Saturation genome editing of BAP1 functionally classifies somatic and germline variants.

Many variants that we inherit from our parents or acquire de novo or somatically are rare, limiting the precision with which we can associate them with disease. We performed exhaustive saturation genome editing (SGE) of BAP1, the disruption of which is linked to tumorigenesis and altered neurodevelopment. We experimentally characterized 18,108 unique variants, of which 6,196 were found to have abnormal functions, and then used these data to evaluate phenotypic associations in the UK Biobank. We also characterized variants in a large population-ascertained tumor collection, in cancer pedigrees and ClinVar, and explored the behavior of cancer-associated variants compared to that of variants linked to neurodevelopmental phenotypes. Our analyses demonstrated that disruptive germline BAP1 variants were significantly associated with higher circulating levels of the mitogen IGF-1, suggesting a possible pathological mechanism and therapeutic target. Furthermore, we built a variant classifier with >98% sensitivity and specificity and quantify evidence strengths to aid precision variant interpretation.

Age Estimation of Children and Young Adults of Jharkhand Using Mineralization of Third Molars and Its Relation to Chronological Age: A Retrospective Analysis.

Background Dental age estimation plays an enormous role in the determination of an individual's identity and age in forensic and anthropological fields. The estimation of the chronological age of the individual is also important in the diagnosis, treatment planning, and treatment outcomes in the dental field. The third molar has some inimitable characteristics in terms of its size, shape, formation, and long path of eruption and usually erupts after puberty, which seems to be a reliable method of age estimation in adulthood. To establish the individual's identity, inference of age has gained considerable attention in forensics, and the aspect of dentistry has broadened nowadays. Thus the present study was conducted. Methodology The digital orthopantomograms of 720 patients who were exposed to X-rays for routine examination were assessed, and calcification of the tooth was observed. In order to ensure the blinding of the examiners, radiographs were numerically coded. Clinical stages of the tooth were categorised into erupted, pre-erupted, and missing. Statistical analysis was performed by IBM SPSS Statistics for Windows, Version 25.0 (IBM Corp., Armonk, NY), with a level of significance set below 5%. Results The age of the patients whose OPGs were assessed ranged from 6 to 22 years, with a mean age of 18.93±3.129 years. Among the 720 participants, 370 (51.4%) were male and 350 (48.6%) were female. When the clinical status of the third molar among all the participants was assessed, in 148 (20.6%) subjects, third molars had erupted; in 188 (26.1%) subjects, the third molars were in the pre-erupted stage; and in 384 (53.30%), third molars were missing. When comparing the clinical status of the third molar in both arches and between genders, it was found that missing molars were common in females and the mandible arch, with statistically significant p-values. A comparison of Demirjian's stages between genders showed that the mean age to attain stage H was 21.37±0.774 years among males and 21.69±0.616 years among females. This means that the calcification of third-molar attainment occurs earlier in males compared with females. In a similar comparison between the upper and lower arches, it was found that calcification of the third molar was attained earlier in the maxillary arch compared to the mandibular arch. Conclusion It was concluded that the third molar is a versatile tooth and its path of mineralization can be used in orthodontics, pedodontics, and forensics to estimate chronological age, and chronological age significantly follows Demirjian's stages of third molar calcification. Third molar calcification occurred earlier in the maxillary arch and males, whereas several impacted molars were higher in females.

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol.

In the current work, we analyzed the origin of difference in stabilities among the germacrene A and hedycaryol-derived carbocations. This study focused on twelve hydrocarbons derived from germacrene A and twelve from hedycaryol, which can be divided into three groups: four molecules containing 6-6 bicyclic rings, four 5-7 bicyclic compounds with the carbocation being on the seven-membered ring and the remaining four 5-7 bicyclic compounds with the carbocation on the five-membered ring. The variations in energy within the groups of carbocations (i.e., 6-6 and two kinds of 5-7 bicyclic carbocations) can be ascribed to intramolecular repulsion interactions, as seen from non-covalent interactions plots. Despite the structural similarities between germacrene A and hedycaryol cations, they possess a somewhat different stability trend. These differences are attributed to C+···OH intramolecular interactions present in some hedycaryol cations, which are absent in the carbocations derived from germecrene A.

