bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial dysfunction, aging, and the mitochondrial unfolded protein response in Caenorhabditis elegans
Authors: Haynes Cole M , Hekimi Siegfried 
Published: November 2022

Abstract
We review the findings that establish that perturbations of various aspects of mitochondrial function, including oxidative phosphorylation, can promote lifespan extension, with different types of perturbations acting sometimes independently and additively on extending lifespan. We also review the great variety of processes and mechanisms that together form the mitochondrial unfolded protein response. We then explore the relationships between different types of mitochondrial dysfunction-dependent lifespan extension and the mitochondrial unfolded protein response. We conclude that, although several ways that induce extended lifespan through mitochondrial dysfunction require a functional mitochondrial unfolded protein response, there is no clear indication that activation of the mitochondrial unfolded protein response is sufficient to extend lifespan, despite the fact that the mitochondrial unfolded protein response impacts almost every aspect of mitochondrial function. In fact, in some contexts, mitochondrial unfolded protein response activation is deleterious. To explain this pattern, we hypothesize that, although triggered by mitochondrial dysfunction, the lifespan extension observed might not be the result of a change in mitochondrial function.
Early or Late-Life Treatment With Acarbose or Rapamycin Improves Physical Performance and Affects Cardiac Structure in Aging Mice
Authors: Herrera Jonathan J , Pifer Kaitlyn , Louzon Sean , Leander Danielle , Fiehn Oliver , Day Sharlene M , Miller Richard A , Garratt Michael 
Published: November 2022

AbstractPharmacological treatments can extend the life span of mice. For optimal translation in humans, treatments should improve health during aging, and demonstrate efficacy when started later in life. Acarbose (ACA) and rapamycin (RAP) extend life span in mice when treatment is started early or later in life. Both drugs can also improve some indices of healthy aging, although there has been little systematic study of whether health benefits accrue differently depending on the age at which treatment is started. Here we compare the effects of early (4 months) versus late (16 months) onset ACA or RAP treatment on physical function and cardiac structure in genetically heterogeneous aged mice. ACA or RAP treatment improve rotarod acceleration and endurance capacity compared to controls, with effects that are largely similar in mice starting treatment from early or late in life. Compared to controls, cardiac hypertrophy is reduced by ACA or RAP in both sexes regardless of age at treatment onset. ACA has a greater effect on the cardiac lipidome than RAP, and the effects of early-life treatment are recapitulated by late-life treatment. These results indicate that late-life treatment with these drugs provide at least some of the benefits of life long treatment, although some of the benefits occur only in males, which could lead to sex differences in health outcomes later in life.
Polygenic risk scores for prediction of breast cancer in Korean women
Authors: Jee Yon Ho , Ho Weang-Kee , Park Sohee , Easton Douglas F , Teo Soo-Hwang , Jung Keum Ji , Kraft Peter 
Published: November 2022

Abstract

Background
Polygenic risk scores (PRSs) for breast cancer, developed using European and Asian genome-wide association studies (GWAS), have been shown to have good discrimination in Asian women. However, prospective calibration of absolute risk prediction models, based on a PRS or PRS combined with lifestyle, clinical and environmental factors, in Asian women is limited.

Methods
We consider several PRSs trained using European and/or Asian GWAS. For each PRS, we evaluate the discrimination and calibration of three absolute risk models among 41 031 women from the Korean Cancer Prevention Study (KCPS)-II Biobank: (i) a model using incidence, mortality and risk factor distributions (reference inputs) among US women and European relative risks; (ii) a recalibrated model, using Korean reference but European relative risks; and (iii) a fully Korean-based model using Korean reference and relative risk estimates from KCPS.

Results
All Asian and European PRS improved discrimination over lifestyle, clinical and environmental (Qx) factors in Korean women. US-based absolute risk models overestimated the risks for women aged ≥50 years, and this overestimation was larger for models that only included PRS (expected-to-observed ratio E/O = 1.2 for women &lt;50, E/O = 2.7 for women ≥50). Recalibrated and Korean-based risk models had better calibration in the large, although the risk in the highest decile was consistently overestimated. Absolute risk projections suggest that risk-reducing lifestyle changes would lead to larger absolute risk reductions among women at higher PRS.

