Safety of Adjunctive Intraarterial Tenecteplase Following Mechanical Thrombectomy: The ALLY Pilot Trial.

Background: Recent studies suggest that the use of adjunctive intraarterial alteplase after mechanical thrombectomy (MT) may improve outcomes; however, there are limited data on the use of intraarterial tenecteplase, a newer-generation lytic, in this acute ischemic stroke patient population. Here, we evaluate the use of intraarterial tenecteplase in the ALLY pilot study (Adjunctive Intraarterial Tenecteplase Following Mechanical Thrombectomy).

Methods: ALLY was a prospective, single-center, nonrandomized pilot study assessing the feasibility and safety of intraarterial tenecteplase up to 4.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Hyperactive delta isoform of PI3Kinase enables long distance regeneration of adult rat corticospinal tract.

Neurons in the central nervous system (CNS) lose regenerative potential with maturity, leading to minimal corticospinal tract (CST) axon regrowth after spinal cord injury (SCI). In young rodents, knockdown of PTEN, which antagonises PI3K signalling by hydrolysing PIP3, promotes axon regeneration following SCI. However, this effect diminishes in adults, potentially due to lower PI3K activation leading to reduced PIP3.

Machine learning derived retinal pigment score from ophthalmic imaging shows ethnicity is not biology.

Few metrics exist to describe phenotypic diversity within ophthalmic imaging datasets, with researchers often using ethnicity as a surrogate marker for biological variability. We derived a continuous, measured metric, the retinal pigment score (RPS), that quantifies the degree of pigmentation from a colour fundus photograph of the eye. RPS was validated using two large epidemiological studies with demographic and genetic data (UK Biobank and EPIC-Norfolk Study) and reproduced in a Tanzanian, an Australian, and a Chinese dataset.

Considerations for social networks and health data sharing: An overview.

The use of network analysis as a tool has increased exponentially as more clinical researchers see the benefits of network data for modeling of infectious disease transmission or translational activities in a variety of areas, including patient-caregiving teams, provider networks, patient-support networks, and adoption of health behaviors or treatments, to name a few. Yet, relational data such as network data carry a higher risk of deductive disclosure. Cases of reidentification have occurred and this is expected to become more common as computational ability increases.

Late Bedtime from the Perspective of Adolescents: A Qualitative Study.

Purpose: Later sleep timing is a key determinant of reduced sleep duration and quality in adolescents and is associated with negative mental and physical outcomes. However, little is known about adolescents' views on late bedtime. The study's purpose is to explore adolescents' perspectives on why they go to sleep late during school nights and what would help them to go to bed earlier.

Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells.

Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for β-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and efficacy. Here, we compare combined CRISPR-Cas9 editing of the BCL11A +58 and +55 enhancers with leading gene modification approaches under clinical investigation. Dual targeting of the BCL11A +58 and +55 enhancers with 3xNLS-SpCas9 and two single guide RNAs (sgRNAs) resulted in superior HbF induction, including in sickle cell disease (SCD) patient xenografts, attributable to simultaneous disruption of core half E-box/GATA motifs at both enhancers.

DE-PASS Best Evidence Statement (BESt): A Systematic Review and Meta-analysis on the Effectiveness of Trials on Device-Measured Physical Activity and Sedentary Behaviour and Their Determinants in Children Aged 5-12 Years.

Background: To combat the high prevalence of physical inactivity among children, there is an urgent need to develop and implement real-world interventions and policies that promote physical activity (PA) and reduce sedentary behaviour (SB). To inform policy makers, the current body of evidence for children's PA/SB interventions needs to be translated.

Objectives: The current systematic review and meta-analysis aimed to identify modifiable determinants of device-measured PA and SB targeted in available intervention studies with randomized controlled trial (RCT) and controlled trial (CT) designs in children and early adolescents (5-12 years) and to quantify the effects of the interventions within their respective settings on the determinants of PA/SB and the outcomes PA and SB.

Orthostatic and Standing Hypertension and Risk of Cardiovascular Disease.

Background: Orthostatic hypertension is an emerging risk factor for adverse events. Recent consensus statements combine an increase in blood pressure upon standing with standing hypertension, but whether these 2 components have similar risk associations with cardiovascular disease (CVD) is unknown.

Methods: The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing blood pressure during visit 1 (1987-1989).

