Patent landscape of small molecule inhibitors of METTL3 (2020-present).

Introduction: Methyltransferase-like protein 3 (METTL3), in complex with METTL14, is the key 'writer' protein for RNA mA methylation, accounting for almost all mRNA mA modifications. Recent studies reveal that METTL3 is implicated in the development and progression of various types of cancers. Targeting METTL3 with small molecule inhibitors represents a promising therapeutic strategy for cancer.

Androgen receptor inhibition increases MHC Class I expression and improves immune response in prostate cancer.

Tumors escape immune detection and elimination through a variety of mechanisms. Here, we used prostate cancer as a model to examine how androgen-dependent tumors undergo immune evasion through downregulation of the major histocompatibility complex class I (MHCI). We report that response to immunotherapy in late-stage prostate cancer is associated with elevated MHC expression.

Management of pediatric lower extremity vascular trauma: adult vs pediatric level I trauma centers.

Background: Pediatric lower extremity vascular injury (PLEVI) is uncommon and the availability of granular data is sparse. This study evaluated the surgical management of PLEVIs between a Level I adult (ATC) vs pediatric (PTC) trauma center.

Methods: We performed a retrospective review of PLEVIs (< 18 years) managed surgically between 01/2009-12/2022.

Powering up targeted protein degradation through active and passive tumour-targeting strategies: Current and future scopes.

Targeted protein degradation (TPD) has emerged as a prominent and vital strategy for therapeutic intervention of cancers and other diseases. One such approach involves the exploration of proteolysis targeting chimeras (PROTACs) for the selective elimination of disease-causing proteins through the innate ubiquitin-proteasome pathway. Due to the unprecedented achievements of various PROTAC molecules in clinical trials, researchers have moved towards other physiological protein degradation approaches for the targeted degradation of abnormal proteins, including lysosome-targeting chimeras (LYTACs), autophagy-targeting chimeras (AUTACs), autophagosome-tethering compounds (ATTECs), molecular glue degraders, and other derivatives for their precise mode of action.

Management of complex pediatric and adolescent liver trauma: adult vs pediatric level 1 trauma centers.

Purpose: Management of high-grade pediatric and adolescent liver trauma can be complex. Studies suggest that variation exists at adult (ATC) vs pediatric trauma centers (PTC); however, there is limited granular comparative data. We sought to describe and compare the management and outcomes of complex pediatric and adolescent liver trauma between a level 1 ATC and two PTCs in a large metropolitan city.

Longitudinal Associations Between Pain, Risk for Posttraumatic Stress Disorder, Posttraumatic Stress Symptoms, and Pain Characteristics in Children After Unintentional Injury.

Objectives: Approximately 20% of children demonstrate persistent posttraumatic stress symptoms (PTSS) after unintentional injury, with more severe pain intensity predicting concurrent and later PTSS. Examining additional pain characteristics like pain behaviors, impairment related to pain, and subjective experiences of pain might provide additional insight into the mechanisms that reinforce relationships between risk for posttraumatic stress disorder (PTSD), PTSS, and pain.

Methods: During hospitalization for unintentional injury, the Screening Tool for Predictors of PTSD (STEPP) was administered and the highest pain score was collected.

Management of Pediatric Lower Extremity Vascular Trauma: Adult vs Pediatric Level I Trauma Centers [RETRACTED].

Background: Pediatric lower extremity vascular injury (PLEVI) is uncommon. Though epidemiologic studies exist, the availability of granular data is sparse. Additionally, few studies compare the management between adult (ATC) and pediatric (PTC) trauma centers.

Standardization of Antibiotic Management and Reduction of Opioid Prescribing in Pediatric Complicated Appendicitis: A Quality Improvement Initiative.

Background: Appendicitis is one of the most common pediatric surgical procedures in the United States. However, wide variation remains in antibiotic prescribing and pain management across and within institutions. We aimed to minimize variation in antibiotic usage and decrease opioid prescribing at discharge for children with complicated appendicitis by implementation of a quality improvement (QI) initiative.

α-Synuclein is the major platelet isoform but is dispensable for activation, secretion, and thrombosis.

Platelets play many roles in the vasculature ensuring proper hemostasis and maintaining integrity. These roles are facilitated, in part, by cargo molecules released from platelet granules via oluble SF ttachment rotein eceptor (SNARE) mediated membrane fusion, which is controlled by several protein-protein interactions. Chaperones have been characterized for t-SNAREs (.

Utilization of Angiography in Pediatric Blunt Abdominal Injury at Adult versus Pediatric Trauma Centers.

Introduction: Angiography has been widely accepted as an adjunct in the management of blunt abdominal trauma in adults. However, the role of angiography with or without angioembolization (AE) is still being defined in pediatric solid organ injury. We sought to compare the use of angiography in solid organ injury (SOI) at pediatric trauma centers (PTCs) versus an adult trauma center (ATC) in a large metropolitan city.

Pain interference, pain type, and quality of life among adults with spina bifida.

Introduction: Individuals with spina bifida (SB) experience nociceptive and neuropathic pain, and women with SB report more pain. However, the relationship between pain type and gender on pain interference and quality of life (QoL) among individuals with SB is less understood.

