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1.
NPJ Precis Oncol ; 8(1): 174, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103508

RESUMO

To enable interrogation of tumor HLA LOH as a clinical diagnostic for precision oncology, we developed and validated an assay that detects HLA LOH within the context of an FDA-approved clinical diagnostic test, Tempus xT CDx. Validation was conducted via: (1) analytical evaluation of 17 archival patient samples and 42 cell line admixtures and (2) independent clinical evaluation of LOH prevalence in the HLA-A gene (HLA-A LOH) across 10,982 patients. To evaluate the prognostic relevance of HLA-A LOH we assessed 256 immunotherapy-treated non-small cell lung cancer (NSCLC) patients. To determine the feasibility of prospectively identifying and enrolling HLA-A LOH patients into a clinical trial, we established BASECAMP-1 (NCT04981119). We observed a positive predictive agreement of 97% and a negative predictive agreement of 100% in samples with ≥ 40% tumor purity. We observed HLA-A LOH in 16.1% of patients (1771/10,982), comparable to previous reports. HLA-A LOH was associated with longer survival among NSCLC adenocarcinoma patients (HR = 0.60, 95% CI [0.37, 0.96], p = 0.032) with a trend towards shorter survival among squamous cell patients (HR = 1.64, 95% CI [0.80, 3.41], p = 0.183). In 20 months, we prospectively screened 1720 subjects using the Tempus AWARE program, identifying 26 HLA-A*02 LOH patients at 8 sites, with 14 (54%) enrolled into BASECAMP-1. In conclusion, we developed and validated an investigational assay that detects tumor HLA LOH within an FDA-approved clinical diagnostic test, enabling HLA LOH utilization in diagnostic, prognostic, and therapeutic applications.

2.
Arch Suicide Res ; : 1-18, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39185950

RESUMO

The weeks following an inpatient psychiatric hospitalization are known to be the highest-risk time for suicide. Interventions are needed that are well-matched to the dynamic nature of suicidal thoughts and easily implementable during this high-risk time. We sought to determine the feasibility and acceptability of a novel registered clinical trial that combined three brief in-person sessions to teach core cognitive-behavioral therapy (CBT) skills during hospitalization followed by smartphone-based ecological momentary intervention (EMI) to facilitate real-time practice of the emotion management skills during the 28 days after hospital discharge. Results from this pilot study (N = 26) supported some aspects of feasibility and acceptability. Regarding feasibility, 14.7% of all screened inpatients met study eligibility criteria. Half (50.3%) of those who were ineligible were ineligible because they were not part of the population for whom this treatment was designed (e.g., symptoms such as psychosis rendered them ineligible for the current study). Those who were otherwise eligible based on symptoms were primarily ineligible due to inpatient stays that were too short. Nearly half (48%) of study participants did not receive all three in-person sessions during their hospitalization. Among enrolled participants, rates of engagement with the smartphone-based assessment and EMI prompts were 51.47%. Regarding acceptability, quantitative and qualitative data supported the perceived acceptability of the intervention, and provided recommendations for future iterations. Well-powered effectiveness (and effectiveness-implementation) studies are needed to determine the effects of this promising and highly scalable intervention approach.

