TAK-994 Mechanistic Investigation into Drug-Induced Liver Injury.

The frequency of drug-induced liver injury (DILI) in clinical trials remains a challenge for drug developers despite advances in human hepatotoxicity models and improvements in reducing liver-related attrition in preclinical species. TAK-994, an oral orexin receptor 2 agonist, was withdrawn from phase II clinical trials due to the appearance of severe DILI. Here, we investigate the likely mechanism of TAK-994 DILI in hepatic cell culture systems examined cytotoxicity, mitochondrial toxicity, impact on drug transporter proteins, and covalent binding.

The skull of the semi-aquatic neotropical lizard Echinosaura horrida (Gymnophthalmidae: Cercosaurinae) reveals new synapomorphies within Gymnophthalmoidea.

The rough teiid or water cork lizard (Echinosaura horrida) is a small reptile from Colombia and Ecuador placed in a genus that contains eight species and well-known phylogenetic relationships. Here we provide a detailed description and illustrations, bone by bone, of its skull, while we discussed its intraspecific variation by comparing high-resolution computed tomography data from two specimens and the variation within the genus by including previously published data from Echinosaura fischerorum. This allowed to propose putative diagnostic character states for Echinosaura horrida and synapomorphies for Echinosaura.

Evaluating the effect of NPO status on mucosal coating during double contrast barium esophagrams.

Introduction: Current guidelines for double contrast barium esophagography studies (BAS) suggest that patients should be nil per os (NPO) prior to completing BAS for optimal esophageal coating, although the time required varies between practices and institutions. It is believed that consumption of food or water disrupts the ability for thick barium contrast to properly coat the esophageal mucosa. Exams that are rescheduled for this reason can lead to delays in care, without substantial evidence that NPO status truly affects esophageal mucosal coating for these exams with current barium mixtures.

The Arabidopsis leaf quantitative atlas: a cellular and subcellular mapping through unified data integration.

Quantitative analyses and models are required to connect a plant's cellular organisation with its metabolism. However, quantitative data are often scattered over multiple studies, and finding such data and converting them into useful information is time-consuming. Consequently, there is a need to centralise the available data and to highlight the remaining knowledge gaps.

Investigation of genetic determinants of cognitive change in later life.

Cognitive decline is a major health concern and identification of genes that may serve as drug targets to slow decline is important to adequately support an aging population. Whilst genetic studies of cross-sectional cognition have been carried out, cognitive change is less well-understood. Here, using data from the TOMMORROW trial, we investigate genetic associations with cognitive change in a cognitively normal older cohort.

Mechanisms of T cell evasion by Epstein-Barr virus and implications for tumor survival.

Epstein-Barr virus (EBV) is a prevalent oncogenic virus estimated to infect greater than 90% of the world's population. Following initial infection, it establishes latency in host B cells. EBV has developed a multitude of techniques to avoid detection by the host immune system and establish lifelong infection.

ACR Appropriateness Criteria® Abnormal Liver Function Tests.

Liver function tests are commonly obtained in symptomatic and asymptomatic patients. Various overlapping lab patterns can be seen due to derangement of hepatocytes and bile ducts function. Imaging tests are pursued to identify underlying etiology and guide management based on the lab results.

Plasma neurofilament light levels show elevation two years prior to diagnosis of amyotrophic lateral sclerosis in the UK Biobank.

Objective: Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease with profound unmet need. In patients carrying genetic mutations, elevations in neurofilament light (NfL) have been shown to precede symptom onset, however, the natural history of NfL in general ALS patients is less characterized.

Methods: We performed a secondary analysis of the UK Biobank Pharma Proteomics Project (UKB-PPP), a subset of the UK Biobank, a population-based cohort study in the United Kingdom, to examine plasma NfL levels in 237 participants subsequently diagnosed with ALS.

Epigenetic Mechanisms in Obesity: Broadening Our Understanding of the Disease.

Now recognized as more than just the result of overeating or the consumption of poor-quality foods, obesity is understood to be a multifactorial disease, strongly correlated with a variety of environment-gene interactions. In addressing the complex public health issue of obesity, medical practitioners, along with their allied healthcare counterparts, face the challenge of reducing its prevalence by utilizing and sharing with patients the current, yet incomplete, scientific knowledge concerning the disease. While continued research is required to strengthen direct cause-effect relationships, substantial evidence links post-translational modifications such as DNA methylation and histone modifications of several candidate "obesity" genes to the predilection for obesity.

Observation of suppressed viscosity in the normal state of He due to superfluid fluctuations.

Evidence of fluctuations in transport have long been predicted in He. They are expected to contribute only within 100μK of T and play a vital role in the theoretical modeling of ordering; they encode details about the Fermi liquid parameters, pairing symmetry, and scattering phase shifts. It is expected that they will be of crucial importance for transport probes of the topologically nontrivial features of superfluid He under strong confinement.

Improving photosynthetic efficiency toward food security: Strategies, advances, and perspectives.

Photosynthesis in crops and natural vegetation allows light energy to be converted into chemical energy and thus forms the foundation for almost all terrestrial trophic networks on Earth. The efficiency of photosynthetic energy conversion plays a crucial role in determining the portion of incident solar radiation that can be used to generate plant biomass throughout a growth season. Consequently, alongside the factors such as resource availability, crop management, crop selection, maintenance costs, and intrinsic yield potential, photosynthetic energy use efficiency significantly influences crop yield.

Everyday advocacy.

When considering advocacy, many people think of the political fundraising form, and assume it is difficult to carry out, or that it requires a big investment of time, energy, or money. However, advocacy comes in many different forms, and can be implemented every day. A more mindful approach and a few small, but critical, steps can take our advocacy to a new, more intentional level; one that we can practice every day.