Utility of Itraconazole in Combination with Liposomal Amphotericin B in Rhizopus oryzae Associated Mucormycosis-An Exploratory Study.

BACKGROUND: During the COVID-19 pandemic-associated mucor epidemic, acute antifungal drug shortage necessitated the exploration of other antifungals based on culture sensitivity. Itraconazole is a cheap, safe, and effective antifungal in sensitive cases. METHODOLOGY: We enrolled itraconazole-sensitive COVID-19-associated mucormycosis during the mucormycosis pandemic. After the intensive phase course of liposomal amphotericin B, Itraconazole was offered in susceptible cases during the maintenance phase along with standard of care. These patients were clinically and radiologically followed for 6 months. RESULTS: We enrolled 14 patients (Male: Female-11:3) of Rhino-orbito-cerebral mucormycosis (ROCM) which included 12 diabetics. All patients had facial swelling, orbital swelling, visual impairment, and headache. MRI showed involvement of bilateral sinus (10/14), orbital extension (13/14), cavernous sinus (5/14), cerebral part of the internal carotid artery (3/14), and brain infarcts (4/14). All 14 patients showed sensitivity to Itraconazole with 12 having minimum inhibitory concentration (MIC) ≤ 1 µg/ml and 2 having MIC ≤ 2 µg/ml. Follow-up at 6 months showed clinical improvement in the majority (11/14) and radiological improvement in six out of seven scanned patients. CONCLUSION: Our study shows the potential therapeutic role of oral Itraconazole in ROCM.

In Silico Approaches to Polyherbal Synergy: Protocol for a Scoping Review.

BACKGROUND: According to the World Health Organization, more than 80% of the world's population relies on traditional medicine. Traditional medicine is typically based on the use of single herbal drugs or polyherbal formulations (PHFs) to manage diseases. However, the probable mode of action of these formulations is not well studied or documented. Over the past few decades, computational methods have been used to study the molecular mechanism of phytochemicals in single herbal drugs. However, the in silico methods applied to study PHFs remain unclear. OBJECTIVE: The aim of this protocol is to develop a search strategy for a scoping review to map the in silico approaches applied in understanding the activity of PHFs used as traditional medicines worldwide. METHODS: The scoping review will be conducted based on the methodology developed by Arksey and O'Malley and the recommendations of the Joanna Briggs Institute (JBI). A set of predetermined keywords will be used to identify the relevant studies from five databases: PubMed, Embase, Science Direct, Web of Science, and Google Scholar. Two independent reviewers will conduct the search to yield a list of relevant studies based on the inclusion and exclusion criteria. Mendeley version 1.19.8 will be used to remove duplicate citations, and title and abstract screening will be performed with Rayyan software. The JBI System for the Unified Management, Assessment, and Review of Information tool will be used for data extraction. The scoping review will be reported based on the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. RESULTS: Based on the core areas of the scoping review, a 3-step search strategy was developed. The initial search produced 3865 studies. After applying filters, 875 studies were short-listed for further review. Keywords were further refined to yield more relevant studies on the topic. CONCLUSIONS: The findings are expected to determine the extent of the knowledge gap in the applications of computational methods in PHFs for any traditional medicine across the world. The study can provide answers to open research questions related to the phytochemical identification of PHFs, criteria for target identification, strategies applied for in silico studies, software used, and challenges in adopting in silico methods for understanding the mechanisms of action of PHFs. This study can thus provide a better understanding of the application and types of in silico methods for investigating PHFs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/56646.

Hydrogen Sensing with Palladium-Based Materials: Mechanisms, Challenges, and Opportunities.

