Engineered GM-CSF polarizes protumorigenic tumor-associated macrophages to an antitumorigenic phenotype and potently synergizes with IL-12 immunotherapy.

Background: The use of immune checkpoint inhibitors (CPIs) has become a dominant regimen in modern cancer therapy, however immune resistance induced by tumor-associated macrophages (TAMs) with immune suppressive and evasion properties limits responses. Therefore, the rational design of immune modulators that can control the immune suppressive properties of TAMs and polarize them, as well as dendritic cells (DCs), toward a more proinflammatory phenotype is a principal objective in cancer immunotherapy.

Methods: Here, using a protein engineering approach to enhance cytokine residence in the tumor microenvironment, we examined combined stimulation of the myeloid compartment via tumor stroma-binding granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance responses in both DCs and T cells via stroma-binding interleukin-12 (IL-12).

Physiologically based Pharmacokinetic/Pharmacodynamic Modeling (PBPK/PD) of Famotidine in Pregnancy.

Famotidine, a H-receptor antagonist, is commonly used to treat heartburn and gastroesophageal reflux disease during pregnancy. However, information on the pharmacokinetics (PK) of famotidine in pregnant patients is limited since pregnant patients are usually excluded from clinical trials. This study aimed to develop and evaluate a physiologically based pharmacokinetic (PBPK) model for famotidine in non-pregnant and pregnant populations, and to combine it with a pharmacodynamic (PD) model to predict the effect of famotidine on intragastric pH.

Double cycling with breath-stacking during partial support ventilation in ARDS: Just a feature of natural variability?

Background: Double cycling with breath-stacking (DC/BS) during controlled mechanical ventilation is considered potentially injurious, reflecting a high respiratory drive. During partial ventilatory support, its occurrence might be attributable to physiological variability of breathing patterns, reflecting the response of the mode without carrying specific risks.

Methods: This secondary analysis of a crossover study evaluated DC/BS events in hypoxemic patients resuming spontaneous breathing in cross-over under neurally adjusted ventilatory assist (NAVA), proportional assist ventilation (PAV +), and pressure support ventilation (PSV).

Orphanhood and caregiver death among children in the United States by all-cause mortality, 2000-2021.

Deaths of parents and grandparent caregivers threaten child well-being owing to losses of care, financial support, safety and family stability, but are relatively unrecognized as a public health crisis. Here we used cause-specific vital statistics death registrations in a modeling approach to estimate the full magnitude of orphanhood incidence and prevalence among US children aged 0-17 years between 2000 and 2021 by cause, child age, race and ethnicity, sex of deceased parent and state, and also accounted for grandparent caregiver loss using population survey data. In 2021, we estimate that 2.

Why Do They Persist? Understanding Living Kidney Donors and Persistence.

Many participants persist through the living kidney donation process, although it is challenging, multifaceted, and burdensome, particularly during the predonation evaluation (PDE) phase. This study uses a constructivist grounded theory approach to analyze the experiences of living kidney donors (LKDs) undergoing evaluation who shared their perspectives in blog reflections. One hundred five (105) blog posts met the inclusion criteria.

Favorable 30-day outcomes of initial open inguinal hernia repair with local anesthesia among frail patients.

Background: Open inguinal hernia repair (OIHR) can be conducted under either general anesthesia (GA) or local anesthesia (LA). Despite a lack of evidence supporting improved perioperative outcomes, GA is the predominant anesthesia type used in OIHR. Frailty is defined as a clinically recognizable state of age-related increased vulnerability.

Right-lateralization of the visual word form area after left-hemisphere perinatal stroke.

In literate adults, an area along the left posterior fusiform gyrus that is often referred to as the "visual word form area" (VWFA) responds particularly strongly to written characters compared to other visually similar stimuli. Theoretical accounts differ in whether they attribute the strong left-lateralization of the VWFA to a left-hemisphere bias towards visual features used in script, to competition of visual word form processing with that of other visual stimuli processed in the same general cortical territory (especially faces), or to the well-established left-lateralization of the language system.Here we used functional magnetic resonance imaging to test the last hypothesis by investigating lateralization of the VWFA in participants (male and female) who have right-hemisphere language due to a large left-hemisphere perinatal stroke.

