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Immune checkpoint inhibitors, as single-agent therapy, have shown modest clinical efficacy in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). As has been successfully shown in other less immunogenic hematologic malignancies, rationally designed combination approaches may be more effective than single-agent checkpoint inhibitors, and may be the approach to pursue in AML/MDS. Hypomethylating agents (HMAs) such as azacitidine, while enhancing anti-tumor immune response, concurrently dampen immune response by upregulating inhibitory immune checkpoint molecule expression. Immune checkpoint molecule upregulation may be an important mechanism of azacitidine resistance. These findings have resulted in multiple clinical trials combining HMAs with immune checkpoint blockade. Clinical trial data have shown encouraging response rates and durable responses without resorting to stem cell transplant. In this review, we discuss preclinical data supporting the use of these agents in combination, and focus on clinical and correlative data emerging from numerous clinical trials investigating HMA-immune checkpoint inhibitor combinations in AML/MDS.

Tobacco consumption among low- and middle-income countries where food insecurity remains a challenge poses several concerns. This review examines the available global evidence linking smokeless tobacco (SLT) use with public health nutrition and its implications. Systematic review of articles extracted from PubMed and Scopus from January 2000 to December 2020. Included studies that demonstrated the relationship between SLT and nutrition-related factors, that is, BMI, malnutrition, anaemia, poor birth outcomes and metabolic disorders. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines have been followed to conduct the systematic evidence review. A total of thirty-four studies were finally used in the systematic review, which included cross-sectional (thirty-one) and cohort (three). SLT use has a huge impact on body weight, alteration in taste, poor oral health, and consumption of fruits and vegetables leading to malnutrition. Maternal use of SLT not only leads to anaemia but also hampers birth outcomes. Increased risk of metabolic syndrome and gallstone disease among SLT users are also well documented in the studies. The review highlights the linkages between SLT usage and poor nutritional outcomes. Tobacco control efforts should be convergent with public health nutrition to achieve overall health benefits. Attention is also required to explore suitable mechanisms for SLT cessation combined with enhancing food and nutrition security at the community level in sync with investments in public health nutrition intervention.

Immune checkpoint therapy with anti-CTLA-4 and anti-PD-1/PD-L1 has revolutionized the treatment of many solid tumors. However, the clinical efficacy of immune checkpoint therapy is limited to a subset of patients with specific tumor types 1 , 2 . Multiple clinical trials with combinatorial immune checkpoint strategies are ongoing; however, the mechanistic rationale for tumor-specific targeting of immune checkpoints is elusive. To garner an insight into tumor-specific immunomodulatory targets, we analyzed 94 patients representing five different cancer types, including those that respond relatively well to immune checkpoint therapy and those that do not, such as glioblastoma multiforme, prostate cancer and colorectal cancer. Through mass cytometry and single-cell RNA sequencing, we identified a unique population of CD73 hi macrophages in glioblastoma multiforme that persists after anti-PD-1 treatment. To test if targeting CD73 would be important for a successful combination strategy in glioblastoma multiforme, we performed reverse translational studies using CD73 −/− mice. We found that the absence of CD73 improved survival in a murine model of glioblastoma multiforme treated with anti-CTLA-4 and anti-PD-1. Our data identified CD73 as a specific immunotherapeutic target to improve antitumor immune responses to immune checkpoint therapy in glioblastoma multiforme and demonstrate that comprehensive human and reverse translational studies can be used for rational design of combinatorial immune checkpoint strategies. Analysis of a mass cytometry dataset for different human solid tumors coupled with murine reverse translational experiments suggests that targeting CD73 could enhance the efficacy of checkpoint inhibitor therapy in glioblastoma.