Effectiveness and Safety of Mechanical Thrombectomy in Large-Vessel-Occlusion Mild Stroke: Insights from the ASSIST Registry.

Background And Purpose: Mechanical thrombectomy (MT) is effective for acute ischemic stroke, yet its indication in mild stroke remains unclear. This study evaluates MT's effectiveness and safety in low NIHSS patients and assesses different MT strategies' impact on procedural success and clinical outcomes.

Materials And Methods: Data from the ASSIST Registry were analyzed, categorizing patients with large vessel occlusion of the anterior circulation into mild (NIHSS≤5) and moderate-severe (NIHSS>5) stroke groups.

Adverse Drug Events in Ambulatory Care: A Cross-Sectional Study.

Background: Adverse drug events (ADEs) are understudied in the ambulatory care setting. We aim to estimate the prevalence and characteristics of ADEs in outpatient care using electronic health records (EHRs).

Methods: This cross-sectional study included EHR data for patients who had an outpatient encounter at an academic medical center from 1 October 2018 through 31 December 2019.

The effect of acute stress response on conspiracy theory beliefs.

The endorsement of conspiracy theories may be increased by subjectively perceived stress. Yet, it is not known whether this correlation is caused by the effects of the acute stress reaction on the brain or other psychological, social, or methodological factors. The effect of an experimentally induced acute stress reaction on conspiracy thinking was tested on a sample (n = 115) of students of medicine.

Electrophysiological Phenotype-Genotype Study of Sustained Monomorphic Ventricular Tachycardia in Inherited, High Arrhythmic Risk, Left Ventricular Cardiomyopathy.

Background: Among inherited cardiomyopathies involving the left ventricle, whether dilated or not, certain genotypes carry a well-established arrhythmic risk, notably manifested as sustained monomorphic ventricular tachycardia (SMVT). Nonetheless, the precise localization and electrophysiological profile of this substrate remain undisclosed across different genotypes.

Methods: Patients diagnosed with cardiomyopathy and left ventricle involvement due to high-risk genetic variants and SMVT treated by electrophysiological study were recruited from 18 European/US centers.

Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons.

Background: Twice-yearly subcutaneous lenacapavir has been shown to be efficacious for prevention of HIV infection in cisgender women. The efficacy of lenacapavir for preexposure prophylaxis (PrEP) in cisgender men, transgender women, transgender men, and gender-nonbinary persons is unclear.

Methods: In this phase 3, double-blind, randomized, active-controlled trial, we randomly assigned participants in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF).

The Incidence of Popeye Deformity After Soft-Tissue Biceps Tenodesis Is Comparable to Biceps Anchor Tenodesis and Lower Than Biceps Tenotomy During Arthroscopic Rotator Cuff Repair.

Purpose: To compare clinical and radiologic outcomes between biceps anchor tenodesis (AT), biceps soft-tissue tenodesis (ST), and biceps tenotomy (TT) for patients with concomitant rotator cuff repair (RCR).

Methods: This retrospective study reviewed patients who underwent arthroscopic RCR for full-thickness rotator cuff tears with AT, ST, or TT with minimum 2-year follow-up. All biceps procedures were performed arthroscopically, and ST consisted of fixation to the transverse humeral ligament.

S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models.

Background: The EF-hand Ca sensor protein S100A1 has been identified as a molecular regulator and enhancer of cardiac performance. The ability of S100A1 to recognize and modulate the activity of targets such as SERCA2a (sarcoplasmic reticulum Ca ATPase) and RyR2 (ryanodine receptor 2) in cardiomyocytes has mostly been ascribed to its hydrophobic C-terminal α-helix (residues 75-94). We hypothesized that a synthetic peptide consisting of residues 75 through 94 of S100A1 and an N-terminal solubilization tag (S100A1ct) could mimic the performance-enhancing effects of S100A1 and may be suitable as a peptide therapeutic to improve the function of diseased hearts.

Molecular adaptation to neoadjuvant immunotherapy in triple-negative breast cancer.

Therapy-induced molecular adaptation of triple-negative breast cancer is crucial for immunotherapy response and resistance. We analyze tumor biopsies from three different time points in the randomized neoadjuvant GeparNuevo trial (NCT02685059), evaluating the combination of durvalumab with chemotherapy, for longitudinal alterations of gene expression. Durvalumab induces an activation of immune and stromal gene expression as well as a reduction of proliferation-related gene expression.