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Background & objectives: Malaria remains a complex challenge in India due to its diverse epidemiology, multi-ethnic population, and multiplicity of malaria vectors. While progress has been made in reducing malaria nationally, persistent pockets hinder elimination efforts. These challenges include hidden reservoirs, inadequate healthcare, suboptimal surveillance, non-compliance, and subclinical infections. Shortage of grassroot level and primary care health staff, transportation issues and general inaccessibility and unavailability of healthcare services are additional challenges. Methods: Mobile healthcare vans have been tried and found useful in enhancing healthcare availability in several health conditions in different settings. Nuh district in Haryana, India is a malaria endemic region; it is indeed one of the districts included by India’s NITI Aayog in the Aspirational Districts Programme, a government initiative that focuses on rapidly transforming and developing the most underdeveloped districts in country. With an aim to improve the healthcare seeking behavior of malaria-endemic community of selected villages of Nuh district, we carried out a study using interventions in two villages of the district, that had mobile malaria clinics and toll-free telephone services in enhancing healthcare access. Results: We found that Sangel village had higher literacy rates (60.6%) as compared to 39.4% in Naushera. Similarly, the unemployment rate was higher for Naushera. It the mobile malaria clinic was deployed from December 2019 to July 2020 and a total of 269 phone calls were received from both the villages. A similar number of rapid tests and microscopy smears were examined and all were negative for malaria. The febrile patients were referred to the nearest healthcare facility. Interpretation & conclusion: The study shows that the community is open to using these healthcare interventions. These initiatives of mobile malaria clinics and toll-free telephone services can bridge healthcare gaps, especially in malaria-endemic regions, aligning with India’s malaria elimination and equitable healthcare access goals.

Abstract Lung cancer is a severe challenge to the health care system with intrinsic resistance to first and second-line chemo/radiotherapies. In view of the sterile environment of lung cancer, several immunotherapeutic drugs including nivolumab, pembrolizumab, atezolizumab, and durvalumab are currently being used in clinics globally with the intention of releasing exhausted T-cells back against refractory tumor cells. Immunotherapies have a limited response rate and may cause immune-related adverse events (irAEs) in some patients. Hence, a deeper understanding of regulating immune checkpoint interactions could significantly enhance lung cancer treatments. In this review, we explore the role of miRNAs in modulating immunogenic responses against tumors. We discuss various aspects of how manipulating these checkpoints can bias the immune system’s response against lung cancer. Specifically, we examine how altering the miRNA profile can impact the activity of various immune checkpoint inhibitors, focusing on the PD-1/PD-L1 pathway within the complex landscape of lung cancer. We believe that a clear understanding of the host’s miRNA profile can influence the efficacy of checkpoint inhibitors and significantly contribute to existing immunotherapies for lung cancer patients. Additionally, we discuss ongoing clinical trials involving immunotherapeutic drugs, both as standalone treatments and in combination with other therapies, intending to advance the development of immunotherapy for lung cancer.

Introduction: With the rising use of medications, Adverse Drug Reactions (ADRs) have emerged as a significant public health issue. Therefore, establishing a robust pharmacovigilance system across the nation has become imperative. The present study focussed to analyse the trends and frequency of ADRs to enhance the safety of drug prescriptions and ensure public health protection. Aim: To assess the pattern of adverse effects, drugs implicated, causality, severity, and outcomes of ADRs reported to the ADR monitoring centre in the Department of Pharmacology, Government TD Medical College, Alappuzha, Kerala, India. Materials and Methods: This was a cross-sectional study in which 262 ADRs reported to the Department of Pharmacology, Government TD Medical College, Alappuzha, Kerala, India from May 2022 to April 2023 were analysed for patient demographics, drug and ADR characteristics, and the outcomes of the ADR. Causality and severity assessments of these ADRs were performed using the World Health Organisation (WHO)-Uppsala Monitoring Centre (UMC) scale and the modified Hartwig and Siegel’s scale, respectively. Data were tabulated using Microsoft Excel and expressed as mean, standard deviation, frequency, and percentage as appropriate, with the help of descriptive statistics using Epi Info 7 software. Results: A total of 262 ADRs were analysed. The mean age of the patients was 47.4±20.1 years. The majority were females 160 (61.1%). The intravenous route was the most common route involved in ADRs 158 (59.8%), followed by the oral route 91 (34.5%). Skin reactions accounted for more than half of the ADRs 151 (53.2%), followed by blood dyscrasias 48 (16.9%). Antibiotics were the most common group of implicated drugs 124 (44.9%), followed by anticancer drugs 43 (15.6%) and antitubercular drugs 34 (12.3%). Among antibiotics, cephalosporins (36.3%) were the most frequently encountered, followed by penicillins (30.6%). A total of 148 patients (56.5%) had recovered by the day of reporting, 146 (55.7%) ADRs were found to be ‘possible’ using the WHO-UMC causality scale, and 144 (54.9%) ADRs were classified as moderate severity. Conclusion: The study identified a widespread occurrence of ADRs, some of which increased healthcare costs due to prolonged hospital stays. The high incidence of ADRs from antimicrobials is concerning, as it contributes to antimicrobial resistance. This underscores the urgent need for prudent antimicrobial usage. The present study emphasises the importance of ADR reporting among healthcare workers and the necessity for hospitals to establish ADR reporting strategies for optimal patient care.

Introduction: Prescription patterns significantly impact healthcare quality and patient outcomes. Evaluating these patterns using World Health Organisation (WHO) indicators helps identify areas for improvement and ensures rational drug use. The present study was conducted to evaluate prescription patterns via WHO indicators, aiming to uncover insights, identify discrepancies and enhance prescription quality within the institute for improved healthcare outcomes. Aim: To evaluate drug prescription patterns using WHO prescription indicators in the prescriptions of outdoor patients at a tertiary care teaching hospital in Chhattisgarh, India. Materials and Methods: A cross-sectional study was conducted in the Department of Pharmacology at Department of Pharmacology, Pt. J.N.M. Medical College, Raipur, Chhattisgarh, India, from July 15, 2023, to October 15, 2023 (a duration of 3 months), involving 1,000 outpatient prescriptions at Dr. Bhimrao Ambedkar Memorial Hospital (BRAM), Raipur, Chhattisgarh. Ethical clearance was obtained from the Institutional Ethics Committee (IEC) (No./MCI/Ethics/2023/45 Raipur, dated 12/07/2023). Data were collected using a digital form and analysed statistically. Parameters evaluated included the average number of medicines per prescription, the percentage of drugs prescribed by generic name, the percentage of prescriptions containing antibiotics, the percentage of prescriptions containing injections, and the percentage of drugs prescribed from the Essential Drug List (EDL). Descriptive statistics were used to summarise the data, and analysis was performed using Microsoft (MS) Excel 2021. Results: The present study included 1,000 prescriptions. A total of 4,320 medicines were prescribed across these prescriptions, with 2,853 (66.04%) prescribed by their generic name. Injections accounted for 483 (11.18%) prescriptions, while antibiotics were included in 663 (15.34%) prescriptions. Additionally, 2,973 (68.81%) medicines were prescribed from the EDL. The average number of medicines prescribed per prescription was 4.3. Conclusion: The study revealed that while certain aspects of prescription practices aligned with WHO indicators, notable discrepancies persisted. The percentage of antibiotics prescribed per prescription was in accordance with WHO guidelines. Strategic measures are needed to enhance prescription practices and align them more closely with WHO guidelines.

