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A significant increase in the incidence of fungal infections and drug resistance has been observed in the past decades due to limited availability of broad-spectrum antifungal drugs. Nanomedicines have shown significant antimicrobial potential against various drug-resistant microbes. Silver nanoparticles (AgNps) are known for their antimicrobial properties and lower host toxicity; however, for clinical applications, evaluation of their impact at cellular and molecular levels is essential. The present study aims to understand the cellular and molecular mechanisms of AgNp-induced toxicity in a common fungal pathogen, . AgNps were synthesized by chemical reduction method and characterized using UV-visible spectroscopy, X-ray powder diffraction, transmission electron microscopy, scanning electron microscopy-energy dispersive X-ray spectroscopy, energy dispersive X-ray fluorescence, and zeta potential. The anti- activity of AgNps was assessed by broth microdilution and spot assays. Effects of AgNps on cellular and molecular targets were assessed by monitoring the intracellular reactive oxygen species (ROS) production in the absence and presence of natural antioxidant, changes in surface morphology, cellular ultrastructure, membrane microenvironment, membrane fluidity, membrane ergosterol, and fatty acids. Spherical AgNps (10-30 nm) showed minimum inhibitory concentration (minimum concentration required to inhibit the growth of 90% of organisms) at 40 μg/mL. Our results demonstrated that AgNps induced dose-dependent intracellular ROS which exerted antifungal effects; however, even scavenging ROS by antioxidant could not offer protection from AgNp mediated killing. Treatment with AgNps altered surface morphology, cellular ultrastructure, membrane microenvironment, membrane fluidity, ergosterol content, and fatty acid composition, especially oleic acid. To summarize, AgNps affected multiple cellular targets crucial for drug resistance and pathogenicity in the fungal cells. The study revealed new cellular targets of AgNps which include fatty acids like oleic acid, vital for hyphal morphogenesis (a pathogenic trait of ). Yeast to hypha transition being pivotal for virulence and biofilm formation, targeting virulence might emerge as a new paradigm for developing nano silver-based therapy for clinical applications in fungal therapeutics.

Abstract Chemotherapy-induced nausea and vomiting (CINV) is a significant contributor to the treatment morbidity experienced by patients with cancer. With effective prophylactic anti-emetics given prior to administration of moderately or highly emetogenic chemotherapy (MEC or HEC) it is expected that 70-80% of patients will have no CINV. Fosaprepitant is an intravenous prodrug of aprepitant that acts as an anti-emetic by blocking the neurokinin (NK-1) receptor. Fosaprepitant in combination with dexamethasone and 5-HT3 antagonist like ondansetron has been shown to be effective in preventing CINV in patients receiving MEC or HEC. The current review discusses the pharmacology and clinical indications for the use of fosaprepitant. The evidence for the effectiveness of fosaprepitant in the prevention of CINV and the commonly observed adverse events with its administration is discussed in this review.

This case report documents an extremely rare presentation of primary uterine yolk sac tumour (YST) in a premenopausal woman in her late 40s, who presented with heavy menstrual bleeding. Imaging was suggestive of a uterine tumour with rising serum germ cell markers. In the absence of preoperative histology, a surgical staging was performed, confirming pathological diagnosis and immunohistochemistry (SALL4 and alpha-fetoprotein (AFP) positive). She received adjuvant chemotherapy as per protocol. With a short disease-free interval, she had a rise in serum AFP with recurrence in the lungs, which was successfully treated with second-line chemotherapy. This case uniquely highlights the importance of comprehensive tumour marker assessment, the role of marker-guided surveillance in early relapse detection, and demonstrates the feasibility of successful salvage therapy. The case expands current knowledge of extragonadal YST management, encourages vigilance for atypical presentations and underscores the value of individualised multimodality care—even in aggressive, relapsed disease—for achieving complete remission.

