Mapping spatial organization and genetic cell-state regulators to target immune evasion in ovarian cancer.

The drivers of immune evasion are not entirely clear, limiting the success of cancer immunotherapies. Here we applied single-cell spatial and perturbational transcriptomics to delineate immune evasion in high-grade serous tubo-ovarian cancer. To this end, we first mapped the spatial organization of high-grade serous tubo-ovarian cancer by profiling more than 2.

A Conserved Local Structural Motif Controls the Kinetics of PTP1B Catalysis.

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin and leptin signaling pathways, making it a highly attractive target for the treatment of type II diabetes. For PTP1B to perform its enzymatic function, a loop referred to as the "WPD loop" must transition between open (catalytically incompetent) and closed (catalytically competent) conformations, which have both been resolved by X-ray crystallography. Although prior studies have established this transition as the rate-limiting step for catalysis, the transition mechanism for PTP1B and other PTPs has been unclear.

Discovery and Validation of the Binding Poses of Allosteric Fragment Hits to Protein Tyrosine Phosphatase 1b: From Molecular Dynamics Simulations to X-ray Crystallography.

Fragment-based drug discovery has led to six approved drugs, but the small sizes of the chemical fragments used in such methods typically result in only weak interactions between the fragment and its target molecule, which makes it challenging to experimentally determine the three-dimensional poses fragments assume in the bound state. One computational approach that could help address this difficulty is long-timescale molecular dynamics (MD) simulations, which have been used in retrospective studies to recover experimentally known binding poses of fragments. Here, we present the results of long-timescale MD simulations that we used to prospectively discover binding poses for two series of fragments in allosteric pockets on a difficult and important pharmaceutical target, protein tyrosine phosphatase 1b (PTP1b).

Reconstructing codependent cellular cross-talk in lung adenocarcinoma using REMI.

Cellular cross-talk in tissue microenvironments is fundamental to normal and pathological biological processes. Global assessment of cell-cell interactions (CCIs) is not yet technically feasible, but computational efforts to reconstruct these interactions have been proposed. Current computational approaches that identify CCI often make the simplifying assumption that pairwise interactions are independent of one another, which can lead to reduced accuracy.

Exploring Black adolescent males' experiences with racism and internalized racial oppression.

We explore Black male high school students' perceptions of racial oppression, their internalization of racial oppression, and the impact of these experiences on their academic lives. Using constructivist grounded theory, 10 semi-structured interviews were conducted with Black adolescent boys. Results identified five core categories: (a) racial socialization, (b) understandings of and experiences with racism, (c) emotional and behavioral responses to racism, (d) internalization of racial oppression, and (e) school resistance and support needed.

Optimism and distress tolerance in the social adjustment of nurses: examining resilience as a mediator and gender as a moderator.

Background: As nursing is recognised as one of the most stressful occupations in healthcare organisations, nurses are vulnerable to adjustment challenges.

Aims: The authors examine the association between optimism, distress tolerance and social adjustment through the mediating role of resilience and the moderating role of gender among Iranian nurses.

Methods: The sample consisted of 183 nurses working in six private hospitals in Iran.

What types of racial messages protect Asian American adolescents from discrimination? A latent interaction model.

In this brief report, the authors investigate how different types of parental racial-ethnic socialization messages (i.e., cultural socialization/pluralism, promotion of mistrust, and preparation for racial bias) moderate the relationship between racial discrimination and psychological distress in a sample of 187 Asian American adolescents.

Renal Saturation and Acute Kidney Injury in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia.

Objective: To investigate the range of renal near-infrared spectroscopy (NIRS) measures in neonates undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE) and to determine the association between renal NIRS measures and the development of acute kidney injury (AKI).

Study Design: A retrospective chart review was conducted of neonates with moderate to severe HIE who received therapeutic hypothermia at a tertiary care center from 2014 to 2016. Neonates had routine continuous NIRS monitoring of cerebral and renal saturation (Rsat) as part of their clinical care for 72 hours of cooling and until 24 hours after rewarming.

