KMT2A degradation is observed in decitabine-responsive acute lymphoblastic leukemia cells.

Hypermethylation of tumor suppressor genes is a hallmark of leukemia. The hypomethylating agent decitabine covalently binds, and degrades DNA (cytosine-5)-methyltransferase 1 (DNMT1). Structural similarities within DNA-binding domains of DNMT1, and the leukemic driver histone-lysine N-methyltransferase 2A (KMT2A) suggest that decitabine might also affect the latter.

Impact of non-contrast-enhanced imaging input sequences on the generation of virtual contrast-enhanced breast MRI scans using neural network.

Objective: To investigate how different combinations of T1-weighted (T1w), T2-weighted (T2w), and diffusion-weighted imaging (DWI) impact the performance of virtual contrast-enhanced (vCE) breast MRI.

Materials And Methods: The IRB-approved, retrospective study included 1064 multiparametric breast MRI scans (age: 52 ± 12 years) obtained from 2017 to 2020 (single site, two 3-T MRI). Eleven independent neural networks were trained to derive vCE images from varying input combinations of T1w, T2w, and multi-b-value DWI sequences (b-value = 50-1500 s/mm).

Psychometric Assessment of Anxiety Measures in a Pilot Study of African American Patients with Obstructive Sleep Apnea.

African American patient populations are disproportionately diagnosed with severe obstructive sleep apnea (OSA) compared to non-Hispanic white adults. Research suggests a link between OSA and anxiety. However, OSA and anxiety symptoms may present differently across minority groups.

Cohort Builder: A Software Pipeline for Generating Patient Cohorts with Predetermined Baseline Characteristics from Medical Records and Raw Ophthalmic Imaging Data.

In clinical research, the analysis of patient cohorts is a widely employed method for investigating relevant healthcare questions. The ability to automatically extract large-scale patient cohorts from hospital systems is vital in order to unlock the potential of real-world clinical data, and answer pivotal medical questions through retrospective research studies. However, existing medical data is often dispersed across various systems and databases, preventing a systematic approach to access and interoperability.

Equivalent immunogenicity across three RSVpreF vaccine lots in healthy adults 18-49 years of age: Results of a randomized phase 3 study.

Background: Bivalent RSV prefusion F subunit vaccine (RSVpreF), comprised of equal quantities of stabilized prefusion F antigens from the major circulating subgroups (RSV A, RSV B), is licensed for prevention of RSV-associated lower respiratory tract illness (LRTI) in older adults and for maternal vaccination for prevention of RSV-associated LRTI in infants. To support licensure and large-scale manufacturing, this lot consistency study was conducted to demonstrate equivalence in immunogenicity across 3 RSVpreF lots.

Methods: This phase 3, multicenter, parallel-group, placebo-controlled, randomized (1:1:1:1), double-blind study evaluated immunogenicity, safety, and tolerability of RSVpreF in healthy 18-49-year-old adults.

Enteral N-acetylcysteine to reduce serum cobalt concentrations secondary to prosthetic knee-associated metallosis: A case report.

Purpose: Cobalt metallosis is a rare but dangerous complication of total joint arthroplasty resulting from deterioration of the joint leading to metal-on-metal friction and breakdown. Potential manifestations vary in severity and include dilated cardiomyopathy, thyroid dysfunction, cognitive disturbances, neuropathy, fatigue, and weakness. The therapeutic role of N-acetylcysteine in metallosis has been investigated due to its ability to chelate with heavy metal ions, such as cobalt and chromium.

A multi-institutional feasibility study of intra-arterial chemotherapy in children with retinoblastoma. A Children's Oncology Group study (COG ARET12P1).

Background: Intra-arterial chemotherapy (IA) as a treatment to salvage the eye with advanced retinoblastoma is increasingly utilized based on successes reported by institutions around the world mainly through retrospective studies.

Objective: To study the feasibility of delivering melphalan directly into the ophthalmic artery in a multi-institutional prospective study in children with newly diagnosed unilateral group D retinoblastoma.

Methods: The Children's Oncology Group (COG) initiated study ARET12P1 in 2014 and was open to nine institutions.

A Phase 2 Extension Study Evaluating the Immunogenicity, Safety, and Tolerability of 3 or 4 Doses of a Clostridioides difficile Vaccine in Healthy US Adults Aged 65 to 85 Years.

