An effective and economic estimation of population mean in stratified random sampling using a linear cost function.

Improvement in the estimation of population mean has been an area of interest in sampling theory. So many estimators have been suggested for elevated estimation of the population mean in stratified random sampling, but there is still a gap for more closely estimating the population mean. In this paper, the authors propose a ratio-product-cum-exponential-cum-logarithmic type estimator for the enhanced estimation of population mean by implying one auxiliary variable in stratified random sampling using conventional ratio, exponential ratio, and logarithmic ratio type estimators. The suggested estimator is a generalization of ratio, exponential ratio, and logarithmic ratio type estimators, and therefore these are special cases of the proposed estimator. The proposed estimator's bias and MSE are determined and compared with those of influential estimators, with the linear cost function being used to investigate and compare alternatives. Use Cramer's rule to determine the optimal value of the proposed estimator. The proposed estimator is more effective than other existing estimators, according to theoretical observations. For various applications, we suggest using a proposed estimator with the minimal MSE, which is verified by a numerical example, to have practical applicability of theoretical conclusions in real life.

Stubborn Swellings: A Rare Case of Kimura's Disease Presenting as Parotid Swellings.

Kimura disease (KD) is a rare chronic inflammatory disorder characterized by the development of painless subcutaneous nodules, predominantly in the head and neck region. Diagnosis relies on a high index of clinical suspicion and clinicopathological correlation, with core biopsy serving as the gold standard for a definitive diagnosis. While the disease itself is benign, it can cause significant morbidity if left untreated. This case report describes a 48-year-old male who presented with bilateral infraauricular swellings, pruritus, and elevated serum IgE levels along with eosinophilia. Imaging and histopathological correlation confirmed the diagnosis of KD. Combination therapy of corticosteroids and cyclosporine resulted in significant clinical improvement, highlighting the efficacy of the approach while avoiding surgical resection. This case emphasizes the importance of radiologic-pathologic correlation along with the use of serology to effectively diagnose KD, even in atypical presentations.

Quantitative and qualitative analysis of metallic ion release of orthodontic brackets in three different pH conditions - An invitro study.

Background: Fluoridated mouth rinses improve anti-cariogenic environment but decrease oral pH below critical value, affecting orthodontic bracket surface topography and causing corrosive changes over prolonged use. This invitro study aimed to quantitatively and qualitatively assess the surface topography and metallic ion release of the stainless steel (SS) brackets at varying acidic and alkaline pH. Materials and methods: Forty unused SS brackets were divided into four groups (Group A, B, C, D) and immersed for 48- hours in solutions of artificial saliva and sodium fluoride (0.2 %) mouth rinse at varying pH of 5.5,6.7,7 and 8. The surface morphologic changes were analyzed under scanning electron microscope (SEM) at 50×, 150×, and 500× magnification. The changes in slot area were scored using the customized scale. The Energy Dispersive Xray Spectroscopy Analysis (EDAX) was used to estimate the probed elements' atomic and weight percentage. Results: The mean score of the scale was 3.4 for the brackets immersed in the acidic solution which was statistically significant (p = 0.00)and for alkaline and neutral solutions (p = 0.00). Chromium was found to be significantly higher in the alkaline solution (p = 0.016) followed by the neutral solution. Carbon was found excess in acidic solution than the neutral and alkaline solution. Conclusion: Quantitative and qualitative analysis of the ion release in stainless steel brackets using SEM and EDAX revealed the corrosive effect of fluoride ion causing maximum surface changes in acidic medium and chromium release in alkaline pH.

Organic matter degradation in the deep, sulfidic waters of the Black Sea: insights into the ecophysiology of novel anaerobic bacteria.

