A Type II-B Cas9 nuclease with minimized off-targets and reduced chromosomal translocations in vivo.

Streptococcus pyogenes Cas9 (SpCas9) and derived enzymes are widely used as genome editors, but their promiscuous nuclease activity often induces undesired mutations and chromosomal rearrangements. Several strategies for mapping off-target effects have emerged, but they suffer from limited sensitivity. To increase the detection sensitivity, we develop an off-target assessment workflow that uses Duplex Sequencing.

Can a Home-Based Collaborative Care Model Reduce Health Services Utilization for Older Medicaid Beneficiaries Living with Depression and Co-occurring Chronic Conditions? A Quasi-experimental Study.

Depression remains a major public health issue for older adults, increasing risk of costly health services utilization. While home-based collaborative care models (CCM) like PEARLS have been shown to effectively treat depression in low-income older adults living with multiple chronic conditions, their economic impact is unclear. We conducted a quasi-experimental study to estimate PEARLS effect on health service utilization among low-income older adults.

Partnering with community-based organizations to improve equitable access to depression care for underserved older adults in the U.S.: Qualitative formative research.

Background: Embedding evidenced-based programs (EBPs) like PEARLS outside clinical settings can help reduce inequities in access to depression care. Trusted community-based organizations (CBOs) reach older adults who are underserved; however, PEARLS adoption has been limited. Implementation science has tried to close this know-do gap, however a more intentional focus on equity is needed to engage CBOs.

Integrated collaborative care intervention for depression and obesity in primary care: translation from research to practice.

The objective of this study was to present lessons learned about engagement, delivery modality and pandemic impact while delivering a collaborative care intervention with a socioeconomically, racially and ethnically diverse sample. Participants completed a post-intervention survey (n = 41) on experiences and preferred intervention delivery modality, coronavirus 2019 (COVID-19) Impact Survey (n = 50) and provided open-ended feedback about the intervention (n = 27). Intervention process data included attendance, modality, and withdrawals.

Cross-trial prediction of depression remission using problem-solving therapy: A machine learning approach.

Background: Psychotherapy is a standard depression treatment; however, determining a patient's prognosis with therapy relies on clinical judgment that is subject to trial-and-error and provider variability.

Purpose: To develop machine learning (ML) algorithms to predict depression remission for patients undergoing 6 months of problem-solving therapy (PST).

Method: Using data from the treatment arm of 2 randomized trials, ML models were trained and validated on ENGAGE-2 (ClinicalTrials.

Mediating Effects of Neural Targets on Depression, Weight, and Anxiety Outcomes of an Integrated Collaborative Care Intervention: The ENGAGE-2 Mechanistic Pilot Randomized Clinical Trial.

Background: Integrated treatments for comorbid depression (often with anxiety) and obesity are lacking; mechanisms are poorly investigated.

Methods: In a mechanistic pilot trial, adults with body mass index ≥30 and Patient Health Questionnaire-9 scores ≥10 were randomized to usual care ( = 35) or an integrated behavioral intervention ( = 71). Changes at 6 months in body mass index and Depression Symptom Checklist-20 scores were co-primary outcomes, and Generalized Anxiety Disorder Scale-7 score was a secondary outcome.

A Systematic Review of the Effect of on Wound Healing.

Background: Under metabolic stress conditions, there is a higher demand for nutrients which needs to be met. This is to reduce the risk of delay in wound healing which could lead to chronic wound.

Aim: This is a systematic review of the effect of on wound healing.

Functionalized Poly(-isopropylacrylamide)-Based Microgels in Tumor Targeting and Drug Delivery.

Over the past several decades, the development of engineered small particles as targeted and drug delivery systems (TDDS) has received great attention thanks to the possibility to overcome the limitations of classical cancer chemotherapy, including targeting incapability, nonspecific action and, consequently, systemic toxicity. Thus, this research aims at using a novel design of Poly(-isopropylacrylamide) p(NIPAM)-based microgels to specifically target cancer cells and avoid the healthy ones, which is expected to decrease or eliminate the side effects of chemotherapeutic drugs. Smart NIPAM-based microgels were functionalized with acrylic acid and coupled to folic acid (FA), targeting the folate receptors overexpressed by cancer cells and to the chemotherapeutic drug doxorubicin (Dox).

Problem-solving therapy-induced amygdala engagement mediates lifestyle behavior change in obesity with comorbid depression: a randomized proof-of-mechanism trial.

Background: Depression hinders obesity treatment; elucidating mechanisms may enable treatment enhancements.

Objectives: The aim was to investigate whether changes in neural targets in the negative affect circuit following psychotherapy mediate subsequent changes in weight and behaviors.

Methods: Adults (n = 108) with obesity and depression were randomly assigned to usual care or an intervention that delivered problem-solving therapy (PST) for depression over 2 mo.

The Effect of Amino Acids on Wound Healing: A Systematic Review and Meta-Analysis on Arginine and Glutamine.

Under stress conditions, the metabolic demand for nutrients increases, which, if not met, may slow down or indeed stop the wound from healing, thus, becoming chronic wounds. This study aims to perform a systematic review and meta-analysis of the effect of arginine and glutamine supplementation on wound healing. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed for the systematic review and ten electronic databases were used.

Early changes in neural circuit function engaged by negative emotion and modified by behavioural intervention are associated with depression and problem-solving outcomes: A report from the ENGAGE randomized controlled trial.

