BBBper: A Machine Learning-based Online Tool for Blood-Brain Barrier (BBB) Permeability Prediction.

AIMS: Neuronal disorders have affected more than 15% of the world's population, signifying the importance of continued design and development of drugs that can cross the Blood-Brain Barrier (BBB). BACKGROUND: BBB limits the permeability of external compounds by 98% to maintain and regulate brain homeostasis. Hence, BBB permeability prediction is vital to predict the activity of a drug-like substance. OBJECTIVE: Here, we report about developing BBBper (Blood-Brain Barrier permeability prediction) using machine learning tool. METHOD: A supervised machine learning-based online tool, based on physicochemical parameters to predict the BBB permeability of given chemical compounds was developed. The user-end webpage was developed in HTML and linked with back-end server by a python script to run user queries and results. RESULT: BBBper uses a random forest algorithm at the back end, showing 97% accuracy on the external dataset, compared to 70-92% accuracy of currently available web-based BBB permeability prediction tools. CONCLUSION: The BBBper web tool is freely available at http://bbbper.mdu.ac.in.

North India Cancer Risk: A Detailed Review with Focus on Jammu and Kashmir Demographics.

BACKGROUND: Cancer is a global medical challenge, and research is at its peak to understand the unique mechanisms of cancer cells. The expanding field of epidemiology, including molecular and environmental studies, helps us better understand the distribution of molecular changes and environmental risk factors in the population. AIM: In the present review, we aimed to find out the different genes and environmental factors that are associated with different cancers in the Jammu & Kashmir (J&K) region of the North Indian population. METHOD: A Systematic approach of literature survey was used to curate research data based on genetic and environmental epidemiology specifying the J&K region. RESULT: Of 640 articles found initially and screening of 490 records, 97 studies were included for the final review. It was observed that numerous genes that are strongly linked to various cancer types have been discovered as a result of the rising genotyping trend, which has grown in the demography exponentially over the last few decades. The majority of these genes are related to cell cycle regulation, cell growth signaling, and apoptosis regulation. Additionally, high promoter hypermethylation of various genes which were found to be attributed to the presence of distinct dietary patterns. The most important environmental risk attributes were salt tea consumption and dried pickles. DISCUSSION & CONCLUSION: In conclusion, the J&K population possesses many common polymorphisms in various genes with a small effect size that makes individuals more prone to different forms of cancers interacting with different environmental factors. What we can't do is, change the gene sequence or molecular changes which are the main changes for determining the susceptibility of any altered condition but what we can do is lower/ limit the exposure to the environmental factors which is a key element playing with the susceptibility's threshold. Therefore, limiting exposure to environmental factors could be a major step in lowering the risk of disease.

Conformation matters: siRNAs with antisense strands with 5'-(E)-vinyl-phosphonate-α-L-LNA elicit stronger RNAi-mediated gene silencing than those with 5'-(E)-vinyl-phosphonate-LNA.

Conformationally constrained nucleotides, LNA or α-L-LNA, at the 5' terminus of the antisense strand impeded gene silencing of small interfering RNA (siRNA) by hindering phosphorylation, thereby deterring loading into the RNA-induced silencing complex. Installation of a phosphate mimic, (E)-vinyl phosphonate (VP), improved activity considerably. Gene silencing was more efficient when the antisense strand of the siRNA was modified with 5'-VP-α-L-LNA, which adopts a C3'-exo (south) conformation, than when the antisense strand was modified with 5'-VP-LNA, which adopts a C3'-endo (north) pucker. These data underscore the critical role of conformation of nucleotides in RNA interference.

ER stress aggravates NOD1-mediated inflammatory response leading to impaired nutrient metabolism in hepatoma cells.

