Combination strategies with PARP inhibitors in BRCA-mutated triple-negative breast cancer: overcoming resistance mechanisms.

Triple-negative breast cancer (TNBC) is a particularly aggressive breast cancer subtype, characterised by a higher incidence in younger women, rapid metastasis, and a generally poor prognosis. Patients with TNBC and BRCA mutations face additional therapeutic challenges due to the cancer's intrinsic resistance to conventional therapies. Poly (ADP-ribose) polymerase inhibitors (PARPis) have emerged as a promising targeted treatment for BRCA-mutated TNBC, exploiting vulnerabilities in the homologous recombination repair (HRR) pathway.

Assessing Influence of Mismatch Repair Mutations on Survival in Patients After Resection of Pancreatic Ductal and Periampullary Adenocarcinoma.

: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States. Previous studies have indicated that microsatellite instability and deficient mismatch repair (MMR) may be associated with improved survival in patients with pancreatic cancer. Here, we aim to investigate the impact of deficient MMR (dMMR) status on oncologic outcomes in patients after resection of PDAC and periampullary adenocarcinoma.

An Electrochemical CMOS Biosensor Array Using Phase-Only Modulation With 0.035% Phase Error And In-Pixel Averaging.

This paper presents a 16×20 CMOS biosensor array based on electrochemical impedance spectroscopy (EIS), a highly sensitive label-free technique for rapid disease detection at point-of-care. This high-density system implements a polar-mode detection with phase-only EIS measurement over a 5 kHz - 1 MHz frequency range. The design features predominantly digital readout circuitry, ensuring scalability with technology, along with a load-compensated transimpedance amplifier at the front, all within a 140×140 μm; pixel.

The non-canonically organized members of MIR395 gene family in Brassica juncea are associated with developmentally regulated, sulfate-stress responsive bidirectional promoters that exhibit orientation-dependent differential transcriptional activity.

Several MICRORNA genes belonging to same family or different families are often found in homologous or non-homologous clusters. Among the various classes, head-to-head arranged genes form one of the largest categories of non-canonically organized genes. Such head-to-head arranged, non-canonically organized genes possibly share cis-regulatory region with the intergenic sequence having the potential to function as bi-directional promoter (BDP).

Carotid Artery Doppler: A Possible Non-invasive Diagnostic Approach to Assessing the Severity of Coronary Artery Disease.

Background And Objectives: Carotid artery Doppler ultrasound is being explored for its potential as a non-invasive tool for evaluating coronary artery disease (CAD) severity and cardiovascular risk. This study aimed to investigate the association between carotid Doppler parameters and CAD severity, as determined by the Gensini score (GS) and multi-vessel disease presence.

Methods: Ninety patients undergoing coronary angiography (CAG) and carotid ultrasound were retrospectively analysed.

Comparison of the effect of two recruitment manoeuvres to conventional ventilation on lung atelectasis in paediatric laparoscopic surgery- a prospective randomised controlled trial.

Background: There is a high incidence of pulmonary atelectasis during paediatric laparoscopic surgeries. The authors hypothesised that utilising a recruitment manoeuvre or using continuous positive airway pressure may prevent atelectasis compared to conventional ventilation.

Objective: The primary objective was to compare the degree of lung atelectasis diagnosed by lung ultrasound (LUS) using three different ventilation techniques in children undergoing laparoscopic surgeries.

A mathematical framework for analysing particle flow in a network with multiple pools.

In many real-world systems, the entry rate of particles into a lane is affected by the occupancy of nearby pools. For instance, in biological networks, the concentration of molecules on the side of a membrane affects the entry of particles through the membrane. To understand the behaviour of such networks, we develop a network model of ribosome flow models (RFMs) having multiple pools where each RFM captures the dynamics of particle flow in a lane and competes for the finite resources present at the nearby pool.

Role of preoperative zinc, magnesium and budesonide gargles in Postoperative Sore Throat (POST) - a randomised control trial.

Background: Post-operative sore throat (POST) has an incidence ranging from 21 to 80%. To prevent the development of POST, several pharmacological measures have been tried. Aim of this study was to compare the efficacy of preoperative zinc, magnesium and budesonide gargles in reducing the incidence and severity of POST in patients who underwent endotracheal intubation for elective surgeries.

The Clinical Implications of KRAS Mutations and Variant Allele Frequencies in Pancreatic Ductal Adenocarcinoma.

The KRAS proto-oncogene is a major driver of pancreatic tumorigenesis and is nearly ubiquitously mutated in pancreatic ductal adenocarcinoma (PDAC). KRAS point mutations are detected in over 90% of PDAC cases, and these mutations have been shown to be associated with worse therapy response and overall survival. Pathogenic KRAS mutations are mostly limited to codons 12, 13 and 61, with G12D, G12V, G12R, Q61H, and G13D accounting for approximately 95% of the mutant cases.