Background: Depression exerts a staggering toll that is worsened with co-occurring chronic conditions such as obesity. It is imperative to develop more effective interventions for depression and to identify objective and biological plausible neural mechanisms to understand intervention outcomes. The current study uses functional neuroimaging to determine whether a behavioural intervention changes the negative affect circuit and whether these changes relate to subsequent improvements in both symptom and problem-solving outcomes in depressed patients with co-occurring obesity.

Using RE-AIM to examine the potential public health impact of an integrated collaborative care intervention for weight and depression management in primary care: Results from the RAINBOW trial.

Background: An integrated collaborative care intervention was used to treat primary care patients with comorbid obesity and depression in a randomized clinical trial. To increase wider uptake and dissemination, information is needed on translational potential.

Methods: The trial collected longitudinal, qualitative data at baseline, 6 months (end of intensive treatment), 12 months (end of maintenance treatment), and 24 months (end of follow-up).

Sex Moderates Treatment Effects of Integrated Collaborative Care for Comorbid Obesity and Depression: The RAINBOW RCT.

Background: Sex influences health and related behaviors due to biological and psychosocial/socioeconomic factors. Assessing sex-specific responses to integrated treatment for comorbid obesity and depression could inform intervention targeting.

Purpose: To test (a) whether sex moderates the effects of integrated collaborative care on weight and depression outcomes through 24 months and (b) whether treatment response at 6 months predicts 12 and 24 month outcomes by sex.

The factor structure of depressive symptoms in patients with obesity enrolled in the RAINBOW clinical trial.

Background: Examining variability in the presenting symptoms of depression may be particularly important in characterizing depression in patients with comorbid conditions such as obesity. Identifying the underlying constructs of depression in such patients may produce phenotypic information to aid diagnosis and treatment decisions.

Objective: To examine the latent factors of symptoms using the depression Symptom Checklist (SCL-20) and the Patient Health Questionnaire (PHQ-9), separately, in patients with obesity and elevated depressive symptoms.

Increasing Social Connectedness for Underserved Older Adults Living With Depression: A Pre-Post Evaluation of PEARLS.

Objective: To evaluate PEARLS effectiveness for increasing social connectedness among underserved older adults with depression.

Design: Multisite, pre-post single-group evaluation.

Setting: Community-based social service organizations (N = 16) in five U.

Correction: Variability in engagement and progress in efficacious integrated collaborative care for primary care patients with obesity and depression: Within-treatment analysis in the RAINBOW trial.

[This corrects the article DOI: 10.1371/journal.pone.

The ENGAGE-2 study: Engaging self-regulation targets to understand the mechanisms of behavior change and improve mood and weight outcomes in a randomized controlled trial (Phase 2).

Despite evidence for effective integrated behavior therapy for treating comorbid obesity and depression, treatment response is highly variable and the underlying neurobiological mechanisms remain unknown. This hampers efforts to identify mechanistic targets in order to optimize treatment precision and potency. Funded within the NIH Science of Behavior Change (SOBC) Research Network, the 2-phased ENGAGE research project applies an experimental precision medicine approach to address this gap.

First-Year Economic and Quality of Life Effects of the RAINBOW Intervention to Treat Comorbid Obesity and Depression.

Objective: Obesity and depression are prevalent and often co-occurring conditions in the United States. The Research Aimed at Improving Both Mood and Weight (RAINBOW) randomized trial demonstrated the effectiveness of an integrated intervention for adults with both conditions. Characterizing the intervention's economic effects is important for broader dissemination and implementation.

Variability in engagement and progress in efficacious integrated collaborative care for primary care patients with obesity and depression: Within-treatment analysis in the RAINBOW trial.

Introduction: The RAINBOW randomized clinical trial validated the efficacy of an integrated collaborative care intervention for obesity and depression in primary care, although the effect was modest. To inform intervention optimization, this study investigated within-treatment variability in participant engagement and progress.

Methods: Data were collected in 2014-2017 and analyzed post hoc in 2018.

Understanding mechanisms of integrated behavioral therapy for co-occurring obesity and depression in primary care: a mediation analysis in the RAINBOW trial.

The RAINBOW trial demonstrated that an integrated collaborative care intervention was effective for improving weight and depression. This study examined mediation of the treatment effect by a priori specified lifestyle behaviors and cognitive functioning. Participants were randomized to a 12-month integrated intervention (n = 204) or usual care (n = 205).

Effect of an Intervention for Obesity and Depression on Patient-Centered Outcomes: An RCT.

Introduction: An integrated collaborative care intervention was successful for treating comorbid obesity and depression. The effect of the integrated intervention on secondary outcomes of quality of life and psychosocial functioning were examined, as well as whether improvements in these secondary outcomes were correlated with improvements in the primary outcomes of weight and depressive symptoms.

Study Design: This RCT compared an integrated collaborative care intervention for obesity and depression to usual care.

Design and Fabrication of an Automatable, 3D Printed Perfusion Device for Tissue Infusion and Perfusion Engineering.

Tissue decellularization for generating extracellular matrices has become a staple of regenerative medicine in the recent decades, extending from the research setting to clinical usage. Although methods and protocols for tissue decellularization are abundant throughout the literature, they can be time intensive and typically require specific overhead in terms of equipment. To reduce these barriers to entry, a functional and reproducible prototype of a tissue infusion/perfusion device (TIPD) has been designed and fabricated using three-dimensional printed parts in conjunction with commercially available components.