Balancing anticancer therapy efficacy and safety in advanced hepatocellular carcinoma: a case report.

Background: Hepatocellular carcinoma (HCC) is a significant health problem associated with several risk factors, increasingly driven by non-alcoholic steatohepatitis and metabolic syndrome. This association poses a challenge for the primary treatments of HCC, which may include immune checkpoint inhibitors and vascular endothelial growth factor inhibitors, due to their potential cardiotoxic effect. Therefore, it is imperative to balance the therapeutic effects of these agents with their potential cardiovascular adverse events.

New Horizons in Menopause, Menopausal Hormone Therapy, and Alzheimer's Disease: Current Insights and Future Directions.

Accumulating evidence suggests that the effects of menopausal hormone therapy (MHT) on risk of Alzheimer's disease (AD) and all-cause dementia are influenced by timing of initiation relative to age and time-since-menopause and the type of formulation. Randomized clinical trials (RCTs) of MHT conducted in older postmenopausal women indicate an increased risk of dementia. While RCTs conducted in midlife are lacking, observational research has provided evidence for associations between midlife estrogen-only therapy (ET) use and a reduced risk of AD dementia, whereas estrogen-progestogen therapy (EPT) is associated with more variable outcomes.

Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity.

We have assessed antiviral activity and induction of protective immunity of fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain of SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The lipopeptides block SARS-CoV-2 infection in cell lines and lung-derived organotypic cultures. Intranasal administration in mice allows the maintenance of homeostatic transcriptomic immune profile in lungs, prevents body-weight loss, decreases viral load and shedding, and protects mice from death caused by SARS-CoV-2 variants.

IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer.

Tertiary lymphoid structures (TLSs) are de novo ectopic lymphoid aggregates that regulate immunity in chronically inflamed tissues, including tumours. Although TLSs form due to inflammation-triggered activation of the lymphotoxin (LT)-LTβ receptor (LTβR) pathway, the inflammatory signals and cells that induce TLSs remain incompletely identified. Here we show that interleukin-33 (IL-33), the alarmin released by inflamed tissues, induces TLSs.

Chimeric antigen receptor macrophages (CAR-M) sensitize HER2+ solid tumors to PD1 blockade in pre-clinical models.

We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we develop clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduce tumor burden, prolong survival, remodel the TME, increase intratumoral T cell and natural killer (NK) cell infiltration, and induce antigen spreading.

Psychometric Evaluation of the Scleroderma Skin Questionnaire: A Novel Patient Reported Outcome for Skin Disease in Patients with Systemic Sclerosis.

Objective: To evaluate the psychometric properties of the Scleroderma Skin Questionnaire (SSQ), a novel patient-reported outcome (PRO) to assess systemic sclerosis (SSc) related skin symptoms.

Methods: The SSQ was administered to 799 adults (mean age 52.7; 82% female) enrolled in the SSc Collaborative National Quality and Efficacy Registry (CONQUER).

Observation of broadband super-absorption of electromagnetic waves through space-time symmetry breaking.

Using time as an additional design parameter in electromagnetism, photonics, and wave physics is attracting considerable research interest, motivated by the possibility to explore physical phenomena and engineering opportunities beyond the limits of time-invariant systems. Here, we report the experimental demonstration of enhanced broadband absorption of electromagnetic waves in a continuously modulated time-varying system, exceeding one of the key theoretical limits of linear time-invariant absorbers. This is achieved by harnessing the frequency-wave vector transitions and enhanced interference effects enabled by breaking both continuous space- and time-translation symmetries in a periodically time-modulated absorbing structure operating at radio frequencies.

General Kernel Machine Methods for Multi-Omics Integration and Genome-Wide Association Testing With Related Individuals.

Integrating multi-omics data may help researchers understand the genetic underpinnings of complex traits and diseases. However, the best ways to integrate multi-omics data and use them to address pressing scientific questions remain a challenge. One important and topical problem is how to assess the aggregate effect of multiple genomic data types (e.

Global regulators enable bacterial adaptation to a phenotypic trade-off.

Cellular fitness depends on multiple phenotypes that must be balanced during evolutionary adaptation. For instance, coordinating growth and motility is critical for microbial colonization and cancer invasiveness. In bacteria, these phenotypes are controlled by local regulators that target single operons, as well as by global regulators that impact hundreds of genes.

Advanced Restriction Imaging and Reconstruction Technology for Prostate Magnetic Resonance Imaging (ART-Pro): A Study Protocol for a Multicenter, Multinational Trial Evaluating Biparametric Magnetic Resonance Imaging and Advanced, Quantitative Diffusion Magnetic Resonance Imaging for the Detection of Prostate Cancer.

Multiparametric magnetic resonance imaging (mpMRI) is strongly recommended by current clinical guidelines for improved detection of clinically significant prostate cancer (csPCa). However, the major limitations are the need for intravenous (IV) contrast and dependence on reader expertise. Efforts to address these issues include use of biparametric magnetic resonance imaging (bpMRI) and advanced, quantitative magnetic resonance imaging (MRI) techniques.

Role of A-Site Cation Hydrogen Bonds in Hybrid Organic-Inorganic Perovskites: A Theoretical Insight.