ABSTRACT Purpose: To compare transperineal (TP) vs transrectal (TR) magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) fusion-guided prostate biopsy (PBx) in a large, ethnically diverse and multiracial cohort. Materials and Methods: Consecutive patients who underwent multiparametric (mp) MRI followed by TP or TR TRUS-fusion guided PBx, were identified from a prospective database (IRB #HS-13-00663). All patients underwent mpMRI followed by 12-14 core systematic PBx. A minimum of two additional target-biopsy cores were taken per PIRADS≥3 lesion. The endpoint was the detection of clinically significant prostate cancer (CSPCa; Grade Group, GG≥2). Statistical significance was defined as p

To evaluate the clinicopathological profiles of patients presenting with testicular lymphomas. In our study from February 2020 to August 2023, 6 rare cases of testicular non hodgkin’s lymphomas were diagnosed in a three and a half year period and were divided based on primary or secondary involvement. Immunohistochemistry (IHC) was performed on all cases and results were compared based on clinicopathological profile. The mean age was 57 years. Most common presenting complaint was unilateral or bilateral testicular swelling, associated with pain in some cases. B symptoms were present only in one case. Out of 6 cases, 3 showed primary involvement and 3 were secondarily involved. On applying IHC, 3 cases were diagnosed as Diffuse Large B-Cell Lymphoma (DLBCL), Non-Germinal Centre subtype and 3 as DLBCL, Germinal Centre subtype.Testicular lymphomas are rare highly malignant tumors and pose a strong diagnostic difficulty for both clinician and pathologist. Hence, clinical suspicion should always be maintained in cases of testicular swelling for proper workup of the patient. Keywords: Testicular lymphoma, Diffuse large B-cell lymphoma, Testis, Extranodal

Abstract Background Protein biomarkers have been broadly investigated in cerebrospinal fluid and blood for the detection of neurodegenerative diseases, yet a clinically useful diagnostic test to detect early, pre-symptomatic Alzheimer’s disease (AD) remains elusive. We conducted this study to quantify Aβ40, Aβ42, total Tau (t-Tau), hyperphosphorylated Tau (ptau181), glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) in eye fluids relative to blood. Methods In this cross-sectional study we collected vitreous humor, aqueous humor, tear fluid and plasma in patients undergoing surgery for eye disease. All six biomarkers were quantitatively measured by digital immunoassay. Spearman and Bland–Altman correlation analyses were performed to assess the agreement of levels between ocular fluids and plasma. Results Seventy-nine adults underwent pars-plana vitrectomy in at least one eye. Of the 79, there were 77 vitreous, 67 blood, 56 tear fluid, and 51 aqueous samples. All six biomarkers were quantified in each bio-sample, except GFAP and NfL in tear fluid due to low sample volume. All six biomarkers were elevated in vitreous humor compared to plasma samples. T-Tau, ptau181, GFAP and NfL were higher in aqueous than in plasma, and t-Tau and ptau181 concentrations were higher in tear fluid than in plasma. Significant correlations were found between Aβ40 in plasma and tears (r = 0.5; p = 0.019), t-Tau in plasma and vitreous (r = 0.4; p = 0.004), NfL in plasma and vitreous (r = 0.3; p = 0.006) and plasma and aqueous (r = 0.5; p = 0.004). No significant associations were found for Aβ42, ptau181 and GFAP among ocular fluids relative to plasma. Bland–Altman analysis showed aqueous humor had the closest agreement to plasma across all biomarkers. Biomarker levels in ocular fluids revealed statistically significant associations between vitreous and aqueous for t-Tau (r = 0.5; p = 0.001), GFAP (r = 0.6; p

Abstract This research addresses the scalable and inexpensive synthesis of α-Fe2O3via hydrothermal method without any precipitating agent as well as the enhancement of solar driven photocatalytic and H2 production through doping different chromium proportions. Competency of α-Fe2O3, both pure and doped with chromium, to function as photocatalyst was evaluated by its interaction with multiple dyes, which was real-time monitored utilizing (Internet of Things) IoT technique. By adding chromium, the rate of deterioration increased substantially from 15 to 94% for TB under sunlight in a remarkably brief 20 min by employing a very small amount of Cr0.8Fe1.2O3 (0.3 g/L), as evidenced by high degree of mineralization i.e. 85% and LC-HRMS. Also, the rapid breakdown of Trypan Blue (TB) was indicated by BOD5/COD ratio. Moreover, Cr-doped α-Fe2O3 displays excellent H2 production (~ 132 μmol h−1 g−1) as compared to α-Fe2O3. This work highlights the potential utilization of Cr-doped α-Fe2O3 for the purification of industrial waste water and green energy harvesting.

Abstract Pigeonpea (Cajanus cajan L.) is a nutritious crop with antioxidant potential, making it valuable for health supplements and medicinal products. Pigeonpea seed coat possess a rich source of antioxidant properties, particularly in dark colour seed coat varieties. Recently, antioxidant-based drugs for the prevention and treatment of complex diseases have evoked a great deal of research interest in natural antioxidants. We resolved genomic regions by conducted a genome-wide association study (GWAS) using a high-throughput 62 K SNP “CcSNPnks” genic chip to identify SNP markers associated with antioxidant properties in 287 diverse panel of pigeonpea genotypes. Evaluated their antioxidant activity using a spectrophotometric technique based on ferric ion-reducing antioxidant potential (FRAP) and calculated the gallic acid equivalents (GAE) per 100 g of extract. Significant differences in antioxidant activities were found among genotypes, ranging from 3.27 mg in ICPL-13271 to 16.85 mg in UP 9-I for ferric iron-reducing activity. The GWAS identified four distinct marker trait association (MTA) that exhibit a strong correlation with antioxidant properties. We identified significant marker trait associations with chr 2 (AX-165372487), chr 6 (AX-165348296) code for RGA1 protein, chr 10 (AX-165367685) codes for alkaline ceramidase (transcript variant), and chr 11 (AX-165411944) codes for (DL)-glycerol-3-phosphatase 2. The identified protein, RGA1, is involved in reducing ROS accumulation in response to stress by up-regulating the transcription of superoxide dismutases. It suppresses GA-induced vegetative growth and floral initiation. Rapidly degraded in response to GA and involved in fruit and flower development. Furthermore, the population structure analysis identified four distinct sub-populations with admixture types, effectively grouping all genotypes based on their ancestry. Our findings advance the understanding of the genetic underpinning antioxidant concentrations, holding potential for applications in crop breeding and aligning with consumer preferences. This study provides a cornerstone for future research into exploiting marker-assisted breeding to produce pigeonpea cultivars.

Ulcerative Colitis (UC) is a chronic Inflammatory Bowel Disease (IBD) that affects the inner lining of the colon, imposing a significant burden on healthcare systems worldwide. Symptoms include bloody stools and abdominal pain. The prevalence of UC is increasing, particularly among young adults. The pathogenesis involves immune responses, genetics and environmental factors. Diagnostic delays are common, leading to complications and increased costs. Early diagnosis is crucial for preventing complications. Endoscopy is the primary diagnostic tool. Treatment aims to reduce inflammation and achieve remission. Delayed diagnosis can lead to long-term complications such as Colorectal Cancer (CRC) and bowel stenosis. Prompt recognition and management are essential for minimising the disease burden and optimising care. The present study delves into the complex nature of UC, a chronic IBD, revealing its epidemiology, pathogenesis, diagnostic challenges, treatment strategies, prognosis, complications and the impact of delayed diagnosis on patients’ quality of life. The study highlights the evolving understanding of UC pathogenesis, incorporating immune responses, genetics, environmental factors and biomarkers. It also discusses diagnostic delays due to symptom similarities and the need for increased awareness among healthcare providers and the public. The study also discusses advanced diagnostic methods and therapeutic approaches, including novel drug targets and surgical interventions. It also highlights the negative consequences of delayed diagnosis, including increased morbidity, psychological distress and socioeconomic burden. The study emphasises the need for collaborative efforts to ensure timely and appropriate care for UC patients.

