Phylogenetic evidence clarifies the history of the extrusion of Indochina.

The southeastward extrusion of Indochina along the Ailao Shan-Red River shear zone (ARSZ) is one of two of the most prominent consequences of the India-Asia collision. This plate-scale extrusion has greatly changed Southeast Asian topography and drainage patterns and effected regional climate and biotic evolution. However, little is known about how Indochina was extruded toward the southeast over time. Here, we sampled 42 plant and animal clades (together encompassing 1,721 species) that are distributed across the ARSZ and are not expected to disperse across long distances. We first assess the possible role of climate on driving the phylogenetic separations observed across the ARSZ. We then investigate the temporal dynamics of the extrusion of Indochina through a multitaxon analysis. We show that the lineage divergences across the ARSZ were most likely associated with the Indochinese extrusion rather than climatic events. The lineage divergences began at ~53 Ma and increased sharply ~35 Ma, with two peaks at ~19 Ma and ~7 Ma, and one valley at ~13 Ma. Our results suggest a two-phase model for the extrusion of Indochina, and in each phase, the extrusion was subject to periods of acceleration and decrease, in agreement with the changes of the India-Asia convergence rate and angle from the early Eocene to the late Miocene. This study highlights that a multitaxon analysis can illuminate the timing of subtle historical events that may be difficult for geological data to pinpoint and can be used to explore other tectonic events.

The shape of the Himalayan "Arc": An Ellipse pinned by syntaxial strike-slip fault tips.

Trans-Himalayan geodetic data show that, between both syntaxes, India/Asia convergence is steadily oriented ≈ N20°E. However, surface faulting near both syntaxes, along the 2005 and 1950 earthquake ruptures, imply long-term thrusting directed ≈ 130° apart, and post-LGM (last Glacial Maximum) shortening rates of ≈ 5 to 6 mm/y, ≈ 2 to 3 times slower than in Nepal (≈ 15 to 20 mm/y). Syntaxial earthquakes' return-time are also ≈ 3 times longer (>2,000 y) than in Nepal (≈ 700 y). In a structural frame centered halfway between the syntaxial cusps, the tectonic features of the range show remarkable symmetry. In map view, the overall shapes of the Main Front Thrust (MFT) and the Main Central Thrust (MCT) closely fit ellipses, with major-to-minor axis ratios of ≈ 2.5 to 3. This suggests that the range growth atop subducting India is "pinned" by the strike-slip faults that bound it to the east and west. Discrete Element Modeling corroborates a late-Tertiary elliptical range growth. This accounts for the ≈ 65° angles and twofold to threefold decrease in active thrusting between Nepal and the syntaxes, for the maximum Himalayan heights (≥8,000 m), larger magnitudes (≥8), and shorter return-time (≈ 700 y) of great earthquakes in Nepal, for the existence of two 500- to 600 km-long, south-concave mountain ranges north of both syntaxes and for the ≈ 9 mm/y, N100 to 110°E extension across southern Tibet. It also suggests that predictions of impending or frequent great earthquakes in the eastern- and westernmost Himalayas may be overstated.

The genetic admixture and assimilation of Ahom: a historic migrant from Thailand to India.

The Northeastern region of India is considered a gateway for modern humans' dispersal throughout Asia. This region is a mixture of various ethnic and indigenous populations amalgamating multiple ancestries. One reason for such amalgamation is that, South Asia experienced multiple historic migrations from various parts of the world. A few examples explored genetically are Jews, Parsis and Siddis. Ahom is a dynasty that historically migrated to India during the 12th century. However, this putative migration has not been studied genetically at high resolution. Therefore, to validate this historical evidence, we genotyped autosomal data of the Modern Ahom population residing in seven sister states of India. Principal Component and Admixture analyses haave suggested a substantial admixture of the Ahom population with the local Tibeto-Burman populations. Moreover, the haplotype-based analysis has linked these Ahom individuals mainly with the Kusunda (a language isolated from Nepal) and Khasi (an Austroasiatic population of Meghalaya). Such unexpected presence of widespread population affinities suggests that Ahom mixed and assimilated a wide variety of Trans-Himalayan populations inhabiting this region after the migration. In summary, we observed a significant deviation of Ahom from their ancestral homeland (Thailand) and extensive admixture and assimilation with the local South Asian populations.