Nucleotide-binding Oligomerization Domain 1 (NOD1) is a cytosolic pattern recognition receptor that senses specific bacterial peptidoglycan moieties, leading to the induction of inflammatory response. Besides, sensing peptidoglycan, NOD1 has been reported to sense metabolic disturbances including the ER stress-induced unfolded protein response (UPR). However, the underpinning crosstalk between the NOD1 activating microbial ligands and the metabolic cues to alter metabolic response is not yet comprehensively defined. Here, we show that underlying ER stress aggravated peptidoglycan-induced NOD1-mediated inflammatory response in hepatoma cells. The HepG2 cells, undergoing ER stress induced by thapsigargin exhibited an amplified inflammatory response induced by peptidoglycan ligand of NOD1 (i.e. iE-DAP). This aggravated inflammatory response disrupted lipid and glucose metabolism, characterized by de novo lipogenic response, and increased gluconeogenesis in HepG2 cells. Further, we characterized that the aggravation of NOD1-induced inflammatory response was dependent on inositol-requiring enzyme 1-α (IRE1-α) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) activation, in conjunction with calcium flux. Altogether, our findings suggest that differential UPR activation makes liver cells more sensitive towards bacterial-derived ligands to pronounce inflammatory response in a NOD1-dependent manner that impairs hepatic nutrient metabolism.

Celiac trunk arterial variations and their clinical implications: Role of imaging.

The awareness of anatomical variations of hepatic arteries and celiac trunk is very important in interventional radiology, liver transplant and intra-abdominal oncologic surgeries. Radiology plays an important role in the identification of these variants non-invasively. Digital subtraction angiography was the gold standard for their identification. Computed tomography (CT) angiography non-invasively provides detailed knowledge of various anatomical vascular variations. This pictorial review highlights the role of multidetector computed tomography (MDCT) in the identification of celiac trunk-hepatic arterial system variations and clinical consequences.

A critical insight into the physicochemical stability of macular carotenoids with respect to their industrial production, safety profile, targeted tissue delivery, and bioavailability.

Lutein, zeaxanthin, and mesozeaxanthin, collectively termed as macular pigments, are key carotenoids integral to optimized central vision of the eye. Therefore, nutraceuticals and functional foods have been developed commercially using carotenoid rich flowers, such as marigold and calendula or single celled photosynthetic algae, such as the Dunaliella. Industrial formulation of such products enriched in macular pigments have often suffered from serious bottlenecks in stability, delivery, and bioavailability. The two chief factors largely responsible for decreasing the shelf-life have been solubility and oxidation of these pigments owing to their strong lipophilic nature and presence of conjugated double bonds. In this regard, oil-based formulations have often been found to be more suitable than powder-based formulations in terms of shelf life and targeted delivery. In some cases, addition of phenolic acids in the formulations have also augmented the product value by enhancing micellization. In this regard, a novel proprietary formulation of these pigments has been developed in our laboratory utilizing marigold extracts in a colloidal solution of extra virgin olive oil and canola oil fortified with antioxidants like thyme oil, tocopherol, and ascorbyl palmitate. This review article presents an updated insight into the stability and bioavailability of industrially manufactured macular carotenoids together with their safety and solubility issues.

Motility and pairwise interactions of chemically active droplets in one-dimensional confinement.

Self-propelled droplets serve as ideal model systems to delve deeper into understanding the motion of biological microswimmers by simulating their motility. Biological microorganisms are renowned for showcasing a diverse array of dynamic swimming behaviors when confronted with physical constraints. This study aims to elucidate the impact of physical constraints on swimming characteristics of biological microorganisms. To achieve this, we present observations on the individual and pairwise behavior of micellar solubilized self-propelled 4-cyano-4'-pentyl-biphenyl (5CB) oil droplets in a square capillary channel filled with a surfactant trimethyl ammonium bromide aqueous solution. To explore the effect of the underlying Péclet number of the swimming droplets, the study is also performed in the presence of additives such as high molecular weight polymer polyethylene oxide and molecular solute glycerol. The capillary confinement restricts droplet to predominantly one-dimensional motion, albeit with noticeable differences in their motion across the three scenarios. Through a characterization of the chemical and hydrodynamic flow fields surrounding the droplets, we illustrate that the modification of the droplets' chemical field due to confinement varies significantly based on the underlying differences in the Péclet number in these cases. This alteration in the chemical field distribution notably affects the individual droplets' motion. Moreover, these distinct chemical field interactions between the droplets also lead to variations in their pairwise motion, ranging from behaviors like chasing to scattering.

Artificial blood for therapeutic and laboratory usage: Where do we stand?

