Orchestrated desaturation reprogramming from stearoyl-CoA desaturase to fatty acid desaturase 2 in cancer epithelial-mesenchymal transition and metastasis.

Background: Adaptative desaturation in fatty acid (FA) is an emerging hallmark of cancer metabolic plasticity. Desaturases such as stearoyl-CoA desaturase (SCD) and fatty acid desaturase 2 (FADS2) have been implicated in multiple cancers, and their dominant and compensatory effects have recently been highlighted. However, how tumors initiate and sustain their self-sufficient FA desaturation to maintain phenotypic transition remains elusive.

Antifouling Immunomodulatory Copolymer Architectures That Inhibit the Fibrosis of Implants.

Immune reactions to medical implants often lead to encapsulation by fibrotic tissue and impaired device function. This process is thought to initiate by protein adsorption, which enables immune cells to attach and mount an inflammatory response. Previously, several antifibrotic materials have been either designed to reduce protein adsorption or discovered via high-throughput screens (HTS) to favorably regulate inflammation.

Unbiased Drug Target Prediction Reveals Sensitivity to Ferroptosis Inducers, HDAC and RTK Inhibitors in Melanoma Subtypes.

Background: The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem.

Objective: Here, we mine large-scale MM proteogenomic data to identify druggable targets and forecast treatment efficacy and resistance.

Big brother or big opportunity? Utilization of EHR use metadata in the inpatient setting: A mixed methods study at 16 organizations.

Background: Clinician electronic actions within the electronic health record (EHR) are captured seamlessly in real-time during regular work activities in all major EHRs. Analysis of this EHR use metadata, such as audit log data, is increasingly used to understand the impact of work design on critical patient, workforce, and organizational outcomes.

Objective: Understand experiences and perspectives influencing the use and implementation of audit log data into practice.

Integrating Hydrogels and Biomedical Plastics via In Situ Physical Entanglements and Covalent Bonding.

Both rigid plastics and soft hydrogels find ample applications in engineering and medicine but bear their own disadvantages that limit their broader applications. Bonding these mechanically dissimilar materials may resolve these limitations, preserve their advantages, and offer new opportunities as biointerfaces. Here, a robust adhesion strategy is proposed to integrate highly entangled tough hydrogels and diverse plastics with high interfacial adhesion energy and strength.

Online native hydrophobic interaction chromatography-mass spectrometry of antibody-drug conjugates.

Hydrophobic interaction chromatography (HIC) is commonly used to determine the drug-to-antibody ratio (DAR) and drug load distribution of antibody-drug conjugates (ADCs). However, identifying various DAR species separated by HIC is challenging due to the traditional use of mobile phases that are incompatible with mass spectrometry (MS). Existing approaches used to couple HIC with MS often encounter issues, such as complex instrumentation, compromised separation efficiency, and reduced MS sensitivity.

Eyespot peek-a-boo: Leaf rolls enhance the antipredator effect of insect eyespots.

Animal colour patterns are often accompanied by specific, synergistic behaviours to most effectively defend prey against visual predators. Given the inherent context-dependence of colour perception, understanding how these colour-behaviour synergies function in a species' natural environment is crucial. For example, refuge-building species create a unique visual environment where most (or all) of the body is obscured unless closely inspected.

Real-World Effectiveness of Bebtelovimab Versus Nirmatrelvir/Ritonavir in Outpatients with COVID-19.

Introduction: This real-world study assessed the effectiveness of bebtelovimab (BEB) versus nirmatrelvir/ritonavir (NR) among outpatients with COVID-19 during the Omicron variant era.

Methods: We conducted a cohort study evaluating patients treated with BEB or NR from February to August 2022 (study period). Follow-up began the day after treatment and continued for 30 days.

Beauvoir, Ernaux, and Me: On Age, Disability, and Dying Well.