BACKGROUND: Recent studies have reported the identity and functions of key anaerobes involved in the degradation of organic matter (OM) in deep (> 1000 m) sulfidic marine habitats. However, due to the lack of available isolates, detailed investigation of their physiology has been precluded. In this study, we cultivated and characterized the ecophysiology of a wide range of novel anaerobes potentially involved in OM degradation in deep (2000 m depth) sulfidic waters of the Black Sea. RESULTS: We have successfully cultivated a diverse group of novel anaerobes belonging to various phyla, including Fusobacteriota (strain S5), Bacillota (strains A1T and A2), Spirochaetota (strains M1T, M2, and S2), Bacteroidota (strains B1T, B2, S6, L6, SYP, and M2P), Cloacimonadota (Cloa-SY6), Planctomycetota (Plnct-SY6), Mycoplasmatota (Izemo-BS), Chloroflexota (Chflx-SY6), and Desulfobacterota (strains S3T and S3-i). These microorganisms were able to grow at an elevated hydrostatic pressure of up to 50 MPa. Moreover, this study revealed that different anaerobes were specialized in degrading specific types of OM. Strains affiliated with the phyla Fusobacteriota, Bacillota, Planctomycetota, and Mycoplasmatota were found to be specialized in the degradation of cellulose, cellobiose, chitin, and DNA, respectively, while strains affiliated with Spirochaetota, Bacteroidota, Cloacimonadota, and Chloroflexota preferred to ferment less complex forms of OM. We also identified members of the phylum Desulfobacterota as terminal oxidizers, potentially involved in the consumption of hydrogen produced during fermentation. These results were supported by the identification of genes in the (meta)genomes of the cultivated microbial taxa which encode proteins of specific metabolic pathways. Additionally, we analyzed the composition of membrane lipids of selected taxa, which could be critical for their survival in the harsh environment of the deep sulfidic waters and could potentially be used as biosignatures for these strains in the sulfidic waters of the Black Sea. CONCLUSIONS: This is the first report that demonstrates the cultivation and ecophysiology of such a diverse group of microorganisms from any sulfidic marine habitat. Collectively, this study provides a step forward in our understanding of the microbes thriving in the extreme conditions of the deep sulfidic waters of the Black Sea. Video Abstract.

Immunomodulation by juglone alleviates acute graft-versus-host disease without compromising the graft-versus-leukaemia activity in mice.

BACKGROUND AND PURPOSE: Acute graft-versus-host disease (GVHD) remains a major barrier to successful transplantation outcomes. Recent studies have shown that pharmacotherapy for GVHD should target both the innate and adaptive inflammatory immune responses. Juglone, a redox-active phytochemical found in walnuts, has shown potent anti-inflammatory effects in models of colitis and inflammatory bowel disease. However, its effects on T-cell-mediated immune responses remain largely unknown. Considering the overlapping mediators of inflammation in GVHD and the aforementioned conditions, we investigated the use of juglone as a prophylactic agent for GVHD. EXPERIMENTAL APPROACH: Immunomodulatory activity and mechanism of action of juglone were studied using murine splenic leukocytes in vitro. The GVHD prophylactic efficacy of orally administered juglone was evaluated using a murine model of allogeneic haematopoietic stem cell transplantation based on an MHC mismatch. KEY RESULTS: Juglone exhibited immunomodulatory activity by (i) inhibiting the activation of dendritic cells and CD4+ T-cells, (ii) inhibiting cytokine secretion and lymphocyte proliferation, and (iii) inducing exhaustion of CD4+ T-cells, as shown by increased expression of CTLA-4 (CD152) and Fas (CD95). Oral administration of juglone significantly reduced mortality and morbidity associated with GVHD while maintaining graft-versus-leukaemia activity. This was accompanied by a decrease in the number of naïve CD4+ cells, and an increase in the number of CD4+ and CD8+ central memory T-cells. CONCLUSION AND IMPLICATIONS: Juglone is a potent immunomodulator for GVHD prophylaxis. Our study is the first to provide a dosage framework for the oral administration of juglone that can be used for clinical development.

Rab7-dependent regulation of goblet cell protein CLCA1 modulates gastrointestinal homeostasis.

