A Narrative Review of Cardiometabolic Profiles among U.S. Adults: Temporal Trends and Implications.

Purpose Of Review: To provide a narrative overview of trends and disparities in the cardiometabolic profiles of U.S. adults by synthesizing findings from nationally representative studies conducted between 1999 and 2020.

Non-parametric Bayesian deep learning approach for whole-body low-dose PET reconstruction and uncertainty assessment.

Positron emission tomography (PET) imaging plays a pivotal role in oncology for the early detection of metastatic tumors and response to therapy assessment due to its high sensitivity compared to anatomical imaging modalities. The balance between image quality and radiation exposure is critical, as reducing the administered dose results in a lower signal-to-noise ratio (SNR) and information loss, which may significantly affect clinical diagnosis. Deep learning (DL) algorithms have recently made significant progress in low-dose (LD) PET reconstruction.

A literature-based cost-effectiveness analysis of device-assisted suturing versus needle-driven suturing during laparotomy closure.

Purpose: Small-bites suturing technique for laparotomy closure is now recommended as the standard of care. However, uptake of the practice remains slow. A medical technology called the SutureTOOL has been developed which can facilitate implementation of small-bites.

Impact of preoperative frailty status on decision regret following elective hernia repair.

Purpose: Decision regret following hernia repair is common, particularly for patients who experience complications. Frailty is a risk factor for complications, but whether frailty is independently associated with regret remains unknown.

Methods: We retrospectively reviewed the Michigan Surgical Quality Collaborative Core Optimization Hernia Registry, a representative sample of adult patients from > 70 hospitals across Michigan.

Active targeting of type 1 diabetes therapies to pancreatic beta cells using nanocarriers.

Type 1 diabetes is an autoimmune disease characterised by the destruction of pancreatic beta cells, resulting in lifelong insulin dependence. Although exogenous insulin can maintain glycaemic control, this approach does not protect residual or replacement pancreatic beta cells from immune-mediated death. Current therapeutics designed to protect functional beta cell mass or promote beta cell proliferation and regeneration can have off-target effects, resulting in higher dose requirements and adverse side effects.

A physiologically based pharmacokinetic (PBPK) model describing the kinetics of a commercial mixture α-, β-, and γ-hexabromocyclododecane exposure in mice.

Hexabromocyclododecane (HBCD) is a brominated flame retardant, that is added, but not chemically bonded, to consumer products. HBCD is sold as a commercial-grade HBCD mixture containing three major stereoisomers: alpha (α), beta (β), and gamma (γ), with relative amounts of 12% for α-HBCD, 6% for β-HBCD, and 82% for γ-HBCD. HBCDs are widely measured in the environment and in biological matrices.

Stereoselective Synthesis of ()-Acrylic Nitriles from the Ruthenium-Catalyzed Coupling Reaction of Nitriles with Unsaturated Carbonyl Compounds via C-C Bond Cleavage.

Acrylic nitriles are a versatile class of synthetic precursors for a variety of pharmaceutically active compounds, as well as for nitrile polymers. We devised a stereoselective synthesis of ()-acrylic nitriles from the Ru-catalyzed coupling reaction of nitriles with unsaturated carbonyl compounds via C-C bond cleavage. Both carbon KIE and Hammett correlation data indicated that C-C bond cleavage is the rate-determining step for the coupling reaction.

The family's role in mental health care: Perceptions of Bay Area Muslims.

This qualitative study examines perceptions of Muslims living in the San Francisco Bay Area, California, United States, regarding the family's role in mental health help-seeking and well-being. This study employed a community-based participatory research approach through content analysis of three focus group ( = 37) discussions conducted with the help of a community advisory board comprised San Francisco Bay Area Muslim community members. Four main themes were generated.

Association of Self-Recognition of Hearing Loss With Hospitalizations in Older Adults in the United States.

Background: Hearing loss is highly prevalent and associated with increased health care utilization. Recognition of hearing loss may play an important role in self-advocacy in difficult communication situations and prevent negative outcomes.

Objectives: To investigate the associations between self-recognition of hearing loss and hospitalization outcomes.

Pembrolizumab ± paricalcitol in metastatic pancreatic cancer postmaximal cytoreduction.

Lessons Learned: Intravenous paricalcitol did not improve the efficacy of pembrolizumab, likely related to the short half-life.

Background: Immunotherapy has limited benefit in the treatment of advanced pancreatic cancer with the tumor microenvironment playing a key role in immune resistance. In preclinical studies, vitamin D receptor (VDR) agonists have been shown to sensitize pancreatic tumors to PD-1 blockade.

Is it time to retire preoperative radiation for localized esophageal and gastro-esophageal adenocarcinoma?

Whether preoperative chemoradiotherapy (CRT) or perioperative chemotherapy is superior for localized esophageal or gastro-esophageal junction (GEJ) cancers has been a topic of long-standing debate. For years, standard of care in the United States for localized esophageal or GEJ adenocarcinoma (EAC) has been physician's choice between the 2 strategies. More recently, adjuvant immunotherapy has also been introduced into the treatment approach for those who received neoadjuvant CRT.

Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.

Jan and mini-Jan, a model system for potato functional genomics.

Potato (Solanum tuberosum) is the third-most important food crop in the world. Although the potato genome has been fully sequenced, functional genomics research of potato lags behind that of other major food crops, largely due to the lack of a model experimental potato line. Here, we present a diploid potato line, 'Jan,' which possesses all essential characteristics for facile functional genomics studies.

A Death From Necrotizing Wound Infection After Cesarean Section: Resurgence of Group A Streptococcal Puerperal Sepsis.

Necrotizing wound infections are potentially lethal complications of surgeries, including cesarean deliveries. A 32-year-old female with obesity and hidradenitis suppurativa (HS) underwent uncomplicated cesarean section. Four days later, she developed abdominal pain and imaging showed ascites; she was treated with antibiotics.

Early and multiple doses of zoledronate mitigates rebound bone loss following withdrawal of RANKL inhibition.

Rebound bone loss following denosumab discontinuation is an important barrier in the effective long-term treatment of skeletal disorders. This is driven by increased osteoclastic bone resorption following the offset of RANKL inhibition, and sequential osteoclast-directed therapy has been utilised to mitigate this. However, current sequential treatment strategies intervene following the offset of RANKL inhibition and this approach fails to consistently prevent bone loss.

Rectification of planar orientation angle switches behavior and replenishes contractile junctions.

In the early Drosophila embryo, germband elongation is driven by oriented cell intercalation through t1 transitions, where vertical (dorsal-ventral aligned) interfaces contract and then resolve into new horizontal (anterior-posterior aligned) interfaces. Here, we show that contractile events produce a continuous "rectification" of cell interfaces, in which interfaces systematically rotate toward more vertical orientations. As interfaces rotate, their behavior transitions from elongating to contractile regimes, indicating that the planar polarized identities of cell-cell interfaces are continuously re-interpreted in time depending on their orientation angle.

Engineering of a lysosomal-targeted GAA enzyme.

Pompe disease is a tissue glycogen disorder caused by genetic insufficiency of the GAA enzyme. GAA enzyme replacement therapies for Pompe disease have been limited by poor lysosomal trafficking of the recombinant GAA molecule through the native mannose-6-phosphate-mediated pathway. Here, we describe the successful rational engineering of a chimeric GAA enzyme that utilizes the binding affinity of a modified IGF-II moiety to its native receptor to bypass the mannose-6-phosphate-mediated lysosomal trafficking pathway, conferring a significant increase in cellular uptake of the GAA enzyme.

Photocatalytic Three-Component Reductive Coupling Synthesis of -Difluorohomoallyl Secondary Amines.

-Difluorohomoallyl amines, an important class of -difluoroalkenes, are prevalent moieties in many bioactive compounds. However, limited methods are suitable for the synthesis of this type of compound containing secondary amines. Here, we display a photocatalytic multicomponent protocol for the synthesis of -difluoroalkenes containing secondary amines, which makes use of readily available materials: arylamines, alkyl aldehydes, and α-trifluoromethyl alkenes.

Reduced autoimmunity associated with deletion of host CD73.

CD73 is ubiquitously expressed and regulates critical functions across multiple organ systems. The sequential actions of CD39 and CD73 accomplish the conversion of adenosine triphosphate to adenosine and shift the adenosine triphosphate-driven proinflammatory immune cell milieu toward an anti-inflammatory state. This immunological switch is a major mechanism by which regulatory T (Treg) cells control inflammation.

CD209d/e promotes inflammation and lung injury during influenza virus infection.

Influenza virus infects millions each year, contributing greatly to human morbidity and mortality. Upon viral infection, pathogen-associated molecular patterns activate pattern recognition receptors on host cells, triggering an immune response. The CD209 protein family, homologs of DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin), is thought to modulate immune responses to viruses.

Prion protein modulation of virus-specific T cell differentiation and function during acute viral infection.

The differentiation and functionality of virus-specific T cells during acute viral infections are crucial for establishing long-term protective immunity. While numerous molecular regulators impacting T cell responses have been uncovered, the role of cellular prion proteins (PrPc) remains underexplored. Here, we investigated the impact of PrPc deficiency on the differentiation and function of virus-specific T cells using the lymphocytic choriomeningitis virus (LCMV) Armstrong acute infection model.

Defining a novel DYRK1A-gp130/IL-6R-pSTAT axis that regulates Th17 differentiation.

Dysregulated differentiation of naïve CD4+ T cells into T helper 17 (Th17) cells is likely a key factor predisposing to many autoimmune diseases. Therefore, better understanding how Th17 differentiation is regulated is essential to identify novel therapeutic targets and strategies to identify individuals at high risk of developing autoimmunity. Here, we extend our prior work using chemical inhibitors to provide mechanistic insight into a novel regulator of Th17 differentiation, the kinase dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A).