PEPhub: a database, web interface, and API for editing, sharing, and validating biological sample metadata.

Background: As biological data increases, we need additional infrastructure to share it and promote interoperability. While major effort has been put into sharing data, relatively less emphasis is placed on sharing metadata. Yet, sharing metadata is also important, and in some ways has a wider scope than sharing data itself. Results: Here, we present PEPhub, an approach to improve sharing and interoperability of biological metadata. PEPhub provides an API, natural language search, and user-friendly web-based sharing and editing of sample metadata tables. We used PEPhub to process more than 100,000 published biological research projects and index them with fast semantic natural language search. PEPhub thus provides a fast and user-friendly way to finding existing biological research data, or to share new data. Availability: https://pephub.databio.org.

The REACH (Resiliency, Engagement, and Accessibility for Comorbid HIV/PTSD/SUD populations) Protocol: Using a Universal Screener to Improve Mental Health and Enhance HIV Care Outcomes.

Among people living with HIV (PLWH), 50% report substance use disorders (SUDs), and 30-61% report posttraumatic stress disorder (PTSD). Comorbid PTSD/SUD/HIV has been linked to faster HIV progression and twice the rate of death, lower medical adherence and retention, and increased viral load compared to PLWH without co-occurring PTSD or SUD. A critical first step in establishing comprehensive mental health services for PLWH is the implementation of an evidence-based screening protocol for PTSD and SUDs to facilitate referrals to specialty mental health providers. Guided by the Consolidated Framework for Implementation Research, this mixed-methods study aimed to examine the feasibility of delivering the REACH (Resiliency, Engagement, and Accessibility for Comorbid HIV/PTSD/SUD populations) Screening protocol. Three case managers were instructed to provide the REACH screening electronically to all patients that they saw for enrollment or re-enrollment appointments over 3 months (n=102). Of the 70 patients who completed the screener, 27% had clinically significant PTSD symptoms and 48.6% had SUD concerns. Qualitative feedback revealed themes related to beliefs about SU and PTSD, attitudes toward screening, comfort in the discussion of SU and PTSD, and referral and treatment considerations. Discussion includes lessons learned for implementation of this assessment of PTSD/SUD in PLWH as a novel approach to increase mental health engagement and promote health equity, with the potential long-term impact of improving HIV care outcomes via ameliorating mental health/SUD, and implications for prevention of HIV transmission. Implementation science can be leveraged to understand the gap in the utilization of existing evidence-based screening tools in HIV care settings.

T2 mapping in myocardial disease: a comprehensive review.

Cardiovascular magnetic resonance (CMR) is considered the gold standard imaging modality for myocardial tissue characterization. Elevated transverse relaxation time (T2) is specific for increased myocardial water content, increased free water, and is used as an index of myocardial edema. The strengths of quantitative T2 mapping lie in the accurate characterization of myocardial edema, and the early detection of reversible myocardial disease without the use of contrast agents or ionizing radiation. Quantitative T2 mapping overcomes the limitations of T2-weighted imaging for reliable assessment of diffuse myocardial edema and can be used to diagnose, stage, and monitor myocardial injury. Strong evidence supports the clinical use of T2 mapping in acute myocardial infarction, myocarditis, heart transplant rejection, and dilated cardiomyopathy. Accumulating data support the utility of T2 mapping for the assessment of other cardiomyopathies, rheumatologic conditions with cardiac involvement, and monitoring for cancer therapy-related cardiac injury. Importantly, elevated T2 relaxation time may be the first sign of myocardial injury in many diseases and oftentimes precedes symptoms, changes in ejection fraction, and irreversible myocardial remodeling. This comprehensive review discusses the technical considerations and clinical roles of myocardial T2 mapping with an emphasis on expanding the impact of this unique, noninvasive tissue parameter.

Respiratory sinus arrhythmia predicts perceived therapy process of a group-based acceptance and commitment therapy intervention.

Engagement in psychotherapy is partially contingent on present-moment focus, mindfulness, and emotion regulation skills. These skills can be linked to parasympathetic functioning with theoretical explanations provided by polyvagal and neurovisceral integration theories. The specific aims of this project were to evaluate relationships between a measure of parasympathetic functioning (respiratory sinus arrythmia [RSA]) and measures of client reports of engagement in an experiential and emotionally evocative group-based intervention. Twenty-one community residents received group-based acceptance and commitment therapy (ACT) for work stress. RSA was measured 1 week before the intervention. Client ratings of relationship support, task focus, and hindering experiences were assessed after each session. Results indicated that clients perceived the ACT intervention to be supportive, task-focused, and without significant therapy-hindering experiences. Higher levels of RSA were significantly associated with higher levels of relationship support. These results support predictions derived from the polyvagal and neurovisceral integration theories.

Trimethylamine N-oxide and incident atherosclerotic events in high-risk individuals with diabetes: an ACCORD trial post hoc analysis.

