Miracle-dz/UniFAR-FTUs huggingface dataset:
The vascular Na,K-ATPase: clinical implications in stroke, migraine, and hypertension

Abstract In the vascular wall, the Na,K-ATPase plays an important role in the control of arterial tone. Through cSrc signaling, it contributes to the modulation of Ca2+ sensitivity in vascular smooth muscle cells. This review focuses on the potential implication of Na,K-ATPase-dependent intracellular signaling pathways in severe vascular disorders; ischemic stroke, familial migraine, and arterial hypertension. We propose similarity in the detrimental Na,K-ATPase-dependent signaling seen in these pathological conditions. The review includes a retrospective proteomics analysis investigating temporal changes after ischemic stroke. The analysis revealed that the expression of Na,K-ATPase α isoforms is down-regulated in the days and weeks following reperfusion, while downstream Na,K-ATPase-dependent cSrc kinase is up-regulated. These results are important since previous studies have linked the Na,K-ATPase-dependent cSrc signaling to futile recanalization and vasospasm after stroke. The review also explores a link between the Na,K-ATPase and migraine with aura, as reduced expression or pharmacological inhibition of the Na,K-ATPase leads to cSrc kinase signaling up-regulation and cerebral hypoperfusion. The review discusses the role of an endogenous cardiotonic steroid-like compound, ouabain, which binds to the Na,K-ATPase and initiates the intracellular cSrc signaling, in the pathophysiology of arterial hypertension. Currently, our understanding of the precise control mechanisms governing the Na,K-ATPase/cSrc kinase regulation in the vascular wall is limited. Understanding the role of vascular Na,K-ATPase signaling is essential for developing targeted treatments for cerebrovascular disorders and hypertension, as the Na,K-ATPase is implicated in the pathogenesis of these conditions and may contribute to their comorbidity.
Human Dimensions of Urban Deer-related Vehicle Accidents in Berkeley, CA

The neighborhoods of Berkeley, California are an excellent habitat for the Columbian black-tailed deer (Odocoileus hemionus columbianus). Despite a large number of deer-related car accidents in Berkeley, the associated economic and health costs have yet to be adequately addressed by government agencies. Participation from neighborhood residents and wildlife experts is necessary to develop a public-approved contemporary wildlife management plan. Surveys were administered to 50 residents from high, medium, and no accident areas (N = 150) to measure public perceptions of causes of accidents, public opinion of animosity towards deer, and public opinion of different potential management plans. Results indicated 61% of surveyed residents believed accidents occurred due to people driving fast. Of the residents who disliked deer, 82% of residents were involved in accidents. Of the residents who liked deer, 89% was not involved in accidents. Residents favored humanitarian forms of acceptable management plans, with 83% of residents approving Light Reflectors and 73% of residents approving public education programs. Even though 21% of residents approved of hunting, 91% of hunting- approved residents have been in an accident. Results support the hypothesis that people who have bad experiences with deer are more likely to dislike deer than those without bad experiences and that residents with more negative experiences with deer tend to support more lethal forms of management. Speed bumps and road signs may be the most effective and environmentally friendly management plan. However, cost/benefit studies should be researched to see if the management program will be feasible and efficient.
Comparison of two‐stage and joint TGI‐OS modeling using data from six atezolizumab clinical studies in patients with metastatic non‐small cell lung cancer