Inflammation in ulcerative colitis is typically restricted to the mucosal layer of distal gut. Disrupted mucus barrier, coupled with microbial dysbiosis, has been reported to occur prior to the onset of inflammation. Here, we show the involvement of vesicular trafficking protein Rab7 in regulating the colonic mucus system. We identified a lowered Rab7 expression in goblet cells of colon during human and murine colitis. In vivo Rab7 knocked down mice (Rab7KD) displayed a compromised mucus layer, increased microbial permeability, and depleted gut microbiota with enhanced susceptibility to dextran sodium-sulfate induced colitis. These abnormalities emerged owing to altered mucus composition, as revealed by mucus proteomics, with increased expression of mucin protease chloride channel accessory 1 (CLCA1). Mechanistically, Rab7 maintained optimal CLCA1 levels by controlling its lysosomal degradation, a process that was dysregulated during colitis. Overall, our work establishes a role for Rab7-dependent control of CLCA1 secretion required for maintaining mucosal homeostasis.

A computational strategy for estimation of mean using optimal imputation in presence of missing observation.

In this study, we suggest an optimal imputation strategy for the elevated estimation of the population mean of the primary variable utilizing the known auxiliary parameters for the missing observations. Under this strategy, we suggest a new modified Searls type estimator, and we study its sampling properties, mainly bias and mean squared error (MSE), for an approximation of order one. The introduced estimator is compared theoretically with the estimators of population mean in competition under the imputation method. The efficiency conditions for the introduced estimator to be more efficient than the estimators in the competition are derived. To be sure about the efficiencies, these efficiency conditions are verified through the three natural populations. We have also conducted a simulation study and generated an artificial population with the same parameters as a natural population. The estimator with minimum MSE and the highest Percentage Relative Efficiency (PRE) is recommended for practical use in different areas of applications.

TB-free Ebeye: Results from integrated TB and noncommunicable disease case finding in Ebeye, Marshall Islands.

Background: Tuberculosis (TB) incidence rates in the Republic of the Marshall Islands are among the highest in the world, 480/100,000 in 2017. In response, the Health Ministry completed islandwide screening in Ebeye Island in 2017. Methods: Participants were interviewed to obtain TB history, exposures, and symptoms. TB assessment included chest radiography with sputum collection for GeneXpert® MTB-RIF if indicated. TB diagnosis was made by consensus of visiting TB experts. Participants were also screened for Hansen's disease (HD) and diabetes mellitus (DM). For persons aged ≥21 years, blood pressure, cholesterol, and blood glucose were assessed. Results: A total of 5,166 persons (90.0 % of target population) completed screening leading to the identification of 39 new cases of TB (755/100,000) and 14 persons with HD (270/100,000). DM was detected in 1,096 persons (27 %), including in 351 persons not previously diagnosed. The rate of hypertension was 61 % and of hypercholesterolemia was 15 %. New or prevalent TB diagnosis was associated with newly diagnosed or history of DM (aOR 4.68, 2.15-10.20). Conclusions: In Ebeye, an integrated TB screening campaign found TB, HD, DM, and hypertension. TB and DM were strongly associated.

Neuroendocrine neoplasms of the gallbladder: A single institute analysis of outcomes and prognostic factors.

INTRODUCTION: Neuroendocrine neoplasms (NENs) are classified as neuroendocrine tumors (NETs), neuroendocrine carcinomas (NECs), and mixed neuroendocrine and nonneuroendocrine neoplasms (MiNENs) according to World Health Organization classification. We present our experience of NENs of the gallbladder (GB) from a high-volume cancer hospital. MATERIALS AND METHODS: The present study is a retrospective analysis of all patients with GB NENs who presented between January 2015 and June 2023. The patient details and treatment received with follow-up were noted. The primary endpoint was overall survival (OS). RESULTS: A total of 147 patients were included in the study. The median age was 52 (27-81) years. There was a female predominance (70.7%). NEC was the most common subtype (84.4%) followed by MiNEN (12.9%) and NET (2.7%). The most common stage at presentation was metastatic (70.7%) followed by locally advanced (21.8%), and early disease (7.5%). The median follow-up was 9.92 (1.77-76.06) months. Median OS was 6.14 (3.93-8.35) months. Median OS in patients who received multimodality treatment was 20.20 (17.99-22.41) months versus 4.00 (2.91-5.10) months in those who did not receive it. CONCLUSION: GB NENs are rare, but aggressive tumors with NEC being the most common type. Multimodality treatment yields favorable outcomes. However, the development of better systemic therapy is needed to help improve survival further.

