Anthracyclines disaggregate and restore mutant p63 function: a potential therapeutic approach for AEC syndrome.

Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) syndrome is a rare genetic disorder caused by mutations in the TP63 gene, which encodes a transcription factor essential for epidermal gene expression. A key feature of AEC syndrome is chronic skin erosion, for which no effective treatment currently exists. Our previous studies demonstrated that mutations associated with AEC syndrome lead to p63 protein misfolding and aggregation, exerting a dominant-negative effect.

Advanced Automated Model for Robust Bone Marrow Segmentation in Whole-body MRI.

Rationale And Objectives: To establish an advanced automated bone marrow (BM) segmentation model on whole-body (WB-)MRI in monoclonal plasma cell disorders (MPCD), and to demonstrate its robust performance on multicenter datasets with severe myeloma-related pathologies.

Materials And Methods: The study cohort comprised multi-vendor, multi-protocol imaging data acquired with varying field strength across 8 different centers. In total, 210 WB-MRIs of 207 MPCD patients were included.

Leveraging mRNA technology for antigen based immuno-oncology therapies.

The application of messenger RNA (mRNA) technology in antigen-based immuno-oncology therapies represents a significant advancement in cancer treatment. Cancer vaccines are an effective combinatorial partner to sensitize the host immune system to the tumor and boost the efficacy of immune therapies. Selecting suitable tumor antigens is the key step to devising effective vaccinations and amplifying the immune response.

Surgical management of short-segment Hirschsprung disease.

Hirschsprung disease (HSCR) is the most common congenital motility disorder of the intestine, characterized by the absence of ganglion cells in the myenteric and submucosal plexuses, leading to functional bowel obstruction. Short-segment Hirschsprung disease (SS-HSCR) accounts for the majority of cases, with surgical resection being the cornerstone of treatment. Despite advances in surgical techniques, considerable variability exists in practice regarding the timing of surgery, the choice of technique, and the length of aganglionic rectal cuff to resect.

Cohort profile: the BangladEsh Longitudinal Investigation of Emerging Vascular and nonvascular Events (BELIEVE) cohort study.

Purpose: Bangladesh has experienced a rapid epidemiological transition from communicable to non-communicable diseases (NCDs) in recent decades. There is, however, limited evidence about multidimensional determinants of NCDs in this population. The BangladEsh Longitudinal Investigation of Emerging Vascular and nonvascular Events (BELIEVE) study is a household-based prospective cohort study established to investigate biological, behavioural, environmental and broader determinants of NCDs.

Burnt Plastic (Pyroplastic) from the M/V Ship Fire and Plastic Spill Contain Compounds That Activate Endocrine and Metabolism-Related Human and Fish Transcription Factors.

In May 2021, the M/V ship fire disaster led to the largest maritime spill of resin pellets (nurdles) and burnt plastic (pyroplastic). Field samples collected from beaches in Sri Lanka nearest to the ship comprised nurdles and pieces of pyroplastic. Three years later, the toxicity of the spilled material remains unresolved.

Variants and vaccines impact nasal immunity over three waves of SARS-CoV-2.

Viral variant and host vaccination status impact infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet how these factors shift cellular responses in the human nasal mucosa remains uncharacterized. We performed single-cell RNA sequencing (scRNA-seq) on nasopharyngeal swabs from vaccinated and unvaccinated adults with acute Delta and Omicron SARS-CoV-2 infections and integrated with data from acute infections with ancestral SARS-CoV-2. Patients with Delta and Omicron exhibited greater similarity in nasal cell composition driven by myeloid, T cell and SARS-CoV-2 cell subsets, which was distinct from that of ancestral cases.

How many stroke survivors develop problematic spasticity requiring pharmacological therapy? An international (Europe and USA) observational study protocol.

Introduction: Current care plans for stroke survivors typically focus on acute management, resulting in many stroke survivors being discharged to their communities without adequate follow-up, despite their often experiencing significant post-stroke complications, such as post-stroke spasticity (PSS). While studies have explored the incidence and prevalence of PSS, little is known about how early PSS develops and how many stroke survivors develop 'problematic' PSS that would benefit from pharmacological treatment.

Methods And Analysis: EPITOME is a prospective, international, observational, epidemiological study of participants (aged 18-90 years) who develop paresis within days 3-14 of a first-ever stroke that occurred within the past 4 weeks.

Enhancing fine-tuning efficiency and design optimization of an eight-channel 3T transmit array via equivalent circuit modeling and Eigenmode analysis.

Background: Radiofrequency (RF) transmit arrays play a crucial role in various MRI applications, offering enhanced field control and improved imaging capabilities. Designing and optimizing these arrays, particularly in high-field MRI settings, poses challenges related to coupling, resonance, and construction imperfections. Numerical electromagnetic simulation methods effectively aid in the initial design, but discrepancies between simulated and fabricated arrays often necessitate fine-tuning.

Effectiveness of Synchronous Postdischarge Contacts on Health Care Use and Patient Satisfaction : A Systematic Review and Meta-analysis.

Background: Postdischarge contacts (PDCs) after hospitalization are common practice, but their effectiveness in reducing use of acute care after discharge remains unclear.

Purpose: To assess the effects of PDC on 30-day emergency department (ED) visits, 30-day hospital readmissions, and patient satisfaction.

Data Sources: MEDLINE, Embase, and CINAHL searched from 2012 to 25 May 2023.

Multimodality Imaging Evaluation of Diseases of the Pulmonic Valve and Right Ventricular Outflow Tract for the Adult Cardiologist.

