Evaluating Meta-Learners to Analyze Treatment Heterogeneity in Survival Data: Application to Electronic Health Records of Pediatric Asthma Care in COVID-19 Pandemic.

An important aspect of precision medicine focuses on characterizing diverse responses to treatment due to unique patient characteristics, also known as heterogeneous treatment effects (HTE) or individualized treatment effects (ITE), and identifying beneficial subgroups with enhanced treatment effects. Estimating HTE with right-censored data in observational studies remains challenging. In this paper, we propose a pseudo-ITE-based framework for analyzing HTE in survival data, which includes a group of meta-learners for estimating HTE, a variable importance metric for identifying predictive variables to HTE, and a data-adaptive procedure to select subgroups with enhanced treatment effects.

Predictive strength of inflammatory scores for in-hospital mortality in infective endocarditis.

Background: Inflammatory markers have been proposed as prognostic tools for predicting in-hospital mortality in infective endocarditis (IE). Nonetheless, it is unclear whether these markers provide additional prognostic value over established indicators. This study compared nine different inflammation scores to assess their effectiveness in enhancing the prediction of in-hospital mortality.

Absolute quantification of amine metabolites in human cerebrospinal fluid via MS1-centric isotopic N,N-dimethyl leucine (iDiLeu) labeling.

Quantitative measurement of metabolites is essential to understand biological and disease processes. Absolute quantification by spiking heavy isotope-labeled internal standards and analyzing on mass spectrometry (MS) platform is a key method to determine the concentration of metabolites in biological samples. However, MS-based absolute quantification is often challenged by the commercial availability and high costs of isotope-labeled internal standards.

TP53 Mutant Variant Allele Frequency and Cytogenetics Determine Prognostic Groups in MDS/AML for Transplantation.

Results following hematopoietic stem cell transplantation (HSCT) for TP53-mutated myeloid malignancies are disappointing. Several HSCT centers decline to perform HSCT for patients with TP53 mutation because of poor outcomes. In this study, we analyzed 240 patients with TP53-mutated myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) that underwent HSCT.

Far Cortical Locking Versus Standard Constructs for Locked Plate Fixation in the Treatment of Acute, Displaced Fractures of the Distal Femur: A Multicenter Randomized Trial.

Background: Fixation of distal femoral fractures remains a challenge, and nonunions are common with standard constructs. Far cortical locking (FCL) constructs have been purported to lead to improved fracture-healing as compared with that achieved with traditional locking bridge plates. We sought to test this hypothesis in a comparative effectiveness clinical trial.

An Enigmatic Wild Passerine Mortality Event in the Eastern United States.

The ability to rapidly respond to wildlife health events is essential. However, such events are often unpredictable, especially with anthropogenic disturbances and climate-related environmental changes driving unforeseen threats. Many events also are short-lived and go undocumented, making it difficult to draw on lessons learned from past investigations.

Virus-Mimicking Polymer Nanocomplexes Co-Assembling HCV E1E2 and Core Proteins with TLR 7/8 Agonist-Synthesis, Characterization, and In Vivo Activity.

Hepatitis C virus (HCV) is a major public health concern, and the development of an effective HCV vaccine plays an important role in the effort to prevent new infections. Supramolecular co-assembly and co-presentation of the HCV envelope E1E2 heterodimer complex and core protein presents an attractive vaccine design strategy for achieving effective humoral and cellular immunity. With this objective, the two antigens were non-covalently assembled with an immunostimulant (TLR 7/8 agonist) into virus-mimicking polymer nanocomplexes (VMPNs) using a biodegradable synthetic polyphosphazene delivery vehicle.

A New Risk Prediction Model for the Assessment of Myocardial Injury in Elderly Patients Undergoing Non-Elective Surgery.

Currently, recommended pre-operative risk assessment models including the revised cardiac risk index (RCRI) are not very effective in predicting postoperative myocardial damage after non-elective surgery, especially for elderly patients. This study aimed to create a new risk prediction model to assess myocardial injury after non-cardiac surgery (MINS) in elderly patients and compare it with the RCRI, a well-known pre-operative risk prediction model. This retrospective study included 370 elderly patients who were over 65 years of age and had non-elective surgery in a tertiary hospital.