Taking cues from machine learning, compartmental and time series models for SARS-CoV-2 omicron infection in Indian provinces.

SARS-CoV-2, the virus responsible for COVID-19, posed a significant threat to the world. We analyzed COVID-19 dissemination data in the top ten Indian provinces by infection incidences using the Susceptible-Infectious-Removed (SIR) model, an Autoregressive Integrated Moving Average (ARIMA) time series model, a machine learning model based on the Random Forest, and distribution fitting. Outbreaks are expected to continue if the Basic Reproduction Number (R0) > 1, and infection waves are anticipated to end if the R0 < 1, as determined by the SIR model. Different parametric probability distributions are also fitted. Data collected from December 12, 2021, to March 31, 2022, encompassing data from both before and during the implementation of strict control measures. Based on the estimates of the model parameters, health agencies and government policymakers can develop strategies to combat the spread of the disease in the future, and the most effective technique can be recommended for real-world application for other outbreaks of COVID-19. The best method out of these could be also implemented further on the epidemiological data of other similar infectious agents.

Withania Somnifera Extract Mitigates Experimental Acute Graft versus Host Disease Without Abrogating Graft Versus Leukemia Effect.

Acute graft versus host disease (aGvHD) is the major contributor of nonrelapse mortality in alloHSCT. It is associated with an inflammatory immune response manifesting as cytokine storm with ensuing damage to target organs such as liver, gut, and skin. Prevention of aGvHD while retaining the beneficial graft versus leukemia (GvL) effect remains a major challenge. Withania somnifera extract (WSE) is known for its anti-inflammatory, immune-modulatory, and anticancer properties, which are appealing in the context of aGvHD. Herein, we demonstrated that prophylactic and therapeutic use of WSE in experimental model of alloHSCT mitigates aGvHD-associated morbidity and mortality. In the prophylaxis study, a dose of 75 mg/kg of WSE offered greatest protection against death due to aGvHD (hazard ratio [HR] = 0.15 [0.03-0.68], P ≤ .01), whereas 250 mg/kg was most effective for the treatment of aGvHD (HR = 0.16 [0.05-0.5], P ≤ .01). WSE treatment protected liver, gut, and skin from damage by inhibiting cytokine storm and lymphocytic infiltration to aGvHD target organs. In addition, WSE did not compromise the GvL effect, as alloHSCT with or without WSE did not allow the leukemic A20 cells to grow. In fact, WSE showed marginal antileukemic effect in vivo. WSE is currently under clinical investigation for the prevention and treatment of aGvHD.

Visual, rapid, and cost-effective BK virus detection system for renal transplanted patients using gold nanoparticle coupled loop-mediated isothermal amplification (nanoLAMP).

A substantial percentage of kidney transplant recipients show transplant failure due to BK virus-induced nephropathy. This can be clinically controlled by the rapid and timely detection of BK virus infection in immune-compromised patients. We report a rapid (two hours from sample collection, processing, and detection), cost-effective (< 2$), highly sensitive and BKV-specific nanoLAMP (loop-mediated isothermal amplification) diagnostic methodology using novel primers and gold nanoparticles complex-based visual detection. The standardized nanoLAMP showed an analytical sensitivity of 25 copies/µl and did not cross-react with closely related JC and SV40 viruses. This nanoLAMP showed diagnostic sensitivity and specificity as 91% and 96%, respectively, taking 50 BK virus-negative (confirmed by qPCR from the plasma of healthy donors) and 57 positive BKV patient samples (confirmed by clinical parameters and qPCR assay). This simple two-step, low-cost, and quick (1-2 h/test) detection would be advantageous over the currently used diagnostic methodology. It may change the paradigm for polyomavirus infection-based failure of renal transplant.

Trastuzumab Plus Gemcitabine-Cisplatin for Treatment-Naïve Human Epidermal Growth Factor Receptor 2-Positive Biliary Tract Adenocarcinoma: A Multicenter, Open-Label, Phase II Study (TAB).

