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Montane systems, formed by a series of climatic oscillations and temporal topographic metamorphoses, have broken up the contiguous distribution of widespread species and accelerated allopatric speciation. We used a partial fragment of the mitochondrial cytochrome b (cytb) gene to address speciation across the entire range of the Siberian ibex Capra sibirica. We demonstrated that the Siberian ibex is a polytypic species, plausibly formed by a combination of at least 2 species and/or 3 to 4 sub-species. Bayesian phylogeny showed that the Indian-Tajikistan (I-T) clade is adequately diverged from the other clades based on the mean intra-specific distance criterion, and warrants recognition as a distinct species. We provide pragmatic evidence for the endorsement of the I-T clade as a distinct species of Siberian ibex and urge prioritization of the conservation of this species at global and regional scales.

Introduction: Intracranial artery calcification (ICAC) is a common finding on computed tomography (CT) in patients presenting with large vessel occlusion acute ischemic stroke (LVO-AIS) and could serve as a useful biomarker of intracranial atherosclerosis and altered intracranial vessel pliability in patients undergoing endovascular thrombectomy (EVT)., Methods: This was a retrospective cohort study analyzing consecutive patients undergoing CT head prior to EVT between 2016 and 2020. Extent of ICAC proximal to the target vessel was scored using a validated grading scale examining thickness and circumferential extent of calcifications. The relationship between 3 levels of ICAC burden and procedural, clinical, and safety outcomes was analyzed., Results: Among 86 patients meeting inclusion criteria, ICAC of any degree was present in 72.1 %. Median ICAC score was 3 [IQR 0-4]. There was a U-shaped association between ICAC score and successful reperfusion: 90.9 %, 65.7 %, and 94.4 % in the low, intermediate, and high ICAC score groups, respectively (p = 0.008). Use of rescue intervention, most often angioplasty and stenting, was greatest in the high ICAC score group: 3.0 % vs. 5.7 % vs. 22.2 % (p = 0.05). Functional independence at 90 days did not differ significantly among groups (41.7 % vs. 31.0 % vs. 15.4 %, p = 0.26), nor did rates of symptomatic intracranial hemorrhage (15.2 % vs. 14.3 % vs. 16.7 %, p = 0.97)., Conclusions: ICAC is seen on CT in nearly three-quarters of patients with LVO-AIS. Extent of ICAC has a U-shaped association with successful reperfusion, in part due to more frequent use of rescue interventions in patients with extensive ICAC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: David S. Liebeskind reports a relationship with Cerenovus that includes: consulting or advisory. David S. Liebeskind reports a relationship with Genentech that includes: consulting or advisory. David S. Liebeskind reports a relationship with Medtronic that includes: consulting or advisory. David S. Liebeskind reports a relationship with Stryker that includes: consulting or advisory. David S. Liebeskind reports a relationship with Rapid Medical that includes: consulting or advisory. Geoffrey P. Colby reports a relationship with Stryker Neurovascular that includes: consulting or advisory. Geoffrey P. Colby reports a relationship with Medtronic that includes: consulting or advisory. Geoffrey P. Colby reports a relationship with MicroVention Inc that includes: consulting or advisory. Geoffrey P. Colby reports a relationship with Cerenovus that includes: consulting or advisory. Geoffrey P. Colby reports a relationship with Rapid Medical that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Female hormone-dependent cancers depend on estrogen for their growth. Numerous studies have explored the antitumor effect of dietary isoflavones on female hormone-dependent cancers. Still, few clinical evidence supports the use of isoflavones in female hormone-dependent cancer patients. This study was performed to examine the impact of dietary isoflavones on tumor growth of female hormone-dependent cancers and accelerate the transformation of research from bench to bedside. We searched PubMed Medline, Web of Science, and Google Scholar for relevant articles related to the effect of dietary isoflavone on tumor growth of experimental animal models of female hormone-dependent cancers from 1998 to 2024. The effects of dietary isoflavones on tumor growth were analyzed between the control and treatment groups using comprehensive meta-analysis software (CMA). We included 30 studies describing tumor growth focused on female hormone-dependent cancer types, including breast, ovarian, and uterine cancers. Overall, a pooled analysis revealed that dietary isoflavones reduced tumor volume (Hedge's g = -1.151, 95% CI = -1.717 to -0.585, p = 0.000) and tumor weight (Hedge's g = -2.584, 95% CI = -3.618 to -1.549, p = 0.000). On the other hand, dietary isoflavones increased tumor area (Hedge's g = 1.136, 95% CI = 0.752 to 1.520, p = 0.000). Dietary isoflavones have potential benefits and risks in female hormone-dependent cancers. Therefore, caution should be exercised when considering the intake of dietary isoflavones in female hormone-dependent cancer patients, particularly in the form of supplements., (© 2024 John Wiley & Sons Ltd.)

