bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lineage Reversion Drives WNT Independence in Intestinal Cancer
Authors: Han Teng , Goswami Sukanya , Hu Yang , Tang Fanying , Zafra Maria Paz , Murphy Charles , Cao Zhen , Poirier John T. , Khurana Ekta , Elemento Olivier , Hechtman Jaclyn F. , Ganesh Karuna , Yaeger Rona , Dow Lukas E. 
Published: June 2020

Abstract

The WNT pathway is a fundamental regulator of intestinal homeostasis, and hyperactivation of WNT signaling is the major oncogenic driver in colorectal cancer. To date, there are no described mechanisms that bypass WNT dependence in intestinal tumors. Here, we show that although WNT suppression blocks tumor growth in most organoid and in vivo colorectal cancer models, the accumulation of colorectal cancer–associated genetic alterations enables drug resistance and WNT-independent growth. In intestinal epithelial cells harboring mutations in KRAS or BRAF, together with disruption of TP53 and SMAD4, transient TGFβ exposure drives YAP/TAZ-dependent transcriptional reprogramming and lineage reversion. Acquisition of embryonic intestinal identity is accompanied by a permanent loss of adult intestinal lineages, and long-term WNT-independent growth. This work identifies genetic and microenvironmental factors that drive WNT inhibitor resistance, defines a new mechanism for WNT-independent colorectal cancer growth, and reveals how integration of associated genetic alterations and extracellular signals can overcome lineage-dependent oncogenic programs.

Significance:
Colorectal and intestinal cancers are driven by mutations in the WNT pathway, and drugs aimed at suppressing WNT signaling are in active clinical development. Our study identifies a mechanism of acquired resistance to WNT inhibition and highlights a potential strategy to target those drug-resistant cells.
This article is highlighted in the In This Issue feature, p. 1426
Soil and Seed: Coconspirators in Therapy-Induced Myeloid Neoplasms
Authors: Shannon Kevin , Link Daniel C. 
Published: June 2020

Abstract

Summary:
In this issue of Blood Cancer Discovery, Stoddart and colleagues describe cooperative effects of exposing both the bone marrow microenvironment of recipient mice and donor hematopoietic stem and progenitor cells (HSPC) to an alkylating agent in a genetically accurate model of therapy-induced myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) characterized by chromosome 5q deletions. The authors further implicate senescence of alkylator-treated mesenchymal stem cells (MSC) as contributing to the microenvironmental damage and subsequent therapy-induced myeloid neoplasms (tMN). Loss of Trp53 function and somatic mutations in other DNA damage response (DDR) genes were associated with overt AML in this model. Together, these studies shed new light on the complex pathogenesis of tMN and establish a robust model for biologic and preclinical investigation.
See related article by Stoddart et al., p. 32.
Prognostic Value of Dynamic Changes in Pulmonary Congestion During Exercise Stress Echocardiography in Heart Failure With Preserved Ejection Fraction
Authors: Coiro Stefano , Simonovic Dejan , Deljanin-Ilic Marina , Duarte Kevin , Carluccio Erberto , Cattadori Gaia , Girerd Nicolas , Ambrosio Giuseppe 
Published: June 2020

Background:
Patients with heart failure (HF) with preserved ejection fraction (HFpEF) typically develop dyspnea and pulmonary congestion upon exercise. Lung ultrasound is a simple diagnostic tool, providing semiquantitative assessment of extravascular lung water through B-lines. It has been shown that patients with HFpEF develop B-lines upon submaximal exercise stress echocardiography; however, whether exercise-induced pulmonary congestion carries prognostic implications is unknown. This study aimed at evaluating the prognostic value of B-line assessment during exercise in patients with HFpEF.

Methods:
Sixty-one New York Heart Association class I to II patients with HFpEF underwent standard echocardiography, lung ultrasound (28-scanning point method), and BNP (B-type natriuretic peptide) assessment during supine exercise echocardiography (baseline and peak exercise). The primary end point was a composite of cardiovascular death or HF hospitalization at 1 year.