PURPOSE: Human epidermal growth factor receptor 2 (HER2) overexpression is seen in 4%-16% of biliary tract cancers (BTCs). We aimed to evaluate the clinical activity of gemcitabine-cisplatin (GC) plus anti-HER2 antibody trastuzumab as initial treatment in HER2-positive BTCs. METHODS: This study was an investigator-initiated, open-label, single-arm, multi-institutional, phase II trial in adult patients with HER2-positive (defined as immunohistochemistry [IHC] 3+ or IHC 2+ and fluorescent in situ hybridization-positive), treatment-naïve BTCs. The primary end point of the study was 6-month progression-free survival (PFS). Next-generation sequencing was performed on tissue samples to evaluate mutational status. RESULTS: From March 2020 to August 2022, of the 876 screened patients, 118 (13.4%) were found to have HER2-positive status, of whom 90 were enrolled in the study. Most patients had GBC (n = 96; 96%) with two or more sites of metastatic disease (n = 70; 78%). With a median follow-up of 17.3 (95% CI, 15.22 to 19.32) months, 72 patients had disease progression with a median PFS of 7 (95% CI, 6.2 to 7.8) months. The diagnosis to event 6-month PFS rate was 75.6% (95% CI, 66.6 to 84.6). A complete or partial response was seen in 50 (55.5%) patients and 22 (24.4%) patients had stable disease as the best response to treatment, for an overall disease control rate of 80%. The presence of isolated TP53 mutations was associated with inferior PFS compared with other mutations (TERT promoter, HER2, PIK3CA, etc) or no detected mutations (6.51 v 12.02 v 10.58 months; P < .001). CONCLUSION: The combination of GC and trastuzumab achieved its primary end point of improving PFS compared with historical data in the treatment-naïve HER2-positive BTC. Evaluating additional mutations such as TP53 and PIK3CA along with HER2 testing may help to preferentially select patients for anti-HER2 therapy in the future (Clinical Trial Registry India number: CTRI/2019/11/021955).

Modeling Global Monkeypox Infection Spread Data: A Comparative Study of Time Series Regression and Machine Learning Models.

The global impact of COVID-19 has heightened concerns about emerging viral infections, among which monkeypox (MPOX) has become a significant public health threat. To address this, our study employs a comprehensive approach using three statistical techniques: Distribution fitting, ARIMA modeling, and Random Forest machine learning to analyze and predict the spread of MPOX in the top ten countries with high infection rates. We aim to provide a detailed understanding of the disease dynamics and model theoretical distributions using country-specific datasets to accurately assess and forecast the disease's transmission. The data from the considered countries are fitted into ARIMA models to determine the best time series regression model. Additionally, we employ the random forest machine learning approach to predict the future behavior of the disease. Evaluating the Root Mean Square Errors (RMSE) for both models, we find that the random forest outperforms ARIMA in six countries, while ARIMA performs better in the remaining four countries. Based on these findings, robust policy-making should consider the best fitted model for each country to effectively manage and respond to the ongoing public health threat posed by monkeypox. The integration of multiple modeling techniques enhances our understanding of the disease dynamics and aids in devising more informed strategies for containment and control.

Factors Affecting Biochemical and Echocardiographic Indices in Type 2 Diabetes Mellitus Patients Without Overt Symptoms of Heart Failure: A Cross-Sectional Study.