Magnesium (Mg) has attracted considerable attention as a biodegradable material for medical implants owing to its excellent biocompatibility, mitigating long-term toxicity and stress shielding. Nevertheless, challenges arise from its rapid degradation and low corrosion resistance under physiological conditions. To overcome these challenges, titanium (biocompatibility and corrosion resistance) has been integrated into Mg. The incorporation of titanium significantly improves mechanical and corrosion resistance properties, thereby enhancing performance in biological settings. Mg-Ti alloys are produced through mechanical alloying and spark plasma sintering (SPS). The SPS technique transforms powder mixtures into bulk materials while preserving structural integrity, resulting in enhanced corrosion resistance, particularly Mg80-Ti20 alloy in simulated body fluids. Moreover, Mg-Ti alloy revealed no more toxicity when assessed on pre-osteoblastic cells. Furthermore, the ability of Mg-Ti-based alloy to create composites with polymers such as PLGA (polylactic-co-glycolic acid) widen their biomedical applications by regulating degradation and ensuring pH stability. These alloys promote temporary orthopaedic implants, offering initial load-bearing capacity during the healing process of fractures without requiring a second surgery for removal. To address scalability constraints, further research is necessary to investigate additional consolidation methods beyond SPS. It is essential to evaluate the relationship between corrosion and mechanical loading to confirm their adequacy in physiological environments. This review article highlights the importance of mechanical characterization and corrosion evaluation of Mg-Ti alloys, reinforcing their applicability in fracture fixation and various biomedical implants.

The utilization of satellite images in conservation research is becoming more prevalent due to advancements in remote sensing technologies. To achieve accurate classification of wildlife habitats, it is important to consider the different capabilities of spectral and spatial resolution. Our study aimed to develop a method for accurately classifying habitat types of the Himalayan ibex (Capra sibirica) using satellite data. We used LISS IV and Sentinel 2A data to address both spectral and spatial issues. Furthermore, we integrated the LISS IV data with the Sentinel 2A data, considering their individual geometric information. The Random Forest approach outperformed other algorithms in supervised classification techniques. The integrated image had the highest level of accuracy, with an overall accuracy of 86.17% and a Kappa coefficient of 0.84. Furthermore, to delineate the suitable habitat for the Himalayan ibex, we employed ensemble modelling techniques that incorporated Land Cover Land Use data from LISS IV, Sentinel 2A, and Integrated image, separately. Additionally, we incorporated other predictors including topographical features, soil and water radiometric indices. The integrated image demonstrated superior accuracy in predicting the suitable habitat for the species. The identification of suitable habitats was found to be contingent upon the consideration of two key factors: the Soil Adjusted Vegetation Index and elevation. The study findings are important for advancing conservation measures. Using accurate classification methods helps identify important landscape components. This study offers a novel and important approach to conservation planning by accurately categorising Land Cover Land Use and identifying critical habitats for the species., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Dutta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The objective of this study was to determine the impact of the stage-based classification of fetal growth restriction (FGR) on the magnitude of FGR, preterm births (PTBs), and birthweight (BW) in a rural population of Madhya Pradesh in Central India., Methods: The program covered 168 public sector centers for pregnant women and infants that provided services to nearly 220,000 people. The third-trimester assessments included fetal biometry, growth and environment assessments, and Doppler assessments. Fetal growth was staged using the Barcelona protocol as stages 1-4 FGR, small for gestational age, and no FGR. The data from the last ultrasound assessment before childbirth were considered. Regular training programs covering preconception care, antenatal and postnatal care were organized in the local language for the public sector community health workers of the program district. Childbirth outcomes were collected from the obstetric service of the local public sector hospital., Results: The analysis included 1,229 pregnancies from 2019 to 2023. The overall magnitude of FGR using estimated fetal weight <10th centile was 19.61% and reduced to 13.34% with the stage-based classification. The magnitude of FGR using the stage-based classification reduced from 27.59% in 2019 to 8.95% in 2023. The PTB in the stage-based FGR subgroup declined from 35.0% in 2019 to 3.45% in 2023 and 96.55% of the stage 1 FGR babies in 2023 were delivered at term. The overall mean BW in the program area improved from 2,772.41 (357.11) g in 2019 to 2,819.68 (377.31) g in 2023. The perinatal mortality rate (8.95 per 1,000 pregnancies) in the program area for 2019-2023 was much lower than the 31.9 per 1,000 pregnancies reported for Madhya Pradesh., Conclusion: The change to a stage-based classification of FGR integrated with low-dose aspirin and fetal Doppler studies reduced the incidence of FGR and PTB and perinatal mortality and increased BW in this rural community., (© 2024 S. Karger AG, Basel.)

Conversion of pantothenate to phosphopantothenate in humans is the first dedicated step in the coenzyme A (CoA) biosynthesis pathway and is mediated by four isoforms of pantothenate kinase. These enzymes are allosterically regulated by acyl-CoA levels, which control the rate of CoA biosynthesis. Small molecule activators of the PANK enzymes that overcome feedback suppression increase CoA levels in cultured cells and animals and have shown great potential for the treatment of pantothenate kinase-associated neurodegeneration and propionic acidemias. In this study, we detail the further optimization of PANK pyridazine activators using structure-guided design and focus on the cellular CoA activation potential, metabolic stability, and solubility as the primary drivers of the structure-activity relationship. These studies led to the prioritization of three late-stage preclinical lead PANK modulators with improved pharmacokinetic profiles and the ability to substantially increase brain CoA levels. Compound 22 (BBP-671) eventually advanced into clinical testing for the treatment of PKAN and propionic acidemia.

