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In India, Mizoram has the highest incidence of gastric cancer (GC) which might be associated with environmental factors such as diet, Helicobacter pylori (H.pylori) and Epstein-Barr virus (EBV) infections, and somatic genomic alterations. We performed PCR cum sequencing and fragment analysis for detection of H. pylori/EBV infection and microsatellite Instability (MSI) in GC patients (N = 68). Somatic mutations were identified by targeted and exome sequencing. We found 87% of GC patients infected with H. pylori and or EBV. Pathogenic infections were mostly mutually exclusive with only 16% of coinfection. TP53, MUC6, and ARID1A were significantly mutated. Two molecular subgroups with distinctive mutational profiles were identified: (1) patients harboring mutations in TP53 and (2) patients harboring mutations in RTK/RAS/PI3-K signaling pathway and chromatin-remodeling genes. Therefore, EBV and H. pylori infections and somatic mutations in the genes involved in RTK/RAS/PI3K signaling pathway, chromatin-remodeling, and TP53 might drive GC development and progression in Mizo patients., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, financial or otherwise., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Isomerization is extensively utilized in the petroleum industry, and this study demonstrates an energy-efficient process utilizing an ionic liquid catalyst. 1-Ethyl-3-methylimidazolium triflate [Emim][TFO] as an ionic liquid was immobilized on solid support Fe/SBA-15. Variants of the catalyst were developed with the Fe constant at 5% and different ratios of ionic liquid. In the catalyst Fe/[Emim][TFO]/SBA-15, the metal Fe was loaded via the impregnation method, and subsequently, the ionic liquid variants Fe/[Emim][TFO](10)/SBA-15, Fe/[Emim][TFO](20)/SBA-15, and Fe/[Emim][TFO](30)/SBA-15 were synthesized. The physical properties of the synthesized catalyst were studied using standard characteristic techniques. The process performance was studied for variants of each parameter, which include temperature, hydrogen flow rate, pressure, and weight hourly space velocity. The iso-products of n -heptane and n -octane were obtained with an appreciable conversion of >90% and a selectivity of >95% with the catalyst Fe/[Emim][TFO](20)/SBA-15 among the other synthesized catalysts. The process yielded a high quantum of iso-products with negligible cracked products at a low temperature of 140 °C. The catalyst Fe/[Emim][TFO](20)/SBA-15 at 140 °C delivered the highest yield of iso-alkanes among the three catalysts. Iso-alkanes are instrumental tools for increasing the octane number of a fuel. This study delivers high iso-alkane content fuel, which can provide the best anti knock capability and enhance fuel efficiency for the life of modern high-powered engines. The results demonstrate a process that is energy-efficient, economic, and environmentally friendly.

This study aimed to investigate the efficacy of a rice straw biosorbent in batch adsorption for the removal of chromium (Cr(VI)) and lead (Pb(II)) heavy-metal ions from wastewater. The biosorbent was chemically synthesized and activated by using concentrated sulfuric acid. The produced biosorbent was then characterized by using Fourier transform infrared (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD) analyses, which provided insights into surface morphology and functional groups. The study examined the effects of pH, rice straw dose, ion concentration, and contact time on metal ion adsorption. Optimal conditions for efficient removal (95.57% for Cr(VI) and 85.68% for Pb(II)) were achieved at a pH of 2.0, a biosorbent dose of 2 g/L, an initial concentration of 20 mg/L, and a contact time of 50 min in synthetic solutions. The isotherms and kinetics model fitting results found that both metal ion adsorption processes were multilayer on the hetero surface of rice straw biosorbent via rate diffusion kinetics. Thermodynamic investigations were conducted, and the results strongly indicate that the adsorption process is endothermic and spontaneous. Notably, the results indicated that the highest desorption rate was achieved by adding 0.3 N HCl to the system., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Despite being the second least populated state, Mizoram exhibits the highest incidence rate of cancer in India. Its inhabitants, constituting an endogamous and isolated population, have embraced their own distinct culture, way of life and dietary preferences, setting them apart from the rest of mainland India. In 2003, the Mizoram Population Based Cancer Registry (PBCR) was established under the auspices of the National Centre for Disease Informatics and Research (NCDIR), a division of the Indian Council of Medical Research (ICMR), in collaboration with the Department of Health & Family Welfare of the Government of Mizoram, India., Methods: Cancer incidence and mortality data were extracted from the Mizoram PBCR spanning the years 2003-2020. The Age Standardized Incidence Rate (ASIR) and Age Standardized Mortality Rate (ASMR) were computed per 100,000 individuals, utilizing Segi's World Standard Population as the benchmark. The trajectory of these changes was analysed employing the Joinpoint Regression Analysis Program, Version 4.9.1.0.13, to unveil the Annual Percent Change (APC) with a 95% Confidence Interval and a Significance test (p < 0.05) using Monte Carlo Permutation. The resulting graphical visualizations were generated using Flourish Studio.15., Findings: The overall ASIR for all cancer sites among men was 197.2 per 100,000, while for women, it was 164.9 per 100,000. Among men, the most prevalent cancer site was the Stomach (ASIR = 41.4), followed by Head & Neck, Lung, Oesophagus, Colorectal, Liver, Urinary, Non-Hodgkin's Lymphoma and Prostate cancers. Conversely, among women, Lung cancer exhibited the highest incidence (ASIR = 26.7), succeeded by Cervical, Breast, Stomach, Head & Neck, Colorectal, Oesophagus, Liver and Ovarian cancers. Stomach cancer emerged as the leading cause of death among men (ASMR = 22.6) and among women, Lung cancer held the highest ASMR (15.9). Joinpoint regression analysis revealed a rising trend in incidence and mortality over time for overall cancer sites. Among the primary cancer sites contributing to incidence and mortality, an increase in APC was observable for all, except Stomach cancer, in both men and women. The diagnostic approach, except for cases of cancer with unknown primary sites, involved a microscopic method., Interpretation: This cross-sectional study examines PBCR reports spanning from 2003 to 2020, shedding light on a consistent uptick in cancer incidence and mortality trends in Mizoram. Stomach cancer emerges as the most prevalent and primary cause of cancer-related deaths among men, while Lung cancer takes a parallel role in women. The elevated cancer incidence and the growing trend among younger generations might stem from the static lifestyle and dietary patterns prevalent within the endogamous tribal population, potentially contributing to a genetic predisposition. The escalation in mortality rates could be attributed to a dearth of specialized diagnostic facilities and skilled human resources, treatment strategies guided by genomic research and transportation challenges. This underscores the urgent requirement for comprehensive scientific exploration across diverse facets. The implementation of easily accessible diagnostic facilities in proximity and genetic testing for pharmacogenomics to enhance prognoses would also aid in mitigating the burden and advancing the healthcare system's effectiveness., Funding: Population Based Cancer Registry (PBCR) was supported by National Centre for Disease Informatics and Research (NCDIR) of the Indian Council of Medical Research (ICMR), India., Competing Interests: The authors declare that they have no conflict of interests., (© 2023 The Author(s).)