Disorders of the pulmonic valve (PV) receive considerably less attention than other forms of valvular heart disease. Due to the dramatically improved survival of children with congenital heart disease over the last 5 decades, there has been a steady increase in the prevalence of adults with congenital heart disease, which necessitates that clinicians become familiar with the anatomy and the evaluation of right ventricular outflow tract and PV anomalies. A multimodality imaging approach using echocardiography, cardiac computed tomography, and magnetic resonance imaging is essential for a comprehensive evaluation of the anatomy and function of the right ventricular outflow tract, PV, and supravalvular region.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

Neither Bone Marrow Aspirate Concentrate nor Platelet-Rich Plasma Improves Patient-Reported Outcomes After Surgical Management of Acetabular Labral Tears; However, Bone Marrow Aspirate Concentrate May Be Effective for Moderate Cartilage Damage: A Systematic Review.

Purpose: To (1) systematically assess which orthobiologic agents are being used in acetabular labral repairs and (2) report all available outcomes for patients undergoing operative management for labral repairs with orthobiologic agents.

Methods: The PubMed, Embase, and Cochrane databases were queried in August 2023. Articles were included if they used an orthobiologic agent during hip arthroscopy for acetabular labral repair and reported functional outcomes.

Male National Basketball Association G-League and Collegiate Basketball Athletes Have a High Prevalence of Radiographic Ankle Abnormalities.

Purpose: To characterize radiographic foot/ankle bony abnormalities in elite-level, asymptomatic male basketball athletes and to investigate the association between anthropometric (age, height, weight) or sport-specific characteristics (total exposures, player position, pregame ankle taping) and the prevalence of abnormal radiographic findings in asymptomatic basketball athletes.

Methods: Elite-level basketball players who underwent routine, preseason static radiographic imaging, including anteroposterior, lateral, and mortise views of the ankle were included. Radiographs were collected from asymptomatic athletes participating in preseason history and physical with negative anterior drawer/talar tilt test.

Promoting Physical Activity in People With Parkinson's Disease Through a Smartphone App: A Pilot Study.

Background And Purpose: Physical activity has beneficial symptomatic effects for people with Parkinson's disease (PD), but increasing-and sustaining-a physically active lifestyle remains challenging. We investigated the feasibility (ability to increase step counts) and usability of a behavioral intervention using a motivational smartphone application to remotely increase physical activity in PD.

Methods: We performed a 4-week, double-blind pilot trial.

Effect of intravenous urokinase vs best medicine treatment on functional outcome for patients with acute minor stroke (TRUST): a randomized controlled trial.

Background: The benefits of intravenous thrombolysis in patients with acute minor stroke remain controversial. For the aim of providing a better therapeutic strategy, high-quality trials are required to validate the efficacy of thrombolytic medicine other than intravenous recombinant tissue plasminogen and tenecteplase. In the trial, we evaluate the efficacy and safety of urokinase (UK) in acute minor stroke.

Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials.

Background: The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor-tezacaftor-deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor-tezacaftor-deutivacaftor compared with standard of care elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older.

Urinary Kidney Injury Biomarker Profiles in Healthy Individuals and After Nephrotoxic and Ischemic Injury.

Two observational studies were conducted to support an initiative to qualify translational kidney safety biomarkers as clinical drug development tools that identify tubular injury prior to changes in estimated glomerular filtration rate (eGFR). Normal healthy volunteers provided three morning spot urine collections over 4 weeks. Patients undergoing surgical resection and intrathoracic cisplatin for malignant pleural mesothelioma provided urine samples pre- and postoperatively at 4, 8, and 12 hours and daily for 6 days.

Systematic Review of Randomized Controlled Trials Evaluating the Use of Platelet-Rich Plasma for Knee Osteoarthritis: Adherence to Minimum Information for Studies Evaluating Biologics in Orthopaedics.

Background: The Minimum Information for Studies Evaluating Biologics in Orthopedics (MIBO) guidelines were developed in May 2017 to encourage improved reporting standards, promote increased transparency and reproducibility, and enhance clinical evaluation capabilities. The MIBO guidelines consist of 23 checklist items considered necessary to critically appraise clinical studies evaluating platelet-rich plasma (PRP).

Purpose: To assess randomized controlled trials that evaluated PRP for the treatment of knee osteoarthritis in order to systematically review their adherence to the MIBO guidelines.

Land Use Change Consistently Reduces α- But Not β- and γ-Diversity of Bees.

Land use change threatens global biodiversity and compromises ecosystem functions, including pollination and food production. Reduced taxonomic α-diversity is often reported under land use change, yet the impacts could be different at larger spatial scales (i.e.

International Consensus Guidance for the Management of Glucocorticoid Related Complications in Neuromuscular Disease.

Introduction/aims: Glucocorticoid (GC)-related adverse reactions and risks are commonly seen during the treatment of immune-mediated and inflammatory neuromuscular disorders. There is wide variation in the management of associated complications. The aim of this study is to develop international consensus guidance on the management of GC-related complications in neuromuscular disorders.

Selective learning for sensing using shift-invariant spectrally stable undersampled networks.

The amount of data collected for sensing tasks in scientific computing is based on the Shannon-Nyquist sampling theorem proposed in the 1940s. Sensor data generation will surpass 73 trillion GB by 2025 as we increase the high-fidelity digitization of the physical world. Skyrocketing data infrastructure costs and time to maintain and compute on all this data are increasingly common.