Background: Skin conditions form a major bulk of diseases in the community. With a disproportionately low number of dermatologists in the country, and a greatly unequal distribution between urban versus rural areas, ineffective treatment and mismanagement of skin conditions are, however, commonplace., Objective: To develop standard treatment workflows (STWs) for certain skin diseases for use by clinicians at primary, secondary, and tertiary care centers., Methodology: Seven members, from various academic institutes across the country, were selected for formulation of the STWs. They were provided logistic and technical support by the ICMR, Department of Health Research (DHR), and WHO India office. Multiple rounds of online and physical discussions were performed to identify topics that would be most useful in the management of skin diseases for the health care personnel (HCP) and subsequently to frame the STW content., Results: The selected diseases included acne and rosacea, alopecia, bacterial skin infections, cutaneous adverse drug reactions, dermatophytosis, eczema/dermatitis, immunobullous dermatoses, psoriasis, scabies, varicella and herpes, vitiligo, and urticaria. There was one separate module on rational use of topical corticosteroids. The STWs for these conditions have been finalised and are available as physical posters in health centers and can also be accessed online and through mobile applications., Conclusion: Thirteen STW modules have been prepared with a view to optimize management of skin diseases at various levels of health care system of the country., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Dermatology Online Journal.)

Landscape features can impede dispersal, gene flow, and population demography, resulting in the formation of several meta-populations within a continuous landscape. Understanding a species' ability to overcome these barriers is critical for predicting genetic connectivity and population persistence, and implementing effective conservation strategies. In the present study, we conducted a fine-scale spatial genetic analysis to understand the contemporary gene flow within red panda populations in the Eastern Himalayas. Employing geometric aspects of reserve design, we delineated the critical core habitats for red pandas, which comprise 14.5 % of the landscape (12,189.75 Km 2 ), with only a mere 443 Km 2 falling within the protected areas. We identified corridors among the core habitats, which may be vital for the species' long-term genetic viability. Furthermore, we identified substantial landscape barriers, including Sela Pass in the western region, Siang river in the central region, and the Dibang river, Lohit river, along with Dihang, Dipher, and Kumjawng passes in the eastern region, which hinder gene flow. We suggest managing red panda populations through the creation of Community Conservation Reserves in the identified core habitats, following landscape-level management planning based on the core principles of geometric reserve design. This includes a specific emphasis on identified core habitats of red panda (CH-RP 5 and CH-RP 8) to facilitate corridors and implement meta-population dynamics. We propose the development of a comprehensive, long-term conservation and management plan for red pandas in the transboundary landscape, covering China, Nepal, and Bhutan., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim  This article determines the compliance rates with low-dose aspirin (LDA) and outcomes in a group of pregnant women identified at high risk for preeclampsia (PE) and fetal growth restriction (FGR) at 11 to 14 gestational weeks (GWs) in a rural district of central India. Methods  A single, experienced fetal radiologist assessed all enrolled pregnant women using trimester-specific antenatal screening protocols that included mean arterial blood pressure assessment, and fetal ultrasound and Doppler studies. A trimester-specific individualized risk for preterm PE and FGR was estimated for each woman. Pregnant women categorized as high risk for preterm PE or FGR based on a 1 in 150 criteria at 11 to 14 GW were recommended LDA 150 mg once daily at bedtime. Outcome measures included compliance with LDA assessed, incidence of PE and FGR, preterm delivery (<37 GW), birth weight, stillbirths, and perinatal mortality. Results  The data of 488 pregnant women with longitudinal trimester-specific assessments from 11 to 14 GW till childbirth was analyzed. At the third trimester assessment, 215 (80.83%) of the high-risk women were compliant with LDA. The incidence of PE, FGR, and preterm births was significantly higher in LDA noncompliant women, and the mean birth weight was significantly higher in LDA-compliant high-risk women. Conclusion  Good compliance for LDA is possible in rural populations with adequate counseling. Starting LDA at 11 to 14 GW for high-risk pregnant women lowered the incidence of PE, FGR, and preterm birth rates and improved birth weight in the study population., Competing Interests: Conflict of Interest None declared., (Indian Radiological Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objectives: Breast cancer is the most common cancer and the leading cause of cancer-related death among women. An Estrogen Receptor (ER) antagonist called tamoxifen is used as an adjuvant therapy for ER-positive breast cancers. Approximately 40% of patients develop tamoxifen resistance (TAMR) while receiving treatment. Cancer cells can rewire their metabolism to develop resistant phenotypes, and their metabolic state determines how receptive they are to chemotherapy., Methods: Metabolite extraction from human MCF-7 and MCF-7/TAMR cells was done using the methanol-methanol-water extraction method. After treating the dried samples with methoxamine hydrochloride in pyridine, the samples were derivatized with 2,2,2-Trifluoro-N-methyl-N-(trimethylsilyl)-acetamide, and Chlorotrimethylsilane (MSTFA + 1% TMCS). The Gas chromatography/mass spectrometry (GC-MS) raw data were processed using MSdial and Metaboanalyst for analysis., Results: Univariate analysis revealed that 35 metabolites were elevated in TAMR cells whereas 25 metabolites were downregulated. N-acetyl-D-glucosamine, lysine, uracil, tyrosine, alanine, and o-phosphoserine were upregulated in TAMR cells, while hydroxyproline, glutamine, N-acetyl-L-aspartic acid, threonic acid, pyroglutamic acid, glutamine, o-phosphoethanolamine, oxoglutaric acid, and myoinositol were found to be downregulated. Multivariate analysis revealed a distinct separation between the two cell lines, as evidenced by their metabolite levels. The enriched pathways of deregulated metabolites included valine, leucine, and isoleucine degradation, Citric Acid Cycle, Warburg effect, Malate-Aspartate shuttle, glucose-alanine cycle, propanoate metabolism, and Phospholipid biosynthesis., Conclusion: This study revealed dysregulation of various metabolic processes in TAMR cells, which may be crucial in elucidating the molecular basis of the mechanisms underlying acquired tamoxifen resistance., Competing Interests: None., (AJTR Copyright © 2024.)

