Liver Transplant From a Deceased Donor With Cystinosis: A Case Report.

Many inherited metabolic disorders (IMD) are associated with end-organ damage necessitating organ transplantation. Although utilization of deceased donors with history of IMD warrants caution, there may be circumstances under which such donors could be considered as suitable organ donor candidates. We present the first known report of liver transplantation from a deceased donor with cystinosis.

Spatial tumor immune heterogeneity facilitates subtype co-existence and therapy response in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) displays a high degree of spatial subtype heterogeneity and co-existence, linked to a diverse microenvironment and worse clinical outcome. However, the underlying mechanisms remain unclear. Here, by combining preclinical models, multi-center clinical, transcriptomic, proteomic, and patient bioimaging data, we identify an interplay between neoplastic intrinsic AP1 transcription factor dichotomy and extrinsic macrophages driving subtype co-existence and an immunosuppressive microenvironment.

Curative Resection for Metastatic Solid Pseudopapillary Neoplasm of Pancreas-a Case Series.

Solid pseudopapillary neoplasm (SPN) is an unusual tumor of the pancreas. Unlike ductal adenocarcinoma, SPN is commoner in young women and is indolent with better prognosis. Fifteen percent of patients, however, develop metastases, often synchronous and involving the liver or peritoneum.

Insulin receptor loss impairs mammary tumorigenesis in mice.

Breast cancer (BC) prognosis and outcome are adversely affected by obesity. Hyperinsulinemia, common in the obese state, is associated with higher risk of death and recurrence in BC. Up to 80% of BCs overexpress the insulin receptor (INSR), which correlates with worse prognosis.

Hourglass, a rapid analysis framework for heterogeneous bioimaging data, identifies sex disparity in IL-6/STAT3-associated immune phenotypes in pancreatic cancer.

Integration and mining of bioimaging data remains a challenge and lags behind the rapidly expanding digital pathology field. We introduce Hourglass, an open-access analytical framework that streamlines biology-driven visualization, interrogation, and statistical assessment of multiparametric datasets. Cognizant of tissue and clinical heterogeneity, Hourglass systematically organizes observations across spatial and global levels and within patient subgroups.

Homodimeric Minimal Factor H: Tracking and Extended Dosing Studies in Factor H Deficient Mice.

C3 glomerulopathy (C3G) is associated with dysregulation of the alternative pathway (AP) of complement and treatment options remain inadequate. Factor H (FH) is a potent regulator of the AP. An in-depth analysis of FH-related protein dimerised minimal (mini)-FH constructs has recently been published.

Spatially confined sub-tumor microenvironments in pancreatic cancer.

Intratumoral heterogeneity is a critical frontier in understanding how the tumor microenvironment (TME) propels malignant progression. Here, we deconvolute the human pancreatic TME through large-scale integration of histology-guided regional multiOMICs with clinical data and patient-derived preclinical models. We discover "subTMEs," histologically definable tissue states anchored in fibroblast plasticity, with regional relationships to tumor immunity, subtypes, differentiation, and treatment response.

GATA6 Expression Distinguishes Classical and Basal-like Subtypes in Advanced Pancreatic Cancer.

Purpose: To determine the impact of basal-like and classical subtypes in advanced pancreatic ductal adenocarcinoma (PDAC) and to explore GATA6 expression as a surrogate biomarker.

Experimental Design: Within the COMPASS trial, patients proceeding to chemotherapy for advanced PDAC undergo tumor biopsy for RNA-sequencing (RNA-seq). Overall response rate (ORR) and overall survival (OS) were stratified by subtypes and according to chemotherapy received.

A Four-Chemokine Signature Is Associated with a T-cell-Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer.

Purpose: The molecular drivers of antitumor immunity in pancreatic ductal adenocarcinoma (PDAC) are poorly understood, posing a major obstacle for the identification of patients potentially amenable for immune-checkpoint blockade or other novel strategies. Here, we explore the association of chemokine expression with effector T-cell infiltration in PDAC.

Experimental Design: Discovery cohorts comprised 113 primary resected PDAC and 107 PDAC liver metastases.

Intracholecystic papillary-tubular neoplasms of the gallbladder - A clinicopathological study of 36 cases.

Intracholecystic papillary-tubular neoplasms (ICPNs) account for <0.5% of all cholecystectomies. There is a lack of significant published data from the Indian subcontinent on ICPN to the best of our knowledge.

