State-of-the-Art Liver Cancer Organoids: Modeling Cancer Stem Cell Heterogeneity for Personalized Treatment.

Liver cancer poses a global health challenge with limited therapeutic options. Notably, the limited success of current therapies in patients with primary liver cancers (PLCs) may be attributed to the high heterogeneity of both hepatocellular carcinoma (HCCs) and intrahepatic cholangiocarcinoma (iCCAs). This heterogeneity evolves over time as tumor-initiating stem cells, or cancer stem cells (CSCs), undergo (epi)genetic alterations or encounter microenvironmental changes within the tumor microenvironment.

Backbone assignment of the N-terminal domain of the A subunit of the Bacillus cereus GerI germinant receptor.

The nutrient germinant receptors (GRs) in spores of Bacillus species consist of a cluster of three proteins- designated A, B, and C subunits- that play a critical role in initiating the germination of dormant spores in response to specific nutrient molecules. The Bacillus cereus GerI GR is essential for inosine-induced germination; however, the roles of the individual subunits and the mechanism by which germinant binding activates GR function remain unclear. In this study, we report the backbone chemical shift assignments of the N-terminal domain (NTD) of the A subunit of GerI (GerIA).

ds-FCRN: three-dimensional dual-stream fully convolutional residual networks and transformer-based global-local feature learning for brain age prediction.

The brain undergoes atrophy and cognitive decline with advancing age. The utilization of brain age prediction represents a pioneering methodology in the examination of brain aging. This study aims to develop a deep learning model with high predictive accuracy and interpretability for brain age prediction tasks.

The effect of different timings of protein supplementation on variable outcomes in hemodialysis patients: a randomized clinical trial.

Background: Oral nutritional supplements (ONS) are commonly prescribed to provide protein and energy to hemodialysis (HD) patients. There is a debate about the appropriate timing to administer ONS. We aimed to study the effect of different timings of ONS on variable outcomes in HD patients.

Effectiveness and cytokine profile of combined anti-vascular endothelial growth factor and corticosteroid therapy for chronic retinal vein occlusion.

Purpose: To investigate whether sub-Tenon injection of triamcinolone acetonide (STTA) combined with anti-vascular endothelial growth factor (VEGF) prolongs the recurrence intervals of macular edema (ME) for chronic retinal vein occlusion (RVO) and to investigate the differences in intraocular inflammatory cytokines between good responders (GRs) and non-responders (NRs).

Methods: This retrospective, observational study involved 42 eyes of 42 patients with ME due to chronic RVO who had received only anti-VEGF for ≥ 1 year and were transitioned to combination therapy. GRs were defined as patients whose recurrence intervals were prolonged by ≥ 2 weeks compared with patients receiving anti-VEGF alone.

Localization of Cholecystokinin/Sulfakinin Neuropeptides in Biomphalaria glabrata, an Intermediate Host for Schistosomiasis.

Snails belonging to the genus Biomphalaria serve as obligatory intermediate hosts for the trematode Schistosoma mansoni, the causative agent for the most widespread form of schistosomiasis. The simpler nervous systems of gastropod molluscs, such as Biomphalaria, provide advantageous models for investigating neural responses to infection at the cellular and network levels. The present study examined neuropeptides related to cholecystokinin (CCK), a major multifunctional regulator of central nervous system (CNS) function in mammals.

Public opinion outweighs knowledge: A dual-process framework for understanding acceptance of genetic modification among scientists and laypeople.

Communication research on scientific issues has traditionally relied on the deficit model, which posits that increasing scientific knowledge leads to public acceptance. However, this model's effectiveness is questioned due to inconclusive impacts of knowledge on acceptance. To address this, we propose a dual-process framework combining the deficit model (with scientific knowledge as a key predictor) and a normative opinion process model (where perceived majority opinion plays a crucial role) to predict people's risk/benefit perceptions and their support for genetic modification (GM).