Background In the west, survival following treatment of childhood acute lymphoblastic leukaemia (ALL) approaches 90%. Outcomes in India do not exceed 70%. To address this disparity, the Indian Collaborative Childhood Leukaemia group (ICiCLe) developed in 2013 a contemporary treatment protocol for uniform risk-stratified management of first presentation ALL based on cytogenetics and minimal residual disease levels (MRD). A multicentre randomised clinical trial opened in 2016 (ICiCLe-ALL-14) and examines the benefit of randomised interventions to decrease toxicity and improve outcomes. Methods Patients 1–18 years with newly diagnosed ALL are categorised into four risk groups based on presentation features, tumour genetics and treatment response. Standard risk includes young (< 10 years) B cell precursor ALL (BCP-ALL) patients with low presentation leucocyte count (< 50 × 10 9 /L) and no high-risk features. Intermediate risk includes BCP-ALL patients with no high-risk features but are older and have high presentation leucocyte counts and/or bulky disease. High risk includes BCP-ALL patients with any high-risk feature, including high-risk genetics, central nervous system leukaemia, poor prednisolone response at treatment day 8 and high MRD (≥ 0·01%) at the end of induction. Patients with T-lineage ALL constitute the fourth risk group. All patients receive four intensive treatment blocks (induction, consolidation, interim maintenance, delayed intensification) followed by 96 weeks of maintenance. Treatment intensity varies by risk group. Clinical data management is based on a web-based remote data capture system. The first randomisation examines the toxicity impact of a shorter induction schedule of prednisolone (3 vs 5 weeks) in young non-high-risk BCP-ALL. The second randomisation examines the survival benefit of substituting doxorubicin with mitoxantrone in delayed intensification for all patients. Primary outcome measures include event-free survival (overall, by risk groups), sepsis rates in induction (first randomisation) and event-free survival rates following second randomisation. Discussion ICiCLe-ALL-14 is the first multicentre randomised childhood cancer clinical trial in India. The pre-trial phase allowed standardisation of risk-stratification diagnostics and established the feasibility of collaborative practice, uniform treatment, patient enrolment and data capture. Pre-trial observations confirm the impact of risk-stratified therapy in reducing treatment-related deaths and costs. Uniform practice across centres allows patients to access care locally, potentially decreasing financial hardship and dislocation. Trial registration Clinical Trials Registry-India (CTRI) CTRI/2015/12/006434 . Registered on 11 December 2015

Silver nanoparticles (AgNps) have attracted maximal attention among all metal nanoparticles, and the study of their biological properties has gained impetus for further medical adoption. This study evaluated the cellular and molecular mechanisms associated with the action of AgNps against an opportunistic pathogen, . Spherical, stable AgNp (average size 21.6 nm) prepared by a chemical reduction method showed minimum inhibitory concentration (required to inhibit the growth of 90% of organisms) at 40 μg/mL. AgNps have been reported to induce oxidative stress-mediated programmed cell death through the accumulation of intracellular reactive oxygen species (ROS). However, this study demonstrated that intracellular levels of AgNp-induced ROS could be reversed by using antioxidant ascorbic acid, but the sensitivity of AgNp-treated cells could not be completely reversed. Moreover, in addition to the generation of ROS, the AgNps were found to affect other cellular targets resulting in altered membrane fluidity, membrane microenvironment, ergosterol content, cellular morphology, and ultrastructure. Thus, the generation of ROS does not seem to be the sole major cause of AgNp-mediated cell toxicity in . Rather, the multitargeted action of AgNps, generation of ROS, alterations in ergosterol content, and membrane fluidity together seem to have potentiated anti- action. Thus, this \"nano-based drug therapy\" is likely to favor broad-spectrum activity, multiple cellular targets, and minimum host toxicity. AgNps, therefore, appear to have the potential to address the challenges in multidrug resistance and fungal therapeutics.

Purpose Incidence of breast cancer (BC), particularly in young women, are rising in India. Without population-based mammography screening, rising rates cannot be attributed to screening. Investigations are needed to understand the potential drivers of this trend. Methods An international team of experts convened to discuss the trends, environmental exposures, and clinical implications associated with BC in India and outlined recommendations for its management. Results Panels were structured across three major BC themes ( n  = 10 presentations). The symposium concluded with a semi-structured Think Tank designed to elicit short-term and long-term goals that could address the challenges of BC in India. Conclusion There was consensus that the prevalence of late-stage BC and the high BC mortality rates are associated with the practice of detection, which is primarily through clinical and self-breast exams, as opposed to mammography. Triple-Negative BC (TNBC) was extensively discussed, including TNBC etiology and potential risk factors, the limited treatment options, and if reported TNBC rates are supported by rigorous scientific evidence. The Think Tank session yielded long-term and short-term goals to further BC reduction in India and included more regional etiological studies on environmental exposures using existing India-based cohorts and case–control studies, standardization for molecular subtyping of BC cases, and improving the public’s awareness of breast health.

