The yeast checkpoint kinase Dun1p represses transcription of RNR genes independently of catalytic activity or Rad53p during respiratory growth.

One of the key events in DNA damage response (DDR) is activation of checkpoint kinases leading to activation of ribonucleotide reductase (RNR) and increased synthesis of deoxyribonucleotide triphosphates (dNTPs), required for DNA repair. Among other mechanisms, the activation of dNTP synthesis is driven by derepression of genes encoding RNR subunits RNR2, RNR3, and RNR4, following checkpoint activation and checkpoint kinase Dun1p-mediated phosphorylation and inactivation of transcriptional repressor Crt1p. We report here that in the absence of genotoxic stress during respiratory growth on nonfermentable carbon source acetate, inactivation of checkpoint kinases results in significant growth defect and alters transcriptional regulation of RNR2-4 genes and genes encoding enzymes of the tricarboxylic acid (TCA) and glyoxylate cycles and gluconeogenesis.

Swarm systems as a platform for open-ended evolutionary dynamics.

Artificial swarm systems have been extensively studied and used in computer science, robotics, engineering and other technological fields, primarily as a platform for implementing robust distributed systems to achieve pre-defined objectives. However, such swarm systems, especially heterogeneous ones, can also be utilized as an ideal platform for creating open-ended evolutionary dynamics that do not converge toward pre-defined goals but keep exploring diverse possibilities and generating novel outputs indefinitely. In this article, we review Swarm Chemistry and its variants as concrete sample cases to illustrate beneficial characteristics of heterogeneous swarm systems, including the cardinality leap of design spaces, multi-scale structures/behaviours and their diversity, and robust self-organization, self-repair and ecological interactions of emergent patterns, all of which serve as the driving forces for open-ended evolutionary processes.

Projection-targeted photopharmacology reveals distinct anxiolytic roles for presynaptic mGluR2 in prefrontal- and insula-amygdala synapses.

Dissecting how membrane receptors regulate neural circuits is critical for deciphering principles of neuromodulation and mechanisms of drug action. Here, we use a battery of optical approaches to determine how presynaptic metabotropic glutamate receptor 2 (mGluR2) in the basolateral amygdala (BLA) controls anxiety-related behavior in mice. Using projection-specific photopharmacological activation, we find that mGluR2-mediated presynaptic inhibition of ventromedial prefrontal cortex (vmPFC)-BLA, but not posterior insular cortex (pIC)-BLA, connections produces a long-lasting decrease in spatial avoidance.

Inter-network functional connectivity increases by beta-amyloid and may facilitate the early stage of tau accumulation.

Alzheimer's disease (AD) is pathologically marked by tau tangles and beta-amyloid (Aβ) plaques. It has been hypothesized that Aβ facilitates spread of tau outside of the medial temporal lobe (MTL), but exact mechanism of this facilitation remains unclear. We aimed to test the hypothesis that abnormal Aβ induces an increase in inter-network functional connectivity, which in turn induces early-stage tau elevation in limbic network.

Caffeine ameliorates metabolic-associated steatohepatitis by rescuing hepatic Dusp9.

Caffeine (CAFF) is abundant in black coffee. As one of the most widely consumed beverages globally, coffee has been the focus of increasing clinical and basic research, particularly regarding its benefits in alleviating metabolic dysfunction-associated steatotic liver disease (MASLD). However, the therapeutic effects of CAFF on metabolic-associated steatohepatitis (MASH) and the underlying mechanisms remain unclear.

Effect of lemborexant on sleep architecture in participants with insomnia disorder and mild obstructive sleep apnea.

Objective/background: Comorbid insomnia with obstructive sleep apnea (COMISA) is associated with worse daytime function and more medical/psychiatric comorbidities vs either condition alone. COMISA may negatively impact sleep duration and reduce rapid eye movement (REM) sleep, thereby impairing cognition. These post-hoc analyses evaluated the effect of lemborexant (LEM), a dual-orexin-receptor antagonist approved for adults with insomnia, on sleep architecture in participants with COMISA.

A Comparison of Different Machine Learning Classifiers in Predicting Xerostomia and Sticky Saliva due to Head and Neck Radiotherapy using a Multi-objective, Multimodal Radiomics Model.

Although radiotherapy techniques are the primary treatment for head and neck cancer (HNC), they are still associated with substantial toxicity, and side effect. Machine learning (ML) based radiomics models for predicting toxicity mostly rely on features extracted from pre-treatment imaging data. This study aims to compare different models in predicting radiation-induced xerostomia and sticky saliva in both early and late stage of HNC patients using CT and MRI image features along with demographics and dosimetric information.

Hand-Assisted Laparoscopic Surgery (HALS) as an Alternative to Unplanned Laparoscopic Conversion to Open Surgery (LCOS) in Colectomies for Acute Diverticulitis.

Background: In difficult colorectal cases, surgeons may opt for a hand-assisted laparoscopic (HALS) colectomy or attempt a laparoscopic surgery that may require an unplanned conversion to open (LCOS). We aimed to compare the clinical outcomes of these 2 types of surgeries.

Methods: Colectomies for acute diverticulitis with a HALS or LCOS surgery were selected from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) 2022 Targeted Colectomy Database.

Key Strategies to Promote Professional Wellness and Reduce Burnout in Oncology Clinicians.

