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Abstract HNF4A and HNF1A encode transcription factors that are important for the development and function of the pancreas and liver. Mutations in both genes have been directly linked to Maturity Onset Diabetes of the Young (MODY) and type 2 diabetes (T2D) risk. To better define the pleiotropic gene regulatory roles of HNF4A and HNF1A, we generated a comprehensive genome-wide map of their binding targets in pancreatic and hepatic cells using ChIP-Seq. HNF4A was found to bind and regulate known (ACY3, HAAO, HNF1A, MAP3K11) and previously unidentified (ABCD3, CDKN2AIP, USH1C, VIL1) loci in a tissue-dependent manner. Functional follow-up highlighted a potential role for HAAO and USH1C as regulators of beta cell function. Unlike the loss-of-function HNF4A/MODY1 variant I271fs, the T2D-associated HNF4A variant (rs1800961) was found to activate AKAP1, GAD2 and HOPX gene expression, potentially due to changes in DNA-binding affinity. We also found HNF1A to bind to and regulate GPR39 expression in beta cells. Overall, our studies provide a rich resource for uncovering downstream molecular targets of HNF4A and HNF1A that may contribute to beta cell or hepatic cell (dys)function, and set up a framework for gene discovery and functional validation.

Abstract Background Liver transplantation (LT) is offered as a cure for Hepatocellular carcinoma (HCC), however 15–20% develop recurrence post-transplant which tends to be aggressive. In this study, we examined the transcriptome profiles of patients with recurrent HCC to identify differentially expressed genes (DEGs), the involved pathways, biological functions, and potential gene signatures of recurrent HCC post-transplant using deep machine learning (ML) methodology. Materials and methods We analyzed the transcriptomic profiles of primary and recurrent tumor samples from 7 pairs of patients who underwent LT. Following differential gene expression analysis, we performed pathway enrichment, gene ontology (GO) analyses and protein-protein interactions (PPIs) with top 10 hub gene networks. We also predicted the landscape of infiltrating immune cells using Cibersortx. We next develop pathway and GO term-based deep learning models leveraging primary tissue gene expression data from The Cancer Genome Atlas (TCGA) to identify gene signatures in recurrent HCC. Results The PI3K/Akt signaling pathway and cytokine-mediated signaling pathway were particularly activated in HCC recurrence. The recurrent tumors exhibited upregulation of an immune-escape related gene, CD274, in the top 10 hub gene analysis. Significantly higher infiltration of monocytes and lower M1 macrophages were found in recurrent HCC tumors. Our deep learning approach identified a 20-gene signature in recurrent HCC. Amongst the 20 genes, through multiple analysis, IL6 was found to be significantly associated with HCC recurrence. Conclusion Our deep learning approach identified PI3K/Akt signaling as potentially regulating cytokine-mediated functions and the expression of immune escape genes, leading to alterations in the pattern of immune cell infiltration. In conclusion, IL6 was identified to play an important role in HCC recurrence.

Primary breast stromal sarcomas are rare entities arising from connective tissue within the breast, accounting for

Background: Cytological study of pleural fluid helps establishing the underlying cause of pleural effusion. It is considered the most important tool in diagnosing malignancy in effusions. However, accurate identification of cellular morphology can be a problem in conventional cytology. Cell block preparation from pleural effusion aids in this diagnosis due to the preservation of tissue architecture, and multiple sections can be obtained for further studies. Aims and Objectives: The objectives of this study were to compare the diagnostic results of conventional cytology and cell block studies of suspected malignant pleural effusions and find out the diagnostic agreement or concordance between the two methods. Materials and Methods: A record-based study was conducted at the Department of Pathology on conventional cytology and cell block study reports of 150 suspected malignant pleural effusion cases over 35 months. The diagnoses were expressed in five categories – non-diagnostic, negative for malignancy, atypia of undetermined significance, suspicious for malignancy, and malignant. χ2 test was used to identify the percentage of malignancy reported. Agreement of both methods was assessed through Kappa statistics. Results: About 4.67% of cases were reported as malignant by conventional cytology, whereas cell block study diagnosed malignancy in 19.33% of cases. Relative diagnostic agreement between the two methods was 0.73 and concordance by Cohen’s Kappa was 0.34, which signifies fair concordance. Conclusion: Cell block study, though having a fair concordance, is much superior to conventional cytology smears in detecting malignant cells and diagnosing a pleural effusion as malignant.

