third-generation cephalosporins, fluoroquinolones and carbapenems. We observed increasing frequencies of phenotypic extended spectrum beta-lactamase and carbapenem resistance over time. E. coli and K. pneumoniae infections in travellers, particularly those to Asia, may be challenging to empirically treat. Our analysis highlights the significant health risks these infections pose to travellers and emphasises the escalating global threat of AMR. Enhanced, systematic AMR surveillance in travellers is needed, along with prospective data on infection risk post travel-related AMR organism acquisition.

ECONOMIC RELATIONS OF TÜRKIYE WITH THE TURKIC STATES OF SOUTH CAUCASUS AND CENTRAL ASIA

In the present era, the Turkic states are experiencing an upward trajectory in the expansion of their relationships, particularly in the economic sphere. After the collapse of the USSR, the Turkic states that regained their independence – Azerbaijan, Kazakhstan, Kyrgyzstan, Turkmenistan, and Uzbekistan – followed different dynamics of economic development. These Turkic states are located in regions of significant geopolitical and geostrategic importance, spanning a wide area from the Adriatic to the Great Wall of China. The purpose of the study is to examine the dynamics of the development of economic relations between Türkiye and the Turkic states of South Caucasus and Central Asia in the modern era. The main objectives are to examine the economic potential of the Turkic states and Türkiye’s economic policy towards the Turkic states of the South Caucasus and Central Asia, to analyze the development dynamics and characteristics of the economic relations between Türkiye and the Turkic states of these two regions.

Incidence distributions, risk factors and trends of vaginal cancer: A global population-based study.

This study aimed to investigate the incidence, risk factors and trends for vaginal cancer. Retrospective observational design. Data were collected from multiple sources, including the Global Cancer Observatory, Cancer Incidence in Five Continents Plus, Global Burden of Disease, World Bank and the United Nations. Individuals diagnosed with vaginal cancer. The study collected data on vaginal cancer from the specified sources. The age-standardised rate (ASR) of vaginal cancer was calculated for different regions and age groups. Multivariable and univariable linear regression analyses were performed to examine the associations between risk factors and the incidence of vaginal cancer. Trend analysis was conducted using joinpoint regression analysis, and the average annual percentage change (AAPC) was calculated to quantify the temporal trend. The main outcome measures of the study were the incidence of vaginal cancer, risk factors associated with the disease and the trend of its incidence over time. There were 17 908 newly reported cases of vaginal cancer (ASR = 0.36, 95% CI 0.30-0.44) in 2020, with the highest ASRs reported in South-Central Asia and Southern Africa. Risk factors associated with a higher incidence of vaginal cancer included a higher prevalence of unsafe sex and human immunodeficiency virus (HIV) infection. The temporal trend showed an overall rising incidence globally, with Iceland (AAPC = 29.56, 95% CI 12.12-49.71), Chile (AAPC = 22.83, 95% CI 13.20-33.27), Bahrain (AAPC = 22.05, 95% CI 10.83-34.40) and the UK (AAPC = 1.40, 95% CI 0.41-2.39) demonstrating the most significant rising trends. The significant regional disparities and risk factors associated with vaginal cancer underscore the necessity for targeted interventions and education, particularly in regions with a lower human development index (HDI) and a higher prevalence of human papillomavirus (HPV) infection. The increasing incidence trend emphasises the need for enhanced HPV vaccination rates to prevent the development of vaginal cancer.

Ornamented stirrup from the elite early Medieval burial at Balyk-Sook (Central Altai)