Results:

B-lines, E/e′, and BNP significantly increased during exercise (
P
<0.001 for all). By multivariable analysis, both peak (hazard ratio, 1.50 [95% CI, 1.21–1.85],
P
<0.001), and change (hazard ratio 1.34 [95% CI, 1.12–1.62],
P
=0.002) B-lines were retained as independent predictors of outcome (hazard ratios per 1 B-line increment), along with BNP and E/e′ ratio. Importantly, adding peak B-line on top of a clinical model significantly improved prognostic accuracy (C-index increase, 0.157 [0.056–0.258],
P
=0.002) and net reclassification (continuous net reclassification improvement, 0.51 [0.09–0.74],
P
=0.016), with similar results for B-line change.

Conclusions:
Detection of exercise-induced pulmonary congestion by lung ultrasound is an independent predictor of outcome in patients with HFpEF; its use may help refining the routine risk stratification of these patients on top of well-established clinical variables.
Risk of Ischemic Stroke Increases Over the Spectrum of Metabolic Syndrome Severity
Authors: DeBoer Mark D. , Filipp Stephanie L. , Sims Mario , Musani Solomon K. , Gurka Matthew J. 
Published: June 2020

Background and Purpose:

Ischemic stroke is associated with the metabolic syndrome (MetS) as diagnosed using dichotomous criteria; however, these criteria exhibit racial/ethnic discrepancies. Our goal was to assess whether ischemic stroke risk extended over the spectrum of worsening MetS severity using a sex- and race/ethnicity-specific MetS-severity
Z
score.

Methods:

We used Cox-proportional hazards models to assess the relationship between baseline MetS-
Z
score and incident ischemic stroke among participants of the Atherosclerosis Risk in Communities study and Jackson Heart Study who were free from diabetes, coronary heart disease or stroke at baseline, evaluating 13 141 white and black individuals with mean follow-up of 18.6 years.

Results:
We found that risk of ischemic stroke increased consistently with MetS severity, with a hazard ratio of 1.75 (95% CI, 1.35–2.27) for those >75th percentile compared to those <25th percentile. This risk was highest for white females (hazard ratio, 2.63 [CI, 1.70–4.07]) though without significant interaction by sex and race. Relationships between stroke and all the individual components of MetS were only noted for white females, though again without sex-race interactions. Hazard ratio’s for systolic blood pressure and stroke were significant among all sex/racial subgroups.

Conclusions:
Ischemic stroke risk increased over the spectrum of MetS severity in the absence of baseline diabetes mellitus, further implicating potential etiologic risks from processes underlying MetS. Individuals with elevated MetS severity should be counselled toward lifestyle modification to lower ischemic stroke risk.
Recent distribution of Eurytemora velox (Lilljeborg, 1853) (Copepoda, Calanoida) in brackish and fresh waters of Ukraine
Authors: Samchyshyna Larysa , Gromova Yulia , Zorina-Sakharova Kateryna 
Published: June 2020

Abstract
The brackish water calanoid copepod Eurytemora velox has become a widespread species in inland fresh waters of Ukraine. Nowadays it is one of the dominant crustacean species in the littoral zooplankton of the main Ukrainian rivers: Dnieper, Danube and Pivdenny Buh. We present a survey on E. velox localities in, mainly, fresh waters of Ukraine, data on some quite isolated populations of E. velox in the Carpathian region, as well as new records of the species in the upper parts of some rivers. These data will provide a more complete view of the inland distribution of E. velox in Ukraine.
Representatives of the genus Eurytemora Giesbrecht, 1881 (Calanoida, Temoridae) in aquatic ecosystems of Belarus
Authors: Vezhnavets Vasil V. , Litvinova Anastasiya G. 
Published: June 2020

