Unraveling the glyco-immunity nexus in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease, and standard of care therapies have failed to yield significant clinical benefit, with invasive surgery being the only curative treatment for patients with early-stage disease. Tumor-associated glycans in pancreatic cancer have direct effects on the survival and propagation of the tumor proper and contribute to an immunosuppressed tumor microenvironment. The existence of a “tumor glycocode” in PDAC and the role of hypersialylation in this cancer have been hugely underscored.

Convenient one-pot synthesis of 1-(4-(4-(2-[F]fluoroethoxy)phenyl)piperazin-1-yl)ethanone ([F]FEt-PPZ) for imaging tumors expressing sigma-1 receptors.

The overexpression of the sigma-1 receptor (σ1R) in a variety of cancers makes it a potential target for developing anticancer drugs or diagnostic/therapeutic radiopharmaceuticals. Molecules with piperidine or piperazine substructures have shown high binding affinity towards σ1R. Docking and MD simulation studies on commercially available piperidine/piperazine-containing compounds identified 1-(4-(4-hydroxyphenyl)piperazin-1-yl)ethanone (PPZ) as a potential ligand for targeting σ1R.

A rare case of co-occurrence of lupus nephritis and lymphoma.

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder known to increase the risk of lymphomas, typically after prolonged immunosuppressive therapy. We report a rare case of a 45-year-old woman who presented with fever, polyarthritis, and anasarca, and was concurrently diagnosed with lupus nephritis and marginal zone lymphoma without prior immunosuppression. Initial evaluation revealed hematologic abnormalities, renal involvement, and axillary lymphadenopathy.

Caribou and Reindeer Population Cycles Are Driven by Top-Down and Bottom-Up Mechanisms Across Space and Time.

Anthropogenic change is reshaping the regulation and stability of animal population dynamics across broad biogeographic gradients. For example, abiotic and biotic interactions can cause gradients in population cycle period and amplitude, but this research is mostly constrained to small mammals. Caribou and reindeer ( spp.

Massive experimental quantification allows interpretable deep learning of protein aggregation.

Protein aggregation is a pathological hallmark of more than 50 human diseases and a major problem for biotechnology. Methods have been proposed to predict aggregation from sequence, but these have been trained and evaluated on small and biased experimental datasets. Here we directly address this data shortage by experimentally quantifying the aggregation of >100,000 protein sequences.

Humanized Anti-MUC16 Antibody-Conjugated Contrast Agents for Magnetic Resonance Imaging of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is diagnosed at a late stage with distant metastasis in an overwhelming 50% of cases, and the prognosis is poor. Treating this extremely aggressive disease with standard-of-care therapies has led to modest benefits in overall survival, mainly due to a lack of targeted early treatment modalities, as early detection has not yet been possible. Mucin-16 (MUC16) is a glycoprotein overexpressed in more than 60% of patients with PDAC and is a tumor-specific biomarker.

Nocardiosis in Renal Allograft Recipients.

Introduction: The aim of the study was to study the clinical profile and outcomes of nocardiosis in renal allograft recipients.

Methods: This was a retrospective study of clinical outcomes in consecutive renal allograft recipients with infection over a 22-year period (2000-2022) from a tertiary care center in Southern India. The clinical data were obtained from electronic medical records and patient files.

Concomitant Histological Features of Membranous Nephropathy and Anti-Neutrophil Cytoplasmic Antibody Associated Vasculitis.

The simultaneous occurrence of vasculitic glomerulonephritis and membranous nephropathy is unusual. We report two cases that presented to our outpatient department with rapidly progressive renal failure. On evaluation, in one patient, anti-myeloperoxidase (MPO) titers were high, and renal biopsy was suggestive of concurrent necrotizing and diffuse crescentic anti-MPO anti-neutrophil cytoplasmic antigen-associated glomerulonephritis with the circumferential cellular crescent formation and membranous glomerulopathy.

