PHLDA2 promotes breast cancer metastasis by co-opting a developmental program for placental vascular remodeling.

Identifying drivers of metastasis is essential for developing new treatments for patients with advanced disease. Here, we identify as a robust driver of breast cancer metastasis. Previous work established as an imprinted gene expressed by trophoblasts which are critical for vascular remodeling during placental development.

A biopsychosocial approach to improving multidimensional frailty status in community-dwelling older adults: a protocol for a cluster randomized controlled trial.

Background: Frailty is a significant clinical syndrome affecting aging populations, leading to increased risks of negative outcomes such as falls, disability, hospitalization, and premature mortality. The concept has evolved from a simplistic view to a complex view that incorporates physical, psychological, cognitive, and social domains. Early intervention is crucial, yet research on the interactions among these domains is limited.

The International Work Addiction Scale (IWAS): A screening tool for clinical and organizational applications validated in 85 cultures from six continents.

Background And Aims: Despite the last decade's significant development in the scientific study of work addiction/workaholism, this area of research is still facing a fundamental challenge, namely the need for a valid and reliable measurement tool that shows cross-cultural invariance and, as such, allows for worldwide studies on this phenomenon.

Methods: An initial 16-item questionnaire, developed within an addiction framework, was administered alongside job stress, job satisfaction, and self-esteem measures in a total sample of 31,352 employees from six continents and 85 cultures (63.5% females, mean age of 39.

Comparison of precision of a paperless electronic input method versus the conventional paper form in an andrology laboratory: a prospective study.

Background: Manual counting for semen analysis is recommended by the World Health Organization. Technicians performing this usually record their results on a paper worksheet and then enter the data into an electronic laboratory information system. One disadvantage of this approach is the chance of post-analytical transcription errors, which can be reduced by checking the computer entries before reporting by another technician.

Ethical Challenges of Artificial Intelligence in Medicine.

Artificial intelligence (AI) and machine learning (ML) have become critical components in the transformation of healthcare. They offer enhanced diagnostic accuracy, personalized treatment plans, and support for clinical decision-making. However, with these advancements come significant ethical challenges, including concerns around transparency, bias, data privacy, and the potential displacement of healthcare professionals.

Bactrim-Induced Hepatotoxicity.

Sulfamethoxazole/trimethoprim (SMX/TMP) is a commonly used antimicrobial agent for treating common bacterial infections such as urinary tract infection (UTI), combined with doxycycline for community-acquired methicillin-resistant (MRSA), and invaluable in pneumonia (PJP), previously classified as . Of its known adverse reactions, hepatotoxicity rarely comes to mind, but indeed, it is a recognized but very rare adverse reaction that may lead to liver failure in adults and even rarer in children. We present a case of hepatotoxicity in a 43-year-old male patient on no prior medication who developed jaundice and highly elevated liver enzymes one week after the administration of Bactrim for the treatment of UTI in association with prostatism, symptoms of decreased urinary force due to obstruction of flow through the prostate gland.

Fecal deoxycholic acid associates with diet, intestinal microbes, and total bilirubin in primary sclerosing cholangitis.

Background & Aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with a strong association with inflammatory bowel disease and variable disease progression. We aimed to gain insights into the role of fecal bile acids (BA) on disease progression by determining the relationships between fecal BA, diet, and gut microbes, with markers of disease progression, BA synthesis, and farnesoid X receptor (FXR) activity.

Methods: BA levels in serum and stool, dietary intake, and markers of BA synthesis, and FXR activity were measured in 26 patients with early stage, large duct PSC.

The mitochondrial calcium uniporter transports Ca via a ligand-relay mechanism.

The mitochondrial calcium uniporter (mtCU) is a multicomponent Ca -specific channel that imparts mitochondria with the capacity to sense the cytosolic calcium signals. The metazoan mtCU comprises the pore-forming subunit MCU and the essential regulator EMRE, arranged in a tetrameric channel complex, and the Ca sensing peripheral proteins MICU1-3. The mechanism of mitochondrial Ca uptake by mtCU and its regulation is poorly understood.

MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations.

The mammalian mitochondrial proteome is under dual genomic control, with 99% of proteins encoded by the nuclear genome and 13 originating from the mitochondrial DNA (mtDNA). We previously developed MitoCarta, a catalogue of over 1000 genes encoding the mammalian mitochondrial proteome. This catalogue was compiled using a Bayesian integration of multiple sequence features and experimental datasets, notably protein mass spectrometry of mitochondria isolated from fourteen murine tissues.

Towards an improved understanding of drug excipient interactions to enable rapid optimization of nanosuspension formulations.

