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Abstract 10X Visium, a popular Spatial transcriptomics (ST) method, faces limited adoption due to its high cost and restricted sample usage per slide. To address these issues, we propose Microarray Integrated Spatial Transcriptomics (MIST), combining conventional tissue microarray (TMA) with Visium, using laser-cutting and 3D printing to enhance slide throughput. Our design facilitates independent replication and customization in individual labs to suit specific experimental needs. We provide a step-by-step guide from designing TMAs to the library preparation step. We demonstrate MIST’s cost-effectiveness and technical benefits over Visium and GeoMx Nanostring. We also introduce ‘AnnotateMap’, a novel computational tool for efficient analysis of multiple ROIs processed through MIST.

Abstract Background Mesenchymal stem cells (MSCs) have emerged as promising candidates for immune modulation in various diseases that are associated with dysregulated immune responses like Graft-versus-Host-Disease (GVHD). MSCs are pleiotropic and the fate of MSCs following administration is a major determinant of their therapeutic efficacy. Methods Human MSCs were derived from bone marrow (BM) and Wharton’s Jelly (WJ) and preconditioned through exposure to hypoxia and induction of apoptosis, either sequentially or simultaneously. The immune programming potential of preconditioned MSCs was evaluated by assessing their effects on T cell proliferation, induction of Tregs, programming of effector T-cell towards Th2 phenotype, macrophage polarization in the direct co-culture of MSCs and aGVHD patients-derived PBMNCs. Additionally, efferocytosis of MSCs and relative change in the expression of immunomodulatory soluble factors were examined. Results Our study demonstrated that hypoxia preconditioned apoptotic MSCs (BM-MSCs, WJ-MSCs) bear more immune programming ability in a cellular model of acute Graft-versus-Host-Disease (aGVHD). Our findings revealed that WJ-MSCsHYP+APO were superior to BM-MSCsHYP+APO for immune regulation. These induced the differentiation of CD4+T-cell into Tregs, enhanced Th2 effector responses, and simultaneously mitigated Th1- and Th17 responses. Additionally, this approach led to the polarization of M1 macrophages toward an M2 phenotype. Conclusion Our study highlights the potential of WJ-MSCs conditioned with hypoxia and apoptosis concurrently, as a promising therapeutic strategy for aGVHD. It underscores the importance of considering MSC apoptosis in optimizing MSCs-based cellular therapy protocols for enhanced therapeutic efficacy in aGvHD. Graphical Abstract

Background Primary lung sarcoma (PLS) differs in management protocols and prognosis from the more common primary lung carcinoma (PLC). It becomes imperative to raise a high index of suspicion on radiological and pathological features.

Ethylene glycol is a toxic alcohol, and its ingestion can cause neurological, cardiovascular, and renal complications, including coma and death. It causes an elevated osmolar gap, and its metabolites, glycolate, and oxalate, are responsible for elevated anion gap metabolic acidosis. Early diagnosis and management of this condition are critical in the emergency department (ED).The point-of-care (POC) blood gas analyzer, commonly used in the emergency department, measures lactic acid using the lactate oxidase method, which measures the hydrogen peroxide generated from lactate. In contrast, the laboratory analyzer measuring venous lactate uses the lactate dehydrogenase method. Glycolic acid, a metabolite of ethylene glycol, is structurally similar to L-lactic acid, and it cross-reacts with lactate on the POC analyzer. Glycolic acid metabolized by lactate oxidase also leads to increased hydrogen peroxide production similar to L-lactic acid, resulting in spuriously elevated lactate. This discrepancy causes higher lactate levels in POC measurement than the laboratory-measured lactate, a condition called lactate gap.We present two patients with altered levels of consciousness who had elevated osmolar gap and lactate gap at presentation to the emergency department. Ethylene glycol poisoning was suspected, given the discrepancy between POC lactate and laboratory-measured venous lactate levels. We promptly initiated treatment with fomepizole and hemodialysis while waiting for ethylene glycol levels, prompting early recovery.We hypothesize that ED physicians should use the lactate gap as an initial diagnostic tool for early diagnosis of ethylene glycol poisoning, and hospitalists and nephrologists can use the closure of the lactate gap to decide on dialysis termination.

IntroductionThe prevalence of Renal cell carcinoma (RCC) is increasing among adults. Histopathologic samples obtained after surgical resection or from biopsies of a renal mass require subtype classification for diagnosis, prognosis, and to determine surveillance. Deep learning in artificial intelligence (AI) and pathomics are rapidly advancing, leading to numerous applications such as histopathological diagnosis. In our meta-analysis, we assessed the pooled diagnostic performances of deep neural network (DNN) frameworks in detecting RCC subtypes and to predicting survival.MethodsA systematic search was done in PubMed, Google Scholar, Embase, and Scopus from inception to November 2023. The random effects model was used to calculate the pooled percentages, mean, and 95% confidence interval. Accuracy was defined as the number of cases identified by AI out of the total number of cases, i.e. (True Positive + True Negative)/(True Positive + True Negative + False Positive + False Negative). The heterogeneity between study-specific estimates was assessed by the I2 statistic. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to conduct and report the analysis.ResultsThe search retrieved 347 studies; 13 retrospective studies evaluating 5340 patients were included in the final analysis. The pooled performance of the DNN was as follows: accuracy 92.3% (95% CI: 85.8–95.9; I2 = 98.3%), sensitivity 97.5% (95% CI: 83.2–99.7; I2 = 92%), specificity 89.2% (95% CI: 29.9–99.4; I2 = 99.6%) and area under the curve 0.91 (95% CI: 0.85–0.97.3; I2 = 99.6%). Specifically, their accuracy in RCC subtype detection was 93.5% (95% CI: 88.7–96.3; I2 = 92%), and the accuracy in survival analysis prediction was 81% (95% CI: 67.8–89.6; I2 = 94.4%).DiscussionThe DNN showed excellent pooled diagnostic accuracy rates to classify RCC into subtypes and grade them for prognostic purposes. Further studies are required to establish generalizability and validate these findings on a larger scale.