Abstract Background Oral cancer poses a significant health challenge due to limited treatment protocols and therapeutic targets. We aimed to investigate the invasive margins of gingivo-buccal oral squamous cell carcinoma (GB-OSCC) tumors in terms of the localization of genes and cell types within the margins at various distances that could lead to nodal metastasis. Methods We collected tumor tissues from 23 resected GB-OSCC samples for gene expression profiling using digital spatial transcriptomics. We monitored differential gene expression at varying distances between the tumor and its microenvironvent (TME), and performed a deconvulation study and immunohistochemistry to identify the cells and genes regulating the TME. Results We found that the tumor–stromal interface (a distance up to 200 µm between tumor and immune cells) is the most active region for disease progression in GB-OSCC. The most differentially expressed apex genes, such as FN1 and COL5A1, were located at the stromal ends of the margins, and together with enrichment of the extracellular matrix (ECM) and an immune-suppressed microenvironment, were associated with lymph node metastasis. Intermediate fibroblasts, myocytes, and neutrophils were enriched at the tumor ends, while cancer-associated fibroblasts (CAFs) were enriched at the stromal ends. The intermediate fibroblasts transformed into CAFs and relocated to the adjacent stromal ends where they participated in FN1-mediated ECM modulation. Conclusion We have generated a functional organization of the tumor–stromal interface in GB-OSCC and identified spatially located genes that contribute to nodal metastasis and disease progression. Our dataset might now be mined to discover suitable molecular targets in oral cancer.

The clinical manifestation of leishmaniasis has historically been determined by the Leishmania species involved. However, recent emergence of novel Leishmania lineages has caused atypical pathologies. We isolated and characterized 2 new Leishmania donovani parasites causing cutaneous leishmaniasis in Himachal Pradesh, India.

Purpose: Untreated stress, anxiety, and depression during the perinatal period can lead to adverse maternal and infant outcomes. Yoga, the practice of body–mind–spirit techniques has been shown to reduce stress, anxiety, and depression. Aims: The aim of the study was to examine the feasibility and limited efficacy of the 4-week practice of pregnancy tele-yoga module (PTYM) delivered and monitored through an online platform. Methodology: A multicentric, open-label, exploratory study was conducted in the antenatal clinics (ANCs) of three tertiary care hospitals in India. Pregnant women between 13 and 32 weeks of gestation were invited to participate. PTYM was taught by the trained research staff. A YouTube link demonstrating the PTYM developed by the researchers was shared with consenting participants. Using the Yoga Performance Assessment (YPA), research staff monitored the online performance of the PTYM. Pre- and postintervention, women were assessed using the Depression, Anxiety, and Stress Scale-21 (DASS-21). Results: Preintervention, among 162 consented pregnant women, anxiety (62.34%) was the most common mental health condition, followed by stress (55.55%) and depression (45.67%). YPA at the end of week 1, week 2, week 3, and week 4 was 19.45, 21.35, 24.15, and 28.45, respectively. Postintervention anxiety, stress, and depression persisted in 19.78%, 11.44%, and 10.41% of women. Pregnant women with stress (DASS-21 ≥15; n = 90), anxiety (DASS-21 ≥8; n = 101), and depressive (DASS-21 ≥10; n = 74) symptoms after undergoing 4 weeks of PTYM reported significant reduction in the scores. Conclusion: The current study demonstrated the feasibility and limited efficacy of PTYM in ANCs of a tertiary care hospital in India.

Background: Pemphigus is a potentially life-threatening autoimmune blistering disease which characteristically affects skin and mucosae. Pulse therapy for the treatment of pemphigus has been in vogue for several years and considered better than conventional corticosteroids. Aims and objectives: This study was conducted to evaluate the efficacy and safety of pulse therapy in pemphigus patients treated over a period of 10 years. Materials and Methods: This retrospective study was based on medical records of Pemphigus patients treated at Department of Dermatology from January 2008 to December 2017. Diagnosis of pemphigus was made on clinical ground, Tzanck smear and histopathology of skin/mucous membrane lesions. Patients were put on DCP/DAP depending on the completion of family. Results: A total of 124 patients were included in the study. Age of patients ranged from 18 years to 72 years with mean of 41.21±12.71 years. Amongst 124 patients, 114 (92%) had pemphigus vulgaris and 10 (8%) had pemphigus foliaceous. 89 patients received DCP and 35 patients received DAP therapy. Number of pulses received by patients in phase I ranged from 4 to 27, average being 8.16±4.63. 106 patients completed the phase I of which 83 completed the phase II. 54 patients had successfully completed phase III of which 22 are currently in phase IV and 28 patients have completed their five year follow up period and considered as cured. Conclusion: Pulse therapy is a cheap and easily available mode of therapy in treatment of pemphigus in India even in the present era of modern molecules like Rituximab. With pulse therapy, it is now possible to induce and maintain remission, and achieve cure, provided the patients strictly adhere to the prescribed schedule.

Abstract Background Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after TNT may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. Methods In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N +) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N + vs N0) and distance from anal verge (0–4; 4–8; 8–12 cm). Patients will be randomized to receive neoadjuvant long-course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3–4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8–12 (± 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 312 evaluable patients (156 per arm) will provide statistical power of 90.5% to detect a 17% increase in cCR rate, at a one-sided alpha = 0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse event rates. Biospecimens including archival tumor tissue, plasma and buffy coat, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and had accrued 330 patients as of May 2024. Study support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Discussion Building on data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed The Janus Rectal Cancer Trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. Trial registration Clinicaltrials.gov ID: NCT05610163; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

Introduction: There is a wide variation in stroke epidemiology in India due to the differences in culture and the variability in the distribution of risk factors across the states. The present meta-analysis provides a pooled estimate of age, gender, and region-based stroke epidemiology in India based on epidemiological transition level (ETL) groups described in the Global Burden of Disease (GBD) Study (2016). Methods: We searched in PubMed and Google Scholar, and relevant studies published till February 2022 were included. Observational studies conducted in the Indian setting were included and global or Indian studies that exclusively estimated the prevalence, incidence, or mortality data among patients with stroke were excluded. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was used for the risk-of-bias assessment and publication bias was evaluated by funnel plots and Egger’s test. The R software was used to perform this meta-analysis; I2 statistics were calculated to measure heterogeneity among studies. Results: We included 58 studies in the systematic review, and after quality assessment, 47 studies were finally included for meta-analysis. The sample sizes of the included studies ranged from 40 to 4989 and the mean age of the participants ranged from 31.7 (Standard Deviation, SD-7.4) to 70.5 (SD-10.7). The burden of stroke was estimated based on the ETL groups described in the GBD Study 2016. We found a male preponderance (64.5%; 95% confidence interval [CI]: 62.5%-68.3%) in the gender distribution of strokes and 75.2% (95% CI: 68.7%-81.7%) of the stroke occurred above the age of 50 years. Ischemic stroke is the predominant subtype of stroke in India, with a higher proportion in the middle ETL region (74.0%; 95% CI: 65.1%-81.3%) as compared to those with low ETL (67.2%; 95% CI: 49.9%-80.8%) and high ETL regions (67.5%; 95% CI: 57.0%-76.4%). Conclusion: There was a significant heterogeneity among the included studies. Majority of strokes occurred in the age group of more than 50 years with a male preponderance. Ischemic stroke was the most common type of stroke with its proportion varying from 67% to 74% depending on ETL. PROSPERO Registration: CRD42022316774.

Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative approach in patients with relapsed and high-risk leukemia. This retrospective analysis aimed to investigate outcomes and risk factors associated with HSCT in children and young adults with hematological malignancies in a resource-limited setting. Methods: We retrospectively evaluated 48 pediatric and young adult patients diagnosed with hematological malignancies who underwent HSCT at our institution between April 2017 and Jan 2023. Result: The median age of the cohort was 10 years (6 months - 21 years), and the majority of patients underwent transplants for acute lymphoblastic leukemia (ALL) (n = 24; 50 %) and acute myeloid leukemia (n = 18; 37.5%). Median time to neutrophil and platelet engraftment were 15 days (range 9–28) and 18 days (range 9–40), respectively. One patient had primary graft failure. Cytomegalovirus reactivation occurred in 21 patients (43.8%). Seventeen patients received escalated donor lymphocyte infusion (DLI). With a median follow-up of 902 days (52–2490), the probability of event free survival and overall survival (OS) was 65.9% and 69.4%. OS for lymphoid and myeloid malignancies were 64.7% and 75.2%, respectively. Kaplan-Meier probabilities of OS for patients in first complete remission (CR), CR2, CR3, or with refractory disease were 80%, 76.2%, 0%, and 40%, respectively (p = 0.02). OS of the patients undergoing matched sibling donor (n = 17) or haploidentical HSCT (n = 31) was 70.6% and 69%, respectively (p = 0.989). Conclusions: Our study demonstrates excellent outcomes of patients with hematological malignancies undergoing allogeneic HSCT with similar outcomes in HLA-identical sibling donors and haploidentical first-degree family donors. Prophylactic DLI might be considered in patients with high-risk leukemia to prevent relapse, including ALL.

Background: Hepatitis B virus (HBV) infection is a serious public health issue that must be addressed. Aim: The goal of this study was to investigate the correlation between serological status for hepatitis Be antigen (HBeAg)/anti-HBe, serum transaminase levels, and serum HBV-DNA in patients with chronic HBV infection. Methods: A retrospective observational study with 620 patients with persistent HBV infection (mean age, 36.35 years; 506 men) was conducted. All patients tested positive for hepatitis B surface antigen (HBsAg). Liver profile, HBeAg, and anti-HBe antibody tests were conducted for all patients. Additionally, serum HBV DNA was examined using a DNA assay in these individuals. Results: Of 620 patients, 114 (18.39%) were HBeAg-positive and 506 (81.61%) HBeAg-negative. A detectable level of HBV DNA was found in 89.79% of HBeAg-positive/anti-HBe negative patients compared to HBeAg-negative/anti-HBe positive carriers 33.69% (P value

ABSTRACT Purpose: To create a nomogram to predict the absence of clinically significant prostate cancer (CSPCa) in males with non-suspicion multiparametric magnetic resonance imaging (mpMRI) undergoing prostate biopsy (PBx). Materials and Methods: We identified consecutive patients who underwent 3T mpMRI followed by PBx for suspicion of PCa or surveillance follow-up. All patients had Prostate Imaging Reporting and Data System score 1-2 (negative mpMRI). CSPCa was defined as Grade Group ≥2. Multivariate logistic regression analysis was performed via backward elimination. Discrimination was evaluated with area under the receiver operating characteristic (AUROC). Internal validation with 1,000x bootstrapping for estimating the optimism corrected AUROC. Results: Total 327 patients met inclusion criteria. The median (IQR) age and PSA density (PSAD) were 64 years (58-70) and 0.10 ng/mL2 (0.07-0.15), respectively. Biopsy history was as follows: 117 (36%) males were PBx-naive, 130 (40%) had previous negative PBx and 80 (24%) had previous positive PBx. The majority were White (65%); 6% of males self-reported Black. Overall, 44 (13%) patients were diagnosed with CSPCa on PBx. Black race, history of previous negative PBx and PSAD ≥0.15ng/mL2 were independent predictors for CSPCa on PBx and were included in the nomogram. The AUROC of the nomogram was 0.78 and the optimism corrected AUROC was 0.75. Conclusions: Our nomogram facilitates evaluating individual probability of CSPCa on PBx in males with PIRADS 1-2 mpMRI and may be used to identify those in whom PBx may be safely avoided. Black males have increased risk of CSPCa on PBx, even in the setting of PIRADS 1-2 mpMRI

Abstract Background Liver transplantation is an effective treatment for liver failure. There is a large unmet demand, even as not all donated livers are transplanted. The clinical selection criteria for donor livers based on histopathological evaluation and liver function tests are variable. We integrated transcriptomics and histopathology to characterize donor liver biopsies obtained at the time of organ recovery. We performed RNA sequencing as well as manual and artificial intelligence-based histopathology (10 accepted and 21 rejected for transplantation). Results We identified two transcriptomically distinct rejected subsets (termed rejected-1 and rejected-2), where rejected-2 exhibited a near-complete transcriptomic overlap with the accepted livers, suggesting acceptability from a molecular standpoint. Liver metabolic functional genes were similarly upregulated, and extracellular matrix genes were similarly downregulated in the accepted and rejected-2 groups compared to rejected-1. The transcriptomic pattern of the rejected-2 subset was enriched for a gene expression signature of graft success post-transplantation. Serum AST, ALT, and total bilirubin levels showed similar overlapping patterns. Additional histopathological filtering identified cases with borderline scores and extensive molecular overlap with accepted donor livers. Conclusions Our integrated approach identified a subset of rejected donor livers that are likely suitable for transplantation, demonstrating the potential to expand the pool of transplantable livers.

Background: This study aimed to evaluate perception of medical students regarding online mode of assessments and to compare the academic outcomes of various methodologies adopted for online formative assessments. Methods: This was a descriptive cross-sectional study. This study was conducted in the department of biochemistry at the constituent medical college of Health University in India and included 150 first year medical undergraduates of either gender. The institutional ethical clearance and written informed consent was taken prior to the study from all the enrolled participants. A series of online formative assessments were designed in the form of multiple choice, short answer questions, case-based learning, and viva-voce to satisfy each learning outcome. Google platform was used for conducting online formative assessment. The participants were asked to fill questionnaire based on 5-point Likert scale to obtain information on challenges and perceptions related to OFA. Academic performance was evaluated and compared for various modes of assessments. Results: The mean age of the participants was 19.34±0.947 years. Most of the students were from urban areas and majority (73.33%) preferred MCQs. 60.67% respondents favored conduction of e-assessments. 80.67% of students agreed that solving clinical cases in the online assessments contributed to clinical learning. Conclusions: Formative online assessment can be used as an intervention to reshape medical education sector during times when infection controls and physical isolation measures are crucial to avoid spread of disease. Keywords: Formative assessment; medical education; online assessment.