Introduction: The TOAST (Trial of ORG 10172 in Acute Stroke Treatment) is the most commonly used ischemic stroke subtype classification system worldwide and a required field in the US National Get With The Guidelines-Stroke (GWTG-Stroke) registry. However, stroke diagnostics have advanced substantially since the TOAST classification was designed 30 years ago, potentially making it difficult to apply reliably., Methods: In this prospective diagnostic accuracy study, we analyzed consecutive ischemic stroke patients admitted to a Comprehensive Stroke Center between July-October 2021. Clinical practice TOAST classification diagnoses rendered by the stroke team in the electronic medical record (EMR) at discharge were retrieved from GWTG-Stroke registry and compared to a reference ("gold") standard diagnosis derived from agreement between two expert raters after review of the EMR and patient imaging., Results: Among 49 patients; age was 72.3 years (±12.1), 53% female, and presenting NIHSS median 3 (IQR 1-11). Work-up included: brain imaging in 100%; cardiac rhythm assessment in 100%; cervical/cerebral vessel imaging in 98%; TTE ± TEE in 92%; and TCD emboli evaluation in 51%. Reference standard diagnoses were: LAA-6%, SVD-14%, CE-39%, OTH-10%, UND-M (more than one cause)-20%, and UND-C (cryptogenic)-10%. GWTG-Stroke TOAST diagnoses agreed with reference standard diagnoses in 30/49 (61%). Among the 6 subtype diagnoses, specificity was generally high (84.8%-97.7%), but sensitivity suboptimal for LAA (33%), OTH (60%), UND-M (10%), and UND-C (20%). Positive predictive value was suboptimal for 5 of the 6 subtypes: LAA (13%), SVD (58%), OTH (75%), UND-M (50%), and UND-C (50%)., Discussion: Clinical practice TOAST classification subtype diagnoses entered into the GWTG-Stroke registry were accurate in only 61% of patients, a performance rate that, if similarly present at other centers, would hamper the ability of the national registry to provide dependable insights into subtype-related care. Development of an updated ischemic stroke subtype classification system, with algorithmic logic embedded in electronic medical records, is desirable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rathburn, Mun, Sharma and Saver.)

Background: Increased mitochondrial activities contributing to cancer cell proliferation, invasion, and metastasis have been reported in different cancers; however, studies on the therapeutic targeting of mitochondria in regulating cell proliferation and invasiveness are limited. Because mitochondria are believed to have evolved through bacterial invasion in mammalian cells, antibiotics could provide an alternative approach to target mitochondria, especially in cancers with increased mitochondrial activities. In this study, we investigated the therapeutic potential of bacteriostatic antibiotics in regulating the growth potential of colorectal cancer (CRC) cells, which differ in their metastatic potential and mitochondrial functions., Methods: A combination of viability, cell migration, and spheroid formation assays was used to measure the effect on metastatic potential. The effect on mitochondrial mechanisms was investigated by measuring mitochondrial DNA copy number by qPCR, biogenesis (by qPCR and immunoblotting), and functions by measuring reactive oxygen species, membrane potential, and ATP using standard methods. In addition, the effect on assembly and activities of respiratory chain (RC) complexes was determined using blue native gel electrophoresis and in-gel assays, respectively). Changes in metastatic and cell death signaling were measured by immunoblotting with specific marker proteins and compared between CRC cells., Results: Both tigecycline and tetracycline effectively reduced the viability, migration, and spheroid-forming capacity of highly metastatic CRC cells. This increased sensitivity was attributed to reduced mtDNA content, mitochondrial biogenesis, ATP content, membrane potential, and increased oxidative stress. Specifically, complex I assembly and activity were significantly inhibited by these antibiotics in high-metastatic cells. Significant down-regulation in the expression of mitochondrial-mediated survival pathways, such as phospho-AKT, cMYC, phospho-SRC, and phospho-FAK, and upregulation in cell death (apoptosis and autophagy) were observed, which contributed to the enhanced sensitivity of highly metastatic CRC cells toward these antibiotics. In addition, the combined treatment of the CRC chemotherapeutic agent oxaliplatin with tigecycline/tetracycline at physiological concentrations effectively sensitized these cells at early time points., Conclusion: Altogether, our study reports that bacterial antibiotics, such as tigecycline and tetracycline, target mitochondrial functions specifically mitochondrial complex I architecture and activity and would be useful in combination with cancer chemotherapeutics for high metastatic conditions., (© 2024. The Author(s).)

