Developing a roadmap to reach and sustain 90% full immunization coverage through a cross-sectoral system strengthening strategy in Bihar, India.

INTRODUCTION: Reducing childhood mortality by curtailing the incidence of vaccine preventable diseases is contingent upon a robust and high-performing routine immunization system. According to the available data, the full immunization coverage (FIC) in the state of Bihar (India) has reached ~ 71%. While the government aspires to reach 90% FIC, a systematic evidence-based investigation of the reasons behind underimmunization as well as the identification of drivers and enablers to reach and sustain 90% FIC is critical. This study aimed to review the factors leading to underimmunized children in the state of Bihar and develop a forward-looking roadmap to reach and sustain 90% FIC by adopting a system strengthening approach. METHOD: We conducted a desk review, followed by extensive stakeholder interviews and field visits to document and analyze the data and evidence relevant to routine immunization system performance in the state of Bihar. The stakeholders included the State Immunization Officer, District Immunization Officers, Block-level health officials, representatives from development agencies, healthcare workers, and caregivers. A total of eighty-six structured interviews were conducted, which included qualitative and quantitative parameters. RESULT: While positive results were observed from the assessment of Bihar's immunization system, the implementation of targeted strategies for supply, service delivery and demand can provide a means to achieve FIC of 90%. The roadmap developed by the Government of Bihar enlists 40 + interventions across key thematic areas and has been prioritized over a 5-year time horizon as short, medium, and long-term milestones to achieve 90% FIC. These interventions include strengthening the data availability and quality, improving the governance and review mechanism, augmenting the capacity of health workers involve with immunization programme, and initiatives to increase demand for immunization services. CONCLUSION: The Bihar's Immunization Roadmap development project work follows a methodical approach to assess and identify intervention to improve immunization coverage and can provide information and reference to other states and countries that are aiming to formulate similar action plans.

GGE biplot analysis for cane yield and sugar yield in advanced clones of sugarcane (Saccharum sp. complex).

The present investigation was taken up to study the G × E interaction and stability in 14 sugarcane clones during 2020-2021 and 2021-2022 at four different locations namely Pantnagar, Kashipur, Dhanauri (Haridwar), and Dhakrani (Dehradun) for cane yield (CY) and sugar yield (SY) at the 10-month and 12-month stages. The research aimed to identify stable, high-yielding sugarcane clones adaptable to diverse environmental conditions, enhancing productivity and profitability for farmers in Uttarakhand, India. The combined ANOVA revealed significant differences among the clones (22.20% to 29.54% variation), environments (35% to 39.62% variation), and their interactions (19.91% to 24.16% variation) for CY and SY at both stages. To analyze the stability of genotypes and G × E interactions, the GGE biplot method was employed. The first two PCs explained 77.94% for CY, 74.39% for SY at the 10-month stage, and 81.01% for SY at 12-month stage of the total variation of the GGE model. The GGE biplots revealed that for CY, the mega-environment exhibited CoPant 16222 and CoPant 16223 as the winning genotypes. For SY at the 10-month stage, CoPant 17221 and CoPant 16222 were the best clones in two different mega-environments, while at the 12-month stage, the mega-environment showed CoPant 16222 and CoPant 16223 as the winning genotypes. Dehradun (2020) and Kashipur (2020) were identified as the best test environments for selecting widely and specifically adapted genotypes, respectively, for CY and SY at the 10-month as well as 12-month stages. In a nutshell, GGE biplot analysis identified the best-performing sugarcane clones and best test environments in Uttarakhand, India. Clone CoPant 16222 showed high mean performance and stability for cane and sugar yield, making it suitable for recommendation to farmers.

An Exploratory-Descriptive Analysis of Training Programs for Leadership in Health Research and Services in India.