Background Multisectoral collaboration is essential for advancing primary health care (PHC). In low- and middle-income countries (LMICs), limited institutional capacities, governance issues, and inadequate stakeholder engagement impede multisectoral collaboration. India faces similar challenges, especially at the meso-level (districts and subdistricts). Owing to its dependence on context, and insufficient evidence, understanding “How” to improve multisectoral collaboration remains challenging. This study aims to elicit specific recommendations to strengthen meso-level stewardship in India for multisectoral collaboration. The findings from this study may offer lessons for other LMICs. Methods Using purposive, maximum variation sampling, the study team conducted semi-structured interviews with 20 diverse participants, including policymakers, implementers, development agency representatives, and academics experienced in multisectoral initiatives. The interviews delved into participants’ experiences, the current situation, enablers, and recommendations for enhancing stakeholder engagement and capacities at the meso-level for multisectoral collaboration. Results Context and power are critical elements to consider in fostering effective collaboration. Multisectoral collaboration was particularly successful in three distinct governance contexts: the social-democratic context as in Kerala, the social governance context in Chhattisgarh, and the public health governance context in Tamil Nadu. Adequate health system input and timely guidance instil confidence among local implementers to collaborate. While power plays a role through local leadership’s influence in setting agendas, convening stakeholders, and ensuring accountability. To nurture transformative local leaders for collaboration, holistic, equity-driven, community-informed approaches are essential. The study participants proposed several concrete steps: at the state level, establish “central management units” for supervising local implementers and ensuring bottom-up feedback; at the district level, rationalise committees and assign deliverables to stakeholders; and at the block level, expand convergence structures and involve local self-governments. Development partners can support data-driven priority setting, but local implementers with contextual familiarity should develop decentralised plans collaboratively, articulating rationales, activities, and resources. Finally, innovative training programs are required at all levels, fostering humility, motivation, equity awareness, leadership, problem- solving, and data use proficiency. Conclusion This study offers multiple solutions to enhance local implementers’ engagement in multisectoral efforts, advocating for the development, piloting, and evaluation of innovative approaches such as the block convergence model, locally-led collaboration efforts, and novel training methods for local implementers.

Objectives The present study aimed to examine the association of multimorbidity status with food insecurity among disadvantaged groups such as Scheduled Castes (SCs), Scheduled Tribes (STs), and Other Backward Class (OBCs) in India. Method The data for this study was derived from the first wave of the Longitudinal Ageing Study in India (LASI),2017–18, focusing on 46,953 individuals aged 45 years and over who belong to SCs, STs, and OBCs groups. Food insecurity was measured based on the set of five questions developed by the Food and Nutrition Technical Assistance Program (FANTA). Bivariate analysis was performed to examine the prevalence of food insecurity by multimorbidity status along with socio-demographic and health-related factors. Multivariable logistic regression analysis and interaction models were used. Results The overall prevalence of multimorbidity was about 16% of the study sample. The prevalence of food insecurity was higher among people with multimorbidity compared to those without multimorbidity. Unadjusted and adjusted models suggested that people with multimorbidity were more likely to be food insecure than people without multimorbidity. While middle-aged adults with multimorbidity and men with multimorbidity had a higher risk of food insecurity. Conclusion The findings of this study suggest an association between multimorbidity and food insecurity among socially disadvantaged people in India. Middle-aged adults experiencing food insecurity tend to reduce the quality of their diet and consume a few low-cost, nutritionally deficient meals to maintain caloric intake, putting them again at risk for several negative health outcomes. Therefore, strengthening disease management could reduce food insecurity in those facing multimorbidity.

Purpose Performance appraisal (PA) is one of the most indispensable human resource management practices as many critical decisions regarding employees’ performance are heavily based on the PA results as they are responsible for various attitude-related outcomes. This study aims to investigate the relationship between PA justice and affective commitment (AC) of employees in the Indian banking sector, and to examine the moderating effects of age and gender on this relationship. Design/methodology/approach A total of 298 employees from the banking sector were randomly selected to examine the relationship between PA justice and AC along with the moderating role of age and gender on this relationship through structural equation modelling using AMOS 21. Findings The findings of the study supported hypothesized relationships as PA justice significantly predicted the AC of bank employees in India. The moderating effects of age and gender on the relationship of PA justice and AC are found to be high for older employees and female employees, respectively. Research limitations/implications As the present study was cross-sectional, so any inferences regarding causality are limited. Theoretical and managerial implications have been discussed in the context of banking sector. Originality/value The paper contributes new insights to the existing literature by examining the moderating effects of age and gender on the relationship of PA justice and AC in the context of Indian banking sector.