Tumors are composed of heterogeneous populations of dysregulated cells that grow in specialized niches that support their growth and maintain their properties. Tumor heterogeneity and metastasis are among the major hindrances that exist while treating cancer patients, leading to poor clinical outcomes. Although the factors that determine tumor complexity remain largely unknown, several genotypic and phenotypic changes, including DNA mutations and metabolic reprograming provide cancer cells with a survival advantage over host cells and resistance to therapeutics. Furthermore, the presence of a specific population of cells within the tumor mass, commonly known as cancer stem cells (CSCs), is thought to initiate tumor formation, maintenance, resistance, and recurrence. Therefore, these CSCs have been investigated in detail recently as potential targets to treat cancer and prevent recurrence. Understanding the molecular mechanisms involved in CSC proliferation, self-renewal, and dormancy may provide important clues for developing effective therapeutic strategies. Autophagy, a catabolic process, has long been recognized to regulate various physiological and pathological processes. In addition to regulating cancer cells, recent studies have identified a critical role for autophagy in regulating CSC functions. Autophagy is activated under various adverse conditions and promotes cellular maintenance, survival, and even cell death. Thus, it is intriguing to address whether autophagy promotes or inhibits CSC functions and whether autophagy modulation can be used to regulate CSC functions, either alone or in combination. This review describes the roles of autophagy in the regulation of metabolic functions, proliferation and quiescence of CSCs, and its role during therapeutic stress. The review further highlights the autophagy-associated pathways that could be used to regulate CSCs. Overall, the present review will help to rationalize various translational approaches that involve autophagy-mediated modulation of CSCs in controlling cancer progression, metastasis, and recurrence.

Background: Captive breeding programs play a vital role in conservation of threatened species, necessitating an understanding of genetic diversity among captive individuals to ensure long-term genetic viability, appropriate mate selection, and successful reintroduction to native habitats., Methods and Results: We did not observe any recent genetic bottleneck, and population showed moderate genetic diversity. The estimated effective population size, representing individuals capable of contributing genetically to future generations, was estimated as 18.6 individuals (11.4-35.1 at 95% CI). Based on the genetic make-up and allelic diversity, we found seventeen pangolins (11 females and 6 males) were genetically unrelated and relatively more potent than others., Conclusion: In this study, we evaluated the captive breeding program of the Indian pangolin population at the Pangolin Conservation Breeding Centre in Nandankanan Zoological Park, Bhubaneswar, Odisha. We highlight the significance of genetic monitoring within the captive population of Indian pangolin for preserving genetic diversity and ensuring the long-term survival of the species. We established the genetic profiles of all 29 pangolins and identified 17 pangolins to be prioritized for enhanced breeding and future zoo exchange programs. We appreciate the zoo authorities for promoting genetic assessment of pangolin for better and more effective monitoring of the captive breeding of the endangered Indian pangolin., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Macroenzymes, formed by polymerization of physiological enzymes with immunoglobulins, have slower renal clearance rates due to their higher molecular mass. They are usually incidentally detected, have no pathophysiological importance, and can potentially lead to over-treatment and iatrogenic morbidity. We present, possibly for the first time, a macro-lipasemia variant of macroenzyme, detected in a 14-year-old girl with type-1 diabetes admitted with severe hyperglycaemia and pain abdomen. Raised lipase levels (414 U/L), initially raised the suspicion of underlying pancreatitis, which was ruled out by the clinical symptoms and normal ultrasound and CT imaging of the pancreas. Upper gastrointestinal endoscopy revealed pangastritis, which could explain the mild upper abdominal pain in the child. She improved with proton pump inhibitor therapy and was discharged after 5 days of hospital admission after good glycaemic control using multiple subcutaneous injections of insulin. Post-polyethylene glycol (PEG) precipitation, the recovery of lipase activity in PEG treated serum sample was 30.6% (127 U/L), which confirmed the presence of macrolipase. An increased clinical suspicion and performing a cheap reliable test (PEG precipitation), whenever there is clinical biochemical discordance can help us in diagnosing more patients with macroenzymes and macrolipasemia.

