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.

Mcl-1 is a Gatekeeper Molecule to Regulate the Crosstalk Between Ferroptotic Agent-Induced ER Stress and TRAIL-Induced Apoptosis.

We previously reported that ferroptosis interplays with apoptosis through the integration of two independent pathways: the endoplasmic reticulum (ER) stress signaling pathway and the mitochondria-dependent apoptotic signaling pathway. In this study, we investigated a potential gatekeeper molecule, Mcl-1, between the two signal transduction pathways. Morphology studies and cell death analyses confirmed that a combination treatment of ferroptotic agent erastin (ERA) and apoptotic agent TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) synergistically enhances TRAIL-induced apoptosis in human pancreatic adenocarcinoma BxPC3 and human colorectal carcinoma HCT116 cells.

Nutritional Interventions to Attenuate Quadriceps Muscle Deficits following Anterior Cruciate Ligament Injury and Reconstruction.

Following anterior cruciate ligament (ACL) injury, quadriceps muscle atrophy persists despite rehabilitation, leading to loss of lower limb strength, osteoarthritis, poor knee joint health and reduced quality of life. However, the molecular mechanisms responsible for these deficits in hypertrophic adaptations within the quadriceps muscle following ACL injury and reconstruction are poorly understood. While resistance exercise training stimulates skeletal muscle hypertrophy, attenuation of these hypertrophic pathways can hinder rehabilitation following ACL injury and reconstruction, and ultimately lead to skeletal muscle atrophy that persists beyond ACL reconstruction, similar to disuse atrophy.

Atrial Fibrillation Related Titin Truncation Is Associated With Atrial Myopathy in Patient-Derived Induced Pluripotent Stem Cell Disease Models.

Background: Protein-truncating mutations in the titin gene are associated with increased risk of atrial fibrillation. However, little is known about the underlying pathophysiology.

Methods: We identified a heterozygous titin truncating variant (TTNtv) in a patient with unexplained early onset atrial fibrillation and normal ventricular function.

Penfluridol targets septin7 to suppress endometrial cancer by septin7-Orai/IP3R-Ca-PIK3CA pathway.

Phenotypic screening of existing drugs is a good strategy to discover new drugs. Herein, 33 psychotherapeutic drugs in our drug library were screened by phenotypic screening and penfluridol (PFD) was found to exhibit excellent anti-endometrial cancer (EC) activity both and . Furthermore, the molecular target of PFD was identified as septin7, a tumor suppressor in EC.

Prolonged neurologic symptoms following immune effector cell-associated neurotoxicity syndrome in patients with large B cell lymphoma treated with chimeric antigen receptor-modified T cell therapy.

Background: While immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-defined adverse effect associated with chimeric antigen receptor-modified T cell (CAR-T) therapy, some patients develop prolonged neurologic symptoms. Few studies have examined characteristics and outcomes of patients who develop such symptoms.

Objective: To provide an analysis of patients who developed ICANS in a single-center cohort of patients with large B-cell lymphoma (LBCL) who received commercial CAR-T and compare characteristics and outcomes between patients with vs.

Microbiota translocation following intestinal barrier disruption promotes Mincle-mediated training of myeloid progenitors in the bone marrow.

Impairment of the intestinal barrier allows the systemic translocation of commensal bacteria, inducing a proinflammatory state in the host. Here, we investigated innate immune responses following increased gut permeability upon administration of dextran sulfate sodium (DSS) in mice. We found that Enterococcus faecalis translocated to the bone marrow following DSS treatment and induced trained immunity (TI) hallmarks in bone-marrow-derived mouse macrophages and human monocytes.

Eye Movements and the Intraorbital Subarachnoid Space: Potential Contribution of Altered Cerebrospinal Fluid Pumping in Optic Neuropathies.

Purpose: The optic nerve (ON) is mechanically perturbed by eye movements that shift cerebrospinal fluid (CSF) within its surrounding dural sheath. This study compared changes in ON length and CSF volume within the intraorbital ON sheath caused by eye movements in healthy subjects and patients with optic neuropathies.