Comparison of Efficacy and Safety of Fixed Dose Combination of Rosuvastatin and Choline Fenofibrate to Fixed Dose Combination of Rosuvastatin and Fenofibrate in Patients of Mixed Dyslipidemia: A Randomized, Open-label, Multicentre Clinical Trial in Indian Population.

Introduction: This study was conducted to evaluate the safety and efficacy of fixed-dose combination (FDC) of rosuvastatin and choline fenofibrate in comparison to rosuvastatin and fenofibrate FDC among Indian patients of mixed dyslipidemia. This would be a first study evaluating FDC of rosuvastatin and choline fenofibrate in Indian population.

Methods: A multicenter, open-label, randomized, active controlled, comparative, parallel-design study was conducted at 12 centers spread all across India.

Role of transglutaminase 2 in A adenosine receptor- and β-adrenoceptor-mediated pharmacological pre- and post-conditioning against hypoxia-reoxygenation-induced cell death in H9c2 cells.

Pharmacologically-induced pre- and post-conditioning represent attractive therapeutic strategies to reduce ischaemia/reperfusion injury during cardiac surgery and following myocardial infarction. We have previously reported that transglutaminase 2 (TG2) activity is modulated by the A adenosine receptor and β-adrenoceptor in H9c2 cardiomyoblasts. The primary aim of this study was to determine the role of TG2 in A adenosine receptor and β-adrenoceptor-induced pharmacological pre- and post-conditioning in the H9c2 cells.

β-adrenoceptor-induced modulation of transglutaminase 2 transamidase activity in cardiomyoblasts.

Tissue transglutaminase 2 (TG2) is modulated by protein kinase A (PKA) mediated phosphorylation: however, the precise mechanism(s) of its modulation by G-protein coupled receptors coupled to PKA activation are not fully understood. In the current study we investigated the potential regulation of TG2 activity by the β-adrenoceptor in rat H9c2 cardiomyoblasts. Transglutaminase transamidation activity was assessed using amine-incorporating and protein cross-linking assays.

Mitochondrial Sirtuin Network Reveals Dynamic SIRT3-Dependent Deacetylation in Response to Membrane Depolarization.

Mitochondrial sirtuins, SIRT3-5, are NAD-dependent deacylases and ADP-ribosyltransferases that are critical for stress responses. However, a comprehensive understanding of sirtuin targets, regulation of sirtuin activity, and the relationships between sirtuins remains a key challenge in mitochondrial physiology. Here, we employ systematic interaction proteomics to elucidate the mitochondrial sirtuin protein interaction landscape.

A1 adenosine receptor-induced phosphorylation and modulation of transglutaminase 2 activity in H9c2 cells: A role in cell survival.

The regulation of tissue transglutaminase (TG2) activity by the GPCR family is poorly understood. In this study, we investigated the modulation of TG2 activity by the A1 adenosine receptor in cardiomyocyte-like H9c2 cells. H9c2 cells were lysed following stimulation with the A1 adenosine receptor agonist N(6)-cyclopentyladenosine (CPA).

Randomized comparative trial of efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children.

Objective: Paracetamol and ibuprofen are widely used for fever in children as monotherapy and as combined therapy. None of the treatments is proven clearly superior to others. Hence, the study was planned to compare the efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children.

Management of colorectal cancer liver metastasis in a patient with immune thrombocytopaenia.

Immune thrombocytopaenia (ITP) was referred to previously as idiopathic thrombocytopaenic purpura and is usually of autoimmune or viral aetiology. Colorectal cancer liver metastasis with concomitant ITP is rare and only three cases have been reported in the English literature. Adverse effects of adjuvant chemotherapy may aggravate ITP.

Spontaneous choledochal cyst rupture in pregnancy with concomitant chronic pancreatitis.

Choledochal cysts are rare cystic transformations of the biliary tree that are increasingly diagnosed in adult patients. We report here a case of spontaneous rupture of a choledochal cyst in a pregnant young lady with chronic pancreatitis.

Benign biliary papillomatosis in a patient with a choledochal cyst presenting as haemobilia: a case report.

Biliary papillomatosis is a rare condition usually detected on imaging or postoperative histopathology. It may be asymptomatic or present with features of cholangitis. We report the management of a patient presenting with haemobilia.