Abstract
The main biological features of two species of the genus Eurytemora have been studied: the relict E. lacustris (Poppe, 1887) and the alien E. velox (Lilljeborg, 1853), which can be found in natural environments on the territory of the Republic of Belarus.
The relict species E. lacustris has been found only in two mesotrophic dimictic lakes belonging to the Baltic Sea basin: Volchin (maximum depth 32.9 m) and Vecheliye (35.9 m). E. velox has now colonized the main rivers of the south of Belarus and their accessory reservoirs belonging to the basins of the Baltic and Black seas.
E. lacustris is characterized by an uneven distribution in the water column and location in deep water layers with temperatures below 13°C. Seasonal and daily vertical migrations have been established for E. lacustris. With age, the amplitude of migrations increases, reaching values of more than 10 m of depth for adults. E. velox is recorded in the coastal biotopes of watercourses and shallow water bodies.
In the recent two years, the average density of E. lacustris in Lake Vecheliye has been established as about 2000 ind./m3, while their percentage in the zooplankton was 6%. In Lake Volchin, its density has been 2-5 times lower in the same period, and there this species’ percentage in the plankton did not exceed 2%. The density of E. velox varies from 20 to 12 000 ind./m3, their average density is 1631 ind./m3, and their percentual share in the zooplankton does not exceed 1%.
For E. lacustris, the body length at all stages of development has been determined. It has been established that males have a greater body length in comparison with females, due to the relatively longer male abdomen, which is not typical for other species of freshwater planktonic copepods.
In Belarus, E. lacustris is a bicyclic species, whereas E. velox is polycyclic.
Telehealth and hospital performance: Does it matter?
Authors: Zhao Mei , Hamadi Hanadi , Xu Jing , Haley D Rob , Park Sinyoung , White-Williams Cynthia 
Published: June 2020

Introduction Previous studies indicated that telehealth services may improve hospital performance. However, the extent to which these telehealth provisions would improve hospital total performance score under the hospital value-based purchasing (HVBP) programme is not clear. The aim of this study is to examine the association between telehealth provision and hospital performance. Methods We performed a retrospective analysis of the association between the provision of telehealth services and 2699 hospital’s total performance score (TPS) on the 2018 HVBP programme and its four domains. Multivariate regression models were used to analyse TPS and hospital performance on each domain. Telehealth services offered by a hospital was categorically operationalized as hospitals with no telehealth services, with one to two telehealth services, and with three or more telehealth services. Results Hospitals with one to two telehealth services have TPS (ß coefficient = 1.50; 95% confident intervals (CI): 0.28, 2.73; p < 0.05) and hospitals with three or more telehealth services have higher efficiency and cost reduction (ß = 1.10; 95% CI: 0.32, 1.87; p < 0.01) domain scores. However, the impact of telehealth on clinical care, person and community engagement, and safety domain scores was not significant. Discussion The expansion of hospital telehealth service provision can improve not only the efficiency of care, but also the total performance of the hospital. Since total performance is directly associated with hospital payments from the government, these findings have significant practice and policy implications. In addition, the effect of telehealth on other quality measures such as clinical care and safety needs further investigation.
Fast intrinsic optical signal correlates with activation phase of phototransduction in retinal photoreceptors
Authors: Yao Xincheng , Kim Tae-Hoon 
Published: June 2020

Quantitative assessment of physiological condition of retinal photoreceptors is desirable for better detection and treatment evaluation of eye diseases that can cause photoreceptor dysfunctions. Functional intrinsic optical signal (IOS) imaging, also termed as optoretinography (ORG) or optophysiology, has been proposed as a high-resolution method for objective assessment of retinal physiology. Fast IOS in retinal photoreceptors shows a time course earlier than that of electroretinography a-wave, promising an objective marker for noninvasive ORG of early phototransduction process in retinal photoreceptors. In this article, recent observations of fast photoreceptor-IOS in animal and human retinas are summarized, and the correlation of fast photoreceptor-IOS to five steps of phototransduction process is discussed. Transient outer segment conformational change, due to inter-disc space shrinkage correlated with activation phase of phototransduction, has been disclosed as a primary source of the fast photoreceptor-IOS. Impact statement As the center of phototransduction, retinal photoreceptors are responsible for capturing and converting photon energy to bioelectric signals for following visual information processing in the retina. This article summarizes experimental observation and discusses biophysical mechanism of fast photoreceptor-intrinsic optical signal (IOS) correlated with early phase of phototransduction. Quantitative imaging of fast photoreceptor-IOS may provide objective optoretinography to advance the study and diagnosis of age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and other eye diseases that can cause photoreceptor dysfunctions.
First-line imatinib vs second- and third-generation TKIs for chronic-phase CML: a systematic review and meta-analysis
Authors: Vener Claudia , Banzi Rita , Ambrogi Federico , Ferrero Annalisa , Saglio Giuseppe , Pravettoni Gabriella , Sant Milena 
Published: June 2020