Conclusions
Absolute risk models incorporating PRS trained in European and Asian GWAS and population-appropriate average age-specific incidences may be useful for risk-stratified interventions in Korean women.
Epidemiology and trends in stroke mortality in the USA, 1975–2019
Authors: Ananth Cande V , Brandt Justin S , Keyes Katherine M , Graham Hillary L , Kostis John B , Kostis William J 
Published: November 2022

Abstract

Background
Whether changes in stroke mortality are affected by age distribution and birth cohorts, and if the decline in stroke mortality exhibits heterogeneity by stroke type, remains uncertain.

Methods
We undertook a sequential time series analysis to examine stroke mortality trends in the USA among people aged 18–84 years between 1975 and 2019 (n = 4 332 220). Trends were examined for overall stroke and by ischaemic and haemorrhagic subtypes. Mortality data were extracted from the US death files, and age-sex population data were extracted from US census. Age-standardized stroke mortality rates and incidence rate ratio (IRR) with 95% confidence interval [CI] were derived from Poisson regression models.

Results
Age-standardized stroke mortality declined for females from 87.5 in 1975 to 30.9 per 100 000 in 2019 (IRR 0.27, 95% CI 0.26, 0.27; average annual decline -2.78%, 95% CI -2.79, -2.78). Among males, age-standardized mortality rate declined from 112.1 in 1975 to 38.7 per 100 000 in 2019 (RR 0.26, 95% CI 0.26, 0.27; average annual decline -2.80%, 95% CI -2.81, -2.79). Stroke mortality increased sharply with advancing age. Decline in stroke mortality was steeper for ischaemic than haemorrhagic strokes.

Conclusions
Stroke mortality rates have substantially declined, more so for ischaemic than haemorrhagic strokes.
Safety and Immunogenicity of Ad26-Vectored HIV Vaccine With Mosaic Immunogens and a Novel Mosaic Envelope Protein in HIV-Uninfected Adults: A Phase 1/2a Study
Authors: Stieh Daniel J , Barouch Dan H , Comeaux Christy , Sarnecki Michal , Stephenson Kathryn E , Walsh Stephen R , Sawant Sheetal , Heptinstall Jack , Tomaras Georgia D , Kublin James G , McElrath M Juliana , Cohen Kristen W , De Rosa Stephen C , Alter Galit , Ferrari Guido , Montefiori David , Mann Philipp , Nijs Steven , Callewaert Katleen , Goepfert Paul A , Edupuganti Srilatha , Karita Etienne , Seaman Michael S , Corey Lawrence , Baden Lindsey R , Pau Maria G , Schuitemaker Hanneke , Tomaka Frank ,   the ASCENT/HVTN118/HPX2003 Study Team, Ake Julie A , Buchbinder Susan , Crowell Trevor A , Euler Zelda , Frank Ian , Goedhart Dimitri , Johnson Jennifer A , Keefer Michael , Kelley Colleen F , Mayer Kenneth H , Nkolola Joseph , Peter Lauren , Robb Merlin L , Rouphael Nadine , Scheppler Lorenz , Sobieszczyk Magda , Van Tieu Hong , Collins Matthew H , Phadke Varun K 
Published: November 2022

Abstract

Background
Developing a cross-clade, globally effective HIV vaccine remains crucial for eliminating HIV.

Methods
This placebo-controlled, double-blind, phase 1/2a study enrolled healthy HIV-uninfected adults at low risk for HIV infection. They were randomized (1:4:1) to receive 4 doses of an adenovirus 26-based HIV-1 vaccine encoding 2 mosaic Gag and Pol, and 2 mosaic Env proteins plus adjuvanted clade C gp140 (referred to here as clade C regimen), bivalent protein regimen (clade C regimen plus mosaic gp140), or placebo. Primary end points were safety and antibody responses.