Strengthening the argument for a large Greater India.

The Sangdanlin section in southern Tibet represents a geologic Rosetta stone to constrain the initiation of the India-Asia collision from its sedimentary and paleomagnetic records. However, geoscientists have arrived at fundamentally divergent interpretations surrounding the age of the strata and its paleomagnetic record. Here, we report paleontologic, petrographic, and paleomagnetic data from the Sangdanlin section that recognize the sequence as a thrust complex containing interlaced Barremian-Albian (Early Cretaceous) and Paleocene strata, each separated by thrust faults. Recognizing two complexly interwoven formations of distinctly different ages contradicts a continuous stratigraphic superposition. Assigning an Early Cretaceous, instead of Paleocene, age to the units collected for paleomagnetic data revises paleogeographic models thereby supporting a large (2,000 to 3,000 km) extent of Greater India, with collision initiating at 55 ± 5 Ma in the western Himalayas. A contiguous plate in the Neotethys Ocean precludes that Asia's southern margin was built through a succession of accreted terrains.

Environmental Surveillance for Salmonella Typhi and its Association With Typhoid Fever Incidence in India and Malawi.

BACKGROUND: Environmental surveillance (ES) for Salmonella Typhi potentially offers a low-cost tool to identify communities with a high burden of typhoid fever. METHODS: We developed standardized protocols for typhoid ES, including sampling site selection, validation, characterization; grab or trap sample collection, concentration; and quantitative PCR targeting Salmonella genes (ttr, staG, and tviB) and a marker of human fecal contamination (HF183). ES was implemented over 12 months in a historically high typhoid fever incidence setting (Vellore, India) and a lower incidence setting (Blantyre, Malawi) during 2021-2022. RESULTS: S. Typhi prevalence in ES samples was higher in Vellore compared with Blantyre; 39/520 (7.5%; 95% confidence interval [CI], 4.4%-12.4%) vs 11/533 (2.1%; 95% CI, 1.1%-4.0%) in grab and 79/517 (15.3%; 95% CI, 9.8%-23.0%) vs 23/594 (3.9%; 95% CI, 1.9%-7.9%) in trap samples. Detection was clustered by ES site and correlated with site catchment population in Vellore but not Blantyre. Incidence of culture-confirmed typhoid in local hospitals was low during the study and zero some months in Vellore despite S. Typhi detection in ES. CONCLUSIONS: ES describes the prevalence and distribution of S. Typhi even in the absence of typhoid cases and could inform vaccine introduction. Expanded implementation and comparison with clinical and serological surveillance will further establish its public health utility.

Undernourished Household Contacts Are at Increased Risk of Tuberculosis (TB) Disease, but not TB Infection-a Multicenter Prospective Cohort Analysis.

Undernutrition is the leading risk factor for tuberculosis (TB) globally and in India. This multicenter prospective cohort analysis from India suggests that undernutrition is associated with increased risk of TB disease but not TB infection among household contacts of persons with TB.

The Impact of Preventive Treatment for Multidrug- and Rifampin-Resistant Tuberculosis Exceeds Trial-Based Estimates.