Abstract
Imatinib, the first tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), improves overall survival (OS), but the introduction of newer TKIs requires the definition of the optimal first-line TKI for newly diagnosed Philadelphia chromosome–positive (Ph+) chronic-phase (CP) CML. This systematic review of randomized controlled trials (RCTs) compares the efficacy and safety of imatinib vs second-generation (dasatinib, nilotinib, bosutinib) and third-generation TKIs (ponatinib) in adults with newly diagnosed Ph+ CP CML, concentrating on OS, progression-free survival (PFS), and hematological and nonhematological adverse events. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. Seven RCTs published between 1990 and 2019 (involving 3262 participants) satisfied the eligibility criteria. Two RCTs (imatinib vs nilotinib and imatinib vs dasatinib) found no difference in 5-year OS or PFS. Second- and third-generation TKIs improved 3-month major molecular responses (relative risk [RR], 4.28; 95% confidence interval [CI], 2.20-8.32) and other efficacy outcomes, decreased accelerated/blastic-phase transformations (RR, 0.44; 95% CI, 0.26-0.74), but were associated with more cases of thrombocytopenia (RR, 1.57; 95% CI, 1.20-2.05), cardiovascular events (RR, 2.54; 95% CI, 1.49-4.33), and pancreatic (RR, 2.29; 95% CI, 1.32-3.96) and hepatic effects (RR, 3.51; 95% CI 1.55-7.92). GRADE showed that the certainty of the evidence ranged from high to moderate. This study shows that, in comparison with imatinib, second- and third-generation TKIs improve clinical responses, but the safer toxicity profile of imatinib may make it a better option for patients with comorbidities.
CD4+ T-cell killing of multiple myeloma cells is mediated by resident bone marrow macrophages
Authors: Haabeth Ole Audun W. , Hennig Kjartan , Fauskanger Marte , Løset Geir Åge , Bogen Bjarne , Tveita Anders 
Published: June 2020

Abstract
CD4+ T cells may induce potent antitumor immune responses through interaction with antigen-presenting cells within the tumor microenvironment. Using a murine model of multiple myeloma, we demonstrated that adoptive transfer of idiotype-specific CD4+ T cells may elicit curative responses against established multifocal myeloma in bone marrow. This finding indicates that the myeloma bone marrow niche contains antigen-presenting cells that may be rendered tumoricidal. Given the complexity of the bone marrow microenvironment, the mechanistic basis of such immunotherapeutic responses is not known. Through a functional characterization of antitumor CD4+ T-cell responses within the bone marrow microenvironment, we found that killing of myeloma cells is orchestrated by a population of bone marrow–resident CD11b+F4/80+MHC-IIHigh macrophages that have taken up and present secreted myeloma protein. The present results demonstrate the potential of resident macrophages as powerful mediators of tumor killing within the bone marrow and provide a basis for novel therapeutic strategies against multiple myeloma and other malignancies that affect the bone marrow.
Addressing chronic persistent headaches after MTBI as a neuropathic pain state
Authors: Leung Albert 
Published: June 2020

AbstractAn increasing number of patients with chronic persistent post-traumatic headache (PPTH) after mild traumatic brain injury (MTBI) are being referred to headache or pain specialists as conventional treatment options for primary headache disorders have not been able to adequately alleviate their debilitating headache symptoms. Evolving clinical and mechanistic evidences support the notation that chronic persistent MTBI related headaches (MTBI-HA) carry the hallmark characteristics of neuropathic pain. Thus, in addition to conventional treatment options applicable to non-traumatic primary headache disorders, other available treatment modalities for neuropathic pain should be considered. In this comprehensive review article, the author reveals the prevalence of MTBI-HA and its clinical manifestation, discusses existing clinical and mechanistic evidence supporting the classification of chronic persistent MTBI-HA as a neuropathic pain state, and explores current available treatment options and future directions of therapeutic research related to MTBI-HA.
The association between sleep duration, bedtimes, and early pubertal timing among Chinese adolescents: a cross-sectional study
Authors: Diao Hua , Wang Hong , Yang Lianjian , Li Ting 
Published: June 2020

Abstract
Background and objective
Early pubertal timing is associated with sleep among Western adolescents, but little is known about this association in Chinese adolescents, especially with regard to the association between bedtimes and early pubertal timing. This paper aimed to identify the association between sleep duration, bedtimes, and early pubertal timing in Chinese adolescents.

