bluuebunny/crossref_metadata_2025_split huggingface dataset:
Holographic subregion complexity in unbalanced holographic superconductors
Authors: Shi Yu , Pan Qiyuan , Jing Jiliang 
Published: March 2021

AbstractBy using the subregion CV conjecture, we numerically investigate the behavior of the holographic subregion complexity (HSC) and compare it with the holographic entanglement entropy (HEE) in the unbalanced holographic superconductors, which indicates that both the HEE and HSC can be used as good probes to the phase transition in unbalanced holographic superconductors. We observe that the HEE and HSC exhibit a similar linear growth behavior with the change of width for a strip geometry. However, for different fixed widths, the HSC exhibits different behaviors with the change of the temperature, while the behavior of HEE remains consistent. In particular, we find that there are certain conditions that make it difficult to observe the phase transition of this system through the HSC approach. Furthermore, we also note that the unbalance parameter has different effects on the HSC, while the HEE always increases as the unbalance parameter increases.
Amelioration of bone fragility by pulsed electromagnetic fields in type 2 diabetic KK-Ay mice involving Wnt/β-catenin signaling
Authors: Shao Xi , Yang Yongqing , Tan Zhifen , Ding Yuanjun , Luo Erping , Jing Da , Cai Jing 
Published: March 2021

Type 2 diabetes mellitus (T2DM) results in compromised bone microstructure and quality, and subsequently increased risks of fractures. However, it still lacks safe and effective approaches resisting T2DM bone fragility. Pulsed electromagnetic fields (PEMFs) exposure has proven to be effective in accelerating fracture healing and attenuating osteopenia/osteoporosis induced by estrogen deficiency. Nevertheless, whether and how PEMFs resist T2DM-associated bone deterioration remain not fully identified. The KK-Ay mouse was used as the T2DM model. We found that PEMF stimulation with 2 h/day for 8 wk remarkably improved trabecular bone microarchitecture, decreased cortical bone porosity, and promoted trabecular and cortical bone material properties in KK-Ay mice. PEMF stimulated bone formation in KK-Ay mice, as evidenced by increased serum levels of bone formation (osteocalcin and P1NP), enhanced bone formation rate, and increased osteoblast number. PEMF significantly suppressed osteocytic apoptosis and sclerostin expression in KK-Ay mice. PEMF exerted beneficial effects on osteoblast- and osteocyte-related gene expression in the skeleton of KK-Ay mice. Nevertheless, PEMF exerted no effect on serum biomarkers of bone resorption (TRAcP5b and CTX-1), osteoclast number, or osteoclast-specific gene expression ( TRAP and cathepsin K). PEMF upregulated gene expression of canonical Wnt ligands (including Wnt1, Wnt3a, and Wnt10b), but not noncanonical Wnt5a. PEMF also upregulated skeletal protein expression of downstream p-GSK-3β and β-catenin in KK-Ay mice. Moreover, PEMF-induced improvement in bone microstructure, mechanical strength, and bone formation in KK-Ay mice was abolished after intragastric administration with the Wnt antagonist ETC-159. Together, our results suggest that PEMF can improve bone microarchitecture and quality by enhancing the biological activities of osteoblasts and osteocytes, which are associated with the activation of the Wnt/β-catenin signaling pathway. PEMF might become an effective countermeasure against T2DM-induced bone deterioration. NEW & NOTEWORTHY PEMF improved trabecular bone microarchitecture and suppressed cortical bone porosity in T2DM KK-Ay mice. It attenuated T2DM-induced detrimental consequence on trabecular and cortical bone material properties. PEMF resisted bone deterioration in KK-Ay mice by enhancing osteoblast-mediated bone formation. PEMF also significantly suppressed osteocytic apoptosis and sclerostin expression in KK-Ay mice. The therapeutic potential of PEMF on T2DM-induced bone deterioration was associated with the activation of Wnt/ß-catenin signaling.
The Dolaflexin-based Antibody–Drug Conjugate XMT-1536 Targets the Solid Tumor Lineage Antigen SLC34A2/NaPi2b
Authors: Bodyak Natalya D. , Mosher Rebecca , Yurkovetskiy Aleksandr V. , Yin Mao , Bu Charlie , Conlon Patrick R. , Demady Damon R. , DeVit Michael J. , Gumerov Dmitry R. , Gurijala Venu R. , Lee Winnie , McGillicuddy Dennis , Park Peter U. , Poling Laura L. , Protopova Marina , Qin LiuLiang , Stevenson Cheri A. , Ter-Ovanesyan Elena , Uttard Alex , Xiao Dongmei , Xu Jian , Xu Ling , Bergstrom Donald A. , Lowinger Timothy B. 
Published: March 2021