Population Genomics Reveals Local Adaptation Related to Temperature Variation in Two Stream Frog Species: Implications for Vulnerability to Climate Warming.

Identifying populations at highest risk from climate change is a critical component of conservation efforts. However, vulnerability assessments are usually applied at the species level, even though intraspecific variation in exposure, sensitivity and adaptive capacity play a crucial role in determining vulnerability. Genomic data can inform intraspecific vulnerability by identifying signatures of local adaptation that reflect population-level variation in sensitivity and adaptive capacity.

Relaxometry and contrast-free cerebral microvascular quantification using balanced steady-state free precession MR fingerprinting.

Purpose: This study proposes a novel, contrast-free Magnetic Resonance Fingerprinting (MRF) method using balanced Steady-State Free Precession (bSSFP) sequences for the quantification of cerebral blood volume (CBV), vessel radius (R), and relaxometry parameters (T , T , T *) in the brain.

Methods: The technique leverages the sensitivity of bSSFP sequences to intra-voxel frequency distributions in both transient and steady-state regimes. A dictionary-matching process is employed, using simulations of realistic mouse microvascular networks to generate the MRF dictionary.

Psychometric Examination of the Proposed Specifiers for Conduct Disorder Self-Report (PSCD) Among an Adult Community Sample From Brazil.

The Proposed Specifiers for Conduct Disorder (PSCD) is a promising novel scale that measures psychopathic traits and includes an additional conduct disorder factor that taps the antisocial dimension of psychopathy. The current study sought to broaden the application of PSCD by examining the factor structure, convergent and discriminant validity, and connections to delinquency in a young adult sample ( = 450;  = 31.91 years,  = 13.

The interplay of sex and genotype in disease associations: a comprehensive network analysis in the UK Biobank.

Background: Disease comorbidities and longer-term complications, arising from biologically related associations across phenotypes, can lead to increased risk of severe health outcomes. Given that many diseases exhibit sex-specific differences in their genetics, our objective was to determine whether genotype-by-sex (GxS) interactions similarly influence cross-phenotype associations. Through comparison of sex-stratified disease-disease networks (DDNs)-where nodes represent diseases and edges represent their relationships-we investigate sex differences in patterns of polygenicity and pleiotropy between diseases.

Incidence of hospital-acquired infections due to carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa in critically ill patients in Italy: a multicentre prospective cohort study.

Background: Carbapenem-Resistant Gram-Negative Bacteria, including Carbapenem-Resistant Enterobacterales (CRE) and Carbapenem-Resistant Pseudomonas aeruginosa (CRPA), are common causes of infections in intensive care units (ICUs) in Italy.

Objective: This prospective observational study evaluated the epidemiology, management, microbiological characterization, and outcomes of hospital-acquired CRE or CRPA infections treated in selected ICUs in Italy.

Methods: The study included patients with hospital-acquired infections due to CRE and CRPA treated in 20 ICUs from June 2021 to February 2023.

The association between the dietary index for gut microbiota and metabolic dysfunction-associated fatty liver disease: a cross-sectional study.

Background: The relationship between the gut microbiome and metabolic dysfunction-associated fatty liver disease (MAFLD) has garnered increasing attention. However, the association between the dietary index for gut microbiota (DI-GM), a measure of microbiome diversity, and MAFLD has yet to be fully explored.

Methods: Data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) were analyzed, including 7243 participants.

Association of clinical knowledge with patient care ownership among resident physicians: a nationwide cross-sectional study in Japan.

Purpose: Both clinical knowledge and patient care ownership (PCO) are crucial to the provision of quality patient care and should be acquired during training. However, the association between these two concepts is under-examined. Here, we conducted a nationwide cross-sectional study to investigate the association between clinical knowledge and PCO among resident physicians in Japan.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.

Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity.