Burnout in oncologists has been increasing, especially after the COVID-19 pandemic. This is concerning because burnout can have both personal and professional repercussions, as well as a negative impact on patients and organizational financial health. Drawing on information and ideas discussed at an ASCO Town Hall session at the 2023 Annual Meeting developed by the State of Cancer Care in America Editorial Board, this study reviews key organizational strategies for improving professional well-being and argues for the importance of measuring and researching the well-being of the oncology workforce to ensure healthy work environments.

Understanding the vital role of campus-based food pantries: Insights into usage patterns, characteristics and eating behaviors among private university students.

This study examined characteristics and usage patterns of students who use a campus-based food pantry at a private university. Student clients of a campus-based food pantry at a private university ( = 30). A qualitative study was conducted using semi-structured interviews.

Measuring Intentional Communication in Infants at Elevated Likelihood of Autism: Validity, Reliability, and Responsiveness of a Novel Coding Scale.

Purpose: Intentional communication acts, or purposefully directed vocalizations and gestures, are particularly difficult for infants at elevated likelihood for eventual diagnosis of autism. The ability to measure and track intentional communication in infancy thus has the potential to aid early identification and intervention efforts. This study assesses the validity of a novel measure of intentional communication intended for use within semistructured caregiver-infant interactions.

Evaluating Surgeon-influenced Factors for Total Knee Arthroplasty Value-based Reimbursement.

Introduction: Clinical outcome measures used under value-based reimbursement models require risk stratification of patient demographics and medical history. Only certain perioperative patient factors may be influenced by the surgeon. The study evaluated surgeon-influenced modifiable factors associated with achieving literature-defined KOOS score thresholds to serve as the foundation of the newly established alternative payment models for total knee arthroplasties (TKA).

Protocol to boost the robustness and accuracy of spatial transcriptomics algorithms using ensemble techniques.

Spatial transcriptomics enhances our understanding of cellular organization by mapping gene expression data to precise tissue locations. Here, we present a protocol for using weighted ensemble method for spatial transcriptomics (WEST), which uses ensemble techniques to boost the robustness and accuracy of existing algorithms. We describe steps for preprocessing data, obtaining embeddings from individual algorithms, and ensemble integrating all embeddings as a similarity matrix.

Century-long West Antarctic snow accumulation changes induced by tropical teleconnections.

Ice core measurements reveal dipole-like snow accumulation trends over West Antarctica throughout the 20th century, with an increase of >2000 billion metric tons over the Antarctic Peninsula and Ellsworth Land but a decrease of ~500 billion metric tons over Marie Byrd Land. Although atmospheric teleconnections were frequently revealed, linking variability between tropics and higher latitudes on interannual and decadal timescales, centennial-scale teleconnection is absent from literature. Here, using statistical analysis and numerical experiments, we reveal that changes of tropical oceans throughout the 20th century drive the long-term Antarctic snowfall trend.

Vascularization of human islets by adaptable endothelium for durable and functional subcutaneous engraftment.

Tissue-specific endothelial cells (ECs) are critical for the homeostasis of pancreatic islets and most other tissues. In vitro recapitulation of islet biology and therapeutic islet transplantation both require adequate vascularization, which remains a challenge. Using human reprogrammed vascular ECs (R-VECs), human islets were functionally vascularized in vitro, demonstrating responsive, dynamic glucose-stimulated insulin secretion and Ca influx.

Heterogeneity analysis provides evidence for a genetically homogeneous subtype of bipolar-disorder.

Background: Bipolar Disorder (BD) is a complex disease. It is heterogeneous, both at the phenotypic and genetic level, although the extent and impact of this heterogeneity is not fully understood. One way to assess this heterogeneity is to look for patterns in the subphenotype data.

Trauma-related psychopathologies after extracorporeal membrane oxygenation support: A systematic review and meta-analysis.

Extracorporeal Membrane Oxygenation (ECMO) use is associated with substantial psychiatric morbidity in patients and their families. This systematic review and meta-analysis quantifies the prevalence of post-traumatic stress disorder (PTSD), anxiety, and depression among ECMO survivors and their families. Included studies enrolled patients on ECMO or their families and reported at least one trauma-related psychopathology.

Natural Language Processing Identifies Under-Documentation of Symptoms in Patients on Hemodialysis.

Background: Patients on hemodialysis (HD) have a high burden of emotional and physical symptoms. These symptoms are often under-recognized. NLP can be used to identify patient symptoms from the EHR.

Default Bulk Ordering and Text Messaging to Enhance Outreach for Lipid Screening: A Randomized Clinical Trial.

Importance: A comprehensive lipid panel is recommended by guidelines to evaluate atherosclerotic cardiovascular disease risk, but uptake is low.

Objective: To evaluate whether direct outreach including bulk orders with and without text messaging increases lipid screening rates.

Design, Setting, And Participants: Pragmatic randomized clinical trial conducted from June 6, 2023, to September 6, 2023, at 2 primary care practices at an academic health system among patients aged 20 to 75 years with at least 1 primary care visit in the past 3 years who were overdue for lipid screening.

Effective Field Theory of Conformal Boundaries.

We introduce an effective field theory (EFT) for conformal impurity by considering a pair of transversely displaced impurities and integrating out modes with mass inversely proportional to the separation distance. This EFT captures the universal signature of the impurity seen by a heavy local operator. We focus on the case of conformal boundaries and derive universal formulas from this EFT for the boundary structure constants at high energy.