Objective: To assess relationships among pain interference, pain quality, participation-related QoL, and gender among adults with SB.

Protective antibody threshold of RTS,S/AS01 malaria vaccine correlates antigen and adjuvant dose in mouse model.

Mouse models are useful for the early down-selection of malaria vaccine candidates. The Walter Reed Army Institute of Research has optimized a transgenic Plasmodium berghei sporozoite challenge model to compare the efficacy of Plasmodium falciparum circumsporozoite protein (CSP) vaccines. GSK's RTS,S vaccine formulated in the adjuvant AS01 can protect malaria-naïve individuals against malaria.

The complementary roles of VAMP-2, -3, and -7 in platelet secretion and function.

Platelet secretion requires Soluble N-ethylmaleimide Sensitive Attachment Protein Receptors (SNAREs). Vesicle SNAREs/Vesicle-Associated Membrane Proteins (v-SNAREs/VAMPs) on granules and t-SNAREs in plasma membranes mediate granule release. Platelet VAMP heterogeneity has complicated the assessment of how/if each is used and affects hemostasis.

Increases in adolescent firearm injuries were associated with school closures during COVID-19.

Background: Mitigation measures, including school closures, were enacted to protect the public during the COVID-19 pandemic. However, the negative effects of mitigation measures are not fully known. Adolescents are uniquely vulnerable to policy changes since many depend on schools for physical, mental, and/or nutritional support.

Ferric Chloride-Induced Arterial Thrombosis and Sample Collection for 3D Electron Microscopy Analysis.

Cardiovascular diseases are a leading cause of mortality and morbidity worldwide. Aberrant thrombosis is a common feature of systemic conditions like diabetes and obesity, and chronic inflammatory diseases like atherosclerosis, cancer, and autoimmune diseases. Upon vascular injury, usually the coagulation system, platelets, and endothelium act in an orchestrated manner to prevent bleeding by forming a clot at the site of the injury.

Trends in Adolescent Firearm-Related Injury: A Time Series Analysis.

Background: Firearm-related injury (FRI) became the leading cause of death among children/adolescents in 2019.

Purpose: This study sought to determine changes over time in the population of adolescents affected by FRI in Atlanta, Georgia, such that high risk cohorts could be identified.

Research Design: City-wide retrospective cohort review.

Function and evolution of the aquaporin IsAQP1 in the Lyme disease vector Ixodes scapularis.

Ticks are important vectors of pathogenic viruses, bacteria, and protozoans to humans, wildlife, and domestic animals. Due to their life cycles, ticks face significant challenges related to water homeostasis. When blood-feeding, they must excrete water and ions, but when off-host (for stretches lasting several months), they must conserve water to avoid desiccation.

Dome1-JAK-STAT signaling between parasite and host integrates vector immunity and development.

Ancestral signaling pathways serve critical roles in metazoan development, physiology, and immunity. We report an evolutionary interspecies communication pathway involving a central tick receptor termed Dome1, which acquired a mammalian cytokine receptor motif exhibiting high affinity for interferon-gamma (IFN-γ). Host-derived IFN-γ facilitates Dome1-mediated activation of the JAK-STAT pathway.

miR-542-5p targets c-myc and negates the cell proliferation effect of SphK1 in intestinal epithelial cells.

Intestinal epithelial barrier defects occur commonly during a variety of pathological conditions, though their underlying mechanisms are not completely understood. Sphingosine-1-phosphate (S1P) has been shown to be a critical regulator of proliferation and of maintenance of an intact intestinal epithelial barrier, as is also sphingosine kinase 1 (SphK1), the rate-limiting enzyme for S1P synthesis. SphK1 has been shown to modulate its effect on intestinal epithelial proliferation through increased levels of c-myc.

Angina pain associated with isolated R-IIP modified Lipton classification coronary artery anomaly.

We report a case of a patient that presented with typical angina pain and associated risk factors for coronary artery disease (CAD). Subsequent cardiac catheterisation led to the discovery of an isolated R-IIP modified Lipton classification coronary artery anomaly with follow-up coronary computed tomography angiography (CCTA) confirmation. This case report includes images of the CCTA and left heart catheterisation results, along with a discussion of the potential for increased risk of atherosclerosis in our patient, and a proposed explanation of his presentation with prototypical angina pain, despite lack of apparent atherosclerosis.

PTSD Risk Factors and Acute Pain Intensity Predict Length of Hospital Stay in Youth after Unintentional Injury.

: Many hospitals have adopted screening tools to assess risk for posttraumatic stress disorder (PTSD) after pediatric unintentional injury in accordance with American College of Surgeons recommendations. The Screening Tool for Early Predictors of PTSD (STEPP) is a measure initially developed to identify youth and parents at high risk for meeting diagnostic criteria for PTSD after injury. Acute pain during hospitalization has also been examined as a potential predictor of maladaptive outcomes after injury, including PTSD.

Nutrition and behavior change: a review of recent literature.

Purpose Of Review: The current article will highlight recent trends and novel approaches to behavior change strategies in nutrition. Physicians, nurses, and other healthcare professionals play key roles in counseling patients on lifestyle change, which is critical for patients with chronic conditions. Nutrition science continues to advance, and new approaches to behavior change are needed for successful implementation at the individual and population level.