The scarcity of blood for transfusion purposes has been widely acknowledged. Surgical therapeutic processes, war zones, and post-disaster treatments demand a huge amount of blood. Modern-day laboratories also require blood for bioengineering experimentation. Therefore, an artificially devised solution capable of mimicking the blood functions from biological and engineering relevance would be a noteworthy discovery of contemporary science. The experience drawn from discarded century-old blood substitutes has led us to technologically more advanced present-day solutions, which are better at carrying out the physiological functions of blood. Aiming at safety, stability, non-toxicity, and compatibility in terms of immuno-response, a remarkable number of substitutes are being tried to mimic the physiological properties and functions of red blood cells, platelets, plasma, and white blood cells. Despite significant efforts and time devoted, for transfusion, no product so far has been able to replace natural blood. This article puts together the important developments in blood substitutes that have evolved over the years, including substitutes for clinical as well as engineering requirements. It also points out the recent endeavors of synthesizing blood cells through modern synthetic routes. It has been highlighted that none of the blood substitutes have achieved the required efficacy so that they can be used in vivo. Finally, the emerging trends and future research needs have been stressed upon.

Integrating In-silico and In-vitro approaches to identify plant-derived bioactive molecules against spore coat protein CotH3 and high affinity iron permease FTR1 of Rhizopus oryzae.

Rhizopus oryzae is one of the major causative agents of mucormycosis. The disease has a poor prognosis with a high mortality rate, and resistance towards current antifungal drugs poses additional concern. The disease treatment is complicated with antifungals; therefore, surgical approach is preferred in many cases. A comprehensive understanding of the pathogenicity-associated virulence factors of R. oryzae is essential to develop new antifungals against this fungus. Virulence factors in R. oryzae include cell wall proteins, spore germination proteins and enzymes that evade host immunity. The spore coat protein (CotH3) and high-affinity iron permease (FTR1) have been identified as promising therapeutic targets in R. oryzae. In-silico screening is a preferred approach to identify hit molecules for further in-vitro studies. In the present study, twelve bioactive molecules were docked within the active site of CotH3 and FTR1. Further, molecular dynamics simulation analysis of best-docked protein-ligand structures revealed the dynamics information of their stability in the biological system. Eugenol and isoeugenol exhibited significant binding scores with both the protein targets of R. oryzae and followed the Lipinski rule of drug-likeness. To corroborate the in-silico results, in-vitro studies were conducted using bioactive compounds eugenol, isoeugenol, and myristicin against R. oryzae isolated from the soil sample. Eugenol, isoeugenol exhibited antifungal activity at 156 µg/mL whereas myristicin at 312 µg/mL. Hence, the study suggested that eugenol and isoeugenol could be explored further as potential antifungal molecules against R. oryzae.

Alternaria alternata species complex impairing solanaceous vegetables in Northern parts of India: an emerging problem in Solanum lycopersicum L.

Severe incidence of Alternaria spp. was observed in the three solanaceous vegetables viz. tomato, potato and brinjal grown in National Capital Region of Delhi and Haryana. The symptomatic plants exhibited necrotic brown lesions on the leaves initiating from the lower older leaves and extending to stem, affecting the whole plant. Subsequently, black sooty sporulation was observed in fruits of tomato and brinjal crop. During the survey, tomato crop was most susceptible with 98.99% incidence, followed by brinjal with 82.36% and potato with 61.19% incidence. The mean plant disease index varied between 9.98% and 65.99% among the three crops. Isolation and characterization of the causal agent from symptomatic plants revealed association of small-spored Alternaria spp. in all crops. Further, morphological and Internal Transcribed Spacer (ITS) sequencing phylogenetic analysis ascertained the fungus belong to Alternaria section of Alternaria genus. As tomato was found most susceptible, host plant resistance was explored among 197 tomato germplasm/breeding lines under epiphytotic conditions. It was found that 08 accessions exhibited moderate resistance against pathogen. The findings in the study suggest that small-spored Alternaria is an emerging problem in the solanaceous vegetables and warrants attention for effective management of the disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04059-7.

Dual Aliovalent Dopants Cu, Mn Engineered Eco-Friendly QDs for Ultra-Stable Anti-Counterfeiting.