Palladium morphologies are prominently used in Hydrogen gas sensing applications owing to their unique characteristics and properties. In this review article, Palladium nanoparticles, thin films, and alloys were designated as the scope of Palladium morphologies. The aim of this review article is to explore Hydrogen sensing using Palladium, focusing on the recent advancements in the field.. The principles underlying Hydrogen sensing mechanisms with Palladium are discussed initially, highlighting the unique properties of Palladium that make it a promising material for this purpose. Special attention is given to the surface interactions and structural modifications that influence the sensitivity and selectivity of Palladium-based sensors The study also addresses key challenges and recent innovations in the field which contribute to the enhancement of Palladium-based Hydrogen sensing capabilities. The current state of research is critically examined to identify gaps in knowledge and future research directions are highlighted. The prospects and challenges associated with the use of Palladium for Hydrogen sensing, emphasizing its pivotal role in advancing sensor technologies for Hydrogen detection are also discussed.

Development of Simultaneous HPTLC Method and Validation for the Quality Assessment of Ayurvedic Formulation-Ayush Kvatha Churna by Using Marker Compound Rosmarinic Acid, Trans-Cinnamaldehyde and Piperine.

Ayurveda emphasizes the propagation of nature in maintaining health. In the present scenario, we have seen the faith of people in herbal drugs during the Covid 19 outbreak. The raises in the number of peoples have been using herbal drugs to boost immunity against infectious diseases shows the popularity of this ancient system of medicine. The standardization of Ayush Kvatha Churna (AKC), work set out to establish a straightforward, accurate and sensitive HPTLC method for the identification and quantification of marker compounds. The Rosmarinic acid, trans-Cinnamaldehyde and Piperine were used for the estimation of markers in Ayush Kvatha Churna by using HPTLC with a solvent system, consisting of Toluene: Ethyl acetate: Ethyl alcohol: Formic acid (5.6:2.4:2: 0.3 v/v/v/v). The Rf value 0.33 for Rosmarinic Acid, 0.69 for Piperine and 0.77 for trans-Cinnamaldehyde was observed and it is exactly complying with the corresponding bands in Ayush Kvatha Churna. The technique has been effectively verified and validated, enabling it to be used for the standardization or quantitative analysis of Rosmarinic acid, trans-Cinnamaldehyde and piperine in Ayush Kvatha Churna.

Antimicrobial therapeutic protein extraction from fruit waste and recent trends in their utilization against infections.

Fruits are a very good source of various nutrients that can boost overall human health. In these days, the recovery of therapeutic compounds from different fruit wastes is trending in research, which might not only minimize the waste problem but also encounter a higher demand for various enzymes that could have antimicrobial properties against infectious diseases. The goal of this review is to focus on the recovery of therapeutic enzymes from fruit wastes and its present-day tendency for utilization. Here we discussed different parts of fruit waste, such as pulp, pomace, seed, kernel, peel, etc., that produce therapeutic enzymes like amylase, cellulose, lipase, laccase, pectinase, etc. These bioactive enzymes are present in different parts of fruit and could be used as therapeutics against various infectious diseases. This article provides a thorough knowledge compilation of therapeutic enzyme isolation from fruit waste on a single platform, distinctly informative, and significant review work on the topic that is envisioned to encourage further research ideas in these areas that are still under-explored. This paper explains the various aspects of enzyme isolation from fruit and vegetable waste and their biotherapeutic potential that could provide new insights into the development of biotherapeutics and attract the attention of researchers to enhance translational research magnitude further.

The Roles of Oil-Water Interfaces in Forming Ultrasmall CaSO4 Nanoparticles.