Objective: To investigate the effectiveness of a virtual hackathon in fostering interdisciplinary working amongst undergraduate students in global surgery., Methodology: In this study, we developed a 3 day event consisting of guest lectures, a documentary screening and a hackathon supported by academics and experts in the field, to provide students with the opportunity to learn more about and work in interdisciplinary teams within global surgery. Students had the option to attend just the lectures or both the lectures and hackathon. Quantitative and qualitative results were collected through a pre and post session survey., Results: A total of 21 responses were received for the hackathon and 26 responses for the general event (response rate for event = 26 %, response rate for hackathon = 24.7 %). There was a significant improvement in understanding of interdisciplinary working in global surgery between the pre and post-session survey, with an increase in median from 3 (IQR = 2-3.5, n = 21) to 4 (IQR = 4-5, n = 21) (p < 0.05). Respondents noted that the benefits of a hackathon were that it was very engaging, and brought in diversity of thought and expertise. The drawbacks to the hackathon were that it was fast-paced, required prior knowledge and the virtual platform it was hosted on., Conclusion: Our study demonstrates that hackathons are an effective, inclusive and equitable way for students to engage in and learn about interdisciplinary working. It is important that as institutions recognise and develop global surgery courses, these courses reflect the interdisciplinary nature of the field., Competing Interests: The authors have no competing interests., (© 2023 The Authors.)

Background: Deep brain stimulation (DBS) has been proposed to improve symptoms of obsessive-compulsive disorder (OCD) but is not yet an established therapy., Aims: To identify relevant guidelines and assess their recommendations for the use of DBS in OCD., Method: Medline, Embase, American Psychiatric Association PsycInfo and Scopus were searched, as were websites of relevant societies and guideline development organisations. The review was based on the PRISMA recommendations, and the search strategy was verified by a medical librarian. The protocol was developed and registered with PROSPERO (CRD42022353715). The guidelines were assessed for quality using the AGREE II instrument., Results: Nine guidelines were identified. Three guidelines scored >80% on AGREE II. 'Scope and Purpose' and 'Editorial Independence' were the highest scoring domains, but 'Applicability' scores were low. Eight guidelines recommended that DBS is used after all other treatment options have failed to alleviate OCD symptoms. One guideline did not recommend DBS beyond a research setting. Only one guideline performed a cost-effectiveness analysis; the other eight did not provide details on safe or effective DBS protocols., Conclusion: Despite a very limited evidence base, eight of the nine identified guidelines supported the use of DBS for OCD as a last line of therapy; however, multiple aspects of DBS provision were not addressed.

Introduction: Endodontics faces several clinical difficulties while treating young necrotic permanent teeth. The use of regenerative endodontic procedures (REPs) enables apical closure, improved canal wall thickness, and root growth. The objective of this study was to assess the effects of these regenerative procedures on immature necrotic permanent teeth., Methods: This prospective clinical study was conducted at the tertiary care hospital for the study period of 2 years. This study includes 30 necrotic permanent immature teeth that were studied in 30 subjects of both genders. A standard REP protocol was used to treat every tooth. A follow-up visit was scheduled for each patient at timely intervals. Various study parameters as well as the demographics were assessed at each visit. To examine various parameters, a calibrated endodontist also performed a radiographic evaluation., Results: Our findings point to excellent rates of survival, clinical success, and apical pathological resolution for 29 teeth. After 2 years, there were significant variations in the root thickness area and the average root length. The apical diameter significantly decreased during the research period, with 30.8% of the instances exhibiting full apical closure. Apical diameter, root length, and thickness changed more frequently in teeth with the level of the immaturity of the root, although the variations were not significant., Conclusions: REP treatment for teeth preceded symptom relief. Increased root thickness, root length, and apical closure were seen at 30 months, even if the clinically meaningful change was not attained in all patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Autism spectrum disorder (ASD) is a neurodevelopmental disability that causes social impairment, debilitated verbal or nonverbal conversation, and restricted/repeated behavior. Recent research reveals that mitochondrial dysfunction and oxidative stress might play a pivotal role in ASD condition. The goal of this case-control study was to investigate oxidative stress and related alterations in ASD patients. In addition, the impact of mitochondrial DNA (mtDNA) mutations, particularly MT-ATP6, and its link with oxidative stress in ASD was studied. We found that ASD patient's plasma had lower superoxide dismutase (SOD) and higher catalase (CAT) activity, resulting in lower SOD/CAT ratio. MT-ATP6 mutation analysis revealed that four variations, 8865 G>A, 8684 C>T, 8697 G>A, and 8836 A>G, have a frequency of more than 10% with missense and synonymous (silent) mutations. It was observed that abnormalities in mitochondrial complexes (I, III, V) are more common in ASD, and it may have resulted in MT-ATP6 changes or vice versa. In conclusion, our findings authenticate that oxidative stress and genetics both have an equal and potential role behind ASD and we recommend to conduct more such concurrent research to understand their unique mechanism for better diagnosis and therapeutic for ASD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Socioeconomic and urban-rural inequalities in the population-level double burden of child malnutrition threatens global nutrition targets 2025, especially in East and Southern Africa. We aimed to quantify these inequalities from nationally representative household surveys in the East and Southern African region. 13 Demographic and Health Surveys between 2006 and 2018 including 72,231 children under five years old were studied. Prevalence of stunting, wasting and overweight (including obesity) were disaggregated by wealth quintiles, maternal education categories and urban-rural residence for visual inspection of inequalities. The slope index of inequality (SII) and the relative index of inequality (RII) were estimated for each country. Regional estimates of child malnutrition prevalence and socioeconomic and urban-rural inequalities were generated from pooling country-specific estimates using random-effects meta-analyses. Regional stunting and wasting prevalence were higher among children living in the poorest households, with mothers with the lowest educational level and in rural areas. In contrast, regional overweight (including obesity) prevalence was higher among children living in the richest households, with mothers with the highest educational level and urban areas. This study indicates pro-poor inequalities are present in child undernutrition and pro-rich inequalities are present in child overweight including obesity. These findings re-emphasise the need for an integrated approach to tackling the population-level double burden of child malnutrition in the region. Policy makers must target specific populations that are vulnerable to child malnutrition, to avoid further widening of socioeconomic and urban-rural inequalities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Caleyachetty 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.)

The synthesis of dihydropyridone derivatives has been reported by ring rearrangement of pyrans using iodine and formic acid as a catalyst separately. Dihydropyridones were crystallized subjected for single-crystal X-ray crystallography to acquire their structural parameters. The different non-covalent interactions involved within the supramolecular systems were studied and validated using Hirshfeld surface plot analysis. N-H⋅⋅⋅O interactions between the lactam group dominate. Still, other non-covalent interactions such as C-H⋅⋅⋅N, C-H⋅⋅⋅O, C-H⋅⋅⋅C, N-H⋅⋅⋅N, C-H⋅⋅⋅π, and lone pair⋅⋅⋅π systems act as the driving force in facilitating the self-assembly of the dihydropyridone supramolecules. The synthesized compounds were analyzed by in vitro techniques using human lung adenocarcinoma (A549) to evaluate their cytotoxic activities. Ethyl 4-(4-chlorophenyl)-5-cyano-2-methyl-6-oxo-1,4,5,6- tetrahydropyridine-3-carboxylate has shown the highest cytotoxicity among all the synthesized compounds. Molecular recognition properties of the dihydropyridone compounds were also studied, employing molecular docking tools to gain insight into the binding mode inside the allosteric binding pocket of the Eg5 protein through non-covalent interactions., (© 2023 Wiley-VCH GmbH.)

