bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDK1 is up-regulated by temozolomide in an NF-κB dependent manner in glioblastoma
Authors: Voce David J. , Bernal Giovanna M. , Cahill Kirk E. , Wu Longtao , Mansour Nassir , Crawley Clayton D. , Campbell Paige-Ashley S. , Arina Ainhoa , Weichselbaum Ralph R. , Yamini Bakhtiar 
Published: March 2021

AbstractThe alkylating agent, temozolomide (TMZ), is the most commonly used chemotherapeutic for the treatment of glioblastoma (GBM). The anti-glioma effect of TMZ involves a complex response that includes G2-M cell cycle arrest and cyclin-dependent kinase 1 (CDK1) activation. While CDK1 phosphorylation is a well-described consequence of TMZ treatment, we find that TMZ also robustly induces CDK1 expression. Analysis of this pathway demonstrates that CDK1 is regulated by NF-κB via a putative κB-site in its proximal promoter. CDK1 was induced in a manner dependent on mature p50 and the atypical inhibitor κB protein, BCL-3. Treatment with TMZ induced binding of NF-κB to the κB-site as assessed by gel shift analysis and chromatin immunoprecipitation. Examination of a CDK1 promoter-reporter demonstrated the functional relevance of the κB-site and underlined the requirement of p50 and BCL-3 for activation. Targeted knockdown of CDK1 or chemical inhibition with the selective CDK1 inhibitor, RO-3306, potentiated the cytotoxic effect of TMZ. These results identify CDK1 as an NF-κB target gene regulated by p50 and BCL-3 and suggest that targeting CDK1 may be a strategy to improve the efficacy of TMZ against GBM.
Proof-of-concept trial results of the HeartMan mobile personal health system for self-management in congestive heart failure
Authors: Clays Els , Puddu Paolo Emilio , Luštrek Mitja , Pioggia Giovanni , Derboven Jan , Vrana Marilena , De Sutter Johan , Le Donne Rita , Baert Anneleen , Bohanec Marko , Ciancarelli Maria Costanza , Dawodu Amos Adeyemo , De Pauw Michel , De Smedt Delphine , Marino Flavia , Pardaens Sofie , Schiariti Michele Salvatore , Valič Jakob , Vanderheyden Marc , Vodopija Aljoša , Tartarisco Gennaro 
Published: March 2021

AbstractThis study tested the effectiveness of HeartMan—a mobile personal health system offering decisional support for management of congestive heart failure (CHF)—on health-related quality of life (HRQoL), self-management, exercise capacity, illness perception, mental and sexual health. A randomized controlled proof-of-concept trial (1:2 ratio of control:intervention) was set up with ambulatory CHF patients in stable condition in Belgium and Italy. Data were collected by means of a 6-min walking test and a number of standardized questionnaire instruments. A total of 56 (34 intervention and 22 control group) participants completed the study (77% male; mean age 63 years, sd 10.5). All depression and anxiety dimensions decreased in the intervention group (p < 0.001), while the need for sexual counselling decreased in the control group (p < 0.05). Although the group differences were not significant, self-care increased (p < 0.05), and sexual problems decreased (p < 0.05) in the intervention group only. No significant intervention effects were observed for HRQoL, self-care confidence, illness perception and exercise capacity. Overall, results of this proof-of-concept trial suggest that the HeartMan personal health system significantly improved mental and sexual health and self-care behaviour in CHF patients. These observations were in contrast to the lack of intervention effects on HRQoL, illness perception and exercise capacity.
Shared cognitive mechanisms of hypnotizability with executive functioning and information salience
Authors: Faerman Afik , Spiegel David 
Published: March 2021

AbstractIn recent years, evidence linked hypnotizability to the executive control and information salience networks, brain structures that play a role in cognitive conflict resolution and perseveration (insisting on applying a previously learned logical rule on a new set). Despite the growing body of neuroimaging evidence, the cognitive phenotype of hypnotizability is not well understood. We hypothesized that higher hypnotizability would correspond to lower perseveration and set-shifting. Seventy-two healthy adults were tested for hypnotizability and executive functions (perseveration and set-shifting). Multiple regression analyses were performed to test the relationship between hypnotizability and perseveration and set-shifting. Higher hypnotizability was associated with lower perseveration after accounting for age and education. Hypnotizability significantly predicted perseveration but not set-shifting. Our results indicate an inverse relationship between trait hypnotizability and perseveration, an executive function that utilizes regions of both the executive control and the salience systems. This suggests that hypnotizability may share a common cognitive mechanism with error evaluation and implementation of logical rules.
Increases in Great Lake winds and extreme events facilitate interbasin coupling and reduce water quality in Lake Erie
Authors: Jabbari Aidin , Ackerman Josef D. , Boegman Leon , Zhao Yingming 
Published: March 2021