Background: Ectoparasites are organisms that live in the skin for varying lengths of time and can cause disease. These infestations are highly prevalent in poor and underdeveloped areas. There is a paucity of studies regarding their prevalence in rural areas like the upper Karnali region of Nepal. We conducted a hospital-based study to know the burden of these infestations in the area. Methods: A hospital-based descriptive study was done from March 2023 to February 2024. Data were collected from medical records of the dermatology outpatient department (OPD) and all the clinically diagnosed cases of ectoparasitic infestation were studied. Data were presented as frequency and percentage; seasonal pattern of the diseases was also reported. Results: A total of 6,698 patients attended dermatology OPD during the study period, among whom 1340 had ectoparasitic infestations, resulting in a proportion of 20.01% in this group. Two infestations were found, namely, scabies and pediculosis capitis, with a proportion of 18.36% and 1.65%, respectively. Females represented almost half of the patients with ectoparasitic infestations (49.63%), but about 98% with pediculosis. Ectoparasitic infestation was most common in children aged 0–9 years, i.e., 31.31% and pediculosis was most common in children of 10–19 years (31.81%). Ectoparasitic infestations (41.94%), both scabies (41.7%) and pediculosis (44.55%) were most common during the monsoon season. Conclusion: The ectoparasitic infestations were common the patients presenting to the hospital. Scabies was the most common ectoparasitic infestation and a major public health problem.

Key Clinical Message Both C‐anti‐neutrophil cytoplasmic antibody (ANCA) and P‐ANCA vasculitis were reported to be associated with COVID‐19 infection. The ideal management of COVID‐19‐associated ANCA vasculitis is unclear, as the experiences were limited to case reports. We presented a case of COVID‐19‐associated C‐ANCA vasculitis, successfully treated with steroids and rituximab therapy without any significant adverse reactions.

(1) Background: Renal insufficiency is a risk factor for cardiac implantable electronic device (CIED) infection. (2) Methods: A comprehensive search was conducted from multiple electronic databases to identify studies. Using the random effects model, we calculated the pooled rates of CIED infection and their 95% confidence intervals. We also calculated the pooled odds ratios to determine the risk of CIED infections due to chronic kidney disease (CKD) and end-stage renal disease (ESRD). We utilized the Cochran Q and I2 statistics to detect and quantify heterogeneity. (3) Results: A total of 17 studies comprising 359,784 patients with renal insufficiency were added to the meta-analysis. Out of these, 263,819 were CKD patients and 89,617 were ESRD patients. The pooled rate of CIED infection in patients with CKD was 4.3% (95% CI: 2–8.8; I2: 95.7), and in patients with ESRD, it was 4.8% (95% CI: 2.6–8.7; I2: 99.4). The pooled risk of CIED infection in the CKD population was OR 2.5 (95% CI: 1.9–3.3; p < 0.001; I2: 21.1), and in the ESRD population, it was OR 2.4 (95% CI: 1.01–5.7; p = 0.046; I2: 88.8). ESRD was associated with higher mortality, OR 2.5 (95% CI: 1.4–4.4.8; p = 0.001; I2: 95). (4) Conclusions: The presence of renal insufficiency increases the number of CIED infections. In particular, patients with ESRD have an increased risk of mortality.

Background : Acupressure, which is related to acupuncture, is a noninvasive therapy suitable for use in children. However, data examining acupressure’s effects on the pain of local anesthetic injection in children are sparse. Objectives: The purpose of this study was to evaluate acupressure’s effects on the pain of local anesthetic injection in children. Methods : This randomized, double-blind, parallel-group clinical study included 37 5- to 10-year-olds who had an inferior alveolar nerve block (IANB) for a mandibular extraction and were randomized to one of two groups: acupressure (study group) or non-acupressure (control group). The Wong-Baker FACES Pain Rating Scale (WBFPS) and the Sound, Eye, Motor (SEM) scale were utilized for subjective and objective pain assessment during injection. Results : The objective and subjective assessment of pain during injection significantly differed between the groups, with the acupressure group displaying lower scores. Conclusion : Acupressure at the extra one point (EX-HN1) reduced pain during IANB injection in 5- to 10-year-olds and can be used as an adjunct to conventional measures like topical anesthesia to reduce pain.

PURPOSESerial patient-reported outcome (PRO) measurements in clinical practice are associated with a better quality of life and survival. Recording electronic PROs using smartphones is an efficient way to implement this. We aimed to assess the feasibility of the electronically filled Edmonton Symptom Assessment System (e-ESAS) scale in the lower-middle–income country (LMIC) setting.METHODSBaseline clinical features and conventional paper-based ESAS (p-ESAS) were collected in newly diagnosed patients with solid organ tumors. Text message link was sent to these patients for filling e-ESAS. ESAS was categorized into physical, psychological, and total symptom domains. Scores were divided into none to mild (0-3) and moderate to severe (4-10). Intraclass correlation coefficients (ICCs) were used to determine the correlation between p-ESAS and e-ESAS. Multivariable logistic regression was used to identify independent factors affecting symptom burden.RESULTSOf 1,160 participants who filled out p-ESAS, 595 completed both e-ESAS and p-ESAS questionnaires and were included in the final analysis. Moderate to severe physical, psychological, and total symptom scores were seen in 39.8%, 40%, and 39% of participants. Tiredness and anxiety were the most common physical and psychological symptoms, respectively. ICCs between the p-ESAS and e-ESAS varied between 0.75 and 0.9. Total symptom scores were independently predicted by metastatic disease (odds ratio [OR], 1.83; 95% CI, 1.26 to 2.67; P = .001) and a higher level of education (OR, 0.42; 95% CI, 0.25 to 0.72; P = .001).CONCLUSIONPaper-based and electronically filled ESASs have good intraobserver reliability across individual symptoms and domain scores in a representative cohort at a tertiary care institute in the LMIC. This may help us incorporate e-ESAS in routine clinical care in the real-world setting with financial, infrastructural, and manpower limitations.