BACKGROUND: There are several leadership training programs for health researchers in India. However, there is a need to develop context-tailored leadership and mentoring approaches. OBJECTIVE: The objective of the study is to critically analyze the available leadership training programs in India for health researchers and service providers, for the leadership domains incorporated and overall training approaches. MATERIALS AND METHODS: We used an exploratory-descriptive design to identify and review leadership training programs for health researchers and service providers/managers that had been offered by Indian institutions between 2013 and 2018. Our analytic approach was based on "transformational leadership" and "leader-member exchange" theories of leadership, curricula of popular leadership training programs worldwide, and the International Clinical Epidemiology Network model for leadership in health research in India based on a nationwide primary study. RESULTS: We identified and reviewed 20 leadership training programs. These were heterogeneous in aim, scope (broad-based/thematic), course content, design, target participants and class profile, mode of delivery and training method, duration, frequency, and fund arrangements. The programs infrequently included topics on soft skills, mentoring, risk mitigation, collaboration for research, funding dynamics, institutional transformation, self-view and peer perception, and personal well-being. The programs insufficiently addressed contextual challenges of career exploration and risk mitigation, project management, strategic planning, and decision-making, ethics and integrity, negotiations, networking and collaboration, understanding funding dynamics, and mentoring. Only three programs linked to the training to the participants' ecosystem. CONCLUSIONS: There is a need to develop customized course contents and training strategies that address the requirements of the local context vis-à-vis globally connected research ecosystems.

Role of central endpoint adjudication and challenges in trials on neonatal sepsis-a case of ProSPoNS trial.

Despite progress in reducing the infant mortality in India, the neonatal mortality decline has been slower, necessitating concerted efforts to achieve Sustainable Development Goal-3. A promising strategy aiming to prevent neonatal sepsis in high-risk, vulnerable, low birth weight neonates through an innovative intervention includes probiotic supplementation. This article communicates the decision by the ProSPoNS trial investigators to establish a Central Endpoint Adjudication Committee (CEAC) as an addendum to the protocol published in Trials in 2021 for the purpose of clarifying the primary outcome. In the published protocol, the study hypothesis and primary objective are based on "sepsis," the primary outcome has been specified as sepsis/PSBI, whereas the sample size estimation was performed based on the "physician diagnosed sepsis." To align all the three above, the investigators meeting, held on 17th-18th August 2023, at MGIMS Sevagram, Wardha, deliberated and unanimously agreed that "physician diagnosed sepsis" is the primary study outcome which includes sepsis/PSBI. The CEAC, chaired by an external subject expert and members including trial statistician, a microbiologist, and all site principal investigators will employ four criteria to determine "physician diagnosed sepsis": (1) blood culture status, (2) sepsis screen status, (3) PSBI/non-PSBI signs and symptoms, and (4) the clinical course for each sickness event. Importantly, this clarification maintains consistency with the approved study protocol (Protocol No. 5/7/915/2012 version 3.1 dated 14 Feb 2020), emphasizing the commitment to methodological transparency and adherence to predefined standards. The decision to utilize the guidance of a CEAC is recommended as the gold standard in multicentric complex clinical trials to achieve consistency and accuracy in assessment of outcomes.Trial registrationClinical Trial Registry of India (CTRI) CTRI/2019/05/019197. Registered on 16 May 2019.

Periodate activation and pH regulation using ball-milled metal-oxide-mineral-biochar composite for removal of antibiotics from contaminated water.

The inclusion of mineral salts in carbon activators are beneficial for advanced oxidation processes (AOPs). Herein, we present the application of ball-milled biochar with phosphate salt for periodate (IO4-) activation and degradation of antibiotics in contaminated water. Physical characterization results showed that the catalyst is infused with Mg3(PO4)2 and ball-milling increased the specific surface area to 216 m2 g-1 from 46 m2 g-1 while reducing the particle size to less than 1.0 µ. The optimized system successfully eliminated >99% of diclofenac while maintaining the pH of the reaction medium to circumneutral levels. Scavenger and ESR experiments revealed the degradation is triggered by O2•-, 1O2 and •OH species within the system. Electrochemical studies confirmed electron transfer during diclofenac degradation. The reported system demonstrated high degradation efficiency under both neutral and acidic pH conditions. Based on the by-product analysis, the degradation pathway of diclofenac was elucidated. Further, the toxicity assessment for the identified intermediates showed minimum toxicity of the degraded products. This mineral-biochar composite exhibited promising performance in eliminating other antibiotic substances. Therefore, the present finding highlights the importance of raw materials selection for producing mineral-biochar composite that provide new insights into IO4- activation for antibiotic removal by maintaining the natural pH.

Prevalence of osteoporosis and associated factors among people aged 50 years and older in the Madhesh province of Nepal: a community-based cross-sectional study.

