Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial.

Early data from the DYNAMIC study of circulating tumor DNA (ctDNA)-guided adjuvant chemotherapy (ACT) versus standard approach met its primary outcome demonstrating reduced ACT use without compromising 2-year recurrence-free survival (RFS) for stage II colon cancer. We report here other prespecified analyses of overall survival, ctDNA clearance and ctDNA level. At a median follow-up of 59.

Delineation of Aflatoxicosis on Health and Performance of Water Buffalo () and Its Therapeutic and Nutritional Management.

A symptom of reduced feed intake, conception and progressive emaciation was noticed in the Murrah buffalo farm of the institute with tail gangrene in some buffaloes and the sudden death of many animals. Thus, the objective of the study was for the systemic investigation to find out the causative agents and necessary ameliorative measures. The tail lesion includes alopecia, scales, necrosis, oedematous and a painful area.

Nanocarrier-mediated modulation of cGAS-STING signaling pathway to disrupt tumor microenvironment.

The cGAS-STING signaling plays an important role in the immune response in a tumor microenvironment (TME) of triple-negative breast cancer (TNBC). The acute and controlled activation of cGAS-STING signaling results in tumor suppression, while chronic activation of cGAS-STING signaling results in immune-suppressive TME that could result in tumor survival. There is a need, therefore, to develop therapeutic strategies for harnessing tumor suppressive effects of cGAS-STING signaling while minimizing the risks associated with chronic activation.

Solving unknown primary cancer with earlier diagnosis - the SUPER-ED trial: study protocol for a stepped-wedge cluster randomised controlled trial to support earlier diagnosis for people presenting with malignancy of undefined primary origin.

Background: People with malignancy of undefined primary origin (MUO) have a poor prognosis and may undergo a protracted diagnostic workup causing patient distress and high cancer related costs. Not having a primary diagnosis limits timely site-specific treatment and access to precision medicine. There is a need to improve the diagnostic process, and healthcare delivery and support for these patients.

miRNA-6236 Regulation of Postischemic Skeletal Muscle Angiogenesis.

Background: Peripheral arterial disease affects >200 million people worldwide and is characterized by impaired blood flow to the lower extremities. There are no effective medical treatments available. Using the mouse hind-limb ischemia model and miRNA sequencing, we identified a novel miRNA, miR-6236, whose expression significantly elevated in ischemic mouse limbs compared with nonischemic limbs.

Impact of age at first calving on fertility and production performance in Murrah buffalo.

The present study analyses the effect of age at first calving (AFC) on future fertility and productivity in Murrah buffaloes. The data of 314 buffalo heifers of animal farm section, ICAR-CIRB, Hisar were collected over a period of 9 years from 2010 to 2018. The buffalo heifers were categorized into six groups according to the AFC named as 30-35, 36-41, 42-47, 48-53, 54-59 and 60-65 months.

Induction of DEPP1 by HIF Mediates Multiple Hallmarks of Ischemic Cardiomyopathy.

Background: HIF (hypoxia inducible factor) regulates many aspects of cardiac function. We and others previously showed that chronic HIF activation in the heart in mouse models phenocopies multiple features of ischemic cardiomyopathy in humans, including mitochondrial loss, lipid accumulation, and systolic cardiac dysfunction. In some settings, HIF also causes the loss of peroxisomes.

Novel components in the nuclear factor-kappa B (NF-κB) signaling pathways of endothelial cells under hyperglycemic-ischemic conditions.

Diabetes worsens the outcomes of a number of vascular disorders including peripheral arterial disease (PAD) at least in part through induction of chronic inflammation. However, in experimental PAD, recovery requires the nuclear factor-kappa B (NF-κB) activation. Previously we showed that individually, both ischemia and high glucose activate the canonical and non-canonical arms of the NF-κB pathway, but prolonged high glucose exposure specifically impairs ischemia-induced activation of the canonical NF-κB pathway through activation of protein kinase C beta (PKCβ).

Interim management of Pierre Robin sequence using a custom-made face mask.