Abstract
Target selection for antibody–drug conjugates (ADC) frequently focuses on identifying antigens with differential expression in tumor and normal tissue, to mitigate the risk of on-target toxicity. However, this strategy restricts the possible target space. SLC34A2/NaPi2b is a sodium phosphate transporter expressed in a variety of human tumors including lung and ovarian carcinoma, as well as the normal tissues from which these tumors arise. Previous clinical trials with a NaPi2b targeting MMAE-ADCs have shown objective durable responses. However, the protein-based biomarker assay developed for use in that study was unable to discern a statistically significant relationship between NaPi2b protein expression and the probability of response. XMT-1536 is a NaPi2b targeting ADC comprised of a unique humanized antibody conjugated with 10–15 auristatin F- hydroxypropylamide (AF-HPA) payload molecules via the Dolaflexin platform. AF-HPA is a cell-permeable, antimitotic compound that is slowly metabolized intratumorally to an active, very low-permeable metabolite, auristatin F (AF), resulting in controlled bystander killing. We describe the preclinical in vitro and in vivo antitumor effects of XMT-1536 in models of ovarian and lung adenocarcinoma. Pharmacokinetic analysis showed approximately proportional increases in exposure in rat and monkey. Systemic free AF-HPA and AF concentrations were observed to be low in all animal species. Finally, we describe a unique IHC reagent, generated from a chimeric construct of the therapeutic antibody, that was used to derive a target expression and efficacy relationship in a series of ovarian primary xenograft cancer models.
Exploiting Tumor Neoantigens to Target Cancer Evolution: Current Challenges and Promising Therapeutic Approaches
Authors: Gupta Ravi G. , Li Fenge , Roszik Jason , Lizée Gregory 
Published: March 2021

Abstract

Immunotherapeutic manipulation of the antitumor immune response offers an attractive strategy to target genomic instability in cancer. A subset of tumor-specific somatic mutations can be translated into immunogenic and HLA-bound epitopes called neoantigens, which can induce the activation of helper and cytotoxic T lymphocytes. However, cancer immunoediting and immunosuppressive mechanisms often allow tumors to evade immune recognition. Recent evidence also suggests that the tumor neoantigen landscape extends beyond epitopes originating from nonsynonymous single-nucleotide variants in the coding exome. Here we review emerging approaches for identifying, prioritizing, and immunologically targeting personalized neoantigens using polyvalent cancer vaccines and T-cell receptor gene therapy.

Significance:
Several major challenges currently impede the clinical efficacy of neoantigen-directed immunotherapy, such as the relative infrequency of immunogenic neoantigens, suboptimal potency and priming of de novo tumor-specific T cells, and tumor cell–intrinsic and –extrinsic mechanisms of immune evasion. A deeper understanding of these biological barriers could help facilitate the development of effective and durable immunotherapy for any type of cancer, including immunologically “cold” tumors that are otherwise therapeutically resistant.
Objective Sleep Efficiency Predicts Cardiovascular Disease in a Community Population: The Sleep Heart Health Study
Authors: Yan Bin , Yang Jian , Zhao Binbin , Fan Yajuan , Wang Wei , Ma Xiancang 
Published: March 2021

Background
There was little evidence about the role of objective sleep efficiency (SE) in the incidence of major cardiovascular disease (CVD) events. The purpose of this study was to investigate the correlation between objective SE and CVD based on polysomnography.