Suspensions of drug nanoparticles known as nanosuspensions have emerged as a successful enabling formulation approach for poorly soluble drug candidates. These nanoparticles typically require stabilization with specific polymer or surfactant excipients to prevent aggregation from occurring. This study demonstrates the necessity of formulating drug nanosuspensions with amphiphilic excipients possessing long hydrophobic alkyl or polymer block chains to produce stable nanoparticles.

GluN2A NMDA Receptor Enhancement Improves Brain Oscillations, Synchrony, and Cognitive Functions in Dravet Syndrome and Alzheimer's Disease Models.

NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via allosteric modulation are largely unknown. We examine the in vivo effects of GNE-0723, a positive allosteric modulator of GluN2A-subunit-containing NMDARs, on brain network and cognitive functions in mouse models of Dravet syndrome (DS) and Alzheimer's disease (AD).

Vitamin E Acetate as a Plausible Cause of Acute Vaping-related Illness.

The United States Federal Centers for Disease Control and Prevention (CDC) has been working with state investigators on reported cases of lung illnesses linked to e-cigarette or vaping products. Symptoms of difficulty breathing, shortness of breath, chest pains, gastrointestinal sickness leading to serious lung damage and death has been linked to the risk behavior of using vaping products bought on the streets in healthy young people. CDC has detected vitamin E acetate as a chemical of concern among people with the lung injury.

Clinical Outcomes Following the Use of Archived Proviral HIV-1 DNA Genotype to Guide Antiretroviral Therapy Adjustment.

Background: Evidence regarding the safety of using proviral HIV-1 DNA genotype (DNA GT) to guide antiretroviral therapy (ART) is limited. We hypothesized that HIV RNA would not increase following ART adjustment guided by DNA GT in a university HIV clinic.

Methods: Data were obtained from electronic medical records of adult persons living with HIV-1 (PWH) who underwent DNA GT testing and changed ART between October 2014 and November 2017.

Electroacupuncture for tapering off long-term benzodiazepine use: A randomized controlled trial.

Objective: To evaluate the efficacy of using electroacupuncture as an adjunct treatment in enhancing the benzodiazepine cessation rate in long-term benzodiazepine users.

Methods: This was a randomized, assessor- and subject-blinded, controlled trial. One hundred and forty-four long-term benzodiazepine users were randomly assigned to receive either electroacupuncture or placebo acupuncture (a sham itervention using non-invasive placebo needles) combined with a gradual benzodiazepine tapering schedule for 4 weeks.

Electroacupuncture for tapering off long-term benzodiazepine use: study protocol of randomized controlled trial.

Background: Conventional approaches for benzodiazepine tapering have their limitations. Anecdotal studies have shown that acupuncture is a potential treatment for facilitating successful benzodiazepine tapering. As of today, there was no randomized controlled trial examining its efficacy and safety.

Chemically Diverse Group I p21-Activated Kinase (PAK) Inhibitors Impart Acute Cardiovascular Toxicity with a Narrow Therapeutic Window.

p21-activated kinase 1 (PAK1) has an important role in transducing signals in several oncogenic pathways. The concept of inhibiting this kinase has garnered significant interest over the past decade, particularly for targeting cancers associated with PAK1 amplification. Animal studies with the selective group I PAK (pan-PAK1, 2, 3) inhibitor G-5555 from the pyrido[2,3-d]pyrimidin-7-one class uncovered acute toxicity with a narrow therapeutic window.

Adolescent Emotional Pathology and Lifetime History of Alcohol or Drug Use With and Without Comorbid Tobacco Use.

Objective: Use of drugs and alcohol, including tobacco, is linked to adolescent emotional psychopathology. Given that tobacco use is becoming less common over recent years, its co-use with drugs/alcohol may mark a more severe profile of emotional symptomatology. However, it is unclear whether teens with a lifetime history of using drug/alcohol and tobacco exhibit additional elevations in emotional psychopathology and/or multiple forms of emotional psychopathology compared to teens with lifetime drug/alcohol use without comorbid tobacco use.

Inhibition of the kinase ITK in a mouse model of asthma reduces cell death and fails to inhibit the inflammatory response.

Interleukin-2 (IL-2)-inducible T cell kinase (ITK) mediates T cell receptor (TCR) signaling primarily to stimulate the production of cytokines, such as IL-4, IL-5, and IL-13, from T helper 2 (TH2) cells. Compared to wild-type mice, ITK knockout mice are resistant to asthma and exhibit reduced lung inflammation and decreased amounts of TH2-type cytokines in the bronchoalveolar lavage fluid. We found that a small-molecule selective inhibitor of ITK blocked TCR-mediated signaling in cultured TH2 cells, including the tyrosine phosphorylation of phospholipase C-γ1 (PLC-γ1) and the secretion of IL-2 and TH2-type cytokines.