Analysis of Repeat Hepatitis C Viremia After Sustained Virologic Response in a Large Cohort of U.S. Veterans.

Background: Chronic hepatitis C virus (HCV) infection affects >1% of the U.S. population, higher among U.

The Evolution of Treatment-Free Remission.

One of the most remarkable achievements of the TKI era has been the capacity to induce deep molecular remissions that are sustainable off therapy in chronic myeloid leukemia (CML) patients - treatment-free remission (TFR). TFR was first described in a handful of patients within 3-4 years of imatinib approval. In 2004 TFR was tested in a small French pilot study, followed soon after by the French STIM and Australasian TWISTER studies.

The β Common Cytokine Receptor Family Reveals New Functional Paradigms From Structural Complexities.

Cytokines are small proteins that are critical for controlling the growth and activity of hematopoietic cells by binding to cell surface receptors and transmitting signals across membranes. The β common (βc) cytokine receptor family, consisting of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 cytokine receptors, is an architype of the heterodimeric cytokine receptor systems. We now know that signaling by cytokine receptors is not always an "all or none" phenomenon.

Real-World Treatment Patterns and Healthcare Resource Use for Patients with Myelofibrosis: Results from the METER Study.

Myelofibrosis (MF) is a myeloproliferative neoplasm that was most commonly treated with hydroxyurea (HU) prior to approval of ruxolitinib (RUX), now the standard of care. Factors that influence changes in MF treatment in real-world settings are not well understood. The METER study (NCT05444972) was a multi-country retrospective chart review of MF treatment patterns, treatment effectiveness, and healthcare resource utilization.

Anticancer Effect of C19-Position Substituted Geldanamycin Derivatives Targeting NRF2-NQO1-activated Esophageal Squamous Cell Carcinoma.

In esophageal squamous cell carcinoma, genetic activation of NRF2 increases resistance to chemotherapy and radiotherapy, which results in a significantly worse prognosis for patients. Therefore NRF2-activated cancers create an urgent clinical need to identify new therapeutic options. In this context, we previously identified the geldanamycin family of HSP90 inhibitors, which includes 17DMAG, to be synthetic lethal with NRF2 activity.

Correction: Reaching adolescents with health services: Systematic development of an adolescent health check-ups and wellbeing programme in Ghana (Y-Check, Ghana).

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

Psychosocial Interventions for Preventing Mental Health Conditions in Adolescents With Emotional Problems: A Meta-Analysis.

Mental health conditions constitute a major burden of disease for adolescents globally and can lead to significant adverse consequences. This systematic review aimed to identify if psychosocial interventions are effective in preventing mental health conditions in adolescents already experiencing emotional problems. We searched for randomized controlled trials comparing psychosocial interventions for preventing mental health conditions with care as usual in adolescents aged 10-19 who are experiencing symptoms of emotional problems.

Geldanamycin, a Naturally Occurring Inhibitor of Hsp90 and a Lead Compound for Medicinal Chemistry.

Geldanamycin remains a driver in the medicinal chemistry of heat shock protein 90 (Hsp90) inhibition, even half a century after its original isolation from nature. This Perspective focuses on the properties of the benzoquinone ring of the natural product that enable a range of functionalization reactions to take place. Therefore, inherent reactivity at C-17, where the methoxy group serves as a vinylogous ester, and at C-19 that demonstrates nucleophilic, enamide-type character toward electrophiles, and also as a conjugate acceptor to react with nucleophiles, has facilitated the synthesis of semisynthetic derivatives.

Germline genetic variants that predispose to myeloproliferative neoplasms and hereditary myeloproliferative phenotypes.

Epidemiological evidence of familial predispositions to myeloid malignancies and myeloproliferative neoplasms (MPN) has long been recognised, but recent studies have added to knowledge of specific germline variants in multiple genes that contribute to the familial risk. These variants may be common risk alleles in the general population but have low penetrance and cause sporadic MPN, such as the JAK2 46/1 haplotype, the variant most strongly associated with MPN. Association studies are increasingly identifying other MPN susceptibility genes such as TERT, MECOM, and SH2B3, while some common variants in DDX41 and RUNX1 appear to lead to a spectrum of myeloid malignancies.

CBL mutations in chronic myelomonocytic leukemia often occur in the RING domain with multiple subclones per patient: Implications for targeting.

Chronic myelomonocytic leukemia (CMML) is a rare blood cancer of older adults (3 in every 1,000,000 persons) characterized by poor survival and lacking effective mutation-specific therapy. Mutations in the ubiquitin ligase Cbl occur frequently in CMML and share biological and molecular features with a clonal disease occurring in children, juvenile myelomonocytic leukemia (JMML). Here we analyzed the clinical presentations, molecular features and immunophenotype of CMML patients with CBL mutations enrolled in a prospective Phase II clinical trial stratified according to molecular markers.

Association of hepatitis delta virus infection and hepatocellular carcinoma, hepatic decompensation, all-cause and liver-related death in a national cohort.