This paper introduces a cutting-edge approach for crop prediction that harnesses IoT-enabled soil sensors and machine learning models, specifically targeting cardamom, black pepper, and coffee in Idukki District, Kerala, India. The study aims to bridge the gap between soil nutrient analysis and precision agriculture by integrating a JXCT 7-in-1 soil sensor with Arduino UNO. This sensor provides accurate real-time measurements of soil moisture, temperature, pH, electrical conductivity, nitrogen, phosphorus, and potassium levels, which are critical for assessing soil health and suitability. The dataset used comprises 300 soil samples for cardamom, 320 for black pepper, and 300 for coffee, providing a robust foundation for analysis. Data from these sensors were processed using XGBoost and AdaBoost algorithms. Among the models, XGBoost achieved the highest accuracy of 91.2% and an AUC of 0.93, while AdaBoost also demonstrated strong performance with an AUC of 0.91. The results confirm the effectiveness of the system in providing precise crop suitability predictions and supporting farmers in making informed decisions based on comprehensive soil data. This approach not only improves crop yields and promotes sustainable farming practices but also shows potential for broader application in different regions and crops. Future research could expand the dataset and incorporate additional IoT devices to enhance the system’s accuracy and agricultural impact.

Background Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia (TRS), only 40% of people with TRS respond, and there is limited evidence for augmentation agents. Cannabidiol (CBD) reduces positive symptoms in individuals with schizophrenia, but no trials have specifically examined its efficacy in those with clozapine-resistant schizophrenia. Aims To examine the clinical efficacy of CBD augmentation in people with clozapine-resistant schizophrenia. Method This is a 12-week randomised, placebo-controlled, double-blind, parallel-group trial (registration number: ACTRN12622001112752). We will recruit 88 individuals with clozapine-resistant schizophrenia, randomised (1:1) to 1000 mg daily CBD versus placebo. Eligible individuals will be aged between 18 and 64 years, fulfil DSM-IV criteria for schizophrenia or schizoaffective disorder, have a total PANSS (Positive and Negative Syndrome Scale) score ≥60, have received oral clozapine for at least 18 weeks and have a clozapine level of >350 ng/mL. Interim analyses will be conducted at 25, 50 and 75% recruitment; these will also provide an opportunity to reallocate participants dependent on conditional power. The primary endpoint will be the difference in PANSS positive scores at the end of week 12. Secondary endpoints include depression, anxiety, sleep, quality of life, alcohol consumption, change in weight and metabolic syndrome components, and neurocognitive measures, as well as safety and tolerability. Discussion Novel treatments for clozapine-resistant schizophrenia are urgently needed. If found to be effective, CBD may have a role as a novel and safe adjunct to clozapine.

Extracellular biophysical cues such as matrix stiffness are key stimuli tuning cell fate and affecting tumor progression in vivo. However, it remains unclear how cancer spheroids in a 3D microenvironment perceive matrix mechanical stiffness stimuli and translate them into intracellular signals driving progression. Mechanosensitive Piezo1 and TRPV4 ion channels, upregulated in many malignancies, are major transducers of such physical stimuli into biochemical responses. Most mechanotransduction studies probing the reception of changing stiffness cues by cells are, however, still limited to 2D culture systems or cell-extracellular matrix models, which lack the major cell–cell interactions prevalent in 3D cancer tumors. Here, we engineered a 3D spheroid culture environment with varying mechanobiological properties to study the effect of static matrix stiffness stimuli on mechanosensitive and malignant phenotypes in oral squamous cell carcinoma spheroids. We find that spheroid growth is enhanced when cultured in stiff extracellular matrix. We show that the protein expression of mechanoreceptor Piezo1 and stemness marker CD44 is upregulated in stiff matrix. We also report the upregulation of a selection of genes with associations to mechanoreception, ion channel transport, extracellular matrix organization, and tumorigenic phenotypes in stiff matrix spheroids. Together, our results indicate that cancer cells in 3D spheroids utilize mechanosensitive ion channels Piezo1 and TRPV4 as means to sense changes in static extracellular matrix stiffness, and that stiffness drives pro-tumorigenic phenotypes in oral squamous cell carcinoma.

Objective: To evaluate oral health care practices, health status, and dental treatment needs in children with Autism Spectrum Disorder (ASD). Methods: This cross-sectional study included 96 children diagnosed with ASD per the DSM-V criteria and 96 typically developing healthy children. The WHO form assessed oral health status and dental treatment needs. Results: Over 50 % of ASD children had mild/moderate autism, 35.4 % had severe autism, and 13.5 % had autistic traits. ASD children experienced more toothbrushing difficulties compared to non-ASD children. Based on Nyvad's criteria and decayed/filled teeth (dft) index, non-ASD children had higher caries prevalence than ASD children, indicating less need for restorative treatments in the ASD group. However, ASD children had poorer plaque scores than non-ASD children. A significantly higher percentage of ASD children exhibited harmful oral behaviors, including mouth breathing, lip biting, bruxism, nail biting, object biting, and self-injury (p

Objectives: Aim of this study was to explore the immune-related lncRNAs having prognostic role and establishing risk score model for better prognosis and immunotherapeutic coherence for esophageal cancer (EC) patients. Methods: To determine the role of immune-related lncRNAs in EC, we analyzed the RNA-seq expression data of 162 EC patients and 11 non-cancerous individuals and their clinically relevant information from the cancer genome atlas (TCGA) database. Bioinformatic and statistical analysis such as Differential expression analysis, co-expression analysis, Kaplan Meier survival analysis, Cox proportional hazards model, ROC analysis of risk model was employed. Results: Utilizing a cutoff criterion (log2FC > 1 + log2FC

Chronic obstructive pulmonary disease (COPD) is characterized by permanent airflow obstruction due to abnormalities of the airways and alveoli. This study investigated the potential role of Aspergillus species in acute exacerbations of COPD (AECOPD) and evaluated the diagnostic utility of serum Aspergillus galactomannan antigen. This cross-sectional study, carried out at the Jawaharlal Institute of Postgraduate Medical Education and Research from January 2021 to June 2022, involved COPD patients aged ≥40 years. Serum galactomannan and serum Aspergillus-specific antibodies were analyzed, along with the collection of demographic details, symptoms, and comorbidities. Statistical analyses, including univariate analysis and receiver operating characteristic (ROC) curve analysis, were performed. Among the 61 recruited COPD patients, 24.5% showed serum galactomannan positivity. Significant associations were found between galactomannan positivity, hemoptysis, and previous tuberculosis. ROC analysis revealed modest diagnostic accuracy (area under the ROC=0.6027) with a sensitivity of 44.4% and a specificity of 83.7% at a cut-off of 0.5. Univariate analysis did not show any potential links between diabetes, hypertension, previous exacerbations, and severe gold stages with a risk of exacerbation. Serum galactomannan antigen showed limited sensitivity, and its routine testing may not be justified for predicting exacerbation risk. Further studies are warranted to validate these findings and explore other diagnostic methods using bronchoalveolar lavage galactomannan antigen in AECOPD.

The paper presents a hybrid difference method to solve a coupled system of singularly perturbed reaction–diffusion problems over an adaptive mesh. The solution to the problem manifests a distinctive multi-scale nature, characterized by localized narrow regions where the solution undergoes exponential changes. The mesh-generating procedure relies upon equidistributing a non-negative monitor function. The method utilizes a suitable combination of the cubic and exponential spline difference schemes over a layer adaptive mesh. The proposed method is unconditionally stable and uniformly convergent. The convergence obtained is optimal, being free from logarithmic factors. Moreover, it is free from directional bias. Numerical experiments have been performed and presented for two model problems. The results obtained are in agreement with the theoretical estimates.

