How I Treat Higher-Risk MDS.

Myelodysplastic syndromes/neoplasms (MDS) are a widely heterogenous group of myeloid malignancies characterized by morphologic dysplasia, a defective hematopoiesis, and recurrent genetic abnormalities. The original and revised International Prognostic Scoring Systems (IPSS) have been used to risk-stratify patients with MDS to guide treatment strategies. In higher-risk MDS, the therapeutic approach is geared toward delaying leukemic transformation and prolonging survival.

Development of the Lee Symptom Scale-Skin Sclerosis for chronic GVHD-associated sclerosis.

Sclerosis is a highly morbid manifestation of chronic GVHD (cGVHD), associated with distressing symptoms and significant long-term disability. A patient-reported outcome measure (PRO) for cGVHD-associated sclerosis is essential to advance therapeutic trials. We aimed to develop a PRO for adults with cGVHD-associated sclerosis and evaluate and refine its content validity.

Antiseizure Medications in Poststroke Seizures: A Systematic Review and Network Meta-Analysis.

Background And Objectives: The most effective antiseizure medications (ASMs) for poststroke seizures (PSSs) remain unclear. We aimed to determine outcomes associated with ASMs in people with PSS.

Methods: We systematically searched electronic databases for studies on patients with PSS on ASMs.

Spontaneous Anthropocentric Language Use in University Students' Explanations of Biological Concepts Varies by Topic and Predicts Misconception Agreement.

Previous research has shown that students employ intuitive thinking when understanding scientific concepts. Three types of intuitive thinking-essentialist, teleological, and anthropic thinking-are used in biology learning and can lead to misconceptions. However, it is unknown how commonly these types of intuitive thinking, or cognitive construals, are used spontaneously in students' explanations across biological concepts and whether this usage is related to endorsement of construal-consistent misconceptions.

Naturally occurring variation in a cytochrome P450 modifies thiabendazole responses independently of beta-tubulin.

Widespread anthelmintic resistance has complicated the management of parasitic nematodes. Resistance to the benzimidazole (BZ) drug class is nearly ubiquitous in many species and is associated with mutations in beta-tubulin genes. However, mutations in beta-tubulin alone do not fully explain all BZ resistance.

Acceptability of a dapivirine levonorgestrel vaginal ring in two Phase 1 trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019): Implications for multipurpose prevention technology development.

End-user feedback early in product development is important for optimizing multipurpose prevention technologies for HIV and pregnancy prevention. We evaluated the acceptability of the 90-day dapivirine levonorgestrel ring (DPV-LNG ring) used for 14 days compared to a dapivirine-only ring (DVR-200mg) in MTN-030/IPM 041 (n = 23), and when used for 90 days cyclically or continuously in MTN-044/IPM 053/CCN019 (n = 25). We enrolled healthy, non-pregnant, HIV-negative women aged 18-45 in Pittsburgh, PA and Birmingham, AL (MTN-030 only).

Digital tools and technologies used in food fortification: A scoping review.

Food fortification (i.e., industrial fortification and biofortification) increases the micronutrient content of foods to improve population nutrition.

FDA Approval Summary: Tovorafenib for Relapsed or Refractory BRAF-altered Pediatric Low-Grade Glioma.

On April 23, 2024, FDA granted accelerated approval to tovorafenib, a type II RAF kinase inhibitor, for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. Efficacy was evaluated in FIREFLY-1 (NCT04775485), a single-arm, open-label, multicenter trial that enrolled patients 6 months to 25 years of age with relapsed or refractory pLGG with an activating BRAF alteration who had received prior systemic therapy. The major efficacy outcome measure was radiologic overall response rate (ORR), defined as the proportion of patients with complete response, partial response, or minor response as determined by blinded independent central review using Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria.

Injury induced endotheliopathy: overview, diagnosis, and management.

Purpose Of Review: This review aims to examine recent advances in the understanding of injury-induced endotheliopathy and therapeutics to mitigate its development in critically injured patients.

Recent Findings: Clinical studies have clearly demonstrated that syndecan-1 ectodomains can be found in circulation after various types of trauma and injury and correlates with worse outcomes. As the mechanisms of endotheliopathy are better understood, pathologic hyperadhesive forms of von Willebrand factor, along with a relative deficiency of its cleaving enzyme, a disintegrin and metalloprotease with thrombospondin type I motifs, member 13 (ADAMTS13), have emerged as additional biomarkers.

Preferred and Actual Location of Death in Adolescents and Young Adults With Cancer.

Importance: Adolescent and young adult (AYA) patients with advanced cancer often die in hospital settings. Data characterizing the degree to which this pattern of care is concordant with patient goals are sparse.

Objective: To evaluate the extent of concordance between the preferred and actual location of death among AYA patients with cancer.

Knowledge and Use of Menthol-Mimicking Cigarettes Among Adults in the US.