The article presents an ornamented iron stirrup from a rich and noble early Medieval burial in the Balyk-Sook area in the central part of the Russian Altai. This burial is unique not only for South Siberia, but also for neighbor-ring regions, as within it, with the warrior, four horses and protective armour were found. During the course of restoration work, it was established that the arcs and the plate loop of the stirrup were originally gilded and en-graved with complex floral ornamentation, the stirrup foot was decorated with gold wire inlay in the form of floral curls. This is the first find of such type in Altai. The burial containing the stirrup was radiocarbon dated to the sec-ond half of the 7th — third quarter of the 8th c. The author provides a wide range of similarities among the “status” or “ceremonial” stirrups from funerary and memorial sites of nomadic nobility, including the Kagans from South Siberia, Central Asia, and Eastern and Central Europe, including the such sites of Kagan status as Shoroon Bumbagar in Central Mongolia and Yeleke sazy in Eastern Kazakhstan, Uibat and Tashebinsk Chaatases in the Minusinsk Basin, the Pereshchepinsk hoard and the Voznesenka memorial complex in Eastern Europe, rich Avar burials in Central Europe, and others. Massive and high stirrups with a plate loop were specifically considered during the Medieval period as “status” stirrups, and in some cases they were additionally decorated with orna-mentation. They could be cast in gold or silver, covered with gold or silver leaf, decorated with complex ornamen-tation in various techniques, or decorated with shaped cuts in the stirrup foot. While Avar stirrups, based on Byzan-tine coins in burials, are dated to the late 6th — early 7th c., radiocarbon dating and analogies show that Central Asian stirrups belong to a later period — second half of the 7th — 8th c., and in some cases to the 9th c. Highly ornamented stirrups from the monuments of South Siberia and Central Asia were probably made on order by Chinese masters for the Turkic-speaking nobility, or may have been received as diplomatic gifts from Tang China.

Considering climate change impact on the global potential geographical distribution of the invasive Argentine ant and little fire ant.

The Argentine ant (Linepithema humile) and the little fire ant (Wasmannia auropunctata) are among the top 100 invasive alien species globally, causing significant ecological and economic harm. Therefore, it is crucial to study their potential geographic distribution worldwide. This study aimed to predict their global distribution under current and future climate conditions. We used distribution data from various sources, including CABI, GBIF, and PIAKey, and key climate variables selected from 19 environmental factors to model their potential geographic distribution using MaxEnt. The AUC values were 0.925 and 0.937 for L. humile and W. auropunctata, respectively, indicating good predictive performance. Suitable areas for L. humile were mainly in southern North America, northern South America, Europe, central Asia, southern Oceania, and parts of Africa, while W. auropunctata suitable areas were mostly in southern North America, most of South America, a small part of Europe, southern Asia, central Africa, and some parts of Oceania. Under climate change scenario, suitable areas for L. humile increased, while highly suitable areas for W. auropunctata decreased. The top four countries with the largest areas of overlapping suitable habitat under current climate were Brazil, China, Australia, and Argentina, while under future SSP585 climate scenario, the top four countries were Brazil, China, Indonesia, and Argentina. Some countries, such as Estonia and Finland, will see an overlapping adaptation area under climate change. In conclusion, this study provides insight into controlling the spread and harm of L. humile and W. auropunctata.

Trends in imported infections among migrants and travellers to Spain: a decade of analysis through the +Redivi network (2012-2022).

High-speed global travel, increased trade, world population growth, migration, urbanization and climate change have favoured the emergence and spread of pathogens. We aimed to analyse the evolution of imported infections in Spain during 2012-2022 and the potential impact of some of the abovementioned factors on differential morbidity patterns. In this retrospective study (January 2012 to December 2022), we analysed data collected by the +Redivi network across 25 health centres. The network's standardised database records new cases of imported infections, including patient demographics, travel history, pre-travel advice and diagnostic information. To assess outcome rates over time and potential interactions, we constructed penalized weighted models to reduce the bias related to a low event rate and used weighted logistic regression for morbidity outcomes. We recorded 25 632 episodes, comprising 13 913 migrants, 4047 visiting friends and relatives (VFR) immigrants, 392 VFR travellers and 7280 travellers. Most immigrants came from South America (48.3%), Sub-Saharan Africa (28.5%), North Africa (6.6%), South Central Asia (5.4%) and Central America/Caribbean (5.3%). The most common regions visited by travellers were Sub-Saharan Africa (33.5%), South America (24.5%), Central America/Caribbean (13.5%), Southeast Asia (12%) and South Central Asia (10%). The proportion of diagnoses of malaria, strongyloidiasis and unspecified self-limiting febrile syndrome < 3weeks remained unchanged during the study period. An increased frequency of diagnosis was reported for schistosomiasis, blastocystosis, giardiasis, dengue, diarrhoea, new cases of HIV, latent and pulmonary tuberculosis, whereas a decrease was reported for syphilis, chikungunya fever, Chagas disease and eosinophilia. We detected interactions between time and sex or type of participant across the different diagnoses. Our study underscores the importance of epidemiological data in understanding infectious diseases dynamics among travellers and migrants, emphasizing how demographic shifts, migration trends and healthcare policies affect disease profiles. Comprehensive data play an essential role in enhancing public health policies and travel advice.