Methods
An anonymous cross-sectional survey was conducted among primary and junior middle students (grades 3 to 9) from QiJiang District, ChongQing, China. Participants were recruited by applying stratified cluster sampling. Pubertal timing, sleep duration, and bedtimes were assessed using the Pubertal Development Scale and a self-designed sleep questionnaire. We utilized multivariable logistic linear regression (MLLR) to test the association between sleep duration, bedtimes, and pubertal timing.

Results
A total of 5461 adolescents were evaluated, with mean age and BMI values of 11.41 ± 2.05 and 18.03 ± 3.03, respectively, of whom 1257 (23.02%) were in early pubertal timing. In MLLR controlling for age, BMI, family economic status, and other covariates, sufficient sleep (b = − 0.214, P = 0.032, OR = 0.808, 95% CI 0.664–0.982) was negatively related to early pubertal timing, and later bedtime (b = 0.195, P < 0.001, OR = 1.215, 95% CI 1.104–1.338) was positively associated with early pubertal timing.

Conclusion
Students with early pubertal timing had less sleep duration and later bedtimes, which may be the result of increased stress caused by physical and psychological changes. Therefore, more attention should be paid to pubertal health education for adolescents during puberty. Further longitudinal studies are needed to confirm the causality between sleep and early pubertal timing in Chinese adolescents.
Lipidome analysis of milk composition in humans, monkeys, bovids, and pigs
Authors: Mitina Aleksandra , Mazin Pavel , Vanyushkina Anna , Anikanov Nikolay , Mair Waltraud , Guo Song , Khaitovich Philipp 
Published: June 2020

AbstractBackgroundLipids contained in milk are an essential source of energy and structural materials for a growing neonate. Furthermore, lipids’ long-chain unsaturated fatty acid residues can directly participate in neonatal tissue formation. Here, we used untargeted mass spectrometric measurements to assess milk lipid composition in seven mammalian species: humans, two macaque species, cows, goats, yaks, and pigs.ResultsAnalysis of the main milk lipid class, triacylglycerides (TAGs), revealed species-specific quantitative differences in the composition of fatty acid residues for each of seven species. Overall, differences in milk lipid composition reflect evolutionary distances among species, with each species group demonstrating specific lipidome features. Among them, human milk contained more medium and long-chain unsaturated fatty acids compared to other species, while pig milk was the most distinct, featuring the highest proportion of long-chain polyunsaturated fatty acids.ConclusionsWe show that milk lipidome composition is dynamic across mammalian species, changed extensively in pigs, and contains features particular to humans.
Immune activation of murine RAW264.7 macrophages by sonicated and alkalized paramylon from Euglena gracilis
Authors: Guo Qingqing , Bi Decheng , Wu Mingcan , Yu Boming , Hu Lang , Liu Chenchen , Gu Liang , Zhu Hui , Lei Anping , Xu Xu , Wang Jiangxin 
Published: June 2020

Abstract
Background
Euglena is a new super health food resource that is rich in the natural polysaccharide paramylon, a linear β-1,3-glucan with various biological activities including activity on the immune system in different cell lines and animals. Despite these reports, the immune regulation mechanism of paramylon is still unclear.

Results
We investigate the signaling pathways paramylon impacts in immune macrophages. In RAW264.7 macrophages, sonicated and alkalized paramylon oligomers up-regulated inducible nitric oxide synthase (iNOS) and increased secretion of nitric oxide (NO), interleukin (IL)-6 and tumor necrosis factor (TNF)-α, in a concentration-dependent manner. In addition, paramylon activated the nuclear factor-κB(NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways and inhibiting these pathways attenuated the paramylon-induced secretion of the above immune-mediators.

Conclusions
These results demonstrate that Euglena gracilis paramylon modulates the immune system via activation of the NF-κB and MAPK signaling pathways and thus has potential therapeutic benefits.