Phase I trial of hydroxychloroquine to enhance palbociclib and letrozole efficacy in ER+/HER2- breast cancer.

Endocrine therapy with CDK4/6 inhibitors is standard for estrogen receptor-positive, HER2-negative metastatic breast cancer (ER+/HER2- MBC), yet clinical resistance develops. Previously, we demonstrated that low doses of palbociclib activate autophagy, reversing initial G1 cell cycle arrest, while high concentrations induce off-target senescence. The autophagy inhibitor hydroxychloroquine (HCQ) induced on-target senescence at lower palbociclib doses.

p53-loss induced prostatic epithelial cell plasticity and invasion is driven by a crosstalk with the tumor microenvironment.

Prostate cancer is a heterogeneous disease with a slow progression and a highly variable clinical outcome. The tumor suppressor genes PTEN and TP53 are frequently mutated in prostate cancer and are predictive of early metastatic dissemination and unfavorable patient outcomes. The progression of solid tumors to metastasis is often associated with increased cell plasticity, but the complex events underlying TP53-loss-induced disease aggressiveness remain incompletely understood.

Impacts of irrigation expansion on moist-heat stress based on IRRMIP results.

Irrigation rapidly expanded during the 20 century, affecting climate via water, energy, and biogeochemical changes. Previous assessments of these effects predominantly relied on a single Earth System Model, and therefore suffered from structural model uncertainties. Here we quantify the impacts of historical irrigation expansion on climate by analysing simulation results from six Earth system models participating in the Irrigation Model Intercomparison Project (IRRMIP).

A low-cost printed circuit board-based centrifugal microfluidic platform for dielectrophoresis.

In recent decades, electrokinetic handling of microparticles and biological cells found many applications ranging from biomedical diagnostics to microscale assembly. The integration of electrokinetic handling such as dielectrophoresis (DEP) greatly benefits microfluidic point-of-care systems as many modern assays require cell handling. Compared to traditional pump-driven microfluidics, typically used for DEP applications, centrifugal CD microfluidics provides the ability to consolidate various liquid handling tasks in self-contained discs under the control of a single motor.

Mucus-penetrating microbiota drive chronic low-grade intestinal inflammation and metabolic dysregulation.

Metabolic syndrome is, in humans, associated with alterations in the composition and localization of the intestinal microbiota, including encroachment of bacteria within the colon's inner mucus layer. Possible promoters of these events include dietary emulsifiers, such as carboxymethylcellulose (CMC) and polysorbate-80 (P80), which, in mice, result in altered microbiota composition, encroachment, low-grade inflammation and metabolic syndrome. While assessments of gut microbiota composition have largely focused on fecal/luminal samples, we hypothesize an outsized role for changes in mucus microbiota in driving low-grade inflammation and its consequences.

Crucial role of subsurface ocean variability in tropical cyclone genesis.

The upper ocean provides thermal energy to tropical cyclones. However, the impacts of the subsurface ocean on tropical cyclogenesis have been largely overlooked. Here, we show that the subsurface variabilities associated with the variation in the 26 °C isothermal depth have pronounced impacts on tropical cyclogenesis over global oceans.

Gender differences in cognitive impairment among the elderly in rural West Texas counties.

Background: The prevalence of Alzheimer's disease or dementia in the elderly population has been increasing both nationally and globally. Males and females are impacted differently when it comes to cognitive health, and this can be influenced by various risk factors.

Objective: This study highlights the sociodemographic, chronic disease, and genetic biomarker risk factors associated with gender differences and cognitive impairments in the elderly population living in Cochran, Parmer, and Bailey counties of rural West Texas.

Evaluation of an image-rich quiz-based iOS app as a study resource for the ABR Core exam.

The American Board of Radiology Core exam requires that trainees demonstrate knowledge of critical concepts across 12 domains spanning a range of imaging modalities and anatomic regions. Mobile apps have become popular components of medical and radiology education since the inception of smartphones. Numerous medical educational apps are accessible via smartphone devices and tablets, regardless of operating system, for medical training and learning purposes.

Pediatric Surgical Outreach: An Underutilized Resource for Increasing Children's Surgical Capacity in Canada.

Background: Wait times for children's hospital-based surgical services are at unprecedented levels. Opportunities to increase most children's hospital-based service capacity are sparse, and community-based services are a potential patient-centered alternative. The aim of this study was to understand the current state of pediatric surgical outreach in Canada as an option to address these challenges.

Dose verification of 2 targets simultaneously for single-isocenter stereotactic radiation therapy and radiosurgery plans.

Most of conventional 2-dimensional (2D) methods verify dose of multiple targets separately one-by-one for Single-isocenter Multiple-target (SIMT) brain plans, which are inefficient and sub-optimal. This study presented a practical method to verify the dose of 2 targets simultaneously for improved efficiency and accuracy. Fifteen Stereotactic Radiation Therapy (SRT) and sixteen Stereotactic Radiosurgery (SRS) plans were used for this study.

Midwives' perceived knowledge, perceptions, and experiences of managing paternal postnatal depression in Tanzania: A qualitative descriptive study.

Background: Paternal postnatal depression (PPND) is an under-recognized condition that affects new fathers' psychological and emotional well-being, which may impact family dynamics, work performance, and childcare. Despite its significance, there is limited awareness and understanding of its management and implications among midwives, especially in Africa.