In natural and engineered environmental systems, calcium sulfate (CaSO4) nucleation commonly occurs at dynamic liquid-liquid interfaces. Although CaSO4 is one of the most common minerals in oil spills and oil-water separation, the mechanisms driving its nucleation at these liquid-liquid interfaces remain poorly understood. In this study, using in situ small-angle X-ray scattering (SAXS), we examined CaSO4 nucleation at oil-water interfaces and found that within 60 minutes of reaction, short rod-shaped nanoparticles (with a radius of gyration (Rg) of 17.2 ± 2.7 nm and a length of 38.2 ± 5.8 nm) had formed preferentially at the interfaces. Wide-angle X-ray scattering (WAXS) analysis identified these nanoparticles as gypsum (CaSO4·2H2O). In addition, spherial nanoparticles measuring 4.1 nm in diameter were observed at oil-water interfaces, where surface-enhanced Raman spectroscopy (SERS) revealed an elevated pH compared to the bulk solution. The negatively charged oil-water interfaces preferentially adsorb calcium ions, collectively promoting CaSO4 formation there. CaSO4 particle formation at the oil-water interface follows a nonclassical nucleation (N-CNT) pathway by forming ultrasmall amorphous spherical particles which then aggregate to form intermediate nanoparticles, subsequently growing into nanorod-shaped gypsum. These findings of this study provide insights into mineral scaling during membrane separation and can inform more efficient oil transport in energy recovery systems.

Efficacy of Topical Turmeric, Calendula officinalis, and Tulsi (Ayurvedic Gel) in the Management of Erosive Lichen Planus: A Placebo-Controlled Study.

Background: Chronic mucocutaneous symptoms are a hallmark of lichen planus (LP), an inflammatory disease of the stratified squamous epithelium. The most severe type of mucosal lichen is oral erosive lichen planus (OELP). Materials and Methods: Thirty patients were included in this prospective trial, with fifteen patients each assigned to Group A and Group B. Patients were given a choice between a placebo gel and an ayurvedic gel comprising pure turmeric, Calendula officinalis, and tulsi powder in an oral basis. At each appointment, the patients' reactions to therapy were scored on the Tel Aviv-San Francisco Scale, whereas the degree of the fire was rated using a Visual Analog Scale. Data analysis was carried out using IBM's Statistical Package for the Social Sciences (SPSS) Insights version 21. Results: After receiving ayurvedic gel, patients in Group A reported much less burning than those in Group B (placebo). Group A responded better to therapy overall than Group B. Conclusion: This study's findings support the use of an ayurvedic gel made from pure turmeric, Calendula officinalis, and tulsi powder for the treatment of erosive lichen planus.

Morphometric Analysis of Sella Turcica and a Proposed Novel Sella Turcica Index - A Digital Lateral Cephalometric Study.

Background: The sella turcica is a structure readily seen on lateral cephalograms and sella point is routinely traced for various cephalometric analyses. The aim of the present study was to evaluate the morphometric variation in size and shape of sella turcica via lateral cephalogram. The objectives were to introduce a novel sella turcica index (STI) and assess its reliability that could be helpful in gender determination. Materials and Methods: A total of 80 lateral cephalograms of the patients of age group 10-30 years were included for the study. The morphological variations of the sella turcica was done based on the classification given by Axelsson et al. (2004). The length, depth and perimeter of the sella turcica was measured and STI derived and calculated. The data was further subjected to discriminant analysis to validate the gender outcome. Reliability of the novel index was determined by calculating the sensitivity and specificity. Results: The overall most common morphological type of sella turcica was Type A (56.25%) followed by Type B (18.75%) and Type E (13.75%). The mean perimeter and depth of sella turcica was higher in females whereas the mean length of sella turcica was higher in males. The mean STI was higher in males and statistically highly significant. The sensitivity and specificity of this index was 72.5% and 90% respectively. Conclusion: A significant relationship was observed between the morphometric measurements of sella turcica and gender. STI could be of great help as a reliable tool for personal identification in forensic sciences. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04082-9.

Electronic Tongue Based on ZnO/ITO@glass for Electrochemical Monitoring of Spiciness Levels.