Massive experimental quantification of amyloid nucleation allows interpretable deep learning of protein aggregation.

Protein aggregation is a pathological hallmark of more than fifty human diseases and a major problem for biotechnology. Methods have been proposed to predict aggregation from sequence, but these have been trained and evaluated on small and biased experimental datasets. Here we directly address this data shortage by experimentally quantifying the amyloid nucleation of >100,000 protein sequences.

Structural Basis for Multivalent MUC16 Recognition and Robust Anti-Pancreatic Cancer Activity of Humanized Antibody AR9.6.

Mucin-16 (MUC16) is a target for antibody-mediated immunotherapy in pancreatic ductal adenocarcinoma (PDAC) among other malignancies. The MUC16-specific monoclonal antibody AR9.6 has shown promise for PDAC immunotherapy and imaging.

Anorexia Nervosa: Evaluating Disparities in Places of Death in the United States Over 22 Years Using the CDC WONDER Database.

Introduction: Anorexia nervosa is a severe and occasionally fatal eating disorder characterized by extreme weight loss and a distorted body image in which the affected individuals typically exhibit a strong fear of gaining weight, leading to rigid dietary restrictions and excessive activity. This condition can cause severe health problems, such as hunger, cardiovascular issues, and organ destruction. Anorexia nervosa is a key subject for research in the context of end-of-life care disparities due to its psychological and physical challenges.

In-situ and airborne hyperspectral data for detecting agricultural activities in a dense forest landscape.

Maintaining rich biodiversity and being a habitat and resource for humans, tropical forests are one of the most important global biomes. These forest ecosystems have been experiencing a host of unregulated anthropogenic activities including illegal tourism, and shifting cultivation. The presence of human-habitats in the restricted zones of forest ecosystems is a direct indicator of the human activities that may accelerate deterioration of forest quality by area and tree species composition.

A response surface modeling and optimization of photocatalytic degradation of 2,4-dichlorophenol in water using hierarchical nano-assemblages of CuBiO particles.

Photocatalytic degradation, as an advanced oxidation process (AOPs), offers a great advantage to target persistent organic pollutants (POPs) in water. RSM in the present study which is statistical means for optimizing processes like photocatalysis with minimum laboratory experimentation. RSM has a history of being a potent design experiment tool for creating new processes, modifying their designs, and optimizing their performances.

Selecting deep neural networks that yield consistent attribution-based interpretations for genomics.

Deep neural networks (DNNs) have advanced our ability to take DNA primary sequence as input and predict a myriad of molecular activities measured via high-throughput functional genomic assays. Post hoc attribution analysis has been employed to provide insights into the importance of features learned by DNNs, often revealing patterns such as sequence motifs. However, attribution maps typically harbor spurious importance scores to an extent that varies from model to model, even for DNNs whose predictions generalize well.

Correcting gradient-based interpretations of deep neural networks for genomics.

Post hoc attribution methods can provide insights into the learned patterns from deep neural networks (DNNs) trained on high-throughput functional genomics data. However, in practice, their resultant attribution maps can be challenging to interpret due to spurious importance scores for seemingly arbitrary nucleotides. Here, we identify a previously overlooked attribution noise source that arises from how DNNs handle one-hot encoded DNA.

Response Surface Methodology (RSM) modelling for the photocatalytic optimization study of benzophenone removal using CuWO/NiO nanocomposite.

Emerging contaminants are posing a new water quality challenge, worldwide. The majority of pharmaceutical and personal care products used by us have been regarded as emerging contaminants. Benzophenone is one such chemical found in personal care products, specially in sunscreen creams as an UV-filter.

The (Sialyl) Tn antigen: Contributions to immunosuppression in gastrointestinal cancers.

Cellular signaling pathways are intricately regulated to maintain homeostasis. During cancer progression, these mechanisms are manipulated to become harmful. O-glycosylation, a crucial post-translational modification, is one such pathway that can lead to multiple isoforms of glycoproteins.

