Synthetic gene circuits drive disease-fighting T cells.

Immune cells can be programmed to deliver targeted therapies in models of brain and inflammatory disease.

Health and University Students: The Mediator Role of Emotion Regulation Between Academic Stressors and Health Behaviors.

Purpose: To determine the role of Health Behaviors and Cognitive Emotion Regulation Strategies in the relationship between Health and Academic Stress.

Design: A cross-sectional study with in-person administration of questionnaires.

Setting: Data collection took place at nine public and private universities in Peru, involving a diverse group of students from different faculties.

Unveiling the impact of hypodermis on gene expression for advancing bioprinted full-thickness 3D skin models.

3D skin models have been explored as an alternative method to the use of animals in research and development. Usually, human skin equivalents comprise only epidermis or epidermis/dermis layers. Herein, we leverage 3D bioprinting technology to fabricate a full-thickness human skin equivalent with hypodermis (HSEH).

Antibiotic-induced loss of gut microbiome metabolic output correlates with clinical responses to CAR T-cell therapy.

Antibiotic (ABX)-induced microbiome dysbiosis is widespread in oncology, adversely affecting outcomes and side effects of various cancer treatments, including immune checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T) therapies. In this study, we observed that prior exposure to broad-spectrum ABXs with extended anaerobic coverage such as piperacillin-tazobactam and meropenem was associated with worse anti-CD19 CAR-T therapy survival outcomes in patients with large B-cell lymphoma (N = 422) than other ABX classes. In a discovery subset of these patients (n = 67), we found that the use of these ABXs was in turn associated with substantial dysbiosis of gut microbiome function, resulting in significant alterations of the gut and blood metabolome, including microbial effectors such as short-chain fatty acids (SCFAs) and other anionic metabolites, findings that were largely reproduced in an external validation cohort (n = 58).

Comprehensive antitumor immune response boosted by dual inhibition of SUMOylation and MEK in MYC-expressing KRAS-mutant cancers.

Precision medicine has drastically changed cancer treatment strategies including KRAS-mutant cancers which have been undruggable for decades. While intrinsic or acquired treatment resistance remains unresolved in many cases, epigenome-targeted therapy may be an option to overcome. We recently discovered the effectiveness of blocking small ubiquitin-like modifier (SUMO) signaling cascade (SUMOylation) in MYC-expressing KRAS-mutant cancer cells using a SUMO-activating enzyme E inhibitor TAK-981 that results in SUMOylation inhibition.

GLP-1, GIP, and Glucagon Agonists for Obesity Treatment: A Hunger Perspective.

For centuries, increasingly sophisticated methods and approaches have been brought to bear to promote weight loss. Second only to the Holy Grail of research on aging, the idea of finding a single and simple way to lose weight has long preoccupied the minds of laymen and scientists alike. The effects of obesity are far-reaching and not to be minimized; the need for more effective treatments is obvious.

Identification, Characterization, and Antibacterial Evaluation of Five Endophytic Fungi from Müll. Arg., an Amazon Plant.

Endophytic fungi, residing within plants without causing disease, are known for their ability to produce bioactive metabolites with diverse properties such as antibacterial, antioxidant, and antifungal activities, while also influencing plant defense mechanisms. In this study, five novel endophytic fungi species were isolated from the leaves of Müll. Arg.

Electrospun nonwoven fabric of poly(ε-caprolactone)/n-phosphonium chitosan for antiviral applications: Fabrication, characterization, and potential efficacy.

This work reports the virucidal properties of nonwoven fibers developed via electrospinning with polycaprolactone (PCL) and chitosan quaternized with phosphonium salt (NPCS), emphasizing the influence of NPCS concentration on the structure of fibers and their performance against the MHV-3 coronavirus. The addition of NPCS enhances solutions conductivity and viscosity, leading to fibers containing a finer porous structure with a more hydrophilic and smoother surface, thereby making them a potent barrier against respiratory particles, which is a key factor for protective face masks. In terms of degradation, NPCS paced-up the process, suggesting potential environmental benefits.

