Differential long-term tamoxifen therapy benefit by menopausal status in breast cancer patients: secondary analysis of a controlled randomized clinical trial.

Background: Estrogen receptor-positive breast cancer patients have a long-term risk of distant metastatic disease, and premenopausal patients have a higher risk. Randomized studies with long-term follow-up are essential to understand treatment benefit. We elucidated the long-term tamoxifen therapy benefit by menopausal status in the Stockholm tamoxifen trials with 20 years complete follow-up.

Evaluating parental knowledge and attitudes toward childhood hearing loss: a cross-sectional study in Rawalpindi, Pakistan.

Background: Childhood hearing loss poses a significant public health challenge in Pakistan, with prevalence rates over double the global average. Parental knowledge and attitudes play a crucial role in timely detection and intervention. However, limited research explores this issue within the Pakistani context.

Association of Gestational Iron-deficiency Anemia with Antenatal Depression among Pregnant Women: A Case-control Study from Tertiary Care Hospitals, Lahore.

Objective: The goal of this study is to investigate the potential association between gestational anemia and antenatal depression in pregnant women.

Methods: It is a case-control study consisting of 684 pregnant women under 18 years recruited in different tertiary care hospitals, in Lahore, between June 2023 and December 2023. Utilizing an online questionnaire, data collection encompassed demographics, dietary habits, and the Edinburgh Postnatal Depression Scale (EPDS).

Gamify4LexAmb: a gamification-based approach to address lexical ambiguity in natural language requirements.

Ambiguity is a common challenge in specifying natural language (NL) requirements. One of the reasons for the occurrence of ambiguity in software requirements is the lack of user involvement in requirements elicitation and inspection phases. Even if they get involved, it is hard for them to understand the context of the system, and ultimately unable to provide requirements correctly due to a lack of interest.

CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma.

Therapeutic approaches for clear cell renal cell carcinoma (ccRCC) remain limited; however, chimeric antigen receptor (CAR) T-cell therapies may offer novel treatment options. CTX130, an allogeneic CD70-targeting CAR T-cell product, was developed for the treatment of advanced or refractory ccRCC. We report that CTX130 showed favorable preclinical proliferation and cytotoxicity profiles and completely regressed RCC xenograft tumors.

PHLDA2-mediated phosphatidic acid peroxidation triggers a distinct ferroptotic response during tumor suppression.

Although the role of ferroptosis in killing tumor cells is well established, recent studies indicate that ferroptosis inducers also sabotage anti-tumor immunity by killing neutrophils and thus unexpectedly stimulate tumor growth, raising a serious issue about whether ferroptosis effectively suppresses tumor development in vivo. Through genome-wide CRISPR-Cas9 screenings, we discover a pleckstrin homology-like domain family A member 2 (PHLDA2)-mediated ferroptosis pathway that is neither ACSL4-dependent nor requires common ferroptosis inducers. PHLDA2-mediated ferroptosis acts through the peroxidation of phosphatidic acid (PA) upon high levels of reactive oxygen species (ROS).

Strikingly High Activity of 15-Lipoxygenase Towards Di-Polyunsaturated Arachidonoyl/Adrenoyl-Phosphatidylethanolamines Generates Peroxidation Signals of Ferroptotic Cell Death.

The vast majority of membrane phospholipids (PLs) include two asymmetrically positioned fatty acyls: oxidizable polyunsaturated fatty acids (PUFA) attached predominantly at the sn2 position, and non-oxidizable saturated/monounsaturated acids (SFA/MUFA) localized at the sn1 position. The peroxidation of PUFA-PLs, particularly sn2-arachidonoyl(AA)- and sn2-adrenoyl(AdA)-containing phosphatidylethanolamines (PE), has been associated with the execution of ferroptosis, a program of regulated cell death. There is a minor subpopulation (≈1-2 mol %) of doubly PUFA-acylated phospholipids (di-PUFA-PLs) whose role in ferroptosis remains enigmatic.