Despite large collections of cancer genomics data being openly available, the inability to quickly interrogate this information remains a barrier for researchers and oncologists. Here we present Melvin, an Amazon Alexa skill to explore cancer genomics data through simple conversations.

Abstract The coding variant (p.Arg192His) in the transcription factor PAX4 is associated with an altered risk for type 2 diabetes (T2D) in East Asian populations. In mice, Pax4 is essential for beta cell formation but its role on human beta cell development and/or function is unknown. Participants carrying the PAX4 p.His192 allele exhibited decreased pancreatic beta cell function compared to homozygotes for the p.192Arg allele in a cross-sectional study in which we carried out an intravenous glucose tolerance test and an oral glucose tolerance test. In a pedigree of a patient with young onset diabetes, several members carry a newly identified p.Tyr186X allele. In the human beta cell model, EndoC-βH1, PAX4 knockdown led to impaired insulin secretion, reduced total insulin content, and altered hormone gene expression. Deletion of PAX4 in human induced pluripotent stem cell (hiPSC)-derived islet-like cells resulted in derepression of alpha cell gene expression. In vitro differentiation of hiPSCs carrying PAX4 p.His192 and p.X186 risk alleles exhibited increased polyhormonal endocrine cell formation and reduced insulin content that can be reversed with gene correction. Together, we demonstrate the role of PAX4 in human endocrine cell development, beta cell function, and its contribution to T2D-risk.

Abstract Renal defects in maturity onset diabetes of the young 3 (MODY3) patients and Hnf1a -/- mice suggest an involvement of HNF1A in kidney development and/or its function. Although numerous studies have leveraged on Hnf1α -/- mice to infer some transcriptional targets and function of HNF1A in mouse kidneys, species-specific differences obviate a straightforward extrapolation of findings to the human kidney. Additionally, genome-wide targets of HNF1A in human kidney cells have yet to be identified. Here, we leveraged on human in vitro kidney cell models to characterize the expression profile of HNF1A during renal differentiation and in adult kidney cells. We found HNF1A to be increasingly expressed during renal differentiation, with peak expression on day 28 in the proximal tubule cells. HNF1A ChIP-Sequencing (ChIP-Seq) performed on human pluripotent stem cell (hPSC)-derived kidney organoids identified its genome-wide putative targets. Together with a qPCR screen, we found HNF1A to activate the expression of SLC51B, CD24, and RNF186 genes. Importantly, HNF1A-depleted human renal proximal tubule epithelial cells (RPTECs) and MODY3 human induced pluripotent stem cell (hiPSC)-derived kidney organoids expressed lower levels of SLC51B. SLC51B-mediated estrone sulfate (E1S) uptake in proximal tubule cells was abrogated in these HNF1A-deficient cells. MODY3 patients also exhibit significantly higher excretion of urinary E1S. Overall, we report that SLC51B is a target of HNF1A responsible for E1S uptake in human proximal tubule cells. As E1S serves as the main storage form of nephroprotective estradiol in the human body, lowered E1S uptake and increased E1S excretion may reduce the availability of nephroprotective estradiol in the kidneys, contributing to the development of renal disease in MODY3 patients.