Synthesis of thermally and pH-responsive poly(2-(dimethylamino)ethyl methacrylate)-based hydrogel reinforced with cellulose nanocrystals for sustained drug release.

Hydrogels are widely employed in biomedical applications due to their high swelling potential, tailored mechanical properties, biocompatibility, and ability to incorporate drugs to modify their release behavior. This study explored the synthesis of dual stimuli-responsive composite hydrogels by combining poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) with 4, 8, and 12 % (w/w) of cellulose nanocrystals (CNC) through in-situ free-radical polymerization, modifying their properties for topical anti-inflammatory release. Although PDMAEMA-based hydrogels have been known for their responsiveness to pH and temperature stimuli, which are useful for modulating the release profile of drugs, their use as a matrix for anti-inflammatory topical applications remains unexplored.

JAK2/mTOR inhibition fails to prevent acute GVHD despite reduced Th1/Th17 cells: final phase 2 trial results.

Our phase 1 graft-versus-host disease (GVHD) prevention trial of JAK2 inhibitor, pacritinib (PAC; recommended phase 2 dose: 100 mg orally twice a day on day 0 to +70) plus sirolimus and tacrolimus (SIR/TAC) demonstrated the regimen was safe and free of pan-JAK myelosuppression after allogeneic hematopoietic cell transplantation (alloHCT). PAC inhibits interleukin 6 (IL-6) receptor activity and pathogenic T helper cell 1 (Th1)/Th17 differentiation in preclinical models and the phase 1 trial. Herein, we report on our completed phase 2 trial of PAC/SIR/TAC after 8/8 human leukocyte antigen matched alloHCT.

A Three-Step Submandibular Retropharyngeal Approach to the Craniovertebral Junction: Is Less Always More?

: Accessing the craniovertebral junction poses unique challenges due to its anatomical complexity and proximity to critical structures, such as the cord-brainstem junction, great vessels of the neck, cranial nerves, oropharynx, and rhinopharynx. Among the approaches that have been developed over the years, the submandibular retropharyngeal approach offers good antero-lateral access without the need of transgressing mucosal layers. In its traditional form, however, this approach involves multiple sequential steps and requires intricate dissection, extensive retraction, and meticulous maneuvering, which can increase operative time and produce approach-related morbidity.

Dual inhibition of SUMOylation and MEK conquers MYC-expressing KRAS-mutant cancers by accumulating DNA damage.

Background: KRAS mutations frequently occur in cancers, particularly pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer. Although KRAS inhibitors have recently been approved, effective precision therapies have not yet been established for all KRAS-mutant cancers. Many treatments for KRAS-mutant cancers, including epigenome-targeted drugs, are currently under investigation.

Expanding geographic distribution knowledge of (Batsch) Kühner (Agaricales, Hymenogastraceae) with a novel Antarctic record.

Background: The investigation of Agaricales diversity in the Antarctica is limited, with only seven genera reported for the region. stands out as the genus with the highest species diversity, including 12 species in Antarctica. This research reports the presence of in the region, providing the first complete morphological description for the specimen developing in Antarctica.

The Influence of Gun Victimization on Support for Gun Control Legislation.

The primary objective of the current study was to add to the literature and broaden our understanding of gun violence victims by examining attitudes towards gun legislation held by victims of gun violence. To our knowledge, there are only two quantitative studies that have examined the impact of victimization on attitudes towards gun control legislation. A secondary objective was to examine the link between impressions of the National Rifle Association (NRA) and gun policy preferences, which remains an understudied area in the gun legislation literature.

Linking Patient Encounters across Primary and Ancillary Electronic Health Record Systems: A Comparison of Two Approaches.

