bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sunitinib therapy for imatinib-resistant and/or intolerant gastrointestinal stromal tumors: comparison of safety and efficacy between standard and reduced dosage regimens
Authors: Sasaki Kenta , Kanda Tatsuo , Matsumoto Yoshifumi , Ishikawa Takashi , Hirota Seiichi , Saijo Yasuo 
Published: January 2023

AbstractBackgroundSunitinib therapy for patients with imatinib-resistant and/or intolerant gastrointestinal stromal tumors (GISTs) often causes severe adverse events (AEs) that lead to treatment discontinuation.MethodsWe retrospectively reviewed the clinical records of imatinib-resistant and/or intolerant GIST patients who underwent sunitinib therapy in our institutions between 2007 and 2020. Forty-one patients were enrolled and divided into two groups on the basis of the starting dosage: the standard dosage group (50 mg/day, 21 patients) and the reduced dosage group (37.5 mg/day, 20 patients). Tolerability, safety and clinical efficacy of the two groups were compared.ResultsThree patients (14%) in the standard dosage group and another three (15%) in the reduced dosage group (P = 1.000) discontinued sunitinib therapy because of AEs. The incidences of grade 3 or more severe treatment-related AEs were 90 and 75%, respectively (P = 0.238). Two possible treatment-related deaths were noted in the standard dosage group. Clinical efficacy was comparable between the two groups: median time to treatment failure and overall survival were 4.5 months [interquartile range (IQR), 3.6–9.0] and 13.7 months (IQR, 7.5–22.9) in the standard dosage group and 4.6 months (IQR, 2.7–17.0) and 13.4 months (IQR, 9.3–36.8) in the reduced dosage group, respectively.ConclusionsThe reduced dosage of 37.5 mg sunitinib tended to decrease toxicity and the incidences of severe AEs and treatment-related deaths. This reduced dosage regimen showed equivalent clinical efficacy including patient survival. The reduced dosage of 37.5 mg sunitinib can be adopted as an alternative therapy for patients with imatinib-resistant and/or intolerant GISTs.
LncRNA15691 promotes T-ALL infiltration by upregulating CCR9 via increased MATR3 stability
Authors: Zeng Xingruo , Lei Yufei , Pan Shan , Sun Jiaxing , He Hengjing , Xiao Di , Jamal Muhammad , Shen Hui , Zhou Fuling , Shao Liang , Zhang Quiping 
Published: January 2023

Abstract
Our previous studies demonstrated that CCR9 plays an important role in several aspects of T-cell acute lymphoblastic leukemia progression and that CCR9 is a potential therapeutic target. However, the underlying mechanism that regulates CCR9 expression remains incompletely understood. In this study, bioinformatics analysis and validation in clinical samples revealed the lncRNA15691 to be positively correlated with CCR9 mRNA expression and significantly upregulated in T-cell acute lymphoblastic leukemia samples and CCR9high T-cell acute lymphoblastic leukemia cell lines. LncRNA15691, a previously uncharacterized lncRNA, was found to be located in both the cytoplasm and the nucleus via fluorescence in situ hybridization assay. In addition, lncRNA15691 upregulated the expression of CCR9 and was involved in T-cell acute lymphoblastic leukemia cell invasion. In vivo experiments showed that lncRNA15691 promoted leukemia cell homing/infiltration into the bone marrow, blood, and spleen, whereas the CCR9 ligand, CCL25, augmented the extramedullary infiltration of CCR9low leukemia cells overexpressing lncRNA15691 into blood, spleen, and liver. Subsequently, RNA protein pull-down assays, coupled with liquid chromatography–tandem mass spectrometry, were used to uncover potential lncRNA15691-interacting proteins, which were then validated by RNA immunoprecipitation. These mechanistic studies revealed that lncRNA15691 upregulated CCR9 expression via directly binding to and stabilizing MATR3 by inhibiting its nuclear degradation mediated by PKA. Collectively, our study revealed a novel mechanism of regulating CCR9 expression and implicated lncRNA15691 as a potential novel biomarker for T-cell acute lymphoblastic leukemia infiltration.
Single-cell transcriptome sequencing of macrophages in common cardiovascular diseases
Authors: Li Lanfang , Ma Qiuxiao , Wang Min , Mou Junyu , Han Yanwei , Wang Jialu , Ye Jingxue , Sun Guibo 
Published: January 2023

