Combinatorial therapies for epigenetic, immunotherapeutic, and genetic targeting of chordoma.

Purpose: Chordoma, a rare malignancy of the axial skeleton and skull base, presents significant therapeutic challenges due to the high rates of tumor recurrence and resistance. While surgical resection and radiation therapy remain the gold standard of treatment, the lack of additional treatment options necessitates the exploration of novel therapies. Combinatorial therapies hold significant potential in shaping patient prognosis.

Policy and perceptions of pregnancy during training among residents of various subspecialties.

Purpose Of The Study: Increased risk for adverse birth outcomes, long work hours, limited control over one's own schedule, and concern for making up time may color resident perceptions of their pregnancy during residency. We aimed to survey residents across four different specialties about their personal experiences with pregnancy during training.

Study Design: Using a novel, validated, anonymous web-based survey instrument, we assessed experiences around pregnancy during residency training nation-wide.

Combination of polymeric micelle formulation of TGFβ receptor inhibitors and paclitaxel produces consistent response across different mouse models of Triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is notoriously difficult to treat due to the lack of targetable receptors and sometimes poor response to chemotherapy. The transforming growth factor beta (TGFβ) family of proteins and their receptors (TGFRs) are highly expressed in TNBC and implicated in chemotherapy-induced cancer stemness. Here, we evaluated combination treatments using experimental TGFR inhibitors (TGFβi), SB525334 (SB), and LY2109761 (LY) with paclitaxel (PTX) chemotherapy.

Excision of a supergiant spinal schwannoma: illustrative case.

Background: The authors report on a patient who presented with an extremely large presacral schwannoma and subsequent mass effect-induced hydronephrosis and kidney failure. To the authors' knowledge, this case represents the largest radiographically verified spinal schwannoma in the medical literature. The tumor presented here was more than three times as large as a typical giant schwannoma.

Machine Learning for the Prediction of Surgical Morbidity in Placenta Accreta Spectrum.

Objective:  We sought to create a machine learning (ML) model to identify variables that would aid in the prediction of surgical morbidity in cases of placenta accreta spectrum (PAS).

Study Design:  A multicenter analysis including all cases of PAS identified by pathology specimen confirmation, across five tertiary care perinatal centers in New York City from 2013 to 2022. We developed models to predict operative morbidity using 213 variables including demographics, obstetrical information, and limited prenatal imaging findings detailing placental location.

Hospital Admission Rates and Mortality Among Emergency Department Patients with COVID-19 Discharged with Remote Patient Monitoring with or without HOME - A Value-Based Approach.

Background: The pandemic caused by the novel Coronavirus 2019 (COVID-19) overwhelmed healthcare systems with emergency department (ED) and hospital overcrowding. Our hospital system was able to discharge a subset of COVID-19 patients home with remote patient monitoring (RPM) and home oxygen (HOME) if needed, which opened up beds for the more critical patients. The objective of this study was to review the all-cause 30-day mortality and admission rates for patients chosen for our program, and to additionally examine the financial impact.

Quantitative assessment of morphological changes in lipid droplets and lipid-mito interactions with aging in brown adipose.

The physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LDs) within the brown adipocytes and a high abundance of iron-containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle-to-organelle contacts. For example, the contact sites that mediate mitochondria-LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids.

Myelin basic protein mRNA levels affect myelin sheath dimensions, architecture, plasticity, and density of resident glial cells.

Myelin Basic Protein (MBP) is essential for both elaboration and maintenance of CNS myelin, and its reduced accumulation results in hypomyelination. How different Mbp mRNA levels affect myelin dimensions across the lifespan and how resident glial cells may respond to such changes are unknown. Here, to investigate these questions, we used enhancer-edited mouse lines that accumulate Mbp mRNA levels ranging from 8% to 160% of wild type.

Synergistic Targeting of Innate Receptors TLR7 and NOD2 for Therapeutic Intervention in Multiple Sclerosis.