Pierre Robin sequence poses a great challenge for anesthesiologists during laryngoscopy and intubation, making oxygenation and ventilation difficult. The role of early surgical intervention is recommended for the improvement of the airway and overall survival of the neonate. The situation becomes even more challenging, when the neonate may not be fit for such surgical interventions.

Harnessing the synergistic potential of NK1R antagonists and selective COX-2 inhibitors for simultaneous targeting of TNBC cells and cancer stem cells.

Triple-negative breast cancer (TNBC) lacks the expression of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), rendering it unresponsive to endocrine therapy and HER2 targeted treatments. Though certain chemotherapeutics targeting the cell cycle have shown efficacy to a certain extent, the presence of chemotherapy-resistant cancer stem cells (CSCs) presents a significant challenge in tackling TNBC. Multiple lines of evidence suggest the upregulation of neuropeptide Substance P (SP), its NK-1 receptor (NK1R) and the Cyclooxygenase-2 (COX-2) enzyme in TNBC patients.

Quality by Design in Pharmaceuticals: A Review of its Impact on Regulatory Compliance and Product Quality.

The pharmaceutical industry has embraced the quality-by-design (QbD) approach as a promising development, formulation and manufacturing strategy. QbD provides a systematic and science-based framework for designing and producing high-quality products, with a particular focus on identifying, assessing and controlling risks throughout the development process. This review aims to assess the benefits of implementing QbD in pharmaceutical processes, evaluate its impact on regulatory compliance and explore its potential to enhance drug product quality.

Repurposing pantoprazole in combination with systemic therapy in advanced head and neck squamous cell carcinoma: a phase I/II randomized study.

Pantoprazole decreases the acidity of the tumor microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to cytotoxic therapy. We conducted a phase I/II randomized controlled trial in adult patients with head and neck squamous cell carcinoma (HNSCC) planned for first-line palliative chemotherapy.

Preparation of a Rigid and Nearly Coplanar Bis-tetracene Dimer through an Application of the CANAL Reaction.

A rigid tetracene dimer with a substantial interchromophore distance has been prepared through an application of the recently developed catalytic arene-norbornene annulation (CANAL) reaction. An iterative cycloaddition route was found to be unsuccessful, so a shorter route was adopted whereby fragments were coupled in the penultimate step to form a 13:1 mixture of two diastereomers, the major of which was isolated and crystallized. Constituent tetracene moieties are linked with a rigid, well-defined bridge and feature a near-co-planar mutual orientation of the acenes.

Nitrosamine Impurities in Herbal Formulations: A Review of Risks and Mitigation Strategies.

Nitrosamines are a class of chemical compounds that have been found to be impurities in a variety of pharmaceutical products. These impurities have raised concerns due to their potential carcinogenic effects. Recent studies have identified nitrosamines as impurities in a number of pharmaceutical products including angiotensin II receptor blockers (ARBs) and proton pump inhibitors (PPIs).

Endothelial Progenitor Cells and Macrophage Subsets Recruitment in Postischemic Mouse Hind Limbs.

Introduction: Peripheral arterial disease (PAD) occurs from atherosclerotic obstruction of arteries in the lower extremities. Restoration of perfusion requires angiogenesis and arteriogenesis through migration and differentiation of endothelial progenitor cells (EPCs) and macrophages at the site of injury. The time of recruitment has not been fully investigated.

Diabetes mellitus in peripheral artery disease: Beyond a risk factor.

Peripheral artery disease (PAD) is one of the major cardiovascular diseases that afflicts a large population worldwide. PAD results from occlusion of the peripheral arteries of the lower extremities. Although diabetes is a major risk factor for developing PAD, coexistence of PAD and diabetes poses significantly greater risk of developing critical limb threatening ischemia (CLTI) with poor prognosis for limb amputation and high mortality.

Virtual Reality based Gaze-sensitive Aiming Task Platform: Role of Attention Allocation in Task Performance for Individuals with Autism and Typically Developing Individuals.