Hybrid organic-inorganic halide perovskites (HOIPs) have garnered a significant amount of attention due to their exceptional photoelectric conversion efficiency. However, they still face considerable challenges in large-scale applications, primarily due to their instability. One key factor influencing this instability is the lattice softness attributed to the A-site cations.

The role of human intestinal mucus in the prevention of microplastic uptake and cell damage.

An increase in plastic waste and its release into the environment has led to health concerns over microplastics (MPs) in the environment. The intestinal mucosal layer is a key defense mechanism against ingested MPs, preventing the migration of particles to other parts of the body. MP migration through intestinal mucus is challenging to study due to difficulties in obtaining intact mucus layers for testing and numerous formulations, shapes, and sizes of microplastics.

Patient-reported outcomes in genital gender-affirming surgery.

Purpose Of Review: We reviewed the latest articles in patient-reported outcomes as it relates to genital gender-affirming surgery (GGAS) and provide a narrative summary of each article.

Recent Findings: The current landscape of patient-reported outcomes measures (PROMs) within GGAS largely consists of various ad hoc questionnaires. Within the last two years, one new PROM, validated within the transgender and gender-diverse (TGD) community, have been described.

A novel susceptibility locus to () identified by genetic mapping of automated microscopy computer vision data in grapevines.

Powdery mildew, caused by the fungus , is one of the primary causes of grape yield loss across the globe. While numerous resistance loci have been identified in various grapevine species, the genetic determinants of susceptibility to remain largely unexplored. Understanding the genetics of susceptibility for pathogenesis is equally important for developing durable resistance grapevines against this pathogen.

"New Normal:" Opportunities and Challenges Faced by Syringe Service Programs Following the Effects of the COVID-19 Pandemic.

Syringe services programs (SSPs) provide critical evidence-based public health services that decrease harms from drug use for people who use drugs (PWUD). Many SSPs have experienced significant and evolving COVID-19-related disruptions. We aimed to characterize the impacts of COVID-19 on SSP operations in the United States approximately two years into the pandemic.

2-[F]Fluoropropionic Acid PET Imaging of Doxorubicin-Induced Cardiotoxicity.

Purpose: Treatment of pediatric cancers with doxorubicin is a common and predictable cause of cardiomyopathy. Early diagnosis of treatment-induced cardiotoxicity and intervention are major determinants for the prevention of advanced disease. The onset of cardiomyopathies is often accompanied by profound changes in lipid metabolism, including an enhanced uptake of short-chain fatty acids (SCFA).

Governance and resilience as entry points for transforming food systems in the countdown to 2030.

Due to complex interactions, changes in any one area of food systems are likely to impact-and possibly depend on-changes in other areas. Here we present the first annual monitoring update of the indicator framework proposed by the Food Systems Countdown Initiative, with new qualitative analysis elucidating interactions across indicators. Since 2000, we find that 20 of 42 indicators with time series have been trending in a desirable direction, indicating modest positive change.

Activation of three targets by a TAL effector confers susceptibility to bacterial blight of cotton.

Bacterial transcription activator-like effectors (TALEs) promote pathogenicity by activating host susceptibility (S) genes. To understand the pathogenicity and host adaptation of Xanthomonas citri pv. malvacearum (Xcm), we assemble the genome and the TALE repertoire of three recent Xcm Texas isolates.

Best Practice Guidelines for Collecting Microbiome Samples in Research Studies.

Microbiome research has the potential to provide valuable information regarding the complex relationship between microbial communities and the human body. To help facilitate the translation of this potentially revolutionary research to clinical medicine, common guidelines and best practices are necessary. These guidelines should be based on the key findings of recent research in the field and address the primary areas of discrepancy in the previously published literature.

Opioid use and abuse in adolescents and young adults; dealing with science, laws and ethics: Charming the COBRAS.

The subject of substance use disorders in the pediatric population remains a disturbing conundrum for clinicians, researchers and society in general. Many of our youth are at risk of being damaged and even killed by drug addictions that result from the collision of rapidly developing as well as vulnerable central nervous systems encountering the current global drug addiction crisis. A major motif of this chemical calamity is opioid use disorder in adolescents and young adults that was stimulated by the 19th century identification of such highly addictive drugs as morphine, heroin and a non-opiate, cocaine.

The trochlea for the intermediate tendon of the digastric muscle: a review.

This review explores the novel perspective that the intermediate tendon of the digastric muscle may function as an anatomical trochlear pulley system within the human body, challenging the traditional understanding of trochlear systems. While widely recognized trochlear units include structures like the medial part of the humerus and the superior oblique muscle of the orbit, the review focuses on the unique anatomical arrangement of the intermediate tendon of the digastric muscle in connection with the anterior and posterior bellies of the digastric muscles. Despite current debates within the anatomical community about labeling the digastric muscles as having a trochlea, this paper delves into the scientific definition of a trochlear pulley system, presenting the intermediate tendon of the digastric muscle as a potential trochlea.

Nanopore RNA direct sequencing identifies that mA modification is essential for sorbitol-controlled resistance to Alternaria alternata in apple.

Sorbitol, a main photosynthate and transport carbohydrate in all tree fruit species in Rosaceae, acts as a signal controlling resistance against Alternaria (A.) alternata in apple by altering the expression of the MdNLR16 resistance gene via the MdWRKY79 transcription factor. However, it is not known if N-methyladenosine (mA) methylation of the mRNAs of these genes participates in the process.