Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab.

Background & Aims: Atezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS).

Methods: In this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with advanced HCC who progressed on first-line A/B.

A rare case of double pituitary prolactinomas: the diagnostic application of intraoperative ultrasonography and DNA methylation markers.

The aim of this study is to describe the management and evolution of a patient with the rare condition of double lactotroph tumors and assess the role of intraoperative ultrasonography (IOUS) for their detection and methylation-based liquid biopsy for their diagnosis and monitoring. A 29-year-old woman diagnosed with double lactotroph tumors through hormonal and MRI workup underwent surgical resection due to cabergoline intolerance. To detect a tumor missing through visual inspection, IOUS was performed.

Investigating the structure-property correlations of pyrolyzed phenolic resin as a function of degree of carbonization.

Carbon-carbon (C/C) composites are attractive materials for high-speed flights and terrestrial atmospheric reentry applications due to their insulating thermal properties, thermal resistance, and high strength-to-weight ratio. It is important to understand the evolving structure-property correlations in these materials during pyrolysis, but the extreme laboratory conditions required to produce C/C composites make it difficult to quantify the properties . This work presents an atomistic modeling methodology to pyrolyze a crosslinked phenolic resin network and track the evolving thermomechanical properties of the skeletal matrix during simulated pyrolysis.

How digital paywalls shape news coverage.

The internet has significantly transformed how news is produced, consumed, and distributed. As a result, the news industry has transitioned from ad-supported to subscription-based models regulated by digital paywalls. In the light of this disruption, it is crucial to investigate not only how news consumers adapt to this change but also how economic incentives shape content coverage.

Spatio-temporal patterns of tigers in response to prey species and anthropogenic activities.

Understanding factors influencing the spatio-temporal patterns of apex predators is prerequisite for their conservation. We studied space use and diel activity of tigers () in response to prey availability and anthropogenic activities with trail cameras in Nepal during December 2022-March 2023. We used hierarchical occupancy models to evaluate how prey availability (space use of prey species) and anthropogenic activities (number of humans and livestock) contributed to the tigers' space use, while accounting for landscape effects on their detection probability.

Maternal deposition of hormones and contaminants shape the gonadal transcriptome in American alligators.

Environmental conditions influence the maternal deposition of hormones into eggs, which is hypothesized to adaptively modify developmental outcomes in offspring. However, most ecosystems harbour environmental contaminants capable of disrupting endocrine signaling, and maternal exposure to these compounds has the potential to further alter offspring traits. Studies rarely examine maternally derived hormones and contaminants along with offspring phenotypes, and we know little about their interrelationships and potential interactions.

Context-specific eQTLs provide deeper insight into causal genes underlying shared genetic architecture of critically ill COVID-19 and idiopathic pulmonary fibrosis.

Most genetic variants identified through genome-wide association studies (GWAS) are suspected to be regulatory in nature, but only a small fraction colocalize with expression quantitative trait loci (eQTLs, variants associated with expression of a gene). Therefore, it is hypothesized but largely untested that integration of disease GWAS with context-specific eQTLs will reveal the underlying genes driving disease associations. We used colocalization and transcriptomic analyses to identify shared genetic variants and likely causal genes associated with critically ill COVID-19 and idiopathic pulmonary fibrosis.

Submucosal Microbiome Profiles in Paired and Unpaired Samples From Healthy and Peri-Implantitis Dental Implants.

Background: This cross-sectional study aimed to compare the composition of the submucosal microbiome of peri-implantitis with paired and unpaired healthy implant samples.

Methods: We evaluated submucosal plaque samples obtained in 39 cases, including 13 cases of peri-implantitis, 13 cases involving healthy implants from the same patient (paired samples), and 13 cases involving healthy implants from different individuals (unpaired samples). The patients were evaluated using next-generation genomic sequencing (Illumina) based on 16S rRNA gene amplification.

Reductive acetogenesis is a dominant process in the ruminant hindgut.