Nutritional Counseling During Chemotherapy Treatment: A Systematic Review of Feasibility, Safety, and Efficacy.

Dietary interventions during chemotherapy hold promise for clinical and supportive care outcomes. We systematically investigated the feasibility, safety, and efficacy of nutritional counseling conducted during chemotherapy. Studies prospectively implemented nutrition counseling during chemotherapy.

Deep Learning for Predicting Spheroid Viability: Novel Convolutional Neural Network Model for Automating Quality Control for Three-Dimensional Bioprinting.

Spheroids serve as the building blocks for three-dimensional (3D) bioprinted tissue patches. When larger than 500 μm, the desired size for 3D bioprinting, they tend to have a hypoxic core with necrotic cells. Therefore, it is critical to assess the viability of spheroids in order to ensure the successful fabrication of high-viability patches.

Novel Fast-Setting and Mechanically-Strong Calcium Phosphate Pulp-Capping Cement with Metformin Release to Enhance Dental Pulp Stem Cells.

Traditional pulp-capping materials like mineral trioxide aggregate (MTA) offer excellent biocompatibility and sealing, but limitations such as prolonged setting time, low bioactivity, and high costs persist. Metformin, with its potential in craniofacial regeneration, could enhance dentin synthesis by targeting pulp cells. This study aimed to: (1) develop a calcium phosphate cement with chitosan (CPCC) with improved physio-mechanical properties; (2) incorporate metformin (CPCC-Met) to assess release; and (3) evaluate human dental pulp stem cells (hDPSCs) response.

Overview of historical occupational exposure to trichloroethylene in China.

Objectives: Trichloroethylene (TCE) is a carcinogen that has been causally linked to kidney cancer and possibly other cancer sites including the liver and lymphatic system. Its use in China has increased since the early 1990s due to the growing metal and electronic industries. We aimed to summarize the major sources of occupational exposure to TCE over time in China.

ESAT-6 protein suppresses allograft rejection by inducing CD4Foxp3 regulatory T cells through IκBα/cRel pathway.

Background: Maintenance immunosuppression is required for suppression of alloimmunity or allograft rejection. However, continuous use of immunosuppressants may lead to various side effects, necessitating the use of alternative immunosuppressive drugs. The early secreted antigenic target of 6 kDa (ESAT-6) is a virulence factor and immunoregulatory protein of mycobacterium tuberculosis (Mtb), which alters host immunity through dually regulating development or activation of various immune cells.

Atacama Large Aperture Submillimeter Telescope (AtLAST) science: Probing the transient and time-variable sky.

The study of transient and variable events, including novae, active galactic nuclei, and black hole binaries, has historically been a fruitful path for elucidating the evolutionary mechanisms of our universe. The study of such events in the millimeter and submillimeter is, however, still in its infancy. Submillimeter observations probe a variety of materials, such as optically thick dust, which are hard to study in other wavelengths.

Effects of vitamin D supplementation on cardiac biomarkers: Results from the STURDY trial.

Objectives: In observational studies, older adults with low serum vitamin D levels are at higher risk of cardiovascular disease (CVD), but randomized trials have failed to demonstrate reduction in CVD risk from vitamin D supplementation, possibly because the doses of vitamin D supplements tested were too low. Our objective was to determine if higher doses of vitamin D supplementation reduce high-sensitivity cardiac troponin (hs-cTnI) and N-terminal pro-b-type natriuretic peptide (NT-proBNP), markers of subclinical CVD.

Methods: The Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a double-blind, randomized, response-adaptive trial that tested the effects of 4 doses of vitamin D3 supplementation (200, 1000, 2000, 4000 IU/day) on fall risk among older adults with low serum 25-hydroxyvitamin D concentrations (10-29 ng/mL).

