Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes.

Special histologic subtypes of breast cancer (BC) exhibit unique phenotypes and molecular profiles with diagnostic and therapeutic implications, often differing in behavior and clinical trajectory from common BC forms. Novel methodologies, such as artificial intelligence may improve classification. Genetic predisposition plays roles in a subset of cases.

SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation.

Many essential proteins require pyridoxal 5'-phosphate, the active form of vitamin B6, as a cofactor for their activity. These include enzymes important for amino acid metabolism, one-carbon metabolism, polyamine synthesis, erythropoiesis, and neurotransmitter metabolism. A third of all mammalian pyridoxal 5'-phosphate-dependent enzymes are localized in the mitochondria; however, the molecular machinery involved in the regulation of mitochondrial pyridoxal 5'-phosphate levels in mammals remains unknown.

A Call for a Neoadjuvant Kidney Cancer Consortium: Lessons Learned from Other Cancer Types.

Neoadjuvant systemic treatment strategies have improved outcomes in several solid tumour types. This success has not yet been replicated in renal cell carcinoma (RCC). A consensus and international collaboration are urgently needed for the development of adaptive perioperative immunotherapy strategies for patients with RCC at high risk of recurrence.

Using artificial intelligence to optimize anti-seizure treatment and EEG-guided decisions in severe brain injury.

Electroencephalography (EEG) is invaluable in the management of acute neurological emergencies. Characteristic EEG changes have been identified in diverse neurologic conditions including stroke, trauma, and anoxia, and the increased utilization of continuous EEG (cEEG) has identified potentially harmful activity even in patients without overt clinical signs or neurologic diagnoses. Manual annotation by expert neurophysiologists is a major resource limitation in investigating the prognostic and therapeutic implications of these EEG patterns and in expanding EEG use to a broader set of patients who are likely to benefit.

Age Self Care-Resilience, a medical group visit program targeting pre-frailty: A mixed methods pilot clinical trial.

Background: Pre-frailty is highly prevalent and multimodal lifestyle interventions are effective for preventing transition to frailty. However, little is known about the potential for medical group visits (MGV) to prevent frailty progression.

Objectives: To assess the feasibility and acceptability of the MGV Age Self Care-Resilience.

Characteristics of children and adolescents with multidrug-resistant and rifampicin-resistant tuberculosis and their association with treatment outcomes: a systematic review and individual participant data meta-analysis.

Background: There are few data on the treatment of children and adolescents with multidrug-resistant (MDR) or rifampicin-resistant (RR) tuberculosis, especially with more recently available drugs and regimens. We aimed to describe the clinical and treatment characteristics and their associations with treatment outcomes in this susceptible population.

Methods: We conducted a systematic review and individual participant data meta-analysis.

Clinical outcomes of patients with unsuccessful mechanical thrombectomy versus best medical management of medium vessel occlusion stroke in the middle cerebral artery territory.

Background: Current randomized controlled trials are investigating the efficacy and safety of mechanical thrombectomy (MT) in patients with medium vessel occlusion (MeVO) stroke. Whether best medical management (MM) is more efficient than unsuccessful vessel recanalization during MT remains unknown.

Methods: This was a retrospective cohort study using data from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021.

US children from non-English-speaking households are less likely to undergo vision testing.

Purpose: To investigate the association between primary household language and vision testing among children living in the United States from 2016 to 2020.

Methods: This analysis used data for children aged 3-17 years from the National Survey of Children's Health (NSCH), combining survey responses from 2016 to 2020. Primary household language and whether vision testing occurred were determined by survey responses.

Implantable Cardioverter-Defibrillators and Cardiovascular Resynchronization Therapy with Left Ventricular Assist Devices: A MOMENTUM 3 Trial Analysis.

Background: The benefit of implantable cardioverter-defibrillators (ICD) and cardiovascular resynchronization therapy (CRT-D) in patients supported with a HeartMate 3 left ventricular assist device (LVAD) remains uncertain.

Methods: An analysis of the MOMENTUM 3 randomized clinical trial and the first 1000 patients in the Continued Access Protocol trial. Patients were divided into three groups based on the presence of ICD and/or CRT-D: No device (n=153, 11%), ICD only (n=699, 50.

Targeting alarmins in asthma- From the bench to the clinic.

Over the past two decades, mechanistic studies of allergic and type 2 (T2)-mediated airway inflammation have led to multiple approved therapies for the treatment of moderate-to-severe asthma. The approval and availability of these monoclonal antibodies targeting immunoglobulin E, a type 2 cytokine (IL-5) and/or cytokine receptors (IL-5Rα, IL-4Rα) has been central to the progresses made in the management of moderate-to-severe asthma over this period. However, there are persistent gaps in clinician's ability to provide precise care given that many patients with type 2-high asthma do not respond to the IgE or T2 cytokine-targeting therapies and patients with type 2-low asthma have limited therapeutic options.

Long term outcomes post-ICD in Chagas cardiomyopathy and non-ischemic cardiomyopathy: A comparative analysis.