Abstract Small cell lung carcinomas (SCLC) are aggressive tumors with high propensity to metastasize. Recent NCCN guidelines have incorporated immunotherapy in extensive stage SCLC. Limited benefit in few patients compounded by side effects of unwonted immune-checkpoint-inhibitor (ICPI) usage necessitates identification of potential biomarkers predicting response to ICPIs. Attempting this, we analysed expression of various immunoregulatory molecules in tissue biopsies and paired blood samples of SCLC patients. In 40 cases, immunohistochemistry for expression of immune inhibitory receptors CTLA-4, PD-L1 and IDO1 was performed. Matched blood samples were quantified for IFN-γ, IL-2, TNF-α and sCTLA-4 levels using immunoassay and additionally for IDO1 activity (Kynurenine/Tryptophan ratio) using LC–MS. Immunopositivity for PD-L1, IDO1 and CTLA-4 was identified in 9.3%, 6.2% and 71.8% cases, respectively. Concentration of serum IFN-γ (p-value

Abstract Background Peripheral neuropathy is a common dose-limiting side effect of paclitaxel. To date, there is no effective strategy to prevent paclitaxel-induced peripheral neuropathy. A recent small phase II study demonstrated the potential role of oral gabapentin in this setting. This phase III study is aimed to assess the efficacy of oral gabapentin in preventing paclitaxel-induced neuropathy. Objective To compare the efficacy of oral gabapentin with placebo in preventing clinically significant peripheral neuropathy (NCI CTCAEv5.0 grade 2 or higher) in patients receiving paclitaxel. Methods This is a randomized, placebo-controlled, double-blind, parallel-group superiority trial. The primary outcome is the development of grade 2 or higher chemotherapy-induced peripheral neuropathy. Secondary outcomes include any grade neuropathy, the percentage change in sensory nerve conduction velocities in peripheral nerves, time to development of any grade neuropathy, paclitaxel dose reductions and delays due to peripheral neuropathy, patient-reported outcomes, adverse events, and adherence to oral therapy. A total of 136 patients receiving paclitaxel will be randomly allocated (stratified by weekly vs. non-weekly administration) to receive either oral gabapentin or placebo till three weeks after the last dose of chemotherapy or occurrence of the primary outcome. Conclusion This study aims to find if oral gabapentin reduces the incidence of grade 2 or higher chemotherapy-induced peripheral neuropathy in patients receiving paclitaxel. Trial registration The trial is registered prospectively with the Clinical Trials Registry of India (CTRI/2022/02/040030) on April 4, 2022.

Abstract Background Diabetes mellitus (DM) is a growing disease across the world; diabetes is a complex metabolic disorder in which blood glucose concentration level increases and continue for a prolonged period due to a decrease secretion of insulin or action, resulting in the disorder of carbohydrate, lipid, and protein metabolism. The plant-related bioactive compounds have proven their efficacy with least toxicities and can be utilized for the disease treatment. Our objective is to elucidate the mechanism of action of plant bioactive compounds which can give future direction in diabetes treatment. Main body In this review paper, we briefly study more than 200 research papers related to disease and bioactive compounds that have therapeutic applicability in treatment. The plant contains many bio-active compounds which possess in vitro and in vivo anti-diabetic effect which may be responsible for the hypoglycaemic property by inhibiting the digestive enzyme i.e. alpha-amylase and alpha-glucosidase, by producing mimetic action of insulin, by reducing the oxidative stress, by showing antihyperglycemic activity and hypolipidemic activity, by inhibition of aldose reductase, and by increasing or enhancing glucose uptake and insulin secretion. Conclusion Our study revealed that terpenes, tannin, flavonoids, saponin, and alkaloids are important bioactive constituents for anti-diabetic activity. The mechanistic approach on alpha-glucosidase and alpha-amylase, hypolipidemic activity, and AR inhibitory action clear-cut explain the therapeutic applicability of these bioactive compounds in disease. Plants that contain these bioactive compounds can be good drug candidates for future research on diabetes treatment.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of inflammatory myofibroblastic tumor (IMT) harboring anaplastic lymphoma kinase (ALK) gene fusions and is associated with high risk of local recurrence and poor prognosis. Herein, we present a young, non-smoking male who presented with complaints of cough and dyspnoea and was found to harbor a large right lower lobe lung mass. Biopsy showed a high-grade epithelioid to rhabdoid tumor with ALK and desmin protein expression. The patient initially received 5 cycles of crizotinib and remained stable for 1 year; however, he then developed multiple bony metastases, for which complete surgical resection was performed. Histopathology confirmed the diagnosis of EIMS, with ALK gene rearrangement demonstrated by fluorescence in situ hybridization. Postoperatively, the patient is asymptomatic with stable metastatic disease on crizotinib and has been started on palliative radiotherapy. EIMS is a very rare subtype of IMT that needs to be included in the differential diagnosis of ALKexpressing lung malignancies in young adults.