3.
Oncol Ther ; 12(3): 509-524, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39037536

RESUMO

INTRODUCTION: A dynamic molecular biomarker that can identify early efficacy of immune checkpoint inhibitor (ICI) therapy remains an unmet clinical need. Here we evaluate if a novel circulating tumor DNA (ctDNA) assay, xM, used for treatment response monitoring (TRM), that quantifies changes in ctDNA tumor fraction (TF), can predict outcome benefits in patients treated with ICI alone or in combination with chemotherapy in a real-world (RW) cohort. METHODS: This retrospective study consisted of patients with advanced cancer from the Tempus de-identified clinical genomic database who received longitudinal liquid-based next-generation sequencing. Eligible patients had a blood sample ≤ 40 days prior to the start of ICI initiation and an on-treatment blood sample 15-180 days post ICI initiation. TF was calculated via an ensemble algorithm that utilizes TF estimates derived from variants and copy number information. Patients with molecular response (MR) were defined as patients with a ≥ 50% decrease in TF between tests. In the subset of patients with rw-imaging data between 2 and 18 weeks of ICI initiation, the predictive value of MR in addition to rw-imaging was compared to a model of rw-imaging alone. RESULTS: The evaluable cohort (N = 86) was composed of 14 solid cancer types. Patients received either ICI monotherapy (38.4%, N = 33) or ICI in combination with chemotherapy (61.6%, N = 53). Patients with MR had significantly longer rw-overall survival (rwOS) (hazard ratio (HR) 0.4, P = 0.004) and rw-progression free survival (rwPFS) (HR 0.4, P = 0.005) than patients with molecular non-response (nMR). Similar results were seen in the ICI monotherapy subcohort; HR 0.2, P = 0.02 for rwOS and HR 0.2, P = 0.01 for rwPFS. In the subset of patients with matched rw-imaging data (N = 51), a model incorporating both MR and rw-imaging was superior in predicting rwOS than rw-imaging alone (P = 0.02). CONCLUSIONS: xM used for TRM is a novel serial quantitative TF algorithm that can be used clinically to evaluate ICI therapy efficacy.

4.
Clin Psychol Psychother ; 31(2): e2967, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572780

RESUMO

Transdiagnostic models of psychopathology address many of the shortcomings common to categorical diagnostic systems. These empirically derived models conceptualize psychopathology as a few broad interrelated and hierarchically arranged dimensions, with an overarching general psychopathology dimension, the p-factor, at the apex. While transdiagnostic models are gaining prominence in mental health research, the lack of available tools has limited their clinical translation. The present study explored the potential of creating transdiagnostic scales from the joint factor structure of the Personality Assessment Inventory, Alternative Model of Personality Disorder trait scales (AMPD), and the clinical scales of the SPECTRA: Indices of Psychopathology (SPECTRA). Exploratory factor analysis in a clinical sample (n = 212) identified five factors corresponding to the Negative Affect/Internalizing, Detachment, Antagonism/Externalizing, Disinhibition/Externalizing, and Thought Disorder transdiagnostic dimensions. Goldberg's "Bass-Ackward" method supported a hierarchical structure. Five composite transdiagnostic scales were created by summing each factor's highest loading PAI and SPECTRA scales. A global psychopathology scale was created by summing the five composite scales. All the composite scales demonstrated adequate internal consistency. Correlations between the composite scales and the NEO Five-Factor Inventory-3 provide initial validity evidence for four composite and global scales. The composite thought disorder scale had no conceptually corresponding NEO domain. Clinical implications and study limitations are discussed.


Assuntos
Transtornos da Personalidade , Psicopatologia , Humanos , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/psicologia , Personalidade , Determinação da Personalidade , Inventário de Personalidade
5.
J Pers Assess ; 106(1): 72-82, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37220386

RESUMO

The Personality Assessment Inventory (PAI) is a broadband measure of psychopathology that is widely used in applied settings. Researchers developed regression-based estimates that use the PAI to measure constructs of the Alternative Model for Personality Disorders (AMPD) - a hybrid dimensional and categorical approach to conceptualizing personality disorders. Although prior work has linked these estimates to formal measures of the AMPD, there is little work investigating the clinical correlates of this scoring approach of the PAI. The current study examines associations between these PAI-based AMPD estimates and life data in a large, archival dataset of psychiatric outpatients and inpatients. We found general support for the criterion validity of AMPD estimate scores, such that a theoretically consistent pattern of associations emerged with indicators such as prior academic achievement, antisocial behavior, psychiatric history, and substance abuse. These results provide preliminary support to this scoring approach for use in clinical samples.


