First-in-Human Phase 1 study of a CD16A bispecific innate cell engager, AFM24, targeting EGFR-expressing solid tumors.

Purpose: Innate immune cell-based therapies have shown promising antitumor activity against solid and hematologic malignancies. AFM24, a bispecific innate cell engager, binds CD16A on natural killer (NK) cells/macrophages and EGFR on tumor cells, redirecting antitumor activity towards tumors. The safety and tolerability of AFM24 was evaluated in this Phase 1/2a dose escalation/dose expansion study in patients with recurrent or persistent, advanced solid tumors known to express EGFR.

Biological, linguistic, and individual factors govern voice qualitya).

Voice quality serves as a rich source of information about speakers, providing listeners with impressions of identity, emotional state, age, sex, reproductive fitness, and other biologically and socially salient characteristics. Understanding how this information is transmitted, accessed, and exploited requires knowledge of the psychoacoustic dimensions along which voices vary, an area that remains largely unexplored. Recent studies of English speakers have shown that two factors related to speaker size and arousal consistently emerge as the most important determinants of quality, regardless of who is speaking.

Within-session propulsion asymmetry changes have a limited effect on gait asymmetry post-stroke.

Background: Biomechanical gait impairments, such as reduced paretic propulsion, are common post-stroke. Studies have used biofeedback to increase paretic propulsion and reduce propulsion asymmetry, but it is unclear if these changes impact overall gait asymmetry. There is an implicit assumption that reducing propulsion asymmetry will improve overall gait symmetry, as paretic propulsion has been related to numerous biomechanical impairments.

Motif distribution and DNA methylation underlie distinct Cdx2 binding during development and homeostasis.

Transcription factors guide tissue development by binding to developmental stage-specific targets and establishing an appropriate enhancer landscape. In turn, DNA and chromatin modifications direct the genomic binding of transcription factors. However, how transcription factors navigate chromatin features to selectively bind a small subset of all the possible genomic target loci remains poorly understood.

Longitudinal sex-at-birth and age analyses of cortical structure in the ABCD Study®.

While the brain continues to develop during adolescence, such development may depend on sex-at-birth. However, the elucidation of such differences may be hindered by analytical decisions (e.g.

Outcomes and predictors of unplanned intensive care unit admission for pediatric trauma patients.

Background: Unplanned intensive care unit (ICU) admission (UIA) is associated with increased morbidity in adult trauma patients, however, is not well studied in pediatric trauma patients (PTPs). We sought to identify predictors of UIA, hypothesizing PTPs with UIA have increased odds of mortality.

Methods: The 2017-2019 Trauma Quality Improvement Program (TQIP) database was queried for PTPs ≤16-years-old admitted to non-ICU level of care.

Updating the kidney donor risk index: Removing donor race and hepatitis C virus status.

This study reports the results of a recalculation of the kidney donor risk index (KDRI) formula requested by the Organ Procurement and Transplantation Network's Minority Affairs Committee to remove donor race and hepatitis C virus (HCV) status variables. The updated KDRI model was fit on adult, deceased donor, solitary kidney, first-time transplants from 2018 through 2021. Deceased donors from 2018 through 2021 were included in a counterfactual analysis to evaluate how the kidney donor profile index (KDPI) would change if race and HCV seropositivity were excluded.

Geographical and Socioeconomic Disparities in Substance and Opioid Use Disorders Among Inflammatory Bowel Disease Hospitalizations in the United States From the National Inpatient Sample.

We compared substance use disorder (SUD) prevalence among adult inflammatory bowel disease (IBD) hospitalizations with non-IBD controls from the 2016-2018 National Inpatient Sample, assessing correlations with demographics, socioeconomic status, geographic regions, depression, and anxiety. The primary aim focused on SUD, defined as substance abuse or dependence (: F10-F19) excluding unspecified use or remission, among hospitalizations documenting IBD (Crohn's disease or ulcerative colitis; : K50-51) as one admitting diagnosis (IBD-D). The prevalence of SUD among hospitalizations with and without IBD was compared.

Novel CO loaded nanoparticle ultrasound-activated contrast agent: A potential urinary catheter-free modality to detect vesicoureteral reflux.

Background: The current gold-standard for detecting vesicoureteral reflux (VUR) is the voiding cystourethrogram (VCUG). However, VCUGs require ionizing radiation and bladder catheterization that can be challenging to perform and traumatic for pediatric patients and their parents.

Objective: To investigate the feasibility of a novel urinary catheter-free modality for diagnosing VUR using in vitro and ex vivo models.

Neurobehavioral plasticity in the rodent gustatory system induced by regular consumption of a low-calorie sweetener during adolescence.

Habitual consumption of low-calorie sweeteners (LCS) during juvenile-adolescence can lead to greater sugar intake later in life. Here, we investigated if exposure to the LCS Acesulfame Potassium (Ace-K) during this critical period of development reprograms the taste system in a way that would alter hedonic responding for common dietary compounds. Results revealed that early-life LCS intake not only enhanced the avidity for a caloric sugar (fructose) when rats were in a state of caloric need, it increased acceptance of a bitterant (quinine) in Ace-K-exposed rats tested when middle-aged.

Indirect Ballistic Injury Resulting in Non-ST-Segment Elevation Myocardial Infarction.