Abstract
Macrophages are strategically located throughout the body at key sites in the immune system. A key feature in atherosclerosis is the uptake and accumulation of lipoproteins by arterial macrophages, leading to the formation of foam cells. After myocardial infarction, macrophages derived from monocytes infiltrate the infarcted heart. Macrophages are also closely related to adverse remodeling after heart failure. An in-depth understanding of the functions and characteristics of macrophages is required to study heart health and pathophysiological processes; however, the heterogeneity and plasticity explained by the classic M1/M2 macrophage paradigm are too limited. Single-cell sequencing is a high-throughput sequencing technique that enables the sequencing of the genome or transcriptome of a single cell. It effectively complements the heterogeneity of gene expression in a single cell that is ignored by conventional sequencing and can give valuable insights into the development of complex diseases. In the present review, we summarize the available research on the application of single-cell transcriptome sequencing to study the changes in macrophages during common cardiovascular diseases, such as atherosclerosis, myocardial infarction, and heart failure. This article also discusses the contribution of this knowledge to understanding the pathogenesis, development, diagnosis, and treatment of heart diseases.
A novel Lagrangian formulation to construct relativistic rotating stars: towards its application to their evolution calculations
Authors: Okawa Hirotada , Fujisawa Kotaro , Yasutake Nobutoshi , Ogata Misa , Yamamoto Yu , Yamada Shoichi 
Published: January 2023

ABSTRACT
We present a new formulation to construct numerically equilibrium configurations of rotating stars in general relativity. Having in mind the application to their quasi-static evolutions on a secular time-scale, we adopt a Lagrangian formulation of our own devising, in which we solve force-balance equations to seek for the positions of fluid elements corresponding to the grid points, instead of the ordinary Eulerian formulation. Unlike previous works in the literature, we do not employ the first integral of the Euler equation, which is not obtained analytically in general. We assign a mass, specific angular momentum and entropy to each fluid element in contrast to the previous Eulerian methods, in which the spatial distribution of the angular velocity or angular momentum is specified. These distributions are determined after the positions of all fluid elements (or grid points) are derived in our formulation. We solve the large system of algebraic non-linear equations that are obtained by discretizing the time-independent Euler and Einstein equations in the finite-element method by using our new multidimensional root-finding scheme, named the W4 method. To demonstrate the capability of our new formulation, we construct some rotational configurations, both barotropic and baroclinic. As toy models, we also solve three evolutionary sequences that mimic the cooling, mass-loss, and mass-accretion.
Mantle mineralogy limits to rocky planet water inventories
Authors: Guimond Claire Marie , Shorttle Oliver , Rudge John F 
Published: January 2023

ABSTRACT
Nominally anhydrous minerals in rocky planet mantles can sequester multiple Earth-oceans’ worth of water. Mantle water storage capacities therefore provide an important constraint on planet water inventories. Here we predict silicate mantle water capacities from the thermodynamically-limited solubility of water in their constituent minerals. We report the variability of upper mantle and bulk mantle water capacities due to (i) host star refractory element abundances that set mantle mineralogy, (ii) realistic mantle temperature scenarios, and (iii) planet mass. We find that transition zone minerals almost unfailingly dominate the water capacity of the mantle for planets of up to ∼1.5 Earth masses, possibly creating a bottleneck to deep water transport, although the transition zone water capacity discontinuity is less pronounced at lower Mg/Si. The pressure of the ringwoodite-perovskite phase boundary defining the lower mantle is roughly constant, so the contribution of the upper mantle reservoir becomes less important for larger planets. If perovskite and postperovskite are relatively dry, then increasingly massive rocky planets would have increasingly smaller fractional interior water capacities. In practice, our results represent initial water concentration profiles in planetary mantles where their primordial magma oceans are water-saturated. This work is a step towards understanding planetary deep water cycling, thermal evolution as mediated by rheology and melting, and the frequency of ocean planets.
Investigating the high time-resolution statistics of pulsar radio signals using spectral self-noise
Authors: Faustmann A , Schwardt L , van Tonder V , Gilmore J , Buchner S 
Published: January 2023