Anomalous peroxidase activity of cytochrome c is the primary pathogenic target in Barth syndrome.

Barth syndrome (BTHS) is a life-threatening genetic disorder with unknown pathogenicity caused by mutations in TAFAZZIN (TAZ) that affect remodeling of mitochondrial cardiolipin (CL). TAZ deficiency leads to accumulation of mono-lyso-CL (MLCL), which forms a peroxidase complex with cytochrome c (cyt c) capable of oxidizing polyunsaturated fatty acid-containing lipids. We hypothesized that accumulation of MLCL facilitates formation of anomalous MLCL-cyt c peroxidase complexes and peroxidation of polyunsaturated fatty acid phospholipids as the primary BTHS pathogenic mechanism.

Differences in hepatocellular iron metabolism underlie sexual dimorphism in hepatocyte ferroptosis.

Males show higher incidence and severity than females in hepatic injury and many liver diseases, but the mechanisms are not well understood. Ferroptosis, an iron-mediated lipid peroxidation-dependent death, plays an important role in the pathogenesis of liver diseases. We determined whether hepatocyte ferroptosis displays gender difference, accounting for sexual dimorphism in liver diseases.

Multiple motor disorders in cerebral palsy.

Aim: To characterize motor disorders in children and young people with cerebral palsy (CP).

Method: This was a cross-sectional study of 582 children and young people with CP (mean age 9 years 7 months; range 11 months-19 years 9 months; standard deviation 4 years 11 months; 340 males) attending a rehabilitation clinic at a specialized children's hospital (May 2018-March 2020). Data on motor disorders, topography, functional classifications, and non-motor features, such as epilepsy, intellectual disability, and sensory impairments, were collected using the Australian Cerebral Palsy Register CP Description Form.

Differences in Hepatocellular Iron Metabolism Underlie Sexual Dimorphism in Hepatocyte Ferroptosis.

Males show higher incidence and severity than females in hepatic injury and many liver diseases, but the mechanisms are not well understood. Ferroptosis, an iron-mediated lipid peroxidation-dependent death, plays an important role in the pathogenesis of liver diseases. We determined whether hepatocyte ferroptosis displays gender difference, accounting for sexual dimorphism in liver diseases.

Discovering selective antiferroptotic inhibitors of the 15LOX/PEBP1 complex noninterfering with biosynthesis of lipid mediators.

Programmed ferroptotic death eliminates cells in all major organs and tissues with imbalanced redox metabolism due to overwhelming iron-catalyzed lipid peroxidation under insufficient control by thiols (Glutathione (GSH)). Ferroptosis has been associated with the pathogenesis of major chronic degenerative diseases and acute injuries of the brain, cardiovascular system, liver, kidneys, and other organs, and its manipulation offers a promising new strategy for anticancer therapy. This explains the high interest in designing new small-molecule-specific inhibitors against ferroptosis.

Effectiveness of Electroconvulsive Therapy for Preventing Relapse and Recurrence of Depression in Adults With Major Depressive Disorder: An Updated Meta-Analysis of Randomized Clinical Trials.

The present meta-analysis aimed to assess the impact of electroconvulsive therapy (ECT) in preventing the relapse and recurrence of depression in adults with major depressive disorders. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two authors conducted a systematic search of online databases, such as PubMed, PsycINFO, and EMBASE, using keywords, such as "electroconvulsive therapy," "depressive disorders," and "recurrence.

Callus γδ T cells and microbe-induced intestinal Th17 cells improve fracture healing in mice.

IL-17A (IL-17), a driver of the inflammatory phase of fracture repair, is produced locally by several cell lineages including γδ T cells and Th17 cells. However, the origin of these T cells and their relevance for fracture repair are unknown. Here, we show that fractures rapidly expanded callus γδ T cells, which led to increased gut permeability by promoting systemic inflammation.

Effect of Phosphodiesterase-5 (PDE-5) Inhibitors on Clinical Outcomes in Patients With Pulmonary Hypertension: A Meta-Analysis of Randomized Control Trials.