Background: The microbes residing in ruminant gastrointestinal tracts play a crucial role in converting plant biomass to volatile fatty acids, which serve as the primary energy source for ruminants. This gastrointestinal tract comprises a foregut (rumen) and hindgut (cecum and colon), which differ in structures and functions, particularly with respect to feed digestion and fermentation. While the rumen microbiome has been extensively studied, the cecal microbiome remains much less investigated and understood, especially concerning the assembling microbial communities and overriding pathways of hydrogen metabolism.

Screening high-risk Veterans for cirrhosis: taking a stepwise population health approach.

Background: Because cirrhosis is often unrecognized, we aimed to develop a stepwise screening algorithm for cirrhosis in the Veterans Health Administration (VHA) and assess this approach's feasibility and acceptability.

Methods: VHA hepatology clinicians ("champions") were invited to participate in a pilot program from June 2020 to October 2022. The VHA Corporate Data Warehouse was queried to identify Veterans with possible undiagnosed cirrhosis using Fibrosis-4 (FIB-4) ≥ 3.

Species- and strain-specific microbial modulation of interferon, innate immunity, and epithelial barrier in 2D air-liquid interface respiratory epithelial cultures.

Background: The microbiome regulates the respiratory epithelium's immunomodulatory functions. To explore how the microbiome's biodiversity affects microbe-epithelial interactions, we screened 58 phylogenetically diverse microbes for their transcriptomic effect on human primary bronchial air-liquid interface (ALI) cell cultures.

Results: We found distinct species- and strain-level differences in host innate immunity and epithelial barrier response.

C-28 linker length modulates the activity of second-generation HIV-1 maturation inhibitors.

Maturation inhibitors (MIs) block HIV-1 maturation by preventing the cleavage of the capsid protein and spacer peptide 1 (CA-SP1). Bevirimat (BVM), a first-in-class MI, displayed sub-optimal efficacy in clinical trials due to presence of SP1:V7A polymorphism in the Gag protein.This polymorphism is inherently present in HIV-1 subtype C and conferred resistance to BVM.

Genotype-driven sensitivity of mice to tick-borne encephalitis virus correlates with differential host responses in peripheral macrophages and brain.

Background: Tick-borne encephalitis (TBE) is the most common tick-borne viral infection in Eurasia. Outcomes range from asymptomatic infection to fatal encephalitis, with host genetics likely playing a role. BALB/c mice have intermediate susceptibility to TBE virus (TBEV) and STS mice are highly resistant, whereas the recombinant congenic strain CcS-11, which carries 12.

NPT100-18A rescues mitochondrial oxidative stress and neuronal degeneration in human iPSC-based Parkinson's model.

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by protein aggregates mostly consisting of misfolded alpha-synuclein (αSyn). Progressive degeneration of midbrain dopaminergic neurons (mDANs) and nigrostriatal projections results in severe motor symptoms. While the preferential loss of mDANs has not been fully understood yet, the cell type-specific vulnerability has been linked to a unique intracellular milieu, influenced by dopamine metabolism, high demand for mitochondrial activity, and increased level of oxidative stress (OS).

Characteristics of Patients with Hereditary Angioedema Who Reduced Lanadelumab Treatment Administration Frequency: A Retrospective Observational Study of US Claims Data.

Background: Lanadelumab is the only long-term prophylaxis indicated for reduced administration frequency in patients with hereditary angioedema who have been well controlled for > 6 months. Understanding the characteristics of patients who reduce administration frequency will help identify populations where frequency modifications may be appropriate.

Objective: We aimed to describe characteristics of patients who did and did not reduce lanadelumab administration frequency to inform real-world dosing regimens, and characteristics indicative of sustained frequency reduction.

Use of Antihyperglycemic Medications Among US People with Limited English Proficiency.

Background: Language barriers can impact pharmaceutical disease management leading to potential health disparities among limited English proficiency (LEP) people with diabetes mellitus (DM) in the United States (US).