Two‐stage and joint modeling approaches are the two main approaches to investigate the link between longitudinal tumor size data and overall survival (OS) and anticipate clinical trial outcome. We here used a large database composed of one phase II and five phase III clinical trials evaluating atezolizumab (an immunotherapy) in monotherapy or in combination with chemotherapies in 3699 patients with non‐small cell lung cancer to evaluate the differences between both approaches in terms of parameter estimates, magnitude of covariate effects, and ability to predict OS. Although the two‐stage approach may underestimate the magnitude of the impact of tumor growth rate (KG) on OS compared to joint modeling approach (hazard ratios [HRs] of 0.42–2.52 vs. 0.25–2.85, respectively, for individual KG varying from the 5th and 95th percentiles), this difference did not lead into poorer performance of the two‐stage approach to describe the OS distribution in the six clinical studies. Overall, two‐stage and joint modeling approaches accurately predicted OS HR with a median (range) difference with the observed OS HR of 0.02 (0.01–0.18) and 0.03 (0.00–0.19), in all cases considered, respectively (e.g., for IMpower150: 0.80 [0.66–0.95] vs. 0.82 [0.70–0.95], respectively, whereas the observed OS HR was 0.80). In our setting, the two‐stage approach accurately predicted the benefit of atezolizumab on OS. Further work is needed to verify if similar results are achieved using phase Ib or phase II clinical trials where the number of patients and measurements is limited as well as in other cancer indications.
The Association of Professional Burnout and Turnover Intentions Among Intensive Care Units Physicians: A Cross-Sectional Study

Intensive Care Units (ICU) workers work in highly stressful conditions that make them prone to professional burnout, which can lead to high turnover rates. This study explores professional burnout levels among ICU workers in Kuwait general governmental hospitals (GGHs), their turnover intentions, and the correlation factors. A cross-sectional self-administered survey study was conducted. Professional burnout level was measured using the Copenhagen Burnout Inventory (CBI), while turnover intention was measured using the Turnover Intention Scale (TIS-6). Data were analyzed using STATA software, and descriptive, correlative, and comparative analyses were performed. Eighty-nine ICU physicians filled out the questionnaire. Most of the participants were males, married, non-Kuwaiti nationals, with 10 to 20 years of experience, and the mean age of respondents was 39.2. The total professional burnout score was high was 54.7 (17.6). There were high total average scores for the personal and work-related domains. Participants who were younger than 35 years of age and graduated before 5 to 10 years had higher levels of professional burnout compared to other groups. More than half of the sample expressed their intention to leave their current job as an ICU physician. However, no association was found between turnover intentions and levels of burnout. High levels of professional burnout of turnover intentions were seen among ICU physicians in Kuwait. Policies should be adopted to reduce and mitigate professional burnout among ICU physicians and increase their retention. Future research should further investigate professional burnout among ICU staff, the associated factors, and its relation to their turnover intention.
Visualization of Self-Assembly and Hydration of a β-Hairpin through Integrated Small and Wide-Angle Neutron Scattering

Fundamental understanding of the structure and assembly of nanoscale building blocks is crucial for the development of novel biomaterials with defined architectures and function. However, accessing self-consistent structural information across multiple length scales is challenging. This limits opportunities to exploit atomic scale interactions to achieve emergent macroscale properties. In this work we present an integrative small- and wide-angle neutron scattering approach coupled with computational modeling to reveal the multiscale structure of hierarchically self-assembled β hairpins in aqueous solution across 4 orders of magnitude in length scale from 0.1 Å to 300 nm. Our results demonstrate the power of this self-consistent cross-length scale approach and allows us to model both the large-scale self-assembly and small-scale hairpin hydration of the model β hairpin CLN025. Using this combination of techniques, we map the hydrophobic/hydrophilic character of this model self-assembled biomolecular surface with atomic resolution. These results have important implications for the multiscale investigation of aqueous peptides and proteins, for the prediction of ligand binding and molecular associations for drug design, and for understanding the self-assembly of peptides and proteins for functional biomaterials.
LiberRoad: Probing into the Journey of Chinese Classics Through Visual Analytics

Books act as a crucial carrier of cultural dissemination in ancient times. This work involves joint efforts between visualization and humanities researchers, aiming at building a holistic view of the cultural exchange and integration between China and Japan brought about by the overseas circulation of Chinese classics. Book circulation data consist of uncertain spatiotemporal trajectories, with multiple dimensions, and movement across hierarchical spaces forms a compound network. LiberRoad visualizes the circulation of books collected in the Imperial Household Agency of Japan, and can be generalized to other book movement data. The LiberRoad system enables a smooth transition between three views (Location Graph, map, and timeline) according to the desired perspectives (spatial or temporal), as well as flexible filtering and selection. The Location Graph is a novel uncertainty-aware visualization method that employs improved circle packing to represent spatial hierarchy. The map view intuitively shows the overall circulation by clustering and allows zooming into single book trajectory with lenses magnifying local movements. The timeline view ranks dynamically in response to user interaction to facilitate the discovery of temporal events. The evaluation and feedback from the expert users demonstrate that LiberRoad is helpful in revealing movement patterns and comparing circulation characteristics of different times and spaces.
Assembly and annotation of the black spruce genome provide insights on spruce phylogeny and evolution of stress response