Capsaicin, a chemical compound present in chili peppers, is widely acknowledged as the main contributor to the spicy and hot sensations encountered during consumption. Elevated levels of capsaicin can result in meals being excessively spicy, potentially leading to health issues, such as skin burning, irritation, increased heart rate and circulation, and discomfort in the gastrointestinal system and even inducing nausea or diarrhea. The level of spiciness that individuals can tolerate may vary, so what may be considered incredibly hot for one person could be mild for another. To ensure food safety, human healthcare, regulatory compliance, and quality control in spicy food products, capsaicin levels must be measured. For these purposes, a reliable and stable sensor is required to quantify the capsaicin level. To leverage the effect of zinc oxide (ZnO), herein, we demonstrated the one-step fabrication process of an electronic tongue (E-Tongue) based on an electrochemical biosensor for the determination of capsaicin. ZnO was electrodeposited on the indium tin oxide (ITO) surface. The biosensor demonstrated the two notable linear ranges from 0.01 to 50 µM and from 50 to 500 µM with a limit of detection (LOD) of 2.1 nM. The present study also included the analysis of real samples, such as green chilis, red chili powder, and dried red chilis, to evaluate their spiciness levels. Furthermore, the E-Tongue exhibited notable degrees of sensitivity, selectivity, and long-term stability for a duration of more than a month. The development of an E-Tongue for capsaicin real-time monitoring as a point-of-care (POC) device has the potential to impact various industries and improve safety, product quality, and healthcare outcomes.

Pan-Indian Clinical Registry of Invasive Fungal Infections Among Patients in the Intensive Care Unit: Protocol for a Multicentric Prospective Study.

BACKGROUND: Fungal infections are now a great public health threat, especially in those with underlying risk factors such as neutropenia, diabetes, high-dose steroid treatment, cancer chemotherapy, prolonged intensive care unit stay, and so on, which can lead to mycoses with higher mortality rates. The rates of these infections have been steadily increasing over the past 2 decades due to the increasing population of patients who are immunocompromised. However, the data regarding the exact burden of such infection are still not available from India. Therefore, this registry was initiated to collate systematic data on invasive fungal infections (IFIs) across the country. OBJECTIVE: The primary aim of this study is to create a multicenter digital clinical registry and monitor trends of IFIs and emerging fungal diseases, as well as early signals of any potential fungal outbreak in any region. The registry will also capture information on the antifungal resistance patterns and the contribution of fungal infections on overall morbidity and inpatient mortality across various conditions. METHODS: This multicenter, prospective, noninterventional observational study will be conducted by the Indian Council of Medical Research through a web-based data collection method from 8 Advanced Mycology Diagnostic and Research Centers across the country. Data on age, gender, clinical signs and symptoms, date of admission, date of discharge or death, diagnostic tests performed, identified pathogen details, antifungal susceptibility testing, outcome, and so on will be obtained from hospital records. Descriptive and multivariate statistical methods will be applied to investigate clinical manifestations, risk variables, and treatment outcomes. RESULTS: These Advanced Mycology Diagnostic and Research Centers are expected to find the hidden cases of fungal infections in the intensive care unit setting. The study will facilitate the enhancement of the precision of fungal infection diagnosis and prompt treatment modalities in response to antifungal drug sensitivity tests. This registry will improve our understanding of IFIs, support evidence-based clinical decision-making ability, and encourage public health policies and actions. CONCLUSIONS: Fungal diseases are a neglected public health problem. Fewer diagnostic facilities, scanty published data, and increased vulnerable patient groups make the situation worse. This is the first systematic clinical registry of IFIs in India. Data generated from this registry will increase our understanding related to the diagnosis, treatment, and prevention of fungal diseases in India by addressing pertinent gaps in mycology. This initiative will ensure a visible impact on public health in the country. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54672.

