"We're Not Gonna Aid You in Shooting Up": Stigma's Relationship to Harm Reduction in People Who Inject Drugs.

Background: Harm reduction, when applied to drug use, prioritizes improving patient-centered health outcomes and reducing drug-related harm. In order for harm reduction strategies to be adopted by people who inject drugs (PWID), they need to be promoted, accessible, and accepted in that population and the community-at-large. While PWID face stigma at multiple levels, less is known about how stigma influences uptake and acceptance of harm reduction services and strategies among PWID.

A Comparison of ChatGPT and Fine-Tuned Open Pre-Trained Transformers (OPT) Against Widely Used Sentiment Analysis Tools: Sentiment Analysis of COVID-19 Survey Data.

Background: Health care providers and health-related researchers face significant challenges when applying sentiment analysis tools to health-related free-text survey data. Most state-of-the-art applications were developed in domains such as social media, and their performance in the health care context remains relatively unknown. Moreover, existing studies indicate that these tools often lack accuracy and produce inconsistent results.

Adherence to Patient-Reported Symptom Monitoring and Subsequent Clinical Interventions for Patients With Multiple Myeloma in Outpatient Care: Longitudinal Observational Study.

Background: The use of software to monitor patient-reported outcome measures (PROMs) can improve outcomes for patients with cancer receiving anticancer therapy; however, evidence from applications used in routine clinical practice is lacking.

Objective: We aimed to investigate adherence to and patient perceptions of a weekly, web-based PROM symptom monitoring program in routine clinical practice for patients with Multiple Myeloma. Moreover, we aimed to capture how clinical alerts prompted by the system influenced clinical care.

Elevated Plasma Immunoglobulin Levels Prior to Heart Transplantation Are Associated with Poor Post-Transplantation Survival.

Cardiac allograft vasculopathy (CAV) and antibody-mediated rejection are immune-mediated, long-term complications that jeopardize graft survival after heart transplantation (HTx). Interestingly, increased plasma levels of immunoglobulins have been found in end-stage heart failure (HF) patients prior to HTx. In this study, we aimed to determine whether increased circulating immunoglobulin levels prior to transplantation are associated with poor post-HTx survival.

Test-Retest Reliability of an Adaptive Thermal Pain Calibration Procedure in Healthy Volunteers.

Quantitative sensory testing (QST) allows researchers to evaluate associations between noxious stimuli and acute pain in clinical populations and healthy participants. Despite its widespread use, our understanding of QST's reliability is limited, as reliability studies have used small samples and restricted time windows. We examined the reliability of pain ratings in response to noxious thermal stimulation in 171 healthy volunteers (n = 99 female, n = 72 male) who completed QST on multiple visits ranging from 1 day to 952 days between visits.

A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration.

Myocardial regeneration is restricted to early postnatal life, when mammalian cardiomyocytes still retain the ability to proliferate. The molecular cues that induce cell cycle arrest of neonatal cardiomyocytes towards terminally differentiated adult heart muscle cells remain obscure. Here we report that the miR-106b~25 cluster is higher expressed in the early postnatal myocardium and decreases in expression towards adulthood, especially under conditions of overload, and orchestrates the transition of cardiomyocyte hyperplasia towards cell cycle arrest and hypertrophy by virtue of its targetome.

The cancer patient's perspective of COVID-19-induced distress-A cross-sectional study and a longitudinal comparison of HRQOL assessed before and during the pandemic.

Background: To permit timely mitigation of adverse effects on overall clinical outcome, it is essential to understand how the pandemic influences distress and health-related quality of life (HRQOL) in cancer patients during the coronavirus disease 2019 (COVID-19) pandemic.

Methods: In this cross-sectional study, adult cancer patients, without COVID-19 symptoms, completed a 13-item questionnaire about the pandemic's impacts on distress and everyday-life; associations with age, sex, or impaired HRQOL were then assessed by binary logistic regressions. In a subsample of patients with HRQOL assessment available from both before and during the pandemic, we evaluated the pandemic's impact on longitudinal changes in HRQOL reported within 6 months before versus during the COVID-19 lockdown using McNemar's test, and thresholds for clinical importance.

miR-132/212 Impairs Cardiomyocytes Contractility in the Failing Heart by Suppressing SERCA2a.

Compromised cardiac function is a hallmark for heart failure, mostly appearing as decreased contractile capacity due to dysregulated calcium handling. Unfortunately, the underlying mechanism causing impaired calcium handling is still not fully understood. Previously the miR-132/212 family was identified as a regulator of cardiac function in the failing mouse heart, and pharmaceutically inhibition of miR-132 is beneficial for heart failure.

Multi-omics integration identifies key upstream regulators of pathomechanisms in hypertrophic cardiomyopathy due to truncating MYBPC3 mutations.

Background: Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the cardiac muscle, frequently caused by mutations in MYBPC3. However, little is known about the upstream pathways and key regulators causing the disease. Therefore, we employed a multi-omics approach to study the pathomechanisms underlying HCM comparing patient hearts harboring MYBPC3 mutations to control hearts.

The prognostic value of additional copies of 1q21 in multiple myeloma depends on the primary genetic event.

Hyperdiploidy (HRD) and specific immunoglobulin heavy locus (IGH) translocations are primary chromosomal abnormalities (CA) in multiple myeloma (MM). In this retrospective study of 794 MM patients we aimed to investigate clinical features and common CA including gain(1q) in separate subgroups defined by primary CA. In the entire group, we confirmed that gain(1q) was associated with short time to next treatment and adverse overall survival (OS).

H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts.