An innovative form of 2D/0D g-C 3 N 4 /CeO 2 nanostructure was synthesized using a simple precursor decomposition process. The 2D g-C 3 N 4 directs the growth of 0D CeO 2 quantum dots, while also promoting good dispersion of CeO 2 QDs. This 2D/0D nanostructure shows a capacitance of 202.5 F/g and notable rate capability and stability, outperforming the g-C 3 N 4 electrode, reflecting the state-of-the-art g-C 3 N 4 binary electrodes. The binary combination of materials also enables an asymmetric device (g-C 3 N 4 /CeO 2 QDs//AC) to deliver the highest energy density (9.25 Wh/kg) and power density (900 W/kg). The superior rate capacity and stability endorsed the quantum structural merits of CeO 2 QDs and layered g-C 3 N 4 , which offer more accessible sites for ion transport. These results suggest that the g-C 3 N 4 /CeO 2 QDs nanostructure is a promising electrode material for energy storage devices.

The gastrointestinal system, also referred to as the gut, is a universe that colonizes trillions of microbes. In addition to its digestive functions, the gut represents a biosystem that determines all the health vectors. It is now recognized as one of the body's defense systems, and good gut health regulates the body's immune responses. Disturbance of this barrier can trigger many diseases, including respiratory tract infections, as there is a close correlation between the gut microbiome and the chances of triggering illness. This review investigates the various factors affecting the gut microbiome, the diseases that can result from the dysregulation of the same, and their molecular mechanisms. The most basic solution to tackle this problem is to maintain the gut microbiome at the desired level. Timely diagnosis and interventions are needed for the proper management of the ensuing conditions. It is important to address the effects of factors on the gut microbiome and thereby regulate this level. The study also found that dysregulation in the system can lead to various diseases such as asthma, COPD, lung cancer following their respective pathways. In short, this paper reinforces the importance of the gut microbiome, the need to maintain its average level, and the need for proper interventions to treat the consequences. The manuscript posit that medications, diet as well and good physiological conditions of the human body can alter the microbiome and can ward off respiratory infections., Competing Interests: Conflict of interestThe authors declare that they have no competing interests., (© Association of Microbiologists of India 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Over the years, betel quid chewing and tobacco use have attracted considerable interest as they are implicated as the most likely causative risk factors of oral and esophageal cancers. Although areca nut use and betel quid chewing may lead to apoptosis, chronic exposure to areca nut and slaked lime may promote pre-malignant and malignant transformation of oral cells. The putative mutagenic and carcinogenic mechanisms may involve endogenous nitrosation of areca and tobacco alkaloids as well as the presence of direct alkylating agents in betel quid and smokeless tobacco. Metabolic activation of carcinogenic N -nitrosamines by phase-I enzymes is required not only to elicit the genotoxicity via the reactive intermediates but also to potentiate the mutagenicity with the sporadic alkylations of nucleotide bases, resulting in the formation of diverse DNA adducts. Persistent DNA adducts provides the impetus for genetic and epigenetic lesions. The genetic and epigenetic factors cumulatively influence the development and progression of disorders such as cancer. Accumulation of numerous genetic and epigenetic aberrations due to long-term betel quid (with or without tobacco) chewing and tobacco use culminates into the development of head and neck cancers. We review recent evidence that supports putative mechanisms for mutagenicity and carcinogenicity of betel quid chewing along with tobacco (smoking and smokeless) use. The detailed molecular mechanisms of the extent of accumulation and patterns of genetic alterations, indicative of the prior exposure to carcinogens and alkylating agents because of BQ chewing and tobacco use, have not yet been elucidated., Competing Interests: 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., (© 2023 The Authors.)

Parkinson's disease (PD) is an age associated neurological disorder which is specified by cardinal motor symptoms such as tremor, stiffness, bradykinesia, postural instability, and non-motor symptoms. Dopaminergic neurons degradation in substantia nigra region and aggregation of αSyn are the classic signs of molecular defects noticed in PD pathogenesis. The discovery of microRNAs (miRNA) predicted to have a pivotal part in various processes regarding regularizing the cellular functions. Studies on dysregulation of miRNA in PD pathogenesis has recently gained the concern where our review unravels the role of miRNA expression in PD and its necessity in clinical validation for therapeutic development in PD. Here, we discussed how miRNA associated with ageing process in PD through molecular mechanistic approach of miRNAs on sirtuins, tumor necrosis factor-alpha and interleukin-6, dopamine loss, oxidative stress and autophagic dysregulation. Further we have also conferred the expression of miRNAs affected by SNCA gene expression, neuronal differentiation and its therapeutic potential with PD. In conclusion, we suggest more rigorous studies should be conducted on understanding the mechanisms and functions of miRNA in PD which will eventually lead to discovery of novel and promising therapeutics for PD., (© 2022 Wiley Periodicals LLC.)

Objectives: To examine the frequency of repetitive behaviors among children with autism spectrum disorder (ASD) and compare it to age-matched developmentally delayed (DD) and typically developing children (TD)., Methods: Twenty-five children (3-8 y) with a diagnosis of ASD were compared to two age-matched control groups namely the DD and TD groups. The Repetitive Behaviors Scale-Revised (RBS-R) was administered to the parents to assess the frequency, severity, and impairment associated with restricted, repetitive behaviors, and interests (RRBIs) displayed. The study was cleared by the institute ethics committee., Results: The three groups were well matched on age and sex distribution and comparisons on the RBS-R showed that the ASD group had a significantly higher total score (F = 51.52, p = 0.0001) and number of items endorsed on the scale (F = 37.91, p = 0.0001). Stepwise multiple regression analysis revealed that 35.8% of the variance in the total RRBI score of the ASD children was explained by the age and severity of autism (F = 6.12. p = .008). Older children with severe ASD features had significantly higher total RRBI scores., Conclusions: RRBIs are not just specific to autism and should not be used in isolation to identify children with autism. Gaining a complete understanding of the complexity and variability of the restricted interests would help in improving the diagnostic procedures and in the development of a comprehensive therapeutic plan., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Background: Rifampicin resistance (RR) is a surrogate marker of multidrug-resistant tuberculosis. The aim of this study is to determine the frequency of the commonly mutated probes for rpoB gene and locate the residential areas of the Rifampicin Resistant-TB (RR-TB) patients in a high endemic zone of Northeast India., Methods: Archived data of 13,454 Xpert MTB/RIF reports were evaluated retrospectively between 2014 and 2021. Socio-demographic and available clinical information were reviewed and analyzed for RR-TB cases only. Logistic Regression was used to analyze the parameters with respect to probe types. P-value ≤ 0.05 was considered to be statistically significant., Results: 2,894 patients had Mycobacterium tuberculosis infection out of which 460 were RR-TB, which was most prevalent among 25-34 years. The most common mutation occurred in probe A (25.9 %) followed by E (23.5 %), D (9.8 %), B (2.6 %) and the least in C (0.2 %). High prevalence (34.3 %) of probe mutation combinations were also found: probes AB (0.4 %), AD (32.8 %), AE (0.4 %), DE (0.2 %) and ADE (0.4 %). Seventeen patients (3.7 %) were found without any missing probes. RR-TB patients were mostly located in Aizawl North -III, South -II and East -II constituencies., Conclusion: This study provides genetic pattern of drug resistance accountable for RR over the past years in Mizoram which will help local clinicians in the initiation of correct treatment. Also, our findings provide a baseline data on the magnitude of RR-TB within the state and identification of the residential areas can help local health authorities in planning surveillance programs to control the spread of RR-TB., Competing Interests: 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., (© 2022 Published by Elsevier Ltd.)