Background: This phase 2 extension explored the long-term antibody persistence of an investigational Clostridioides difficile vaccine and the safety, tolerability, and immunogenicity of dose 4 approximately 12 months post-dose 3.

Methods: One year post-dose 3, healthy US 65- to 85-year-olds (N = 300) were randomized to dose 4 of vaccine at previously received antigen levels (100 or 200 μg) or placebo. Assessments included safety and percentages of participants achieving neutralizing antibody titers above prespecified thresholds (≥219 and ≥2586 neutralization units/mL for toxins A and B, respectively).

Incorporating Metacognitive Strategy Training Into Semantic Treatment Promotes Restitutive and Substitutive Gains in Naming: A Single-Subject Investigation.

Purpose: This study tested the effectiveness of a modified semantic feature analysis (SFA) treatment protocol that incorporated metacognitive strategy training (MST). Regarding its restitutive component, SFA most reliably results in improved word retrieval for treated items and untreated, semantically related items, but evidence of response generalization is often small/inconsistent. Regarding its substitutive component, SFA is thought to facilitate successful communication via habituation of the SFA circumlocution strategy.

Vincristine/irinotecan/temsirolimus upfront window treatment of high-risk hepatoblastoma: A report from the Children's Oncology Group AHEP0731 Study Committee.

Background: Survival for children with metastatic hepatoblastoma (HB) remains suboptimal. We report the response rate and outcome of two courses of vincristine/irinotecan/temsirolimus (VIT) in children with high-risk (HR)/metastatic HB.

Procedures: Patients with newly diagnosed HB received HR window chemotherapy if they had metastatic disease or a serum alpha-fetoprotein (AFP) level less than 100 ng/mL.

Underreporting of patient-reported outcomes in cystic fibrosis randomized controlled trials using CONSORT-PRO and RoB 2.0.

Background: Patient-reported outcomes (PROs) are increasingly used in randomized controlled trials (RCTs) to foster patient-centered healthcare. The aim of this investigation was to assess the completeness of reporting of PROs in RCTs pertaining to cystic fibrosis (CF).

Methods: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for RCTs concerning CF that included PROs as a primary or secondary outcome.

Reporting of Patient-Reported Outcome Measures in Randomized Controlled Trials on Shoulder Rotator Cuff Injuries Is Suboptimal and Requires Standardization.

Purpose: To evaluate the completeness of patient-reported outcomes (PROs) reporting using Consolidated Standards of Reporting Trials Patient-Reported Outcome (CONSORT-PRO) in randomized controlled trials (RCTs) involving rotator cuff injuries.

Methods: We performed a comprehensive search of MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for published RCTs focused on rotator cuff injuries that included at least one PRO measure. We included RCTs published from 2006 to 2020.

Effective tumor cell abrogation via Venetoclax-mediated BCL-2 inhibition in KMT2A-rearranged acute B-lymphoblastic leukemia.

Dysregulation of the intrinsic BCL-2 pathway-mediated apoptosis cascade is a common feature of hematological malignancies including acute B-lymphoblastic leukemia (B-ALL). The KMT2A-rearranged high-risk cytogenetic subtype is characterized by high expression of antiapoptotic protein BCL-2, likely due to the direct activating binding of KMT2A fusion proteins to the BCL2 gene. The BCL-2 inhibitor venetoclax (VEN) has proven great clinical value in other blood cancers, however, data on B-ALL is sparse and past studies have not so far described the effects of VEN on gene and protein expression profiles.

Prospective Evaluation of Coronavirus Disease 2019 (COVID-19) Vaccine Responses Across a Broad Spectrum of Immunocompromising Conditions: the COVID-19 Vaccination in the Immunocompromised Study (COVICS).

Background: We studied humoral responses after coronavirus disease 2019 (COVID-19) vaccination across varying causes of immunodeficiency.

Methods: Prospective study of fully vaccinated immunocompromised adults (solid organ transplant [SOT], hematologic malignancy, solid cancers, autoimmune conditions, human immunodeficiency virus [HIV]) versus nonimmunocompromised healthcare workers (HCWs). The primary outcome was the proportion with a reactive test (seropositive) for immunoglobulin G to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain.