Background: H3K27ac histone acetylome changes contribute to the phenotypic response in heart diseases, particularly in end-stage heart failure. However, such epigenetic alterations have not been systematically investigated in remodeled non-failing human hearts. Therefore, valuable insight into cardiac dysfunction in early remodeling is lacking.

Patients with double/triple copy number gains on C-MYC, BCL2, and/or BCL6 treated with standard chemotherapy have a similarly poor prognosis than those with high-grade B cell lymphoma with C-MYC and BCL2 and/or BCL6 rearrangements: a single-center experience on a consecutive cohort of large B cell lymphomas.

High-grade B cell lymphomas with rearrangements on C-MYC and BCL2 and/or BCL6 (HGBL with MYC and BCL2 and/or Bcl6 rearrangement) are associated with worse clinical outcomes and thus were introduced as a separate new category in the recently updated WHO classification. From 2012 to 2016, we analyzed a consecutive cohort of large B cell lymphomas (LBCLs) for C-MYC, BCL2, and BCL6 rearrangements and correlated our results with clinical-pathological parameters. Ten of 78 (13%) cases had a C-MYC and BCL2 and/or BCL6 rearrangement, so-called double or triple hit (DH), while double/triple copy number gains (CNGs) were found in eight (10%) patients.

Cardiomyocyte Specific Deletion of ADAR1 Causes Severe Cardiac Dysfunction and Increased Lethality.

Adenosine deaminase acting on RNA 1 (ADAR1) is a double-stranded RNA-editing enzyme that is involved in several functions including the deamination of adenosine to inosine, RNA interference (RNAi) mechanisms and microRNA (miRNA) processing, rendering ADAR1 essential for life. To investigate whether maintenance of ADAR1 expression is required for normal myocardial homeostasis, we bypassed the early embryonic lethality of ADAR1-null mice through the use of a tamoxifen-inducible Cre recombinase under the control of the cardiac-specific α-myosin heavy chain promoter (αMHC). Targeted ADAR1 deletion in adult mice caused a significant increase in lethality accompanied by severe ventricular remodeling and quick and spontaneous cardiac dysfunction, induction of stress markers and overall reduced expression of miRNAs.

Complementing clinical cancer registry data with patient reported outcomes: A feasibility study on routine electronic patient-reported outcome assessment for the Austrian Myelome Registry.

Objectives: Routinely assessed patient-reported outcomes (PROs), such as quality of life (QOL), are important to supplement clinical cancer data but requires rigorous implementation. This study aims at depicting the implementation procedure and evaluating the feasibility of routine electronic PRO monitoring (ePRO) for collecting data supplementing the Austrian Myeloma Registry (AMR).

Methods: Integration of ePRO monitoring into clinical routine was planned according to the Replicating Effective Programs framework.

One-fits-all pretreatment protocol facilitating Fluorescence In Situ Hybridization on formalin-fixed paraffin-embedded, fresh frozen and cytological slides.

Background: The Fluorescence In Situ Hybridization (FISH) technique is a very useful tool for diagnostic and prognostic purposes in molecular pathology. However, clinical testing on patient tissue is challenging due to variables of tissue processing that can influence the quality of the results. This emphasizes the necessity of a standardized FISH protocol with a high hybridization efficiency.

Modifying Graft-versus-Host Disease in a Humanized Mouse Model by Targeting Macrophages or B-Cells.

Humanized mouse models can well be modified to study specific aspects of Graft-versus-Host Disease (GvHD). This paper shows the results of both macrophage depletion and (early) B-cell depletion in a humanized mouse model using RAG2 c mice injected with HuPBMCs. Macrophage depletion showed a significant decrease in survival and also lead to a change in the histomorphology of the xenogeneic reaction.

The Translational Landscape of the Human Heart.

Gene expression in human tissue has primarily been studied on the transcriptional level, largely neglecting translational regulation. Here, we analyze the translatomes of 80 human hearts to identify new translation events and quantify the effect of translational regulation. We show extensive translational control of cardiac gene expression, which is orchestrated in a process-specific manner.

High-beta/low-gamma frequency activity reflects top-down predictive coding during a spatial working memory test.

Numerous mental health disorders are characterized by cognitive impairments that result in poor vocational and social outcomes. Among the cognitive domains commonly affected, working memory deficits have been noted in patients with attention-deficit/hyperactivity disorder (Martinussen et al. in J Am Acad Child Adolesc Psychiatry 44:377-384, 2005), post-traumatic stress disorder (Honzel et al.

Clinical versus histological grading in the assessment of cutaneous graft versus host disease.

Background: Skin biopsies are often used in daily practice for the diagnosis of acute (aGvHD) or chronic graft versus host disease (cGvHD). With the latest understanding in pathogenesis and new National Institute of Health (NIH) classifications for aGvHD and cGvHD, there is a need to evaluate the current prognostic value of histological grading cutaneous GvHD and its correlation to the clinical grade.

Methods: In a retrospective study with 120 skin biopsies (all taken for suspected GvHD) from 110 patients (all classified according to the NIH), biopsies were revised and graded, blinded for clinical information, for either acute of chronic features.

Therapeutic Delivery of miR-148a Suppresses Ventricular Dilation in Heart Failure.

Heart failure is preceded by ventricular remodeling, changes in left ventricular mass, and myocardial volume after alterations in loading conditions. Concentric hypertrophy arises after pressure overload, involves wall thickening, and forms a substrate for diastolic dysfunction. Eccentric hypertrophy develops in volume overload conditions and leads wall thinning, chamber dilation, and reduced ejection fraction.