Profile of sexually transmitted infections among attendees of special clinics (Suraksha) at an apex regional sexually transmitted disease centre in North India ­ a five-year study

Introduction: Sexually transmitted infections (STIs) present significant global and national health challenges, particularly in India. Objective: To estimate the prevalence and characteristics of STIs among attendees at the Suraksha Clinic in the Apex Regional STD Centre, Safdarjung Hospital. Methods:Retrospective data from January 2018 to December 2022 were statistically analyzed using Excel and SPSS. The study included the examination for diagnosis of various STIs, such as syphilis, human immunodeficiency virus (HIV), gonorrhoea, chlamydiasis, trichomoniasis, candidiasis, bacterial vaginosis, chancroid, and genital herpes. Gender distribution and syndromic diagnoses, including vaginal/cervical discharge and genital ulcers, were also considered. Referrals to Integrated Counseling and Testing Centres for HIV testing were analyzed. Results: The outcomes reveal a substantial burden of STIs, with 3.06% showing reactivity to syphilis, 1.74% testing positive for HIV, 3.36% for gonorrhoea, 11.78% for chlamydiasis, 1.05% for trichomoniasis, 26.24% for candidiasis, 9.97% for bacterial vaginosis, 7.80% for chancroid, 11.64% for herpes genitalis, and 4.01% for other non-STIs. Attendees' interactions included 34.36% of referrals to Integrated Counseling and Testing Centres for HIV testing. The gender distribution showed 58.92% male and 40.94% female attendees. Conclusion: Syndromic diagnoses, including vaginal/cervical discharge (21.22%) and genital warts (8.00%), highlight prevalent conditions, necessitating routine screening, early detection, and targeted interventions for effective disease control and prevention. These findings underscore the significance of integrated screening, patient education, and proactive strategies to safeguard public health in the face of rising STI rates.

Introdução: As infecções sexualmente transmissíveis (IST) apresentam desafios de saúde globais e nacionais significativos, particularmente na Índia. Objetivo: Estimar a prevalência e as características das IST entre os pacientes atendidos na Clínica Suraksha do Centro Regional de doenças sexualmente transmissíveis (DST) Apex, Hospital Safdarjung. Métodos: Dados retrospectivos de janeiro de 2018 a dezembro de 2022 foram analisados estatisticamente utilizando Excel e Statistical Package for the Social Sciences (SPSS). O estudo inclui o exame para diagnóstico de diversas IST, como sífilis, HIV, gonorreia, clamídia, tricomoníase, candidíase, vaginose bacteriana, cancroide e herpes genital. A distribuição por gênero e os diagnósticos sindrômicos, incluindo corrimento vaginal/cervical e úlceras genitais, também foram considerados. Foram analisados encaminhamentos para Centros Integrados de Aconselhamento e Testagem para testagem de HIV. Resultados: Os resultados revelam uma carga substancial de IST, com 3,06% apresentando reatividade à sífilis, 1,74% testando positivo para HIV, 3,36% para gonorreia, 11,78% para clamídia, 1,05% para tricomoníase, 26,24% para candidíase, 9,97% para vaginose bacteriana, 7,80% para cancroide, 11,64% para herpes genital e 4,01% para outras infecções não IST. As interações dos participantes incluíram 34,36% de encaminhamentos para Centros Integrados de Aconselhamento e Testagem para testes de HIV. A distribuição por gênero mostrou 58,92% de participantes do sexo masculino e 40,94% do sexo feminino. Conclusão: Os diagnósticos sindrômicos, incluindo corrimento vaginal/cervical (21,22%) e verrugas genitais (8,00%), destacam condições prevalentes, necessitando de exames de rotina, detecção precoce e intervenções direcionadas para controle e prevenção eficazes de doenças. Estas conclusões sublinham a importância do rastreio integrado, da educação dos pacientes e de estratégias proativas para salvaguardar a saúde pública diante do aumento das taxas de IST.

VWD domain stabilization by autocatalytic Asp-Pro cleavage.