Results
In total 152/155 participants (clade C, n = 26; bivalent protein, n = 103; placebo, n = 26) received ≥1 injection. The highest adverse event (AE) severity was grade 3 (local pain/tenderness, 12%, 2%, and 0% of the respective groups; solicited systemic AEs, 19%, 15%, 0%). HIV-1 mosaic gp140-binding antibody titers were 79 595 ELISA units (EU)/mL and 137 520 EU/mL in the clade C and bivalent protein groups (P &lt; .001) after dose 4 and 16 862 EU/mL and 25 162 EU/mL 6 months later. Antibody response breadth against clade C gp140 and clade C/non-clade C gp120 was highest in the bivalent protein group.

Conclusions
Adding mosaic gp140 to the clade C regimen increased and broadened the elicited immune response without compromising safety or clade C responses.
Clinical Trials Registration. NCT02935686.
Regional Variation in Contractile Patterns and Muscle Activity in Infant Pig Feeding
Authors: Mayerl C J , Adjerid K A , Edmonds C E , Gould F D H , Johnson M L , Steer K E , Bond L E , German R Z 
Published: November 2022

SynopsisAt the level of the whole muscle, contractile patterns during activity are a critical and necessary source of variation in function. Understanding if a muscle is actively lengthening, shorting, or remaining isometric has implications for how it is working to power a given behavior. When feeding, the muscles associated with the tongue, jaws, pharynx, and hyoid act together to transport food through the oral cavity and into the esophagus. These muscles have highly coordinated firing patterns, yet also exhibit high levels of regional heterogeneity in both their timing of activity and their contractile characteristics when active. These high levels of variation make investigations into function challenging, especially in systems where muscles power multiple behaviors. We used infant pigs as a model system to systematically evaluate variation in muscle firing patterns in two muscles (mylohyoid and genioglossus) during two activities (sucking and swallowing). We also evaluated the contractile characteristics of mylohyoid during activity in the anterior and posterior regions of the muscle. We found that the posterior regions of both muscles had different patterns of activity during sucking versus swallowing, whereas the anterior regions of the muscles did not. Furthermore, the anterior portion of mylohyoid exhibited concentric contractions when active during sucking, whereas the posterior portion was isometric during sucking and swallowing. This difference suggests that the anterior portion of mylohyoid in infant pigs is functioning in concert with the tongue and jaws to generate suction, whereas the posterior portion is likely acting as a hyoid stabilizer during sucking and swallowing. Our results demonstrate the need to evaluate both the contractile characteristics and activity patterns of a muscle in order to understand its function, especially in cases where there is potential for variation in either factor within a single muscle.
Research progress of intelligent operation and maintenance of high-speed railway bridges
Authors: Long Yan , Guo Wei , Yang Na , Dong Cheng , Liu Ming , Cai Yujun , Zhang Zhuanzhuan 
Published: November 2022

Abstract
The new generation of information technology, such as artificial intelligence, brings new opportunities for the efficient and intelligent development of high-speed railway (HSR) bridge operation and maintenance. Intelligent technology integrates the damage identification and maintenance of HSR bridges, and profoundly changes the development of HSR bridge operation and maintenance. The application of intelligent technology in the upgrading of detection equipment, the improvement of data and image processing efficiency, three-dimensional information reconstruction, and other aspects will form new technologies for automatic, efficient, and intelligent detection, monitoring, maintenance and disaster management, and control of HSR bridges. To assess the research and development trends in this field, this paper expounded the relevant research and application in the field of intelligent operation and maintenance of HSR bridges from the development status of HSR bridges, the application of intelligent equipment and algorithms in this field, and summarized the problems and future development for the intelligent operation and maintenance of HSR bridges.
The discourse of awe in the traditions recorded in the name of the Baal Shem Tov inSefer Degel Mahaneh Ephraim: A distant reading leading to a close reading
Authors: Sachs Shmueli Leore 
Published: November 2022

