The Platform Identifies Drug-Like Probes that Regulate Endogenous Protein Levels within Physiological Contexts.

Traditional phenotypic drug discovery platforms have suffered from poor scalability and a lack of mechanistic understanding of newly discovered phenotypic probes. To address this, we created Endo- (EGS), a high-throughput enabled screening platform that identifies bioactive small molecules capable of regulating endogenous protein expression encoded by any preselected target gene within a biologically appropriate context. As a proof-of-concept, successfully identified drug candidates that up-regulate endogenous expression of neuronal a gene that causes a neurodevelopmental disorder when haploinsufficient.

Theory protection: Do humans protect existing associative links?

Theories of associative learning often propose that learning is proportional to prediction error, or the difference between expected events and those that occur. Spicer et al. (2020) suggested an alternative, that humans might instead selectively attribute surprising outcomes to cues that they are not confident about, to maintain cue-outcome associations about which they are more confident.

Mycobacterium porcinum Skin and Soft Tissue Infections After Vaccinations - Indiana, Kentucky, and Ohio, September 2018-February 2019.

During December 2018-February 2019, a multistate investigation identified 101 patients with vaccination-associated adverse events among an estimated 940 persons in Kentucky, Indiana, and Ohio who had received influenza; hepatitis A; pneumococcal; or tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines at the workplace during September 11-November 28, 2018. These vaccines had been administered by staff members of a third-party health care company contracted by 24 businesses. Company A provided multiple vaccine types during workplace vaccination events across 54 locations in these adjoining states.

Similarities and differences: Comment on Chan et al. (2021).

Spicer et al. (2020) reported a series of causal learning experiments in which participants appeared to learn most readily about cues when they were not certain of their causal status and proposed that their results were a consequence of participants' use of theory protection. In the present issue, Chan et al.

Implementing stakeholder engagement to explore alternative models of consent: An example from the PREP-IT trials.

Introduction: Cluster randomized crossover trials are often faced with a dilemma when selecting an optimal model of consent, as the traditional model of obtaining informed consent from participant's before initiating any trial related activities may not be suitable. We describe our experience of engaging patient advisors to identify an optimal model of consent for the PREP-IT trials. This paper also examines surrogate measures of success for the selected model of consent.

An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.

Backgrounds & Aims: Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology.

Predictors of survival following surgical resection of limited-stage small cell lung cancer.

Background: Adjuvant chemotherapy, postoperative radiation (PORT), and prophylactic cranial irradiation (PCI) have been individually examined in limited-stage small cell lung cancer (SCLC). There is a paucity of data on the effectiveness of each adjuvant treatment modality when used in combination after surgical resection of SCLC.

Methods: Data were collected from 5 cancer centers on all patients with limited-stage SCLC who underwent surgical resection between 1986 and 2019.

Theory protection in associative learning: Humans maintain certain beliefs in a manner that violates prediction error.

Three experiments were conducted to investigate a possible role for certainty in human causal learning. In these experiments, human participants were initially trained with a set of cues, each of which was followed by the presence or absence of an outcome. In a subsequent training stage, 2 of these cues were trained in a causal compound, and the change in associative strength for each of the cues was compared, using a procedure based on Rescorla (2001).

Multimodality Therapy for N2 Non-Small Cell Lung Cancer: An Evolving Paradigm.

Background: Induction chemoradiation for resectable N2 non-small cell lung cancer (NSCLC) is used with the intent to optimize locoregional control, whereas induction chemotherapy given in systemic doses is meant to optimally target potential distant disease. However, the optimal preoperative treatment regimen is still unknown and practice patterns continue to vary widely. We compared multiinstitutional oncologic outcomes for N2 NSCLC from 4 experienced lung cancer treatment centers.

Clinicoradiographic Predictors of Aggressive Biology in Lung Cancer With Ground Glass Components.

Background: Ground glass opacities pose diagnostic challenges, and even after malignancy is confirmed, prognosis is often unclear. We sought to identify clinicoradiographic features that could predict aggressive tumor biology in lung adenocarcinoma with associated ground glass components.

Methods: A retrospective review of patients with resected lung adenocarcinoma from 2008 to 2013 was performed.

Toddler socioemotional behavior in a northern plains Indian tribe: associations with maternal psychosocial well-being.

M.C. Sarche, C.