Pediatric Aural Foreign Body Extraction: Comparison of Efficacies Among Clinical Settings and Retrieval Methods.

Objectives: To compare the efficacy of aural foreign body (FB) extractions among medical care settings and determine if certain methods of extraction resulted in higher failure rates and procedural complications.

Study Design: Case series with chart review.

Setting: Emergency departments (EDs), urgent cares (UCs), pediatric primary care providers (PCPs), and otolaryngologists (ENTs).

Optimization of Nursing-Specific Flu Alerts.

Clinical decision support interventions, such as alerts and reminders, can improve clinician compliance with practice guidelines and patient outcomes. Alerts that trigger at inappropriate times are often dismissed by clinicians, reducing desired actions rather than increasing them. A set of nursing-specific alerts related to influenza screening and vaccination were optimized so that they would "trigger" less often but function adequately to maintain institutional flu vaccination compliance.

Robust Fabrication of Polymeric Nanowire with Anodic Aluminum Oxide Templates.

Functionalization of a surface with biomimetic nano-/micro-scale roughness (wires) has attracted significant interests in surface science and engineering as well as has inspired many real-world applications including anti-fouling and superhydrophobic surfaces. Although methods relying on lithography include soft-lithography greatly increase our abilities in structuring hard surfaces with engineered nano-/micro-topologies mimicking real-world counterparts, such as lotus leaves, rose petals, and gecko toe pads, scalable tools enabling us to pattern polymeric substrates with the same structures are largely absent in literature. Here we present a robust and simple technique combining anodic aluminum oxide (AAO) templating and vacuum-assisted molding to fabricate nanowires over polymeric substrates.

Dexmedetomidine in Adult Patients in Cardiac Surgery Critical Care: An Evidence-Based Review.

Although several options are available for postoperative sedation in the intensive care unit, the selective α2-adrenoceptor agonist dexmedetomidine may offer advantages for patients after cardiac surgery. The author conducted a review of the literature on the use of dexmedetomidine in the cardiac surgery population to determine possible advantages and disadvantages in this patient population. Although the use of dexmedetomidine has not been conclusively shown to change overall morbidity and mortality and may be associated with higher drug cost, its other demonstrated effects offer advantages for postoperative cardiac surgery patients that other forms of sedation cannot match.

Evidence-based supported employment for people with psychiatric disabilities in Australia: Progress in the past 15 years.

Objective: This report summarizes the major developments in Australia since the first introduction of Individual Placement and Support (IPS) in 2005 in order to outline the current situation and discuss future challenges and opportunities.

Method: Using an informal snowball sampling method, all those known to be involved in IPS implementations in Australia in the last 5 years were contacted.

Results: The program has expanded from 2 full-time employment specialists in 2005 to 87.

Lactation Consultation Sustains Breast Milk Intake in Infants With Cystic Fibrosis.

Guidelines recommend breastfeeding in cystic fibrosis (CF) but breastfeeding rates decline rapidly in CF. We initiated a quality improvement project to improve breastfeeding in CF by incorporating International Board-Certified Lactation Consultants (IBCLC) into the initial CF-diagnosis visit to support mothers who were breastfeeding at diagnosis. In the preintervention group, only 8/14 (57%) continued to provide breast milk after the first visit, whereas postintervention, 16/17 (94%) mothers continued to do so (P = 0.

The Use of Prayer During Life-Threatening Illness: A Connectedness to God, Inner-Self, and Others.

To explore how prayers were used as expressions of spirituality among community-dwelling African Americans in response to life-threatening illness. Fifty-eight older African American adults residing in the Southeastern US participated in a qualitative descriptive study. Through prayers, participants requested the strength to endure, protection, healing and expressed gratitude.

A Rodent Model of Anxiety: The Effect of Perinatal Immune Challenges on Gastrointestinal Inflammation and Integrity.

Objectives: Gastrointestinal (GI) inflammation and GI integrity deficits are common comorbidities of neuropsychiatric disorders. Ongoing research suggests that these aberrations may be contributing to heightened immune signals that have the potential to disrupt neuronal homeostasis and exacerbate behavioural deficits. The current study aimed to determine whether the well-characterized animal model of neuropsychopathology, the maternal immune activation (MIA) model, produced GI inflammation and integrity disruptions in association with anxiety-like behaviour.