Assuntos
Transtornos da Personalidade , Personalidade , Humanos , Manual Diagnóstico e Estatístico de Transtornos Mentais , Inventário de Personalidade , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/psicologia , Determinação da Personalidade
6.
J Pers Assess ; : 1-13, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38078648

RESUMO

The Thematic Apperception Test (TAT) is the second most commonly used performance-based task in clinical practice. However, traditional TAT administration is time-consuming and raises accessibility issues. This study examines the effect of administration modifications (i.e., examiner handwriting versus typing, examiner recording versus participant recording, and re-prompting versus no re-prompting) on narrative length and richness as measured by the Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G). A four-card TAT protocol was administered to 150 college students under one of five conditions. The resulting narratives were scored by two trained raters using the SCORS-G. MANOVA procedures showed (a) no significant differences between examiner handwriting versus typing; (b) the shortest, blandest narratives were produced when the examiner recorded the narratives without re-prompting; and (c) the longest, richest narratives were produced when the participant typed the narratives with re-prompts on the computer screen. Clinical and research implications and future directions will be discussed.

7.
JCO Precis Oncol ; 7: e2300378, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38061006

RESUMO

PURPOSE: Homologous recombination deficiency (HRD) is a well-described phenotype of some prostate cancers; however, current biomarkers for HRD are imperfect and rely on detection of single gene alterations in the homologous recombination repair (HRR) pathway, which may not capture the complexity of HRD biology. RNA signature-based methods of HRD identification present a potentially dynamic assessment of the HRD phenotype; however, its relationship with HRR gene alterations is not well characterized in prostate cancer. METHODS: A HRD assay on the basis of an RNA signature associated with biallelic BRCA1/2 loss was applied to a retrospective cohort study of 985 men with prostate cancer analyzed on the Tempus xT platform. HRD status was defined by a binary threshold on a continuous scale. RESULTS: In this cohort, of the 126 (13%) patients found to be HRD+ by RNA signature (HRD-RNA+), 100 (79%) had no coexisting HRR gene alteration. Among samples with biallelic BRCA1/2 loss, 78% (7/9) were classified as HRD-RNA+, while 8% (2/25) of samples with BRCA1/2 monoallelic loss were HRD-RNA+. Biallelic and monoallelic ATM loss exhibited HRD-RNA+ at a lower prevalence: 6.7% (1/15) and 7.1% (1/14), respectively, compared with HRD-RNA+ prevalence among samples without any HRR gene loss (13%; 100/782). HRD-RNA+ was associated with a significantly higher prevalence of TP53 and AR gene alterations relative to HRD-RNA- after correction for multiple comparisons, 59% versus 39% (q = 0.003) and 23% versus 12% (q = 0.024), respectively. CONCLUSION: Use of an RNA-based HRD signature significantly expands the fraction of patients with prostate cancer who may derive benefit from poly (ADP-ribose) polymerase inhibitors (PARPis) compared with using HRR gene mutations alone. Further studies are needed to evaluate functional HRD significance and inform future usage as a predictive biomarker for PARPi selection.


Assuntos
Proteína BRCA1 , Neoplasias da Próstata , Masculino , Humanos , Proteína BRCA1/genética , Reparo de DNA por Recombinação/genética , Recombinação Homóloga/genética , Estudos Retrospectivos , Proteína BRCA2/genética , Neoplasias da Próstata/genética , Inibidores de Poli(ADP-Ribose) Polimerases
8.
Psychol Sport Exerc ; 68: 102464, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37665906

RESUMO

INTRODUCTION: Early childhood is recognised as a critical window of opportunity for physical literacy development, however early childhood educators typically lack the training required to effectively provide appropriate physical literacy opportunities for children. We examined the effects of an online physical literacy professional development program-relative to continuing with 'standard' practice-on early childhood educators' physical literacy knowledge and application. METHODS: We conducted a parallel two-arm randomised controlled trial, in which 88 early childhood educators were randomly assigned to an online professional development program designed to support educators' physical literacy instructional skills (intervention arm; n = 37), or a 'standard practice' control condition (n = 51). Data were collected prior to and after the four-week intervention period. We measured educators' physical literacy knowledge and application (our primary outcome) through independent coding of open-ended survey responses, and educators' self-reported perceptions of values, confidence, behaviours, and barriers (secondary outcomes). Between-group differences were assessed through analysis of covariance. RESULTS: One intervention arm participant withdrew from the study, resulting in 87 participants included in analysis. Educators in the intervention arm scored significantly higher on post-intervention physical literacy knowledge (d = 0.62) and application (d = 0.33) than those in the control arm. Educators in the intervention arm also scored significantly higher than controls on confidence in teaching physical activity (d = 0.42) and significantly lower than controls on perceived personal barriers to physical activity (d = 0.53). Thirteen participants in the intervention arm (36%) did not begin the online professional development program. CONCLUSION: Improvements in physical literacy instructional outcomes indicate the potential for further investigation into broader implementation of online professional development programs of this nature in the future.