ABSTRACTWhile observations of the stationary component of pulsar radio signals have in many ways formed the basis of our understanding of radio pulsars, the statistical deviations of these signals contain information that has become increasingly relevant. Using high time–frequency resolution data from the MeerKAT telescope, we study the self-noise of the autocorrelation function of six radio pulsars. The self-noise of the autocorrelation function is used to investigate the statistics of the observed radio signals on nanosecond time-scales and for five pulsars it is found to deviate from the expected form for a Gaussian process. Comparing the measured distribution of the intensity fluctuations of the on-pulse window to simulated models, we find that a mixture model comprising a Gaussian process and a Bernoulli-sampled Gaussian process is able to produce the excess self-noise while also producing the observed distribution of intensities. The parameters of the mixture model describing the signals are estimated for three of the pulsars in our sample group. Studies of the statistics presented in this work provide observational information for constraining the numerous theories of pulsar radio emission mechanisms. The mixture model suggested in this work would produce excess timing residuals for high signal-to-noise ratio observations when compared to that expected for a Gaussian process. Additionally, the measure of spectral self-noise provides a means of separating Gaussian and non-Gaussian processes that provides a potential basis for the development of alternative pulsar detection algorithms.
PISN-explorer: hunting the descendants of very massive first stars
Authors: Aguado D S , Salvadori S , Skúladóttir Á , Caffau E , Bonifacio P , Vanni I , Gelli V , Koutsouridou I , Amarsi A M 
Published: January 2023

ABSTRACT
The very massive first stars (m &gt; 100 $\rm M_{\odot }$) were fundamental to the early phases of reionization, metal enrichment, and supermassive black hole formation. Among them, those with $140\le \rm m/\rm M_{\odot }\le 260$ are predicted to evolve as Pair Instability Supernovae (PISN) leaving a unique chemical signature in their chemical yields. Still, despite long searches, the stellar descendants of PISN remain elusive. Here we propose a new methodology, the PISN-explorer, to identify candidates for stars with a dominant PISN enrichment. The PISN-explorer is based on a combination of physically driven models, and the FERRE code; and applied to data from large spectroscopic surveys (APOGEE, GALAH, GES, MINCE, and the JINA data base). We looked into more than 1.4 million objects and built a catalogue with 166 candidates of PISN descendants. One of which, 2M13593064+3241036, was observed with UVES at VLT and full chemical signature was derived, including the killing elements, Cu and Zn. We find that our proposed methodology is efficient in selecting PISN candidates from both the Milky Way and dwarf satellite galaxies such as Sextans or Draco. Further high-resolution observations are highly required to confirm our best selected candidates, therefore allowing us to probe the existence and properties of the very massive First Stars.
Influence of fine-scale habitat characteristics on sage-grouse nest site selection and nest survival varies by mesic and xeric site conditions
Authors: Brussee Brianne E , Coates Peter S , O’Neil Shawn T , Ricca Mark A , Dudko Jonathan E , Espinosa Shawn P , Gardner Scott C , Casazza Michael L , Delehanty David J 
Published: January 2023

AbstractResource managers and scientists across western U.S. agencies seek methodologies for identifying environmental attributes important to both wildlife conservation and broad-scale land stewardship. The Greater Sage-Grouse (Centrocercus urophasianus; hereafter, sage-grouse) exemplifies a species in need of this broad-scale approach given widespread population declines that have resulted from loss and degradation of habitat from natural and anthropogenic disturbances. These include agricultural land conversion, conifer expansion, energy development, and wildfire coupled with ecological conversion by invasive plants such as cheatgrass (Bromus tectorum). Development of habitat assessments and conservation actions for sage-grouse benefit from studies that link demographic responses to habitat selection patterns. To address this, we examined nest survival of sage-grouse in relation to fine-scale habitat patterns (i.e., field-based habitat measurements) that influenced nest site selection, using data from nests of telemetered females at 17 sites over 6 years in Nevada and northeastern California, USA. Importantly, sites spanned mesic and xeric average precipitation conditions that contributed substantially to vegetation community structure across cold desert ecosystems of the North American Great Basin. Vegetative cover immediately surrounding sage-grouse nests was important for both nest site selection and nest survival, but responses varied between mesic and xeric sites. For example, while taller perennial grasses were selected at xeric sites, we found no evidence of selection for perennial grass at mesic sites, indicating a functional response to availability of habitat features between hydrographic regions. Furthermore, perennial grass height and forb height both had positive effects on nest survival at xeric sites, but we found varying effects at mesic sites. We emphasize that precipitation conditions driving ecosystem productivity vary regionally among sagebrush communities, shaping vegetation structure and suitable habitat conditions for nesting sage-grouse.
Relative Aerobic Load of Daily Activities After Stroke
Authors: Blokland Ilse J , Schiphorst Linda F A , Stroek Jessie R , Groot Floor P , van Bennekom Coen A M , van Dieen Jaap H , de Koning Jos J , Houdijk Han 
Published: January 2023