Integrative Personal Omics Profiles during Periods of Weight Gain and Loss.

Advances in omics technologies now allow an unprecedented level of phenotyping for human diseases, including obesity, in which individual responses to excess weight are heterogeneous and unpredictable. To aid the development of better understanding of these phenotypes, we performed a controlled longitudinal weight perturbation study combining multiple omics strategies (genomics, transcriptomics, multiple proteomics assays, metabolomics, and microbiomics) during periods of weight gain and loss in humans. Results demonstrated that: (1) weight gain is associated with the activation of strong inflammatory and hypertrophic cardiomyopathy signatures in blood; (2) although weight loss reverses some changes, a number of signatures persist, indicative of long-term physiologic changes; (3) we observed omics signatures associated with insulin resistance that may serve as novel diagnostics; (4) specific biomolecules were highly individualized and stable in response to perturbations, potentially representing stable personalized markers.

Vitamin D supplementation decreases serum 27-hydroxycholesterol in a pilot breast cancer trial.

Purpose: 27-hydroxycholesterol (27HC), an endogenous selective estrogen receptor modulator (SERM), drives the growth of estrogen receptor-positive (ER+) breast cancer. 1,25-dihydroxyvitamin D (1,25(OH)D), the active metabolite of vitamin D, is known to inhibit expression of CYP27B1, which is very similar in structure and function to CYP27A1, the synthesizing enzyme of 27HC. Therefore, we hypothesized that 1,25(OH)D may also inhibit expression of CYP27A1, thereby reducing 27HC concentrations in the blood and tissues that express CYP27A1, including breast cancer tissue.

Assessing biological and technological variability in protein levels measured in pre-diagnostic plasma samples of women with breast cancer.

Background: Quantitative proteomics allows for the discovery and functional investigation of blood-based pre-diagnostic biomarkers for early cancer detection. However, a major limitation of proteomic investigations in biomarker studies remains the biological and technical variability in the analysis of complex clinical samples. Moreover, unlike 'omics analogues such as genomics and transcriptomics, proteomics has yet to achieve reproducibility and long-term stability on a unified technological platform.

Mentoring ethnic minority counseling and clinical psychology students: A multicultural, ecological, and relational model.

The aim of the current study was to understand the role of race and culture in successful mentoring relationships in graduate school. We examined the practices of 9 faculty mentors working with 15 ethnic minority doctoral students in counseling and clinical psychology. Grounded theory was used to discern unifying patterns and to formulate a theory of multicultural mentoring.

Clinical recovery from surgery correlates with single-cell immune signatures.

Delayed recovery from surgery causes personal suffering and substantial societal and economic costs. Whether immune mechanisms determine recovery after surgical trauma remains ill-defined. Single-cell mass cytometry was applied to serial whole-blood samples from 32 patients undergoing hip replacement to comprehensively characterize the phenotypic and functional immune response to surgical trauma.

Family support, self-esteem, and perceived racial discrimination among Asian American male college students.

This study was conducted to examine under what situation (i.e., when individuals used more or less family support) and for whom (i.

Payment for obesity services: examples and recommendations for stage 3 comprehensive multidisciplinary intervention programs for children and adolescents.

Objective: The Reimbursement and Payment Subcommittee of the National Association of Children's Hospitals and Related Institutions FOCUS on a Fitter Future group sought to guide medical providers, patients, and payers to better serve obese children and adolescents to enable optimum health. Recommendations are provided for the essential components of a stage 3 comprehensive multidisciplinary intervention program as defined by the 2007 Expert Committee recommendations. In addition, suggestions are offered for a stepwise approach to implement these recommendations.

Evaluation of a school-based internship program for Chinese immigrant adolescents in the United States.

The experiences of five Chinese immigrant adolescents who became participatory action researchers (PAR) (Fine et al,, 2002) through a school-based internship program in the United States are analyzed and presented. Evaluation of the project was conducted using content analysis of student researchers' journal entries. Discovery Oriented Approach analysis (Mahrer & Boulet, 1999; Mahrer 1988) was implemented and revealed the following main domains: Learning and Growth, Program Evaluation, Adjustment and Coping, Identity Development and Social Role, Pride, Social Support, Empathy, and Group Process.