Assuntos
Pessoal de Educação , Alfabetização , Pré-Escolar , Criança , Humanos , Exercício Físico , Conhecimento , Processos Mentais
9.
J Clin Psychol Med Settings ; 30(1): 61-71, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35717453

RESUMO

The emergence of the 2019 novel coronavirus (COVID-19) has dramatically altered how psychologists deliver its training. At least for the time being, virtual care has become the primary method for delivering mental health services. This has allowed patients and clinicians to continue to access and provide services in a way that would have been impossible years ago. Not only has this shift impacted patients, but it has also impacted supervision and training. The impact has been especially profound on inpatient units where the psychiatric and medical acuity is high of patients and the therapeutic milieu is an important aspect of treatment. The purpose of this paper is to review the impact of COVID-19 on pre-doctoral psychology interns during their rotation on an inpatient psychiatry unit at the start of the pandemic (January to June of 2020) and use these experiences to onboard the next class of interns in the new academic year (July 2020 to June 2021) using a hybrid model of in-person and virtual training experiences. At the end of 2020/2021 rotation, we voluntarily asked interns to complete a questionnaire that was developed based on the qualitative experiences of the previous class to assess the effectiveness of this hybrid model. We also surveyed multi-disciplinary staff members who were essential personnel and required to work in person during this time about their experiences of safety and support. With this information, we explore and offer guidance to other inpatient training sites who are likely to encounter similar challenges during this time. In particular, we discuss the integration of virtual technology into this training experience, as well as the restructuring of clinical and supervisory experiences. We highlighted several short-term strategies that we have flexibly adapted to our inpatient unit. The lessons learned herein seek to guide supervisors and trainees alike in adapting their psychology training programs to meet the evolving demands of COVID-19.


Assuntos
COVID-19 , Internato e Residência , Serviços de Saúde Mental , Humanos , Assistência ao Paciente , Currículo
10.
Cancer Immunol Immunother ; 72(2): 339-350, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35881197

RESUMO

BACKGROUND: Adjuvant immune checkpoint blockade (ICB) following chemoradiotherapy and adding ICB to chemotherapy have been key advances for stages III-IV non-small cell lung cancer (NSCLC) treatment. However, known biomarkers like PD-L1 are not consistently indicative of ICB response. Other markers within the tumor immune microenvironment (TIME) may better reflect ICB response and/or resistance mechanisms, but an understanding of how TIMEs differ between stage III and IV NSCLC has not been explored. METHODS: Real-world data from unresectable, stage III-IV, non-squamous, pretreatment NSCLCs (stage III n = 106, stage IV n = 285) were retrospectively analyzed. PD-L1 immunohistochemistry (IHC) was compared to CD274 gene expression. Then, differential gene expression levels, pathway enrichment, and immune infiltrate between stages were calculated from whole-transcriptome RNA-seq. Analyses were stratified by EGFR status. RESULTS: PD-L1 IHC and CD274 expression in tumor cells were highly correlated (n = 295, P < 2.2e-16, ⍴ = 0.74). CTLA4 expression was significantly increased in stage III tumors (P = 1.32e-04), while no differences were observed for other ICB-related genes. Metabolic pathway activity was significantly enriched in stage IV tumors (P = 0.004), whereas several immune-related KEGG pathways were enriched in stage III. Stage IV tumors had significantly increased macrophage infiltration (P = 0.0214), and stage III tumors had a significantly higher proportion of CD4 + T cells (P = 0.017). CD4 + T cells were also relatively more abundant in EGFR-mutant tumors vs. wild-type (P = 0.0081). CONCLUSION: Directly comparing the TIMEs of stage III and IV NSCLC, these results carry implications for further studies of ICB response in non-resectable stage III NSCLC and guide further research of prognostic biomarkers and therapeutic targets.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Antígeno B7-H1/metabolismo , Estudos Retrospectivos , Biomarcadores , Microambiente Tumoral , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptores ErbB , Biomarcadores Tumorais
11.
Z Rheumatol ; 2022 Dec 09.
Artigo em Alemão | MEDLINE | ID: mdl-36484837