The study aimed at isolation and screening of fungal amylase producer, optimization of solid state fermentation conditions for maximum amylase production by the best amylase producer, and characterization of the crude amylases, so produced. Aspergillus fumigatus NTCC1222 showed the highest amylase activity (164.1 U/mL) in secondary screening under SSF conditions and was selected for further studies. The test strain showed maximum amylase production (341.7 U/mL) and supernatant protein concentration (9.7 mg/mL) for incubation period (6 days), temperature (35°C), initial pH (6.0), nutrient salt solution as moistening agent, and beef extract as nitrogen source. Pomegranate peel produced maximum amylase activity, but wheat bran (only slightly lesser amylase activity as compared to that of pomegranate peel) was chosen for further studies, keeping in mind the seasonal availability of pomegranate peel. TLC confirmed the amylase produced to be α-type and 60 kDa was the molecular weight of the partially purified amylase. The enzyme showed maximum enzyme activity at pH 6.0, temperature of 55°C, and incubation time of 60 minutes. UV (616.0 U/mL) and chemical (814.2 U/mL) mutation enhanced amylase activity as compared to wild test strain. The study indicates that Aspergillus fumigatus NTCC1222 can be an important source of amylase and the crude enzyme, hence obtained, can be cost effectively applied in multiple sections of textile wet processing.

Amyloids are high-order proteinaceous formations deposited in both intra- and extracellular spaces. These aggregates have tendencies to deregulate cellular physiology in multiple ways; for example, altered metabolism, mitochondrial dysfunctions, immune modulation, etc. When amyloids are formed in brain tissues, the endpoint often is death of neurons. However, interesting but least understood is a close connection of amyloids with another set of conditions in which brain cells proliferate at an extraordinary rate and form tumor inside brain. Glioblastoma is one such condition. Increasing number of evidence indicate a possible link between amyloid formation and depositions in brain tumors. Several proteins associated with cell cycle regulation and apoptotic pathways themselves have shown to possess high tendencies to form amyloids. Tumor suppressor protein p53 is one prominent example that mutate, oligomerize and form amyloids leading to loss- or gain-of-functions and cause increased cell proliferation and malignancies. In this review article, we present available examples, genetic links and common pathways that indicate that possibly the two distantly placed pathways: amyloid formation and developing cancers in the brain have similarities and are mechanistically intertwined together.

The South Asian region, including India, faces an increased prevalence of illicit drug use. Key challenges include rising opioid use, injecting drug use and spread of stimulant use from some pockets to other regions of the country. Challenges faced are poor surveillance, lack of evidence-based and structured prevention programmes, wide treatment gaps and inadequate social capital for reintegration of substance users into society. The drug control efforts in India have resulted in an improved drug offence surveillance system, increased community awareness, a growing network of drug treatment centres and resource-building measures. India has made pioneering efforts in the field of harm reduction in the South Asian region. The steps taken have the potential of applicability across other South Asian, as well as most low- and middle-income, countries around the world.

Background District Residency Programme (DRP) was introduced by National Medical Commission as mandatory three-months training program for postgraduate residents. The program was for the first time implemented in April 2023 in Rajasthan. However, it ran into several teething problems, especially for residents. With a lack of any precedence, this study was planned to explore experiences and challenges of residents posted in DRP. Methods Cross-sectional study was conducted at 12 DRP sites attached to SMS Medical College, Jaipur between August-October 2023. A self-administered questionnaire was used to collect information from residents who had completed DRP. Questions were scored on a five-point Likert scale. Mann-Whitney U test and Kruskal-Wallis H test was used to show association. Results Only around 17% residents felt that the learning objectives of DRP were fulfilled and nearly 60% residents felt isolated from academic activities and parent department. Over half of the residents were never posted with their concerned specialty services. Around four-fifth residents felt concerned about safety at least sometimes and more than three-fourth residents were dissatisfied with basic amenities. Kruskal-Wallis and Mann-Whitney tests showed significant association of gender and specialisation strata with multiple outcome variables. Conclusion The study finds high degree of dissatisfaction among residents towards learning objectives, academic learning, and basic amenities during DRP. There was also a clear lack of specialty-exposure and high concerns of safety, especially for female residents. The study findings should alarm and inform policymakers and administrators to improve DRP implementation so as to better achieve laid objectives.