Regulation of neuroinflammation is critical for maintaining central nervous system (CNS) homeostasis and holds therapeutic promise in autoimmune diseases such as multiple sclerosis (MS). Previous studies have highlighted the significance of selective innate signaling in triggering anti-inflammatory mechanisms, which play a protective role in an MS-like disease, experimental autoimmune encephalomyelitis (EAE). However, the individual intra-CNS administration of specific innate receptor ligands or agonists, such as for toll-like receptor 7 (TLR7) and nucleotide-binding oligomerization-domain-containing protein 2 (NOD2), failed to elicit the desired anti-inflammatory response in EAE.

Selective Btk inhibition by PRN1008/PRN473 blocks human CLEC-2, and PRN473 reduces venous thrombosis formation in mice.

Platelet C-type lectin-like receptor 2 (CLEC-2) is a hem-immunoreceptor tyrosine-based activation motif-containing receptor that has a critical role in venous thrombosis but minimal involvement in hemostasis. CLEC-2 can be blocked by Btk inhibitors. Treatment with ibrutinib is associated with increased bleeding due to off-target inhibition of Src family kinases (SFKs).

Patient actor training improves preexposure prophylaxis delivery for adolescent girls and young women in Kenya: a cluster randomized trial.

Objective: To evaluate effectiveness of a standardized patient actor (SP) training intervention to improve quality of preexposure prophylaxis (PrEP) services for adolescent girls and young women (AGYW) in Kenya.

Design: Cluster randomized trial and mystery shopper evaluation.

Methods: Twelve of 24 maternal child health and family planning facilities were randomized to SP training.

Quantitative Assessment of Morphological Changes in Lipid Droplets and Lipid-Mito Interactions with Aging in Brown Adipose.

The physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LD) within the brown adipocytes and a high abundance of iron-containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle-to-organelle contacts. Particularly, the contact sites that mediate mitochondria-LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids.

Chronic thromboembolic pulmonary hypertension and balloon pulmonary angioplasty - Where are we in 2024?

Pulmonary endarterectomy (PEA) is the first-line treatment for patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, some patients with CTEPH are considered inoperable, and in the last decade, balloon pulmonary angioplasty (BPA) has emerged as a viable therapeutic option for these patients with prohibitive surgical risk or recurrent pulmonary hypertension following PEA. Numerous international centers have increased their procedural volume of BPA and have reported improvements in pulmonary hemodynamics, patient functional class and right ventricular function.

Piloting an Evidence-Based Assessment Protocol for Incarcerated Adolescents.

Although evidence-based assessment is considered an essential component of evidence-based practice, few adolescents have access to evidence-based assessment. Despite experiencing high rates of mental health disorders, incarcerated justice-involved adolescents are rarely able to access evidence-based psychiatric care. In this article, we discuss the components of an evidence-based assessment protocol designed and piloted with incarcerated adolescents involved in Rhode Island's juvenile justice system.

Higher rates of mental health screening of adolescents recorded after provider training using simulated patients in a Kenyan HIV clinic: results of a pilot study.

Background: Kenyan adolescent girls and young women (AGYW) experience a dual burden of HIV and common mental disorders (CMD). HIV clinics are a key entry point for AGYW in need of integrated CMD and HIV care; however, rates of screening and referral for CMDs are low. Our objective was to test an evidence-based provider training strategy, simulated patient encounters (SPEs), on CMD service delivery for AGYW in a Kenyan HIV clinic.

Epigenetic dynamics during capacitation of naïve human pluripotent stem cells.

Human pluripotent stem cells (hPSCs) are of fundamental relevance in regenerative medicine. Naïve hPSCs hold promise to overcome some of the limitations of conventional (primed) hPSCs, including recurrent epigenetic anomalies. Naïve-to-primed transition (capacitation) follows transcriptional dynamics of human embryonic epiblast and is necessary for somatic differentiation from naïve hPSCs.

CT and X-ray contrast agents: Current clinical challenges and the future of contrast.

Computed tomography (CT) is a powerful and widely used imaging technique in modern medicine. However, it often requires the use of contrast agents to visualize structures with similar radiographic density. Unfortunately, current clinical contrast agents (CAs) for CT have remained largely unchanged for decades and come with several significant drawbacks, including serious nephrotoxicity and short circulation half-lives.