BACKGROUND: The high prevalence of osteoporosis has increased the economic burden on the health system globally. The burden of osteoporosis and its associated factors have not been adequately assessed in community settings in the Nepalese context thus far. Therefore, this study aimed to assess the prevalence of osteoporosis and its associated factors, lifestyle behaviors, and dietary calcium intake. METHODS: A community-based cross-sectional study was conducted among 395 people aged 50 years and older in the Madhesh Province of Nepal between July 2022 and August 2023. The Osteoporosis Self-assessment Tools for Asians (OSTA) index was used to measure osteoporosis. A structured questionnaire was used to collect sociodemographic information, anthropometric data, lifestyle behavior, daily dietary calcium intake, and frequency of calcium-rich food consumption. A food frequency questionnaire and 24-hour recall methods were used to assess dietary intake. The chi-square test, binary logistic regression and Mann‒Whitney U test were applied to measure the association between predictors and the outcome of interest. RESULTS: The prevalence of no risk, moderate risk and high risk of osteoporosis were 38.7%, 39%, and 22.3% respectively. The risk of osteoporosis was higher in females (aOR = 5.18, CI: 2.10-12.75, p < 0.001) and increased risk with advancing age (aOR = 32.49, CI: 14.02-75.28, p < 0.001). Similarly, underweight was associated with increased odds of having osteoporosis (aOR = 13.42, CI = 4.58-39.30, p < 0.001). The incidence of osteoporosis was strongly associated with daily calcium intake of 225 mg (100, 386). CONCLUSION: This study revealed a high prevalence of osteoporosis among people aged 50 years and older due to the combined effect of being underweight and having inadequate calcium intake. Nutritional counselling services encourage people to consume sufficient calcium-rich food and adopt an appropriate lifestyle behaviours to maintain healthy body weight so that osteoporosis and osteoporotic fractures could be prevented. Further research can explore the impact of socioeconomic status and medical comorbidities on a large scale.

Expanding Arsenal against Ocular Diseases through Nanoemulsion: Success So Far and the Road Ahead.

The eye is a most delicate organ protected by several complex biological barriers that are static and dynamic. The presence of these ocular barriers retards drug absorption from topically applied dosage forms at the conjunctival sac. The efficient topical delivery of the drug into the globe is more difficult to achieve and there is a need to develop a topical formulation that may reduce the use of injections and increase patient compliance with decreased frequency of administration. In the advancements of research in nanotechnology, nanoemulsions can be used as biocompatible carriers to deliver the drug to the ocular cavity. The lipophilic globules can increase the solubility of hydrophobic cargos which provides increased permeation ability and ocular bioavailability which can sustain drug release and corneal retention. Because of their small size, these formulations do not cause blurring of vision. Nanoemulsions (NEs) over the past decade have been used to treat several ocular diseases in the anterior eye segment. This review summarizes the economic burden, pathology of ocular diseases, formulation considerations for ocular formulations, and recent advances of these NEs as effective carriers for ocular drug delivery highlighting their performance in pre-clinical studies.

Enhancing drought resilience: machine learning-based vulnerability assessment in Uttar Pradesh, India.

Drought is a natural and complex climatic hazard. It has both natural and social connotations. The purpose of this study is to use machine learning methods (MLAs) for drought vulnerability (DVM) in Uttar Pradesh, India. There were 18 factors used to determine drought vulnerability, separated into two groups: physical drought and meteorological drought. The study found that the eastern part of Uttar Pradesh is high to very highly prone to drought, which is approximately 31.38% of the area of Uttar Pradesh. The receiver operating characteristic curve (ROC) was then used to evaluate the machine learning models (artificial neural networks). According to the findings, the ANN functioned with AUC values of 0.843. For policy actions to lessen drought sensitivity, DVMs may be valuable. Future exploration may involve refining machine learning algorithms, integrating real-time data sources, and assessing the socio-economic impacts to continually enhance the efficacy of drought resilience strategies in Uttar Pradesh.

Oncogenes and tumor suppressor genes: functions and roles in cancers.