BACKGROUND: Several clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug- or rifampin-resistant tuberculosis (MDR/RR-TB) are nearing completion. The potential benefits of delivering TPT to MDR/RR-TB contacts extend beyond the outcomes that clinical trials can measure. METHODS: We developed an agent-based, household-structured TB and MDR/RR-TB transmission model, calibrated to an illustrative setting in India. We simulated contact investigation in households of patients with MDR/RR-TB, comparing an MDR/RR-TPT regimen (assuming 6-month duration, 70% efficacy) and associated active case finding against alternatives of contact investigation without TPT or no household intervention. We simulated the TB and MDR/RR-TB incidence averted relative to placebo over 2 years, as measurable by a typical trial, as well as the incidence averted over a longer time horizon, in the broader population, and relative to no contact investigation. RESULTS: Observing TPT and placebo recipients for 2 years as in a typical trial, MDR/RR-TPT was measured to prevent 72% (interquartile range, 45%-100%) of incident MDR/RR-TB among recipients; the median number needed to treat (NNT) to prevent 1 MDR/RR-TB case was 73, compared to placebo. This NNT decreased to 54 with 13-18 years of observation, to 27 when downstream transmission effects were also considered, and to 12 when the effects of active TB screening were included by comparing to a no-household-contact-intervention scenario. CONCLUSIONS: If forthcoming trial results demonstrate efficacy, the long-term population impact of TPT for MDR/RR-TB-including the large effect of increased active TB detection among MDR/RR-TB contacts-could be much greater than suggested by trial outcomes alone.

Human Passage of Schistosoma incognitum, Tamil Nadu, India, and Review of Autochthonous Schistosomiasis, South Asia.

A fecal survey in Tamil Nadu, India, revealed 2 persons passed schistosome eggs, later identified as Schistosoma incognitum, a parasite of pigs, dogs, and rats. We investigated those cases and reviewed autochthonous schistosomiasis cases from India and Nepal. Whether the 2 new cases represent true infection or spurious passage is undetermined.

Molecular Identification of Fonsecaea monophora, Novel Agent of Fungal Brain Abscess.

A 3-year-old patient in India experiencing headaches and seizures was diagnosed with a fungal infection, initially misidentified as Cladophialophora bantiana. Follow-up sequencing identified the isolate to be Fonsecaea monophora fungus. This case demonstrates the use of molecular methods for the correct identification of F. monophora, an agent of fungal brain abscess.

Emerging Leishmania donovani Lineages Associated with Cutaneous Leishmaniasis, Himachal Pradesh, India, 2023.

The clinical manifestation of leishmaniasis has historically been determined by the Leishmania species involved. However, recent emergence of novel Leishmania lineages has caused atypical pathologies. We isolated and characterized 2 new Leishmania donovani parasites causing cutaneous leishmaniasis in Himachal Pradesh, India.

Detection of OXA-181 Carbapenemase in Shigella flexneri.

We report the detection of OXA-181 carbapenemase in an azithromycin-resistant Shigella spp. bacteria in an immunocompromised patient. The emergence of OXA-181 in Shigella spp. bacteria raises concerns about the global dissemination of carbapenem resistance in Enterobacterales and its implications for the treatment of infections caused by Shigella bacteria.

Access and barriers to genomic classifiers for breast cancer and prostate cancer in India.

The incidence of cancer in general, including breast and prostate cancer specifically, is increasing in India. Breast and prostate cancers have genomic classifiers developed to guide therapy decisions. However, these genomic classifiers are often inaccessible in India due to high cost. These classifiers may also be less suitable to the Indian population, as data primarily from patients in wealthy Western countries were used in developing these genomic classifiers. In addition to the limitations in using these existing genomic classifiers, developing and validating new genomic classifiers for breast and prostate cancer in India is challenging due to the heterogeneity in the Indian population. However, there are steps that can be taken to address the various barriers that currently exist for accurate, accessible genomic classifiers for cancer in India.

Outcome of early detection approach in control of breast, cervical, and oral cancer: Experience from a rural cancer center in India.