Sex disparity and its determinants in childhood cancer in India remain unexplored, with scarce information available through summary statistics of cancer registries. This study analysed the degree of sex bias in childhood cancer in India and its clinical and demographical associations. In this retrospective, multicentre cohort study, we collected individual data of children (aged 0–19 years) with cancer extracted from the hospital-based records of three cancer centres in India between Jan 1, 2005, and Dec 31, 2019, and two population-based cancer registries (PBCRs; Delhi [between Jan 1, 2005, and Dec 31, 2014] and Madras Metropolitan Tumour Registry [between Jan 1, 2005, and Dec 31, 2017]). We extracted data on age, sex, and confirmed diagnosis of malignancy (according to the International Classification of Diseases-10 coding),and excluded participants if they were without a recorded diagnosis, had a benign diagnosis, had missing sex information, resided outside of India, or were a donor for haematopoietic stem cell transplantation (HSCT). The primary outcome was the male-to-female incidence rate ratio (MF-IRR) in the two PBCRs and the male-to-female ratios (MFR) from the hospital-based and the HSCT data. For PBCR data, MF-IRR was estimated by dividing the MFR by the total population at risk. MFR was analysed for patients seeking treatment at the cancer centres and for those undergoing HSCT. Logistic regression analyses were done to explore the association of clinical and demographical variables with sex of the patients seeking treatment and those undergoing HSCT in hospital-based data and multivariable analyses were done to determine independent sociodemographic predictors of sex bias. Annual time trends of MFR and MF-IRR during the 15-year study period were ascertained by time series regression analyses. We included 11 375 children from PBCRs in the study. 26 891 children from hospital-based records were screened, and data from 22 893 (85·1%) were included (including 514 who underwent HSCT). Residence details were missing for 257 (1·1%) of 22 893 patients from hospital-based records. The crude MFR of children at diagnosis was in favour of boys: 2·00 (95% CI 1·92–2·09) in the Delhi PBCR and 1·44 (1·32–1·57) in Madras Metropolitan Tumour Registry. The MF-IRRs for cancer diagnosis were also skewed in favour of boys in both PBCRs (Delhi 1·69 [95% CI 1·61–1·76]; Madras Metropolitan Tumour Registry 1·37 [1·26–1·49]). The MFR for children seeking treatment from hospital-based records was 2·06 (95% CI 2·00–2·12) in favour of boys. In subgroup analyses, the proportion of boys seeking treatment was higher in northern India than southern India (p<0·0001); in private centres than in centres providing subsidised treatment (p<0·0001); in patients with haematological malignancies than those with solid malignancies (p<0·0001); in those residing 100 km or further from the hospital than those within 100 km of a hospital (p<0·0001); and those living in rural areas than those living in urban areas (p=0·0006). The MFR of 514 children who underwent HSCT was 2·81 (95% CI 2·32–3·43) in favour of boys. Time trend analysis showed that MFR did not show any significant annual change in either the overall cohort or in any of the individual centres for hospital-based data; however, the analysis did show a declining MF-IRR in the Delhi PBCR from 2005 to 2014 (p=0·031). The sex ratio for childhood cancer in India has a bias towards boys at the level of diagnosis, which is more pronounced in northern India and in situations demanding greater financial commitment. Addressing societal sex bias and enhancing affordable health care for girls should be pursued simultaneously in India. None. For the Hindi translation of the abstract see Supplementary Materials section.

Immuno-PCR (I-PCR), an ultrasensitive method, combines the versatility of ELISA with the exponential amplification capacity of PCR. Coupling of detection antibodies with the reporter DNA is a critical step of I-PCR. Gold nanoparticles (GNPs) and magnetic beads (MBs) are relatively easy to attach with the antibodies and DNA. Therefore, we designed MB-coupled GNP-based I-PCR (MB-GNP-I-PCR) assay for the detection of antigen. GNPs were synthesized by chemical reduction and seed-mediated synthesis. Functionalized GNPs were prepared by coupling GNPs with the detection antibodies and reporter DNA and were characterized. Detection limit of -specific purified early secreted antigenic target-6 (ESAT-6) (Rv3875) was determined by MB-GNP-I-PCR. Transmission electron microscopy revealed spherical and slightly polydispersed GNPs of ~20 and ~60 nm size. Coupling of antibodies to GNPs was indicated by a shift in absorption maxima from 524 to 534 nm, which was confirmed by transmission electron microscopy. A color reaction with ELISA and the presence of 76 bp product by PCR further validated the coupling of detection antibodies and signal DNA to the functionalized GNPs. Also, attachment of capture antibodies with MBs was confirmed by magneto-ELISA. Detection limit of purified ESAT-6 by MB-GNP-I-PCR was determined to be 10 fg/mL, 10 -fold lower than analogous ELISA. Notably, no sample matrix effect was observed in the saliva samples of healthy individuals spiked with the purified ESAT-6. Unlike conventional I-PCR (solid format), MB-GNP-I-PCR (liquid format) is relatively simple with the reduced background signals, which can be further exploited for the clinical diagnosis of tuberculosis.

