Exploring target selectivity in designing and identifying PI3Kα inhibitors for triple negative breast cancer with fragment-based and bioisosteric replacement approach.

Triple-negative breast cancer (TNBC) is one of the most fatal malignancies in the world, accounting for 42% of all deaths due to metastasis. The significant development is hindered by the multi-drug resistance and poor patient compliance. PIK3CA gene mutation is one of the important causes of TNBC, which causes dysregulation of the cell cycle and cell proliferation.

Non-Alcoholic Fatty Liver Disease Among Newly Diagnosed Type 2 Diabetes Mellitus in North Bihar and Missed Opportunities for Early Diagnosis.

Background: There are no studies investigating missed opportunities for earlier diagnosis in newly/recently detected Type 2 Diabetes Mellitus and Non-alcoholic Fatty Liver Disease in the region of Bihar, India.

Methods: This study is a single-center cross-sectional study undertaken at the Research Centre for Diabetes Hypertension and Obesity, Samastipur, Bihar, India. The study collected data from newly/recently diagnosed persons with T2DM.

Radiotherapy Quality Assurance in the SCOPE2 Trial: What Lessons can be Learned for the Next UK Trial in Oesophageal Cancer?

Aims: The SCOPE2 trial evaluates radiotherapy (RT) dose escalation for oesophageal cancer. We report findings from the accompanying RT quality assurance (RTQA) programme and identify recommendations for PROTIEUS, the next UK trial in oesophageal RT.

Maetrials And Methods: SCOPE2's RTQA programme consisted of a pre-accrual and on-trial component.

Alkoxy-Directed Dienamine Catalysis in [4 + 2]-Cycloaddition: Enantioselective Synthesis of Benzo-[3]-ladderanol.

Despite tremendous progress of dienamine catalysis along with its application in enantioselective synthesis over nearly two decades, certain limitations, especially with respect to the regioselectivity in the dienamine generation step, continue to persist. To overcome these shortcomings of classical dienamine catalysis, we now introduce the concept of alkoxy-directed dienamine catalysis and apply it to the enantioselective arene construction by desymmetrizing -enediones through [4 + 2]-cycloaddition. Catalyzed by a diphenylprolinol silyl ether, this reaction utilizes γ-alkoxy α,β-unsaturated aldehydes as the substrate and proceeds in a highly regioselective fashion through the intermediacy of δ-alkoxy dienamine.

Quality of life among geriatric population living with functional disabilities: A comparison between urban and rural populations of West Bengal.

Introduction: Global elderly population's growth is evident, with projections reaching 2 billion by 2050, while India's geriatric population is expected to rise to 11.6% by 2026. Disparity in quality of life (QOL) and disabilities between urban and rural elderly exist, where rural elderly maintain active roles, while urban counterparts face economic insecurity post retirement.

Prevalence of peripheral neuropathy in children with transfusion-dependent thalassemia: A hospital-based cross-sectional study.

Background: Our study aimed to determine the prevalence of Peripheral Neuropathy (using nerve conduction studies (NCS)) in children with transfusion-dependent thalassemia aged between 5 to 18 years and to study its correlation with chronic anemia, ferritin levels, chelation status, annual transfusion requirement, deficiency of serum Vitamin B12, and Folate levels.

Methods: In this hospital-based cross-sectional study, 100 eligible children were enrolled in a tertiary care teaching hospital in New Delhi, India. Neurological examinations focusing on peripheral neuropathy followed by NCS were performed on all the patients.

Induction of macrophage efferocytosis in pancreatic cancer via PI3Kγ inhibition and radiotherapy promotes tumour control.

Background: The immune suppression mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain unknown, but preclinical studies have implicated macrophage-mediated immune tolerance. Hence, pathways that regulate macrophage phenotype are of strategic interest, with reprogramming strategies focusing on inhibitors of phosphoinositide 3-kinase-gamma (PI3Kγ) due to restricted immune cell expression. Inhibition of PI3Kγ alone is ineffective in PDAC, despite increased infiltration of CD8+ T cells.

Vaccination prior to SARS-CoV-2 infection does not affect the neurologic manifestations of long COVID.