RESUMO

INTRODUCTION: The delegation of medical services to rheumatology assistants (RFA) has proven to be safe and effective in the evaluation of the research project "StaerkeR". Afterwards, the experiences of the participating RFAs and rheumatologists with delegation were surveyed and discussed within the framework of an opinion research project. METHODS: At the end of the project, the participating RFAs and rheumatologists were surveyed via an online questionnaire (quantitative analysis) (21 questions for physicians and 44 questions for RFAs). In addition, focus group meetings were held for the RFAs, which were led by a moderator and a secretary. The results of the focus group sessions (qualitative analyses) were analyzed according to the structured method of Kuckartz. RESULTS: All 31 RFAs and 25 rheumatologists involved in the project participated in the online surveys and 9 RFAs took part in the 2 focus groups. In the online surveys, both the RFAs and the rheumatologists gave predominantly good to very good ratings with respect to RFA training, the implementation of delegation in the practices and outpatient clinics, the role of the RFAs and the overall evaluation of the delegation concept. In the focus group discussions, many possible limitations regarding acceptance and implementation of the delegation concept were mentioned. CONCLUSION: The delegation of medical tasks to RFAs is a concept that is positively assessed and highly accepted by both sides, the rheumatologists and the RFAs. In a comparison between the individual practices and hospital outpatient departments, there is still a clear heterogeneity with respect to the willingness and logistical possibilities in the implementation of the delegation concept.

12.
Nat Commun ; 13(1): 4053, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35831288

RESUMO

The efficacy of immune checkpoint blockade (ICB) varies greatly among metastatic non-small cell lung cancer (NSCLC) patients. Loss of heterozygosity at the HLA-I locus (HLA-LOH) has been identified as an important immune escape mechanism. However, despite HLA-I disruptions in their tumor, many patients have durable ICB responses. Here we seek to identify HLA-I-independent features associated with ICB response in NSCLC. We use single-cell profiling to identify tumor-infiltrating, clonally expanded CD4+ T cells that express a canonical cytotoxic gene program and NSCLC cells with elevated HLA-II expression. We postulate cytotoxic CD4+ T cells mediate anti-tumor activity via HLA-II on tumor cells and augment HLA-I-dependent cytotoxic CD8+ T cell interactions to drive ICB response in NSCLC. We show that integrating tumor extrinsic cytotoxic gene expression with tumor mutational burden is associated with longer time to progression in a real-world cohort of 123 NSCLC patients treated with ICB regimens, including those with HLA-LOH.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Biomarcadores Tumorais/genética , Linfócitos T CD8-Positivos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética
13.
Microbiol Resour Announc ; 11(6): e0040222, 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35575560

RESUMO

The USA300 and USA600 clonal lineages are the cause of many serious Staphylococcus aureus infections. Here, we report the complete genomes of two methicillin-sensitive S. aureus strains isolated from the healthy skin of adults in Colorado, which are most phylogenetically similar to the USA300 and USA600 lineages.

14.
Behav Ther ; 53(2): 267-280, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35227403

RESUMO

The practice of therapeutic skills outside of sessions in which they are learned is one presumed key component of cognitive behavioral therapy (CBT). Yet, our understanding of how skills practice relates to clinical outcomes remains limited. Here, we explored patients' emotional responses to CBT skills practice in a pilot study pairing smartphone-app-delivered skills reminders and guided practice (ecological momentary intervention [EMI]) using ecological momentary assessment (EMA). Participants (n = 25) were adults recently hospitalized for a suicide attempt or severe suicidal thinking. They received brief inpatient CBT (1 to 3 sessions covering core CBT skills from the Unified Protocol), followed by 1 month of EMI and EMA after discharge. On average, participants reported modest reductions in negative affect after skills use (i.e., immediate responses; median time elapsed = 4.30 minutes). Additionally, participants tended to report less negative affect when the timepoint preceding the current assessment included EMI skills practice, rather than EMA alone (i.e., delayed responses; median time elapsed between prompts = 2.17 hours). Immediate effects were unrelated to longer-term clinical outcomes, whereas greater delayed effects were associated with lower symptom severity at follow-up. Future studies should further examine how CBT skills use in daily life may alleviate symptoms.