Chinese immigrant high school students' cultural interactions, acculturation, family obligations, language use, and social support.

When immigrant youth come to the United States, they must learn to interact with dominant and cultural groups as part of the adjustment process. The current study investigated whether the association between Chinese immigrant high school students' (N = 286) English fluency, academic and career/ college help-seeking, multidimensional acculturation, family responsibilities, and social support, predicted their intercultural competence concerns (their interactions across dominant and cultural groups). Results indicate that this was the case.

Development of a mentoring program for Chinese immigrant adolescents' cultural adjustment.

The development and evaluation of a peer mentoring program for Chinese immigrant adolescents' cultural adjustment is described. Twenty-three high school students who recently immigrated from Mainland China participated in the year-long program and 4 high school students served as their peer mentors. Data analyses revealed that the students who participated in the mentoring program had significantly higher peer attachment-trust and need for closeness scores at post-test than at pre-test.

Asian American families' collectivistic coping strategies in response to 9/11.

Our study investigated the use of individualistic and collectivistic coping strategies among Asian American family members of victims of the World Trade Center (WTC) attacks on September 11th, 2001. Interviews were conducted with 11 Asian Americans who had lost a member of their family in the WTC attacks. Using the Discovery-Oriented Research analysis (Mahrer, 1988), results indicated that Asian Americans utilized the following collectivistic coping methods to deal with their losses: individualistic coping, familial coping, intracultural coping, relational universality, forbearance, fatalism/ spirituality, and indigenous healing methods.

Coping attitudes, sources, and practices among Black and Latino college students.

We investigated 130 Black and Latino college students regarding their concerns, attitudes toward professional counseling, sources of support, and coping activities. We found that the Black and Latino cultural emphasis on interdependence influenced attitudes toward using professional resources such as a counselor. We also found a significant two-way interaction between gender and race for attitudes toward professional counseling: Black males had less favorable attitudes in comparison to Black females, while Latino males had more favorable attitudes than did Latino females.

Outcomes of surgical fundoplication in children.

Background & Aims: Surgical fundoplication has been recommended for children with persistent GERD. The purpose of this study was to determine the frequency of postoperative symptoms requiring medical evaluation and/or treatment after fundoplication in children with or without associated medical disorders.

Methods: In a retrospective cohort study, we reviewed the medical records of all children who underwent fundoplication during 1996-1999.

The cultural adjustment and mental health of Japanese immigrant youth.

Interviews were conducted with eight Japanese immigrant youth about their experiences with respect to adjusting to life in the United States, dealing with discrimination, and coping with cultural challenges. They were also questioned about their mental health and family and peer relations. Results indicate that participants managed to maintain bicultural identities and to cope with the problems that they encountered.

Age, acculturation, cultural adjustment, and mental health symptoms of Chinese, Korean, and Japanese immigrant youths.

This study of Chinese, Japanese, and Korean immigrant junior high and high school students (N = 319) investigated the association between age, acculturation, cultural adjustment difficulties, and general mental health concerns. Hierarchical regression analyses determined that among all of the independent variables, age, acculturation, and cultural adjustment difficulties had significant predictive effects on mental health symptoms. Implications for theory, research, and practice are addressed, particularly as they relate to developmental issues among immigrant youths.

Extrahepatic manifestations of hepatitis C among United States male veterans.

Hepatitis C virus (HCV) has been associated with several extrahepatic conditions. To date, most studies assessing these associations involved small numbers of patients and lacked a control group. Using the computerized databases of the Department of Veterans Affairs, we carried out a hospital-based case-control study that examined all cases of HCV-infected patients hospitalized during 1992 to 1999 (n = 34,204) and randomly chosen control subjects without HCV (n = 136,816) matched with cases on the year of admission.