A Phase Ib/II Randomized Study of RO4929097, a Gamma-Secretase or Notch Inhibitor with or without Vismodegib, a Hedgehog Inhibitor, in Advanced Sarcoma.

Purpose: Because the Hedgehog and Notch pathways are often overexpressed in mesenchymal malignancies, we evaluated the efficacy of concurrent inhibition of Notch and Hedgehog signaling using the gamma-secretase inhibitor (GSI) RO4929097 and the smoothened antagonist vismodegib in unresectable or metastatic sarcoma.

Patients And Methods: In this investigator-initiated trial, phase Ib used standard 3+3 dose escalation in which patients first received vismodegib once daily for 21 days, followed by the combination of RO4929097 concurrently with vismodegib in 21-day cycles. In phase II, patients were randomized to RO4929097 alone or in combination with vismodegib.

Parkinson's Disease With Visual Hallucinations Is Associated With Epileptiform Activity on EEG.

Visual hallucinations (VHs) in Parkinson's disease (PD) are the cardinal symptoms which declare the onset of PD psychosis (PDP). The anthropomorphic and zoomorphic VHs of PD resemble those of Charles Bonnet syndrome and temporal lobe epilepsy. In both of these disorders electroencephalography (EEG) abnormalities have been described.

The genetic identity of the earliest human-made hybrid animals, the kungas of Syro-Mesopotamia.

Before the introduction of domestic horses in Mesopotamia in the late third millennium BCE, contemporary cuneiform tablets and seals document intentional breeding of highly valued equids called kungas for use in diplomacy, ceremony, and warfare. Their precise zoological classification, however, has never been conclusively determined. Morphometric analysis of equids uncovered in rich Early Bronze Age burials at Umm el-Marra, Syria, placed them beyond the ranges reported for other known equid species.

Eviction, Healthcare Utilization, and Disenrollment Among New York City Medicaid Patients.

Introduction: Although growing evidence links residential evictions to health, little work has examined connections between eviction and healthcare utilization or access. In this study, eviction records are linked to Medicaid claims to estimate short-term associations between eviction and healthcare utilization, as well as Medicaid disenrollment.

Methods: New York City eviction records from 2017 were linked to New York State Medicaid claims, with 1,300 evicted patients matched to 261,855 non-evicted patients with similar past healthcare utilization, demographics, and neighborhoods.

Uveal Melanoma Exosomes Induce a Prometastatic Microenvironment through Macrophage Migration Inhibitory Factor.

Unlabelled: Uveal melanoma is a rare melanoma subtype different from cutaneous melanoma, with high incidence of liver metastasis and poor prognosis. Cancer cell-derived extracellular vesicles have been shown to induce proinflammatory and prometastatic signaling in the tumor microenvironment and at distant sites. The characterization of uveal melanoma exosome cargo and its role in metastatic spread is essential to identify targets and intervene in the early stages of metastatic development.

Self-reported Race, Serum Creatinine, Cystatin C, and GFR in Children and Young Adults With Pediatric Kidney Diseases: A Report From the Chronic Kidney Disease in Children (CKiD) Study.

Rationale & Objective: Recent reassessment of the use of race in estimated glomerular filtration rate (eGFR) in adults has instigated questions about the role of race in eGFR expressions for children. Little research has examined the associations of self-reported race with measured GFR (mGFR) adjusting for serum creatinine or cystatin C in children and young adults with chronic kidney disease (CKD). This study examined these associations and evaluated the performance of the previously published "U25" (under the age of 25 years) eGFR equations in a large cohort of children and young adults with CKD.

Predicting and Manipulating Cone Responses to Naturalistic Inputs.

Primates explore their visual environment by making frequent saccades, discrete and ballistic eye movements that direct the fovea to specific regions of interest. Saccades produce large and rapid changes in input. The magnitude of these changes and the limited signaling range of visual neurons mean that effective encoding requires rapid adaptation.

Lead service lines and Parkinson's disease prevalence in U.S. States.

Introduction: We recently showed that the prevalence of Parkinson's Disease (PD) in U.S. states is positively associated with the quantity of acid rain.

Alirocumab after acute coronary syndrome in patients with a history of heart failure.

Aims: Patients with heart failure (HF) have not been shown to benefit from statins. In a post hoc analysis, we evaluated outcomes in ODYSSEY OUTCOMES in patients with vs. without a history of HF randomized to the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab or placebo.

Variation in State-Level Eviction Moratorium Protections and Mental Health Among US Adults During the COVID-19 Pandemic.

Importance: Although evictions have been associated with adverse mental health outcomes, it remains unclear which stages of the eviction process are associated with mental distress among renters. Variation in COVID-19 pandemic eviction protections across US states enables identification of intervention targets within the eviction process to improve renters' mental health.

Objective: To measure the association between the strength of eviction protections (ie, stages blocked by eviction moratoriums) and mental distress among renters during the COVID-19 pandemic.

A phase 2 trial of the efficacy and safety of elotuzumab in combination with pomalidomide, carfilzomib and dexamethasone for high-risk relapsed/refractory multiple myeloma.