Individuals with Autism Spectrum Disorder (ASD) often exhibit difficulty in movement preparation and allocating attention towards different Regions of Interest (ROIs) of a visual stimulus. Though research has alluded to differences in movement preparation for aiming tasks between individuals with ASD and typically developing (TD) individuals, there is limited evidence (true for near-aiming tasks) on the contribution of the window (i.e.

Immune and genomic biomarkers of immunotherapy response in cancer of unknown primary.

Background: Cancer of unknown primary (CUP) is a heterogeneous group of metastatic cancers where a primary tissue of origin (TOO) is uncertain. Most patients with CUP have limited treatment options and poor survival outcomes. Immune checkpoint inhibitors (ICIs) can be efficacious in some patients with CUP, but the optimal predictive biomarkers are unknown.

BAG3 Attenuates Ischemia-Induced Skeletal Muscle Necroptosis in Diabetic Experimental Peripheral Artery Disease.

Peripheral artery disease (PAD) is characterized by impaired blood flow to the lower extremities, resulting in ischemic limb injuries. Individuals with diabetes and PAD typically have more severe ischemic limb injuries and limb amputations, but the mechanisms involved are poorly understood. Previously, we identified BAG3 as a gene within a mouse genetic locus termed limb salvage QTL1 on mouse chromosome 7 that determined the extent of limb necrosis following ischemic injury in C57Bl/6 mice.

Uncertainty and the unmet informational needs of patients with cancer of unknown primary (CUP): a cross-sectional multi-site study.

Objective: This study aimed to determine the healthcare experiences, quality of life, and psychosocial needs of patients with cancer of unknown primary (CUP) early after diagnosis; comparing their experiences to patients with advanced cancer of a known primary (non-CUP control patients) and published general population reference data where available.

Methods: This study was a cross-sectional, multi-site study comparing CUP patients (n = 139) compared to non-CUP controls (n = 45). Demographic, clinical information and patient-reported outcome questionnaire data were collected at baseline.

MicroRNA regulation of BAG3.

B-cell lymphoma 2 (Bcl-2)-associated athanogene 3 (BAG3) protein is a member of BAG family of co-chaperones that modulates major biological processes, including apoptosis, autophagy, and development to promote cellular adaptive responses to stress stimuli. Although BAG3 is constitutively expressed in several cell types, its expression is also inducible and is regulated by microRNAs (miRNAs). miRNAs are small non-coding RNAs that mostly bind to the 3'-UTR (untranslated region) of mRNAs to inhibit their translation or to promote their degradation.

Efficacy and cost-effectiveness of an online mindfulness program (MindOnLine) to reduce fear of recurrence among people with cancer: study protocol for a randomised controlled trial.

Introduction: Fear of cancer recurrence (FCR) is a common condition among cancer survivors that can lead to significant levels of distress, anxiety and depression. Online mindfulness programmes may provide the mechanism to support cancer survivors manage FCR and distress, and improve people's well-being over the short, medium and long term. The primary aim of this study is to determine the potential efficacy of MindOnLine, a 9 session mindfulness-based programme for survivors of breast, prostate and colorectal cancer.

Altering Early Life Gut Microbiota Has Long-Term Effect on Immune System and Hypertension in Spontaneously Hypertensive Rats.

Hypertension is regulated by immunological components. Spontaneously hypertensive rats (SHR) display a large population of proinflammatory CD161 + immune cells. We investigated the effect of early post-natal gut microbiota on the development of the immune system and resulting hypertension in the SHR.

A Rare Location of a Repeat Ectopic Pregnancy: A Case Report.

Ectopic pregnancies often recur in the same patients as its etiology is tubal damage, which is rarely unilateral. In the setting of a well-documented history of ectopic pregnancy in the past where a salpingectomy was performed, and the clinical picture now suggests another ectopic, it can be reasonably concluded that the ectopic is in the remaining tube. In the case we present here, the ultrasound findings also suggested a tubal pregnancy in the remaining tube.