Introduction Diabetes is a known risk factor for heart failure (HF), and HF often manifests as a common cardiovascular event in people with type-2 diabetes mellitus (T2DM). Once HF is present, diabetes presents an especially adverse prognosis for subsequent morbidity and mortality. Brain natriuretic peptide (BNP) and n-terminal ProBNP (NT-proBNP) are used as diagnostic biomarkers for HF that are secreted by the ventricles in response to increased myocardial wall stress. If we could unmask some clinical and routine laboratory parameters affecting BNP and ejection fraction (EF), we can predict impending HF and take measures to prevent it. The current study was conducted to investigate the factors affecting BNP and EF for detecting potential HF in T2DM patients who do not exhibit overt HF symptoms. Materials and methods The present cross-sectional study was performed after obtaining ethical clearance from the Institutional Ethics Committee. T2DM patients consulting the Medicine Outpatient Department (OPD) of BRD Medical College Gorakhpur during a two-month period (from 20 July 2023 to 19 September 2023) with age >40 years and duration of T2DM >10 years. Multistage random sampling was done to recruit study participants, and 308 patients participated in the study. Informed consent was obtained from the recruited participants. The chi-square or Fisher's exact test (whichever was applicable) was used to explore the association between categorical variables. Correlation statistics were calculated using Spearman correlation among the NT-proBNP, EF, and other relevant variables. The Statistical Package for Social Sciences (SPSS) (version 21; IBM SPSS Statistics for Windows, Armonk, NY) was used for the analysis, and a two-sided p-value of < 0.05 was considered significant. Results Three hundred and eight diabetic patients satisfying inclusion and exclusion criteria were enrolled as study participants and completed the study. The mean age of the total study subjects was 60.82 ± 9.23 years. There were 161 (52.3%) male and 147 (47.7%) female participants, and about half (153/308, 49.7%) of the participants belonged to the age group 40-60 years. There was a statistically significant association (p = 0.01) between NT-proBNP and glycated hemoglobin. Statistically highly significant (p < 0.001) associations were found between NT-proBNP with duration of T2DM and EF. There was a strong negative correlation (correlation coefficient = -0.743) between EF and NT-proBNP, and this correlation was statistically highly significant with a p-value < 0.001. Conclusion Elevated NT-proBNP levels and impaired EF were found in a significant proportion of these patients, indicating an increased risk of cardiovascular complications. This study highlights a significant association between NT-proBNP and EF in patients with T2DM in those without overt heart failure symptoms. Furthermore, longer T2DM duration and higher HbA1c levels were found to be associated with elevated NT-proBNP levels, while longer T2DM duration and elevated NT-proBNP were linked to lower EF. These findings have important clinical implications, as they suggest that monitoring NT-proBNP levels in patients with T2DM without clinical features of overt heart failure may help identify those at risk for decreased EF and potentially prevent heart failure.

Advancements in lanthanide-based perovskite oxide semiconductors for gas sensing applications: a focus on doping effects and development.

Lanthanide-based perovskite oxide semiconductors have garnered significant attention due to their exceptional electrical and sensing properties, making them promising candidates for gas sensing applications. This review paper focuses on developments and the impact of doping in lanthanide-based perovskite oxide semiconductors for gas sensing purposes. The review explores the factors influencing gas sensing performance, such as operating temperature, dopant selection, and target gas species. The role of dopants in enhancing gas sensing selectivity, sensitivity, response/recovery times, and stability is discussed in detail. Comparisons are drawn between doped perovskite oxide semiconductors, undoped counterparts, and other gas-sensing materials. Practical applications of lanthanide-based perovskite oxide semiconductor gas sensors are outlined, including environmental monitoring, industrial process control, and healthcare. The review also identifies current challenges and future perspectives in the field, such as the exploration of novel doping strategies and integration with emerging technologies like the Internet of Things (IoT). The findings emphasize the potential of these materials in advancing gas sensing technology and the importance of continued research in this field.

IgG4-related disorders of the gastrointestinal tract: Experience from a tertiary care centre with systematic review of Indian literature.

INTRODUCTION: IgG4-related disease (IgG4-RD) is a rare disease entity in India. We aimed at studying the clinical profile of IgG4-RD of gastrointestinal tract (GIT) from our centre, while systematically reviewing data from India. METHODS: Retrospective review of IgG4-RD of GIT was done using electronic medical records between January 2013 and July 2022. Literature search was done for studies of IgG4-RD of the GIT reported from India from 2000 till January 2023. Case series, case reports of IgG4-RD of GIT and case reports describing GIT with multi-organ involvement were included in the review. Primary outcome measure was response to treatment. Secondary outcome measure was relapse after remission. RESULTS: Thirty-one patients were included with 71% (22/31) having autoimmune pancreatitis. The diagnosis was achieved on surgical specimen in 35% (11/31) patients. Steroid was given to 64% (20/31) patients with remission achieved in 70% (14/20) patients. Four patients exhibitted response to prolonged course of steroids with maintenance azathioprine. Relapse was seen in four (20%) patients who achieved remission. Of 731 articles screened, 48 studies (four case series and 44 case reports) were included in the literature review. Of 95 patients described, steroids were given to 65.2% (62/95), while surgery was done in 33.6% (32/95). Remission was seen in 96.6% (85/88) with relapse occurring in 11.4% (10/88) patients on follow-up. CONCLUSION: One-third patients of IgG4-RD of GIT are diagnosed after surgery. Response to steroids is good with relapse occurring in up to 12% patients.