A systematic approach to chronic heart failure care: a consensus statement.

The National Heart Foundation of Australia assembled an expert panel to provide guidance on policy and system changes to improve the quality of care for people with chronic heart failure (CHF). The recommendations have the potential to reduce emergency presentations, hospitalisations and premature death among patients with CHF. Best-practice management of CHF involves evidence-based, multidisciplinary, patient-centred care, which leads to better health outcomes.

IgG4 subclass antibodies impair antitumor immunity in melanoma.

Host-induced antibodies and their contributions to cancer inflammation are largely unexplored. IgG4 subclass antibodies are present in IL-10-driven Th2 immune responses in some inflammatory conditions. Since Th2-biased inflammation is a hallmark of tumor microenvironments, we investigated the presence and functional implications of IgG4 in malignant melanoma.

Trajectories of cognitive development among American Indian young children.

Children who begin kindergarten with stronger skills learn faster than do those who enter with lower skills. Minority children tend to enter kindergarten already at a disadvantage, and the gap widens across time. However, little is known about cognitive development among American Indian young children.

A two-part phase II study of cediranib in patients with advanced solid tumours: the effect of food on single-dose pharmacokinetics and an evaluation of safety, efficacy and imaging pharmacodynamics.

Background: Cediranib (RECENTIN™) is an oral, highly potent VEGF inhibitor. This study evaluated the effect of food on the pharmacokinetics of cediranib and compared the administration of continual cediranib via two dosing strategies using this as a platform to investigate pharmacodynamic imaging biomarkers.

Methods: Sixty patients were randomised to receive two single doses of cediranib in either fed/fasted or fasted/fed state (Part A).

Young Adult Migration from a Northern Plains Indian Reservation: Who Stays and Who Leaves.

We evaluated how ambitions, community ties, monetary sufficiency, employment, and alcohol consumption related to whether young American Indian adults had moved from their Northern Plains reservation. Of 518 Northern Plains reservation residents in 1993, we located 472 in 2003-2005 and found that 89 lived more than a four-hour drive from the reservation. Coding the 472 as to whether they had stayed on/near the reservation or moved away, we ran logistic regressions on data they reported in 1996 to determine which demographic and attitudinal variables were associated with having moved.

Religiosity and Spiritual Engagement in Two American Indian Populations.

Social scientific investigation into the religiospiritual characteristics of American Indians rarely includes analysis of quantitative data. After reviewing information from ethnographic and autobiographical sources, we present analyses of data from a large, population-based sample of two tribes (n = 3,084). We examine salience of belief in three traditions: aboriginal, Christian, and Native American Church.

Maternal correlates of 2-year-old American Indian children's social-emotional development in a Northern Plains tribe.

The developmental experiences of very young American Indian children today are not well documented in the current literature. The present study sought to explore the social-emotional development of American Indian toddlers living on a Northern Plains reservation, as a function of maternal variables. Mothers completed self-report questionnaires about their experiences and their children's development.

Reflections on a proposed theory of reservation-dwelling American Indian alcohol use: comment on Spillane and Smith (2007).

In their recent article, N. Spillane and G. Smith suggested that reservation-dwelling American Indians have higher rates of problem drinking than do either non-American Indians or those American Indians living in nonreservation settings.

A longitudinal study of self-esteem, cultural identity, and academic success among American Indian adolescents.

Latent growth curve modeling was used to estimate developmental trajectories of self-esteem and cultural identity among American Indian high school students and to explore the relationships of these trajectories to personal resources, problem behaviors, and academic performance at the end of high school. The sample included 1,611 participants from the Voices of Indian Teens project, a 3-year longitudinal study of adolescents from 3 diverse American Indian cultural groups in the western United States. Trajectories of self-esteem were clearly related to academic achievement; cultural identity, in contrast, was largely unrelated, with no direct effects and only very small indirect effects.

The relationship of cumulative and proximal adversity to onset of substance dependence symptoms in two American Indian communities.

The proximal and distal effects of adversity on the onset of symptoms of substance dependence during adolescence were explored in two culturally distinct American Indian (AI) reservation communities (Northern Plains and Southwest). Data (N=3084) were from the American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project (AI-SUPERPFP). The age-related risk of symptom onset increased gradually from age 11 through age 16, remained relatively high through age 18, then declined rapidly.