Assuntos
Terapia Cognitivo-Comportamental , Aplicativos Móveis , Avaliação Momentânea Ecológica , Emoções , Humanos , Projetos Piloto , Smartphone
15.
Clin Psychol Psychother ; 29(4): 1447-1456, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35212082

RESUMO

While understanding how internalized representations of others (i.e., object relations) change over the course of treatment is essential for treatment planning and evaluation of progress, few studies have examined the nature of these changes through repeated psychological assessments. In this study, we applied the SCORS-G to Thematic Apperception Test narratives for 61 adult patients with complex psychiatric problems undergoing residential treatment over an 18-month period. Over the course of treatment, patient representations of self and others became more complex, indicating improvements in mentalization. Further, an analysis of default ratings (i.e., an aspect of story 'blandness') suggested that certain shifts in SCORS-G dimensional scores over time were accounted for by greater degree of scorable content across time points, rather than changes specific to the dimensions themselves. Findings from novel exploratory analyses aimed at evaluating the test-retest reliability of both default rating proportion and several emerging alternative scoring approaches (including changes in minimum, maximum and range of scores on individual dimensions) are reported. While the magnitude of change across mean dimensional scores was found to be lower compared to those previously found in outpatient populations, our results suggest that the SCORS-G remains capable of detecting changes in mentalization capacities in individuals contending with longstanding, severe psychiatric impairment and personality-based psychopathology. Implications for treatment, assessment and future research are discussed.


Assuntos
Apego ao Objeto , Cognição Social , Adulto , Humanos , Reprodutibilidade dos Testes , Comportamento Social , Teste de Apercepção Temática
16.
J Pers Disord ; 36(2): 201-216, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34427493

RESUMO

The Alternative Model for Personality Disorders (AMPD) in Section III of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013) conceptualizes personality pathology as a combination of impairment (Criterion A) and traits (Criterion B). One measure used to develop Criterion A was the Social Cognition and Object Relations Scale - Global Rating Method (SCORS-G), which is a multidimensional, object-relational clinician-rated measure of personality functioning. Although there are conceptual links between the AMPD and SCORS-G dimensions, there exists no research examining the relationship. To address this, we examined associations between the SCORS-G dimensions and measures of the AMPD constructs in a large, archival dataset of outpatients and inpatients. More pathological scores on SCORS-G dimensions reflecting self- and interpersonal functioning were associated with greater pathological traits and impairment. Overall, results support further investigation into SCORS-G as a useful measure in AMPD research and assessment.


Assuntos
Transtornos da Personalidade , Teste de Apercepção Temática , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Personalidade , Determinação da Personalidade , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/psicologia
17.
Nat Commun ; 12(1): 6115, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34675193

RESUMO

Genome-wide association studies (GWAS) have implicated the IL33 locus in asthma, but the underlying mechanisms remain unclear. Here, we identify a 5 kb region within the GWAS-defined segment that acts as an enhancer-blocking element in vivo and in vitro. Chromatin conformation capture showed that this 5 kb region loops to the IL33 promoter, potentially regulating its expression. We show that the asthma-associated single nucleotide polymorphism (SNP) rs1888909, located within the 5 kb region, is associated with IL33 gene expression in human airway epithelial cells and IL-33 protein expression in human plasma, potentially through differential binding of OCT-1 (POU2F1) to the asthma-risk allele. Our data demonstrate that asthma-associated variants at the IL33 locus mediate allele-specific regulatory activity and IL33 expression, providing a mechanism through which a regulatory SNP contributes to genetic risk of asthma.