Substrate adaptors are flexible tethering modules that enhance substrate methylation by the arginine methyltransferase PRMT5.

Protein arginine methyltransferase (PRMT) 5 is an essential arginine methyltransferase responsible for the majority of cellular symmetric dimethyl-arginine (SDMA) marks. PRMT5 uses substrate adaptors such as pICln, RIOK1, and COPR5, to recruit and methylate a wide range of substrates. Although the substrate adaptors play important roles in substrate recognition, how they direct PRMT5 activity towards specific substrates remains incompletely understood.

Screening for Health-Related Social Needs: American College of Preventive Medicine's Practice Statement.

Interest is rapidly growing around screening for health-related social needs (HRSN) in direct patient care settings. The screening and provision of HRSN is often done in the context of trying to address social determinants of health (SDOH). While there is emerging evidence that screening and referral for HRSN can improve health outcomes, there are educational, operational, and systemic gaps that need to be filled in order for HRSN screening and referral to be implemented system-wide and result in meaningful improvement in population health outcomes.

Cost analysis of hidden hepatitis D virus infection in Spain.

Introduction: A significant percentage of patients coinfected with hepatitis B virus (HBV) and hepatitis D virus (HDV) are undiagnosed. Coinfected patients progress to advanced liver disease faster than HBV monoinfected patients, thereby consuming more healthcare resources. The aim was to perform an analysis to determine the cost of hidden HDV infection in Spain.

Acral Lentiginous Melanoma. Part I. Epidemiology, Etiology, Clinical Presentation, and Diagnosis.

This review article focuses on acral lentiginous melanoma (ALM), a rare cutaneous malignancy and the least common subtype of cutaneous malignant melanoma (CMM). ALM exhibits distinct characteristics, such as low overall mutation rates and increased chromosomal alterations. It is associated with worse prognosis, more advanced disease, and lower survival rates compared to other CMM subtypes.

Evaluation of Multi-Lingual Simplifications of IR Procedural Reports Using GPT-4.

This study assesses the feasibility of Large Language Models like GPT-4 (OpenAI, San Francisco, CA, USA) to summarize interventional radiology (IR) procedural reports to improve layperson understanding and translate medical texts into multiple languages. 200 reports from eight categories were summarized using GPT-4. Readability was assessed with Flesch-Kincaid Reading Level (FKRL) and Flesch Reading Ease Score (FRES).

Management of environmental impacts of fossil fuel use in refugee camps through transition to renewable energy infrastructure: Case studies in Uganda and Bangladesh.

Many refugee camps exist for decades but associated infrastructure needs are only planned for the very short term, including provision of power. This study advocates a shift in approach to sustainable electrification of essential services in refugee camps for lighting, refrigeration, health, water, education, alongside camp operations. Qualitative and quantitative surveys were conducted in refugee camps in Uganda and Bangladesh which assessed the electrical supply needs across such categories.

The smartphone-assisted sensing platform based on manganese dioxide nanozymes for the specific detection and degradation of hydroquinone.

Hydroquinone (HQ) is a prevalent pollutant in aquatic environments, posing significant risks to ecosystems and human health. Practical methods for the simultaneous detection and degradation of HQ are essential. To address this requirement, a dual-mode detection and degradation strategy has been developed utilizing designed nanozymes (DM) consisting of a porous SiO core and MnO shell.

Study on the damage and variation of Agropyron mongolicum induced by the combined action of discharge plasma and plasma-activated water.

To investigate the effect of combined action of discharge plasma (DP) and plasma-activated water (PAW) in mutagenesis breeding, this study focuses on Agropyron mongolicum. We utilized high-voltage DC pulsed dielectric barrier discharge for seed treatment, alone and in combination with PAW. The research focused on germination rates, evolution of physicochemical properties of imbibition residual solution, reactive oxygen species (ROS), malondialdehyde (MDA), and volatile organic compounds (VOCs) to assess DP-induced damage and variability in Agropyron mongolicum.