Persistent symptoms after COVID-19 constitute the long COVID syndrome, also called post-acute sequelae of SARS-CoV-2 infection (PASC). COVID-19 vaccines reduce the gravity of ensuing SARS-CoV-2 infections. However, whether vaccines also have an impact on PASC remain unknown.

The 'Oma's of the Gammas-Cancerogenesis by γ-Herpesviruses.

Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), which are the only members of the gamma(γ) herpesviruses, are oncogenic viruses that significantly contribute to the development of various human cancers, such as Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma, Kaposi's sarcoma, and primary effusion lymphoma. Oncogenesis triggered by γ-herpesviruses involves complex interactions between viral genetics, host cellular mechanisms, and immune evasion strategies. At the genetic level, crucial viral oncogenes participate in the disruption of cell signaling, leading to uncontrolled proliferation and inhibition of apoptosis.

An In-Vitro Study of the Root Canal Configuration of Mandibular First Premolars in a Bengali Subpopulation Using Cone-Beam Computed Tomography.

Aim: This study aims to analyze the root canal configuration system of mandibular first premolars in the Bengali subpopulation using cone-beam computed tomography (CBCT).

Materials And Methods: Based on Vertucci's classification, the root canal morphology of 100 randomly selected mandibular first premolars in 56 males and 44 females from the Bengali subpopulation of West Bengal was assessed in vitro. The location of the apical foramen, lateral canal, C-shaped canal, types of canal orifice cross-sections, minor constriction diameter, tooth length, and root length were noted.

Modulating the Optical Properties of Cationic Surfactant Cetylpyridinium Chloride and Hydrazine Mediated Copper Nanoclusters.

This study investigates the modulations in the optical properties of cationic surfactant cetylpyridinium chloride (CPC) and hydrazine-mediated copper nanoclusters (CuNCs). By employing a bottom-up approach, we demonstrate the formation of blue-emitting CuNCs facilitated by CPC and hydrazine, where hydrazine acts both as a reducing and stabilizing agent. The optical properties of the CuNCs were systematically tuned by varying the chain length of the diamine, resulting in emissions ranging from blue to yellow.

Production, Delivery, and Regulatory Aspects for Application of Plant-Based Anti-microbial Peptides: a Comprehensive Review.

Antimicrobial peptides (AMPs) are small, positively charged biomolecules produced by various organisms such as animals, microbes, and plants. These AMPs play a significant role in defense mechanisms and protect from adverse conditions. The emerging problem of drug resistance in microbes poses a global health challenge in treating diseases.

Prognostic immune markers in esophageal cancer patients managed with trimodal therapy.

Background: Esophageal cancer (ESC) is an aggressive disease which often presents at an advanced stage. Despite trimodal therapy, 40-50% patients can develop metastatic disease by 18 months. Identification of patients at risk for metastatic spread is challenging with need for improved prognostication.

Sparse high-dimensional decomposition of non-primary auditory cortical receptive fields.

Characterizing neuronal responses to natural stimuli remains a central goal in sensory neuroscience. In auditory cortical neurons, the stimulus selectivity of elicited spiking activity is summarized by a spectrotemporal receptive field (STRF) that relates neuronal responses to the stimulus spectrogram. Though effective in characterizing primary auditory cortical responses, STRFs of non-primary auditory neurons can be quite intricate, reflecting their mixed selectivity.

An Ultramicroporous Physisorbent Sustained by a Trifecta of Directional Supramolecular Interactions.

2D and 3D porous coordination networks (PCNs) as exemplified by metal-organic frameworks, MOFs, have garnered interest for their potential utility as sorbents for molecular separations and storage. The inherent modularity of PCNs has enabled the development of crystal engineering strategies for systematic fine-tuning of pore size and chemistry in families of related PCNs. The same cannot be said about one-dimensional (1D) coordination polymers, CPs, which are understudied with respect to porosity.

A Systematic Review of the Prevalence of Overactive Bladder in Women with Non-Urinary Tract Endometriosis and the Effect of Endometriosis Surgery on Symptoms of Overactive Bladder.