Abstract Background Lipids may influence cellular penetrance by viral pathogens and the immune response that they evoke. We deeply phenotyped the lipidomic response to SARs‐CoV‐2 and compared that with infection with other pathogens in patients admitted with acute respiratory distress syndrome to an intensive care unit (ICU). Methods Mass spectrometry was used to characterise lipids and relate them to proteins, peripheral cell immunotypes and disease severity. Results Circulating phospholipases (sPLA2, cPLA2 (PLA2G4A) and PLA2G2D) were elevated on admission in all ICU groups. Cyclooxygenase, lipoxygenase and epoxygenase products of arachidonic acid (AA) were elevated in all ICU groups compared with controls. sPLA2 predicted severity in COVID‐19 and correlated with TxA2, LTE4 and the isoprostane, iPF2α‐III, while PLA2G2D correlated with LTE4. The elevation in PGD2, like PGI2 and 12‐HETE, exhibited relative specificity for COVID‐19 and correlated with sPLA2 and the interleukin‐13 receptor to drive lymphopenia, a marker of disease severity. Pro‐inflammatory eicosanoids remained correlated with severity in COVID‐19 28 days after admission. Amongst non‐COVID ICU patients, elevations in 5‐ and 15‐HETE and 9‐ and 13‐HODE reflected viral rather than bacterial disease. Linoleic acid (LA) binds directly to SARS‐CoV‐2 and both LA and its di‐HOME products reflected disease severity in COVID‐19. In healthy marines, these lipids rose with seroconversion. Eicosanoids linked variably to the peripheral cellular immune response. PGE2, TxA2 and LTE4 correlated with T cell activation, as did PGD2 with non‐B non‐T cell activation. In COVID‐19, LPS stimulated peripheral blood mononuclear cell PGF2α correlated with memory T cells, dendritic and NK cells while LA and DiHOMEs correlated with exhausted T cells. Three high abundance lipids – ChoE 18:3, LPC‐O‐16:0 and PC‐O‐30:0 – were altered specifically in COVID. LPC‐O‐16:0 was strongly correlated with T helper follicular cell activation and all three negatively correlated with multi‐omic inflammatory pathways and disease severity. Conclusions A broad based lipidomic storm is a predictor of poor prognosis in ARDS. Alterations in sPLA2, PGD2 and 12‐HETE and the high abundance lipids, ChoE 18:3, LPC‐O‐16:0 and PC‐O‐30:0 exhibit relative specificity for COVID‐19 amongst such patients and correlate with the inflammatory response to link to disease severity.

Background: Severe acute respiratory distress syndrome coronavirus 2 pandemic shows a spectrum of symptoms and complications which are variably dependent on individual’s immune status. Vitamin D deficiency, often preexisting, causes poor prognosis in the post-COVID recovery phase of the survivors characterized by increased C-reactive protein (CRP) and decreased D-dimer levels. Aims and Objectives: The aims of this study were to find any correlation exists between vitamin D level and inflammatory marker CRP and D-dimer in post-COVID period. Materials and Methods: Seventy post-COVID recovery patients from the follow-up medicine outpatient department of College of Medicine and Sagore Dutta Hospital were tested for vitamin D, D-dimer, and serum CRP levels. Results: CRP levels of patients with lower vitamin D level (

Graft injury affects over 50% of liver transplant (LT) recipients, but non-invasive biomarkers to diagnose and guide treatment are currently limited. We aimed to develop a biomarker of graft injury by integrating serum metabolomic profiles with clinical variables. Serum from 55 LT recipients with biopsy confirmed metabolic dysfunction-associated steatohepatitis (MASH), T-cell mediated rejection (TCMR) and biliary complications was collected and processed using a combination of LC-MS/MS assay. The metabolomic profiles were integrated with clinical information using a multi-class Machine Learning (ML) classifier. The model’s efficacy was assessed through the Out-of-Bag (OOB) error estimate evaluation. Our ML model yielded an overall accuracy of 79.66% with an OOB estimate of the error rate at 19.75%. The model exhibited a maximum ability to distinguish MASH, with an OOB error estimate of 7.4% compared to 22.2% for biliary and 29.6% for TCMR. The metabolites serine and serotonin emerged as the topmost predictors. When predicting binary outcomes using three models: Biliary (biliary vs. rest), MASH (MASH vs. rest) and TCMR (TCMR vs. rest); the AUCs were 0.882, 0.972 and 0.896, respectively. Our ML tool integrating serum metabolites with clinical variables shows promise as a non-invasive, multi-class serum biomarker of graft pathology.