AbstractClimate change affects physical and biogeochemical processes in lakes. We show significant increases in surface-water temperature (~ 0.5 °C decade−1; > 0.2% year−1) and wave power (> 1% year−1; the transport of energy by waves) associated with atmospheric phenomena (Atlantic Multidecadal Oscillation and Multivariate El Niño/Southern Oscillation) in the month of August between 1980 and 2018 in the Laurentian Great Lakes. A pattern in wave power, in response to extreme winds, was identified as a proxy to predict interbasin coupling in Lake Erie. This involved the upwelling of cold and hypoxic (dissolved oxygen < 2 mg L−1) hypolimnetic water containing high total phosphorus concentration from the seasonally stratified central basin into the normally well-mixed western basin opposite to the eastward flow. Analysis of historical records indicate that hypoxic events due to interbasin exchange have increased in the western basin over the last four decades (43% in the last 10 years) thus affecting the water quality of the one of the world’s largest freshwater sources and fisheries.
Perspective taking as a mechanism for children’s developing preferences for equitable distributions
Authors: Sobel David M. , Blankenship Jayd 
Published: March 2021

AbstractHow do young children develop a concept of equity? Infants prefer dividing resources equally and expect others to make such distributions. Between the ages of 3–8, children begin to exhibit preferences to avoid inequitable outcomes in their distributions, dividing resources unequally if the result of that distribution is a more equitable outcome. Four studies investigated children’s developing preferences for generating equitable distributions, focusing on the mechanisms for this development. Children were presented with two characters with different amount of resources, and then a third character who will distribute more resources to them. Three- to 8-year-olds were asked whether the third character should give an equal number of resources to the recipients, preserving the inequity, or an unequal number to them, creating an equitable outcome. Starting at age 7, children showed a preference for equitable distributions (Study 1, N = 144). Studies 2a (N = 72) and 2b (N = 48) suggest that this development is independent of children’s numerical competence. When asked to take the perspective of the recipient with fewer resources, 3- to 6-year-olds were more likely to make an equitable distribution (Study 3, N = 122). These data suggest that social perspective taking underlies children’s prosocial actions, and supports the hypothesis that their spontaneous capacity to take others’ perspectives develops during the early elementary-school years.
A meta-analysis of Watson for Oncology in clinical application
Authors: Jie Zhou , Zhiying Zeng , Li Li 
Published: March 2021

AbstractUsing the method of meta-analysis to systematically evaluate the consistency of treatment schemes between Watson for Oncology (WFO) and Multidisciplinary Team (MDT), and to provide references for the practical application of artificial intelligence clinical decision-support system in cancer treatment. We systematically searched articles about the clinical applications of Watson for Oncology in the databases and conducted meta-analysis using RevMan 5.3 software. A total of 9 studies were identified, including 2463 patients. When the MDT is consistent with WFO at the ‘Recommended’ or the ‘For consideration’ level, the overall concordance rate is 81.52%. Among them, breast cancer was the highest and gastric cancer was the lowest. The concordance rate in stage I–III cancer is higher than that in stage IV, but the result of lung cancer is opposite (P < 0.05).Similar results were obtained when MDT was only consistent with WFO at the "recommended" level. Moreover, the consistency of estrogen and progesterone receptor negative breast cancer patients, colorectal cancer patients under 70 years old or ECOG 0, and small cell lung cancer patients is higher than that of estrogen and progesterone positive breast cancer patients, colorectal cancer patients over 70 years old or ECOG 1–2, and non-small cell lung cancer patients, with statistical significance (P < 0.05). Treatment recommendations made by WFO and MDT were highly concordant for cancer cases examined, but this system still needs further improvement. Owing to relatively small sample size of the included studies, more well-designed, and large sample size studies are still needed.
Genetic structure of Malus sylvestris and potential link with preference/performance by the rosy apple aphid pest Dysaphis plantaginea
Authors: Denoirjean Thomas , Doury Géraldine , Cornille Amandine , Chen Xilong , Hance Thierry , Ameline Arnaud 
Published: March 2021