Can the fraught relation between disability and aging ever become untangled? What is the place of the catastrophically disabled in a time when giving voice and being seen are significant lodestars of political activism? And what becomes of the caregivers, who often labor in silence, and who hope to work well enough just to get through another day? This essay draws on the memoirs of Simone de Beauvoir, Annie Ernaux, Amy Bloom, and my own experiences to show the complicated imbrications of age, disability, and caretaking. I attempt to demonstrate through these experiences that age and disability, which appear to be intimately woven together, are oftentimes misleadingly connected. I suggest that an ethic of vulnerability, rather, is a more useful heuristic that avoids collapsing the categories of age and disability together.

Reducing the positive margins rate for anal melanoma in the modern era: a national propensity score matched study.

Anal Melanoma (AM) is a rare and aggressive disease lacking standardized treatment protocols. Despite advancements in medical oncology, the 5-year overall survival (OS) remains at 20%. Local surgery (LS) has gained popularity over radical surgery (RS) due to its comparable OS when negative margins are achieved.

A Pooled Pharmacokinetic Analysis for Piperacillin/Tazobactam Across Different Patient Populations: From Premature Infants to the Elderly.

Background And Objectives: The pharmacokinetics (PK) of piperacillin/tazobactam (PIP/TAZ) is highly variable across different patient populations and there are controversies regarding non-linear elimination as well as the fraction unbound of PIP (f). This has led to a plethora of subgroup-specific models, increasing the risk of misusing published models when optimising dosing regimens. In this study, we aimed to develop a single model to simultaneously describe the PK of PIP/TAZ in diverse patient populations and evaluate the current dosing recommendations by predicting the PK/pharmacodynamics (PD) target attainment throughout life.

Patterns of initial treatment and subsequent care escalation among medicare beneficiaries with neck pain: a retrospective cohort study.

Purpose: To compare long-term care escalation encounters among three care patterns for new episodes of neck pain among Medicare beneficiaries.

Methods: We examined Medicare claims spanning a four-year period for beneficiaries with new episodes of neck pain beginning in 2019. All patients were continuously enrolled under Medicare parts A, B, and D and aged 65-99 years.

Update on Strategies to Reduce Early Brain Injury after Subarachnoid Hemorrhage.

Purpose Of Review: Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH) is the most influential clinical determinant of outcomes. Despite significant advances in understanding of the pathophysiology of EBI, currently no treatments to target EBI have been developed. This review summarizes recent advances in EBI research over the past five years with a focus on potential therapeutic targets.

A robust evaluation of TDP-43, poly GP, cellular pathology and behavior in an AAV-C9ORF72 (GC) mouse model.

The GC hexanucleotide repeat expansion in C9ORF72 is the major genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Despite considerable efforts, the development of mouse models of C9-ALS/FTD useful for therapeutic development has proven challenging due to the intricate interplay of genetic and molecular factors underlying this neurodegenerative disorder, in addition to species differences. This study presents a robust investigation of the cellular pathophysiology and behavioral outcomes in a previously described AAV mouse model of C9-ALS expressing 66 GC hexanucleotide repeats.

Mobilization in Neurocritical Care: Challenges and Opportunities.

Purpose Of Review: Mobilization in the Neurological Intensive Care Unit (NICU) significantly improves outcomes and functional recovery while preventing immobility-related complications. The heterogeneity of neurologic conditions necessitates tailored, interdisciplinary mobilization strategies. This article reviews recent research on enhancing the feasibility and effectiveness of mobilization interventions in NICU settings.

Hidden space use behaviors of a nonbreeding migratory bird: the role of environment and social context.

Background: Movement behavior strongly mediates species and environment interactions, yet our understanding is constrained by challenges tracking space use at fine spatiotemporal resolutions.

Methods: Using an automated telemetry array, we quantified variation in and drivers of space use for a nonbreeding population of migratory bird, the American redstart Setophaga ruticilla.

Results: We identified two distinct and common behaviors - territoriality and floating,- that were governed primarily by NDVI as a proxy of resource availability.

Systematic review: Mechanisms of photoactive nanocarriers for imaging and therapy including controlled drug delivery.