PURPOSEThe incidence of symptomatic brain metastasis at diagnosis in non–small-cell lung cancer (NSCLC) is 5%-10%, and up to 40% develop during the disease course. There is a paucity of data supporting the role of brain imaging at diagnosis in asymptomatic cases particularly from resource-constraint settings. Here, we present our experience of mandatory baseline brain imaging with contrast-enhanced computed tomography (CECT) scans of all patients with NSCLC.MATERIALS AND METHODSThis was a prospective observation study of patients with NSCLC with mandatory baseline brain CECT and a CNS examination. All histology proven patients with NSCLC diagnosed between January 2018 and October 2019 were included irrespective of stage.RESULTSA total of 496 patients were enrolled. The median age was 57 years (range, 23-84) with majority being males (75%) and smokers (66%). The prevalence of epidermal growth factor receptor mutations and anaplastic lymphoma kinase fusions was 33.4% and 12%, respectively. Brain imaging leads to upstaging in 7% cases. The prevalence of brain metastases was 21% (n = 104), with half being asymptomatic (51%). Factors associated with higher proportion of brain metastasis were young age (≤ 40 years), adenocarcinoma histology, poor Eastern Cooperative Oncology Group performance status (3 and 4), and high neutrophil-lymphocyte ratio (NLR) (> 2.5). After a median follow-up of 10.8 months (95% CI, 7.33 to 12.73), the median overall survival was 7.46 versus 12.76 months (hazard ratio 0.67; 95% CI, 0.46 to 0.96; P = .03) in patients with and without brain metastases, respectively. On multivariate analyses, high NLR and molecular graded prognostic assessment affected the overall survival significantly.CONCLUSIONIn our study, 21% of patients had brain metastasis at diagnosis detected with a mandatory baseline brain imaging with CECT. NLR and molecular graded prognostic assessment are significant predictors of survival in patients with brain metastasis.

Background: One fifth of patients with epithelial ovarian cancers (EOC) present at an early stage (FIGO stage I & II). However, there is scarcity of literature on the outcomes and its predictors. The aim of the study was to assess relapse free survival (RFS), overall survival (OS) and its predictors in early stage EOC. Patients and Methods: In this retrospectively study, we included all patients with early-stage EOC diagnosed between January 2010 and December 2018. Patients with synchronous malignancies were excluded. Clinical profile, clinico-pathological characteristics and treatment details were recorded. Patient underwent initial surgery followed by adjuvant chemotherapy in high-risk disease. Patients with stage IC, or stage II or clear cell histology or high-grade histology irrespective of stage/histological subtype were defined as high-risk disease. Fertility sparing surgery (FSS) [unilateral salpingo-oopherectomy with complete surgical staging] was performed in patient willing to preserve fertility. Primary objective was to assess RFS and OS in all patients with early stage EOC. Secondary objectives were to assess RFS and OS in early stage EOC with high-risk disease, predictors of RFS and OS, and outcomes of FSS. Survival probabilities were estimated according to Kaplan-Meier and compared by the log rank test. Cox's regression model was used to analyze the significance of various factors affecting relapse free survival (RFS) and overall survival (OS). Results: 195 patients with early stage EOC were recruited with median age of 47 years (range, 16–80 years). FIGO stage I and stage II were seen in 72 % and 18 % patients respectively. Serous subtype was reported in 58 % and high-grade histology in 66 %. 184 patients (94.0%) underwent optimal staging surgery, including 27 (14%) with fertility sparing surgery (FSS). 133 (91.7 %) of 145 patients with high-risk disease received adjuvant chemotherapy (paclitaxel and carboplatin), while 12 (8.3 %) patients opted to remain on observation. At median follow up of 56 months (95 % CI, 46–64 months), 49 (25 %) patients relapsed [including 3 of 27 (11.1 %) who underwent FSS], 18 patients died of progressive disease, while 31 patients were alive and disease free. Estimated OS at 5 years is 87.6 % (95 % CI 79.9–92.5) and RFS is 73.2 % (95 % CI 64.7–80.0). On multivariate analysis tumor grade was predictive of RFS (HR 2.9, p

Background Thyroid transcription factor (TTF-1) is a diagnostic marker expressed in 75%–85% of primary lung adenocarcinomas (ACs). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is the most common targetable driver alteration in lung AC. Previous studies have shown a positive correlation between TTF-1 and EGFR mutation status. We aimed to determine the predictive value of TTF-1 immunoexpression for underlying EGFR mutation status in a large Indian cohort. Methods This retrospective designed study was conducted with medical record data from 2011 to 2020. All cases of primary lung AC and non–small cell lung carcinoma not otherwise specified (NSCLC, NOS) with known TTF-1 expression diagnosed by immunohistochemistry using 8G7G3/1 antibodies and EGFR mutation status diagnosed by quantitative polymerase chain reaction were retrieved, reviewed, and theresults were analyzed. Results Among 909 patient samples diagnosed as lung AC and NSCLC, NOS, TTF-1 was positive in 76.8% cases (698/909) and EGFR mutations were detected in 29.6% (269/909). A strong positive correlation was present between TTF-1 positivity and EGFR mutation status (odds ratio, 3.61; p < .001), with TTF-1 positivity showing high sensitivity (90%) and negative predictive value (87%) for EGFR mutation. TTF-1 immunoexpression did not show significant correlation with uncommon/dual EGFR mutations (odds ratio, 1.69; p = .098). EGFR–tyrosine kinase inhibitor therapy was significantly superior to chemotherapy among EGFR mutant cases irrespective of TTF-1 status; however, no significant differences among survival outcomes were observed. Conclusions Our study confirms a strong positive correlation between TTF-1 expression and common EGFR mutations (exon 19 deletion and exon 21 L858R) in advanced lung AC with significantly high negative predictive value of TTF-1 for EGFR mutations.