Abstract Black spruce (Picea mariana [Mill.] B.S.P.) is a dominant conifer species in the North American boreal forest that plays important ecological and economic roles. Here, we present the first genome assembly of P. mariana with a reconstructed genome size of 18.3 Gbp and NG50 scaffold length of 36.0 kbp. A total of 66,332 protein-coding sequences were predicted in silico and annotated based on sequence homology. We analyzed the evolutionary relationships between P. mariana and 5 other spruces for which complete nuclear and organelle genome sequences were available. The phylogenetic tree estimated from mitochondrial genome sequences agrees with biogeography; specifically, P. mariana was strongly supported as a sister lineage to P. glauca and 3 other taxa found in western North America, followed by the European Picea abies. We obtained mixed topologies with weaker statistical support in phylogenetic trees estimated from nuclear and chloroplast genome sequences, indicative of ancient reticulate evolution affecting these 2 genomes. Clustering of protein-coding sequences from the 6 Picea taxa and 2 Pinus species resulted in 34,776 orthogroups, 560 of which appeared to be specific to P. mariana. Analysis of these specific orthogroups and dN/dS analysis of positive selection signatures for 497 single-copy orthogroups identified gene functions mostly related to plant development and stress response. The P. mariana genome assembly and annotation provides a valuable resource for forest genetics research and applications in this broadly distributed species, especially in relation to climate adaptation.
Salmonella engages CDC42 effector protein 1 for intracellular invasion

Human enterocytes are primary targets of infection by invasive bacterium Salmonella Typhimurium, and studies using nonintestinal epithelial cells established that S. Typhimurium activates Rho family GTPases, primarily CDC42, to modulate the actin cytoskeletal network for invasion. The host intracellular protein network that engages CDC42 and influences the pathogen's invasive capacity are relatively unclear. Here, proteomic analyses of canonical and variant CDC42 interactomes identified a poorly characterized CDC42 interacting protein, CDC42EP1, whose intracellular localization is rapidly redistributed and aggregated around the invading bacteria. CDC42EP1 associates with SEPTIN‐7 and Villin, and its relocalization and bacterial engagement depend on host CDC42 and S. Typhimurium's capability of activating CDC42. Unlike CDC42, CDC42EP1 is not required for S. Typhimurium's initial cellular entry but is found to associate with Salmonella‐containing vacuoles after long‐term infections, indicating a contribution to the pathogen's intracellular growth and replication. These results uncover a new host regulator of enteric Salmonella infections, which may be targeted to restrict bacterial load at the primary site of infection to prevent systemic spread.
Mild Stroke, Serious Problems: Limitations in Balance and Gait Capacity and the Impact on Fall Rate, and Physical Activity