Land degradation has become a key concern worldwide due to changes in meteorological variables and human-caused activities. This study primarily focuses on the rate, impact, and pattern of land degradation in western India. In this instance, we evaluated the effectiveness of land degradation neutrality (LDN) between 2000 and 2020 using an integrative approach based on a PSR (pressure-state-response) model developed by the OECD-UNEP under the UNCCD framework. Here, we mainly used MODIS products (e.g., NDVI, PET, LULC, and NPP). Also, soil organic carbon (SOC) and climatic variables (e.g. precipitation, aridity index and soil moisture) were taken into account. These indicators were analysed using the Google Earth Engine (GEE) code editor platform, and post-processing was done through Q-GIS software. The analysed parameters indicate that the NDVI and NPP values are + 0.20 to + 0.3 and 4.27 × 10 9 to 7.74 × 10 9 kg Cm -2 , respectively. However, overall precipitation and soil moisture depicted a positive trend, and the aridity index adeptly followed a negative trend. Hence, the land degradation rate has increased in the north-western region besides the Aravalli range and neutrality work in the southwest part of the study area. The overall land degradation trend is negative over the last two decades. Therefore, this study anticipates the policymakers and government bodies to understand about land degradation of western India., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In spite of recent advances made in understanding its progression, cancer is still a leading cause of death across the nations. Molecular pathophysiology of these cancer cells largely differs depending on cancer types and even within the same tumor. Pathological mineralization/calcification is seen in various tissues including breast, prostate, and lung cancer. Osteoblast-like cells derived after trans-differentiation of mesenchymal cells usually drive calcium deposition in various tissues. This study aims to explore the presence of osteoblast-like potential in lung cancer cells and its prevention. ALP assay, ALP staining, nodule formation, RT-PCR, RT-qPCR, and western blot analysis experiments were carried out in lung cancer A549 cells to achieve said objective. Expressions of various osteoblast markers (e.g., ALP, OPN, RUNX2, and Osterix) along with osteoinducer genes (BMP-2 and BMP-4) were observed in A549 cells. Moreover, ALP activity and ability leading to nodule formation revealed the presence of osteoblast-like potential in lung cancer cells. Here, BMP-2 treatment increased expressions of osteoblast transcription factors such as RUNX2 and Osterix, enhanced ALP activity, and augmented calcification in this cell line. It was also observed that antidiabetic metformin inhibited BMP-2 mediated increase in osteoblast-like potential and calcification in these cancer cells. The current study noted that metformin blocked BMP-2 mediated increase in epithelial to mesenchymal transition (EMT) in A549 cells. The above findings for the first time unravel that A549 cells possess osteoblast-like potential which drives lung cancer calcification. Metformin might prevent BMP-2 induced osteoblast-like phenotype of the lung cancer cells with concomitant inhibition of EMT to inhibit lung cancer tissue calcification., (© 2023 Wiley Periodicals LLC.)

It is becoming more widely recognised that free-ranging dogs, which have a nearly global distribution, threatening native wildlife. Their increasing population and spread to new areas is of growing concern for the long-term viability of wildlife species. Hence, it is imperative to understand the factors responsible for their infestation and map areas where native species are most vulnerable. Using the random forests algorithm, we modelled the free-ranging dog infestation in the Trans-Himalayan region to pinpoint the high-risk areas where free-ranging dogs are threatening the native wildlife species. We found that the likelihood of free-ranging dog occurrence is most in valley regions and up to 4000 m, often in proximity to roads. Our results also indicated that free-ranging dog prefers areas with wildlife near to protected areas. The predictor variables, such as potential evapotranspiration of the coldest quarter, distance to protected areas, elevation, distance to roads, and potential evapotranspiration of the driest quarter, significantly influence the distribution of the free-ranging dogs. We found that within the Ladakh region of the Trans-Himalayan area, the high-risk zones for free-ranging dogs are located in and around Hemis National Park, Karakoram Wildlife Sanctuary, and Changthang Wildlife Sanctuary. While, in the Lahaul and Spiti region the high-risk areas encompass Pin Valley National Park, Inderkilla National Park, Khirganga National Park, Kugti Wildlife Sanctuary, and several other protected areas. We identified the potentially high-risk areas for implementing strategies to mitigate the possible impact of free-ranging dogs on native wildlife of the Himalayas. Hence, the identified high priority areas can be used for implementing actions for controlling the population growth and further preventing the infestation of the free-ranging dogs into the new areas., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The trans-Himalayan region of India, although have xeric features, still supports a unique assemblage of biodiversity, including some of the charismatic and endemic species. In the present study, we studied blue sheep (Pseudois nayaur) across the distribution range in the Western trans Himalayas of India and found about 18,775 km 2 area suitable for blue sheep. The explicit Bayesian based spatial and non-spatial population structure analysis assigned blue sheep into two genetic populations, i.e., Ladakh and Lahaul-Spiti. We found relatively high genetic divergence in blue sheep which is also supported by the low current flow in Circuitscape model. With the multiple evidences, we explain landscape resistance facilitated by the landscape heterogeneity, and large patches of unsuitable habitats forced population divergence and poor functional connectivity. We found that blue sheep population has been demographically stable in the past, but showed a slight decline within the last few decades. This study is the first range-wide attempt to exhibit landscape features in shaping the spatial distribution, genetic structure and demography patterns of blue sheep in Western Himalayas, and will be of use in the conservation and management planning of blue sheep., (© 2023. Springer Nature Limited.)