Cancer cells frequently rewire their metabolism to support proliferation and evade immune surveillance, but little is known about metabolic targets that could increase immune surveillance. Here we show a specific means of mitochondrial respiratory complex I (CI) inhibition that improves tumor immunogenicity and sensitivity to immune checkpoint blockade (ICB). Targeted genetic deletion of either Ndufs4 or Ndufs6, but not other CI subunits, induces an immune-dependent growth attenuation in melanoma and breast cancer models.

Enhanced sampling of protein conformational changes via true reaction coordinates from energy relaxation.

The bottleneck in enhanced sampling lies in finding collective variables that effectively accelerate protein conformational changes; true reaction coordinates that accurately predict the committor are the well-recognized optimal choice. However, identifying them requires unbiased natural reactive trajectories, which, paradoxically, require effective enhanced sampling. Using the generalized work functional method, we uncover that true reaction coordinates control both conformational changes and energy relaxation, enabling us to compute them from energy relaxation simulations.

Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial.

Background: Intratumoral oncolytic herpes simplex virus 2-GM CSF (OH2) injection has shown safety and antitumor efficacy in patients with solid tumors. Here, we examined the safety and efficacy of OH2 as a single agent or in combination with HX008, an NMPA-approved PD-1 inhibitor, in locally advanced or metastatic sarcoma patients.

Methods: This multicenter, phase 1/2 trial enrolled patients with injectable sarcoma lesions, who had failed at least 1 or more lines of standard treatment.

Effects of Combined Antiemetic Protocol for the Prevention of Postoperative Nausea and Vomiting in Orthognathic Surgery: A Randomized Double Blinded Clinical Study.

Background: Postoperative nausea and vomiting (PONV) after orthognathic surgery remains one of the most common side effects despite the use of several medications.

Purpose: The study aimed to compare the frequencies of PONV between a combination of metoclopramide with granisetron and granisetron alone.

Study Design, Setting, Sample: A randomized double-blind clinical trial was conducted in 66 consecutive patients who underwent orthognathic surgery at the Department of Oral and Maxillofacial Surgery at Bezmialem Vakif University.

Fixation for Osteochondral Lesions of the Talus Leads to Successful Clinical Outcomes in 9 out of 10 Patients: a Systematic Review.

Importance: Osteochondral lesions of the talus (OLT) with an osteochondral fragment are amendable for fixation. Fixation aims to stabilize the osteochondral fragment while retaining the native cartilage. Though fixation for OLT is a promising treatment, no systematic overview of the literature on its efficacy and safety exists.

Development and Validation of a Minimally Invasive Transuterine Experimental Model of Gastroschisis.

Introduction: Perinatal management of gastroschisis remains a subject of substantial research. Current models, including teratogenic, genetic, and surgical approaches, often fail to accurately replicate gastroschisis, exhibiting limitations such as inaccurate phenotyping, low success rates, high mortality, lack of scientific validation, and significant technical challenges. Refined disease models are essential for improving the understanding of GS.

Nitrous oxide production via enzymatic nitroxyl from the nitrifying archaeon .

Ammonia oxidizing archaea (AOA) are among the most abundant microorganisms on earth and are known to be a major source of nitrous oxide (NO) emissions, although biochemical origins of this NO remain unknown. Enzymological details of AOA nitrogen metabolism are broadly unavailable. We report the recombinant expression, purification, and characterization of a multicopper oxidase, Nmar_1354, from the AOA .

Plant BCL-DOMAIN HOMOLOG proteins play a conserved role in SWI/SNF complex stability.

The SWItch/Sucrose Non-Fermenting (SWI/SNF) complexes are evolutionarily conserved, ATP-dependent chromatin remodelers crucial for multiple nuclear functions in eukaryotes. Recently, plant BCL-DOMAIN HOMOLOG (BDH) proteins were identified as shared subunits of all plant SWI/SNF complexes, significantly impacting chromatin accessibility and various developmental processes in Arabidopsis. In this study, we performed a comprehensive characterization of mutants, revealing the role of BDH in hypocotyl cell elongation.