Doping in semiconductor quantum dots (QDs) using optically active dopants tailors their optical, electronic, and magnetic properties beyond what is achieved by controlling size, shape, and composition. Herein, we synergistically modulated the optical properties of eco-friendly ZnInSe2/ZnSe core/shell QDs by incorporating Cu-doping and Mn-alloying into their core and shell to investigate their use in anti-counterfeiting and information encryption. The engineered "Cu:ZnInSe2/Mn:ZnSe" core/shell QDs exhibit an intense bright orange photoluminescence (PL) emission centered at 606 nm, with better color purity than the undoped and individually doped core/shell QDs. The average PL lifetime is significantly extended to 201 ns, making it relevant for complex encryption and anti-counterfeiting. PL studies reveal that in Cu:ZnInSe2/Mn:ZnSe, the photophysical emission arises from the Cu state via radiative transition from the Mn 4T1 state. Integration of Cu:ZnInSe2/Mn:ZnSe core/shell QDs into poly(methyl methacrylate) (PMMA) serves as versatile smart concealed luminescent inks for both writing and printing patterns. The features of these printed patterns using Cu:ZnInSe2/Mn:ZnSe core/shell QDs persisted after 10 weeks of water-soaking and retained 70 % of PL emission intensity at 170 °C, demonstrating excellent thermal stability. This work provides an efficient approach to enhance both the emission and the stability of eco-friendly QDs via dopant engineering for fluorescence anti-counterfeiting applications.

Post-introduction evaluation (PIE) of rotavirus vaccine in India.

Background: India became the first country in the WHO South-East Asia Region (SEAR) to introduce the rotavirus vaccine (RVV) in the Universal immunization programme (UIP) in 2016 with nationwide expansion by 2019. It was a landmark move to reduce the diarrheal disease burden in under-five children. To assess the implementation process of introduction of RVV, Post Introduction Evaluation (PIE) was conducted in March 2022. Methods: The evaluation was conducted across 14 states, 28 districts and 28 health facilities to obtain a nationwide geographical inclusion. Stakeholders involved in program decision-making, planning, training, vaccine delivery, logistics, and communication from all levels (National, state, district, health facility, health worker, caregiver) were interviewed using standardized data collection tool for PIE (adapted from the standard WHO PIE questionnaire) and scripted on a digital tool. Results: A total of 260 interviews were conducted. Political willingness, well-planned preparedness activities, securing vaccines timely, strong supply chain monitoring, availability of domestic RVV products, quality trainings and intense communication activities were the key factors identified for the successful RVV introduction. Key activities during the introduction included cold chain space assessment, trainings of healthcare workforce, dissemination of job aids, updation of recording & reporting formats and strengthening of AEFI surveillance. Lack of community awareness for immunization in a few areas, fear of AEFI amongst some caregivers and local issues with Alternate Vaccine Delivery (AVD) were some reported challenges in achieving high coverage for RVV. Conclusions: Overall, the nationwide roll-out of RVV was smooth and the vaccine has been well-accepted in the community. The assessment emphasizes on having a well-strategized operational and communication planning, which is very crucial for any new vaccine introduction.

Trends of Nanobiosensors in Modern Agriculture Systems.

Sustainable agriculture and the provision of food for all become dependent on the availability of efficient diagnostic techniques for the prompt identification of plant diseases. Current scientific findings suggest that nanotechnology can positively affect the agrifood industry by reducing the adverse effects of agricultural practices on human health and the environment, increasing food security and productivity, and fostering social and economic justice. Nanomaterials' unique physical and chemical characteristics have made it possible to employ them as cutting-edge, effective diagnostic instruments for various plant infections and other significant disease biomarkers. By creating diagnostic instruments and methods, nanobiosensors significantly contribute to the revolution of farming. In real time, nanobiosensors can detect infections, metabolites, pesticides, nutrient levels, soil moisture, and temperature. This helps with precision farming techniques and maximises resource use. To better address agricultural concerns, we have included the most recent research on the concept, types, applications, commercial aspects, and future scope of nanobiosensors in this review.

Strengthening of Vaccine-Preventable Disease (VPD) Surveillance to Enhance National Health Capacity and Security: Perspective from India.