Even when cultivated in uncontaminated soils, tobacco plant has higher propensity to extract and accumulate trace elements. The concentrations (mass fractions) of essential elements (K, Ca, Mg, Na, Cl, Mn, Fe, Cu, and Zn) and 28 non-essential elements in tobacco plant (leaves, stem, and root) of Northeast India and their respective soils were quantitatively measured. Hg mass fraction in all samples analyzed were found to be < 10 mg/kg. The heavy element mass fractions of tobacco are weakly correlated to different soil parameters. The bioconcentration factor values indicated that Cd (7) is selectively absorbed and translocated in the tobacco leaves compared to Zn (1.7), Cu (1.5), Ni (0.12), and Pb (0.1). Under acidic soil conditions, tobacco plant efficiently absorbed and translocated Cl - ion with great ease, whereas it may be a very low accumulator of rare-earth elements. The mass fractions of Mn, Cu, Sb, Cs, Rb, and Pb are very similar to the "reference plant," whereas significantly higher mass fractions of Al, Sc, Ti, Zr, Hf, Ta, Th, and U are present in the roots of tobacco plant relative to the "reference plant." Principal component analysis has revealed that Northeast Indian tobacco can be clearly differentiated from other varieties of tobaccos used in different countries because of their element profiles., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Three series of our lead CLK1 inhibitor DB18 have been designed, synthetized and tested against CLKs and DYRK1A kinases. Their cytotoxicity was subsequently measured on seven representative cancer cell lines. Guided by docking experiments, we focused on the less constrained part of the scaffold, and showed that drastically different substituents can be tolerated here. This work ended with the discovery of another promising derivative 12g , with IC 50 = 0.004 µM in the inhibition of Hs CLK1 and IC 50 = 3.94 µM for the inhibition of Hs DYRK1A. The SAR results are discussed in the light of extensive molecular modeling analyses. Finally, a kinome scan (463 human kinases) confirmed the outstanding selectivity of our lead compound DB18 , suggesting that this scaffold is of prominent interest for selective CLK inhibitors. Altogether, these results pave the way for the development of inhibitors with novel selectivities in this family of kinases.

Background: Minimally invasive surgical (MIS) techniques are considered the gold standard of surgical interventions, but they have a high environmental cost. With global temperatures rising and unmet surgical needs persisting, this review investigates the carbon and material footprint of MIS and summarizes strategies to make MIS greener., Methods: The MEDLINE, Embase, and Web of Science databases were interrogated between 1974 and July 2021. The search strategy encompassed surgical setting, waste, carbon footprint, environmental sustainability, and MIS. Two investigators independently performed abstract/full-text reviews. An analysis of disability-adjusted life years (DALYs) averted per ton of carbon dioxide equivalents (CO2e) or waste produced was generated., Results: From the 2456 abstracts identified, 16 studies were selected reporting on 5203 MIS procedures. Greenhouse gas (GHG) emissions ranged from 6 kg to 814 kg CO2e per case. Carbon footprint hotspots included production of disposables and anaesthetics. The material footprint of MIS ranged from 0.25 kg to 14.3 kg per case. Waste-reduction strategies included repackaging disposables, limiting open and unused instruments, and educational interventions. Robotic procedures result in 43.5 per cent higher GHG emissions, 24 per cent higher waste production, fewer DALYs averted per ton of CO2, and less waste than laparoscopic alternatives., Conclusion: The increased environmental impact of robotic surgery may not sufficiently offset the clinical benefit. Utilizing alternative surgical approaches, reusable equipment, repackaging, surgeon preference cards, and increasing staff awareness on open and unused equipment and desflurane avoidance can reduce GHG emissions and waste., (© Crown copyright 2022.)

Medical research is a highly competitive yet vital part of medical training, spanning all specialties. Extra-curricular, research-related activities are a key method by which students develop interest in their field of choice, and a competitive edge in medical students. The lack of research education and opportunities within medical school teaching tends to force medical students to look beyond their degree to obtain this experience, and is often the reason why students have little research involvement whilst in medical school. Self-reflecting on one's personality and suitability for different types of research is vital, as well as understanding the nature of research and preparing appropriately before undertaking projects. This paper presents twelve tips for medical students who are interested in pursuing research, offering targeted strategies to get involved.

During our work on exploration of molecules with some piperidine-triazole scaffolds, we realized that our compounds display chemical similarity with some σ, as well as dopaminergic receptor ligands. Here we show that this series of molecules has indeed strong affinity both for σ1 and dopamine D4 receptors. Moreover, they appear selective towards σ2, dopamine paralogues D1, D2, D3 and D5 receptors and hERG channel. Extensive molecular dynamics with our lead compound AVRM-13 were carried out on σ1, supporting agonist activity of the ligand. Unexpectedly, several observations suggested the existence of a cation binding domain, a probable regulatory site for calcium., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Blunt cardiac injury (BCI), defined as an injury to the heart from blunt force trauma, ranges from minor to life-threatening. The majority of BCIs are due to motor vehicle accidents; however, injuries caused by falls, blasts, and sports-related injuries also can be sources of BCI. A significant proportion of patients with BCI do not survive long enough to receive medical care, succumbing to their injuries at the scene of the accident. Additionally, patients with blunt trauma often have coexisting injuries (brain, spine, orthopedic) that can obscure the clinical picture; therefore, a high degree of suspicion often is required to diagnose BCI. Traditionally, hemodynamically stable injuries suspicious for BCI have been evaluated with electrocardiograms and chest radiographs, whereas hemodynamically unstable BCIs have received operative intervention. More recently, computed tomography and echocardiography increasingly have been utilized to identify injuries more rapidly in hemodynamically unstable patients. Transesophageal echocardiography can play an important role in the diagnosis and management of several BCIs that require operative repair. Close communication with the surgical team and access to blood products for potentially massive transfusion also play key roles in maintaining hemodynamic stability. With proper surgical and anesthetic care, survival in cases involving urgent cardiac repair can reach 66%-to-75%. This narrative review focuses on the types of cardiac injuries that are caused by blunt chest trauma, the modalities and techniques currently used to diagnose BCI, and the perioperative management of injuries that require surgical correction., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The current study focuses on developing a tumour-targeted functionalised nanocarrier that wraps hollow mesoporous silica nanoparticles. The guanidine carbonate and curcumin are immobilised on the surface of 3-aminopropyl-triethoxy silane (APTES)-decorated hollow mesoporous silica nanoparticles (HMSNP), as confirmed through XPS and NMR analysis. XPS analysis demonstrates that the shape of the hysteresis loops is modified and that pore volume and pore diameter are consequently decreased compared to control. Guanidine (85%) and guanidine-curcumin complex (90%) were successfully encapsulated in HMSNAP and showed a 90% effective and sustained release at pH 7.4 for up to 72 h. Acridine orange/ethidium bromide dual staining determined that GuC-HMNSAP induced more late apoptosis and necrosis at 48 and 72 h compared with Gu-HMNSAP-treated cells. Molecular investigation of guanidine-mediated apoptosis was analysed using western blotting. It was found that cleaved caspases, c-PARP, and GSK-3β (Ser9) had increased activity in MCF-7 cells. GuC-HMSNAP increased the activity of phosphorylation of oncogenic proteins such as Akt (Ser473), c-Raf (Ser249), PDK1 (Ser241), PTEN (Ser380), and GSK-3β (Ser9), thus inducing cell death in MCF-7 cells. Altogether, our findings confirm that GuC-HMNSAP induces cell death by precisely associating with tumour-suppressing proteins, which may lead to new therapeutic approaches for breast cancer therapy.