AbstractThe European crabapple Malus sylvestris, a crop wild relative of Malus domestica, is a major contributor to the cultivated apple genome and represents a potential source of interesting alleles or genes, particularly pest resistance traits. An original approach was used to explore the trophic interaction between M. sylvestris populations and its pest, the rosy apple aphid (Dysaphis plantaginea). Using 13 microsatellite markers, population genetic structure and level of crop-to-wild introgressions were inferred between M. sylvestris seedlings from three sites in Europe (Denmark, France, Romania), and M. domestica seedlings. Genetically characterized plants were also used to analyze aphid feeding behavior and fitness parameters. First, aphids submitted to two genetically close M. sylvestris populations (the Danish and French) exhibited similar behavioral parameters, suggesting similar patterns of resistance in these host plants. Second, the Romanian M. sylvestris population was most closely genetically related to M. domestica. Although the two plant genetic backgrounds were significantly differentiated, they showed comparable levels of sensitivity to D. plantaginea infestation. Third, aphid fitness parameters were not significantly impacted by the host plant’s genetic background. Finally, crop-to-wild introgression seemed to significantly drive resistance to D. plantaginea independent of host plant population genetic structure, with hybrids being less suitable hosts.
Systems-wide effects of short-term feed deprivation in obese mice
Authors: Andersen Daniel , Roager Henrik Munch , Zhang Li , Moll Janne Marie , Frandsen Henrik Lauritz , Danneskiold-Samsøe Niels Banhos , Hansen Axel Kornerup , Kristiansen Karsten , Licht Tine Rask , Brix Susanne 
Published: March 2021

AbstractWhile prolonged fasting induces significant metabolic changes in humans and mice, less is known about systems-wide metabolic changes in response to short-term feed deprivation, which is used in experimental animal studies prior to metabolic challenge tests. We here performed a systems biology-based investigation of connections between gut bacterial composition and function, inflammatory and metabolic parameters in the intestine, liver, visceral adipose tissue, blood and urine in high-fat fed, obese mice that were feed deprived up to 12 h. The systems-wide analysis revealed that feed deprivation linked to enhanced intestinal butyric acid production and expression of the gene encoding the pro-thermogenic uncoupling protein UCP1 in visceral adipose tissue of obese mice. Ucp1 expression was also positively associated with Il33 expression in ileum, colon and adipose tissue as well as with the abundance of colonic Porphyromonadaceae, the latter also correlating to cecal butyric acid levels. Collectively, the data highlighted presence of a multi-tiered system of inter-tissue communication involving intestinal, immune and metabolic functions which is affected by feed deprivation in obese mice, thus pointing to careful use of short-feed deprivation in metabolic studies using obese mice.
Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice
Authors: Sampson Catherine M. , Dimet Andrea L. , Neelakantan Harshini , Ogunseye Kehinde O. , Stevenson Heather L. , Hommel Jonathan D. , Watowich Stanley J. 
Published: March 2021

AbstractObesity is a large and growing global health problem with few effective therapies. The present study investigated metabolic and physiological benefits of nicotinamide N-methyltransferase inhibitor (NNMTi) treatment combined with a lean diet substitution in diet-induced obese mice. NNMTi treatment combined with lean diet substitution accelerated and improved body weight and fat loss, increased whole-body lean mass to body weight ratio, reduced liver and epididymal white adipose tissue weights, decreased liver adiposity, and improved hepatic steatosis, relative to a lean diet substitution alone. Importantly, combined lean diet and NNMTi treatment normalized body composition and liver adiposity parameters to levels observed in age-matched lean diet control mice. NNMTi treatment produced a unique metabolomic signature in adipose tissue, with predominant increases in ketogenic amino acid abundance and alterations to metabolites linked to energy metabolic pathways. Taken together, NNMTi treatment’s modulation of body weight, adiposity, liver physiology, and the adipose tissue metabolome strongly support it as a promising therapeutic for obesity and obesity-driven comorbidities.
MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis
Authors: Kantar Diala , Mur Emilie Bousquet , Mancini Maicol , Slaninova Vera , Salah Yezza Ben , Costa Luca , Forest Elodie , Lassus Patrice , Géminard Charles , Boissière-Michot Florence , Orsetti Béatrice , Theillet Charles , Colinge Jacques , Benistant Christine , Maraver Antonio , Heron-Milhavet Lisa , Djiane Alexandre 
Published: March 2021