Background: The major focus of metabolomics research has been confined to the readily available biofluids—urine and blood serum. However, red blood cells (RBCs) are also readily available, and may be a source of a wealth of information on vertebrates. However, the comprehensive metabolomic characterization of RBCs is minimal although they exhibit perturbations in various physiological states. RBCs act as the host of malarial parasites during the symptomatic stage. Thus, understanding the changes in RBC metabolism during infection is crucial for a better understanding of disease progression. Methods: The metabolome of normal RBCs obtained from Swiss mice was investigated using 1H NMR spectroscopy. Several 1 and 2-dimensional 1H NMR experiments were employed for this purpose. The information from this study was used to investigate the changes in the RBC metabolome during the early stage of infection (~1% infected RBCs) by Plasmodium bergheii ANKA. Results: We identified over 40 metabolites in RBCs. Several of these metabolites were quantitated using 1H NMR spectroscopy. The results indicate changes in the choline/membrane components and other metabolites during the early stage of malaria. Conclusions: The paper reports the comprehensive characterization of the metabolome of mouse RBCs. Changes during the early stage of malarial infection suggest significant metabolic alteration, even at low parasite content (~1%). General significance: This study should be of use in maximizing the amount of information available from metabolomic experiments on the cellular components of blood. The technique can be directly applied to real-time investigation of infectious diseases that target RBCs.

The integration and interpretation of different omics data types is an ongoing challenge for biologists. Here, the authors present a web-based, interactive tool called multiSLIDE for the visualization of protein, phosphoprotein, and RNA data presented as interlinked heatmaps.

Topoisomerase 3β (Top3β) solves topological stress in DNA or RNA metabolism and its mutations are linked to mental disorders. Here, the authors describe transcriptional and behavioural impairments in Top3β-knockout mice and show that these are linked to impaired neurogenesis and synaptic plasticity.

Primary Epstein-Barr virus (EBV)-positive nodal T/NK-cell lymphoma (PTCL-EBV) is a poorly understood disease which shows features resembling extranodal NK/T-cell lymphoma (ENKTL) and is currently not recognized as a distinct entity but categorized as a variant of primary T-cell lymphoma not otherwise specified (PTCL-NOS). Herein, we analyzed copynumber aberrations (n=77) with a focus on global measures of genomic instability and homologous recombination deficiency and performed gene expression (n=84) and EBV miRNA expression (n=24) profiling as well as targeted mutational analysis (n=16) to further characterize PTCL-EBV in relation to ENKTL and PTCL-NOS. Multivariate analysis revealed that patients with PTCL-EBV had a significantly worse outcome compared to patients with PTCL-NOS (P=0.002) but not to those with ENKTL. Remarkably, PTCL-EBV exhibited significantly lower genomic instability and homologous recombination deficiency scores compared to ENKTL and PTCL-NOS. Gene set enrichment analysis revealed that many immune-related pathways, interferon α/γ response, and IL6_JAK_STAT3 signaling were significantly upregulated in PTCLEBV and correlated with lower genomic instability scores. We also identified that NFκB-associated genes, BIRC3, NFKB1 (P50) and CD27, and their proteins are upregulated in PTCL-EBV. Most PTCL-EBV demonstrated a type 2 EBV latency pattern and, strikingly, exhibited downregulated expression of most EBV miRNA compared to ENKTL and their target genes were also enriched in immune-related pathways. PTCL-EBV also showed frequent mutations of TET2, PIK3CD and STAT3, and are characterized by microsatellite stability. Overall, poor outcome, low genomic instability, upregulation of immune pathways and downregulation of EBV miRNA are distinctive features of PTCL-EBV. Our data support the concept that PTCL-EBV could be considered as a distinct entity, provide novel insights into the pathogenesis of the disease and offer potential new therapeutic targets for this tumor.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, providing safe in-person schooling has been a dynamic process balancing evolving community disease burden, scientific information, and local regulatory requirements with the mandate for education. Considerations include the health risks of SARS-CoV-2 infection and its post-acute sequelae, the impact of remote learning or periods of quarantine on education and well-being of children, and the contribution of schools to viral circulation in the community. The risk for infections that may occur within schools is related to the incidence of SARS-CoV-2 infections within the local community. Thus, persistent suppression of viral circulation in the community through effective public health measures including vaccination is critical to in-person schooling. Evidence suggests that the likelihood of transmission of SARS-CoV-2 within schools can be minimized if mitigation strategies are rationally combined. This article reviews evidence-based approaches and practices for the continual operation of in-person schooling.