Abstract

Objective
Individuals after stroke are less active, experience more fatigue, and perform activities at a slower pace than peers with no impairments. These problems might be caused by an increased aerobic energy expenditure during daily tasks and a decreased aerobic capacity after stroke. The aim of this study was to quantify relative aerobic load (ie, the ratio between aerobic energy expenditure and aerobic capacity) during daily-life activities after stroke.

Methods
Seventy-nine individuals after stroke (14 in Functional Ambulation Category [FAC] 3, 25 in FAC 4, and 40 in FAC 5) and 22 peers matched for age, sex, and body mass index performed a maximal exercise test and 5 daily-life activities at a preferred pace for 5 minutes. Aerobic energy expenditure (mL O2/kg/min) and economy (mL O2/kg/unit of distance) were derived from oxygen uptake ($\dot{\mathrm{V}}{\mathrm{O}}_2$). Relative aerobic load was defined as aerobic energy expenditure divided by peak aerobic capacity (%$\dot{\mathrm{V}}{\mathrm{O}}_2$peak) and by $\dot{\mathrm{V}}{\mathrm{o}}_2$ at the ventilatory threshold (%$\dot{\mathrm{V}}{\mathrm{o}}_2$-VT) and compared in individuals after stroke and individuals with no impairments.

Results
Individuals after stroke performed activities at a significantly higher relative aerobic load (39%–82% $\dot{\mathrm{V}}{\mathrm{o}}_2$peak) than peers with no impairments (38%–66% $\dot{\mathrm{V}}{\mathrm{o}}_2$peak), despite moving at a significantly slower pace. Aerobic capacity in individuals after stroke was significantly lower than that in peers with no impairments. Movement was less economical in individuals after stroke than in peers with no impairments.

Conclusion
Individuals after stroke experience a high relative aerobic load during cyclic daily-life activities, despite adopting a slower movement pace than peers with no impairments. Perhaps individuals after stroke limit their movement pace to operate at sustainable relative aerobic load levels at the expense of pace and economy.

Impact
Improving aerobic capacity through structured aerobic training in a rehabilitation program should be further investigated as a potential intervention to improve mobility and functioning after stroke.
Mind the Gap between the Governor and the People: The Common Agency Problem in Russian Authoritarian Federalism
Authors: Klimovich Stanislav 
Published: January 2023

AbstractSince the revival of direct gubernatorial elections in 2012, regional governors in Russia have two formal principals: the president and the people of the region. The principal–agent theory defines this situation as a common agency problem. In the context of authoritarian federalism, direct elections pose a two-fold challenge to Vladimir Putin’s vertical power. First, even if manipulated, elections can lead to unpredictable outcomes for the federal center. Second, in the long run, popular legitimacy incentivizes regional leaders to become more independent from the Kremlin. This study argues that the federal center in Russia has addressed the common agency problem not only by limiting the freedom of choice for the local populations through restrictive electoral law, but also by adopting a recruitment pattern that prefers outsider governors who lack personal connection to the regions of service. An original dataset on regional governors’ selection in 2012–2018 provides empirical evidence for this claim.
COVID-19 admissions and mortality in patients with early inflammatory arthritis: results from a UK national cohort
Authors: Adas Maryam A , Russell Mark D , Cook Emma , Alveyn Edward , Hannah Jennifer , Balachandran Sathiyaa , Oyebanjo Sarah , Amlani-Hatcher Paul , Ledingham Joanna , Norton Sam , Galloway James B 
Published: January 2023

Abstract

Objective
To describe the risks and predictors of coronavirus disease 2019 (COVID-19) hospitalization and mortality among patients with early inflammatory arthritis (EIA), recruited to the National Early Inflammatory Arthritis Audit (NEIAA).