Both epigenetic and genetic changes in the cancer genome act simultaneously to promote tumor development and metastasis. Aberrant DNA methylation, a prime epigenetic event, is often observed in various cancer types. The elevated DNA methyltransferase 1 (DNMT1) enzyme creates DNA hypermethylation at CpG islands to drive oncogenic potential. This study emphasized to decipher the molecular mechanism of endogenous regulation of DNMT1 expression for finding upstream signaling molecules. Cancer database analyses found an upregulated DNMT1 expression in most cancer types including breast cancer. Overexpression of DNMT1 showed an increased cell migration, invasion, and stemness potential whereas 5-azacytidine (DNMT1 inhibitor) and siRNA mediated knockdown of DNMT1 exhibited inhibition of such cancer activities in breast cancer MDA-MB-231 and MCF-7 cells. Infact, cancer database analyses further found a positive correlation of DNMT1 transcript with both cholesterol pathway regulatory genes and BMP signaling molecules. Experimental observations documented that the cholesterol-lowering drug, simvastatin decreased DNMT1 transcript as well as protein, whereas BMP-2 treatment increased DNMT1 expression in breast cancer cells. In addition, expression of various key cholesterol regulatory genes was found to be upregulated in response to BMP-2 treatment. Moreover, simvastatin inhibited BMP-2 induced DNMT1 expression in breast cancer cells. Thus, this study for the first time reveals that both BMP-2 signaling and cholesterol pathways could regulate endogenous DNMT1 expression in cancer cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To evaluate the factors associated with mortality of a multicentric cohort of hospitalized COVID-19 patients, 0-18 y old, from 42 centers across India., Methods: The National Clinical Registry for COVID-19 (NCRC) is an on-going prospective data collection platform enrolling COVID-19 patients diagnosed by real-time PCR or rapid antigen test. The data are collected in prestructured e-capture forms. The sociodemographic, clinical, laboratory, and hospital outcome data from 1 st September 2020 to 20 th February 2022 were analyzed., Results: Of the 1244 enrolled hospitalized COVID-19 patients aged 0-18 y, 98 and 124 were infants and neonates, respectively. Only 68.6% children were symptomatic at admission, with fever being the most common symptom. Diarrhea, rash, and neurological symptoms were also noted. At least 1 comorbidity was present in 260 (21%) children. The in-hospital mortality rate was 6.2% (n = 67), the highest in infants (12.5%). Altered sensorium (aOR: 6.8, CI: 1.9, 24.6), WHO ordinal scale ≥ 4 at admission (aOR: 19.6, CI: 8.0, 47.8), and malignancy (aOR: 8.9, 95% CI: 2.4, 32.3) were associated with higher odds of death. Malnutrition did not affect the outcome. Mortality rates were similar across the three waves of the pandemic, though a significant shift towards the under-five group was observed in the third wave., Conclusion: This multicentric cohort of admitted Indian children showed that the COVID-19 was milder in children than adults, and the pattern was consistent across all waves of the pandemic., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Introduction: Spinal cord injury usually results in disabling conditions. The incidence of spinal trauma is region-specific due to unique geography and demography. The epidemiology of spinal trauma changes with economic and social factors even in different periods. The aim of this study was to find out the prevalence of traumatic spinal cord injury among patients admitted to the Spine Unit in a tertiary care centre., Methods: A descriptive cross-sectional study was done in a tertiary care centre among patients admitted to the Spine Unit from 1 January 2022 to 31 December 2022 after receiving ethical approval from the Institutional Review Committee. Demographic details, mode of injury, level of injuries, neurological grading at the time of admission using American Spinal Injury Association grading, management methods, and complication if any were recorded. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval., Results: Out of 465 patients, the prevalence of traumatic spinal cord injury was 316 (67.95%) (63.72-72.20, 95% Confidence Interval). A total of 243 (76.89%) cases were due to falls. The mean age of patients was 43.13±16.55 years., Conclusions: The prevalence of traumatic spinal cord injury patients was lower than the other studies done in similar settings., Keywords: falls; prevalence; spinal cord injuries.