Importance: Cigarette companies have been introducing synthetic cooling agent menthol-mimicking cigarettes into the US marketplace as menthol cigarette bans are implemented. These cigarettes may reduce the public health benefits of menthol cigarette bans.

Objective: To examine the epidemiology of the use of synthetic cooling agent menthol-mimicking cigarettes among adults in the US.

Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement.

Importance: Osteoporotic fractures are associated with psychological distress, subsequent fractures, loss of independence, reduced ability to perform activities of daily living, and death.

Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on the benefits and harms of screening for osteoporosis to prevent fractures in adults 40 years or older with no known diagnosis of osteoporosis or history of fragility fracture.

Population: Adults 40 years or older without known osteoporosis or history of fragility fractures.

Home Health Care Research for Children With Disability and Medical Complexity.

Pediatric home health care represents a vital system of care for children with disability and medical complexity, encompassing services provided by family caregivers and nonfamily home health care providers and the use of durable medical equipment and supplies. Home health care is medically necessary for the physiologic health of children with disability and medical complexity and for their participation and function within home, school, and community settings. While the study of pediatric home health care in the United States has increased in the last decade, its research remains primarily methodologically limited to observational studies.

Hair Straightener Use in Relation to Prevalent and Incident Fibroids in the Sister Study with a Focus on Black Women.

Background: Uterine fibroids disproportionately affect Black women, and exposure to chemicals from hair relaxers or straighteners ("straighteners") may contribute to fibroid development.

Objectives: We examined the association between straightener use and prevalent young-onset uterine fibroids (diagnosed before age 36 y), as well as incident fibroids (diagnosed age 36-60 y), with a focus on Black women. We also examined differences in associations across birth cohorts as proxies for formulation changes.

Design and implementation of optics for the experiment for cryogenic large-aperture intensity mapping (EXCLAIM).

This work describes the design and implementation of optics for EXCLAIM, the EXperiment for Cryogenic Large-Aperture Intensity Mapping. EXCLAIM is a balloon-borne telescope that will measure integrated line emission from carbon monoxide at redshifts z < 1 and ionized carbon ([CII]) at redshifts z = 2.5 - 3.

A One-Dimensional Energy Balance Model Parameterization for the Formation of CO Ice on the Surfaces of Eccentric Extrasolar Planets.

Eccentric planets may spend a significant portion of their orbits at large distances from their host stars, where low temperatures can cause atmospheric CO to condense out onto the surface, similar to the polar ice caps on Mars. The radiative effects on the climates of these planets throughout their orbits would depend on the wavelength-dependent albedo of surface CO ice that may accumulate at or near apoastron and vary according to the spectral energy distribution of the host star. To explore these possible effects, we incorporated a CO ice-albedo parameterization into a one-dimensional energy balance climate model.

A sensitivity analysis of methodological variables associated with microbiome measurements.

The experimental methods employed during metagenomic sequencing analyses of microbiome samples significantly impact the resulting data and typically vary substantially between laboratories. In this study, a full factorial experimental design was used to compare the effects of a select set of methodological choices (sample, operator, lot, extraction kit, variable region, and reference database) on the analysis of biologically diverse stool samples. For each parameter investigated, a main effect was calculated that allowed direct comparison both between methodological choices (bias effects) and between samples (real biological differences).

Target an arbitrary probability of response using weighted staircase procedures.

Threshold estimation procedures are widely used to measure the stimulus level corresponding to a specified probability of response. The weighted up-and-down procedure, familiar to many due to its use in standard pure-tone audiometry, allows the experimenter to target any probability of response by using different ascending and descending step sizes. Unfortunately, thresholds have a signed mean error that made using weighted staircases inadvisable.

Reverse transcriptase inhibitors diminish systemic proinflammatory responses to bacterial pathogens.

Bacterial infections can induce exuberant immune responses that can damage host tissues. Previously, we demonstrated that systemic infection in mice causes tissue damage in the liver. This liver necrosis is associated with the expression of endogenous retroviruses, chromosomally integrated retroviruses that encode a reverse transcriptase.

Faculty rewards from course-based undergraduate research experiences (CURE) in biochemistry.

In recent years, there has been an increase in the number of course-based undergraduate research experience (CURE) courses. These courses provide research opportunities for many more students than are typically exposed to traditional independent research experiences, including women, historically underrepresented groups in science, and non-traditional students. However, the benefits for faculty who teach CURE courses have been less well documented, potentially discouraging faculty from offering such courses.

Optimizing Exposure Measures in Large-Scale Household Air Pollution Studies: Results from the Multicountry HAPIN Trial.

Repeated measurements of household air pollution may provide better estimates of average exposure but can add to costs and participant burden. In a randomized trial of gas versus biomass cookstoves in four countries, we took supplemental personal 24-h measurements on a 10% subsample for mothers and infants, interspersed between protocol samples. Mothers had up to five postrandomization protocol measurements over 16 months, while infants had three measurements over one year.

Clinical criteria for limbic-predominant age-related TDP-43 encephalopathy.

Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course.