In low- and middle-income countries most of the cancer patients attend the hospital at a late stage and treatment completion of these cases is challenging. The early detection program (EDP), in rural areas of Punjab state, India was initiated to identify breast, cervical, and oral cancer at an early stage by raising awareness and providing easy access to diagnosis and treatment. A total of 361 health education programs and 99 early detection clinics were organized. The symptomatic and self-interested (non-symptomatic individuals who opted for screening) cases visited the detection clinic. They were screened for breast, cervical, and/or oral cancer. Further diagnosis and treatment of screen-positive cases were carried out at Homi Bhabha Cancer Hospital (HBCH), Sangrur. Community leaders and healthcare workers were involved in all the activities. The EDP, Sangrur removed barriers between cancer diagnosis and treatment with the help of project staff. From 2019 to 2023, a total of 221,317 populations were covered. Symptomatic and self-interested individuals attended the breast (1627), cervical (1601), and oral (1111) examinations. 46 breast (in situ-4.3%; localized-52.2%), 9 cervical (localized-77.8%), and 12 oral (localized-66.7%) cancer cases were detected, and treatment completion was 82.6%, 77.8%, and 50.0%, respectively. We compared cancer staging and treatment completion of cases detected through EDP with the cases attended HBCH from Sangrur district in 2018; the difference between two groups is statistically significant. Due to the early detection approach, there is disease down-staging and improvement in treatment completion. This approach is feasible and can be implemented to control these cancers in low- and middle-income countries.

Climate and Gender: Association Between Droughts and Intimate Partner Violence in India.

Extreme climate events are related to women's exposure to different forms of violence. We examined the relationship between droughts and physical, sexual, and emotional intimate partner violence (IPV) in India by using 2 different definitions of drought: precipitation-based drought and socioeconomic drought. We analyzed data from 2 rounds of a nationally representative survey, the National Family Health Survey, where married women were asked about their experiences of IPV in the previous year (2015-2016 and 2019-2021; n = 122,696). Precipitation-based drought was estimated using remote sensing data and geographic information system (GIS) mapping, while socioeconomic drought status was collected from government records. Logistic regression models showed precipitation-based drought to increase the risk of experiencing physical IPV and emotional IPV. Similar findings were observed for socioeconomic drought; women residing in areas classified as drought-impacted by the government were more likely to report physical IPV, sexual IPV, and emotional IPV. These findings support the growing body of evidence regarding the relationship between climate change and women's vulnerability, and highlight the need for gender responsive strategies for disaster management and preparedness.

Breast cancer survival in India across 11 geographic areas under the National Cancer Registry Programme.

BACKGROUND: Population-based cancer survival is a key indicator for assessing the effectiveness of cancer control by a health care system in a specific geographic area. Breast cancer is the most common cancer among women in India, accounting for over one quarter of all female cancers. The objective of this study was to estimate the 5-year survival of female patients who were diagnosed with breast cancer between 2012 and 2015 from the existing Population-Based Cancer Registries (PBCRs) in India. METHODS: In total, 17,331 patients who had breast cancer diagnosed between 2012 and 2015 from 11 PBCRs were followed until June 30, 2021. Active methods were used to track the vital status of registered breast cancer cases. The study conducted survival analysis by calculating the difference between the date of first diagnosis and the date of death or censoring to estimate observed survival and relative survival using the actuarial survival approach and the Ederer-II approach, respectively. RESULTS: The 5-year age-standardized relative survival (95% confidence interval [CI]) of patients with breast cancer was 66.4% (95% CI, 65.5%-67.3%). Mizoram (74.9%; 95% CI, 68.1%-80.8%), Ahmedabad urban (72.7%; 95% CI, 70.3%-74.9%), Kollam (71.5%; 95% CI, 69.2%-73.6%), and Thiruvananthapuram (69.1%; 95% CI, 67.0%-71.2%) had higher survival rates than the national average. Conversely, Pasighat had the lowest survival rate (41.9%; 95% CI, 14.7%-68.6%). The 5-year observed survival rates for localized, regional, and distant metastasis in the pooled PBCRs were 81.0%, 65.5%, and 18.3%, respectively. CONCLUSIONS: The overall disparity in survival rates was observed across 11 PBCRs, with lower survival rates reported in Manipur, Tripura, and Pasighat. Therefore, it is imperative to implement comprehensive cancer control strategies widely throughout the country.

Socio-cultural and financial issues against breast cancer screening behaviour among eligible Indian women: evidence for action.