Purpose: Tuberculosis, a crucial infectious disease is still a health concern globally. India is among the countries with high MDR-TB burden. Currently, sputum smear microscopy using Ziehl Neelsen stain and GeneXpert are the only diagnostic means in Mizoram. This study was done to characterize local tuberculosis strains circulating in Mizoram., Methods: Sputum was cultured using MGIT 960 and DST was performed for Streptomycin, Isoniazid, Rifampicin, Ethambutol and Pyrazinamide. GeneXpert test was done simultaneously. DNA was extracted using Trueprep AUTO v2, molbio diagnostics. Antibiotic Resistance Genes and LSP were amplified and sequenced., Results: Ser315Thr was the most common mutation in katG among MDR-TB isolates. GeneXpert probes A and D drop out upon sequencing showed L511P, H526Q and H526L mutation. The L511P and H526Q mutations were seen in new and treated cases. Discrepancy between MGIT 960 and GeneXpert were observed. LSP-PCR revealed that Indo-Oceanic, East-African Indian, Euro-American and Beijing lineages were found in Mizoram., Conclusion: This study provides mutation information on the resistant genotypes detected with GeneXpert as well as MGIT 960. It also provides information on the lineages of Mycobacterium tuberculosis circulating in the state. Utilization of sequencing technologies is essential in diagnostic laboratories to rule out discrepant results and as a cautionary measure to prevent wrong diagnosis and treatment., (Copyright © 2022 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Aerogels are a unique class of nanoporous ultralight materials exhibiting wide range of textural characteristic properties and tunable porosities. Due to their remarkable features such as low density, high surface area, low refractive index, small thermal conductivity, low dielectric constant and low sound velocity, they exhibit a wide range of applications in different areas such as electronics, thermal and acoustic insulation, chemistry, biomedicine and optics. The special advantages of these materials are that they can be produced in different forms such as monoliths/granular, bead/microspheres, thin films or sheets and as blankets. Aerogels are found to be potential materials for the removal of CO 2 through adsorption or electrochemical reduction. There is a plethora of research on different kinds of aerogels used for CO 2 adsorption process. Research has been going on toward the development of aerogel-based electrocatalyst, which can be used for valorization of CO 2 through electrochemical reduction methods. Although most of the review papers have covered applications of aerogels in CO 2 capture, very few discuss the processing of aerogels, more so on their applications in CO 2 valorization. In this review, we have collated literature of different forms of aerogels currently available and the steps involved in their fabrication process. In addition, we have covered applications of aerogels in CO 2 capture. Furthermore, we focussed on the basic principles involved in the development of an aerogel electrocatalyst as well as recent developments of aerogels in electrochemical CO 2 reduction., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chronic mitral regurgitation leads to a series of downstream pathologic changes, including pulmonary hypertension, right ventricular dilation, tricuspid leaflet tethering, and tricuspid annular dilation, which can result in functional tricuspid regurgitation (FTR). The five-year survival rate for patients with severe FTR is reported to be as low as 34%. While FTR was often left uncorrected during left-heart valvular surgery, under the assumption that correction of the left-sided lesion would reverse the right-heart changes that cause FTR, recent data largely have supported concomitant tricuspid valve repair at the time of mitral surgery. In this review, the authors discuss the potentially irreversible nature of the changes leading to FTR, the likelihood of progression of FTR after mitral surgery, and the evidence for and against concomitant tricuspid valve repair at the time of mitral valve intervention. Lastly, this narrative review also examines advances in transcatheter therapies for the tricuspid valve and the evidence behind concomitant transcatheter tricuspid repair at the time of transcatheter mitral repair., Competing Interests: Conflict of Interest Dr. Neuburger is a consultant for Medtronic. The remaining authors do not have any financial or personal conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Higher-volume centers for pancreatic cancer surgeries have been shown to have improved outcomes such as length of stay. We examined how centralization of pancreatic cancer care within a regional integrated healthcare system improves overall survival., Methods: We conducted a retrospective study of 1621 patients treated for pancreatic cancer from February 2010 to December 2018. Care was consolidated into 4 Centers of Excellence (COE) in surgery, medical oncology, and other specialties. Descriptive statistics, bivariate analysis, Chi-square tests, and Kaplan-Meier analysis were performed., Results: Neoadjuvant chemotherapy use rose from 10% to 31% (p < .001). The median overall survival (OS) improved by 3 months after centralization (p < .001), but this did not reach significance on multivariate analysis., Conclusions: Our results suggest that in a large integrated healthcare system, centralization improves overall survival and neoadjuvant therapy utilization for pancreatic cancer patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The aim of the current study was to examine the efficacy of the leaf, stem and rhizome of Curcuma aeruginosa Roxb. for their phytochemical content, antioxidant and anti-cancer activities. The different parts of C. aeruginosa were subjected to sequential extraction to give three fractions viz., hexane, ethyl acetate and methanol extract. The cytotoxic effect and the mode of action against A-549 human lung adenocarcinoma and HeLa cell lines were examined. C. aeruginosa presented no significant toxic effect in normal human lung cells (L-132). The methanol extracts were found to be the most cytotoxic and further investigation was carried out to understand the effects. The methanol extracts induced DNA damage after 24 h with significant increase in tail DNA and tail moment when compared to untreated control. Up-regulation in the expression of the caspase - 8 and - 3 activity was observed after 48 h of treatment. The mechanism of cell death and apoptosis induced by the methanol extracts on A549 and HeLa cells were studied using fluorescent staining. Bioactive compounds detected from the HPLC revealed phenol and flavonoid compounds: Gallic acid, quercetin, caffeic acid, kaempferol, rutin, coumaric acid and naringenin. GC-MS results identified the presence of sesquiterpenoids: α-curcumene, curzerene curcumenol, curzerenone epicurzerenone, caryophyllene oxide and diterpenoid, andrographolide. These compounds are known for inducing apoptosis in human cancer cells through caspase - dependent pathways. Therefore, C. aeruginosa and its potential to induce apoptosis in cancer cells suggest that they have potential in medical applications., (Copyright © 2022. Published by Elsevier Masson SAS.)