Screening of Bread and Durum Wheat Varieties on Yield and Nutritional Quality for Their Tolerance to Zinc Stress

ABSTRACT Zinc (Zn) deficiency is one of the most prevalent micronutrient deficiencies and is mostly brought on by a diet high in cereal grains with low Zn contents. In order to screen prominent bread (12 varieties) and durum (6 varieties) wheat varieties grown under Zn deficient (control) and sufficient (Zn @ 25 mg kg−1 as soil) condition and a pot experiment was conducted in the screen house of the Department of Soil Science, Chaudhary Charan Singh Haryana Agricultural University, Hisar. In the Zn deficient and sufficient soil, the highest yield was observed in HD-2967 (14.57 & 16.13 g/pot) and PWD-291 (8.68 & 11.70 g/pot) of bread and durum wheat, respectively. In Zn-deficient soil, the highest total protein content and Zn content in grain were observed in DBW-88 (8.17 & 26.50%) and PWD-291 (8.42 & 26.52%) of bread and durum wheat, respectively. All the bread wheat varieties were found to be semi tolerant, i.e. the percentage increase in yield was in the category of 10–25% except WH-52 and RAJ-3765 where increase in yield was more than 25%. The maximum increase in yield was found 28.91% in the WH-542 and the minimum increase (10.70%) in the HD-2967 wheat varieties. For durum wheat, two varieties (WH-912 &WHD-943) were found to be semi tolerant, i.e. the percentage increase in yield was in the category of 10–25%. In conclusion, it was determined that this study is helpful for creating methods for micronutrient biofortification using various wheat varieties in south-central Asia.

A framework on utilizing of publicly availability stream gauges datasets and deep learning in estimating monthly basin-scale runoff in ungauged regions

This study introduces a framework that strategically applies a Long Short-Term Memory (LSTM)-based approach for monthly runoff prediction in South Africa and Central Asia. The framework is distinct in its utilization of newly developed Global Land Data Assimilation System (GLDAS)-derived climate dynamics variables and Global Streamflow Indices and Metadata Archives (GSIM)-derived static descriptors, ensuring a consistent evaluation of Deep Learning (DL) performance across multiple continents, including North and South America, and Western Europe. Seven LSTM models were trained using seven different datasets, each representing a combination of these data-rich regions. We assessed the sensitivity of these seven training data sets to LSTM models by testing these trained models in predicting monthly basin-scale runoff across 214 test catchments located in South Africa and Central Asia. Our results show that runoff predictions generated by LSTM within the test domain could exhibit better prediction skills compared to those derived from GLDAS datasets. The performance of the trained LSTMs appears to be linked to hydrological similarities between the data-rich regions and the test basins. Also, our results indicate the importance of selecting the appropriate input sources for the LSTM models to achieve accurate runoff predictions at the test region. We emphasize the possibility of utilizing LSTM models that are leveraging on either North American catchments or a combination of South American and Western European catchments to predict basin-scale runoff in the test regions. To this end, this study harnesses the burgeoning availability of publicly stream-gauge datasets and DL to enhance water information prediction in ungauged regions, responding to the challenge of geographically unbalanced stream gauge instruments.

Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.

This article presents global cancer statistics by world region for the year 2022 based on updated estimates from the International Agency for Research on Cancer (IARC). There were close to 20 million new cases of cancer in the year 2022 (including nonmelanoma skin cancers [NMSCs]) alongside 9.7 million deaths from cancer (including NMSC). The estimates suggest that approximately one in five men or women develop cancer in a lifetime, whereas around one in nine men and one in 12 women die from it. Lung cancer was the most frequently diagnosed cancer in 2022, responsible for almost 2.5 million new cases, or one in eight cancers worldwide (12.4% of all cancers globally), followed by cancers of the female breast (11.6%), colorectum (9.6%), prostate (7.3%), and stomach (4.9%). Lung cancer was also the leading cause of cancer death, with an estimated 1.8 million deaths (18.7%), followed by colorectal (9.3%), liver (7.8%), female breast (6.9%), and stomach (6.8%) cancers. Breast cancer and lung cancer were the most frequent cancers in women and men, respectively (both cases and deaths). Incidence rates (including NMSC) varied from four-fold to five-fold across world regions, from over 500 in Australia/New Zealand (507.9 per 100,000) to under 100 in Western Africa (97.1 per 100,000) among men, and from over 400 in Australia/New Zealand (410.5 per 100,000) to close to 100 in South-Central Asia (103.3 per 100,000) among women. The authors examine the geographic variability across 20 world regions for the 10 leading cancer types, discussing recent trends, the underlying determinants, and the prospects for global cancer prevention and control. With demographics-based predictions indicating that the number of new cases of cancer will reach 35 million by 2050, investments in prevention, including the targeting of key risk factors for cancer (including smoking, overweight and obesity, and infection), could avert millions of future cancer diagnoses and save many lives worldwide, bringing huge economic as well as societal dividends to countries over the forthcoming decades.