ABSTRACT After emerging in China in late 2019, the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide, and as of mid-2021, it remains a significant threat globally. Only a few coronaviruses are known to infect humans, and only two cause infections similar in severity to SARS-CoV-2: Severe acute respiratory syndrome-related coronavirus, a species closely related to SARS-CoV-2 that emerged in 2002, and Middle East respiratory syndrome-related coronavirus, which emerged in 2012. Unlike the current pandemic, previous epidemics were controlled rapidly through public health measures, but the body of research investigating severe acute respiratory syndrome and Middle East respiratory syndrome has proven valuable for identifying approaches to treating and preventing novel coronavirus disease 2019 (COVID-19). Building on this research, the medical and scientific communities have responded rapidly to the COVID-19 crisis and identified many candidate therapeutics. The approaches used to identify candidates fall into four main categories: adaptation of clinical approaches to diseases with related pathologies, adaptation based on virological properties, adaptation based on host response, and data-driven identification (ID) of candidates based on physical properties or on pharmacological compendia. To date, a small number of therapeutics have already been authorized by regulatory agencies such as the Food and Drug Administration (FDA), while most remain under investigation. The scale of the COVID-19 crisis offers a rare opportunity to collect data on the effects of candidate therapeutics. This information provides insight not only into the management of coronavirus diseases but also into the relative success of different approaches to identifying candidate therapeutics against an emerging disease. IMPORTANCE The COVID-19 pandemic is a rapidly evolving crisis. With the worldwide scientific community shifting focus onto the SARS-CoV-2 virus and COVID-19, a large number of possible pharmaceutical approaches for treatment and prevention have been proposed. What was known about each of these potential interventions evolved rapidly throughout 2020 and 2021. This fast-paced area of research provides important insight into how the ongoing pandemic can be managed and also demonstrates the power of interdisciplinary collaboration to rapidly understand a virus and match its characteristics with existing or novel pharmaceuticals. As illustrated by the continued threat of viral epidemics during the current millennium, a rapid and strategic response to emerging viral threats can save lives. In this review, we explore how different modes of identifying candidate therapeutics have borne out during COVID-19.

Cell cycle progression and lipid metabolism are well-coordinated processes required for proper cell proliferation. In liver diseases that arise from dysregulated lipid metabolism, hepatocyte proliferation is diminished. To study the outcome of CDK1 loss and blocked hepatocyte proliferation on lipid metabolism and the consequent impact on whole-body physiology, we performed lipidomics, metabolomics, and RNA-seq analyses on a mouse model. We observed reduced triacylglycerides in liver of young mice, caused by oxidative stress that activated FOXO1 to promote the expression of Pnpla2/ATGL. Additionally, we discovered that hepatocytes displayed malfunctioning β-oxidation, reflected by increased acylcarnitines (ACs) and reduced β-hydroxybutyrate. This led to elevated plasma free fatty acids (FFAs), which were transported to the adipose tissue for storage and triggered greater insulin secretion. Upon aging, chronic hyperinsulinemia resulted in insulin resistance and hepatic steatosis through activation of LXR. Here, we demonstrate that loss of hepatocyte proliferation is not only an outcome but also possibly a causative factor for liver pathology.