Background After mild stroke persistent balance limitations may occur, creating a risk factor for fear of falling, falls, and reduced activity levels. Objective. To investigate whether individuals in the chronic phase after mild stroke show balance and gait limitations, elevated fall risk, reduced balance confidence, and physical activity levels compared to healthy controls. Methods An observational case-control study was performed. Main outcomes included the Mini-Balance Evaluation Systems Test (mini-BEST), Timed Up and Go (TUG), 10-m Walking Test (10-MWT), and 6-item version Activity-specific Balance Confidence (6-ABC) scale which were measured in 1 session. Objectively measured daily physical activity was measured for 7 consecutive days. Fall rate in daily life was recorded for 12 months. Individuals after a mild stroke were considered eligible when they: (1) sustained a transient ischemic attack or stroke longer than 6 months ago, resulting in motor and/or sensory loss in the contralesional leg at the time of stroke, (2) showed (near-) complete motor function, that is, ≥24 points on the Fugl-Meyer Assessment—Lower Extremity (range: 0-28). Results Forty-seven healthy controls and 70 participants after mild stroke were included. Participants with stroke fell more than twice as often as healthy controls, had a 2 point lower median score on the mini-BEST, were 1.7 second slower on TUG, 0.6 km/h slower on the 10-MWT, and had a 12% lower 6-ABC score. Intensity for both total activity (8%) as well as walking activity (6%) was lower in the participants with stroke, while no differences were found in terms of duration. Conclusions Individuals in the chronic phase after a mild stroke demonstrate persistent balance limitations and have an increased fall risk. Our results point at an unmet clinical need in this population.
PreHevbrio: the first approved 3-antigen hepatitis B vaccine

ABSTRACT Introduction Hepatitis B remains a major cause of death and morbidity worldwide. Universal childhood immunization programs have been very successful, but many adults remain unprotected or are not optimally protected. PreHevbrio [Hepatitis B Vaccine (recombinant)] is a highly immunogenic 3-antigen (S/pre-S1/pre-S2) hepatitis B vaccine (3A-HBV) that recently received marketing authorization in the United States (2021), the European Union, United Kingdom (2022 – brand name PreHevbri), and Canada (2022– brand name PreHevbrio) for the prevention of infection caused by all known subtypes of the hepatitis B virus and the delta virus in adults 18 years and older. Areas covered This review details the development of 3A-HBV and summarizes the results of the phase 3 clinical trials that support its immunogenicity and safety in adults. Expert Opinion 3A-HBV is highly immunogenic in adults of all ages, including older adults and subgroups that respond sub-optimally to conventional single S-antigen hepatitis B vaccines (1A-HBV), such as those with obesity, type 2 diabetes, and smokers. 3A-HBV provides higher seroprotection rates after each vaccination compared to conventional 1A-HBV vaccines, allowing for more rapid protection. The higher overall immunogenicity is also reflected in more durable seroprotection years after vaccination, as supported by a follow-up study to one of the phase 3 studies.
Effects of target-amplitude and background-contrast uncertainty predicted by a normalized template-matching observer

When detecting targets under natural conditions, the visual system almost always faces multiple, simultaneous, dimensions of extrinsic uncertainty. This study focused on the simultaneous uncertainty about target amplitude and background contrast. These dimensions have a large effect on detection and vary greatly in natural scenes. We measured the human performance for detecting a sine-wave target in white noise and natural-scene backgrounds for two levels of prior probability of the target being present. We derived and tested the ideal observer for white-noise backgrounds, a special case of a template-matching observer that dynamically moves its criterion with the background contrast (the DTM observer) and two simpler models with a fixed criterion: the template-matching (TM) observer and the normalized template-matching (NTM) observer that normalizes template response by background contrast. Simulations show that, when the target prior is low, the performance of the NTM observer is near optimal and the TM observer is near chance, suggesting that manipulating the target prior is valuable for distinguishing among models. Surprisingly, we found that the NTM and DTM observers better explain human performance than the TM observer for both target priors in both background types. We argue that the visual system most likely exploits contrast normalization, rather than dynamic criterion adjustment, to deal with simultaneous background contrast and target amplitude uncertainty. Finally, our findings show that the data collected under high levels of uncertainty have a rich structure capable of discriminating between models, providing an alternative approach for studying high dimensions of uncertainty.
Draft genome sequence of Pasteurella multocida strain BD1769 with untypable capsular serotype isolated from a layer chicken

ABSTRACT We report the draft genome sequence of Pasteurella multocida strain BD1769 (GenBank accession numbers JARFTQ010000001–JARFTQ010000021) isolated in 2021 from a layer chicken in Japan. No gene locus for capsular biosynthesis was annotated in the genome of this strain.
Assessment of three‐dimensional RNA structure prediction in CASP15