Methods: Twenty-one healthy controls were compared with 11 patients having primary open angle glaucoma (POAG) at normal intraocular pressure (IOP), and 11 with chronic non-arteritic anterior ischemic optic neuropathy (NA-AION).

Evolution of sleep disordered breathing in infants with achondroplasia.

Purpose: Children with achondroplasia (ACH) are at risk for sudden death in infancy due to sleep disordered breathing (SDB) and foramen magnum stenosis (FMS). Sleep studies and neuroimaging are performed in infants with ACH, but interpretation of infant studies is challenging. We sought to describe baseline data on polysomnography (PSG) indices in infants with achondroplasia as well as effects of age and surgery on these parameters.

Classifying Race in Out-of-Hospital Cardiac Arrest and Potential Disparities: A Retrospective Cohort Study.

Background: Although racial disparities have been described in resuscitation, little is known about potential bias in race classification of out-of-hospital cardiac arrest (OHCA).

Methods: We conducted a retrospective cohort study of adults treated by emergency medical services (EMS) for nontraumatic OHCA in King County, WA between January 1, 2018, and December 31, 2021. We assessed agreement using κ and evaluated patterns of missingness between EMS-assessed race versus comprehensive race classification from hospital and death records.

Heterogeneous and higher-order cortical connectivity undergirds efficient, robust, and reliable neural codes.

We hypothesized that the heterogeneous architecture of biological neural networks provides a substrate to regulate the well-known tradeoff between robustness and efficiency, thereby allowing different subpopulations of the same network to optimize for different objectives. To distinguish between subpopulations, we developed a metric based on the mathematical theory of simplicial complexes that captures the complexity of their connectivity by contrasting its higher-order structure to a random control and confirmed its relevance in several openly available connectomes. Using a biologically detailed cortical model and an electron microscopic dataset, we showed that subpopulations with low simplicial complexity exhibit efficient activity.

The Impact of Family History on Clinical Presentation and Biologic Treatment Response in Patients with Psoriasis: A Multicenter Prospective Cohort Study.

Background: Family history (FH) of psoriasis has been implicated as a risk factor for developing psoriasis. However, whether FH also carries information on clinical presentation and treatment response to biological agents in patients with psoriasis remains unclear.

Objective: This prospective, multicenter observational study aimed to analyze the clinical presentation and efficacy differences between patients with psoriasis with and without a FH.

Quantum-computing-enhanced algorithm unveils potential KRAS inhibitors.

We introduce a quantum-classical generative model for small-molecule design, specifically targeting KRAS inhibitors for cancer therapy. We apply the method to design, select and synthesize 15 proposed molecules that could notably engage with KRAS for cancer therapy, with two holding promise for future development as inhibitors. This work showcases the potential of quantum computing to generate experimentally validated hits that compare favorably against classical models.

A legume-enriched diet improves metabolic health in prediabetes mediated through gut microbiome: a randomized controlled trial.

Healthy dietary patterns rich in legumes can improve metabolic health, although their additional benefits in conjunction with calorie restriction have not been well-established. We investigated effects of a calorie-restricted, legume-enriched, multicomponent intervention diet compared with a calorie-restricted control diet in 127 Chinese prediabetes participants, living in Singapore. The study was a 16-week, single-blind, parallel-design, randomized controlled trial (n = 63 intervention group (IG), n = 64 control group (CG); mean ± SD age 62.

Proximal protection devices for carotid artery stenting - A benchtop assessment of flow reversal performance.

Background And Purpose: Proximal protection devices, such as TransCarotid Artery Revascularization (TCAR, SilkRoad Medical, Sunnyvale), aim to yield better outcomes in carotid artery stenting (CAS) than distal protection devices by preventing plaque embolization to the brain. However, transfemoral catheters may not fully reverse flow from the external carotid artery (ECA) to the internal carotid artery (ICA). We assess a new balloon-sheath device, Femoral Flow Reversal Access for Carotid Artery Stenting (FFRACAS), for this purpose.