Introduction: The effects of COVID-19 infection persist beyond the active phase. Comprehensive description and analysis of the post COVID sequelae in various population groups are critical to minimise the long-term morbidity and mortality associated with COVID-19. This analysis was conducted with an objective to estimate the frequency of post COVID sequelae and subsequently, design a framework for holistic management of post COVID morbidities., Methods: Follow-up data collected as part of a registry-based observational study in 31 hospitals across India since September 2020-October 2022 were used for analysis. All consenting hospitalised patients with COVID-19 are telephonically followed up for up to 1 year post-discharge, using a prestructured form focused on symptom reporting., Results: Dyspnoea, fatigue and mental health issues were reported among 18.6%, 10.5% and 9.3% of the 8042 participants at first follow-up of 30-60 days post-discharge, respectively, which reduced to 11.9%, 6.6% and 9%, respectively, at 1-year follow-up in 2192 participants. Patients who died within 90 days post-discharge were significantly older (adjusted OR (aOR): 1.02, 95% CI: 1.01, 1.03), with at least one comorbidity (aOR: 1.76, 95% CI: 1.31, 2.35), and a higher proportion had required intensive care unit admission during the initial hospitalisation due to COVID-19 (aOR: 1.49, 95% CI: 1.08, 2.06) and were discharged at WHO ordinal scale 6-7 (aOR: 49.13 95% CI: 25.43, 94.92). Anti-SARS-CoV-2 vaccination (at least one dose) was protective against such post-discharge mortality (aOR: 0.19, 95% CI: 0.01, 0.03)., Conclusion: Hospitalised patients with COVID-19 experience a variety of long-term sequelae after discharge from hospitals which persists although in reduced proportions until 12 months post-discharge. Developing a holistic management framework with engagement of care outreach workers as well as teleconsultation is a way forward in effective management of post COVID morbidities as well as reducing mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In view of WHO's "End-TB" strategy, we developed a non-invasive, urine-based ELISA, targeting 2 Mycobacterium tuberculosis antigens namely MPT51 and MPT64 for extrapulmonary TB (EPTB) diagnosis. Suspected EPTB patients (n = 137) [Pleural TB, Abdominal TB and Tuberculous meningitis] were categorized in "Definite" EPTB (n = 10) [Xpert-MTB/RIF and/or culture-positive], "Probable" EPTB (n = 77) and "Non-EPTB" (n = 50) groups using defined composite reference standards. ROC-curves were generated using ELISA results of "Definite" EPTB and "Non-EPTB" groups for both antigens independently and cut-off values were selected to provide 86.3% (95%CI:73.3-94.2) specificity for MPT51 and 92% (95%CI:80.8-97.8) for MPT64. The sensitivity of MPT51-ELISA and MPT64-ELISA was 70% (95%CI:34.7-93.3) and 90% (95%CI:55.5-99.7) for "Definite" EPTB group and 32.5% (95%CI:22.2-44.1) and 30.8% (95%CI:20.8-42.2) for "Probable" EPTB group, respectively. Combining the results of both ELISAs showed a 100% (95%CI:69.1-100) sensitivity in "Definite" EPTB group and 41.6% (95%CI:30.4-53.4) in "Probable" EPTB group, with an 80% (95%CI:66.3-89.9) specificity. The results demonstrated the potential of urine-based ELISAs as screening tests for EPTB diagnosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Primary healthcare caters to nearly 70% of the population in India and provides treatment for approximately 80-90% of common conditions. To achieve universal health coverage (UHC), the Indian healthcare system is gearing up by initiating several schemes such as National Health Protection Scheme, Ayushman Bharat, Nutrition Supplementation Schemes, and Inderdhanush Schemes. The healthcare delivery system is facing challenges such as irrational use of medicines, over- and under-diagnosis, high out-of-pocket expenditure, lack of targeted attention to preventive and promotive health services, and poor referral mechanisms. Healthcare providers are unable to keep pace with the volume of growing new scientific evidence and rising healthcare costs as the literature is not published at the same pace. In addition, there is a lack of common standard treatment guidelines, workflows, and reference manuals from the Government of India. Indian Council of Medical Research in collaboration with the National Health Authority, Govt. of India, and the WHO India country office has developed Standard Treatment Workflows (STWs) with the objective to be utilized at various levels of healthcare starting from primary to tertiary level care. A systematic approach was adopted to formulate the STWs. An advisory committee was constituted for planning and oversight of the process. Specialty experts' group for each specialty comprised of clinicians working at government and private medical colleges and hospitals. The expert groups prioritized the topics through extensive literature searches and meeting with different stakeholders. Then, the contents of each STW were finalized in the form of single-pager infographics. These STWs were further reviewed by an editorial committee before publication. Presently, 125 STWs pertaining to 23 specialties have been developed. It needs to be ensured that STWs are implemented effectively at all levels and ensure quality healthcare at an affordable cost as part of UHC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Grover, Bhargava, Srivastava, Sharma, Cherian, Tandon, Chandershekhar, Ofrin, Bekedam, Pandhi, Mukherjee, Dhaliwal, Singh, Rajshekhar, Roy, Rasaily, Saraf, Kumar, Parmar, Kabra, Chaudhry, Deorari, Tandon, Singh, Khaitan, Agrawala, Gupta, Goel, Bhansali, Dutta, Seth, Singh, Awasthi, Seth, Pandian, Jha, Dwivedi, Tripathi, Thakar, Jindal, Gangadhar, Bajaj, Kant and Chatterjee.)

Pleistocene glaciations had profound impact on the spatial distribution and genetic makeup of species in temperate ecosystems. While the glacial period trapped several species into glacial refugia and caused abrupt decline in large populations, the interglacial period facilitated population growth and range expansion leading to allopatric speciation. Here, we analyzed 40 genomes of four species of ibex and found that Himalayan ibex in the Pamir Mountains evolved independently after splitting from its main range about 0.1 mya following the Pleistocene species pump concept. Demographic trajectories showed Himalayan ibex experienced two historic bottlenecks, one each c. 0.8-0.5 mya and c. 50-30 kya, with an intermediate large population expansion c. 0.2-0.16 mya coinciding with Mid-Pleistocene Transitions. We substantiate with multi-dimensional evidence that Himalayan ibex is an evolutionary distinct phylogenetic species of Siberian ibex which need to be prioritized as Capra himalayensis for taxonomic revision and conservation planning at a regional and global scale.