Coronavirus Disease 2019 (COVID-19) Real World Data Infrastructure: A Big-Data Resource for Study of the Impact of COVID-19 in Patient Populations With Immunocompromising Conditions.

Background: We developed a United States-based real-world data resource to better understand the continued impact of the coronavirus disease 2019 (COVID-19) pandemic on immunocompromised patients, who are typically underrepresented in prospective studies and clinical trials.

Methods: The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing de-identified HealthVerity medical and pharmacy claims data from 1 December 2018 to 31 December 2023, with severe acute respiratory syndrome coronavirus 2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and, for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and End Results registry data.

Results: The CRWDi contains 4 cohorts: patients with cancer; patients with rheumatic diseases receiving pharmacotherapy; noncancer solid organ and hematopoietic stem cell transplant recipients; and people from the general population including adults and pediatric patients.

Integrated SegFlow, µSIA, and UPLC for Online Sialic Acid Quantitation of Glycoproteins Directly from Bioreactors.

This study emphasizes the critical importance of closely monitoring and controlling the sialic acid content in therapeutic glycoproteins, including EPO, interferon-γ, Orencia, Enbrel, and others, as the level of sialylation directly impacts their pharmacokinetics (PK), immunogenicity, potency, and overall clinical performance due to its influence on protein clearance via hepatic asialoglycoprotein receptors (ASGPR). The ASGPR recognizes and binds to glycoproteins exposed to terminal galactose or N-acetylgalactosamine residues, leading to receptor-mediated endocytosis. Recent studies have demonstrated that sialylation of O-linked glycan plays a role in protecting against macrophage galactose lectin (MGL)-mediated clearance.

Multisensory naturalistic decoding with high-density diffuse optical tomography.

Significance: Decoding naturalistic content from brain activity has important neuroscience and clinical implications. Information about visual scenes and intelligible speech has been decoded from cortical activity using functional magnetic resonance imaging (fMRI) and electrocorticography, but widespread applications are limited by the logistics of these technologies.

Aim: High-density diffuse optical tomography (HD-DOT) offers image quality approaching that of fMRI but with the silent, open scanning environment afforded by optical methods, thus opening the door to more naturalistic research and applications.

Behavioural interventions targeting the prevention and treatment of young children's mental health problems in low- and middle-income countries: a scoping review.

Background: Globally, 10% of children and adolescents live with mental health problems and often lack high-quality care. Over 80% of people facing mental health issues reside in low- and middle-income countries (LMICs). Failing to address children's mental health may prolong these challenges into adulthood, impeding their chances for a healthy life.

Pandemic preparedness in Vietnam: a review of health system resilience and areas for improvement.

In this viewpoint, we explore Vietnam's health system vulnerabilities and its national response to the COVID-19 pandemic, as well as critical areas of health system resilience, including health financing, workforce distribution, information systems, and governance. While Vietnam achieved early success through strong governance and mass vaccination campaigns, the pandemic revealed weaknesses in resource procurement, workforce imbalance, and limitations of its health information system. There are challenges in ensuring the rapid disbursement of financial resources and reliance on imported medical supplies, which delayed response times.

Cultural foundations of global health: a critical examination of universal child feeding recommendations.

There has been a rising call to decolonize global health so that it more fully includes the concerns, knowledge, and research from people all over the world. This endeavor can only succeed, we argue, if we also recognize that much of established global health doctrine is rooted in Euro-American beliefs, values, and practice rather than being culturally neutral. This paper examines the cultural biases of child feeding recommendations as a case in point.

Balancing the risks: continuous vs. interrupted anticoagulation during TAVI - what does the evidence say?

Anticoagulation therapy is a critical component of post-transcatheter aortic valve implantation (TAVI) management, aimed at reducing the risk of thromboembolic events and mortality. This review examines the efficacy of continuous versus interrupted anticoagulation strategies in TAVI patients, focusing on mortality, stroke rates, and composite events. A literature review was conducted, analyzing recent studies that evaluate the impact of different anticoagulation regimens on clinical outcomes in TAVI patients.