Phase separation of polyubiquitinated proteins in UBQLN2 condensates controls substrate fate.

Ubiquitination is one of the most common posttranslational modifications in eukaryotic cells. Depending on the architecture of polyubiquitin chains, substrate proteins can meet different cellular fates, but our understanding of how chain linkage controls protein fate remains limited. UBL-UBA shuttle proteins, such as UBQLN2, bind to ubiquitinated proteins and to the proteasome or other protein quality control machinery elements and play a role in substrate fate determination.

Phase separation of polyubiquitinated proteins in UBQLN2 condensates controls substrate fate.

Ubiquitination is one of the most common post-translational modifications in eukaryotic cells. Depending on the architecture of polyubiquitin chains, substrate proteins can meet different cellular fates, but our understanding of how chain linkage controls protein fate remains limited. UBL-UBA shuttle proteins, such as UBQLN2, bind to ubiquitinated proteins and to the proteasome or other protein quality control machinery elements and play a role in substrate fate determination.

Multicenter phase 2 study of oral azacitidine (CC-486) plus CHOP as initial treatment for PTCL.

Peripheral T-cell lymphomas (PTCL) with T-follicular helper phenotype (PTCL-TFH) has recurrent mutations affecting epigenetic regulators, which may contribute to aberrant DNA methylation and chemoresistance. This phase 2 study evaluated oral azacitidine (CC-486) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as initial treatment for PTCL. CC-486 at 300 mg daily was administered for 7 days before C1 of CHOP, and for 14 days before CHOP C2-6.

Laboratory test trends within 72 hours of hospital admission associated with death among COVID-19 patients.

Early identification of patients at risk for severe coronavirus disease 2019 (COVID-19) is crucial for appropriate triage and determination of need for closer monitoring. Few studies have examined laboratory trends in COVID-19 infection and sought to quantify the degree to which laboratory values affect mortality. We conducted a retrospective cohort (n = 407) study of hospitalized patients with COVID-19 early in the course of the pandemic, from March 16th to April 8th, 2020 and compared baseline to repeat laboratory testing 72 hours into admission.

Factors associated with inpatient complications among patients with obesity and COVID-19 at an urban safety-net hospital: A retrospective cohort study.

Objective: Obesity increases morbidity and mortality from Coronavirus disease 2019 (COVID-19). This study characterized inpatient complications among patients with obesity and COVID-19-including myocardial infarction, renal failure requiring dialysis, stroke, secondary bacterial infection, and venous thromboembolism-and identified factors associated with developing at least one inpatient complication at a safety-net hospital with a diverse cohort.

Methods: A retrospective review was performed of all patients admitted for ≥3 days with COVID-19 between 16 March 2020, and 8 April 2020.

Inhibition of Integrin αVβ3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma.

Unlabelled: Bexarotene is a specific retinoid X receptor agonist that has been used for the treatment of cutaneous T-cell lymphoma (CTCL). Because bexarotene causes hypothyroidism, it requires the administration of levothyroxine. However, levothyroxine, in addition to its ubiquitous nuclear receptors, can activate the αVβ3 integrin that is overexpressed in CTCL, potentially interfering the antineoplastic effect of bexarotene.

Psychopathic Personality in Early Childhood: A Critical Comment on Lopez-Romero et al. (2021).

A recent article published in the (López-Romero et al., 2021) described the identification of "putative psychopathic personality" in a school cohort of 3-6-year-old children from Spain. This comment offers cautionary considerations of the original article on scientific grounds and critical comments on policy grounds.

Phase 1 study of oral azacitidine (CC-486) plus R-CHOP in previously untreated intermediate- to high-risk DLBCL.

Resistance to standard immunochemotherapy remains an unmet challenge in diffuse large B-cell lymphoma (DLBCL), and aberrant DNA methylation may contribute to chemoresistance. Promising early-phase results were reported with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) plus subcutaneous azacitidine, a hypomethylating agent. In this phase 1 study, we evaluated CC-486 (oral azacitidine) plus 6 cycles of R-CHOP in patients with previously untreated intermediate- to high-risk DLBCL or grade 3B/transformed follicular lymphoma.

Special Section Introduction: Revitalizing Developmental Research on Adolescent Gun Involvement.

Although firearm violence is universally recognized as a paramount public health problem in the United States, for nearly two decades a Congressional budget amendment prevented federal agencies from funding research aimed at understanding the antecedents and consequences of gun violence. These restrictions have been lifted in recent years; however, the field is struggling to overcome a considerable lapse in developmentally-informed longitudinal research on adolescent gun involvement. Some key areas in need of further investigation include: (a) examining developmental and gender differences in risk factors for adolescent gun carrying, (b) clarifying the mechanisms through which socio-economic disadvantage confers risk for engaging in adolescent gun violence, (c) identifying proximal risk and protective factors that are associated with engagement in adolescent gun violence among high risk youth, and (d) delineating the unique effect the exposure to gun violence has on adolescents' emotional and behavioral problems.

Drug Dealing and Gun Carrying go Hand in Hand: Examining How Juvenile Offenders' Gun Carrying Changes Before and After Drug Dealing Spells across 84 Months.

Objectives: This study aims to examine whether periods of marijuana and other illicit drug dealing ("spells" of dealing) are associated with changes in young male offenders' gun carrying behavior.

Methods: This paper uses 84 months of data from a sample of 479 serious juvenile male offenders who were assessed every six months for three years and then annually for four years. At each assessment, participants reported on engagement in illicit behaviors, including drug dealing and gun carrying, in each month since the prior interview.