PURPOSE: Breast cancer, a common malignancy in Indian women, is preventable and curable upon early diagnosis. Screening is the best control strategy against breast cancer, but its uptake is low in India despite dedicated strategies and programmes. We explored the impact of socio-cultural and financial issues on the uptake of breast cancer screening behaviour among Indian women. METHODS: Breast cancer screening-uptake and relevant social, cultural, and financial data obtained from the National Family Health Survey (NFHS) round 5 were used for analysis. We studied 399,039 eligible females to assess their breast cancer screening behavior and determine the impact of socio-cultural and financial issues on such behavior using multivariable logistic regression. RESULTS: Most participants were 30-34-year-old (27.8%), educated to the secondary level (38.0%), and 81.5% had bank accounts. A third (35.0%) had health insurance, and anaemia was the most common comorbidity (56.1%). Less than 1.0% had undergone breast cancer screening. Higher age, education, urban residence, employment, less privileged social class, and access to the Internet and mass media were predictors of positive screening-uptake behavior (p < 0.05). Mothers of larger number of children, tobacco- and alcohol-users, the richer and having health insurance had negative uptake behavior (p < 0.05). CONCLUSION: A clear impact of socio-cultural and financial factors on breast cancer screening behavior is evident among Indian women. Therefore, apart from the ongoing health system strengthening efforts, our findings call for targeted interventions against prevailing misconceptions and taboos along with economic and social empowerment of women for the holistic success of India's cancer screening strategy.

Burden of female breast cancer in India: estimates of YLDs, YLLs, and DALYs at national and subnational levels based on the national cancer registry programme.

PURPOSE: Female breast cancer (BC) is the leading cause of cancer incidence and mortality in India, and accounted for 13.5% of new cancer cases and 10% of cancer-related deaths in 2020. This study aims to estimate and report the female BC burden in India at state level from 2012 to 2016 in terms of years of life lost, years lived with disability, and disability-adjusted life years (DALYs), and to project the burden for the year 2025. METHODS: The cancer incidence and mortality data from 28 population-based cancer registries were analysed. The mean mortality to incidence ratio was estimated, and mortality figures were adjusted for underreporting. The burden of female BC was estimated at national and subnational levels using Census data, World Health Organisation's lifetables, disability weights, and the DisMod-II tool. A negative binomial regression is employed to project burden for 2025. RESULTS: The burden of BC among Indian women in 2016 was estimated to be 515.4 DALYs per 100,000 women after age standardization. The burden metrics at state level exhibited substantial heterogeneity. Notably, Tamil Nadu, Telangana, Karnataka, and Delhi had a higher burden of BC than states in the eastern and north-eastern regions. The projection for 2025 indicates to a substantial increase, reaching 5.6 million DALYs. CONCLUSION: The female BC burden in India was significantly high in 2016 and is expected to substantially increase. Undertaking a multidisciplinary, context-specific approach for its prevention and control can address this rising burden.

Household cooking fuel and gallbladder cancer risk: a multi-centre case-control study in India.

PURPOSE: Gallbladder cancers (GBC), unique to certain geographical regions, are lethal digestive tract cancers, disproportionately affecting women, with limited information on risk factors. METHODS: We evaluated the association between household cooking fuel and GBC risk in a hospital-based case-control study conducted in the North-East and East Indian states of Assam and Bihar. We explored the potential mediation by diet, fire-vents, 'daily exposure duration' and parity (among women). We recruited biopsy-confirmed GBC (n = 214) men and women aged 30-69 years between 2019 and 2021, and controls frequency-matched by age, sex and region (n = 166). Information about cooking fuel, lifestyle, personal and family history, female reproductive factors, socio-demographics, and anthropometrics was collected. We tested associations using multivariable logistic regression analyses. RESULTS: All participants (73.4% women) were categorised based on predominant cooking fuel use. Group-1: LPG (Liquefied Petroleum Gas) users in the previous 20 years and above without concurrent biomass use (26.15%); Group-2: LPG users in the previous 20 years and above with concurrent secondary biomass use (15.9%); Group-3: Biomass users for ≥ 20 years (57.95%). Compared to group-1, accounting for confounders, GBC risk was higher in group-2 [OR: 2.02; 95% CI: 1.00-4.07] and group-3 [OR: 2.01; 95% CI: 1.08-3.73] (p-trend:0.020). These associations strengthened among women that attenuated with high daily consumption of fruits-vegetables but not with fire-vents, 'daily exposure duration' or parity. CONCLUSION: Biomass burning was associated with a high-risk for GBC and should be considered as a modifiable risk factor for GBC. Clean cooking fuel can potentially mitigate, and a healthy diet can partially reduce the risk among women.