IntroductionPaediatric cancer survivorship is an emerging priority in the current global health agenda. The models of long-term follow-up (LTFU) in Asia may vary widely based on differences in healthcare systems and resources. This study aims to characterise the models of care and current resources available for paediatric cancer survivors in Asian countries.MethodsThis multinational, cross-sectional study conducted from February to May 2024 recruited clinicians practising in an institution/centre in the United Nations geoscheme, using a combination of purposive and snowball sampling. They were identified through the 18th St Jude-Viva Forum in Singapore and local professional societies. Each invited institution nominated a representative to complete a structured questionnaire focusing on the institution’s characteristics of LTFU care, the availability of risk-based screening tests according to the Children’s Oncology Long-term Follow-up Guideline and the availability of recommended services in an LTFU programme.ResultsThe survey included participants representing 87 paediatric oncology units/institutions from 28 Asian countries/regions (response rate 68%). Out of the 87 units/institutions, the majority of institutions provided LTFU care through specialised LTFU clinics (44%) or oncologist-led clinics (45%). Significantly more institutions with specialised LTFU clinics offered assessments by multidisciplinary professionals, for example, motor (74% vs 44%, p=0.008) and speech/language (66% vs 36%, p=0.008) assessments, than those adopting other models of care. Institutions with LTFU clinics were more likely to provide health risk counselling (p=0.045), fertility preservation (p=0.018), pain clinics (p=0.008) and nutrition programmes (p=0.018). Institutions adhering to a specific LTFU guideline were more likely to provide comprehensive visual assessment (p=0.012) and health risk counselling (p<0.001). There were no differences between the economies in providing basic late-effects screening tests.ConclusionOur findings demonstrated that establishing an LTFU clinic according to evidence-based guidelines can facilitate more comprehensive late-effects screening and support for survivors. Regional collaborations should aim to develop resources-stratified recommendations and policies for coordinated and integrated LTFU care in Asian countries.

Background The loss of a child is the most devastating type of bereavement. Despite higher childhood mortality, there is a critical gap in bereavement research within low- and middle-income countries (LMICs). Hence there is a pressing need to develop a culturally and emotionally relevant need assessment tool for bereaved caregivers of children with cancer. Considering that bereaved caregivers and patient advocates hold immense context specific experiential knowledge, it is essential to integrate them while creating such a tool to ensure that the tool reflects real-world challenges, cultural sensitivities, and the psychosocial dimensions of grief in the Indian context. The aim of this study is to develop a culturally relevant bereavement needs assessment tool for caregivers of children with cancer in India, with active involvement of bereaved caregivers and patient advocates. Methods The tool was developed at a tertiary cancer center in south India through a four-phase iterative process involving multidisciplinary professionals, patient advocates, bereaved caregivers (predominantly parents) and public representatives: (1) Brainstorming and item generation, (2) Content validation, (3) Face validation, and (4) Translation. The questionnaire was shared, reviewed, and refined digitally during the development phase. This was part of a larger project to develop a bereavement support program for bereaved caregivers. Results A 26 item pool was refined to 15-item semi-quantitative tool, CANCOPE-PI ( Culture-specific Assessment of Needs in Caregivers Of Pediatric patients who have Expired due to cancer , co-developed with Public Involvement ) covering domains such as basic information, emotional care and mental health support, changes in relationships, daily life and functioning, coping techniques, support group, peer support, connecting with hospital, and remembrance practices through collaborative input from public contributors and subject experts. The tool was translated into Tamil by voluntary members of the public who were proficient in both English and Tamil, using standard forward–backward translation procedures. Conclusions The CANCOPE-PI tool was developed, refined and translated through a participatory approach across all phases. The tool, which truly reflects the voices and experiences of caregivers of children with cancer in India, offers a culturally appropriate aid to assess their bereavement needs, and holds promise for guiding structured psychosocial interventions in pediatric palliative care and enhancing support for grieving families. Plain English summary Losing a child to cancer is one of the most devastating experiences a family can go through. In India, bereavement support services for such families are limited, informal, often not designed with cultural or emotional sensitivity. As a result, the needs of caregivers after their child’s death are poorly understood, and health services have little guidance on how to support them. This study aimed to create a simple and culturally relevant tool to understand what caregivers need during their grief journey. Hence, to achieve this, we worked with caregivers and patient advocates, to partner with us as co-researchers and co-designers of the tool, rather than just be survey respondents. They reviewed every stage of the questionnaire, shared their lived experiences, and suggested meaningful changes based on what real families go through after the death of a child. The result is CANCOPE-PI , a 15-item questionnaire that explores different areas of need, such as emotional support, practical help, sibling support, cultural and spiritual needs, communication with healthcare teams, and preferred types and timing of bereavement support. The tool was shared digitally to make it easy to complete and analyse. Feedback from them played a significant role, in refining the questions to ensure sensitivity and relevance, by reflecting their real-life experiences rather than assumptions. We hope that the CANCOPE-PI tool will help hospitals, palliative care teams, and organisations identify gaps in bereavement services and design better, compassionate, culturally appropriate support for families across India.