Background: The design of smart, photoactivated nanomaterials for targeted drug delivery systems (DDS) has garnered significant research interest due in part to the ability of light to precisely control drug release in specific cells or tissues with high spatial and temporal resolution. The development of effective light-triggered DDS involves mechanisms including photocleavage, photoisomerization, photopolymerization, photosensitization, photothermal phenomena, and photorearrangement, which permit response to ultraviolet (UV), visible (Vis), and/or Near Infrared (NIR) light. This review explores recent advancements in light-responsive small molecules, polymers, and nanocarriers, detailing their underlying mechanisms and utility for drug delivery and/or imaging.

Does going against the norm on women's economic participation increase intimate partner violence risk? A cross-sectional, multi-national study.

Background: Women's economic empowerment (WEE) is believed to reduce the risk of intimate partner violence (IPV), yet the relationship between WEE and IPV has proven to be highly variable. Little attention has been given to how the normative WEE environment may influence this relationship across different settings. This study tests whether IPV is associated with Vanguard WEE, defined as individual economic participation that deviates from community norms.

Improved efficacy of therapeutic HPV DNA vaccine using intramuscular injection with electroporation compared to conventional needle and needle-free jet injector methods.

Background: We have previously developed a candidate therapeutic HPV DNA vaccine (pBI-11) encoding mycobacteria heat shock protein 70 linked to HPV16/18 E6/E7 proteins for the control of advanced HPV-associated oropharyngeal cancer (NCT05799144). While naked DNA vaccines are readily produced, stable, and well tolerated, their potency is limited by the delivery efficiency. Here we compared three different IM delivery strategies, including intramuscular (IM) injection, either with a needle alone or with electroporation at the injection site, and a needle-free injection system (NFIS), for their ability to elicit gene expression and to improve the potency of pBI-11 DNA vaccine.

Cystic lesions and their mimics involving the intrahepatic bile ducts and peribiliary space: diagnosis, complications, and management.

Biliary and peribiliary cystic lesions represent a diverse group of abnormalities, often discovered incidentally during imaging for unrelated conditions. These lesions, typically asymptomatic, necessitate precise imaging modalities to characterize their nature and determine subsequent clinical actions, such as follow-up imaging, biopsy, or surgical referral. The anatomic location of these cystic lesions, whether biliary or peribiliary, influences both diagnostic and prognostic outcomes.

Current and future immunotherapy for breast cancer.

Substantial therapeutic advancement has been made in the field of immunotherapy in breast cancer. The immune checkpoint inhibitor pembrolizumab in combination with chemotherapy received FDA approval for both PD-L1 positive metastatic and early-stage triple-negative breast cancer, while ongoing clinical trials seek to expand the current treatment landscape for immune checkpoint inhibitors in hormone receptor positive and HER2 positive breast cancer. Antibody drug conjugates are FDA approved for triple negative and HER2+ disease, and are being studied in combination with immune checkpoint inhibitors.

Microbial diversity and biogeochemical interactions in the seismically active and CO- rich Eger Rift ecosystem.

The Eger Rift subsurface is characterized by frequent seismic activity and consistently high CO concentrations, making it a unique deep biosphere ecosystem and a suitable site to study the interactions between volcanism, tectonics, and microbiological activity. Pulses of geogenic H during earthquakes may provide substrates for methanogenic and chemolithoautotrophic processes, but very little is currently known about the role of subsurface microorganisms and their cellular processes in this type of environment. To assess the impact of geologic activity on microbial life, we analyzed the geological, geochemical, and microbiological composition of rock and sediment samples from a 238 m deep drill core, running across six lithostratigraphic zones.

Anticipated facilitators and barriers for long-acting injectable antiretrovirals as HIV treatment and prevention in Vietnam: a qualitative study among healthcare workers.

Background: Long-acting injectable antiretrovirals (LAI-ARVs) for HIV prevention and treatment have been demonstrated in clinical trials to be non-inferior to daily oral medications, providing an additional option to help users overcome the challenges of daily adherence. Approval and implementation of these regimens in low- and middle-income settings have been limited.

Method: This study describes the anticipated barriers and facilitators to implementing LAI-ARVs in Vietnam to inform future roll-out.