430 Genome-wide meta-analysis identifies novel risk loci for uterine fibroids across multiple ancestry groups

OBJECTIVES/GOALS: Uterine fibroids are benign tumors of the uterus with a high disease prevalence and burden, yet there are few multi-ancestry genetic studies. This is the largest and most diverse fibroid GWAS to-date. Our goal is to identify novel genetic variants and gene expression pathways associated with fibroids and characterize their biological relevance. METHODS/STUDY POPULATION: We performed a cross-ancestry meta-analysis of GWAS summary statistics from eight datasets. The total sample size was 74,294 cases and 465,810 controls with participants of European (80% of sample), African (4%), East Asian, and Central South Asian (16%) ancestry. We mapped variants to genes with OpenTarget Genetics and used Functional Mapping and Annotation to conduct tissue expression gene-set enrichment and identify lead variants. We used S-PrediXcan to estimate genetically predicted gene expression (GPGE) associated with fibroid risk. This was with models that predicted gene expression across 49 different tissue types. Ingenuity Pathway Analysis compiled significant GPGE genes and their weights with a scientific literature database to identify overlapping pathways. RESULTS/ANTICIPATED RESULTS: We identified 370 independent significant variants. Among these, we identified variants mapped to three novel genes (PAX2, VIP, FOXO3) and eight genes not previously validated (TEKT1, SLC16A11, RPEL1, RASL11B, ASGR1, SLC12A7, TTC28, POLR2A). Many loci have roles in cell cycle regulation or are associated with fibroid risk factors like blood pressure, BMI, and vitamin D levels. Loci were significantly enriched in DNA damage and cell cycle pathways. Of 588 significant predicted expression gene-tissue pairs, 173 unique genes were novel fibroid associations. These genes are also associated with cancers, estradiol, and endometriosis. Top enriched pathways included p53 signaling, HOTAIR, BRCA1DNA damage response, and pulmonary fibrosis signaling. In uterine tissue there were 15 novel GPGE associations. DISCUSSION/SIGNIFICANCE: Using this large and diverse data, we identified novel loci associated with fibroids that are enriched in hormone-response, DNA damage, and cell-cycle pathways. GPGE loci were in tumorigenesis and fibrosis pathways. These novel genetic loci and uterine gene expression findings may provide translational opportunities for novel fibroid treatments.

Clinical spectrum of Transthyretin amyloidogenic mutations among diverse population origins

PurposeCoding mutations in the Transthyretin (TTR) gene cause a hereditary form of amyloidosis characterized by a complex genotype-phenotype correlation with limited information regarding differences among worldwide populations.MethodsWe compared 676 diverse individuals carrying TTR amyloidogenic mutations (rs138065384, Phe44Leu; rs730881165, Ala81Thr; rs121918074, His90Asn; rs76992529, Val122Ile) to 12,430 non-carriers matched by age, sex, and genetically-inferred ancestry to assess their clinical presentations across 1,693 outcomes derived from electronic health records in UK biobank.ResultsIn individuals of African descent (AFR), Val122Ile mutation was linked to multiple outcomes related to the circulatory system (fold-enrichment = 2.96, p = 0.002) with the strongest associations being cardiac congenital anomalies (phecode 747.1, p = 0.003), endocarditis (phecode 420.3, p = 0.006), and cardiomyopathy (phecode 425, p = 0.007). In individuals of Central-South Asian descent (CSA), His90Asn mutation was associated with dermatologic outcomes (fold-enrichment = 28, p = 0.001). The same TTR mutation was linked to neoplasms in European-descent individuals (EUR, fold-enrichment = 3.09, p = 0.003). In EUR, Ala81Thr showed multiple associations with respiratory outcomes related (fold-enrichment = 3.61, p = 0.002), but the strongest association was with atrioventricular block (phecode 426.2, p = 2.81 × 10− 4). Additionally, the same mutation in East Asians (EAS) showed associations with endocrine-metabolic traits (fold-enrichment = 4.47, p = 0.003). In the cross-ancestry meta-analysis, Val122Ile mutation was associated with peripheral nerve disorders (phecode 351, p = 0.004) in addition to cardiac congenital anomalies (fold-enrichment = 6.94, p = 0.003).ConclusionsOverall, these findings highlight that TTR amyloidogenic mutations present ancestry-specific and ancestry-convergent associations related to a range of health domains. This supports the need to increase awareness regarding the range of outcomes associated with TTR mutations across worldwide populations to reduce misdiagnosis and delayed diagnosis of TTR-related amyloidosis.