Methods and Results

A total of 3810 participants from the SHHS (Sleep Heart Health Study) were selected in the current study. CVD was assessed during an almost 11‐year follow‐up period. The primary composite cardiovascular outcome was major adverse cardiovascular events, defined as CVD mortality, congestive heart failure, myocardial infarction, and stroke. The secondary composite cardiovascular outcome was major adverse cardiovascular event plus revascularization. Objective measured SE, including SE and wake after sleep onset, was based on in‐home polysomnography records. Cox regression analysis was used to explore the association between SE and CVD. After multivariate Cox regression analysis, poor SE (<80%) was significantly associated with primary (hazard ratio [HR], 1.338; 95% CI, 1.025–1.745;
P
=0.032) and secondary composite cardiovascular outcomes (HR, 1.250; 95% CI, 1.027–1.521;
P
=0.026); it was also found to be a predictor of CVD mortality (HR, 1.887; 95% CI, 1.224–2.909;
P
=0.004). Moreover, wake after sleep onset of fourth quartile (>78.0 minutes) was closely correlated with primary (HR, 1.436; 95% CI, 1.066–1.934;
P
=0.017), secondary composite cardiovascular outcomes (HR, 1.374; 95% CI, 1.103–1.712;
P
=0.005), and CVD mortality (HR, 2.240; 95% CI, 1.377–3.642;
P
=0.001).

Conclusions
Poor SE and long wake after sleep onset, objectively measured by polysomnography, were associated with the increased risk of incident CVD.
Estrogen Plays a Crucial Role in Rab9‐Dependent Mitochondrial Autophagy, Delaying Arterial Senescence
Authors: Sasaki Yuichi , Ikeda Yoshiyuki , Uchikado Yoshihiro , Akasaki Yuichi , Sadoshima Junichi , Ohishi Mitsuru 
Published: March 2021

Background
The risk of cardiovascular disease is known to increase after menopause. Mitochondria, which undergo quality control via mitochondrial autophagy, play a crucial role in the regulation of cellular senescence. The aim of this study was to investigate whether the effect of estrogen‐mediated protection from senescence on arteries is attributed to the induction of mitochondrial autophagy.

Methods and Results
We used human umbilical vein cells, vascular smooth muscle cells, and 12‐week‐old female C57BL/6 mice. The administration of 17β‐estradiol (E2) to cells inhibited cellular senescence and mitochondrial dysfunction. Furthermore, E2 increased mitochondrial autophagy, maintaining mitochondrial function, and retarding cellular senescence. Of note, E2 did not modulate LC3 (light chain 3), and ATG7 (autophagy related 7) deficiency did not suppress mitochondrial autophagy in E2‐treated cells. Conversely, E2 increased the colocalization of Rab9 with LAMP2 (lysosomal‐associated membrane protein 2) signals. The E2‐mediated effects on mitochondrial autophagy were abolished by the knockdown of either Ulk1 or Rab9. These results suggest that E2‐mediated mitochondrial autophagy is associated with Rab9‐dependent alternative autophagy. E2 upregulated SIRT1 (sirtuin 1) and activated LKB1 (liver kinase B1), AMPK (adenosine monophosphate‐activated protein kinase), and Ulk1, indicating that the effect of E2 on the induction of Rab9‐dependent alternative autophagy is mediated by the SIRT1/LKB1/AMPK/Ulk1 pathway. Compared with the sham‐operated mice, ovariectomized mice showed reduced mitochondrial autophagy and accelerated mitochondrial dysfunction and arterial senescence; these detrimental alterations were successfully rescued by the administration of E2.

Conclusions
We showed that E2‐induced mitochondrial autophagy plays a crucial role in the delay of vascular senescence. The Rab9‐dependent alternative autophagy is behind E2‐induced mitochondrial autophagy.
Impact of Delirium and Its Motor Subtypes on Stroke Outcomes
Authors: Fialho Silva Ivã Taiuan , Assis Lopes Pedro , Timotio Almeida Tiago , Ramos Saint Clair , Caliman Fontes Ana Teresa , Guimarães Silva Daniel , Martins Soares Camila , Oliveira Carneiro Lays , Souza Ian Felipe Barbosa , Ferreira Abreu Fernanda , Nascimento Silva Gabriel , Mascarenhas de Souza Letícia , Brito Pinheiro Thiago , de Souza e Silva Filipe Nolasco , de Santana João Pedro , Kelly Silva Beatriz , Almeida Souza Danilo , Silva Macedo Silvana , Almeida Ismael Leila Silva , Pereira de Jesus Pedro Antonio 
Published: March 2021

Background and Purpose:
Delirium is an acute and fluctuating impairment of attention, cognition, and behavior. Although common in stroke, studies that associate the clinical subtypes of delirium with functional outcome and death are lacking. We aimed to evaluate the influence of delirium occurrence and its different motor subtypes over stroke patients’ prognosis.