Recent Advancements and Future Perspectives on Molecular Biomarkers in Adult Lower-Grade Gliomas.

There has been a significant paradigm shift in the clinical management of lower-grade glioma patients given the recent updates to the 2021 World Health Organization classification along with long-term results from randomized phase III clinical trials. As a result, we are now better able to diagnose and assign patients to the most appropriate treatment course. This review provides a comprehensive summary of the most robust and reliable molecular biomarkers for adult lower-grade gliomas and discusses current challenges facing this patient population that future correlative biology studies combined with advancements in technologies could help overcome.

Estimating financial and health burden by initial Medicare plan choice and history of cancer.

Understanding the downstream consequences of initial Medicare plan selection is necessary to ensure access to and affordability of health care services, especially for older adults with serious illness. We used 2008-2020 data from the Health and Retirement Study to estimate financial and health burden by initial Medicare plan selection (traditional Medicare without supplemental coverage, traditional Medicare plus supplemental coverage, or Medicare Advantage) and self-reported history of cancer. Initially choosing benefits with greater financial protections (either traditional Medicare plus supplemental coverage or Medicare Advantage) relative to traditional Medicare without supplemental coverage was associated with lower levels of out-of-pocket spending and a lower likelihood of reporting cost-related medication nonadherence and fair or poor health.

Association between descending aorta wall thickness or wall area and cardiovascular disease risk factors in cardiovascular disease-free patients: a study based on water-calcium material decomposition and subtraction-based computed tomography dark-blood imaging.

Background: Due to the low contrast between the vascular lumen and vessel wall, conventional computed tomography (CT) is not an effective method for visualizing the vessel wall. The purpose of this study was to assess the feasibility of vessel wall visualization using contrast-enhanced dual-energy CT (DECT)-derived water-calcium material decomposition (WMD) and subtraction-based dark-blood imaging (DBI). An additional objective of this study was to determine the association of descending aorta wall thickness (WT) and wall area (WA) with cardiovascular disease (CVD) risk factors and to ascertain the potential of DECT-derived WT and WA as image markers for identifying individuals at high risk for future CVD.

ON-OFF nanopores for optical control of transmembrane ionic communication.

Nanoscale photoswitchable proteins could facilitate precise spatiotemporal control of transmembrane communication and support studies in synthetic biology, neuroscience and bioelectronics. Here, through covalent modification of the α-haemolysin protein pore with arylazopyrazole photoswitches, we produced 'photopores' that transition between iontronic resistor and diode modes in response to irradiation at orthogonal wavelengths. In the diode mode, a low-leak OFF-state nanopore exhibits a reversible increase in unitary conductance of more than 20-fold upon irradiation at 365 nm.

Double Povidone-Iodine 5% Preparation Before Cataract Surgery for Endophthalmitis Prevention.

Objective: To compare endophthalmitis rates after cataract extraction in patients with different preoperative prophylaxis: double povidone-iodine preparation with topical antibiotics versus a control group.

Methods: All cases of postoperative endophthalmitis over the last 17 years were reviewed. Incidence rates of endophthalmitis for all cataract surgeries (current procedural terminology codes 66982 and 66984) performed by 26 surgeons were calculated.

The Statistical Fragility of Functional Outcomes for Arthroscopic Rotator Cuff Repair With and Without Acromioplasty: A Systematic Review and Meta-analysis.

Background: Views surrounding acromioplasty at the time of arthroscopic rotator cuff repair (RCR) have shifted dramatically over time. In recent years, various studies have argued against acromioplasty, citing equivocal functional outcomes after arthroscopic RCR with or without acromioplasty.

Purpose: To assess the statistical fragility of functional outcomes after arthroscopic RCR with and without acromioplasty using the reverse continuous fragility index (RCFI).