AbstractThis article aims at deciphering distinctive theological characteristics attributed to the legendary founder of Hasidism, Israel Baal Shem Tov (the BeShT), as documented by his Grandson, Moshe Haim Ephraim of Sudylkow. To achieve this objective, I will apply a combination of statistical tools of distant reading with textual analysis of close reading; a first attempt of such a kind in the research of Jewish Mysticism. It will reveal singular characteristics of the reported teachings of the BeShT, while distinguishing them from the textual corpus into which they were integrated, Sefer Degel Mahaneh Ephraim. Contrary to the common portrait of the BeSht as an optimistic preacher focusing mainly on joy and positive appraisal of human sinful conditions, fear of sin is a dominant emotional component in his ethos as documented by his Grandson. Fear and awe function as formative catalyzers of personal religious change. Indeed, he does focus on the mental aspects of divine service and the revelatory character of man’s thoughts, but a sense of trembling and anxiety of sin stands at the core of these discussions. This study demonstrates how the study of Jewish textual traditions may benefit from applying statistical analysis when intertwined with classical methods of close reading.
Reading in Europe—Challenges and lessons learned from the case studies of the READ-IT project
Authors: Benatti Francesca , Vignale François , Antonini Alessio , King Edmund 
Published: November 2022

Abstract
This article reflects on the challenges of combining humanistic and computational research perspectives within the framework of a multicultural and multilingual Digital Humanities project. It analyses the approach of Reading Europe Advanced Data Investigation Tool, a European project funded by JPI-CH, to the framing of its case studies within a wider perspective of interdisciplinary collaboration between humanities, digital humanities, and data science scholars. The analysis of sources ranging chronologically from the 18th century to the present and technologically from manuscript diaries to social media defines a new framework for the history of reading focused on the centrality of the human experience of the reader, and on the evolution of the medium through which reading is conducted. The interdisciplinary collaboration of the project develops a shared laboratory space where practices, languages, and research cultures converge to address both microscope and macroscope questions on the history of reading.
Empirical constraints on the turbulence in QSO host nebulae from velocity structure function measurements
Authors: Chen Mandy C , Chen Hsiao-Wen , Rauch Michael , Qu Zhijie , Johnson Sean D , Li Jennifer I-Hsiu , Schaye Joop , Rudie Gwen C , Zahedy Fakhri S , Boettcher Erin , Cooksey Kathy L , Cantalupo Sebastiano 
Published: November 2022

ABSTRACT
We present the first empirical constraints on the turbulent velocity field of the diffuse circumgalactic medium around four luminous quasi-stellar objects (QSOs) at z ≈ 0.5–1.1. Spatially extended nebulae of ≈50–100 physical kpc in diameter centred on the QSOs are revealed in [O ii] $\lambda \lambda \, 3727,3729$ and/or [O iii] $\lambda \, 5008$ emission lines in integral field spectroscopic observations obtained using Multi-Unit Spectroscopic Explorer on the Very Large Telescope. We measure the second- and third-order velocity structure functions (VSFs) over a range of scales, from ≲5 kpc to ≈20–50 kpc, to quantify the turbulent energy transfer between different scales in these nebulae. While no constraints on the energy injection and dissipation scales can be obtained from the current data, we show that robust constraints on the power-law slope of the VSFs can be determined after accounting for the effects of atmospheric seeing, spatial smoothing, and large-scale bulk flows. Out of the four QSO nebulae studied, one exhibits VSFs in spectacular agreement with the Kolmogorov law, expected for isotropic, homogeneous, and incompressible turbulent flows. The other three fields exhibit a shallower decline in the VSFs from large to small scales. However, with a limited dynamic range in the spatial scales in seeing-limited data, no constraints can be obtained for the VSF slopes of these three nebulae. For the QSO nebula consistent with the Kolmogorov law, we determine a turbulence energy cascade rate of ≈0.2 cm2 s−3. We discuss the implication of the observed VSFs in the context of QSO feeding and feedback in the circumgalactic medium.
JWST unveils heavily obscured (active and passive) sources up to z ∼ 13
Authors: Rodighiero Giulia , Bisigello Laura , Iani Edoardo , Marasco Antonino , Grazian Andrea , Sinigaglia Francesco , Cassata Paolo , Gruppioni Carlotta 
Published: November 2022