Background: Hepatitis Delta Virus (HDV) infection is the most severe form of chronic hepatitis. However, studies on outcomes and causes of death in a United States-born population, with primarily horizontal transmission of HDV, are lacking. The aim of this study was to conduct a national study of patients with hepatitis D to understand the natural history and outcomes compared to patients with hepatitis B virus (HBV).

Variations in antihypertensive medication treatment and blood pressure control among Veterans with HIV and existing hypertension.

Background: Hypertension is a leading risk factor for cardiovascular disease among patients living with HIV (PLWH). Understanding the predictors and patterns of antihypertensive medication prescription and blood pressure (BP) control among PLWH with hypertension (HTN) is important to improve the primary prevention efforts for this high-risk population. We sought to assess important patient-level correlates (eg, race) and inter-facility variations in antihypertension medication prescriptions and BP control among Veterans living with HIV (VLWH) and HTN.

Reaching adolescents with health services: Systematic development of an adolescent health check-ups and wellbeing programme in Ghana (Y-Check, Ghana).

Background: Routine health check-ups may improve adolescent health, but global guidelines are lacking. Phase 1 of the WHO-coordinated Y-Check Research Programme involved three African cities to co-produce a programme of adolescent health check-ups. We describe a systematic approach to developing a routine adolescent health check-ups and wellbeing programme (Y-Check) to contribute evidence on whether adolescent health check-ups should be part of routine health services in Ghana.

Identifying disease-modifying potential in myelofibrosis clinical trials.

The ultimate goal of bringing most new drugs to the clinic in hematologic malignancy is to improve overall survival. However, the use of surrogate end points for overall survival is increasingly considered standard practice, because a well validated surrogate end point can accelerate the outcome assessment and facilitate better clinical trial design. Established examples include monitoring minimal residual disease in chronic myeloid leukemia and acute leukemia, and metabolic response assessment in lymphoma.

Asciminib monotherapy as frontline treatment of chronic-phase chronic myeloid leukemia: results from the ASCEND study.

Asciminib is a myristoyl site BCR::ABL1 inhibitor approved for patients with chronic-phase chronic myeloid leukemia (CP-CML) failing ≥2 prior lines of therapy. The Australasian Leukaemia and Lymphoma Group conducted the Asciminib Evaluation in Newly Diagnosed CML study to assess efficacy of asciminib for newly diagnosed CP-CML. Patients commenced asciminib 40 mg twice daily.

Veteran's Health Administration HIV Care Continuum: 2019 vs 2022.

Background: The diagnosis-based Human Immunodeficiency Virus (HIV) Care Continuum offers a well-established framework for measuring HIV care quality. It is used by the government agencies, community organizations, and health care institutions to "guide the nation's response to HIV" and assesses HIV care from the time of HIV diagnosis through viral suppression. Our objective is to present the Veteran Health Administration's (VHA) HIV Care Continuum, assess postpandemic versus prepandemic performance, and compare VHA performance to Centers for Disease Control and Prevention-published data.

Ligify: Automated Genome Mining for Ligand-Inducible Transcription Factors.

Prokaryotic transcription factors can be repurposed into biosensors for the ligand-inducible control of gene expression, but the landscape of chemical ligands for which biosensors exist is extremely limited. To expand this landscape, we developed Ligify, a web application that leverages information in enzyme reaction databases to predict transcription factors that may be responsive to user-defined chemicals. Candidate transcription factors are then incorporated into automatically generated plasmid sequences that are designed to express GFP in response to the target chemical.

Sodium Dehydroacetate and Dehydroacetic Acid.

The Expert Panel for Cosmetic Ingredient Safety (Panel) first published a safety assessment of Sodium Dehydroacetate and Dehydroacetic Acid in 1985. The Panel previously concluded that Sodium Dehydroacetate and Dehydroacetic Acid are safe as used in the present practices of use and concentration, as stated in that report. Upon re-review in 2003, the Panel reaffirmed the original conclusion, as published in 2006.

Development of a school-based programme for mental health promotion and prevention among adolescents in Nepal and South Africa.

Introduction: Adolescence is a critical time for mental health promotion and prevention and establishing healthy behaviours. Implementing universal, school-based psychosocial interventions can improve short- and long-term health trajectories for adolescents. While these interventions may offer important opportunities for fostering skills and relationships, few school-based interventions have been developed for and tested in low- and middle-income countries (LMICs) where adolescent mental health needs may be significant and under-served.

Adolescent health and well-being check-up programme in three African cities (Y-Check): protocol for a multimethod, prospective, hybrid implementation-effectiveness study.

Background: During adolescence, behaviours are initiated that will have substantial impacts on the individual's short-term and long-term health and well-being. However, adolescents rarely have regular contact with health services, and available services are not always appropriate for their needs. We co-developed with adolescents a health and well-being check-up programme (Y-Check).

Isobutane, Isopentane, Butane, and Propane.

The Expert Panel for Cosmetic Ingredient Safety (Panel) first published the Final Report of the safety of Isobutane, Isopentane, Butane, and Propane in 1982. The Panel previously concluded that these ingredients are considered safe as cosmetic ingredients under the present conditions of concentration and use, as described in that safety assessment. Upon re-review in 2002, the Panel reaffirmed the original conclusion, as published in 2005.