A phase I study of MLN4924 and belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome.

Purpose: Relapsed and/or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome continue to have a poor prognosis with limited treatment options despite advancements in rational combination and targeted therapies. Belinostat (an HDAC inhibitor) and Pevonedistat (a NEDD8 inhibitor) have each been independently studied in hematologic malignancies and have tolerable safety profiles with limited single-agent activity. Preclinical studies in AML cell lines and primary AML cells show the combination to be highly synergistic, particularly in high-risk phenotypes such as p53 mutant and FLT-3-ITD positive cells.

Racial disparities in timing and outcomes for patients undergoing staged single ventricle palliation: a single institution report.

Background: Racial disparities in healthcare have been well documented in the United States. We hypothesise that there will be a racial variance in different clinical variables in single-ventricle patients through stages of palliation.

Materials And Methods: Retrospective single-centre study stratified all single-ventricle patients who reached stage 2 palliation by race: Black and White.

Revealing the Demographic History of the European Nightjar ().

A species' demographic history gives important context to contemporary population genetics and a possible insight into past responses to climate change; with an individual's genome providing a window into the evolutionary history of contemporary populations. Pairwise sequentially Markovian coalescent (PSMC) analysis uses information from a single genome to derive fluctuations in effective population size change over the last ~5 million years. Here, we apply PSMC analysis to two European nightjar () genomes, sampled in Northwest and Southern Europe, with the aim of revealing the demographic history of nightjar in Europe.

Clonal Evolution in 207 Cases of Refractory or Relapsed Acute Myeloid Leukemia.

Clonal evolution (CE) is a driving force behind the development and progression of acute myeloid leukemia (AML). Advances in molecular and cytogenetic assays have improved the depth and breadth of detection of CE in AML, which is defined here as a detected change in cytogenetic or molecular profile at relapsed or refractory (RR) disease. In this study, we demonstrate the clinical impact of CE in a cohort of patients with RR AML treated between 2013 and 2023.

Anticoagulation for Septic Cerebral Venous Thrombosis in Childhood.

Anticoagulation is recommended for most children with cerebral venous thrombosis (CVT) to prevent venous infarction and promote recanalization. An exception is CVT associated with head and neck infection (septic CVT), for which treatment of infection without concomitant use of anticoagulation is recommended. Despite this, the use of anticoagulation in septic CVT is controversial, and children with septic CVT are often anticoagulated due to concerns about thrombus progression and persistence despite infection treatment.

Melody Valve Implantation in the Tricuspid Position After Pediatric Heart Transplantation-A Case Report.

Tricuspid regurgitation (TR) is common after a heart transplant and is associated with worse clinical outcomes. The incidence ranges from 34% immediately after transplant to 20% by 10 years. Most patients can be managed medically; however, severe TR and symptomatic right heart failure warrant tricuspid valve replacement.

Sculpting the future: A narrative review of 3D printing in plastic surgery and prosthetic devices.

Background And Aims: The advent of 3D printing has revolutionized plastic surgery and prosthetic devices, providing personalized solutions for patients with traumatic injuries, deformities, and appearance-related conditions. This review offers a comprehensive overview of 3D printing's applications, advantages, limitations, and future prospects in these fields.

Methods: A literature search was conducted in PubMed, Google Scholar, and Scopus for studies on 3D printing in plastic surgery.

Novel tubing connectors reduce ECMO circuit thrombosis.

Background: Thrombosis within extracorporeal membrane oxygenation (ECMO) circuits is a common complication that dominates clinical management of patients receiving mechanical circulatory support. Prior studies have identified that over 80% of circuit thrombosis can be attributed to tubing-connector junctions.

Methods: A novel connector was designed that reduces local regions of flow stagnation at the tubing-connector junction to eliminate a primary source of ECMO circuit thrombi.

Sorption of Soil Carbon Dioxide by Biochar and Engineered Porous Carbons.

CO is 45 to 50 times more concentrated in soil than in air, resulting in global diffusive fluxes that outpace fossil fuel combustion by an order of magnitude. Despite the scale of soil CO emissions, soil-based climate change mitigation strategies are underdeveloped. Existing approaches, such as enhanced weathering and sustainable land management, show promise but continue to face deployment barriers.

The use of ketorolac may reduce opioid exposure in infants less than 6 months of age undergoing congenital heart surgery.

Objectives: Pain management for infants undergoing cardiothoracic surgery primarily utilises opioid analgesics. There is a paucity of data available for the use of non-steroidal anti-inflammatory medications such as ketorolac in this patient population.

Materials And Methods: This retrospective study evaluated patients between 30 days and 6 months undergoing cardiothoracic surgery.

Ultimate drivers of forced extra-pair copulations in birds lacking a penis: jackdaws as a case-study.

Forced copulation is common, presumably because it can increase male reproductive success. Forced extra-pair copulation (FEPC) occurs in birds, even though most species lack a penis and are widely thought to require female cooperation for fertilization. How FEPC persists, despite a presumed lack of siring success and likely non-negligible costs to the male, is unknown.