AbstractAlterations to cell polarization or to intercellular junctions are often associated with epithelial cancer progression, including breast cancers (BCa). We show here that the loss of the junctional scaffold protein MAGI1 is associated with bad prognosis in luminal BCa, and promotes tumorigenesis. E-cadherin and the actin binding scaffold AMOTL2 accumulate in MAGI1 deficient cells which are subjected to increased stiffness. These alterations are associated with low YAP activity, the terminal Hippo-pathway effector, but with an elevated ROCK and p38 Stress Activated Protein Kinase activities. Blocking ROCK prevented p38 activation, suggesting that MAGI1 limits p38 activity in part through releasing actin strength. Importantly, the increased tumorigenicity of MAGI1 deficient cells is rescued in the absence of AMOTL2 or after inhibition of p38, demonstrating that MAGI1 acts as a tumor-suppressor in luminal BCa by inhibiting an AMOTL2/p38 stress pathway.
Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models
Authors: Tosh Justin L. , Rhymes Elena R. , Mumford Paige , Whittaker Heather T. , Pulford Laura J. , Noy Sue J. , Cleverley Karen ,   LonDownS Consortium, Strydom Andre , Fisher Elizabeth , Wiseman Frances , Nizetic Dean , Hardy John , Tybulewicz Victor , Karmiloff-Smith Annette , Walker Matthew C. , Tybulewicz Victor L. J. , Wykes Rob C. , Fisher Elizabeth M. C. , Wiseman Frances K. 
Published: March 2021

AbstractIndividuals who have Down syndrome (caused by trisomy of chromosome 21), have a greatly elevated risk of early-onset Alzheimer’s disease, in which amyloid-β accumulates in the brain. Amyloid-β is a product of the chromosome 21 gene APP (amyloid precursor protein) and the extra copy or ‘dose’ of APP is thought to be the cause of this early-onset Alzheimer’s disease. However, other chromosome 21 genes likely modulate disease when in three-copies in people with Down syndrome. Here we show that an extra copy of chromosome 21 genes, other than APP, influences APP/Aβ biology. We crossed Down syndrome mouse models with partial trisomies, to an APP transgenic model and found that extra copies of subgroups of chromosome 21 gene(s) modulate amyloid-β aggregation and APP transgene-associated mortality, independently of changing amyloid precursor protein abundance. Thus, genes on chromosome 21, other than APP, likely modulate Alzheimer’s disease in people who have Down syndrome.
Higher choroidal thickness and lower choriocapillaris blood flow signal density based on optical coherence tomography angiography in diabetics
Authors: Zhang Yaoli , Qin Yuanjun , Wang Shuaishuai , Liu Yuyan , Li Xinyu , Sun Xufang 
Published: March 2021

AbstractDiabetes mellitus (DM) is one of the fastest growing chronic diseases in the world and one of the main causes of vision loss. Whether or not diabetic choroidopathy (DC) is involved in the initiation and progression of diabetic ocular complications needs to be explored. We included 54 diabetic eyes from 36 diabetic patients, and 54 healthy eyes from 32 control subjects after propensity scores matching. All of the subjects were given pupil light and dark adaptation examination and optical coherence tomography angiography (OCTA). Scotopic pupil diameter (SPD), pupil contraction amplitude, and velocity of pupil contraction of the diabetic group were significantly lower than that of the healthy control group (P < 0.05).Choroidal thickness at temporal quadrant (at 750 μm) and superior quadrant (at 1500 μm and 2250 μm) increased in diabetic group compared to control group(P < 0.05).In the diabetic group, choriocapillaris blood flow signal density (CCBFSD) in the macular area (diameter = 2000 μm) were significantly decreased compared with the healthy control group (P < 0.05). Apparent changes in pupil and choroidal blood flow were observed in the diabetic patients.
Metallic conduction through van der Waals interfaces in ultrathin $$\hbox{Bi}_2\hbox{Te}_3$$ films
Authors: Hatta Shinichiro , Obayashi Ko , Okuyama Hiroshi , Aruga Tetsuya 
Published: March 2021