Background: Mucocutaneous manifestations in HIV infections are common. However, they have not, so far, been studied in Nepal. The aim of this study was, therefore, to describe mucocutaneous manifestations in Nepalese HIV patients. Materials and Methods: The following is a hospital-based, descriptive, cross-sectional study conducted in the Department of Dermatology and Venereology and Antiretroviral Treatment (ART) Center of Tribhuvan University Teaching Hospital (TUTH) from May 2017, through October 2018. Patients aged 16 years and above diagnosed with HIV were included in the study, for whom history and clinical examinations were performed. The study variables were age, sex, a clinical diagnosis of dermatological problems, clinical stages of HIV/AIDS, as per the World Health Organization (WHO) classification criteria, and the CD4 count. Results: A total of 52 patients were included in the study. The mean age upon presentation was 38.77 ± 10.9 years. The mean CD4 count was 464.27 ± 255.13. Females were more affected than males (female:male = 1.4:1). Mucocutaneous manifestations were the following: fungal infections (10; 19.3%), viral infections (6; 11.6%), parasitic infestations (3; 5.8%), bacterial infections (4; 7.7%), sexually transmitted infections (2; 3.8%), seborrheic dermatitis (3; 5.8%), idiopathic pruritus (3; 5.8%), recurrent oral ulcers (3; 5.8%), urticaria (3; 5.8%), pruritic papular eruptions (2; 3.8%), eczemas (2; 3.8%), acne (2; 3.8%), angular cheilitis (2; 3.8%), xerosis cutis (2; 3.8%), and others (5; 9.6%). Conclusions: The study showed that fungal infections are common in HIV patients, followed by viral infections and parasitic infestations. Seborrheic dermatitis, idiopathic pruritus, recurrent oral ulcers, and urticaria were found to be common inflammatory skin diseases in HIV.

Introduction: The incidence of lung cancer with chest wall (CW) involvement is approximately 5%. Surgical resection with tumor-free margin is the mainstay of the treatment but these patients generally require multimodality management. CW resection for lung cancer is a complex procedure and requires a balance of radical oncological resection and reconstruction. Herein, we shared an experience of primary lung cancer with CW involvement. Materials and Methods: Outcome analysis of a prospectively maintained lung cancer database was done for the patients having primary lung cancer with CW involvement. All the patients underwent radical surgical resection of the primary tumor along with the CW. Results: Among the 208 patients undergoing surgery for non-small cell lung cancer, 20 (9.5%) were found to have CW involvement radiologically. The most common symptom was chronic cough. A total of 11 patients received neoadjuvant chemotherapy (NACT) and the rest were taken for upfront surgery. Six patients had a partial response to NACT and none of them had tumor progression during the chemotherapy. All the patients underwent en bloc resection of the CW with anatomical resection of lung and systematic mediastinal lymphadenectomy. The mean duration of surgery was 199 min and the average blood loss was 560 ml. Reconstruction was done with a combination of prosthetic mesh and pedicled muscle flap. Median disease-free and overall survivals were 21 and 26 months, respectively. Conclusion: Radical resection with reconstruction is required for optimal long-term oncological and functional outcomes for NSCLC with CW involvement.

PURPOSEPatients with advanced and metastatic cervical cancer have a poor prognosis with a 1-year survival rate of 10%-15%. Recently, an antiangiogenic humanized monoclonal antibody bevacizumab has shown to improve the survival of these patients. This study was designed to assess the cost effectiveness of incorporating bevacizumab with standard chemotherapy for the treatment of patients with advanced and metastatic cervical cancer in India.METHODSUsing a disaggregated societal perspective and lifetime horizon, a Markov model was developed for estimating the costs and health outcomes in a hypothetical cohort of 1,000 patients with advanced and metastatic cervical cancer treated with either standard chemotherapy alone or in combination with bevacizumab. Effectiveness data for each of the treatment regimen were assessed using estimates from Gynecologic Oncology Group 240 trial. Data on disease-specific mortality in metastatic cervical cancer, health system cost, and out-of-pocket expenditure were derived from Indian literature. Multivariable probabilistic sensitivity analysis was undertaken to account for parameter uncertainty.RESULTSOver the lifetime of one patient with advanced and metastatic cervical cancer, bevacizumab along with standard chemotherapy results in a gain of 0.275 (0.052-0.469) life-years (LY) and 0.129 (0.032-0.218) quality-adjusted life-years (QALY), at an additional cost of $3,816 US dollars (USD; 2,513-5,571) compared with standard chemotherapy alone. This resulted in an incremental cost of $19,080 USD (7,230-52,434) per LY gained and $34,744 USD (15,782-94,914) per QALY gained with the use of bevacizumab plus standard chemotherapy.CONCLUSIONAddition of bevacizumab to the standard chemotherapy is not cost effective for the treatment of advanced and metastatic cervical cancer in India at a threshold of 1-time per-capita gross domestic product.