Differentiation of Discordant Lesions on Dual-Tracer PET/CT (68Ga-PSMA-11 and 18F-FDG) in Prostate Carcinoma: Diagnosis of Second Primary Malignancies.

We present 2 cases of metastatic castration-resistant prostate carcinoma with discordant lesions on dual-tracer PET/CT (68Ga-PSMA-11 and 18F-FDG PET/CT), which on subsequent histopathologic evaluation revealed second primary malignancies of combined hepatocellular carcinoma and cholangiocarcinoma and poorly differentiated squamous cell carcinoma. These case illustrations emphasize the need to evaluate discordant lesions on dual-tracer PET/CT, which can lead to early diagnosis of second primary malignancies and thereby can provide better management in these patients.

Impact of prophylactic hydroxychloroquine on ultrastructural impairment and cellular SARS-CoV-2 infection in different cells of bronchoalveolar lavage fluids of COVID-19 patients.

Many drugs were recommended as antiviral agents for infection control and effective therapy to reduce the mortality rate for COVID-19 patients. Hydroxychloroquine (HCQ), an antimalarial drug, has been controversially recommended for prophylactic use in many countries, including India, to control SARS-CoV-2 infections. We have explored the effect of prophylactic HCQ from the cells of bronchoalveolar lavage fluids from COVID-19-induced acute respiratory distress syndrome patients to determine the level of infection and ultrastructural alterations in the ciliated epithelium, type II pneumocytes, alveolar macrophages, neutrophils, and enucleated granulocytes. Ultrastructural investigation of ciliated epithelium and type II pneumocytes showed lesser infections and cellular impairment in the prophylactic HCQ+ group than HCQ- group. However, macrophages and neutrophils displayed similar infection and ultrastructural alterations in both patient groups. The enucleated fragments of granulocytes showed phagocytosis of the matured virus in HCQ+ groups. The present report unveils the ultrastructural proof to complement the paradox regarding the role of prophylactic HCQ in COVID-19 patients.

Withaferin-A alleviates acute graft versus host disease without compromising graft versus leukemia effect.

Acute graft versus host disease (aGvHD) contributes to a significant proportion of non-relapse mortality and morbidity in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). Withaferin-A (WA), a phytomolecule obtained from Withania somnifera (Ashwagandha), is known to have anti-inflammatory, anti-proliferative and immunomodulatory properties. The efficacy of WA for the prevention and treatment of aGvHD was evaluated using a murine model of alloHSCT. Prophylactic administration of WA to mice mitigated the clinical symptoms of aGvHD and improved survival significantly compared to the GvHD control [HR = 0.07 (0.01-0.35); P < 0.001]. Furthermore, WA group had better overall survival compared to standard prophylactic regimen of CSA + MTX [HR = 0.19 (0.03-1.1), P < 0.05]. At the same time, WA did not compromise the beneficial GvL effect. In addition, WA administered to animals after the onset of aGvHD could reverse the clinical severity and improved survival, thus establishing its therapeutic potential. Our findings suggest that WA reduced the systemic levels of Th1, Th2 and Th17 inflammatory cytokine and increased the anti-inflammatory cytokine IL-10 levels significantly (P < 0.05). WA also inhibited lymphocytes migration to gut, liver, skin and lung and protected these organs from damage. Ex-vivo, WA inhibited proliferation of human peripheral blood mononuclear cells (hPBMCs), modulated immune cell phenotype and decreased cytokine release. In addition, WA inhibited pJAK2 and pSTAT3 protein levels in mouse splenocytes and hPBMCs. In conclusion, our study demonstrates the utility of WA for the prevention and treatment of aGvHD, which should be further evaluated in a clinical setting.