Methods:
Prospective cohort of stroke patients with symptom onset within 72 hours before research admission. Delirium was diagnosed by Confusion Assessment Method for the Intensive Care Unit, and its motor subtypes were defined according to the Richmond Agitation-Sedation Scale. The main outcome was functional dependence or death (modified Rankin Scale>2) at 90 days comparing: delirium versus no delirium patients; and between motor subtypes. Secondary outcomes included modified Rankin Scale score >2 at 30 days and 90-day-mortality.

Results:
Two hundred twenty-seven patients were enrolled. Delirium occurred in 71 patients (31.3%), with the hypoactive subtype as the most frequent, in 41 subjects (57.8%). Delirium was associated with increased risk of death and functional dependence at 30 and 90 days and higher 90-day mortality. Multivariate analysis showed delirium (odds ratio, 3.28 [95% CI, 1.17–9.22]) as independent predictor of modified Rankin Scale >2 at 90 days.

Conclusions:
Delirium is frequent in stroke patients in the acute phase. Its occurrence—specifically in mixed and hypoactive subtypes—seems to predict worse outcomes in this population. To our knowledge, this is the first study to prospectively investigate differences between delirium motor subtypes over functional outcome three months poststroke. Larger studies are needed to elucidate the relationship between motor subtypes of delirium and functional outcomes in the context of acute stroke.
CYGNSS Observations and Analysis of Low-Latitude Extratropical Cyclones
Authors: Crespo Juan A. , Naud Catherine M. , Posselt Derek J. 
Published: March 2021

AbstractLatent and sensible heat fluxes over the oceans are believed to play an important role in the genesis and evolution of marine-based extratropical cyclones (ETCs) and affect rapid cyclogenesis. Observations of ocean surface heat fluxes are limited from existing in situ and remote sensing platforms, which may not offer sufficient spatial and temporal resolution. In addition, substantial precipitation frequently veils the ocean surface around ETCs, limiting the capacity of spaceborne instruments to observe the surface processes within maturing ETCs. Although designed as a tropics-focused mission, the Cyclone Global Navigation Satellite System (CYGNSS) can observe ocean surface wind speed and heat fluxes within a notable quantity of low-latitude extratropical fronts and cyclones. These observations can assist in understanding how surface processes may play a role in cyclogenesis and evolution. This paper illustrates CYGNSS’s capability to observe extratropical cyclones manifesting in various ocean basins throughout the globe and shows that the observations provide a robust sample of ETCs winds and surface fluxes, as compared with a reanalysis dataset.
Comments on “Flash Flood Verification: Pondering Precipitation Proxies”
Authors: Gourley Jonathan J. , Vergara Humberto 
Published: March 2021

AbstractNew operational tools for monitoring flash flooding based on radar quantitative precipitation estimates (QPEs) have become available to U.S. National Weather Service forecasters. Herman and Schumacher examined QPE exceedance thresholds for several tools and compared them to each other, to flash flood reports (FFRs), and to flash flood warnings. The Next Generation Radar network has been updated with dual-polarization capabilities since the publication of Herman and Schumacher, which has changed the characteristics of the derived QPEs. Updated thresholds on Multi-Radar Multi-Sensor version 12 products that are associated to FFRs are provided and thus can be used as guidance by the operational forecasting community and other end-users of the products.
A Statistical Evaluation of WRF-LES Trace Gas Dispersion Using Project Prairie Grass Measurements
Authors: Rybchuk Alex , Alden Caroline B. , Lundquist Julie K. , Rieker Gregory B. 
Published: March 2021

AbstractIn recent years, new measurement systems have been deployed to monitor and quantify methane emissions from the natural gas sector. Large-eddy simulation (LES) has complemented measurement campaigns by serving as a controlled environment in which to study plume dynamics and sampling strategies. However, with few comparisons to controlled-release experiments, the accuracy of LES for modeling natural gas emissions is poorly characterized. In this paper, we evaluate LES from the Weather Research and Forecasting (WRF) model against Project Prairie Grass campaign measurements and surface layer similarity theory. Using WRF-LES, we simulate continuous emissions from 30 near-surface trace gas sources in two stability regimes: strong and weak convection. We examine the impact of grid resolutions ranging from 6.25 m to 52 m in the horizontal dimension on model results. We evaluate performance in a statistical framework, calculating fractional bias and conducting Welch’s t-tests. WRF-LES accurately simulates observed surface concentrations at 100 m and beyond under strong convection; simulated concentrations pass t-tests in this region irrespective of grid resolution. However, in weakly convective conditions with strong winds, WRF-LES substantially overpredicts concentrations – the magnitude of fractional bias often exceeds 30%, and all but one C-test fails. The good performance of WRF-LES under strong convection correlates with agreement with local free convection theory and a minimal amount of parameterized turbulent kinetic energy. The poor performance under weak convection corresponds to misalignment with Monin-Obukhov similarity theory and a significant amount of parameterized turbulent kinetic energy.
Large-Sample Application of Radar Reflectivity Object-Based Verification to Evaluate HRRR Warm-Season Forecasts
Authors: Duda Jeffrey D. , Turner David D. 
Published: March 2021