The present study investigates the synthesis and analysis of zinc oxide nanoparticles (ZnO NPs) intended for use in electronic devices. ZnO NPs with an average crystallite size of 33 nm and a hexagonal wurtzite structure were produced by the combustion process. Scanning Electron Microscopy (SEM) revealed a densely packed, spherical morphology. Elastic properties, studied through the General Utility Lattice Program (GULP) and Elastic Tensor Analysis (ELATE), reveal the ductile nature of ZnO NPs. Optical studies exhibited a characteristic absorption peak at 366 nm, with a calculated optical band gap of 2.36 eV. Additionally, efforts are being made to determine refractive index (n), electronic polarizability (α) and optical susceptibility (χ). Electrical properties, including dielectric behaviour, AC conductivity, and I–V characteristics, demonstrated the influence of relaxation phenomena and revealed non-ohmic conduction. The dielectric studies show that dielectric constant, dielectric loss, and impedance are frequency and temperature dependent. Richardson-Schottky emission was identified as the predominant conduction mechanism, highlighting the potential of ZnO NPs in electronic devices.

Macrolide antibiotic azithromycin is widely used in clinical practice to treat respiratory tract infections and inflammatory diseases. However, its mechanism of action is not fully understood. Given the involvement of the CD27 pathway in the pathophysiology of various T-lymphocyte-mediated inflammatory, autoimmune, and lymphoproliferative diseases, we examined the impact of AZM on CD27 regulation and potential consequences on CD4+ and CD8+ T-cell phenotypes. Using cellular immunology approaches on healthy donors’ peripheral blood mononuclear cells, we demonstrate AZM-mediated downregulation of surface CD27 expression as well as its extracellular release as soluble CD27. Notably, AZM-exposed CD27high (hi) cells were defective in their ability to expand compared to CD27intermediate (Int) and CD27low (lo) subsets. The defective CD27hi subset expansion was found to be associated with impaired cell proliferation and cell division. At the molecular level, the CD27hi subset exhibited lower mTOR activity than other subsets. Functionally, AZM treatment resulted in marked depletion of helper CD4+ (Th1) and cytotoxic CD8+ T-lymphocyte (Tc1)-associated CXCR3+CD27hi effector cells and inhibition of inflammatory cytokine IFN-γ production. These findings provide mechanistic insights on immunomodulatory features of AZM on T-lymphocyte by altering the CD27 pathway. From a clinical perspective, this study also sheds light on potential clinical benefits observed in patients on prophylactic AZM regimens against various respiratory diseases and opens avenues for future adjunct therapy against Th1- and Tc1-dominated inflammatory and autoimmune diseases.

Abstract The development of neuromorphic devices is a pivotal step in the pursuit of low‐power artificial intelligence. A synaptic analog is one of the building blocks of this vision. The synaptic behavior of molecular La0.7Sr0.3MnO3/tris(8‐hydroxyquinolinato)gallium/AlOx/Co spintronic devices is studied, where the conductance plays the role of the synaptic weight. These devices are arranged in a crossbar configuration, the most effective architecture for the purpose. The conductance of each cross point is controlled separately by the application of voltage pulses: when set in the high conductance potentiated state, the devices show a spin‐valve magnetoresistance, while in the low conductance depressed state, no magnetoresistance is observed. The time dependence of the resistive switching behavior is an important parameter of the synaptic behavior and is very revealing of the underlying physical mechanisms. To study the time dynamics of the resistive switching after the voltage pulses, the response of the device to trains of potentiation and depression pulses, and the time‐resolved conductivity relaxation after the pulses are measured. The results are described with the conductivity model based on impurity energy levels in the organic semiconductor's gap. A flat distribution of the activation energies necessary to move these impurities is hypothesized, which can explain the observed glassy behavior.

Deficiency and insufficient nutrients application are the major factor responsible to reduced carrot root yield. Nutrients in balanced amount are critical aspect for getting optimal root yield for a particular agro-climatic condition. An appropriate nutrient management including potassium and micronutrients might rise and improve the productivity of carrot. The experiment was conducted at Sri Karan Narendra Agriculture University, Jobner, Jaipur, Rajasthan to study the effect of variable potassium and micronutrients formulations on performance of carrot. Results were found to be significant for the yield attributes, yield and economics of carrot. Soil application of potassium (MOP) @150 kg/ ha significantly enhanced the average root weight (189.3 g), root diameter (3.7 cm), shoot: root ratio (0.5), edible root length (23.7 cm), root yield (28.3 t/ha), net returns (₹205161/ha) and B:C ratio (2.7) of carrot. Among the micronutrients formulations, significantly higher average root weight (182.8 g), root diameter (3.7 cm), shoot: root ratio (0.5), edible root length (24.2 cm), root yield (27.8 t/ha), net returns (₹202576/ha) and B:C ratio (2.7) were noticed in foliar application of ZnSO4 @0.5%. Results of interaction shown that soil application of potassium (MOP) @150 kg/ha and ZnSO4 @0.5% significantly better in the average root weight (209.6 g), root yield (31.4 t/ha), net returns (₹2,35,918/ha) and B:C ratio (3.03).

Potato (Solanum tuberosum L.) is one of the most important tuber crops in the world and it is fourth among food crops after rice, wheat and maize. Potato is widely cultivated for its cheap source of carbohydrates, vitamins as well as minerals. In Cameroon, where potato provide a livelihood for most producers, especially in the Western highland, production is challenged by unavailability of appropriate seeds of local varieties or Cameroon improve varieties. Many decades ago, Cipira was released by the Institute of Agricultural Research for Development, Bambui, North West Region, Cameroon as an improved resistant variety. The current study evaluated the performance of Cipira considering seed sizes. Four seed sizes (20mm, 25mm, 30mm and 35mm diameter) were evaluated in a randomized complete block trial in Bambili in 2022 and 2023. Green peach aphid incidence was inversely related to tuber seed sizes (P < 0.05). Aphid population abundance was higher from plants with larger diameter. Late blight and bacterial wilt incidence and disease severity index was significantly higher for plants of smaller tuber seed size. Productivity was 8.06 t ha-1, 6.2 t ha-1, 5.7 t ha-1 and 5.8 t ha-1 from 35mm, 30mm, 25mm and 20mm tuber seed sizes, respectively in 2022. The yield in 2023 was 8.9 t ha-1, 7.8 t ha-1, 7.1 t ha-1, and 6.3 t ha-1, from 35mm, 30mm, 25mm and 20mm, respectively. For improved yield and reduced pest and diseases incidences, Cipira at 30 mm and 35 mm seed sizes are recommended. [Fundam Appl Agric 2024; 9(2.000): 80-90]

Introduction: There is a high number of isoniazid-resistant tuberculosis (TB) in India; estimates imply that over 25% of TB patients there are isoniazid-resistant. Hence, the study aimed to evaluate the effectiveness of therapy for patients with isoniazid-mono-resistant TB and the negative effects of the H-mono-resistant TB Regime. Materials and Methods: It was a hospital-based prospective observational study from September 2021 to August 2022. Hence, 100 patients diagnosed with isoniazid mono-resistance TB enrolled in this study. After obtaining the prior informed consent of all patients willing to approve the collection and publication of their data, including extensive clinical history and radiological, microbiological, and biochemical investigations, this study included all diagnosed cases of isoniazid mono-resistant TB. A descriptive statistical analysis was done for continuous and categorical variables. Differences in characteristics between participants were tested with logistic regression and cross-tabulation. P