AbstractWhile the van der Waals (vdW) interface in layered materials hinders the transport of charge carriers in the vertical direction, it serves a good horizontal conduction path. We have investigated electrical conduction of few quintuple-layer (QL) $$\hbox {Bi}_2\hbox {Te}_3$$

Bi
2

Te
3

films by in situ four-point probe conductivity measurement. The impact of the vdW (Te–Te) interface appeared as a large conductivity increase with increasing thickness from 1 to 2 QL. Angle-resolved photoelectron spectroscopy and first-principles calculations reveal the confinement of bulk-like conduction band (CB) state into the vdW interface. Our analysis based on the Boltzmann equation showed that the conduction of the CB has a long mean free path compared to the surface-state conduction. This is mainly attributed to the spatial separation of the CB electrons and the donor defects located at the Bi sites.
A new bioinformatics approach identifies overexpression of GRB2 as a poor prognostic biomarker for prostate cancer
Authors: Iwata Teppei , Sedukhina Anna S. , Kubota Manabu , Oonuma Shigeko , Maeda Ichiro , Yoshiike Miki , Usuba Wataru , Minagawa Kimino , Hames Eleina , Meguro Rei , Cho Sunny , Chien Stephen H. H. , Urabe Shiro , Pae Sookhee , Palanisamy Kishore , Kumai Toshio , Yudo Kazuo , Kikuchi Eiji , Sato Ko 
Published: March 2021

AbstractA subset of prostate cancer displays a poor clinical outcome. Therefore, identifying this poor prognostic subset within clinically aggressive groups (defined as a Gleason score (GS) ≧8) and developing effective treatments are essential if we are to improve prostate cancer survival. Here, we performed a bioinformatics analysis of a TCGA dataset (GS ≧8) to identify pathways upregulated in a prostate cancer cohort with short survival. When conducting bioinformatics analyses, the definition of factors such as “overexpression” and “shorter survival” is vital, as poor definition may lead to mis-estimations. To eliminate this possibility, we defined an expression cutoff value using an algorithm calculated by a Cox regression model, and the hazard ratio for each gene was set so as to identify genes whose expression levels were associated with shorter survival. Next, genes associated with shorter survival were entered into pathway analysis to identify pathways that were altered in a shorter survival cohort. We identified pathways involving upregulation of GRB2. Overexpression of GRB2 was linked to shorter survival in the TCGA dataset, a finding validated by histological examination of biopsy samples taken from the patients for diagnostic purposes. Thus, GRB2 is a novel biomarker that predicts shorter survival of patients with aggressive prostate cancer (GS ≧8).
First description of a widespread Mytilus trossulus-derived bivalve transmissible cancer lineage in M. trossulus itself
Authors: Skazina Maria , Odintsova Nelly , Maiorova Maria , Ivanova Angelina , Väinölä Risto , Strelkov Petr 
Published: March 2021

AbstractTwo lineages of bivalve transmissible neoplasia (BTN), BTN1 and BTN2, are known in blue mussels Mytilus. Both lineages derive from the Pacific mussel M. trossulus and are identified primarily by their unique genotypes of the nuclear gene EF1α. BTN1 is found in populations of M. trossulus from the Northeast Pacific, while BTN2 has been detected in populations of other Mytilus species worldwide but not in M. trossulus itself. Here we examined M. trossulus from the Sea of Japan (Northwest Pacific) for the presence of BTN. Using hemocytology and flow cytometry of the hemolymph, we confirmed the presence of disseminated neoplasia in our specimens. Cancerous mussels possessed the BTN2 EF1α genotype and two mitochondrial haplotypes with different recombinant control regions, similar to that of common BTN2 lineages. This is the first report of BTN2 in its original host species M. trossulus. A comparison of all available BTN and M. trossulus COI sequences suggests a common and recent origin of BTN2 diversity in populations of M. trossulus outside the Northeast Pacific, possibly in the Northwest Pacific.