Domains known as von Willebrand factor type D (VWD) are found in extracellular and cell-surface proteins including von Willebrand factor, mucins, and various signaling molecules and receptors. Many VWD domains have a glycine-aspartate-proline-histidine (GDPH) amino-acid sequence motif, which is hydrolytically cleaved post-translationally between the aspartate (Asp) and proline (Pro). The Fc IgG binding protein (FCGBP), found in intestinal mucus secretions and other extracellular environments, contains 13 VWD domains, 11 of which have a GDPH cleavage site. In this study, we investigated the structural and biophysical consequences of Asp-Pro peptide cleavage in a representative FCGBP VWD domain. We found that endogenous Asp-Pro cleavage increases the resistance of the domain to exogenous proteolytic degradation. Tertiary structural interactions made by the newly generated chain termini, as revealed by a crystal structure of an FCGBP segment containing the VWD domain, may explain this observation. Notably, the Gly-Asp peptide bond, upstream of the cleavage site, assumed the cis configuration in the structure. In addition to these local features of the cleavage site, a global organizational difference was seen when comparing the FCGBP segment structure with the numerous other structures containing the same set of domains. Together, these data illuminate the outcome of GDPH cleavage and demonstrate the plasticity of proteins with VWD domains, which may contribute to their evolution for function in a dynamic extracellular environment.

Development and validation of multicentre study on novel Artificial Intelligence-based Cardiovascular Risk Score (AICVD).

OBJECTIVE: Cardiovascular diseases (CVD) are one of the most prevalent diseases in India amounting for nearly 30% of total deaths. A dearth of research on CVD risk scores in Indian population, limited performance of conventional risk scores and inability to reproduce the initial accuracies in randomised clinical trials has led to this study on large-scale patient data. The objective is to develop an Artificial Intelligence-based Risk Score (AICVD) to predict CVD event (eg, acute myocardial infarction/acute coronary syndrome) in the next 10 years and compare the model with the Framingham Heart Risk Score (FHRS) and QRisk3. METHODS: Our study included 31 599 participants aged 18-91 years from 2009 to 2018 in six Apollo Hospitals in India. A multistep risk factors selection process using Spearman correlation coefficient and propensity score matching yielded 21 risk factors. A deep learning hazards model was built on risk factors to predict event occurrence (classification) and time to event (hazards model) using multilayered neural network. Further, the model was validated with independent retrospective cohorts of participants from India and the Netherlands and compared with FHRS and QRisk3. RESULTS: The deep learning hazards model had a good performance (area under the curve (AUC) 0.853). Validation and comparative results showed AUCs between 0.84 and 0.92 with better positive likelihood ratio (AICVD -6.16 to FHRS -2.24 and QRisk3 -1.16) and accuracy (AICVD -80.15% to FHRS 59.71% and QRisk3 51.57%). In the Netherlands cohort, AICVD also outperformed the Framingham Heart Risk Model (AUC -0.737 vs 0.707). CONCLUSIONS: This study concludes that the novel AI-based CVD Risk Score has a higher predictive performance for cardiac events than conventional risk scores in Indian population. TRIAL REGISTRATION NUMBER: CTRI/2019/07/020471.

Primary hepatic functional neuroendocrine tumor in an elderly female: Case report.

Key Clinical Message: Primary hepatic neuroendocrine tumor, an exceptionally rare subtype, poses a diagnostic challenge. Oncological resections should be considered, even in elderly patients after following protocolized pre-operative optimizations. Abstract: Neuroendocrine tumors (NETs) are rare tumors that primarily develop in the gastrointestinal and respiratory tracts. While the liver is commonly affected by NET metastases, primary hepatic neuroendocrine tumors (PHNETs) are an exceptionally rare subtype. The characteristic slow growth and nonfunctional nature of PHNETs pose challenges in their diagnosis. Furthermore, PHNETs often exhibit a lack of unique radiological characteristics that differentiate them from other liver tumors, leading to frequent misdiagnosis as hepatocellular carcinoma. We performed left hepatectomy for PHNET in an elderly lady with prolonged stormy postoperative course. This case report of a PHNET highlights the importance of histopathology and immunohistochemistry in the diagnosis and emphasizes that oncological resection, if feasible, is the preferred treatment even in the elderly population.