Rice (Oryza sativa L.) cultivation necessitates an adequate supply of nitrogen to achieve optimal growth and yield. This study, conducted in Nawalparasi West from February to June 2023, aimed to assess the effects of nitrogen management through a foliar spray of nano urea, compared to need-based nitrogen management using the Leaf Color Chart (LCC) and the Recommended Dose of urea Fertilizer (RDF) application. The experiment followed a Randomized Complete Block Design (RCBD) with three replications, incorporating four nitrogen management levels (Control, RDF through urea fertilizer (120 kg/ha), 25% of RDF through basal urea (30 kg/ha) + nano urea, and 25% of RDF through basal urea (30 kg/ha) + (LCC) and two rice varieties (Chaite-5 and Hardinath-1). The results indicated that the LCC-based treatment produced the highest grain yield at 5.18 mt/ha, statistically similar to the yield of the nano urea-based treatment (5.04 mt/ha). The enhanced yields were attributed to more effective tillers per m² (260.17 tillers/m² and 253.17 tillers/m², respectively), longer panicle length (28.12 cm and 25.99 cm), more filled grains per panicle (210.03 and 215.73), and lower sterility percentage (24.93% and 26.95%). Despite comparable yields, nano urea application proved to be more cost-effective [97,926.10 Nepalese Rupees (NRs)] with a higher benefit-cost ratio (1.78) and greater ease of application for farmers compared to the LCC. Varietal responses varied, with Hardinath-1 exhibiting the highest yield with LCC-based nitrogen application (5.37 mt/ha), and Chaite-5 demonstrating the highest yield (4.778 mt/ha); with nano urea-based nitrogen application (5.31 mt/ha). Chaite-5 displayed a greater effective number of tillers per m² (241.42 tillers/m²) and filled grains per panicle (224.56). Consequently, it is suggested that nano urea-based nitrogen application, particularly in conjunction with a variety of Chaite-5, holds the potential for improved productivity.

Abstract Background Achieving effective control and elimination of malaria in endemic regions necessitates a comprehensive understanding of local mosquito species responsible for malaria transmission and their susceptibility to insecticides. Methods The study was conducted in the highly malaria prone Ujina Primary Health Center of Nuh (Mewat) district of Haryana state of India. Monthly entomological surveys were carried out for adult mosquito collections via indoor resting collections, light trap collections, and pyrethrum spray collections. Larvae were also collected from different breeding sites prevalent in the region. Insecticide resistance bioassay, vector incrimination, blood meal analysis was done with the collected vector mosquitoes. Results A total of 34,974 adult Anopheles mosquitoes were caught during the survey period, out of which Anopheles subpictus was predominant (54.7%). Among vectors, Anopheles stephensi was predominant (15.5%) followed by Anopheles culicifacies (10.1%). The Human Blood Index (HBI) in the case of An. culicifacies and An. stephensi was 6.66 and 9.09, respectively. Vector incrimination results revealed Plasmodium vivax positivity rate of 1.6% for An. culicifacies. Both the vector species were found resistant to DDT, malathion and deltamethrin. Conclusion The emergence of insecticide resistance in both vector species, compromises the effectiveness of commonly used public health insecticides. Consequently, the implementation of robust insecticide resistance management strategies becomes imperative. To effectively tackle the malaria transmission, a significant shift in vector control strategies is warranted, with careful consideration and adaptation to address specific challenges encountered in malaria elimination efforts.

Abstract Background Atopic dermatitis (AD) is a biphasic type of skin inflammation characterized by a predominance of type-2 (TH2) and type-1 (TH1) helper T cell-biased immune responses at the acute and persistent chronic phases, respectively. The present study was aimed to evaluate the efficacy of Artemisia dubia folium extract (ADFE) on AD-like skin lesions through developing a murine model for acute and chronic stages of AD. To induce acute phase AD, the dorsal skin of BALB/c mice was sensitized twice a week with 1% 2, 4-dinitrochlorobenzene (DNCB), followed by challenge (twice) in the following week with 0.2% DNCB. To induce persistent chronic AD, some mice were challenged twice a week for 4 more weeks. After the second challenge, the dorsal skin was exposed to 3% ADFE (five times per week) for 2 weeks (acute phase) or 4 weeks (persistent chronic phase). Results The paradigm of TH2 or TH1 predominance at the acute and chronic phase, respectively, was observed in this mouse model. During the acute phase, we observed an increased IL-4/IFN-γ ratio in splenic culture supernatants, an increased IgG1/IgG2a ratio in serum, and elevated serum IgE levels; however, the skew toward TH2 responses was diminished during the chronic stage. Compared with vehicle controls, ADFE reduced the IL-4/IFN-γ and IgG1/IgG2a ratios in acute AD, but both ratios increased during the chronic stage. Conclusions Our results suggest that ADFE concomitantly suppresses the TH2 predominant response in acute AD, as well as the TH1 predominant response in chronic AD. Thus, ADFE is a candidate therapeutic for AD.

The use of chatbots for customer service has gained momentum in recent years. Increasing evidence has shown that chatbots can transform the customer service landscape. Nevertheless, this topic currently lacks adequate bibliometric and visualization research. In order to review and summarise the research on chatbots, the study employs a bibliometric analysis approach to gain a comprehensive understanding of chatbots. The study uses bibliometric analysis of 798 documents sourced from the Scopus database from 2001 to 2022. The combination of biblioshiny (web interface application of Bibliometrix) and VOS viewer software was used to visualize the analysis. The study's findings reveal three prominent areas in the current research: antecedents of the adoption of chatbots, application of chatbots and behavioural & relational outcomes of the application of chatbots. The future directions and implications have been discussed in the study's conclusion.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Background: Pediatric scores such as the Pediatric Early Warning Score (PEWS) are based on parameters available at the bedside. The aim of this study was to assess the utility of PEWS to determine the need for critical care support within the next 24–48 h. this study aimed to see if PEWS could predict a suitable level of care, namely ward, high-dependency unit (HDU), or pediatric intensive care unit (PICU). Subjects and Methods: It was a prospective observational study and a convenient sample method was used with children of age groups from 1 month to 18 years, coming to the pediatrics department being the subject. We correlated the level of care at admission and also after 48 h with PEWS at the time of admission of children already intubated, children on inotropes at the time of admission, children with surgical illness, and children admitted only for procedure/procedural sedation were excluded from this study. The Brighton PEWS was used to calculate PEWS. Results: A total of 953 patients were enrolled in this study. In this study, the likelihood of admission to PICU correlated well with PEWS above 6 with a positive predictive value of 56% and a negative predictive value of 99.43%. Conclusions: The admission PEWS can be used as an effective tool for deciding the level of care area. Score 3 score at HDU/PICU where frequent periodic monitoring should be done.

Abstract Background For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. Methods The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16–26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. Discussion The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC. Trial registration ClinicalTrials.gov: NCT05673148, registered December 21, 2022.

Abstract Background Plasmodium vivax remains a major challenge for malaria control and elimination due to its ability to cause relapsing illness. To prevent relapses the Indian National Center for Vector Borne Diseases Control (NCVBDC) recommends treatment with primaquine at a dose of 0.25 mg/kg/day provided over 14 days. Shorter treatment courses may improve adherence and treatment effectiveness. Methods This is a hospital-based, randomised, controlled, open-label trial in two centres in India. Patients above the age of 16 years, with uncomplicated vivax malaria, G6PD activity of ≥ 30% of the adjusted male median (AMM) and haemoglobin levels ≥ 8 g/dL will be recruited into the study and randomised in a 1:1 ratio to receive standard schizonticidal treatment plus 7-day primaquine at 0.50 mg/kg/day or standard care with schizonticidal treatment plus 14-day primaquine at 0.25 mg/kg/day. Patients will be followed up for 6 months. The primary endpoint is the incidence risk of any P. vivax parasitaemia at 6 months. Safety outcomes include the incidence risk of severe anaemia (haemoglobin < 8 g/dL), the risk of blood transfusion, a > 25% fall in haemoglobin and an acute drop in haemoglobin of > 5 g/dL during primaquine treatment. Discussion This study will evaluate the efficacy and safety of a 7-day primaquine regimen compared to the standard 14-day regimen in India. Results from this trial are likely to directly inform national treatment guidelines. Trial registration Trial is registered on CTRI portal, Registration No: CTRI/2022/12/048283.