Objective: To assess the use of antihyperglycemic medications and estimate their impact on glycemic control by LEP status.

Design: Cross-sectional design.

Leveraging Model Master Files for Long-Acting Injectables.

The U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) hosted a public workshop on May 2-3, 2024, titled "Considerations and Potential Regulatory Applications for a Model Master File (Lachaine et al Can J Psychiatry.

Assessment of Opuntia ficus-indica supplementation on enhancing antioxidant levels.

Opuntia ficus-indica (OFi) is a major fruit source prevalent in semiarid and arid regions across various countries worldwide. It is widely recognised for its potential health benefits; however, most studies investigating its effects have been limited to pre-clinical models, highlighting the need for further validation through clinical trials. This study aimed to evaluate the effectiveness of OFi supplementation in enhancing antioxidant levels.

Rapid structural analysis of bacterial ribosomes in situ.

Rapid structural analysis of purified proteins and their complexes has become increasingly common thanks to key methodological advances in cryo-electron microscopy (cryo-EM) and associated data processing software packages. In contrast, analogous structural analysis in cells via cryo-electron tomography (cryo-ET) remains challenging due to critical technical bottlenecks, including low-throughput sample preparation and imaging, and laborious data processing methods. Here, we describe a rapid in situ cryo-ET sample preparation and data analysis workflow that results in the routine determination of sub-nm resolution ribosomal structures.

Association between changes in genital immune markers and vaginal microbiome transitions in bacterial vaginosis.

Bacterial vaginosis (BV), characterized by an imbalance in the vaginal microbiota, is a prevalent condition among women of reproductive age and a risk factor for human immunodeficiency virus, sexually transmitted infections, and preterm birth. BV is generally considered to induce mucosal inflammation, but the specific pathways and cell types involved are not well characterized. This prospective study aimed to assess associations between microbial changes and mucosal immune responses in BV patients.

Evaluation of ampicillin plus ceftobiprole combination therapy in treating Enterococcus faecalis infective endocarditis and bloodstream infection.

Enterococcus faecalis is responsible for numerous serious infections, and treatment options often include ampicillin combined with an aminoglycoside or dual beta-lactam therapy with ampicillin and a third-generation cephalosporin. The mechanism of dual beta-lactam therapy relies on the saturation of penicillin-binding proteins (PBPs). Ceftobiprole exhibits high affinity binding to nearly all E.

Isolation of PCSK9-specific nanobodies from synthetic libraries using a combined protein selection strategy.

Nanobodies (Nbs) hold great potential to replace conventional antibodies in various biomedical applications. However, conventional methods for their discovery can be time-consuming and expensive. We have developed a reliable protein selection strategy that combines magnetic activated cell sorting (MACS)-based screening of yeast surface display (YSD) libraries and functional ligand-binding identification by Tat-based recognition of associating proteins (FLI-TRAP) to isolate antigen-specific Nbs from synthetic libraries.

SARS-CoV-2 S-protein expression drives syncytia formation in endothelial cells.

SARS-CoV-2 is a viral infection, best studied in the context of epithelial cell infection. Epithelial cells, when infected with SARS-CoV-2 express the viral S-protein, which causes host cells to fuse together into large multi-nucleated cells known as syncytia. Because SARS-CoV-2 infections also frequently present with cardiovascular phenotypes, we sought to understand if S-protein expression would also result in syncytia formation in endothelial cells.

α-Copaene is a potent repellent against the Asian Citrus Psyllid Diaphorina citri.

The Asian Citrus Psyllid (ACP), Diaphorina citri, severely threatens citrus production worldwide by transmitting the greening (= Huanglongbing)-causing bacterium Candidatus Liberibacter asiaticus. There is growing evidence that the push-pull strategy is suitable to partially mitigate HLB by repelling ACP with transgenic plants engineered to produce repellents and attracting the vector to plants with a minimal disease transmission rate. Species that pull ACP away from commercial citrus plants have been identified, and transgenic plants that repel ACP have been developed.