Introduction: Type 2 diabetes mellitus (T2D) confers high atherosclerotic cardiovascular disease (ASCVD) risk. The metabolite trimethylamine N-oxide (TMAO) derived via gut flora has been linked to excess ASCVD. Research design and methods: We analyzed data, biospecimens, and major adverse cardiovascular events (MACEs) from the prospective multicenter randomized Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to assess its value in 330 high-risk individuals with T2D without evident atherosclerotic disease at enrollment. Results: Incident cardiovascular events occurred in 165 cases; 165 controls matched by age, sex, and treatment arm experienced no incident events during follow-up. Cases and controls (mean age 64.5 years) had similar mean glycated hemoglobin (HbA1c) (8.2%) and mean 10-year ASCVD risk (23.5%); groups also had similar use of statins and antihypertensive medications at baseline and follow-up. Baseline plasma TMAO levels did not differ between groups after adjusting for ASCVD risk score, HbA1c, and estimated glomerular filtration rate, nor did TMAO distinguish patients suffering incident MACE from those who remained event-free. Conclusions: TMAO's prognostic value for incident ASCVD events may be blunted when applied to individuals with T2D with poor glycemic control and high baseline ASCVD risk. These results behoove further translational investigations of unique mechanisms of ASCVD risk in T2D.

CDK4/6 inhibition mitigates stem cell damage in a novel model for taxane-induced alopecia.

Taxanes are a leading cause of severe and often permanent chemotherapy-induced alopecia. As the underlying pathobiology of taxane chemotherapy-induced alopecia remains poorly understood, we investigated how paclitaxel and docetaxel damage human scalp hair follicles in a clinically relevant ex vivo organ culture model. Paclitaxel and docetaxel induced massive mitotic defects and apoptosis in transit amplifying hair matrix keratinocytes and within epithelial stem/progenitor cell-rich outer root sheath compartments, including within Keratin 15+ cell populations, thus implicating direct damage to stem/progenitor cells as an explanation for the severity and permanence of taxane chemotherapy-induced alopecia. Moreover, by administering the CDK4/6 inhibitor palbociclib, we show that transit amplifying and stem/progenitor cells can be protected from paclitaxel cytotoxicity through G1 arrest, without premature catagen induction and additional hair follicle damage. Thus, the current study elucidates the pathobiology of taxane chemotherapy-induced alopecia, highlights the paramount importance of epithelial stem/progenitor cell-protective therapy in taxane-based oncotherapy, and provides preclinical proof-of-principle in a healthy human (mini-) organ that G1 arrest therapy can limit taxane-induced tissue damage.

Identification of Priority Areas for Increased Testing Using Geospatial Mapping of Incident HIV Cases Near Charleston, South Carolina.

Analysis of disease incidence using geospatial mapping techniques can enhance targeted public health efforts in resource-limited settings. While data for HIV incidence are readily available for some metropolitan regions, there is no existing resource that maps HIV incidence geospatially for Charleston, South Carolina and surrounding counties. To facilitate the public health approach to address the HIV epidemic in this region, we used data collected by the South Carolina Department of Health and Environmental Control (SC-DHEC) from 2014 to 2015 to generate local geospatial maps of disease incidence and identify specific areas that may benefit from increased testing and educational efforts. We identified specific zip codes in which there were a high number of cases from patients residing in those areas, but a low number of providers reporting new cases, and we describe ongoing efforts to address this disparity. This analysis identifies a local, collaborative approach to address the HIV epidemic using routinely collected surveillance data.

Management of Thoracic Insufficiency Syndrome in Patients With Jeune Syndrome Using the 70 mm Radius Vertical Expandable Prosthetic Titanium Rib.

BACKGROUND: Jeune syndrome (JS) often results in lethal thoracic insufficiency syndrome. Since 1991, vertical expandable prosthetic titanium rib Dynamic PosteroLateral Expansion Thoracoplasty was used at our institution for treatment of JS. This study assesses the safety and efficacy of this procedure. METHODS: Twenty-four JS patients were treated, 2 lost to follow-up, 17 with a minimum of 2-year follow-up retrospectively reviewed for clinical course: Assisted Ventilation Rate, respiratory rate, capillary blood gases, pulmonary function testings, and complications. Upright anteroposterior/lateral radiographs were measured for Cobb angle, kyphosis, lordosis, thoracic width, and thoracic/lumbar spinal height. Computed tomography scan lung volumes were obtained in 12 patients. RESULTS: Mean age at initial implant was 23 months (7 to 62 mo) with an average 8.4 years (2.3 to 15.6 y) of follow-up. Average chest width increased from 121 to 168 mm at follow-up (P<0.001). Preoperatively, 7/17 (41%) patients had scoliosis. The remainder developed scoliosis during treatment, 8 requiring additional implants. Thoracic and lumbar spinal height was normal preoperatively and stayed normal during treatment. Thoracic kyphosis/lumbar lordosis was stable. Average computed tomography scan total lung volumes increased 484 to 740 mm3 (P<0.001), and Assisted Ventilation Rate status tended to improve (P=0.07). Average forced vital capacity was 34% predicted at first test and 27% predicted at last follow-up. Early demise after surgery was common with multisystem disease. Mean respiratory rate decreased from 35 to 24 bpm at last follow-up (P<0.05). Survival rate of the 22 patients was 68%. Migration of the rib cradles/titanium slings occurred in 12 patients, superficial infections in 5 patients, deep infections in 4 patients, and wound dehiscence in 5 patients. Infection rate was 4.6% per procedure. CONCLUSIONS: The survival rate in JS with surgery was nearly 70% (compared with 70% to 80% mortality without treatment) with less ventilator dependence. Both C1 stenosis and scoliosis are common in JS. Spinal height in JS is normal. Complications are frequent, but tolerable in view of the clinical gains and increase in survival.