Summary: Monocytes are known to play a critical role in dengue pathophysiology. However, which monocyte subset expresses what inflammatory mediator(s) and what transcriptional features distinguish each of the monocyte subset in vivo remain poorly understood. In this study we provide a detailed transcriptional analysis of the three human monocyte subsets in healthy children and in children with dengue febrile illness. Notably, we found that the CD14+ CD16high intermediate monocyte subset from dengue patients highly upregulated key genes involved in mediating inflammation, endothelial dysfunction, vascular permeability, tissue extravasation, and clot prevention compared to healthy children. The CD14+CD16low classical monocytes shared some of these features. These two subsets increased massively in patients with severe dengue. By contrast, the CD14−CD16high nonclassical monocyte subset upregulated key genes involved in vasoconstriction, endothelial barrier stability, and are involved in endothelial patrolling while showing a significant decline from circulation. These findings improve our understanding of monocyte responses in dengue.

Abstract Hansen's disease, a chronic granulomatous disease, classically has cutaneous and neurological manifestations. Musculoskeletal manifestation of the disease is underappreciated. This case report conveys that musculoskeletal manifestation of the disease should not be missed, as sometimes it is the only presenting symptom, to avoid delay in correct diagnosis and treatment.

Abstract Background Early diagnosis is crucial for effective medical management of cancer patients. Tissue biopsy has been widely used for cancer diagnosis, but its invasive nature limits its application, especially when repeated biopsies are needed. Over the past few years, genomic explorations have led to the discovery of various blood-based biomarkers. Tumor Educated Platelets (TEPs) have, of late, generated considerable interest due to their ability to infer tumor existence and subtype accurately. So far, a majority of the studies involving TEPs have offered marker-panels consisting of several hundreds of genes. Profiling large numbers of genes incur a significant cost, impeding its diagnostic adoption. As such, it is important to construct minimalistic molecular signatures comprising a small number of genes. Results To address the aforesaid challenges, we analyzed publicly available TEP expression profiles and identified a panel of 11 platelet-genes that reliably discriminates between cancer and healthy samples. To validate its efficacy, we chose non-small cell lung cancer (NSCLC), the most prevalent type of lung malignancy. When applied to platelet-gene expression data from a published study, our machine learning model could accurately discriminate between non-metastatic NSCLC cases and healthy samples. We further experimentally validated the panel on an in-house cohort of metastatic NSCLC patients and healthy controls via real-time quantitative Polymerase Chain Reaction (RT-qPCR) (AUC = 0.97). Model performance was boosted significantly after artificial data-augmentation using the EigenSample method (AUC = 0.99). Lastly, we demonstrated the cancer-specificity of the proposed gene-panel by benchmarking it on platelet transcriptomes from patients with Myocardial Infarction (MI). Conclusion We demonstrated an end-to-end bioinformatic plus experimental workflow for identifying a minimal set of TEP associated marker-genes that are predictive of the existence of cancers. We also discussed a strategy for boosting the predictive model performance by artificial augmentation of gene expression data.

Long-term performance of an axial-flow compressor by the scheduling of inlet guide vanes at off-design conditions has been studied in this paper. The compressors are used in various industries and in aviation sectors for different operations at different climatic conditions; due to diverse climatic conditions the compressor is unable to give good performances as expected. At the design conditions, the results show that the variations in total pressure loss coefficient, volume flow rate, pressure ratio, and others like thermodynamics, aerodynamic properties are different at different stagger angles of 15°, 30° and 45°. BladeGen tools were used to design the inlet guide vanes for the investigations. The performance parameters of the axial flow compressor were analyzed by using ANSYS CFX and were validated using the analytical method. The objective of this study is to minimize the total pressure loss coefficient and improve the aerodynamic characteristics of an inlet guide vanes at different stagger angles and hence reduce the overall fuel consumption. The outcomes of this work give an improved insight into the efficient use of a VIGV in axial flow compressor.

As the second wave in India mitigates, COVID-19 has now infected about 29 million patients countrywide, leading to more than 350 thousand people dead. As the infections surged, the strain on the medical infrastructure in the country became apparent. While the country vaccinates its population, opening up the economy may lead to an increase in infection rates. In this scenario, it is essential to effectively utilize the limited hospital resources by an informed patient triaging system based on clinical parameters. Here, we present two interpretable machine learning models predicting the clinical outcomes, severity, and mortality, of the patients based on routine non-invasive surveillance of blood parameters from one of the largest cohorts of Indian patients at the day of admission. Patient severity and mortality prediction models achieved 86.3% and 88.06% accuracy, respectively, with an AUC-ROC of 0.91 and 0.92. We have integrated both the models in a user-friendly web app calculator, https://triage-COVID-19.herokuapp.com/, to showcase the potential deployment of such efforts at scale.

Background: Flavonoid quercetin is widely found in the plant kingdom. Despite having beneficial effects, quercetin shows toxic potential and its ambiguous nature justifies further study. Effect of quercetin on the murine liver has not been studied yet and its toxicogenomic data are scarce. Method: : In the present study, 500, 1000, 1500 and 2000 mg/kg of quercetin doses were administered to age and body weight matched swiss mice. Serum was taken to detect the hepatotoxicity biomarkers and the liver tissue was processed for histological assessment. A part of liver tissue was used to measure the oxidative stress markers and to analyze the global gene expression. Results: Hepatotoxicity biomarkers e.g. aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were elevated in higher treatment groups of quercetin. Lipid peroxidation level (LPO), reduced glutathione content (GSH) and the expression of stress regulated genes were significantly altered in higher treatment groups of quercetin which indicated the generation of oxidative stress. In global gene expression analysis,155 differentially expressed genes consist of 36 upregulated and 119 downregulated genes were identified at statistical stringent criteria (p< 0.05- and 2-fold change). Pathway analysis revealed that the majority of upregulated genes were related to metabolic pathways and most downregulated genes were related to endocytosis and lysosomal pathways. 60% of total genes were downregulated in gene interaction network of stress signaling. Conclusion: The quantitative modeling suggested a significant relationship between MAP kinase (MAPK) expression and other genes in the stress-signaling sub-network. Altogether, these results indicated that the higher doses of quercetin induce hepatotoxic stress and influence several genes related to multiple biologically relevant pathways.

