Conformational dynamics in specialized CH zinc finger domains enable zinc-responsive gene repression in S. pombe.

Loz1 is a zinc-responsive transcription factor in fission yeast that maintains cellular zinc homeostasis by repressing the expression of genes required for zinc uptake in high zinc conditions. Previous deletion analysis of Loz1 found a region containing two tandem CH zinc-fingers and an upstream "accessory domain" rich in histidine, lysine, and arginine residues to be sufficient for zinc-dependent DNA binding and gene repression. Here we report unexpected biophysical properties of this pair of seemingly classical CH zinc fingers.

Modeling the response to interleukin-21 to inform natural killer cell immunotherapy.

Natural killer (NK) cells are emerging agents for cancer therapy. Several different cytokines are used to generate NK cells for adoptive immunotherapy including interleukin (IL)-2, IL-12, IL-15 and IL-18 in solution, and membrane-bound IL-21. These cytokines drive NK cell activation through the integration of signal transducers and activators of transcription (STAT) and nuclear factor-kappa B (NF-κB) pathways, which overlap and synergize, making it challenging to predict optimal cytokine combinations for both proliferation and cytotoxicity.

Extremely early initiation of vasopressors might not decrease short-term mortality for adults with septic shock: a systematic review and meta-analysis.

Background: The optimal timing for initiating vasopressor therapy in patients with septic shock remains unclear. This study aimed to assess the impact of early versus late vasopressor initiation on clinical outcomes.

Methods: A systematic review and meta-analysis were conducted by searching PubMed, Embase, and Cochrane databases.

Recruitment Challenges and Strategies in a Technology-Based Intervention for Dementia Caregivers: Descriptive Study.

Background: Researchers have encountered challenges in recruiting unpaid caregivers of people living with Alzheimer disease and related dementias for intervention studies. However, little is known about the reasons for nonparticipation in in-home smart health interventions in community-based settings.

Objective: This study aimed to (1) assess recruitment rates in a smart health technology intervention for caregivers of people living with Alzheimer disease and related dementias and reasons for nonparticipation among them and (2) discuss lessons learned from recruitment challenges and strategies to improve recruitment.

Cystic Echinococcus of the Liver.

Introduction: Cystic echinococcosis is a widely endemic helminthic disease caused by infection with metacestodes (larval stage) of the Echinococcus granulosus tapeworm, which is transmitted by dogs and found on every continent except Antarctica. We sought to review the life cycle, epidemiology, symptoms, diagnostic methods, and treatment of Echinococcus granulosus of the liver.

Methods: A comprehensive review was conducted using Medline/PubMed, Google Scholar, Cochrane Library, and the Web of Science accessed between 1990 and 2024.

Surveying helix 12 dynamics within constitutively active estrogen receptors using bipartite tetracysteine display.

Somatic Y537S and D538G mutations within the estrogen receptor alpha ligand-binding domain (ERα-LBD) have been linked to enhanced cell proliferation, survival, and metastases in ER-positive breast cancers. Such mutations are thought to confer ligand-independent receptor activation by increasing the flexibility of helix 12 (H12), a segment within the ERα-LBD that acts as a dynamic regulator of ERα activity. We employed bipartite tetracysteine display coupled with the biarsenical profluorophore FlAsH-EDT to monitor ligand-independent structural transitions of H12 in ERα-LBDs that include Y537S or D538G mutations.

Perceived organizational support for the treatment of opioid use disorder and its association with primary care provider treatment willingness and medication prescribing.

Introduction: Buprenorphine is a highly effective medication for opioid use disorder (MOUD; OUD), which can be prescribed alongside naloxone in the primary care setting as part of a harm reduction approach to OUD. Despite this potential, implementation challenges have limited adoption of MOUD. To address barriers at the organizational level, we need better tools to measure perceived organizational support for the treatment of OUD and use of MOUD in the primary care setting.

Different forms of stigma and rural primary care professionals' willingness to prescribe buprenorphine.

Introduction: Buprenorphine and other medications for opioid use disorder (MOUD) are highly effective but substantially under prescribed in the rural United States. Among the most cited barriers to buprenorphine prescribing is stigma, yet little progress has been made in developing successful strategies to reduce stigma and increase access to life-saving medication. One of the key challenges to developing successful implementation strategies is understanding the different types of stigma that limit implementation.

Regulation of NLRP3/TRIM family signaling in gut inflammation and colorectal cancer.

CRC (Colorectal cancer) ranks among the most prevalent tumors in humans and remains a leading cause of cancer-related mortality worldwide. Numerous studies have highlighted the connection between inflammasome over-activation and the initiation and progression of CRC. The activation of the NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome is dependent on the nuclear NF-kβ (Nuclear Factor kappa-light-chain-enhancer of activated B cells) pathway, leading to the maturation and release of inflammatory cytokines such as IL-1ß (Interleukin 1 beta) and IL-18 (Interleukin 18).