Background: To achieve scientific goals, researchers often require integration of data from a primary electronic health record (EHR) system and one or more ancillary EHR systems used during the same patient care encounter. Although studies have demonstrated approaches for linking patient identity records across different EHR systems, little is known about linking patient encounter records across primary and ancillary EHR systems.

Objectives: We compared a patients-first approach versus an encounters-first approach for linking patient encounter records across multiple EHR systems.

First-in-human study of alpibectir (BVL-GSK098), a novel potent anti-TB drug.

Background: The clinical candidate alpibectir augments the activity of, and overcomes resistance to, the anti-TB drug ethionamide in vitro and in vivo.

Objectives: A Phase 1, double-blind, randomized, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics (PK) and food effect of alpibectir administered as single and multiple oral doses in healthy volunteers (NCT04654143).

Methods: Eighty participants were randomized.

Diversity and Evolution of Frog Visual Opsins: Spectral Tuning and Adaptation to Distinct Light Environments.

Visual systems adapt to different light environments through several avenues including optical changes to the eye and neurological changes in how light signals are processed and interpreted. Spectral sensitivity can evolve via changes to visual pigments housed in the retinal photoreceptors through gene duplication and loss, differential and coexpression, and sequence evolution. Frogs provide an excellent, yet understudied, system for visual evolution research due to their diversity of ecologies (including biphasic aquatic-terrestrial life cycles) that we hypothesize imposed different selective pressures leading to adaptive evolution of the visual system, notably the opsins that encode the protein component of the visual pigments responsible for the first step in visual perception.

Preliminary Technical Validation of LittleBeats™: A Multimodal Sensing Platform to Capture Cardiac Physiology, Motion, and Vocalizations.

Across five studies, we present the preliminary technical validation of an infant-wearable platform, LittleBeats™, that integrates electrocardiogram (ECG), inertial measurement unit (IMU), and audio sensors. Each sensor modality is validated against data from gold-standard equipment using established algorithms and laboratory tasks. Interbeat interval (IBI) data obtained from the LittleBeats™ ECG sensor indicate acceptable mean absolute percent error rates for both adults (Study 1, = 16) and infants (Study 2, = 5) across low- and high-challenge sessions and expected patterns of change in respiratory sinus arrythmia (RSA).

Long-term follow-up of a healthy man with endogenous Streptococcus anginosus endophthalmitis.

We report the long-term follow-up of an immunocompetent patient who presented with slowly progressive endogenous endophthalmitis secondary to Streptococcus anginosus. A 46-year-old healthy man presented with a two-month history of right eye iritis. On examination, visual acuity was 20/60 with intraocular pressure of 6 mm Hg.

Expanding capabilities to evaluate readiness for return to duty after mTBI: The CAMP study protocol.

Unlabelled: Physical Therapists affiliated with Intrepid Spirit Centers evaluate and treat Active Duty Service Members (ADSM) who have duty-limiting post-concussion symptoms to improve the ability to perform challenging tasks associated with military service. The Complex Assessment of Military Performance (CAMP) is a test battery that more closely approximates the occupational demands of ADSM without specific adherence to a particular branch of service or military occupational specialty. Subtasks were developed with military collaborators to include high level skills that all service members must be able to perform such as reacting quickly, maintaining visual stability while moving and changing positions, and scanning for, noting, and/or remembering operationally relevant information under conditions of physical exertion.

Comparative Merits of Available Mortality Data Sources for Clinical Research.

Obtaining reliable data on patient mortality is a critical challenge facing observational researchers seeking to conduct studies using real-world data. As these analyses are conducted more broadly using newly-available sources of real-world evidence, missing data can serve as a rate-limiting factor. We conducted a comparison of mortality data sources from different stakeholder perspectives - academic medical center (AMC) informatics service providers, AMC research coordinators, industry analytics professionals, and academics - to understand the strengths and limitations of differing mortality data sources: locally generated data from sites conducting research, data provided by governmental sources, and commercially available data sets.