The PANDA score: External validation and modification of a simple upfront prediction tool for poor outcomes despite successful stroke thrombectomy.

Background: While endovascular thrombectomy (EVT) has become standard of care for patients' acute ischemic stroke (AIS) due to large vessel occlusion (LVO), many patients still suffer profound neurological disability, also termed futile recanalization (FR). The BAND score, which incorporates baseline disability, age, stroke severity, and treatment time window, is derived as a simple tool for upfront prediction of FR prior to EVT. This study aims to externally validate the BAND score and to incorporate upfront imaging biomarkers into the prediction tool.

Intraoperative Anesthetic Care During Emergent/Urgent Craniotomy or Craniectomy for Intracranial Hypertension or Herniation: A Systematic Review.

This systematic review aimed to identify and describe best practice for the intraoperative anesthetic management of patients undergoing emergent/urgent decompressive craniotomy or craniectomy for any indication. The PubMed, Scopus, EMBASE, and Cochrane databases were searched for articles related to urgent/emergent craniotomy/craniectomy for intracranial hypertension or brain herniation. Only articles focusing on intraoperative anesthetic management were included; those investigating surgical or intensive care unit management were excluded.

How and why funders support engaged research.

Research that better aligns policy, practice, and research communities is gaining momentum around the world. This includes engaged research strategies that bring partners, and their diverse perspectives and kinds of knowledge, together to shape research agendas with on-the-ground-needs and to create dynamic problem-solving processes. These approaches aim to generate more equitable and effective solutions to societal challenges.

Focused Investigation of Facial Nerve Dysfunction After Mandibular Distraction Osteogenesis for Robin Sequence.

Facial nerve dysfunction (FND) is a well-recognized but poorly documented complication of mandibular distraction osteogenesis (MDO) for Robin sequence (RS). This study aims to document the authors' experiences with FND and identify risk factors associated with this adverse event. A retrospective review of a prospectively gathered database was performed to identify patients with RS who underwent MDO at the authors' institution from March 2016 to June 2023.

The Impact of Leadership Training on Burnout and Fulfillment Among Direct Reports.

Goal: Burnout, decreased professional fulfillment, and resultant attrition across the medical professions are increasingly recognized as threats to sustainable and cost-effective healthcare delivery. While the skill level of leaders as perceived by their direct reports has been correlated with rates of burnout and fulfillment, no studies, to our knowledge, have directly evaluated whether intervention via leadership training impacts burnout and fulfillment among direct reports. The goal of this study was to evaluate the effectiveness of a leadership training intervention on direct reports' perceptions of the leadership skills of supervising residents and subsequently on the well-being of the direct reports.

Causal relationship between immune cells and heart failure: A Mendelian randomization study.

This study aimed to evaluate the causal effects of different immune cells on heart failure (HF) using Mendelian randomization (MR). Datasets for immune cell phenotypes and HF were obtained from European Bioinformatics Institute and FinnGen. Then, single nucleotide polymorphisms were screened according to the basic assumptions of MR.

Skin-Integrated Electrogenetic Regulation of Vasculature for Accelerated Wound Healing.

Neo-vascularization plays a key role in achieving long-term viability of engineered cells contained in medical implants used in precision medicine. Moreover, strategies to promote neo-vascularization around medical implants may also be useful to promote the healing of deep wounds. In this context, a biocompatible, electroconductive borophene-poly(ε-caprolactone) (PCL) 3D platform is developed, which is called VOLT, to support designer cells engineered with a direct-current (DC) voltage-controlled gene circuit that drives secretion of vascular endothelial growth factor A (VEGFA).

High-throughput design of a light and strong refractory eutectic medium entropy alloy with outstanding He-ion irradiation resistance.

Light, strong, and radiation-tolerant materials are essential for advanced nuclear systems and aerospace applications. However, the comprehensive properties of current radiation-tolerant materials are far from being satisfactory in harsh operating environments. In this study, a high-throughput-designed NbVTaSi refractory eutectic medium entropy alloy realizes the controllable formation of the β-NbSi phase with a high content and has outstanding comprehensive properties, i.