Cancer, being the most formidable ailment, has had a profound impact on the human health. The disease is primarily associated with genetic mutations that impact oncogenes and tumor suppressor genes (TSGs). Recently, growing evidence have shown that X-linked TSGs have specific role in cancer progression and metastasis as well. Interestingly, our genome harbors around substantial portion of genes that function as tumor suppressors, and the X chromosome alone harbors a considerable number of TSGs. The scenario becomes even more compelling as X-linked TSGs are adaptive to key epigenetic processes such as X chromosome inactivation. Therefore, delineating the new paradigm related to X-linked TSGs, for instance, their crosstalk with autosome and involvement in cancer initiation, progression, and metastasis becomes utmost importance. Considering this, herein, we present a comprehensive discussion of X-linked TSG dysregulation in various cancers as a consequence of genetic variations and epigenetic alterations. In addition, the dynamic role of X-linked TSGs in sex chromosome-autosome crosstalk in cancer genome remodeling is being explored thoroughly. Besides, the functional roles of ncRNAs, role of X-linked TSG in immunomodulation and in gender-based cancer disparities has also been highlighted. Overall, the focal idea of the present article is to recapitulate the findings on X-linked TSG regulation in the cancer landscape and to redefine their role toward improving cancer treatment strategies.

Acetylresveratrol (AC-Res): An Evolving Frontier in Modulating Gene Expression.

BACKGROUND: Acetylresveratrol (AC-Res), to date, is a powerful stilbene phytoalexin generated organically or as a component of a plant's defensive system, is a significant plant phenolic chemical portion and is investigated as a therapy option for a number of disorders. Owing to its inadequate stabilisation and considerable conformation rigidity, the utility of AC-Res as a medication is limited. OBJECTIVE: The current review article outlined the structure of AC-Res, their methods of activity, and the latest technological progress in the administration of these molecules. It is conceivable to deduce that AC-Res has a variety of consequences for the cellular functions of infected cells. METHODS: The literature survey for the present article was gathered from the authentic data published by various peer-reviewed publishers employing Google Scholar and PubMedprioritizing Scopus and Web of Science indexed journals as the search platform focusing on AC-Res pharmacological actions, particularly in the English language. RESULT: Despite its extensive spectrum of biological and therapeutic applications, AC-Res has become a source of increasing concern. Depending on the researchers, AC-Res possesses radioprotective, cardioprotective, neurological, anti-inflammatory, and anti-microbial potential. It also has anti-cancer and antioxidant properties. CONCLUSION: To avoid non-specific cytotoxicity, optimization efforts are presently emphasizing the possible usage of AC-Res based on nanocrystals, nanoparticles and dendrimers, and nanocrystals. Finally, while using AC-Res in biology is still a way off, researchers agree that if they continue to explore it, AC-Res and similar parts will be recognized as actual possibilities for a variety of things in the next years.

Examining social vulnerability to multi-hazards in North-Western Himalayas, India.

The enhancing risk from human action and multi-hazard interaction has substantially complicated the hazard-society relationship. The underlying vulnerabilities are crucial in predicting the probable impact to be caused by multi-hazards. Thus, the evaluation of social vulnerability is decisive in inferring the driving factor and preparing for mitigation strategies. The Himalayan landscape is prone to multiple hazards as well as possesses a multitude of vulnerabilities owing to changing human landscape. Thus, an attempt has been made to inquire into the underlying socioeconomic factors enhancing the susceptibility of the region to multi-hazards. The social vulnerability index (SVIent) has been introduced, consisting of 13 indicators and 33 variables. The variables have been standardized using the maximum and minimum normalization method and the relative importance for each indicator has been determined using Shannon entropy methods to compute SVIent. The findings revealed that female population, population above 60 years old, net irrigated area, migrant population, dilapidated house, nonworkers, bank, and nonworkers seeking jobs were found to be relatively significant contributors to the vulnerability. The western part of the study area was classified as the highly vulnerable category (SVI > 0.40628), attributed to high dependence, and higher share of unemployed workers and high poverty. The SVIent was shown to have positive correlation between unemployment, socioeconomic status, migration, dependency, and household structure significant at two-tailed test. The study's impact can be found in influencing the decision of policymakers and stakeholders in framing the mitigation strategies and policy documents.

Engineering circular RNA for molecular and metabolic reprogramming.