Introduction And Hypothesis: Overactive bladder (OAB) is characterised by urinary urgency, with or without incontinence, often accompanied by daytime frequency and nocturia, in the absence of urinary tract infection or other identifiable causes. Population studies estimate the prevalence of OAB at 12.8% (EPIC study), increasing with age, reaching up to 43% after age 40.

AI-Driven insights in pancreatic cancer imaging: from pre-diagnostic detection to prognostication.

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States, largely due to its poor five-year survival rate and frequent late-stage diagnosis. A significant barrier to early detection even in high-risk cohorts is that the pancreas often appears morphologically normal during the pre-diagnostic phase. Yet, the disease can progress rapidly from subclinical stages to widespread metastasis, undermining the effectiveness of screening.

FOXP3 Transcriptionally Activates Fatty Acid Scavenger Receptor CD36 in Tumour-Induced Treg Cells.

The host immune system is adapted in a variety of ways by tumour microenvironment and growing tumour interacts to promote immune escape. One of these adaptations is manipulating the metabolic processes of cells in the tumour microenvironment. The growing tumour aggressively utilise glucose, its primary energy source available in tumour site, and produce lactate by Warburg effect.

The impact of Asian-Indian criteria for higher body mass index and preservative solutions on haemolysis of stored red blood cells: A prospective observational study.

Introduction: The quality of packed red blood cells (PRBC) is influenced by various factors such as the collection and processing method, storage conditions, type of bag materials used, anticoagulant properties, and donor characteristics. Studies have indicated that haemolysis in stored RBC bags is linked to male sex, older age, high haemoglobin count, and increased body mass index (BMI). The study's primary objective was to investigate whether a high BMI, as per Asian Pacific criteria among donors, is associated with an elevated haemolysis rate in stored RBC.

Mitochondrial dysfunction signatures in idiopathic primary male infertility: a validated proteomics-based diagnostic approach.

Research Question: Male infertility accounts for almost half of all infertility cases worldwide, with idiopathic male infertility accounting for up to 30% of the cases. Sperm proteomics has revealed critical molecular pathway changes in men with infertility. However, the sperm mitochondrial proteome remains poorly understood.

Nonthermal Plasma Boosted Dichloroacetate Induces Metabolic Shifts to Combat Glioblastoma CSCs via Oxidative Stress.

Glioblastoma (GBM) remains a formidable clinical challenge, with cancer stem cells (CSCs) contributing to treatment resistance and tumor recurrence. Conventional treatments often fail to eradicate these CSCs characterized by enhanced resistance to standard therapies through metabolic plasticity making them key targets for novel treatment approaches. Addressing this challenge, this study introduces a novel combination therapy of dichloroacetate (DCA), a metabolic modulator and nonthermal plasma to induce oxidative stress in glioblastomas.

Chronic pancreatitis as a driving factor for pancreatic cancer: An epidemiological understanding.

The retrospective study by Lew (2022) examined the rising hospitalization rates for chronic pancreatitis (CP) and its association with pancreatic ductal adenocarcinoma (PDAC), revealing significant ethno-racial disparities and risk factors. Overweight black men aged 40-59 years and white men over 40 years with higher incomes showed an elevated risk of PDAC among CP patients. The study, which included 14.

Oncometabolites in pancreatic cancer: Strategies and its implications.

Pancreatic cancer (PanCa) is a catastrophic disease, being third lethal in both the genders around the globe. The possible reasons are extreme disease invasiveness, highly fibrotic and desmoplastic stroma, dearth of confirmatory diagnostic approaches and resistance to chemotherapeutics. This inimitable tumor microenvironment (TME) or desmoplasia with excessive extracellular matrix accumulation, create an extremely hypovascular, hypoxic and nutrient-deficient zone inside the tumor.

Quercetin nanocrystal-loaded alginate hydrogel patch for wound healing applications.

Wound healing can often be delayed due to non-favourable physiological conditions. Current treatment strategies have many limitations, and the development of novel therapeutic patches is urgently required. Herein, we have developed a hydrogel-based wound healing patch containing quercetin nanocrystals to enhance quercetin solubility, leading to sustained release and improved bioactivity.