Introduction The rising economic burden of cancer on healthcare system and patients in India has led to the increased demand for evidence in order to inform policy decisions such as drug price regulation, setting reimbursement package rates under publicly financed health insurance schemes and prioritising available resources to maximise value of investments in health. Economic evaluations are an integral component of this important evidence. Lack of existing evidence on healthcare costs and health-related quality of life (HRQOL) makes conducting economic evaluations a very challenging task. Therefore, it is imperative to develop a national database for health expenditure and HRQOL for cancer.Methods and analysis The present study proposes to develop a National Cancer Database for Cost and Quality of Life (CaDCQoL) in India. The healthcare costs will be estimated using a patient perspective. A cross-sectional study will be conducted to assess the direct out-of-pocket expenditure (OOPE), indirect cost and HRQOL among cancer patients who will be recruited at seven leading cancer centres from six states in India. Mean OOPE and HRQOL scores will be estimated by cancer site, stage of disease and type of treatment. Economic impact of cancer care on household financial risk protection will be assessed by estimating prevalence of catastrophic health expenditures and impoverishment. The national database would serve as a unique open access data repository to derive estimates of cancer-related OOPE and HRQOL. These estimates would be useful in conducting future cost-effectiveness analyses of management strategies for value-based cancer care.Ethics and dissemination Approval was granted by Institutional Ethics Committee vide letter no. PGI/IEC-03/2020-1565 of Post Graduate Institute of Medical Education and Research, Chandigarh, India. The study results will be published in peer-reviewed journals and presented to the policymakers at national level.

The present study investigates the effects of alternative fuel properties on combustion performance, in order to ensure reliable combustion performance using various fuel blends for powering an engine. The increasing rate of fuel cost and depletion of fossil fuels has led to the search for alternate fuels. Palm biodiesel derived from palm fatty acids meets the fuel requirements of an aircraft and is compatible with any engine without modifications. Viability of using a blend of present fossil fuels with biodiesel is studied. The engine was operated with petrol, diesel, palm biodiesel and a blend of these three fuels as a pair, with various ratios. The fuel was injected into the combustion chamber at an angle of 45o to the airflow and ignited using a spark plug. The blended fuel is found to have better efficiency than petrol or diesel. Furthermore, the low cost and abundant availability of the biofuel make it a viable alternative to the petroleum-based fuels currently in use. The combustion time and ignition delay are decreased with efficient biofuel due to high oxygen content and high octane number of the biofuel.

This paper presents an experimental study on the development of biocomposite material by using sawdust (SD) and rice husk (RH). The use of composite in the present production has increased dramatically since the 1970’s. Traditional material like aluminum, steel, iron and copper etc. may be easily replaced by using this classical biocomposites. The tensile test, hardness and tear resistance test were conducted in a Universal testing machine as per ASTM D638, ASTM D2240 and ASTM D1004 standard, respectively. Although commercial industries have increasingly been concerned with the low cost, light weight and eco-friendly material, the biocomposite material has also a great potential for reduced production cost and low maintenance which have proven to be a main factor in a push towards recycled biocomposites. In this paper we have fabricated a biocomposite model from materials like sawdust, rice husk. The main reason to use biocomposites is that they are more economical and have high strength to weight ratio compared to glass fibers. Hence fabricated material can be used for various applications.

Germplasm should be conserved in such a way that the genetic integrity of a given accession is maintained. In most genebanks, landraces constitute a major portion of collections, wherein the extent of genetic diversity within and among landraces of crops vary depending on the extent of outcrossing and selection intensity infused by farmers. In this study, we assessed the level of diversity within and among 108 diverse landraces and wild accessions using both phenotypic and genotypic characterization. This included 36 accessions in each of sorghum, pearl millet, and pigeonpea, conserved at ICRISAT genebank. We genotyped about 15 to 25 individuals within each accession, totaling 1,980 individuals using the DArTSeq approach. This resulted in 45,249, 19,052, and 8,211 high-quality single nucleotide polymorphisms (SNPs) in pearl millet, sorghum, and pigeonpea, respectively. Sorghum had the lowest average phenotypic (0.090) and genotypic (0.135) within accession distances, while pearl millet had the highest average phenotypic (0.227) and genotypic (0.245) distances. Pigeonpea had an average of 0.203 phenotypic and 0.168 genotypic within accession distances. Analysis of molecular variance also confirms the lowest variability within accessions of sorghum (26.3%) and the highest of 80.2% in pearl millet, while an intermediate in pigeonpea (57.0%). The effective sample size required to capture maximum variability and to retain rare alleles while regeneration ranged from 47 to 101 for sorghum, 155 to 203 for pearl millet, and 77 to 89 for pigeonpea accessions. This study will support genebank curators, in understanding the dynamics of population within and among accessions, in devising appropriate germplasm conservation strategies, and aid in their utilization for crop improvement.