Methods
NEIAA is an observational cohort. We included adults with EIA from Feb 2020 to May 2021. Outcomes of interest were hospitalization and death due to COVID-19, using NHS Digital linkage. Cox proportional hazards were used to calculate hazard ratios for outcomes according to initial treatment strategy, with adjustment for confounders.

Results
From 14 127 patients with EIA, there were 143 hospitalizations and 47 deaths due to COVID-19, with incidence rates per 100 person-years of 0.93 (95% CI 0.79, 1.10) for hospitalization and 0.30 (95% CI 0.23, 0.40) for death. Increasing age, male gender, comorbidities and ex-smoking were associated with increased risk of worse COVID-19 outcomes. Higher baseline DAS28 was not associated with COVID-19 admissions [confounder adjusted hazard ratio (aHR) 1.10; 95% CI 0.97, 1.24] or mortality (aHR 1.11; 95% CI 0.90, 1.37). Seropositivity was not associated with either outcome. Higher symptom burden on patient-reported measures predicted worse COVID-19 outcomes. In unadjusted models, CS associated with COVID-19 death (HR 2.29; 95% CI 1.02, 5.13), and SSZ monotherapy associated with COVID-19 admission (HR 1.92; 95% CI 1.04, 3.56). In adjusted models, associations for CS and SSZ were not statistically significant.

Conclusion
Patient characteristics have stronger associations with COVID-19 than the initial treatment strategy in patients with EIA. An important limitation is that we have not looked at treatment changes over time.
Manipulation of the Host Endomembrane System by Bacterial Effectors
Authors: Jeon Hyelim , Segonzac Cécile 
Published: January 2023

The endomembrane system, extending from the nuclear envelope to the plasma membrane, is critical to the plant response to pathogen infection. Synthesis and transport of immunity-related proteins and antimicrobial compounds to and from the plasma membrane are supported by conventional and unconventional processes of secretion and internalization of vesicles, guided by the cytoskeleton networks. Although plant bacterial pathogens reside mostly in the apoplast, major structural and functional modifications of the endomembrane system in the host cell occur during bacterial infection. Here, we review the dynamics of these cellular compartments, briefly, for their essential contributions to the plant defense responses and, in parallel, for their emerging roles in bacterial pathogenicity. We further focus on Pseudomonas syringae, Xanthomonas spp., and Ralstonia solanacearum type III secreted effectors that one or both localize to and associate with components of the host endomembrane system or the cytoskeleton network to highlight the diversity of virulence strategies deployed by bacterial pathogens beyond the inhibition of the secretory pathway. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Circadian disruption impairs glucose homeostasis in male but not in female mice and is dependent on gonadal sex hormones
Authors: In het Panhuis Wietse , Schönke Milena , Siebeler Ricky , Banen Dorien , Pronk Amanda C. M. , Streefland Trea C. M. , Afkir Salwa , Sips Hetty C. M. , Kroon Jan , Rensen Patrick C. N. , Kooijman Sander 
Published: January 2023

AbstractCircadian disruption (CD) is the consequence of a mismatch between endogenous circadian rhythms and behavior, and frequently occurs in shift workers. CD has often been linked to impairment of glucose and lipid homeostasis. It is, however, unknown if these effects are sex dependent. Here, we subjected male and female C57BL/6J mice to 6‐h light phase advancements every 3 days to induce CD and assessed glucose and lipid homeostasis. Within this model, we studied the involvement of gonadal sex hormones by injecting mice with gonadotropin‐releasing hormone‐antagonist degarelix. We demonstrate that CD has sex‐specific effects on glucose homeostasis, as CD elevated fasting insulin levels in male mice while increasing fasting glucose levels in female mice, which appeared to be independent of behavior, food intake, and energy expenditure. Absence of gonadal sex hormones lowered plasma insulin levels in male mice subjected to CD while it delayed glucose clearance in female mice subjected to CD. CD elevated plasma triglyceride (TG) levels and delayed plasma clearance of TG‐rich lipoproteins in both sexes, coinciding with reduced TG‐derived FA uptake by adipose tissues. Absence of gonadal sex hormones did not notably alter the effects of CD on lipid metabolism. We conclude that CD causes sex‐dependent effects on glucose metabolism, as aggravated by male gonadal sex hormones and partly rescued by female gonadal sex hormones. Future studies on CD should consider the inclusion of both sexes, which may eventually contribute to personalized advice for shift workers.