AbstractThe Method of Object-based Diagnostic Evaluation (MODE) is used to perform an object-based verification of approximately 1400 forecasts of composite reflectivity from the operational HRRR during April–September 2019. In this study, MODE is configured to prioritize deep, moist convective storm cells typical of those that produce severe weather across the central and eastern United States during the warm season. In particular, attributes related to distance and size are given the greatest attribute weights for computing interest in MODE. HRRR tends to overforecast all objects, but substantially overforecasts both small objects at low-reflectivity thresholds and large objects at high-reflectivity thresholds. HRRR tends to either underforecast objects in the southern and central plains or has a correct frequency bias there, whereas it overforecasts objects across the southern and eastern United States. Attribute comparisons reveal the inability of the HRRR to fully resolve convective-scale features and the impact of data assimilation and loss of skill during the initial hours of the forecasts. Scalar metrics are defined and computed based on MODE output, chiefly relying on the interest value. The object-based threat score (OTS), in particular, reveals similar performance of HRRR forecasts as does the Heidke skill score, but with differing magnitudes, suggesting value in adopting an object-based approach to forecast verification. The typical distance between centroids of objects is also analyzed and shows gradual degradation with increasing forecast length.
Estimating ‘outbreak’-level tornado counts and casualties from environmental variables
Authors: Schroder Zoe , Elsner James B. 
Published: March 2021

AbstractEnvironmental variables are routinely used in estimating when and where tornadoes are likely to occur, but more work is needed to understand how tornado and casualty counts of severe weather outbreak vary with the larger scale environmental factors. Here the authors demonstrate a method to quantify ‘outbreak’-level tornado and casualty counts with respect to variations in large-scale environmental factors. They do this by fitting negative binomial regression models to cluster-level environmental data to estimate the number of tornadoes and the number of casualties on days with at least ten tornadoes. Results show that a 1000 J kg−1 increase in CAPE corresponds to a 5% increase in the number of tornadoes and a 28% increase in the number of casualties, conditional on at least ten tornadoes, and holding the other variables constant. Further, results show that a 10 m s−1 increase in deep-layer bulk shear corresponds to a 13% increase in tornadoes and a 98% increase in casualties, conditional on at least ten tornadoes, and holding the other variables constant. The casualty-count model quantifies the decline in the number of casualties per year and indicates that outbreaks have a larger impact in the Southeast than elsewhere after controlling for population and geographic area.
Engaging peer consultants in mental health services: Narrative research
Authors: Balková Miluše 
Published: March 2021

Aims: The text deals with the specifics of the new job position of peer consultant in mental health services. The aim is to describe, through a literature search, the involvement of people with mental illness in the position of peer consultant in social services and to identify possible ethical aspects associated with this position. Theoretical background: The problem is viewed from the perspective of the service provider. The involvement of people with experience of mental illness (so-called peer consultants) in mental health services is still a little-known issue. These individuals use their experience of the disease to work with service users and can also act as intermediaries between users and professionals. The way a peer consultant works and his involvement in a team of experts can cause various ethical contradictions. Methods: To clarify the issue, a literature search was used, which was conducted for the period 2012 to 2020. Selected studies were analysed on the basis of focus and presented a connection with the practice, the results were compared. Findings were synthesized according to ethical attributes into categories and conclusions were drawn by subsequent logical deduction. Results: The results indicate a positive benefit of introducing the position to social services focused on mental health care. The positive impact is manifested in working with service user, in the functioning of the organization and also in the impact on the community. Successful implementation of the peer consultant position requires managers to prepare well and become familiar with the possible ethical aspects associated with the position.