A new species of (Serpentes, Dipsadidae) from central Panama.

A new species of Laurenti, 1768, from Central Panama is described based on molecular analyses, hemipenial morphology, and external characters. This is the sixth species of to be described for the country; the snake has been suspected to exist since 1977 and has not been thoroughly studied until now. Additionally, morphological comparations including scale counts are done with other species within the genus, and the current geographic distribution of (Werner, 1909), the sister species, is updated.

Liver Fibrosis, Fat, and Iron Evaluation with MRI and Fibrosis and Fat Evaluation with US: A Practical Guide for Radiologists.

Quantitative imaging biomarkers of liver disease measured by using MRI and US are emerging as important clinical tools in the management of patients with chronic liver disease (CLD). Because of their high accuracy and noninvasive nature, in many cases, these techniques have replaced liver biopsy for the diagnosis, quantitative staging, and treatment monitoring of patients with CLD. The most commonly evaluated imaging biomarkers are surrogates for liver fibrosis, fat, and iron.

Evaluation of the "rethink stress" mindset intervention: A metacognitive approach to changing mindsets.

Experimental research has demonstrated that a stress-is-enhancing mindset can be induced and can improve outcomes by presenting information on the enhancing nature of stress. However, experimental evidence, media portrayals, and personal experience about the debilitating nature of stress may challenge this mindset. Thus, the traditional approach of focusing on the more "desired" mindset without arming participants against encounters with the less desired mindsets may not be sustainable in the face of conflicting information.

Where and with whom does a brief social-belonging intervention promote progress in college?

A promising way to mitigate inequality is by addressing students' worries about belonging. But where and with whom is this social-belonging intervention effective? Here we report a team-science randomized controlled experiment with 26,911 students at 22 diverse institutions. Results showed that the social-belonging intervention, administered online before college (in under 30 minutes), increased the rate at which students completed the first year as full-time students, especially among students in groups that had historically progressed at lower rates.

Negative modulation of AMPA receptors bound to transmembrane AMPA receptor regulatory protein γ-8 blunts the positive reinforcing properties of alcohol and sucrose in a brain region-dependent manner in male mice.

Rationale: The development and progression of alcohol use disorder (AUD) are widely viewed as maladaptive neuroplasticity. The transmembrane alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) regulatory protein γ8 (TARP γ-8) is a molecular mechanism of neuroplasticity that has not been evaluated in AUD or other addictions.

Objective: To address this gap in knowledge, we evaluated the mechanistic role of TARP γ-8 bound AMPAR activity in the basolateral amygdala (BLA) and ventral hippocampus (vHPC) in the positive reinforcing effects of alcohol, which drive repetitive alcohol use throughout the course of AUD, in male C57BL/6 J mice.

Rapid, Accurate Classification of Single Emitters in Various Conditions and Environments for Blinking-Based Multiplexing.

Although single-molecule imaging is widely applied in biology and materials science, most studies are limited by their reliance on spectrally distinct fluorescent probes. We recently introduced blinking-based multiplexing (BBM), a simple approach to differentiate spectrally overlapped single emitters based solely on their intrinsic blinking dynamics. The original proof-of-concept study implemented two methods for emitter classification: an empirically derived metric and a deep learning algorithm, both of which have significant drawbacks.

Updates on LI-RADS Treatment Response Criteria for Hepatocellular Carcinoma: Focusing on MRI.

As the incidence of hepatocellular carcinoma (HCC) and subsequent treatments with liver-directed therapies rise, the complexity of assessing lesion response has also increased. The Liver Imaging Reporting and Data Systems (LI-RADS) treatment response algorithm (LI-RADS TRA) was created to standardize the assessment of response after locoregional therapy (LRT) on contrast-enhanced CT or MRI. Originally created based on expert opinion, these guidelines are currently undergoing revision based on emerging evidence.

Temporal segregation of biosynthetic processes is responsible for metabolic oscillations during the budding yeast cell cycle.

Many cell biological and biochemical mechanisms controlling the fundamental process of eukaryotic cell division have been identified; however, the temporal dynamics of biosynthetic processes during the cell division cycle are still elusive. Here, we show that key biosynthetic processes are temporally segregated along the cell cycle. Using budding yeast as a model and single-cell methods to dynamically measure metabolic activity, we observe two peaks in protein synthesis, in the G1 and S/G2/M phase, whereas lipid and polysaccharide synthesis peaks only once, during the S/G2/M phase.

Disruptive Behavior: Impact on Diversity, Equity, and Inclusion (DEI) in Radiology, From the Special Series on DEI.

Radiology has recognized the need to increase the diversity of its workforce for decades; however, women and people of color remain disproportionately underrepresented. A welcoming and inclusive environment is essential to physician recruitment and retention, but disruptive behavior in the workplace can be a barrier to achieving this goal. Disruptive behavior can be overt or subtle, can be intentional or inadvertent, and can occur in different settings throughout a radiologist's career, including during patient care, among colleagues, from department leadership, and even from professional societies.

Isotopically non-stationary metabolic flux analysis of heterotrophic cell cultures.

Fluxes are the ultimate phenotype of metabolism and their accurate quantification is fundamental to any understanding of metabolic networks. Steady state metabolic flux analysis has been the method of choice for quantifying fluxes in heterotrophic cells, but it is unable to measure fluxes during short-lived metabolic states, such as a transient oxidative load. Isotopically non-stationary metabolic flux analysis (INST-MFA) can be performed over shorter timescales (minutes - hours) and might overcome this limitation.