Non-steroidal anti-inflammatory drugs (NSAIDs) are Food and Drug Administration (FDA) approved antipyretic, anti-inflammatory, and analgesic drugs to mitigate pain, however it is associated with gastrointestinal injury and cardiovascular disease in some individuals. Metabolomics has the potential to understand the interaction of host and the drugs, such as NSAIDs administration. This discipline has been used by many researchers to understand the serious side effects of NSAIDs. We highlighted (1) the potential of metabolomics in understanding the pathogenesis of adverse events due to NSAIDs administration; (2) choice of metabolomics techniques, bio sample handling; (3) review of metabolomics studies in the front of NSAIDs in different biofluids and tissues; (4) pathway analysis of the data presented in the published literature. In our analysis we find tricarboxylic acid cycle (TCA), “glycine serine and threonine metabolism,” “alanine, aspartate, and glutamate metabolism,” and fatty acid metabolism to be altered by the NSAIDs like ibuprofen, indomethacin, naproxen, aspirin, and celecoxib. In conclusion, metabolomics allows the use of biological samples to identify useful pathways involved in disease progression, and subsequently inform a greater understanding of the disease pathogenesis. A further in-depth investigation of the associated pathways mentioned above holds the potential for drug targets for side effects mitigation.

Investigation of glucose utilization during an infection is central to the study of energy metabolism. The heavy utilization of glucose by the malaria parasite, and the consequences of this process, have been investigated extensively. However, host glucose utilization during early infection has not been explored to date. In a first attempt, this article investigates the changes in the host glucose utilization in Balb/c mice infected with Plasmodium berghei ANKA using 13C-labeled glucose infusion followed by NMR spectroscopy. The results suggested significant alterations of liver, brain and red blood cell (RBC) glucose utilization during early infection when the parasitemia was

A significant fraction of global population is under the threat of malaria. Majority of annual death is due to the more complicated form of the infection i.e. the cerebral form, also known as Cerebral Malaria (CM). Host parasite interaction is known to cause a cascade of events in various tissues like brain, liver, kidney, and spleen. We have employed (1)H NMR based metabolomics to understand the specific perturbations of various tissues in CM. In our previous paper we have delineated the differences between CM vis-a-vis non-cerebral malaria (NCM) mice in serum, liver and brain. In this paper we focus on their differences of metabolic profile in kidney and spleen as kidney dysfunction and splenomegaly are known to be associated to neurological outcome of the disease. Moreover we have also looked into how the biological compartments (kidney, spleen and serum) interact with each other. The various metabolites involved in such interactions and their correlational aspects across the compartments have been studied in CM, NCM and control mice. The idea was to find out the specific pathways that are altered in CM mice. Our results demonstrate that both the kidney as well as spleen metabolism are differentially perturbed in CM with respect to NCM. The results point out that glutamate levels are decreased in CM mice with respect to NCM mice both in case of spleen and kidney while creatine, myo-inositol and betaine levels are increased in kidney of CM mice with respect to NCM mice. From the analysis of Multiway Principal Component Analysis (MPCA) we see that lipid metabolism and TCA cycle is altered in kidney and spleen.

Malaria, a mosquito-borne disease caused by Plasmodium spp. is considered to be a global threat, specifically for the developing countries. In human subjects considerable information exists regarding post-malarial physiology. However, most murine malarial models are lethal, and most studies deal with acute phases occurring as disease progresses. Much less is known regarding physiological status post-parasite clearance. We have assessed the physiological changes at the organ levels using (1)H NMR based metabonomics in a non lethal self-clearing murine malarial model of P. chabaudi parasites and Balb/C, far beyond the parasite clearance point. The results showed distinct metabolic states between uninfected and infected mice at the peak parasitemia, as well as three weeks post-parasite clearance. Our data also suggests that the response at the peak infection as well as recovery exhibited distinct sexual dimorphism. Specifically, we observed accumulation of acetylcholine in the brain metabolic profile of both the sexes. This might have important implication in understanding the pathophysiology of the post malarial neurological syndromes. In addition, the female liver showed high levels of glucose, dimethylglycine, methylacetoacetate and histidine after three weeks post-parasite clearance, while the males showed accumulation of branched chain amino acids, lysine, glutamine and bile acids.