Aims: To explore midwives' experiences of managing PPND in Tanzania.

Mucosal integrity and acid sensitivity predict proton pump inhibitor response in patients with heartburn and normal acid exposure.

Background: Patients with typical reflux symptoms and normal acid exposure time (AET) are classified as either reflux hypersensitivity (RH) or functional heartburn (FH), some of whom respond to proton pump inhibitors (PPIs). We determined if esophageal psychophysiological parameters predict PPI response in symptomatic RH and FH patients.

Methods: We prospectively recruited adults with heartburn diagnosed with RH or FH on 24-h impedance-pH monitoring off PPI.

Safety, tolerability and therapeutic efficacy of anti-inflammatory drug pirfenidone in acute pancreatitis patients: Protocol for a randomized pilot clinical trial.

Background: Acute Pancreatitis (AP) is a formidable disease with significant morbidity, mortality and healthcare expenditure. There is an emergent need to develop therapeutic agents for this disease as there are no targeted therapies available. We have recently demonstrated that pirfenidone can significantly decrease the severity of AP in animal models.

Treatment with a superoxide dismutase mimetic for joint preservation during 35 and 75 days in orbit aboard the international space station, and after 120 days recovery on Earth.

Reduced weight-bearing during spaceflight has been associated with musculoskeletal degradation that risks astronaut health and performance in transit and upon reaching deep space destinations. Previous rodent experiments aboard the international space station (ISS) have identified that the spaceflight-induced molecular arthritic phenotype was characterized with an increase in oxidative stress. This study evaluated if treatment with a superoxide dismutase (SOD) mimetic on orbit could prevent spaceflight-induced damage to the knee and hip articular cartilage, and the menisci in rodents.

Behavior of simple closed ecological systems; lower nutrient concentrations allow longer persistence of grazer populations.

We expect to develop self-sustaining extraterrestrial colonies, and they will approach being closed ecological systems. Using simple closed ecosystems containing Daphnia magna, three species of algae, and microbes, we tested multiple conditions to study long-term organism survival, which is only possible with adequate nutrient recycling. Closed and open systems behaved differently from one another at high nitrate concentrations; in closed systems, the animals were dead by day 14; in open systems, the Daphnia populations persisted beyond 273 days.

Sex-specific effects on the heart from combined exposure to simulated galactic cosmic radiation and hindlimb unloading.

Future long duration space missions will expose astronauts to higher doses of galactic cosmic radiation (GCR) than those experienced on the international space station. Recent studies have demonstrated astronauts may be at risk for cardiovascular complications due to increased radiation exposure and fluid shift from microgravity. However, there is a lack of direct evidence on how the cardiovascular system is affected by GCR and microgravity since no astronauts have been exposed to exploratory mission relevant GCR doses.

Thoracolumbar spine muscle size and composition changes in long-duration space missions.

Muscle atrophy occurs with extended exposure to microgravity. This study quantified the overall muscle size, lean muscle area and fat infiltration changes pre- to post-flight that occur in the thoracic and lumbar spine with long-duration spaceflight. Pre- and post-flight magnetic resonance imaging (MRI) scans were obtained from 9 crewmembers on long-duration (≥6 months) International Space Station (ISS) missions.

The interplay between personal traits and coping strategies on shift-work tolerance: a cross-sectional study.

The ability to adapt to night shift work varies greatly among individuals, but little is known about how personal traits and coping strategies interact to affect shift-work tolerance. This study aimed to identify how certain personal traits (e.g.

Giant, unruptured, partially thrombosed right MCA aneurysm treated with 2 bypasses and excision.

Aneurysms of the middle cerebral artery (MCA) account for up to 40% of all unruptured intracranial aneurysms [1-3] and 14% to 20% of ruptured ones. [4-5] Giant MCA aneurysms are rare, representing 10% of cases [6], but carry an aggressive natural history, with the UCAS Japan study reporting an annual rupture rate of ∼ 17%. [7].

Adaptive Intervention for School-Age, Minimally Verbal Children With Autism Spectrum Disorder in the Community: Primary Aim Results.

Objective: The goal of this study is to construct a 16-week, two-stage, adaptive intervention consisting of DTT ([discrete trials training], largely considered usual care for children with autism), JASP-EMT (a blended, naturalistic, developmental behavioral intervention involving JASPER [joint attention, symbolic play, engagement and regulation] and EMT [enhanced milieu teaching]), and parent training (P) for improving spontaneous, communicative utterances in school-aged, minimally verbal autistic children. Intervention was delivered both at school (DTT, JASP-EMT) and home (P). This manuscript reports results for the study's primary aim and a closely related secondary aim.

Circadian influences on sudden cardiac death and cardiac electrophysiology.

Cardiologists have analyzed daily patterns in the incidence of sudden cardiac death to identify environmental, behavioral, and physiological factors that trigger fatal arrhythmias. Recent studies have indicated an overall increase in sudden cardiac arrest during daytime hours when the frequency of arrhythmogenic triggers is highest. The risk of fatal arrhythmias arises from the interaction between these triggers-such as elevated sympathetic signaling, catecholamine levels, heart rate, afterload, and platelet aggregation-and the heart's susceptibility (myocardial substrate) to them.