Family functioning in adolescents and young adults with differences of sex development.

Objective: Family functioning influences various psychosocial outcomes for individuals with pediatric chronic health conditions (e.g., Leeman, J.

Evaluation of hazardous substances emitted during mask use.

This study evaluated the inhalation of mask-derived materials by simulating real breathing conditions and examined how the amount of inhaled materials varies with breathing flow rate and duration. Three types of non-certified reusable masks and two types of certified disposable masks were selected. For each mask, five different hazardous materials were captured and analyzed in three replicates with two breathing flow rates of 30 L/min and 85 L/min and two breathing time combinations of 15 min and 60 min.

Development of the Big Ten Academic Alliance Collaborative for Women in Medicine and Biomedical Science: "We Built the Airplane While Flying It".

Women-identifying and women+ gender faculty (hereto described as women+ faculty) face numerous barriers to career advancement in medicine and biomedical sciences. Despite accumulating evidence that career development programming for women+ is critical for professional advancement and well-being, accessibility of these programs is generally limited to small cohorts, only offered to specific disciplines, or otherwise entirely unavailable. Opportunities for additional, targeted career development activities are imperative in developing and retaining women+ faculty.

"I Won't Put Myself or My Family Through That": Decision Preferences, Family Experiences, and Kidney Disease Decision-Making.

Background And Objectives: Chronic kidney disease (CKD) is a major public health concern that uniquely impacts older Black Americans, a population also likely to have family members also diagnosed with CKD. This study aimed to (1) describe how participants viewed their decision preferences considering the experiences of family, and friends previously diagnosed with CKD, and (2) to understand how these social complexities informed their own decisions for future CKD care.

Research Design And Methods: Utilizing a phenomenologically-informed approach, this study explored participants' perceptions of how patients and their family members' experiences with CKD influenced treatment-related decision-making.

Evaluating Clinician Experience in Health Care Transition: Results From Six Health Systems.

Purpose: There is a paucity of evidence examining clinician experiences with structured health-care transition (HCT) programs. Among HCT Learning Collaborative participants, this study describes clinician experiences with implementation of a structured HCT process: Got Transition's 6 Core Elements.

Methods: Representative members from 6 health systems designed a survey to collect clinician feedback regarding HCT and demographic and practice information.

AGA Clinical Practice Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation in At-Risk Individuals.

Background & Aims: Hepatitis B reactivation (HBVr) can occur due to a variety of immune-modulating exposures, including multiple drug classes and disease states. Antiviral prophylaxis can be effective in mitigating the risk of HBVr. In select cases, clinical monitoring without antiviral prophylaxis is sufficient for managing the risk of HBVr.

TARGETING LUNG HEME IRON BY AEROSOL HEMOPEXIN ADMINSTRATION IN SICKLE CELL DISEASE PULMONARY HYPERTENSION.

Lung tissue from human patients and murine models of sickle cell disease pulmonary hypertension (SCD-PH) show perivascular regions with excessive iron accumulation. The iron accumulation arises from chronic hemolysis and extravasation of hemoglobin (Hb) into the lung adventitial spaces, where it is linked to nitric oxide depletion, oxidative stress, inflammation, and tissue hypoxia, which collectively drive SCD-PH. Here, we tested the hypothesis that intrapulmonary delivery of hemopexin (Hpx) to the deep lung is effective at scavenging heme-iron and attenuating the progression of SCD-PH.

Melanocortin 5 receptor signaling protects against podocyte injury in proteinuric glomerulopathies.

Melanocortin therapeutics, exemplified by adrenocorticotropic hormone, have a proven steroidogenic-independent anti-proteinuric and glomerular protective effect. The biological functions of melanocortins are mediated by melanocortin receptors (MCR), including MC1R, which recent studies have shown to protect against glomerular disease. However, the role of other MCRs like MC5R is unknown.

Outcomes of Colectomy for Nonmalignant Polyps and Colon Cancer: A Propensity Score-Matched Analysis.

Introduction: In the United States, while most nonmalignant polyps are effectively treated through endoscopic removal, colectomy remains a treatment option for selected cases of nonmalignant polyps (NMPs) and colon cancer. This study aimed to compare postoperative outcomes for colectomies in these two conditions, hypothesizing similar complication rates.

Methods: We conducted a retrospective review of the American College of Surgeons National Surgical Quality Improvement Program database from 2015 to 2021, including patients who underwent elective colectomies for colon cancer or NMPs.

Health insurance expansion and academic production: The case of Medicare Part D legislation.

Understanding how market demand influences academic research is crucial for comprehending the innovation process and informing policy decisions. This study examines the impact of the 2003 Medicare Part D legislation on biomedical journal article production across diseases. Using a difference-in-differences framework, together with a sample of over 2 million original research articles published between 1987 and 2015 sourced from PubMed database, I find a relatively 18.