Augmenting insect olfaction performance through nano-neuromodulation.

Biological olfactory systems are highly sensitive and selective, often outperforming engineered chemical sensors in highly complex and dynamic environments. As a result, there is much interest in using biological systems to build sensors. However, approaches to read-out information from biological systems, especially neural signals, tend to be suboptimal due to the number of electrodes that can be used and where these can be placed. Here we aim to overcome this suboptimality in neural information read-out by using a nano-enabled neuromodulation strategy to augment insect olfaction-based chemical sensors. By harnessing the photothermal properties of nanostructures and releasing a select neuromodulator on demand, we show that the odour-evoked response from the interrogated regions of the insect olfactory system can not only be enhanced but can also improve odour identification.

The Development of a Clinical Registry Digital Database on Invasive Fungal Infections in India: Advancing Epidemiological Understanding and Patient Care.

A well-structured digital database is essential for any national priority project as it can provide real-time data analysis and facilitate quick decision making. In recent times, particularly after the COVID-19 pandemic, invasive fungal infections (IFIs) have emerged as a significant public health challenge in India, affecting vulnerable population, including immunocompromised individuals. The lack of comprehensive and well-structured data on IFIs has hindered efforts to understand their true burden and optimize patient care. To address this critical knowledge gap, the ICMR has undertaken a Pan-India pioneer initiative to develop a network of Advanced Mycology Diagnostic research centres in different geographical zones of the country (ICMR-MycoNet). Under the aegis of this project, a clinical registry on IFIs in the ICUs is initiated. This process paper presents a detailed account of the steps involved in the establishment of a web-based data entering and monitoring platform to capture data electronically, ensuring robust and secure data collection and management. This system not only allows participating ICMR-MycoNet centres to enter patient information directly into the database using standardized Case Report Form (CRF) but also includes data validation checks to ensure the accuracy and completeness of entered data. It is complemented by a real-time, web-based, and adaptable data visualization platform. This registry aims to provide crucial epidemiological insights, promote evidence-based hospital infection control programs, and ultimately improve patient outcomes in the face of this formidable healthcare challenge.

Periodontal health status in patients with lung cancer: Case-control study.

Objective: The objective of this study was to assess the periodontal health status of individuals with lung cancer in the North Indian population. In addition, the study aimed to determine the levels of human beta-defensin2 (Hbd-2) in the gingival crevicular fluid (GCF) and serum samples collected from the participants. Methods: The study consisted of a total of 90 participants, who were categorized into three groups: Group 1 included 30 healthy individuals, Group 2 comprised 30 patients with chronic periodontitis, and Group 3 involved 30 patients diagnosed with both lung cancer and chronic periodontitis. Various periodontal parameters, including plaque index, gingival index, probing pocket depth, and clinical attachment level (CAL), were assessed in addition to the analysis of human beta defensin2 levels in both the GCF and serum samples of all participants. Results: The study results revealed that all clinical parameters assessed were higher in Group 3 compared to both Group 2 and Group 1. Specifically, the levels of hBD-2 in the GCF were measured as 52.29 ± 46.41 pg/mL in Group 1, 27.15 ± 28.76 pg/mL in Group 2, and 86.01 ± 68.82 pg/mL in Group 3. When comparing the hBD-2 levels in serum, the values were found to be 813.72 ± 269.43 pg/mL in Group 1, 591.50 ± 263.91 pg/mL in Group 2, and 1093.04 ± 674.55 pg/mL in Group 3. These intergroup comparisons indicate variations in hBD-2 levels among the different groups. Conclusions: The study findings demonstrated significantly higher clinical and biochemical markers in patients with both lung cancer and chronic periodontitis, in comparison to individuals with chronic periodontitis alone and healthy participants. These results suggest that Hbd-2 could potentially serve as a valuable diagnostic biomarker for identifying and distinguishing individuals with both lung cancer and chronic periodontitis.