Gunshot-related myocardial injuries typically result from direct penetrating injury by the traversing bullet. We present a case of gunshot-related myocardial injury in the absence of direct penetrating injury to the cardiac structures and describe alternative mechanisms for ballistic-induced injury.

Usage patterns of cognitive assessments during Medicare's Annual Wellness Visit: A national survey.

Introduction: Medicare's Annual Wellness Visit (AWV) is a logical opportunity for early detection of cognitive impairment, but recent data for uptake and cognitive assessments during it are lacking.

Methods: We surveyed Medicare beneficiaries of a nationally representative panel about use of AWV and cognitive assessments and analyzed associations between uptake and beneficiaries' characteristics.

Results: Of 1871 participants, 80% had an AWV, among whom 31% underwent formal cognitive testing, 35% were asked about memory problems, including 15% having both.

Emotional Health of Transgender Youth 24 Months After Initiating Gender-Affirming Hormone Therapy.

Purpose: Limited data exist about the emotional health of transgender youth, either before or after initiation of gender-affirming hormone (GAH). The objectives were: (1) Investigate and verify the factor structure of the National Institutes of Health Toolbox Emotional Battery (NIHTB-EB) among trans and non-binary (TNB) youth; (2) Examine changes in emotional health over 24 months of GAH treatment; and (3) Examine the extent to which changes in emotional health were associated with improved appearance congruence (AC).

Methods: Study respondents were from Trans Youth Care - United States (TYCUS) study, an observational, prospective, longitudinal study of adolescents initiating GAH enrolled between 2016 and 2019.

Development of TAR-200: A novel targeted releasing system designed to provide sustained delivery of gemcitabine for patients with bladder cancer.

Treatment options for recurrent high-risk non-muscle-invasive bladder cancer (HR NMIBC) and muscle-invasive bladder cancer (MIBC) are limited, highlighting a need for clinically effective, accessible, and better-tolerated alternatives. In this review we examine the clinical development program of TAR-200, a novel targeted releasing system designed to provide sustained intravesical delivery of gemcitabine to address the needs of patients with NMIBC and of those with MIBC. We describe the concept and design of TAR-200 and the clinical development of this gemcitabine intravesical system in the SunRISe portfolio of studies.

A first-born twin has a higher risk of acute leukemia in a population-based assessment of cancer in twins in California, and a lower than anticipated rate of twin concordance.

Not available.

Genetically Reprogrammed Exosomes for Immunotherapy of Acute Myeloid Leukemia.

Current treatments for acute myeloid leukemia (AML) remain challenging, characterized by poor clinical outcomes. Exosomes, cell-derived membranous vesicles, has been emerging as a new modality of therapy. Here we designed and generated genetically reprogrammed exosomes with surface displayed antibodies and immunoregulatory proteins, namely programmed immune-engaging exosomes (PRIME Exos).

Neurophysiological Markers of Regulation Success in Everyday Life in Depression.

Background: Self-regulation often is disrupted in depression and is characterized by negative affect and inflexible parasympathetic responses. Yet, our understanding of brain mechanisms of self-regulatory processes largely has been limited to laboratory contexts. Measuring individual differences in self-regulatory processes in everyday life - and their neural correlates - could inform our understanding of depression phenotypes and reveal novel intervention targets that impact everyday functioning.

Rethinking the rise of early onset gastrointestinal cancers: a call to action.

Since the early 1990s, there has been a dramatic rise in gastrointestinal cancers diagnosed in patients under age 50 for reasons that remain poorly understood. The most significant change has been the increase in incidence rates of early-onset colorectal cancer, especially rates of left-sided colon and rectal cancers. Increases in gastric, pancreatic, and other gastrointestinal cancer diagnoses have further contributed to this trend.

Outcomes of mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke patients with ASPECTS 4-5 vs. 6-7: a retrospective, multicenter, and multinational study.

Introduction: Mechanical thrombectomy (MT) efficacy in medium vessel occlusion (MeVO) stroke, particularly in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS), remains less explored.

Methods: This retrospective study analyzed data from 443 AIS patients treated with MT for MeVO and low ASPECTS (4-7) at 37 centers across North America, Asia, and Europe, from September 2017 to July 2021. Patients were categorized into ASPECTS of 4-5 and 6-7.

Real-World Incidence of Anaplastic Lymphoma Kinase alterations in Hispanics with Non-Small Cell Lung Cancer at a Large Academic Institution in Los Angeles.

Race and ethnicity affect the distribution of molecular alterations seen in patients with non-small cell lung cancer (NSCLC). While anaplastic lymphoma kinase (ALK) alterations are known to occur in 4-5% of the population, data specific to the Hispanic population remains limited. This study describes the real-world incidence of ALK alterations in Hispanic patients with NSCLC treated at a large academic institution in Los Angeles, California, USA to further elucidate the underlying factors that shape differences in mutational profiles.

Soluble Fms-like tyrosine kinase-1 polymorphisms associated with severe-spectrum hypertensive disorders of pregnancy.

Background: sFLT-1 has been implicated in the pathogenesis of HDP. We aimed to examine the role of maternal and fetal polymorphisms in risk of HDP and severe-spectrum disease.

Methods: Cases of HDP (143) and controls (169) from mother-baby dyads were recruited at the Los Angeles County Women's and Children's Hospital (WCH).