The Government of India, in collaboration with the World Health Organization (WHO), established the National Polio Surveillance Project (NPSP) in 1997 and initiated acute flaccid paralysis (AFP) surveillance to achieve the goal of polio eradication. The WHO South-East Asia Region, comprising of 11 countries, including India, was certified as polio-free in March 2014. India was also validated to have eliminated maternal and neonatal tetanus in May 2015. Over the years, the surveillance of other vaccine-preventable diseases (VPDs) was integrated with AFP surveillance in the country. Outbreak-based measles-rubella (MR) surveillance was initiated in 2005 using AFP surveillance as a platform, case-based fever-rash (FR) surveillance started in 2021 as one of the strategies to achieve measles and rubella elimination in the country. The surveillance of diphtheria, pertussis, and neonatal tetanus was integrated with AFP surveillance in a phased manner during 2015-2022. The surveillance system for VPDs in India, supported by a laboratory network of 10 polio laboratories, 28 measles-rubella laboratories, and 20 diphtheria-pertussis laboratories, has enhanced the national health capacity and security. The setting up and expansion of the surveillance system in the country involved the important component of capacity building of personnel on various components of surveillance, including case identification, case investigation, sample collection and shipment, data analysis and public health response. These capacities have been used effectively during other emergencies, such as the recent COVID-19 pandemic, as well as during outbreaks of other diseases and natural calamities.

A review of Patient Reported Outcome Measures (PROMs) for characterizing Long COVID (LC)-merits, gaps, and recommendations.

BACKGROUND: Individuals may experience a range of symptoms after the clearance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This condition is termed long COVID (LC) or Post-COVID-19 condition (PCC). Despite the appreciable number of symptoms documented to date, one key challenge remains in the robust characterization of LC outcomes. This review aimed to assess the properties, identify gaps, and provide recommendations for relevant descriptive and evaluative Patient-Reported Outcome Measurement (PROM) instruments that can be used to comprehensively characterize LC. METHODS: To achieve this objective, we identified and reviewed descriptive and evaluative PROM instruments that have been developed and validated to date with people living with LC. Our review assessed their properties, identified gaps, and recommended PROMs suitable for characterizing LC. To ensure a comprehensive and robust characterization of LC, we next identified, reviewed, and selected (with the input of patient partners) PROMs associated with the most frequently reported LC symptoms. The evaluation criteria included psychometric evidence, mode of delivery, cost, and administration time. RESULTS: Traditional matrix mapping revealed Post-COVID Functional Status Scale (PCFS) as a choice instrument for capturing LC outcomes largely because of the comprehensive domains it covered, and the number of psychometric evidence reported in literatures. This instrument can be effectively paired with the Fatigue Severity Scale (FSS), Montreal Cognitive Assessment (MoCA), Patient Health Questionnaire (PHQ-9), Headache Impact Test (HIT), Pittsburgh Sleep Quality Index (PSQI), and DePaul Symptom Questionnaire (DSQ-PEM) to characterize fatigue, cognitive impairment, depression/anxiety, headache, sleeplessness, and post-exertional malaise respectively. CONCLUSION: Our paper identified appropriate PROM instruments that can effectively capture the diverse impacts of LC. By utilizing these validated instruments, we can better understand and manage LC.

Some individuals who once contracted the virus responsible for COVID-19 may continue to experience a range of symptoms persisting for more than 3 months. These symptoms include fatigue, difficulty sleeping, anxiety and difficulty breathing amongst others. This condition is known by many as Long COVID (LC). To understand the health outcomes of patients faced with this condition, standardized Patient Reported Outcome Measurement instruments (PROMs) are pivotal. PROMs are standardized questionnaires completed by patients to measure their symptoms, perceptions of health status, and/or functional well-being. In this paper, we have examined standardized instruments suitable for measuring LC outcomes. We conducted a comprehensive strength and weakness analysis of each instrument reviewed, guided by specific criteria. Based on our strength and weakness analyses, we identified several potential instruments that can be used to reports patients' outcomes concerning LC. The data collected from PROMs provides valuable insights for healthcare practitioners and policy makers, enabling the enhancement of patient-centric care and serving as an instrument for systemic transformation.