Assuntos
Asma/genética , Elementos Facilitadores Genéticos , Interleucina-33/genética , Alelos , Animais , Asma/metabolismo , Cromatina/genética , Cromatina/metabolismo , Feminino , Predisposição Genética para Doença , Humanos , Interleucina-33/metabolismo , Masculino , Camundongos Transgênicos , Fator 1 de Transcrição de Octâmero/genética , Fator 1 de Transcrição de Octâmero/metabolismo , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Peixe-Zebra
18.
Cell Rep ; 36(4): 109429, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34320344

RESUMO

Patient-derived tumor organoids (TOs) are emerging as high-fidelity models to study cancer biology and develop novel precision medicine therapeutics. However, utilizing TOs for systems-biology-based approaches has been limited by a lack of scalable and reproducible methods to develop and profile these models. We describe a robust pan-cancer TO platform with chemically defined media optimized on cultures acquired from over 1,000 patients. Crucially, we demonstrate tumor genetic and transcriptomic concordance utilizing this approach and further optimize defined minimal media for organoid initiation and propagation. Additionally, we demonstrate a neural-network-based high-throughput approach for label-free, light-microscopy-based drug assays capable of predicting patient-specific heterogeneity in drug responses with applicability across solid cancers. The pan-cancer platform, molecular data, and neural-network-based drug assay serve as resources to accelerate the broad implementation of organoid models in precision medicine research and personalized therapeutic profiling programs.


Assuntos
Neoplasias/patologia , Organoides/patologia , Medicina de Precisão , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Fluorescência , Genômica , Antígenos HLA/genética , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Neoplasias/genética , Redes Neurais de Computação , Transcriptoma/genética
19.
Clin Psychol Psychother ; 28(6): 1550-1561, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33837983

RESUMO

This study examines the construct validity of the Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G; Westen, 1995; see also Stein & Mulford, 2018) by exploring the degree of convergence across different narrative sources (i.e., early memories [EM] and psychotherapy narratives [PT]) in relation to patient- and therapist-rated psychotherapy process measures. Using a university-based outpatient sample (n = 81), we found limited convergence for SCORS-G ratings across narrative type. First, paired t tests showed that the means for six of the eight SCORS-G dimensions differed significantly between the EM and PT narratives with the majority having a large magnitude of effect. Moreover, despite 29 significant correlations between a SCORS-G dimension and either an alliance or session quality variable, only two of the eight SCORS-G dimensions significantly correlated with the same process variable across narrative type (e.g., patient-rated session depth with SCORS-G Self Esteem [SE] and Identity and Coherence of Self [ICS]). Importantly, the high degree of theoretical coherence in the associations that emerged between the SCORS-G dimensions and the process variables suggest that the lack of convergence was not due to limited validity of the SCORS-G. Instead, the results underscore the importance of multi-method assessment techniques by highlighting that the manner in which a narrative is elicited will impact the object relational content patients provide. Future research and clinical implications related to the SCORS-G, alliance and psychotherapy process are discussed.


Assuntos
Apego ao Objeto , Cognição Social , Humanos , Avaliação de Processos em Cuidados de Saúde , Psicoterapia , Teste de Apercepção Temática
20.
Clin Psychol Psychother ; 28(4): 929-938, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33386029

RESUMO

The SPECTRA: Indices of Psychopathology is a broadband assessment inventory compatible with contemporary hierarchical models of psychopathology (internalizing, externalizing, reality impairing dimensions and global psychopathology factor). This study explored the SPECTRA's construct validity using a wide range of life event (extra-test) variables in a clinical sample. The life event variables included the following: education level, school failure, childhood adversity, suicide attempts, psychiatric hospitalizations, depression, psychotic symptoms, self-injury, substance abuse, arrests, physical violence, marital status, employment status and current medications. Results showed that all SPECTRA clinical scales had significant life event correlations. For the higher-order Spectra scales, the global index of psychopathology had the greatest number and range of life event correlations. Correlations for the externalizing and reality impairing Spectra scales provided solid validity evidence, while correlations for the internalizing Spectra scale were more diffuse. These findings provide the first non-test-based evidence of construct validity for the SPECTRA.


Assuntos
Psicopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Depressão/psicologia , Escolaridade , Emprego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Transtornos Relacionados ao Uso de Substâncias/psicologia , Tentativa de Suicídio/psicologia , Adulto Jovem
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