Investigating Moral Distress in Clinical Research Professionals-A Deep Dive into Troubled Waters.

Moral distress occurs when professionals are constrained from taking what they believe to be ethically appropriate actions or are forced to take actions they believe are ethically inappropriate, challenging their professional identities and representing systems-level issues within organizations. Moral distress has been recognized in a variety of health care-related fields; however, the phenomenon is still comparatively unexplored among clinical research professionals (CRPs). In this qualitative study, we interviewed ten CRPs to unearth root causes of moral distress in this ethically unique profession.

Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution.

Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cell types and their heterogeneity within the human liver, but the spatial organization at single-cell resolution has not yet been described. Here we apply multiplexed error robust fluorescent in situ hybridization (MERFISH) to map the zonal distribution of hepatocytes, spatially resolve subsets of macrophage and mesenchymal populations, and investigate the relationship between hepatocyte ploidy and gene expression within the healthy human liver. Integrating spatial information from MERFISH with the more complete transcriptome produced by single-nucleus RNA sequencing (snRNA-seq), also reveals zonally enriched receptor-ligand interactions.

International multicenter validation of AI-driven ultrasound detection of ovarian cancer.

Ovarian lesions are common and often incidentally detected. A critical shortage of expert ultrasound examiners has raised concerns of unnecessary interventions and delayed cancer diagnoses. Deep learning has shown promising results in the detection of ovarian cancer in ultrasound images; however, external validation is lacking.

Sun Exposure and Type 2 Diabetes Mellitus: A Prospective Follow-up Cohort Study from Southern Sweden.

Background/aim: An inverse association exists between type 2 diabetes mellitus (T2DM) and both plasma vitamin D levels and sun exposure, but vitamin D supplementation does not reduce the incidence. We sought to assess whether there is a dose-dependency in the association between sun exposure and T2DM.

Patients And Methods: The melanoma in Southern Sweden (MISS) cohort is comprised of one thousand women without cancer from age groups between 25 and 64, drawn from the Southern Swedish Population Registry of 1990 by random selection.

Phase 2 Trial of Topical Application of the Hedgehog Inhibitor Patidegib in Patients With Gorlin Syndrome.

Background: Patients with Gorlin (basal cell nevus) syndrome (GS) have numerous phenotypic abnormalities due to over-activity of the hedgehog (HH) signaling pathway, most commonly due to a heritable mutation in the PTCH1 gene, which encodes a major inhibitor of this pathway. HH inhibitors (HHi) taken orally can reverse some of the manifestations, most prominent of which is the development of numerous cutaneous basal cell carcinomas (BCCs). In order to improve the benefit:risk ratio, we have developed a gel containing a small cyclopamine-derived molecule that can be applied topically in expectation that this mode of delivery can reduce the burden of BCCs without producing the systemic adverse effects that cause patients to stop treatment with oral HHis.

Couple-Focused Smartphone Intervention to Reduce Problem Drinking: Pilot Randomized Control Trial.

Background: Alcohol use disorder is among the most pervasive substance use disorders in the United States, with a lifetime prevalence of 30%. Recommended treatment options include evidence-based behavioral interventions; smartphone-based interventions confer a number of benefits such as portability, continuous access, and stigma avoidance; and research suggests that interventions involving couples may outperform those for patients only. In this context, a behavioral intervention delivered to couples through smartphones may serve as an effective adjunct to alcohol use disorder treatment.

Precision-cut liver slices as an ex vivo model to evaluate antifibrotic therapies for liver fibrosis and cirrhosis.

Background: Considering the lack of successful treatment options and poor prognosis for cirrhosis and cirrhosis-induced HCC, new platforms to investigate antifibrotic therapies are urgently needed. Precision-cut liver slice (PCLS) is a powerful ex vivo culture model that can supplement and potentially replace the traditional models.

Methods: PCLS were prepared from 4 different murine cirrhotic models (choline-deficient, l-amino acid-defined, high-fat diet, thioacetamide, diethylnitrosamine, and carbon tetrachloride) and compared with in vivo murine experiments, in vitro hepatic stellate cells, and human cirrhotic PCLS.

Timely targeted testing for hereditary cancer syndromes - Importance of clinician-facilitated cascade testing in the first year post-diagnosis.

Objective: Cascade testing for hereditary cancer syndromes allows relatives to estimate cancer risk and pursue prevention and early detection strategies. The current paradigm relies on patient coordinated care, resulting in only one-third of relatives successfully completing testing. Studies suggest that team-based approaches, where clinicians facilitate testing, can increase uptake.

p53 Abnormal (Copy Number High) Endometrioid Endometrial Carcinoma Has a Prognosis Indistinguishable From Serous Carcinoma.

Among the 4 molecular subgroups of endometrial carcinoma, the p53 abnormal (copy number high) subgroup has the worst prognosis; however, the histologic characteristics of this subgroup are not well established. Also, it is not well established whether low-grade tumors can belong to the p53 abnormal molecular subgroup and if so, what is the prognostic significance of the p53-mutated molecular subgroup in low-grade tumors. In the current study, we included 146 p53-mutated endometrial carcinomas and performed molecular subgrouping either based on a combination of immunohistochemical studies for p53 and MMR protein expression and POLE mutation testing (81 cases) or based on array-based and sequencing-based technologies (65 cases).