Early prognosis prediction in acute myeloid and acute lymphoid leukemia patients using cell-free DNA concentration ratios.

Cell-free DNA (cfDNA) is a promising biomarker for disease prediction in many cancers, including acute leukemia (acute myeloid leukemia [AML] and acute lymphoblastic leukemia [ALL]). This study investigated the role of cfDNA in predicting relapse or unfavorable outcomes in acute leukemia patients upon initial diagnosis. Paired peripheral blood samples of 25 patients with ALL and AML were compared at baseline and induction/follow-up and clinically correlated with clinicopathological and outcome variables according to the risk category.

Essential Role of Anisotropy in Bioengineered Cardiac Tissue Models.

As regulatory bodies encourage alternatives to animal testing, there is renewed interest in engineering disease models, particularly for cardiac tissues. The aligned organization of cells in the mammalian heart controls the electrical and ionic currents and its ability to efficiently circulate blood to the body. Although the development of engineered cardiac systems is rising, insights into the topographical aspects, in particular, the necessity to design in vitro cardiac models incorporating cues for unidirectional cell growth, is lacking.

regulates multiple aspects of stamen and carpel development and requires dissection and delimitation of differential downstream regulatory network for manipulating fertility traits.

Unlabelled: Unravelling genetic networks regulating developmental programs are key to devising and implementing genomics assisted trait modification strategies. It is crucial to understand the role of small RNAs, and the basis of their ability to modify traits. MIR159 has been previously reported to cause defects in anther development in ; however, the complete spectrum and basis of the defects remained unclear.

A Randomized, Double-Blind, Parallel-Group Phase III Trial Investigating the Glycemic Efficacy and Safety Profile of Fixed-Dose Combination Dapagliflozin and Linagliptin Over Linagliptin Monotherapy in Patients with Inadequately Controlled Type 2 Diabetes with Metformin.

Introduction: The aim of the study was to evaluate the efficacy and safety of fixed-dose combination (FDC) of dapagliflozin (10 mg) and linagliptin (5 mg) in comparison to linagliptin 5 mg (Trajenta) in patients with insufficiently controlled type 2 diabetes mellitus (T2DM) on metformin monotherapy.

Methods: The double-blind, randomized, multicentric, parallel-group phase III trial screened 287 adult patients with T2DM (age 18-65 years) from 16 sites across India. The recruited subjects were undergoing metformin monotherapy ≥ 1000 mg/day for at least 28 days.

Recent advances and future directions in etiopathogenesis and mechanisms of reactive oxygen species in cancer treatment.

A class of exceptionally bioactive molecules known as reactive oxygen species (ROS) have been widely studied in the context of cancer. They play a significant role in the etiopathogenesis for cancer. Implication of ROS in cancer biology is an evolving area, considering the recent advances; insights into their generation, role of genomic and epigenetic regulators for ROS, earlier thought to be a chemical process, with interrelations with cell death pathways- Apoptosis, ferroptosis, necroptosis and autophagy has been explored for newer targets that shift the balance of ROS towards cancer cell death.

How Not To Fix a Tibial Fracture: A Case Report on Treatment By a Quack.

Quackery in the orthopaedic profession has existed for quite a long time. Due to the shortage of orthopaedic healthcare staff in public hospitals and the high costs in private facilities, members of disadvantaged communities turn to unlicensed and unskilled practitioners (quacks). The main factors responsible for the increased number of quacks performing orthopaedic treatment are illiteracy, high treatment cost, mismatch in the orthopaedic surgeon-to-population ratio, especially in rural areas, and the absence of any form of health insurance.

Deletion of the mRNA stability factor (HuR) in pancreatic cancer cells disrupts the tumor microenvironment integrity.

Stromal cells promote extensive fibrosis in pancreatic ductal adenocarcinoma (PDAC), which is associated with poor prognosis and therapeutic resistance. We report here for the first time that loss of the RNA-binding protein human antigen R (HuR, ) in PDAC cells leads to reprogramming of the tumor microenvironment. In multiple models, CRISPR deletion of in PDAC cells resulted in a decrease of collagen deposition, accompanied by a decrease of stromal markers (i.

A Novel 3DNA® Nanocarrier effectively delivers payloads to pancreatic tumors.

Introduction: Standard-of-care systemic chemotherapies for pancreatic ductal adenocarcinoma (PDAC) currently have limited clinical benefits, in addition to causing adverse side effects in many patients. One factor known to contribute to the poor chemotherapy response is the poor drug diffusion into PDAC tumors. Novel treatment methods are therefore drastically needed to improve targeted delivery of treatments.

Assessment of residual gastric volume using point-of-care ultrasonography in adult patients who underwent elective surgery.

Background: Aspiration pneumonitis remains a dreaded complication that may lead to almost 9% of anaesthesia-related deaths. The presence of gastric contents has always been a contributing factor to an increased risk of aspiration. Preoperative gastric ultrasound has been suggested as a modality for determining residual volume in special populations and conditions.