There is a demand for long afterglow composites due to their potential applications in nighttime signal boards, sensors, and biomedical areas. In this study, Polypropylene (PP)/strontium aluminate-based composites [SrAl 2 O 4 :Eu 2+ /Dy 3+ (SAO 1 ) and Sr 4 Al 14 O 25 : Eu +2 , Dy +3 (SAO 2 )] with maleic anhydride grafted PP compatibilizer (PRIEX) were prepared, and their auto-glowing properties were examined. After UV excitation at 320 nm, the PP/5PRIEX/SAO 1 composites showed green emission at 520 nm, and blue emission was observed for PP/5PRIEX/SAO 2 around 495 nm. The intensity of phosphorescence emission and phosphorescence decay was found to be proportional to the filler content (SAO 1 and SAO 2 ). The FTIR analysis excluded the copolymerization reaction between the SAO 1 and SAO 2 fillers and the PP matrix during the high-temperature melt mixing process. The SAO 1 and SAO 2 fillers decreased the overall crystallinity of the composites without affecting the T m and T c (melting and crystallization temperature) values. The thermal stability of the composites was slightly improved with the SAO 1 and SAO 2 fillers, as seen from the TGA curve. Due to the plasticizing effect of the compatibilizer and the agglomeration of the SAO 1 and SAO 2 fillers, the tensile modulus, tensile strength, and storage modulus of the composites was found to be decreased with an increase in the SAO 1 and SAO 2 content. The decreasing effect was more pronounced, especially with the bulk-sized SAO 2 filler.

The COVID-19 pandemic has disrupted neurosurgical training worldwide, with the shutdown of academic institutions and the reduction of elective surgical procedures. This impact has disproportionately affected LMICs (lower- and/or middle-income countries), already burdened by a lack of neurosurgical resources. Thus, a systematic review was conducted to examine these challenges and innovations developed to adapt effective teaching and learning for medical students and neurosurgical trainees. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and The Cochrane Handbook of Systematic Reviews of Interventions. MEDLINE, PubMed, Embase and Cochrane databases were accessed, searching and screening literature from December 2019 to 5th December 2020 with set inclusion and exclusion criteria. Screening identified 1254 articles of which 26 were included, providing data from 96 countries. Twenty-three studies reported transition to online learning, with 8 studies also mentioned redeployment into COVID wards with 2 studies mentioning missed surgical exposure as a consequence. Of 7 studies conducted in LMICs, 3 reported residents suffering financial insecurities from reduced surgical caseload and recession. Significant global disruption in neurosurgical teaching and training has arisen from the COVID-19 pandemic. Decreased surgical exposure has negatively impacted educational provision. However, advancements in virtual technology have allowed for more affordable, accessible training especially in LMICs. Using this, initiatives to reduce physical and mental stress experienced by trainees should be paramount., (© 2021. The Author(s).)

Background: Leukemia is the most common type of cancer in pediatrics. Genomic mutations contribute towards the molecular mechanism of disease progression and also helps in diagnosis and prognosis. This is the first scientific mutational exploration in whole exome of pediatric leukemia patients from a cancer prone endogamous Mizo tribal population, Northeast India., Result: Three non-synonymous exonic variants in NOTCH1 (p.V1699E), MUTYH (p.G143E) and PTPN11 (p.S502P) were found to be pathogenic. A novel in-frame insertion-deletion within the juxtamembrane domain of FLT3 (p.Tyr589&#95;Tyr591delinsTrpAlaGlyAsp) was also observed., Conclusion: These unique variants could have a potential mutational significance and these could be candidate genes in elucidating the possibility of predisposition to cancers within the population. This study merits further investigation for its role in diagnosis and prognosis and also suggests the need for population wide screening to identify unique mutations that might play a key role towards precision medicine., (© 2022. The Author(s).)

Objective: To assess the effects of lockdown and unlock phases mandated in view of COVID-19 on the incidence and characteristics of ocular trauma presenting to a tertiary care hospital., Methods and Analysis: The study was carried out as a hospital record based retrospective comparative analysis on patients presenting with ocular trauma in the lockdown period (March-July 2020) compared with the same time frame of the previous year considered as prelockdown period (March-July 2019) and during the unlock phases (August-December 2020)., Results: Overall, the casualty department saw 464 patients of ocular trauma in the prelockdown period, 173 in the lockdown and 253 in unlock. The study showed a 44% reduction in patients visiting the casualty department for trauma during the lockdown compared with prelockdown, and a 62% reduction specifically in ocular trauma. The unlock phase showed a 21% reduction in ocular trauma compared with prelockdown and a 41% increase compared with the lockdown. In all three phases, the majority of people affected by ocular trauma were middle aged males from a rural background, sustained by assault. The lockdown saw a decrease in outdoor assaults (45%) and road traffic accidents (22%). Trauma sustained by females (18%) increased in the lockdown, as did home-based assaults (150%) and sexual assaults. The presentation of trauma, especially road traffic accidents and outdoor assaults saw a steady rise during the unlock., Conclusion: The lockdown mandated by the government in response to the COVID-19 pandemic had a significant impact on the trends of trauma presenting to healthcare facilities. There was a decrease in the overall number of patients approaching the casualty during the lockdown. However, during the lockdown, there was an increase in home-based trauma as opposed to outdoor assaults being the primary cause of trauma prior to the lockdown., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Stomach adenocarcinoma (STAD) dominates 80-90% of gastric cancer (GC). Over the years, it has been realized that the identification of the genes responsible for gastric carcinogenesis is essential to understand the biomarker discovery., Methods: This study aims to identify candidate genes for biomarker discovery in STAD. RNA-Seq was performed on three paired tumor-normal and one unpaired tumor samples from four GC patients and investigated for differentially expressed genes (DEGs) using DESeq2. Gene set enrichment analysis were performed. The DEGs were compared with two STAD microarray datasets available on Gene Expression Omnibus (GEO) database. Survival study (OS) were performed using KM-Plotter on the common genes between all the datasets., Results: Totally, 148 DEGs were identified, wherein 55 genes were upregulated and 93 genes were downregulated with |log2foldchange| > 1 and Benjamini-Hochberg (BH) Adjusted P value < 0.01. Cell adhesion molecule (CAM) Pathway was found to be the most significant among the upregulated genes. Gastric acid secretion and mineral absorption pathways were the most significant pathways among the downregulated genes. Comparison with two GEO datasets followed by OS analysis revealed two upregulating genes, APOC1 and SALL4 with prognostic significance., Conclusion: Upregulation of APOC1 is associated with marginal overall survival (OS) and SALL4 over-expression was associated with the poor OS using KM-Plotter during 5 years data period. Our study suggests that SALL4 could be a promising biomarker candidate in STAD., (© 2022. The Author(s).)