1H NMR-based metabonomics was used to investigate the multimodal response of mice to malarial parasite infection by P. berghei ANKA. Liver metabolism was followed by NMR spectroscopy through the course of the disease in both male and female mice. Our results showed alterations in the level of several metabolites as a result of the infection. Metabolites like kynurenic acid, alanine, carnitine, and β-alanine showed significant alteration in the liver, suggesting altered kynurenic acid, glucose, fatty acid and amino acid pathways. Distinct sexual dimorphism was also observed in the global analysis of the liver metabolic profiles. Multiway principal component analysis (MPCA) was carried out on the liver, brain, and serum metabolic profile in order to explore the correlation of liver and brain metabolic profile to the metabolite profile of serum. Changes in such correlation profile also indicated distinct sexual dimorphism at the early stage of the disease. Indications are that the females are able to regulate their metabolism in the liver in such a way to maintain homeostasis in the blood. In males, however, choline in liver showed anticorrelation to choline content of serum indicating a higher phospholipid degradation process. The brain-serum correlation profile showed an altered energy metabolism in both the sexes. The differential organellar responses during disease progression have implications in malaria management.

Primary breast stromal sarcomas are rare entities arising from connective tissue within the breast, accounting for <5% of all soft tissue sarcomas and <1% of malignant breast tumors. Primary breast sarcomas are locally aggressive tumors and should be differentiated from malignant phyllodes tumor and metaplastic carcinoma of the breast, which are close mimickers. Here we present 4 cases of primary breast sarcoma that we found over the course of 7 years in our institution who presented with a breast lump. Mastectomy was performed, and they were diagnosed as primary stromal sarcoma of the breast. [ABSTRACT FROM AUTHOR]

Background: Cytological study of pleural fluid helps establishing the underlying cause of pleural effusion. It is considered the most important tool in diagnosing malignancy in effusions. However, accurate identification of cellular morphology can be a problem in conventional cytology. Cell block preparation from pleural effusion aids in this diagnosis due to the preservation of tissue architecture, and multiple sections can be obtained for further studies. Aims and Objectives: The objectives of this study were to compare the diagnostic results of conventional cytology and cell block studies of suspected malignant pleural effusions and find out the diagnostic agreement or concordance between the two methods. Materials and Methods: A recordbased study was conducted at the Department of Pathology on conventional cytology and cell block study reports of 150 suspected malignant pleural effusion cases over 35 months. The diagnoses were expressed in five categories -- non-diagnostic, negative for malignancy, atypia of undetermined significance, suspicious for malignancy, and malignant. Χ2 test was used to identify the percentage of malignancy reported. Agreement of both methods was assessed through Kappa statistics. Results: About 4.67% of cases were reported as malignant by conventional cytology, whereas cell block study diagnosed malignancy in 19.33% of cases. Relative diagnostic agreement between the two methods was 0.73 and concordance by Cohen's Kappa was 0.34, which signifies fair concordance. Conclusion: Cell block study, though having a fair concordance, is much superior to conventional cytology smears in detecting malignant cells and diagnosing a pleural effusion as malignant. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory distress syndrome coronavirus 2 pandemic shows a spectrum of symptoms and complications which are variably dependent on individual's immune status. Vitamin D deficiency, often preexisting, causes poor prognosis in the post-COVID recovery phase of the survivors characterized by increased C-reactive protein (CRP) and decreased D-dimer levels. Aims and Objectives: The aims of this study were to find any correlation exists between vitamin D level and inflammatory marker CRP and D-dimer in post-COVID period. Materials and Methods: Seventy post-COVID recovery patients from the follow-up medicine outpatient department of College of Medicine and Sagore Dutta Hospital were tested for vitamin D, D-dimer, and serum CRP levels. Results: CRP levels of patients with lower vitamin D level (<20 ng/ml) were significantly higher (P<0.001) than the patients with higher vitamin D level. The D-dimer levels of vitamin D deficient group found to be significantly higher than the other group. There is statistically significant negative correlation found between CRP and vitamin D level and significant positive correlation has been found between D-dimer and vitamin D (P<0.001). Conclusion: Vitamin D may have an important role in recovery stage of COVID patients. [ABSTRACT FROM AUTHOR]