ABSTRACT
A wealth of extragalactic populations completely missed at UV-optical wavelengths has been identified in the last decade, combining the deepest HST and Spitzer observations. These dark sources are thought to be dusty and star-forming systems at 3 &lt; z &lt; 5, and major contributors to the stellar mass build up. In this letter, we report an investigation of the deep JWST survey in the SMACS0723 cluster, analysing NIRCam and MIRI images. We search for sources in the F444W band that are undetected in the F200W catalogues. We characterize the properties of these sources via detailed Spectral Energy Distribution (SED) modelling, accounting for a wide set of parameters and star formation histories, after a careful determination of their photometry. Among a robust sample of 20 candidates, we identify a mixed population of very red sources. We highlight the identification of evolved systems, with stellar masses M* ∼ 109–11 M⊙ at 8 &lt; z &lt; 13 characterized by unexpectedly important dust content at those epochs (AV up to ∼5.8 mag), challenging current model predictions. We further identify an extremely red source (F200W-F440W ∼ 7 mag) that can be reproduced only by the spectrum of a passive, quenched galaxy of M* ∼ 1011.56 M⊙ at z ∼ 5, filled of dust (AV ∼ 5 mag).
Executive and social functioning in pediatric posterior fossa tumor survivors and healthy controls
Authors: Ramjan Sameera , Levitch Cara , Sands Stephen , Kim Soo Young , Barnett Marie , Bledsoe Jesse , Holland Alice Ann 
Published: November 2022

AbstractBackgroundExecutive and social functioning difficulty is well established in pediatric brain tumor survivors. Few studies have compared posterior fossa (PF) tumor survivors in comparison to their peers. The relationship between attention, processing speed, working memory, fatigue, and executive and social functioning was investigated to better understand the factors that impact executive and social functioning in PF tumor populations.MethodsSixteen medulloblastomas, 9 low-grade astrocytomas (LGAs), and 17 healthy controls recruited from 4 sites completed measures of working memory and processing speed, and self-reported fatigue. One parent completed questionnaires on executive and social functioning.ResultsThere were no significant differences among all 3 groups on parent-reported executive and social functioning; of note, parents of LGA survivors expressed greater concerns regarding behavioral and cognitive regulation than did parents of medulloblastoma survivors and healthy controls. Parent-reported attention was related to parent-reported emotion, behavior, and cognitive regulation. Worse self-reported fatigue was associated with greater emotional dysregulation for the 2 PF tumor groups.ConclusionsParents of PF tumor survivors described their children as performing similarly to their peers in most facets of executive and social functioning. While LGA survivors are traditionally thought to have more favorable outcomes, our finding of parent-reported executive functioning concerns to be worse for this group highlights the importance of long-term follow-up for all PF tumor survivors. Additionally, significant effects of attention on aspects of executive functioning in PF tumor survivors may inform current clinical practice and the future development of more effective interventions.
Justifying the More Restrictive Alternative: Ethical Justifications for One Health AMR Policies Rely on Empirical Evidence
Authors: Johnson Tess , Matlock William 
Published: November 2022

Abstract
Global consumption of antibiotics has accelerated the evolution of bacterial antimicrobial resistance. Yet, the risks from increasing bacterial antimicrobial resistance are not restricted to human populations: transmission of antimicrobial resistant bacteria occurs between humans, farms, the environment and other reservoirs. Policies that take a ‘One Health’ approach deal with this cross-reservoir spread, but are often more restrictive concerning human actions than policies that focus on a single reservoir. As such, the burden of justification lies with these more restrictive policies. We argue that an ethical justification for preferring One Health policies over less restrictive alternatives relies on empirical evidence as well as theory. The ethical justification for these policies is based on two arguments: (i) comparatively greater effectiveness, and (ii) comparatively better tracking of moral responsibility. Yet the empirical assumptions on which these claims rest are limited by existing empirical knowledge. Using livestock farming as an example, we suggest that scientific research into characterising antimicrobial resistance and linking practices to outcomes ought to be guided (at least in part) by the imperative to supply the context-specific data needed to ethically justify preferring a One Health policy over less restrictive alternatives.