N‒GQDs with an average size of ca. 20-30 nm are utilized for the picomolar detection of inhibitory neurotransmitters, glycine (Gly), in pH ca. 7.0. The crystalline nature, morphology, elemental composition, and chemical state of N-GQDs are investigated by XRD, FE-SEM, HR-TEM, XPS, and FT-IR techniques. The addition of Gly (100 × 10 -9  M; 0 → 1.0 mL) steadily quenches the fluorescence intensity of N-GQD (1 × 10 -6  M) at 432 nm (λ ex 333 nm) due to inner filter effect (IFE) through the formation of ground-state complex, N-GQD•Gly. The excitation-independent N‒GQDs showed an outstanding selectivity and sensitivity towards Gly with binding constant (K a  = 8.97 × 10 -3  M -1 ) and LoD (21.04 pM; S/N = 3). Time-correlated single-photon counting experiment confirms the static quenching of N-GQD (8.77 → 8.85 ns) in the presence of Gly. The interference of other amino acids on the strong binding of the N-GQD•Gly complex in H 2 O is examined. Combinatorial Ex-OR and NOT gate logic circuits that could be useful in neuromorphic computing are developed based on the reversible fluorescence intensity changes of N-GQD upon the addition of Gly (Ф F 0.54 → 0.39). The real-time application of N-GQD was investigated using commercially available relevant milk samples. Remarkably, not less than 99% cytotoxic reactivity of N-GQDs is attained against HeLa cells., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Global land-use changes and rapid infrastructure development necessitate identification and conservation of wildlife corridors. Connectivity through corridors is shaped by species' structural, ecological and behavioral constraints. In multi-use landscapes, species' interactions with humans could additionally influence connectivity. Using the tiger Panthera tigris as a case study, we make simultaneous assessments of potential connectivity, habitat use and examine their links with the species' negative interactions with humans in central India. We assessed potential connectivity across 10, 000 sq. km of the Kanha-Pench forest corridor using graph-theoretic methods. Combining indirect sign surveys and occupancy models, we examined habitat use, and evaluated its congruence with potential connectivity. Next, we estimated spatial probabilities of livestock depredation through application of multi-state occupancy models to interview-based survey data from local residents. Habitat use by tigers was negatively associated with forest fragmentation and anthropogenic disturbance. Livestock depredation was positively associated with size of settlements and areas most frequented by tigers, and negatively with anthropogenic disturbance within forests. We found high congruence between connectivity and habitat use (r = 0.80); but the strong correlation did not hold in areas with very high levels of livestock depredation levels. Our results indicate that when areas of high use by tigers are constrained by limited connectivity, there are higher chances of human-tiger conflict, and these areas may be ecological traps for the species. Interactions with humans can be crucial in mediating connectivity for large carnivores in shared habitats. Our findings present an opportunity to consolidate areas where carnivore conservation and local livelihood needs can be balanced. Our framework also provides a foundation for spatial prioritization that incorporates a plurality of dimensions, with utility for connectivity conservation of other wide-ranging carnivores., 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 © 2021 Elsevier B.V. All rights reserved.)

Four model compounds, nifedipine, indomethacin, felodipine, and ketoconazole, all with nearly identical glass transition temperatures, were chosen to study the effects of thermodynamics and molecular mobility on their crystallization propensities. The time and temperature dependence of the crystallization induction time of each compound was determined by differential scanning calorimetry (DSC) and enabled the generation of their time-temperature-transformation (TTT) diagrams. The relaxation times (τ α ) were measured by dielectric spectroscopy, and the Gibbs free energy (Δ G ) and entropy (Δ S ) difference between the crystalline and amorphous states were obtained by DSC. The temperature dependence of the crystallization induction time (τ 0 ( T )) is a function of the thermodynamic activation barrier and the frequency of "attempted jumps" (1/τ α ( T )) to overcome the barrier. Even though the four model compounds exhibited very similar molecular mobility (relaxation time) over a wide range of temperatures, their crystallization propensities were very different. The observed difference in crystallization propensity was explained in terms of the difference in the thermodynamic barrier, and it is correlated to the empirical relation ( T Δ S 3 )/Δ G 2 .

In this work, HDPE/strontium aluminate-based auto glowing composites (SrAl 2 O 4 : Eu, Dy (AG 1 ) and Sr 4 Al 14 O 25 : Eu, Dy (AG 2 )) were prepared, and their phosphorescence studies were conducted. In HDPE/AG 1 composites, the green emission was observed at ~500 nm after the UV excitation at 320 nm. The HDPE/AG 2 has a blue emission at ~490 nm and, in both cases, the intensity of emission is proportional to the AG 1 and AG 2 content. The DSC data show that the total crystallinity of both the composites was decreased but with a more decreasing effect with the bulky AG 2 filler. The melting and crystallization temperatures were intact, which shows the absence of any chemical modification during high shear and temperature processing. This observation is further supported by the ATR-FTIR studies where no new peaks appeared or disappeared from the HDPE peaks. The tensile strength and modulus of HDPE, HDPE/AG 1 , and HDPE/AG 2 composites were improved with the AG 1 and AG 2 fillers. The rheological studies show the improvement in the complex viscosity and accordingly the storage modulus of the studied phosphorescent HDPE composites. The SEM images indicate better filler dispersion and filler-matrix adhesion, which improves the mechanical characteristics of the studied HDPE composites. The ageing studies in the glowing composites show that there is a decrease in the intensity of phosphorescence emission on exposure to drastic atmospheric conditions for a longer period and the composites become more brittle.

Background: Autoinflammatory disorders are the group of inherited inflammatory disorders caused due to the genetic defect in the genes that regulates innate immune systems. These have been clinically characterized based on the duration and occurrence of unprovoked fever, skin rash, and patient's ancestry. There are several autoinflammatory disorders that are found to be prevalent in a specific population and whose disease genetic epidemiology within the population has been well understood. However, India has a limited number of genetic studies reported for autoinflammatory disorders till date. The whole genome sequencing and analysis of 1029 Indian individuals performed under the IndiGen project persuaded us to perform the genetic epidemiology of the autoinflammatory disorders in India., Results: We have systematically annotated the genetic variants of 56 genes implicated in autoinflammatory disorder. These genetic variants were reclassified into five categories (i.e., pathogenic, likely pathogenic, benign, likely benign, and variant of uncertain significance (VUS)) according to the American College of Medical Genetics and Association of Molecular pathology (ACMG-AMP) guidelines. Our analysis revealed 20 pathogenic and likely pathogenic variants with significant differences in the allele frequency compared with the global population. We also found six causal founder variants in the IndiGen dataset belonging to different ancestry. We have performed haplotype prediction analysis for founder mutations haplotype that reveals the admixture of the South Asian population with other populations. The cumulative carrier frequency of the autoinflammatory disorder in India was found to be 3.5% which is much higher than reported., Conclusion: With such frequency in the Indian population, there is a great need for awareness among clinicians as well as the general public regarding the autoinflammatory disorder. To the best of our knowledge, this is the first and most comprehensive population scale genetic epidemiological study being reported from India., (© 2021. The Author(s).)