We intended to summarize the most recent research pertaining to the use of phosphodiesterase-5 (PDE5) inhibitors in pulmonary hypertension in light of recent developments in the knowledge of the pathophysiological mechanisms and treatments for pulmonary hypertension, with major contributions in the area in the last decade. The aim of this meta-analysis is to determine the efficacy of PDE5 inhibitors for pulmonary hypertension in adults. We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines to carry out this meta-analysis.

Nutrition Care in Cancer Surgery Patients: A Narrative Review of Nutritional Screening and Assessment Methods and Nutritional Considerations.

Malignancy is a catabolic state, which is precipitated with surgical intervention. Malnutrition is one of the main risk factors for poor outcomes of cancer surgery. We need to screen oncological patients for malnutrition using standardized screening tools, by which patients found to be at nutritional risk are then referred to a registered dietitian for further management.

Immunoinformatics-Aided Analysis of RSV Fusion and Attachment Glycoproteins to Design a Potent Multi-Epitope Vaccine.

Respiratory syncytial virus (RSV) usually causes respiratory tract infections of upper airways in infants and young children. Despite recent medical advances, no approved vaccine is available to control RSV infections. Therefore, we conducted an immunoinformatics study to design and evaluate a potential multi-epitope vaccine against RSV.

Reducing Requirements Ambiguity via Gamification: Comparison with Traditional Techniques.

Requirements elicitation is one of the most significant activities of requirements engineering (RE) process. Poorly specified requirements can lead to a failed project. Various elicitation techniques are used to elicit requirements from the users and other stakeholders, each having its own pros and cons.

Twenty-Year Benefit From Adjuvant Goserelin and Tamoxifen in Premenopausal Patients With Breast Cancer in a Controlled Randomized Clinical Trial.

Purpose: To assess the long-term (20-year) endocrine therapy benefit in premenopausal patients with breast cancer.

Methods: Secondary analysis of the Stockholm trial (STO-5, 1990-1997) randomly assigning 924 premenopausal patients to 2 years of goserelin (3.6 mg subcutaneously once every 28 days), tamoxifen (40 mg orally once daily), combined goserelin and tamoxifen, or no adjuvant endocrine therapy (control) is performed.

Ameliorates Ovariectomy-Induced Bone Loss Enhancing Anti-Osteoclastogenic and Immunomodulatory Potential of Regulatory B Cells (Bregs).

Discoveries in the last few years have emphasized the existence of an enormous breadth of communication between osteo-immune systems. These discoveries fuel novel approaches for the treatment of several bone pathologies including osteoporosis. (BL) is a preferred probiotic of choice due to its varied immunomodulatory potential in alleviating various inflammatory diseases.

Inactivation of RIP3 kinase sensitizes to 15LOX/PEBP1-mediated ferroptotic death.

Ferroptosis and necroptosis are two pro-inflammatory cell death programs contributing to major pathologies and their inhibition has gained attention to treat a wide range of disease states. Necroptosis relies on activation of RIP1 and RIP3 kinases. Ferroptosis is triggered by oxidation of polyunsaturated phosphatidylethanolamines (PUFA-PE) by complexes of 15-Lipoxygenase (15LOX) with phosphatidylethanolamine-binding protein 1 (PEBP1).

More than a feeling? An expanded investigation of emotional responsiveness in young children with conduct problems and callous-unemotional traits.

Children with conduct problems and high callous-unemotional (CP+CU) traits are characterized by dampened emotional responding, limiting their ability for affective empathy and impacting the development of prosocial behaviors. However, research documenting this dampening in young children is sparse and findings vary, with attachment-related stimuli hypothesized to ameliorate deficits in emotional responding. Here we test emotional responsiveness across various emotion-eliciting stimuli using multiple measures of emotional responsiveness (behavioral, physiological, self-reported) and attention, in young children aged 2-8 years ( age = 5.