Homozygous missense variants in YKT6 result in loss of function and are associated with developmental delay, with or without severe infantile liver disease and risk for hepatocellular carcinoma.

PURPOSE: YKT6 plays important roles in multiple intracellular vesicle trafficking events but has not been associated with Mendelian diseases. METHODS: We report 3 unrelated individuals with rare homozygous missense variants in YKT6 who exhibited neurological disease with or without a progressive infantile liver disease. We modeled the variants in Drosophila. We generated wild-type and variant genomic rescue constructs of the fly ortholog dYkt6 and compared their ability in rescuing the loss-of-function phenotypes in mutant flies. We also generated a dYkt6KozakGAL4 allele to assess the expression pattern of dYkt6. RESULTS: Two individuals are homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] and exhibited normal prenatal course followed by failure to thrive, developmental delay, and progressive liver disease. Haplotype analysis identified a shared homozygous region flanking the variant, suggesting a common ancestry. The third individual is homozygous for YKT6 [NM_006555.3:c.191A>G p.(Tyr64Cys)] and exhibited neurodevelopmental disorders and optic atrophy. Fly dYkt6 is essential and is expressed in the fat body (analogous to liver) and central nervous system. Wild-type genomic rescue constructs can rescue the lethality and autophagic flux defects, whereas the variants are less efficient in rescuing the phenotypes. CONCLUSION: The YKT6 variants are partial loss-of-function alleles, and the p.(Tyr185Cys) is more severe than p.(Tyr64Cys).

HIV-1 low-level viraemia predicts virological failure in first-line and second-line ART-experienced individuals in India: A retrospective longitudinal study.

OBJECTIVE: To study the prevalence of low-level viraemia (LLV) and its association with virological failure (VF). METHODS: We conducted a retrospective analysis of 3498 participants at YRG CARE, Chennai, India (2013-2018) on antiretroviral therapy (ART) for ≥6 months with two or more plasma viral load (pVL) measurements. Results were stratified for those with pVL <1000 copies/mL: fully suppressed (FS) (pVL <40), low-LLV (pVL 40-199), mid-LLV (pVL 200-399), and high-LLV (pVL 400-999). The study assessed the association with VF (pVL >1000 copies/mL) using Cox proportional hazard model. RESULTS: Among 3498 participants, 2965 (84.8%) were FS and 533 (15.2%) were LLV. During the follow-up, 348 (10%) experienced VF, with 222 (6.3%) experienced after LLV (42% of LLV) and 126 (3.6%) experienced after FS (4.3% of FS). When compared with FS, those with LLV had a greater risk of VF [adjusted hazard ratio (aHR) = 12.7; 95% confidence interval (CI): 10.2-15.9]. First-line participants had a higher VF incidence (aHR = 15.8, 95% CI: 11.4-21.9) than second-line participants (aHR = 5.6, 95% CI: 4.1-7.7). Those with high-LLV had the highest VF risk (aHR = 22.856, 95% CI: 15.204-34.359 vs. aHR = 8.186, 95% CI: 5.564-12.043, for first-line vs. second-line participants, respectively), followed by those with mid-LLV (aHR = 13.375, 95% CI: 8.327-21.483 vs. aHR = 6.261, 95% CI: 4.044-9.695) and low-LLV (aHR = 12.976, 95% CI: 7.974-21.118 vs. aHR = 4.158, 95% CI: 2.826-6.119). CONCLUSIONS: The prevalence of LLV was intermediate in our study population. There was a higher risk of VF among individuals with LLV, and this risk increased with the increasing levels of LLV. Close monitoring of individuals experiencing LLV could help in the early identification of VF.