Background: Chagas cardiomyopathy (CCM) is a significant cause of ventricular arrhythmias and sudden cardiac death (SCD). Although, implantable cardiac defibrillators (ICD) have been used for all forms of non-ischemic cardiomyopathy (NICM), studies on ICD efficacy in CCM are scarce.

Objective: The present study aims to compare the long-term outcomes, mortality rates, and the occurrence of tachycardia therapies after ICD implantation in patients with CCM and NICM.

Causal Estimands for Analyses of Averted and Avertible Outcomes due to Infectious Disease Interventions.

During the coronavirus disease (COVID-19) pandemic, researchers attempted to estimate the number of averted and avertible outcomes due to vaccination campaigns to quantify public health impact. However, the estimands used in these analyses have not been previously formalized. It is also unclear how these analyses relate to the broader framework of direct, indirect, total, and overall causal effects under interference.

Effect modification in settings with "truncation by death".

Epidemiologic studies recruiting individuals with higher-than-population-average mortality can be affected by "truncation by death", whereby the outcome of interest (e.g. quality of life) is considered not to be defined for individuals who die before the end of follow-up.

Structure-guided discovery of viral proteins that inhibit host immunity.

Viruses encode proteins that inhibit host defenses, but sifting through the millions of available viral sequences for immune-modulatory proteins has been so far impractical. Here, we develop a process to systematically screen virus-encoded proteins for inhibitors that physically bind host immune proteins. Focusing on Thoeris and CBASS, bacterial defense systems that are the ancestors of eukaryotic Toll/interleukin-1 receptor (TIR) and cyclic GMP-AMP synthase (cGAS) immunity, we discover seven families of Thoeris and CBASS inhibitors, encompassing thousands of genes widespread in phages.

Association between joint exposure to ambient air pollutants and carotid plaque: The mediating role of cardiometabolic risk factors.

Background: Research has shown that exposure to joint air pollution is related to atherosclerosis, but little evidence has been found for carotid plaques. Our objective is to assess the association between exposure to joint air pollutants and carotid plaque and explore the mediating role of cardiometabolic factors in this relationship.

Methods: The Beijing Health Management Cohort (BMHC) study followed participants recruited from 2013 to 2014 until December 31, 2020.

Antiseizure medications for Lennox-Gastaut Syndrome: Comprehensive review and proposed consensus treatment algorithm.

Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, specific electroencephalogram (EEG) patterns, and significant cognitive and behavioral impairments. To date, eight anti-seizure medications (ASMs) have been specifically approved by the U.S.

Paediatric strategy forum for medicinal product development in diffuse midline gliomas in children and adolescents ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

Fewer than 10 % of children with diffuse midline glioma (DMG) survive 2 years from diagnosis. Radiation therapy remains the cornerstone of treatment and there are no medicinal products with regulatory approval. Although the biology of DMG is better characterized, this has not yet translated into effective treatments.

Childbearing plans' predictive value for birth outcomes: A systematic review to inform mode of delivery decisions.

Objective: Rising cesarean delivery (CD) rates significantly impact maternal health, underscoring the need for comprehensive counseling. This review examines the consistency of childbearing plans over time and their predictive value for childbirth events.

Data Sources: PubMed, EMBASE, Web of Science, and PsycINFO databases up to October 2023.

Safety of topical estrogen therapy during adjuvant endocrine treatment among patients with breast cancer: A meta-analysis based expert panel discussion.

Importance: Endocrine treatments, such as Tamoxifen (TAM) and/or Aromatase inhibitors (AI), are the adjuvant therapy of choice for hormone-receptor positive breast cancer. These agents are associated with menopausal symptoms, adversely affecting drug compliance. Topical estrogen (TE) has been proposed for symptom management, given its' local application and presumed reduced bioavailability, however its oncological safety remains uncertain.

Impact of disease duration and surgical intervention on arousal networks in temporal lobe epilepsy.

Objective: Epilepsy is a common neurological disease affecting nearly 1% of the global population, and temporal lobe epilepsy (TLE) is the most common type. Patients experience recurrent seizures and chronic cognitive deficits that can impact their quality of life, ability to work, and independence. These cognitive deficits often extend beyond the temporal lobe and are not well understood.

Genomic Characterization and Prognostic Significance of Human Epidermal Growth Factor Receptor 2-Low, Hormone Receptor-Positive, Early Breast Cancers From the BIG 1-98 and SOFT Clinical Trials.

Purpose: To investigate whether hormone receptor-positive, human epidermal growth factor receptor 2-low (HR+HER2-low) versus HR+HER2-zero early breast cancers have distinct genomic and clinical characteristics.

Methods: This study included HR+, HER2-negative early breast cancers from patients enrolled in the phase III, randomized BIG 1-98 and SOFT clinical trials that had undergone tumor genomic sequencing. Tumors were classified HR+HER2-low if they had a centrally reviewed HER2 immunohistochemistry (IHC) score of 1+ or 2+ with negative in situ hybridization and HR+HER2-zero if they had an HER2 IHC score of 0.