The significant impact of microplastics in the marine environment has sparked global concern. These tiny plastic particles travel from land to the estuary through rivers, where they become intricately distributed within the estuarine dynamics. The spatial distribution of plastic debris and sedimentation in the estuary is mainly influenced by the dynamics of the estuary, posing a scientific challenge that demands immediate attention. The main objective of this study is to analyse the microplastic contamination in the water samples collected from the Azhikkal estuary in Kannur, India, subsequent to the establishment of a seaport in the region, using a home assembled micro-Raman spectrometer. This research sheds light on the extensive prevalence of microplastics detected in the vicinity of the estuary’s entrance, with a specific focus on the consequences of seaport construction in the surrounding region. Within the surveyed region, a considerable quantity of 1260 microplastic particles and 1480 anthropogenic particles were identified. The predominant plastic varieties observed in this particular area consist of polystyrene (38 %), polysulfone (5 %), polypropylene (1 %), and polyethylene terephthalate (1 %). The predominant microplastics discovered in this region consisted mainly of fragments (82 %) and fibers (15 %), varying in sizes from 10 to 100 μm (36 %), resulting in a higher surface area to volume ratio. The existence of red and blue pigments, such as copper phthalocyanine and indigo blue, in plastic pollution discovered in this vicinity is causing alarm over the potential harmful consequences on marine organisms that rely on these ecosystems. The identification of these pigments in the estuarine region and aquatic environments across the entire nation has not been adequately pursued. Additionally, this research delves into the spread of microplastics in the murky estuarine setting, considering the significant impact of sea surface wind and alterations in buoyancy following the formation of a biofilm on their surface. This leads to the microplastics acquiring hydrophilic characteristics within the turbid estuarine environment.

ABSTRACTThe extensive modification in different land operations fueled by rapid urbanization is a matter of great concern. It is not just a simple process of exchange within different classes as we think; moreover, it is one of the most responsible factors for the change in biological rotations of the natural system. India, one of the fastest-urbanizing nations, is expected to be the home of the most urban residents by 2050, likely resulting in various undesirable issues in emerging and existing cities. The review highlights the apprehensive sides of sprawl and land use/land cover (LULC) changes in the Indian context. It also aims to assist the researchers in exploring the scope and relevance of sprawl measurement techniques for emerging urban settlements through the collected literature. A multi-stage sampling method is used to scrutinize the secondary source-based information regarding the research work. In total, 58 studies of recognized journals have been appraised systematically from 1981 to 2022. The findings reveal that increasing accidental growth caused by rapid urbanization is the leading cause of the change in LULC and irreparable environmental loss. 77.58 percent of studies have reported that geospatial technology, models, and numerical methods are more relevant to urban planners and officials for sprawl measurement and LULC change detection. So, the administration should address the accidental urban growth in its initial phase with a priority for sustainable urbanization.

Cheese whey, a significant byproduct of the dairy industry, poses a substantial environmental challenge due to its organic pollutant load and large size demands for effective and affordable valorization methods. The abundance of lactose and other organic compounds in whey contributes to its elevated Biological Oxygen Demand (BOD) and Chemical Oxygen Demand (COD), further straining natural ecosystems. This study aimed to investigate the nutritional potential of whey and its conversion into value-added products: bioethanol and probiotic drinks. To achieve this, Bacillus megaterium and Bacillus subtilis strains, isolated from soil samples in Nepal, were co-cultured with Lactobacillus sp. and Saccharomyces cerevisiae in the whey broth for fermentation. Ethanol distillation was done using a rotary evaporator to maintain the viability of the fermenting organisms in the broth. Moreover, the probiotic criteria of the fermenting strains were extensively examined. Experimental observations revealed a remarkable concentration of 9.2 g/L of ethanol, resulting in an ethanol yield of 0.23 g/L (42% compared to theoretical yield). Extrapolating this rate, it is theoretically possible to produce an annual global bioethanol output of 5 million tons using whey as a sustainable and abundant resource. Furthermore, the study explores novel advancements in the distillation process, demonstrating the successful extraction of ethanol at room temperature. Additionally, the fermentation organisms employed in this research exhibit robust viability, surviving various in-vitro stresstolerance tests, including temperature, bile salt, pH fluctuations, and gastric juice. These resilient strains also demonstrated long-term stability in fermented whey broth, making them promising candidates for the development of probiotic beverages. This dual approach enables sustainable management of organic waste and presents an opportunity to create value-added products with positive implications for the environment and human health.

Interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD) are chronic respiratory diseases that affect the lungs and airways. ILD encompasses approximately 200 different conditions with known and unknown causes. Various comorbidities, such as cardiovascular, psychological, obstructive sleep apnea, and gastrointestinal disorders, are often associated with them. However, little is known about the relationship and prevalence of hypothyroidism and diabetes mellitus (DM) in ILD and COPD. Therefore, understanding these connections is crucial for proper treatment. This cross-sectional, prospective observational study was conducted at a tertiary care hospital in North India. After obtaining informed consent, we consecutively enrolled 100 patients with ILD and 100 patients with COPD who reported to the Respiratory Medicine Outpatient Department. We collected demographic, clinical, and medical data from the patients and conducted appropriate statistical analysis to determine the prevalence of hypothyroidism and DM in patients with ILD. ILD patients exhibit a significantly higher prevalence of hypothyroidism (24% versus 4%) and DM (24% versus 4%) compared to those with COPD (p

Introduction India’s contribution to the malaria burden was highest in South-East Asia Region in 2021, accounting for 79% of the estimated malaria cases and 83% of malaria-related deaths. Intensified Malaria Control Programme supported by Global Funds to Fight against AIDS, Tuberculosis and Malaria has deployed crucial interventions to reduce the overall burden of malaria in India. Evaluation of utilisation of malaria elimination interventions by the community and assessment of the healthcare system is underway in eleven high malaria endemic states in India. Health system preparedness for malaria elimination, logistics, and supply chain management of diagnostic kits and anti-malarial drugs in addition to the knowledge, attitude and practice of the healthcare workers is also being assessed.Methods and analysis The study is being undertaken in 11 malaria endemic states with a variable annual parasite incidence of malaria. In total, 47 districts (administrative unit of malaria control operations) covering 37 976 households are to be interviewed and assessed. We present here the protocol following which the study is being undertaken at the behest and approval of Ministry of Health and Family Welfare in India.Ethics and dissemination No patients were involved in the study. Study findings will be shared with Institutional ethics board of National Institute for Malaria Research New Delhi (NIMR) in a timely, comprehensive, accurate, unbiased, unambiguous and transparent manner and to the National Vector-borne Disease (Malaria) Control Programme officers and the Community public who participated. Important findings will be communicated through community outreach meetings which are existing in the Health system. Results will be informed to study participants via local fieldwork supervised by District Malaria Officers. Also findings will be published in reputed journals based on Indian Council of Medical Research (ICMR) publication policy.The ICMR-NIMR ethics committee approved the study via letter No. NIMR/ECM/2023/Feb/14 dated 24 April 2023 for version 5. All standard ethical practices will be followed.