Risk and Protective Factors for Gun Violence in Male Juvenile Offenders.

Objective: To examine several risk and protective factors as predictors of future gun violence among male juvenile offenders.

Method: Data came from a longitudinal cohort of 1,170 male juvenile offenders (42.1% Black; 34.

Biomarker-driven management strategies for peripheral T cell lymphoma.

Peripheral T cell lymphomas are heterogeneous diseases which remain treatment challenges. Recent advances in molecular and genomic profiling have provided unprecedented insight into disease pathogenesis driven by distinct cells of origins and molecular pathways. The discovery and clinical application of molecular biomarkers in PTCL subtypes has the potential to transform personalized care for patients with PTCL in diagnosis, prognosis, and therapy.

Perceived Gun Access and Gun Carrying Among Male Adolescent Offenders.

Gun violence takes a significant toll on adolescents in the United States, and there is a lack of longitudinal research on perceptual factors that drive gun carrying. Notably, there is no information on the relationship between perception of gun accessibility and gun carrying. Using data collected between 2000 and 2006 in the Pathways to Desistance Study, we examine the effects of perceived access to guns in a sample of adolescent offenders.

The Classification of Violence Risk.

(Reprinted with permission from 24: 721-730, 2006).

The Direct and Indirect Associations between Childhood Socioeconomic Disadvantage and Adolescent Gun Violence.

We examined whether childhood socioeconomic disadvantage was associated with adolescent gun violence and whether early symptoms of conduct disorder and/or exposure to delinquent peers accounted for the linkage. Participants were 503 predominately Black and White boys who were recruited in 1st grade from Pittsburgh public schools. Multi-informant assessments were conducted regularly from approximately ages 7 to 20.

Proximal predictors of gun violence among adolescent males involved in crime.

The growing public health and legal concerns regarding gun violence has led to a call for research that investigates risk factors for gun violence across a variety of domains. Individual and sociocontextual risk factors have been associated with violence more broadly, and in some instances gun-carrying, however no prior research has investigated the role of these factors in explaining gun violence using longitudinal data. The current study utilized a subsample (N = 161) from the Pathways to Desistance Study, which is a longitudinal sample of serious adolescent offenders to evaluate interindividual and intraindividual differences in relevant risk factors of gun violence.

A Comparison of the Youth Psychopathic Traits Inventory (YPI)-Triarchic Scales and the YPI in a Sample of Justice-Involved Youth.

The Triarchic model (Patrick, Fowles, & Krueger, 2009) posits that psychopathy consists of three elements: Boldness, Meanness, and Disinhibition. Drislane et al. (2015) recently derived scales from the Youth Psychopathic Traits Inventory (YPI; Andershed, Kerr, Stattin, & Levander, 2002) to assess these traits.

Recidivism in a Sample of Serious Adolescent Offenders.

Objectives: A broad research literature in criminology documents key aspects of how criminal offending develops and changes over the life span. We contribute to this literature by showcasing methods that are useful for studying medium-term patterns of subsequent criminal justice system involvement among a sample of serious adolescent offenders making the transition to early adulthood.

Methods: Our approach relies on 7 years of post-enrollment follow-up from the Pathways to Desistance Study.

Gun- and Non-Gun-Related Violence Exposure and Risk for Subsequent Gun Carrying Among Male Juvenile Offenders.

Objective: Although studies have found that youth exposed to violence are more likely to carry guns than non-exposed youth, this association could be due to common causal factors or other pre-existing differences between individuals. In this study, within-individual change models were used to determine whether juvenile offenders exhibit an increased propensity to carry a firearm after being exposed to gun violence and/or non-gun violence. The advantage of this approach is all time-invariant factors are eliminated as potential confounders.

The Observed Longitudinal Relationship between Future Orientation and Substance Use Among a Cohort of Youth with Serious Criminal Offenses.

Background: Future orientation (FO), an essential construct in youth development, encompassing goals, expectations for life, and ability to plan for the future. This study uses a multidimensional measure of future orientation to assess the relationship between change in future orientation and change in substance use over time.

Methods: Data were from the Pathways to Desistence study.

Victim Offender Overlap: Dual Trajectory Examination of Victimization and Offending among Young Felony Offenders over Seven Years.

The relationship between victimization and offending has been shown consistently across different samples, settings, and crime types. This study uses data from the Pathways to Desistance Study to examine dual trajectories of offending between the ages of 15 and 24 in a sample of male felony offenders. The dual trajectory models demonstrate substantial convergence in victimization and offending.

Childhood risk factors associated with adolescent gun carrying among Black and White males: An examination of self-protection, social influence, and antisocial propensity explanations.

Adolescent gun violence is a serious public health issue that disproportionately affects young Black males. Although it has been postulated that differential exposure to childhood risk factors might account for racial differences in adolescent gun carrying, no longitudinal studies have directly examined this issue. We examined whether childhood risk factors indexing neighborhood crime, peer delinquency, and conduct problems predicted the initiation of adolescent gun carrying among a community sample of Black and White boys.

The Link Between Mental Illness and Firearm Violence: Implications for Social Policy and Clinical Practice.

The United States has substantially higher levels of firearm violence than most other developed countries. Firearm violence is a significant and preventable public health crisis. Mental illness is a weak risk factor for violence despite popular misconceptions reflected in the media and policy.