The role of messenger RNA (mRNA) in biological systems is extremely versatile. However, it's extremely short half-life poses a fundamental restriction on its application. Moreover, the translation efficiency of mRNA is also limited. On the contrary, circular RNAs, also known as circRNAs, are a common and stable form of RNA found in eukaryotic cells. These molecules are synthesized via back-splicing. Both synthetic circRNAs and certain endogenous circRNAs have the potential to encode proteins, hence suggesting the potential of circRNA as a gene expression machinery. Herein, we aim to summarize all engineering aspects that allow exogenous circular RNA (circRNA) to prolong the time that proteins are expressed from full-length RNA signals. This review presents a systematic engineering approach that have been devised to efficiently assemble circRNAs and evaluate several aspects that have an impact on protein production derived from. We have also reviewed how optimization of the key components of circRNAs, including the topology of vector, 5' and 3' untranslated sections, entrance site of the internal ribosome, and engineered aptamers could be efficiently impacting the translation machinery for molecular and metabolic reprogramming. Collectively, molecular and metabolic reprogramming present a novel way of regulating distinctive cellular features, for instance growth traits to neoplastic cells, and offer new possibilities for therapeutic inventions.

A method for durian precise fertilization based on improved radial basis neural network algorithm.

Introduction: Durian is one of the tropical fruits that requires soil nutrients in its cultivation. It is important to understand the relationship between the content of critical nutrients, such as nitrogen (N), phosphorus (P), and potassium (K) in the soil and durian yield. How to optimize the fertilization plan is also important to the durian planting. Methods: Thus, this study proposes an Improved Radial Basis Neural Network Algorithm (IM-RBNNA) in the durian precision fertilization. It uses the gray wolf algorithm to optimize the weights and thresholds of the RBNNA algorithm, which can improve the prediction accuracy of the RBNNA algorithm for the soil nutrient content and its relationship with the durian yield. It also collects the soil nutrients and historical yield data to build the IM-RBNNA model and compare with other similar algorithms. Results: The results show that the IM-RBNNA algorithm is better than the other three algorithms in the average relative error, average absolute error, and coefficient of determination between the predicted and true values of soil N, K, and P fertilizer contents. It also predicts the relationship between soil nutrients and yield, which is closer to the true value. Discussion: It shows that the IM-RBNNA algorithm can accurately predict the durian soil nutrient content and yield, which is benefited for farmers to make agronomic plans and management strategies. It uses soil nutrient resources efficiently, which reduces the environmental negative impacts. It also ensures that the durian tree can obtain the appropriate amount of nutrients, maximize its growth potential, reduce production costs, and increase yields.

Strategic enzymatic enantioselective desymmetrization of prochiral cyclohexa-2,5-dienones.

Asymmetric desymmetrization through the selective reduction of one double bond of prochiral 2,5-cyclohexadienones is highly challenging. A novel method has been developed for synthesizing chiral cyclohexenones by employing an ene-reductase (Bacillus subtilis YqjM) enzyme that belongs to the OYE family. Our strategy demonstrates high substrate scope and enantioselectivity towards substrates containing all-carbon as well as heteroatom (O, N)-containing quaternary centers. The mechanistic studies (kH/D = ∼1.8) indicate that hydride transfer is probably the rate-limiting step. Mutation of several active site residues did not affect the stereochemical outcomes. This work provides a convenient way of synthesizing various enantioselective γ,γ-disubstituted cyclohexanones using enzymes.

Challenges of biomedical research collaboration in India: Perceptions of Indian and international researchers.

Biomedical research collaborations are to be contextualized in the larger global health agenda which also opens up new information pathways, expands research networks, and brings additional resources. A qualitative inquiry was employed to understand the perceived benefits and challenges of research collaborations by biomedical scientists from India (Global South [GS] country) and the Global North (GN). In-depth interviews were conducted with 47 biomedical scientists from India and 06 from the GN. The data was analyzed using the grounded theory approach. Complementarity of skills and resources, access to funds, improved quality of work, an opportunity to conduct multi-centric studies, development of collaborative networks, better and larger number of publications, mutual learning, opportunity to work with credible researchers, address common interests, leverage interpersonal and trusted relationships and larger societal good were some of the critical factors for eagerness of participants in joint scientific endeavors. However, the challenging aspects of dissent and disagreements were the power imbalance between the collaborators, the development of a trust deficit, and local administrative issues. The challenges reported in the current publication, also echoed in several previous publications can be surmounted and negotiated amicably when the rules of the game, law of the land, sharing of the credits, and interest of the collaborating parties are addressed and agreed up in a fair and just manner before the start of the collaboration. Overall biomedical partnerships are complex collaborations with its challenges, the processes are dynamic and outcomes are emergent. This requires constant and proactive evolution of the preparation, implementation and sustainability of the collaborative efforts be it national or international.