STAT3 couples activated tyrosine kinase signaling to the oncogenic core transcriptional regulatory circuitry of anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) is an aggressive, CD30 T cell lymphoma of children and adults. ALK fusion transcripts or mutations in the JAK-STAT pathway are observed in most ALCL tumors, but the mechanisms underlying tumorigenesis are not fully understood. Here, we show that dysregulated STAT3 in ALCL cooccupies enhancers with master transcription factors BATF3, IRF4, and IKZF1 to form a core regulatory circuit that establishes and maintains the malignant cell state in ALCL.

Indications, Techniques, and Barriers for Pancreas Transplant Biopsy: A Consensus Perspective From a Survey of US Centers.

Background: Pancreas transplant biopsy practices for the diagnosis of rejection or other pathologies are not well described.

Methods: We conducted a survey of staff at US pancreas transplant programs (March 22, 2022, to August 22, 2022) to assess current program practices and perceptions about the utility and challenges in the performance and interpretation of pancreas allograft biopsies.

Results: Respondents represented 65% (76/117) of active adult pancreas transplant programs, capturing 66% of recent pancreas transplant volume in the United States.

Venetoclax with decitabine or azacitidine in relapsed or refractory acute myeloid leukemia.

Relapsed or refractory acute myeloid leukemia (AML) is associated with poor outcomes and resistance to therapy. The addition of venetoclax, a BCL-2 antagonist, to lower-intensity therapies results in improved survival in the first-line setting compared to monotherapy with a hypomethylating agent or low-dose cytarabine. Despite this, much remains unknown about the performance of venetoclax with a hypomethylating agent following the first-line setting.

Cow's Milk Anemia in Childhood Manifesting as Severe Cerebral Venous Sinus Thrombosis.

We describe a series of 7 toddler-aged children with iron deficiency anemia from excessive cow's milk consumption who presented with cerebral venous sinus thrombosis and no other identifiable risk factors for thrombosis. The deep venous system was involved in 6 patients, 6 had venous infarcts, and 5 have significant neurocognitive sequelae.

Differences in transcription initiation directionality underlie distinctions between plants and animals in chromatin modification patterns at genes and cis-regulatory elements.

Transcriptional initiation is among the first regulated steps controlling eukaryotic gene expression. High-throughput profiling of fungal and animal genomes has revealed that RNA Polymerase II often initiates transcription in both directions at the promoter transcription start site, but generally only elongates productively into the gene body. Additionally, Pol II can initiate transcription in both directions at cis-regulatory elements such as enhancers.

Determination of trace elements in ibuprofen drug products using microwave-assisted acid digestion and inductively coupled plasma-mass spectrometry.

Trace elements are found in most drugs as a result of the drug formulation and drug production methods. An inductively coupled plasma-mass spectrometry method for the determination of 24 trace elements (Mg, Ti, V, Cr, Mn, Cu, Fe, Co, Ni, Zn, As, Se, Mo, Ru, Rh, Pd, Ag, Cd, Sb, Ba, Ir, Pt, Au, and Pb) in solid ibuprofen tablets was established in relation to the ICH Q3D(R1) guideline, to evaluate the possibility of linking trace elemental profiles to drug formulation strategies, and to differentiate between drug products based on the trace elemental profiles. Ten European ibuprofen drug products were evaluated (n=3).

Space microgravity increases expression of genes associated with proliferation and differentiation in human cardiac spheres.

Efficient generation of cardiomyocytes from human-induced pluripotent stem cells (hiPSCs) is important for their application in basic and translational studies. Space microgravity can significantly change cell activities and function. Previously, we reported upregulation of genes associated with cardiac proliferation in cardiac progenitors derived from hiPSCs that were exposed to space microgravity for 3 days.

Differences in transcription initiation directionality underlie distinctions between plants and animals in chromatin modification patterns at genes and cis-regulatory elements.

Transcriptional initiation is among the first regulated steps controlling eukaryotic gene expression. High-throughput profiling of fungal and animal genomes has revealed that RNA Polymerase II (Pol II) often initiates transcription in both directions at the promoter transcription start site (TSS), but generally only elongates productively into the gene body. Additionally, Pol II can initiate transcription in both directions at cis-regulatory elements (CREs) such as enhancers.

Opioid Utilization after Cardiac Surgery in the Pediatric Medicaid-Insured Population.

Objective: To determine the variation of outpatient opioid prescribing across the US in postoperative pediatric cardiac patients.

Study Design: Retrospective, cross-sectional study using a concatenated database of Medicaid claims between from 2016 through 2018 of children 0-17 years, discharged after cardiac surgery and receiving an opioid prescription within 30 days. Filled prescriptions were identified and converted to morphine milligram equivalents (MME).

SpeechMirror: A Multimodal Visual Analytics System for Personalized Reflection of Online Public Speaking Effectiveness.

As communications are increasingly taking place virtually, the ability to present well online is becoming an indispensable skill. Online speakers are facing unique challenges in engaging with remote audiences. However, there has been a lack of evidence-based analytical systems for people to comprehensively evaluate online speeches and further discover possibilities for improvement.