High-risk multiple myeloma (MM) continues to have a poor prognosis and remains a therapeutic challenge. This phase 2 study evaluated the efficacy and safety of elotuzumab in combination with pomalidomide, carfilzomib, and low-dose dexamethasone for patients with high-risk relapsed/refractory (RR)MM (NCT03104270). Of 13 enrolled patients, 11 were evaluable for efficacy.

Treatment of acute respiratory distress syndrome from COVID-19 with extracorporeal membrane oxygenation in obstetrical patients.

Background: Extracorporeal membrane oxygenation therapy has been used as a rescue therapy for patients with severe acute respiratory distress syndrome from COVID-19 who have failed conventional ventilatory strategies. Little is known about the outcome of pregnant and postpartum patients on extracorporeal membrane oxygenation therapy.

Objective: To describe the medical and surgical outcomes of pregnant and postpartum patients who were placed on extracorporeal membrane oxygenation therapy for severe acute respiratory distress syndrome from COVID-19.

Low variability of plant protein intake in the CKiD cohort does not demonstrate changes in estimated GFR nor electrolyte balance.

Background: Vegetable or plant-based sources of protein may confer health benefits in children with progressive kidney disease. Our aims were to understand the effect of the proportion of vegetable protein intake on changes in estimated GFR and to understand the effect of the proportion of vegetable protein intake on serum levels of bicarbonate, phosphorus, and potassium.

Methods: Children with baseline eGFR between 30 and 90 mL/min/1.

Childhood eviction and cognitive development: Developmental timing-specific associations in an urban birth cohort.

Eviction upends children's lives and exacerbates deprivation; it remains largely unexamined as a determinant of cognitive development. We assess whether children evicted in infancy, early childhood, and middle childhood exhibit lower scores on four cognitive assessments (measuring executive function, mathematical reasoning, written language skills, and vocabulary skills) at age 9. Using linear regression and selection weights, we analyze longitudinal data from the Fragile Families and Child Wellbeing Study, a national, urban birth cohort (N = 1724 for eviction during infancy, 2126 for early childhood, 1979 for middle childhood).

A Phase Ib Study of Sotrastaurin, a PKC Inhibitor, and Alpelisib, a PI3Kα Inhibitor, in Patients with Metastatic Uveal Melanoma.

Uveal melanoma (UM) is a rare subset of melanoma characterized by the presence of early initiating GNAQ/11 mutations, with downstream activation of the PKC, MAPK, and PI3Kα pathways. Activity has been observed with the PKC inhibitors sotrastaurin (AEB071) and darovasertib (IDE196) in patients with UM. Inhibition of the PI3K pathway enhances PKC inhibition in in vivo models.

Retinal patterns and the cellular repertoire of neuropsin (Opn5) retinal ganglion cells.

Obtaining a parts list of the sensory components of the retina is vital to understand the effects of light in behavior, health, and disease. Rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) are the best described photoreceptors in the mammalian retina, but recent functional roles have been proposed for retinal neuropsin (Opn5)-an atypical opsin. However, little is known about the pattern of Opn5 expression in the retina.

Power washing pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis is an uncommon cause of insidious onset shortness of breath and hypoxemia. It is caused by an accumulation of surfactant within the alveoli. Left untreated, it can be fatal.

Incorporating concentration-dependent sediment microbial activity into methylmercury production kinetics modeling.

In anoxic environments, anaerobic microorganisms carrying the gene cluster can mediate the transformation of inorganic mercury (Hg(II)) to monomethylmercury (MMHg). The kinetics of Hg(II) transformation to MMHg in periphyton from East Fork Poplar Creek (EFPC) in Oak Ridge, TN have previously been modeled using a transient availability model (TAM). The TAM for Hg(II) methylation combines methylation/demethylation kinetics with kinetic expressions for processes that decrease Hg(II) and MMHg availability for methylation and demethylation (multisite sorption of Hg(II) and MMHg, Hg(II) reduction/Hg(0) oxidation).

Female Sex and Obesity Are Risk Factors for Inadequate Calcium Intake in Youth With Type 1 Diabetes.

People with type 1 diabetes (T1D) are at increased risk of developing low bone mineral density and fractures. Optimization of calcium intake is a key component of pediatric bone health care. Despite the known risk factors for impaired bone health in T1D and the known benefits of calcium on bone accrual, there are limited data describing calcium intake in youth with T1D.

A biomechanical perspective on molar emergence and primate life history.

The strong relationship between M1 emergence age and life history across primates provides a means of reconstructing fossil life history. The underlying process that leads to varying molar emergence schedules, however, remains elusive. Using three-dimensional data to quantify masticatory form in ontogenetic samples representing 21 primate species, we test the hypothesis that the location and timing of molar emergence are constrained to avoid potentially dangerous distractive forces at the temporomandibular joint (TMJ) throughout growth.

A multisociety organizational consensus process to define guiding principles for acute perioperative pain management.

The US Health and Human Services Pain Management Best Practices Inter-Agency Task Force initiated a public-private partnership which led to the publication of its report in 2019. The report emphasized the need for individualized, multimodal, and multidisciplinary approaches to pain management that decrease the over-reliance on opioids, increase access to care, and promote widespread education on pain and substance use disorders. The Task Force specifically called on specialty organizations to work together to develop evidence-based guidelines.