Protocol of a randomized controlled trial examining psychosocial enhancement and standard medication treatment for co-occurring opioid use and mental health disorders: A half fractional factorial randomized controlled trial.

Background: The opioid epidemic disproportionately affects individuals with co-occurring opioid use and mental health disorders (COD), who often have poor treatment engagement. Multicomponent treatment models are popular solutions to increase treatment access and engagement for those with COD. Maintaining Independence and Sobriety through Systems Integration, Outreach and Networking (MISSION) is a hybrid multicomponent linkage and treatment approach that provides assertive community outreach combined with psychosocial treatment.

The educational game SonoQz improves diagnostic performance in ultrasound assessment of ovarian tumors.

Introduction: Our objective was to determine whether the educational game SonoQz can improve diagnostic performance in ultrasound assessment of ovarian tumors.

Material And Methods: The SonoQz mobile application was developed as an educational tool for medical doctors to practice ultrasound assessment, based on still images of ovarian tumors. The game comprises images from 324 ovarian tumors, examined by an ultrasound expert prior to surgery.

The role of pediatricians in the diagnosis and management of IgE-mediated food allergy: a review.

Importance: Food allergy can often cause a significant burden on patients, families, and healthcare systems. The complexity of food allergy management requires a multidisciplinary approach involving different types of healthcare providers, including allergists, dieticians, psychologists, nurses, family practitioners and, of particular relevance for this article, pediatric primary caretakers. Pediatricians may be the first-line healthcare providers for food allergy: strategies for management and guideline adherence have been highlighted.

Reliability of a qualitative movement assessment tool during a single-leg triple hop landing.

Objective: Assess inter- and intra-rater reliability of the Qualitative Analysis of Single Leg Squat (QASLS) during a single-leg triple hop landing in subjects following anterior cruciate ligament reconstruction (ACLR). Explore if differences in reliability existed between novice and experienced clinicians. Determine if QASLS scores differed between the surgical and nonsurgical limbs.

Synergistic effect of two human-like monoclonal antibodies confers protection against orthopoxvirus infection.

The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation of the vaccination campaign against the virus. Consequently, immunity against smallpox and related orthopoxviruses like Monkeypox virus gradually declines, highlighting the need for efficient countermeasures not only for the prevention, but also for the treatment of already exposed individuals. We have recently developed human-like monoclonal antibodies (mAbs) from vaccinia virus-immunized non-human primates.

Critical care nurse leaders' moral distress: A qualitative descriptive study.

Background: Unit-based critical care nurse leaders (UBCCNL) play a role in exemplifying ethical leadership, addressing moral distress, and mitigating contributing factors to moral distress on their units. Despite several studies examining the experience of moral distress by bedside nurses, knowledge is limited regarding the UBCCNL's experience.

Research Aim: The aim of this study was to gain a deeper understanding of the lived experiences of Alabama UBCCNLs regarding how they experience, cope with, and address moral distress.

Enhanced production yields of rVSV-SARS-CoV-2 vaccine using Fibra-Cel macrocarriers.

The COVID-19 pandemic has led to high global demand for vaccines to safeguard public health. To that end, our institute has developed a recombinant viral vector vaccine utilizing a modified vesicular stomatitis virus (VSV) construct, wherein the G protein of VSV is replaced with the spike protein of SARS-CoV-2 (rVSV-ΔG-spike). Previous studies have demonstrated the production of a VSV-based vaccine in Vero cells adsorbed on Cytodex 1 microcarriers or in suspension.

Critical care nurse leaders addressing moral distress: A qualitative study.

Background: Moral distress (MD) occurs when clinicians are constrained from taking what they believe to be ethically appropriate actions. When unattended, MD may result in moral injury and/or suffering. Literature surrounding how unit-based critical care nurse leaders address MD in practice is limited.

Sonographic, Demographic, and Clinical Characteristics of Pre- and Postmenopausal Women with Endometrial Cancer; Results from a Post Hoc Analysis of the IETA4 (International Endometrial Tumor Analysis) Multicenter Cohort.

In this study, we conducted a comparative analysis of demographic, histopathological, and sonographic characteristics between pre- and postmenopausal women diagnosed with endometrial cancer, while also examining sonographic and anthropometric features in 'low' and 'intermediate/high-risk' cases, stratified by menopausal status. Our analysis, based on data from the International Endometrial Tumor Analysis (IETA) 4 cohort comprising 1538 women (161 premenopausal, 1377 postmenopausal) with biopsy-confirmed endometrial cancer, revealed that premenopausal women, compared to their postmenopausal counterparts, exhibited lower parity (median 1, IQR 0-2 vs. 1, IQR 1-2, = 0.

On the Relationship between Feature Selection Metrics and Accuracy.

Feature selection metrics are commonly used in the machine learning pipeline to rank and select features before creating a predictive model. While many different metrics have been proposed for feature selection, final models are often evaluated by accuracy. In this paper, we consider the relationship between common feature selection metrics and accuracy.

Precision-Cut Liver Slices as an model to evaluate antifibrotic therapies for liver fibrosis and cirrhosis.

Background: Precision-Cut Liver Slices (PCLS) are an culture model developed to study hepatic drug metabolism. One of the main benefits of this model is that it retains the structure and cellular composition of the native liver. PCLS also represents a potential model system to study liver fibrosis in a setting that more closely approximates pathology than methods.