Treating Parvovirus Triggered Refractory Hemolytic Anemia with Rituximab in Renal Transplant Recipients - A Report of Two Cases.

Parvovirus B19 is a small (26 nm), nonenveloped, single-stranded DNA (5.6-kb) virus. The only known host for parvovirus B19 is humans.

Learning single-cell chromatin accessibility profiles using meta-analytic marker genes.

Motivation: Single-cell assay for transposase accessible chromatin using sequencing (scATAC-seq) is a valuable resource to learn cis-regulatory elements such as cell-type specific enhancers and transcription factor binding sites. However, cell-type identification of scATAC-seq data is known to be challenging due to the heterogeneity derived from different protocols and the high dropout rate.

Results: In this study, we perform a systematic comparison of seven scATAC-seq datasets of mouse brain to benchmark the efficacy of neuronal cell-type annotation from gene sets.

Psychological well-being and coping strategies among secondary school teachers: A cross-sectional study.

Introduction: Educators, academicians, and teachers are responsible for the development of the nation's human capital. Teacher coping methods are becoming more widely recognized as a key factor in determining teacher effectiveness. The aim of this study was to identify the various coping strategies adopted by high school teachers in Southern India.

Truncated O-Glycan-Bearing MUC16 Enhances Pancreatic Cancer Cells Aggressiveness via α4β1 Integrin Complexes and FAK Signaling.

Elevated levels of Mucin-16 (MUC16) in conjunction with a high expression of truncated O-glycans is implicated in playing crucial roles in the malignancy of pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms by which such aberrant glycoforms present on MUC16 itself promote an increased disease burden in PDAC are yet to be elucidated. This study demonstrates that the CRISPR/Cas9-mediated genetic deletion of MUC16 in PDAC cells decreases tumor cell migration.

Automated radiochemical synthesis of pharmaceutical grade [ F]FLT using 3-N-Boc-5'-O-dimethoxytrityl-3'-O-nosyl-thymidine precursor and its Sep-Pak® purification employing selective elution from reversed phase.

Pharmaceutical grade 3'-deoxy-3'-[ F]fluorothymidine [ F]FLT was synthesized using 3-N-Boc-5'-O-dimethoxytrityl-3'-O-nosyl-thymidine (BOC-Nosyl) precursor, in the general purpose TRACERlab FX modules. Purification of [ F]FLT, via solid phase extraction (SPE) after radiosynthesis, using a combination of different SPE cartridges, yielded satisfactory results, with radiochemical and chemical purity >99%. While the non-decay corrected radiochemical yield (RCY) with 20 mg (24 μmole) of BOC-Nosyl precursor was found to be 6.

Current status and unique attributes of Indian Chilika buffalo for adaptation to brackish water ecology.

Chilika buffalo is native to the Eastern coast of India and well adapted to the largest coastal brackish water lagoon of Asia, Chilika Lake. We present here a report on the Chilika buffalo breed emphasizing the conservational urgency based on unique biochemical and molecular evidence related to liver and kidney functions while comparing it with tropically adapted other water buffalo breeds (Bubalus bubalis) of India. It is found that the Chilika buffalo breed has a better ability to withstand a long dehydration period as evident from its better glomerular filtration and higher expression of the ion transport channel.

Structure activity relationship (SAR) study identifies a quinoxaline urea analog that modulates IKKβ phosphorylation for pancreatic cancer therapy.

Genetic models validated Inhibitor of nuclear factor (NF) kappa B kinase beta (IKKβ) as a therapeutic target for KRAS mutation associated pancreatic cancer. Phosphorylation of the activation loop serine residues (S, S) in IKKβ is a key event that drives tumor necrosis factor (TNF) α induced NF-κB mediated gene expression. Here we conducted structure activity relationship (SAR) study to improve potency and oral bioavailability of a quinoxaline analog 13-197 that was previously reported as a NFκB inhibitor for pancreatic cancer therapy.