We investigated the impact of renal impairment (RI) on the outcome in multiple myeloma (MM) patients following induction and autologous stem cell transplantation (ASCT). Among 349 patients who received a first ASCT for MM, 86 (24.6%) had RI at diagnosis, defined as estimation of glomerular filtration rate (eGFR)

Background: The Indian population is facing highest dengue burden worldwide supporting an urgent need for vaccines. For vaccine introduction, evaluation and interpretation it is important to gain a critical understanding of immune memory induced by natural exposure. However, immune memory to dengue remains poorly characterized in this region. Methods: We enumerated levels of dengue specific memory B cells (MBC), neutralizing (NT) and binding antibodies in healthy adults (n = 70) from New Delhi. Results: NT-antibodies, binding antibodies and MBC were detectable in 86%, 86.56% and 81.63% of the subjects respectively. Among the neutralizing positive subjects, 58%, 27%, 5% and 10% neutralized all four, any three, any two and any one dengue serotypes respectively. The presence of the neutralizing antibodies was associated with the presence of the MBC and binding antibodies. However, a massive interindividual variation was observed in the levels of the neutralizing antibodies (range,

An amendment to this paper has been published and can be accessed via the original article.

Ebselen is a synthetic, lipid-soluble seleno-organic compound. The high electrophilicity of ebselen enables it to react with multiple cysteine residues of various proteins. Despite extensive research on ebselen, its target molecules and mechanism of action remains less understood. We performed biochemical as well as in vivo experiments employing budding yeast as a model organism to understand the mode of action of ebselen. The growth curve analysis and FACS (florescence activated cell sorting) assays revealed that ebselen exerts growth inhibitory effects on yeast cells by causing a delay in cell cycle progression. We observed that ebselen exposure causes an increase in intracellular ROS levels and mitochondrial membrane potential, and that these effects were reversed by addition of antioxidants such as reduced glutathione (GSH) or N-acetyl-l-cysteine (NAC). Interestingly, a significant increase in ROS levels was noticed in gdh3-deleted cells compared to wild-type cells. Furthermore, we showed that ebselen inhibits GDH function by interacting with its cysteine residues, leading to the formation of inactive hexameric GDH. Two-dimensional gel electrophoresis revealed protein targets of ebselen including CPR1, the yeast homolog of Cyclophilin A. Additionally, ebselen treatment leads to the inhibition of yeast sporulation. These results indicate a novel direct connection between ebselen and redox homeostasis.

Gene expression is a multi-step process which requires recruitment of several factors to promoters. One of the factors, Sen1p is an RNA/DNA helicase implicated in transcriptional termination and RNA processing in yeast. In the present study, we have identified a novel function of Sen1p that regulates the expression of ribonucleotide reductase RNR1 gene, which is essential for maintaining genomic integrity. Cells with mutation in the helicase domain or lacking N-terminal domain of Sen1p displayed a drastic decrease in the basal level transcription of RNR1 gene and showed enhanced sensitivity to various DNA damaging agents. Moreover, SEN1 mutants [Sen1-1 (G1747D), Sen1-2 (Δ1-975)] exhibited defects in DNA damage checkpoint activation. Surprisingly, CRT1 deletion in Sen1p mutants (Sen1-1, Sen1-2) was partly able to rescue the slow growth phenotype upon genotoxic stress. Altogether, our observations suggest that Sen1p is required for cell protection against DNA damage by regulating the expression of DNA repair gene RNR1. Thus, the misregulation of Sen1p regulated genes can cause genomic instability that may lead to neurological disorders and premature aging.

Apigenin, a dietary flavonoid, is reported to have several therapeutic effects in different diseases including cancer. Toxicity of Apigenin is however, least explored, and reports are scanty in literature. This warrants dose-specific evaluation of toxicity in vivo. In the present study, Apigenin was administered intraperitoneally to Swiss mice at doses of 25, 50, 100 and 200 mg/kg. Serum levels of alanine amino transferase (ALT), aspartate amino transferase (AST) and alkaline phosphatase (ALP) were measured along with the examination of liver histology, reactive oxygen species (ROS) in blood, lipid peroxidation (LPO), glutathione level, superoxide dismutase activity, catalase activity, glutathione S-transferase activity and gene expression in liver tissue. Increase in ALT, AST, ALP, ROS, ratio of oxidized to reduced glutathione (GSSG/GSH) and LPO, altered enzyme activities along with damaged histoarchitecture in the liver of 100 or 200 mg/kg Apigenin treated animals were found. Microarray analysis revealed the differential expression of genes that correspond to different biologically relevant pathways including oxidative stress and apoptosis. In conclusion, these results suggested the oxidative stress induced liver damage which may be due to the regulation of multiple genes by Apigenin at higher doses in Swiss mice.

RETRACTION NOTICE (26 th March 2024): The article by Rajput PS, Basnet S, Paudel Pk et al. Case Report: A newborn in western Nepal with Harlequin ichthyosis [version 1; peer review: awaiting peer review]. F1000Research 2023, 12:1609 ( https://doi.org/10.12688/f1000research.55349.1) has been retracted from F1000Research by the F1000 Editorial Team. This article was submitted to F1000Research on 21 st July 2021 and was published on 29 th December 2023. During post-publication peer review, a peer reviewer noted that this article was also published in Med Phoenix (Nepal Journals Online) PS Rajput: A Newborn in Western Nepal with Harlequin Ichthyosis: A Case Report ( https://doi.org/10.3126/medphoenix.v7i1.43941). This article was published on 19 th August 2022. As per our policies on retraction, the corresponding author was contacted by the F1000 Editorial Team for an explanation. The corresponding author confirmed that the same article had been published on Med Phoenix and acknowledged that they should have withdrawn their article from F1000Research prior to submitting to Med Phoenix. The decision was made by the F1000 Editorial Team to retract this article, due to the duplicate publication and the need to correct the scientific record. Med Phoenix was contacted by the F1000 Editorial Team to make them aware of this retraction. All authors have seen a copy of this retraction notice. We are aware concerns have been raised by some co-authors about the listing of their names in the authorship list.