The prediction of RNA three‐dimensional structures remains an unsolved problem. Here, we report assessments of RNA structure predictions in CASP15, the first CASP exercise that involved RNA structure modeling. Forty‐two predictor groups submitted models for at least one of twelve RNA‐containing targets. These models were evaluated by the RNA‐Puzzles organizers and, separately, by a CASP‐recruited team using metrics (GDT, lDDT) and approaches (Z‐score rankings) initially developed for assessment of proteins and generalized here for RNA assessment. The two assessments independently ranked the same predictor groups as first (AIchemy_RNA2), second (Chen), and third (RNAPolis and GeneSilico, tied); predictions from deep learning approaches were significantly worse than these top ranked groups, which did not use deep learning. Further analyses based on direct comparison of predicted models to cryogenic electron microscopy (cryo‐EM) maps and x‐ray diffraction data support these rankings. With the exception of two RNA‐protein complexes, models submitted by CASP15 groups correctly predicted the global fold of the RNA targets. Comparisons of CASP15 submissions to designed RNA nanostructures as well as molecular replacement trials highlight the potential utility of current RNA modeling approaches for RNA nanotechnology and structural biology, respectively. Nevertheless, challenges remain in modeling fine details such as noncanonical pairs, in ranking among submitted models, and in prediction of multiple structures resolved by cryo‐EM or crystallography.
Single‐cell DNA from West Greenland marine sediments suggests presence of Protoperidinium tricingulatum in the Arctic

Spiny brown dinoflagellate cysts are commonly used as sea‐ice indicators in the Arctic, but their biological affinities are not well known. We present the first indication of hitherto temperate Protoperidinium tricingulatum in the Arctic based on single‐cell LSU rDNA sequencing from sediments of the Disko Bay‐Vaigat Sound, West Greenland. The morphological similarity of the sequenced cyst morphotype to the sea‐ice indicator Islandinium? cezare morphotype 1 is striking. The morphology of the isolated cysts, as well as those observed in the total cyst assemblage following standard palynological preparation, both resemble either I. cezare morphotype 1 or P. tricingulatum, suggesting that the specimens may in fact be close morphological variants of the same species. In addition, nine LSU rDNA sequences were obtained from morphological variants assigned to Islandinium minutum s.l. : including both subspecies minutum and subspecies barbatum. The two subspecies could not be differentiated based on partial LSU rDNA sequencing. Overall, Arctic spiny brown dinoflagellate cyst species may be morphologically more diverse and taxonomically more complex than shown earlier and further genetic and morphological studies are needed. Importantly, the value of cysts as palaeoecological indicators depends on a sound understanding of their biological affinity and taxonomy.
Demoralization in cancer survivors: an updated systematic review and meta‐analysis for quantitative studies

Demoralization can cause impairments across all life aspects of cancer patients. Cancer patients are also vulnerable during their survivorship. The purpose of this review is to examine the risk of demoralization and associated risk factors among cancer survivors who have completed their primary anti‐cancer treatment or time since diagnosis ≥5 years without recurrence.
Global distribution, receptor binding, and cross-species transmission of H6 influenza viruses: risks and implications for humans

ABSTRACT The H6 subtype of avian influenza virus (AIV) is a pervasive subtype that is ubiquitously found in both wild bird and poultry populations across the globe. Recent investigations have unveiled its capacity to infect mammals, thereby expanding its host range beyond that of other subtypes and potentially facilitating its global transmission. This heightened breadth also endows H6 AIVs with the potential to serve as a genetic reservoir for the emergence of highly pathogenic avian influenza strains through genetic reassortment and adaptive mutations. Furthermore, alterations in key amino acid loci within the H6 AIV genome foster the evolution of viral infection mechanisms, which may enable the virus to surmount interspecies barriers and infect mammals, including humans, thus posing a potential threat to human well-being. In this review, we summarize the origins, dissemination patterns, geographical distribution, cross-species transmission dynamics, and genetic attributes of H6 influenza viruses. This study holds implications for the timely detection and surveillance of H6 AIVs.