Diversity of CFTR variants across ancestries characterized using 454,727 UK biobank whole exome sequences

BackgroundLimited understanding of the diversity of variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene across ancestries hampers efforts to advance molecular diagnosis of cystic fibrosis (CF). The consequences pose a risk of delayed diagnoses and subsequently worsened health outcomes for patients. Therefore, characterizing the spectrum of CFTR variants across ancestries is critical for revolutionizing molecular diagnoses of CF.MethodsWe analyzed 454,727 UK Biobank (UKBB) whole-exome sequences to characterize the diversity of CFTR variants across ancestries. Using the PanUKBB classification, the participants were assigned into six major groups: African (AFR), American/American Admixed (AMR), Central South Asia (CSA), East Asian (EAS), European (EUR), and Middle East (MID). We segregated ancestry-specific CFTR variants, including those that are CF-causing or clinically relevant. The ages of certain CF-causing variants were determined and analyzed for selective pressure effects, and curated phenotype analysis was performed for participants with clinically relevant CFTR genotypes.ResultsWe detected over 4000 CFTR variants, including novel ancestry-specific variants, across six ancestries. Europeans had the most unique CFTR variants [n = 2212], while the American group had the least unique variants [n = 23]. F508del was the most prevalent CF-causing variant found in all ancestries, except in EAS, where V520F was the most prevalent. Common EAS variants such as 3600G > A, V456A, and V520, which appeared approximately 270, 215, and 338 generations ago, respectively, did not show evidence of selective pressure. Sixteen participants had two CF-causing variants, with two being diagnosed with CF. We found 154 participants harboring a CF-causing and varying clinical consequences (VCC) variant. Phenotype analysis performed for participants with multiple clinically relevant variants returned significant associations with CF and its pulmonary phenotypes [Bonferroni-adjusted p < 0.05].ConclusionsWe leveraged the UKBB database to comprehensively characterize the broad spectrum of CFTR variants across ancestries. The detection of over 4000 CFTR variants, including several ancestry-specific and uncharacterized CFTR variants, warrants the need for further characterization of their functional and clinical relevance. Overall, the presentation of classical CF phenotypes seen in non-CF diagnosed participants with more than one CF-causing variant indicates that they may benefit from current CFTR modulator therapies.

Geochronology and Geochemistry of Ore‐related Granitoids in the Giant Gariatong Rb Deposit, Tibet and Implications for Rb Metallogeny in China

AbstractRubidium (Rb) deposits mostly occur in the South China and Central Asia orogenic belts and are often closely associated with highly differentiated granites. This study investigates a newly‐discovered giant Rb deposit at Gariatong in the Central Lhasa terrane in Tibet. Detailed field studies and logging data revealed that the Rb mineralization mainly occurs in monzogranite and is related to greisenization. LA‐ICP‐MS U‐Pb dating of zircon yielded ages of 19.1 ± 0.2 Ma and 19.0 ± 0.2 Ma for greisenized monzogranite and fresh monzogranite, respectively. The monzogranites are characterized as strongly peraluminous, with high contents of SiO2, Al2O3, K2O and Na2O as well as a high differentiation index. They are enriched in light rare earth and large ion lithophile elements with significant negative Eu anomalies and depleted high field‐strength elements. Petrological and geochemical features of these ore‐related monzogranites suggest that they are highly fractionated S‐type granites, derived from remelting of crustal materials in a post‐collisional setting. The geochemistry of zircon and apatite points to a low oxygen fugacity of the ore‐related monzogranite during the magma's evolution. The discovery of the Gariatong Rb deposit suggests that the Central Lhasa terrane may be an important region for rare metal mineralization.