The pandemic of coronavirus disease 2019 (COVID-19) still remains on an upsurge trend. The second wave of this disease has led to panic in many countries, including India and some parts of the world suffering from the third wave. As there are no proper treatment options or remedies available for this deadly infection, supportive care equipment's such as oxygen cylinders, ventilators and heavy use of steroids play a vital role in the management of COVID-19. In the midst of this pandemic, the COVID-19 patients are acquiring secondary infections such as mucormycosis also known as black fungus disease. Mucormycosis is a serious, but rare opportunistic fungal infection that spreads rapidly, and hence prompt diagnosis and treatment are necessary to avoid high rate of mortality and morbidity rates. Mucormycosis is caused by the inhalation of its filamentous (hyphal form) fungi especially in the patients who are immunosuppressed. Recent studies have documented alarming number of COVID-19 patients with mucormycosis infection. Most of these patients had diabetes and were administered steroids for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and were consequently more prone to mucormycosis. Hence, the present review emphasizes mucormycosis and its related conditions, its mechanism in normal and COVID-19 affected individuals, influencing factors and challenges to overcome this black mold infection. Early identification and further investigation of this fungus will significantly reduce the severity of the disease and mortality rate in COVID-19 affected patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Aims: This study aimed to examine the quality of life (QoL) and health satisfaction of undergraduate university students in Sarawak during MCO and its association with socio-demographic profiles., Methods: In this cross-sectional study, QoL and satisfaction of health of 503 undergraduate university students (63.4% females) from a public university was assessed online using the World Health Organization QoL (WHOQOL)-BREF instrument., Results: The overall QoL and satisfaction with health were 3.7 ± 0.87 and 3.9 ± 0.82, respectively. Male students showed significantly lower mean scores for the environmental domains than female students (63.37 ± 16.21 vs 68.10 ± 14.00, P  < .01). Students who lived inside the campus (vs outside campus) showed significantly lower mean score for the physical health (61.49 ± 13.94 vs 67.23 ± 13.93, P  < .01), environmental health (58.35 ± 15.07 vs 70.49 ± 13.21, P  < .01), overall QoL (3.39 ± 0.90 vs 3.84 ± 0.83, P  < .01), and satisfaction with health (3.71 ± 0.90 vs 3.97 ± 0.77, P  < .01). Students with parent's income below RM5000 (vs parent's income more than RM5000) had significantly lower mean score for the environmental domain (65.06 ± 14.35 vs 68.20 ± 15.74, P  < .05). Others ethnicity scored significantly lower than Bumiputera Sarawak and Malay while Bumiputera Sarawak scored significantly lower than Chinese in physical health domain (Malay = 65.73 ± 13.40, Chinese = 63.24 ± 15.35, Bumiputra Sarawak = 67.35 ± 13.30, Others = 60.84 ± 15.88, P  < .05). Malay (69.99 ± 15.20) scored significantly higher than other ethnicities (Chinese = 63.58 ± 15.80; Bumiputera Malaysia = 65.23 ± 13.66; others = 63.98 ± 15.59) in environmental domain ( P  < .01). When comparing between religions, the results also showed there were significant differences between different religion groups in overall QoL (Islam = 3.75 ± 0.93, Christianity = 3.77 ± 0.79, Others = 3.34 ± 1.14, P  < .05), physical health (Islam = 65.00 ± 13.86, Buddhism = 68.40 ± 11.99, Christianity = 64.77 ± 14.94, Others = 61.00 ± 16.03, P  < .05), and environmental health (Islam = 69.66 ± 15.48, Buddhism = 64.99 ± 11.36, Christianity = 64.87 ± 15.61, Others = 62.13 ± 16.28, P  < .05)., Conclusion: By understanding university students' QoL in this global disaster, relevant authorities would provide a better rehabilitation and assistance to those affected ones., Competing Interests: The authors declare there is no conflict of interest., (© 2021 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Among persons with high spinal cord injury (Hi-SCI: > T5), changes in core body temperature (Tcore) and cognitive performance during heat exposure appear related to degree of sympathetic interruption. Twenty men with Hi-SCI (C4-T4, American Spinal Injury Association Impairment Scale [AIS] A-B) and 19 matched, able-bodied controls were acclimated to 27°C baseline (BL) before exposure to 35°C heat challenge (HC). Two groups, differentiated by increase in Tcore during HC, were identified: high responders (HR-SCI: ΔTcore ≥0.5°C; n  = 13, C4-T2) and low responders (LR-SCI: ΔTcore <0.5°C; n  = 7, C4-T4). Tcore, distal skin temperatures (Tsk avg ), and distal microvascular perfusion (LDF both feet ) were measured, as were indices of sympathetic integrity, mean arterial pressure (MAP), and extremity sweat rate (SR avg ). Cognitive performance was assessed at BL and post-HC, using the Stroop Color and Word and Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) Digit Span tests. At BL, Tcore of the HR-SCI group (36.6 ± 0.4°C) was lower than that for the LR-SCI (37.1 ± 0.3°C; p  = 0.011) and control groups (37.3 ± 0.3°C; p  < 0.001). After HC, Tcore was not different among groups. MAP of the HR-SCI group (70.9 ± 9.8 mm Hg) was lower than that of the LR-SCI (81.8 ± 7.0 mm Hg; p  = 0.048) and control groups (89.9 ± 9.9 mm Hg; p  < 0.001). SR avg increased more in the control group (77.0 ± 52.5 nL/cm 2 /min) than in the HR-SCI group (15.5 ± 22.0 nL/cm 2 /min; p  = 0.001). Only the HR-SCI group had significant increases in T-Scores of Stroop Word (7.5 ± 4.4; p  < 0.001), WAIS-IV Digit Span Sequence (1.9 ± 1.8; p  = 0.002), and WAIS-IV Digit Span Total (1.4 ± 1.6; p  = 0.008). Persons with SCI who responded to HC with a greater change in Tcore demonstrated evidence of greater sympathetic interruption and had an associated improvement in cognitive performance.

As the world grapples with the problem of the coronavirus disease 2019 (COVID-19) pandemic and its devastating effects, scientific groups are working towards solutions to mitigate the effects of the virus. This paper aimed to collate information on COVID-19 prediction models. A systematic literature review is reported, based on a manual search of 1,196 papers published from January to December 2020. Various databases such as Google Scholar, Web of Science, and Scopus were searched. The search strategy was formulated and refined in terms of subject keywords, geographical purview, and time period according to a predefined protocol. Visualizations were created to present the data trends according to different parameters. The results of this systematic literature review show that the study findings are critically relevant for both healthcare managers and prediction model developers. Healthcare managers can choose the best prediction model output for their organization or process management. Meanwhile, prediction model developers and managers can identify the lacunae in their models and improve their data-driven approaches.

Over the last few decades, Mizoram has shown an increase in cases of type 2 diabetes mellitus; however, no in-depth scientific records are available to understand the occurrence of the disease. In this study, 500 patients and 500 healthy controls were recruited to understand the possible influence of their dietary and lifestyle habits in relation with type 2 diabetes mellitus. A multivariate analysis using Cox regression was carried out to find the influence of dietary and lifestyle factors, and an unpaired t test was performed to find the difference in the levels of biochemical tests. Out of 500 diabetic patients, 261 (52.3%) were males and 239 (47.7%) were females, and among the control group, 238 (47.7%) were males and 262 (52.3%) were females. Fermented pork fat, Sa-um (odds ratio (OR) 18.98), was observed to be a potential risk factor along with tuibur (OR 0.1243) for both males and females. Creatinine level was found to be differentially regulated between the male and female diabetic patients. This is the first report of fermented pork fat and tobacco (in a water form) to be the risk factors for diabetes. The unique traditional foods like Sa-um and local lifestyle habits like tuibur of the Mizo population may trigger the risk for the prevalence of the disease, and this may serve as a model to study other populations with similar traditional practices., (© 2021. The Author(s).)

Aim: Numerous drugs are being widely prescribed for COVID-19 treatment without any direct evidence for the drug safety/efficacy in patients across diverse ethnic populations. Materials & methods: We analyzed whole genomes of 1029 Indian individuals (IndiGen) to understand the extent of drug-gene (pharmacogenetic), drug-drug and drug-drug-gene interactions associated with COVID-19 therapy in the Indian population. Results: We identified 30 clinically significant pharmacogenetic variants and 73 predicted deleterious pharmacogenetic variants. COVID-19-associated pharmacogenes were substantially overlapped with those of metabolic disorder therapeutics. CYP3A4 , ABCB1 and ALB are the most shared pharmacogenes. Fifteen COVID-19 therapeutics were predicted as likely drug-drug interaction candidates when used with four CYP inhibitor drugs. Conclusion: Our findings provide actionable insights for future validation studies and improved clinical decisions for COVID-19 therapy in Indians.