bluuebunny/crossref_metadata_2025_split huggingface dataset:
High intracellular stability of the spidroin N‐terminal domain in spite of abundant amyloidogenic segments revealed by in‐cell hydrogen/deuterium exchange mass spectrometry
Authors: Kaldmäe Margit , Leppert Axel , Chen Gefei , Sarr Medoune , Sahin Cagla , Nordling Kerstin , Kronqvist Nina , Gonzalvo‐Ulla Marta , Fritz Nicolas , Abelein Axel , Laίn Sonia , Biverstål Henrik , Jörnvall Hans , Lane David P. , Rising Anna , Johansson Jan , Landreh Michael 
Published: December 2019

Proteins require an optimal balance of conformational flexibility and stability in their native environment to ensure their biological functions. A striking example is spidroins, spider silk proteins, which are stored at extremely high concentrations in soluble form, yet undergo amyloid‐like aggregation during spinning. Here, we elucidate the stability of the highly soluble N‐terminal domain (NT) of major ampullate spidroin 1 in the Escherichia coli cytosol as well as in inclusion bodies containing fibrillar aggregates. Surprisingly, we find that NT, despite being largely composed of amyloidogenic sequences, showed no signs of concentration‐dependent aggregation. Using a novel intracellular hydrogen/deuterium exchange mass spectrometry (HDX‐MS) approach, we reveal that NT adopts a tight fold in the E. coli cytosol and in this manner conceals its aggregation‐prone regions by maintaining a tight fold under crowded conditions. Fusion of NT to the unstructured amyloid‐forming Aβ40 peptide, on the other hand, results in the formation of fibrillar aggregates. However, HDX‐MS indicates that the NT domain is only partially incorporated into these aggregates in vivo. We conclude that NT is able to control its aggregation to remain functional under the extreme conditions in the spider silk gland.
Capturing hedge fund risk factor exposures: Hedge fund return replication with ETFs
Authors: Duanmu Jun , Li Yongjia , Malakhov Alexey 
Published: December 2019

AbstractWe develop a new factor selection methodology of spanning the space of hedge fund risk factors with all available exchange traded funds (ETFs). We demonstrate the efficacy of the methodology with out‐of‐sample individual hedge fund return replication by ETF clone portfolios. This is consistent with our interpretation of ETF returns as proxies to risk factors driving hedge fund returns. We further consider portfolios of “cloneable” and “noncloneable” hedge funds, defined as top and bottom in‐sampleR2matches, and demonstrate that our ETF clone portfolios slightly outperform cloneable hedge funds out of sample.
A two‐year comparison on nutritive value and yield of eight lucerne cultivars and one red clover cultivar
Authors: Sousa Dannylo O. , Hansen Hanne H. , Hallin Ola , Nussio Luiz G. , Nadeau Elisabet 
Published: December 2019

AbstractRed clover (Trifolium pratense) and lucerne (Medicago sativa) are among the most common legume species used for ruminant feeding systems. Besides the greater nutritive quality and first‐year ley yield compared to lucerne, red clover decreases its yield over the years. However, under unfavourable soil conditions the persistency of lucerne can be compromised, not performing as expected. This study compared yield and chemical composition of eight lucerne cultivars and one tetraploid red clover cultivar, with similar growth capacity as lucerne, replicated over two years. In the second year, four lucerne cultivars and the red clover cultivar were analysed for crude protein (CP) fractions, dry matter and neutral detergent fibre (NDF) digestibility. A randomized block design was used with three field blocks per cultivar for the multiple comparisons within each year. There were differences in DM yield, concentrations of CP and NDF and CP fractions among the lucerne cultivars, but the differences were inconsistent between years and between growth cycles within year. The red clover cultivar had lower CP and NDF concentrations than a majority of the lucerne cultivars, and greater in vitro organic matter digestibility compared to all of the lucerne cultivars. Also, the red clover cultivar had greater rumen undegradable‐to‐degradable CP ratio but confirmed its lower yield persistency compared to the lucerne cultivars.
Positive and negative pressure irrigation in oval root canals with apical ramifications: a computational fluid dynamics evaluation in micro‐CT scanned real teeth
Authors: Loroño G. , Zaldivar J. R. , Arias A. , Cisneros R. , Dorado S. , Jimenez‐Octavio J. R. 
Published: December 2019

AbstractAimTo compare using computational fluid dynamics (CFD) the flow pattern, irrigant velocity, apical pressure and shear stress produced by negative (MiC) and positive pressure with different types of needles (side‐vented (SV), front‐vented (FV) and notched (N)) at two insertion depths in the apical ramification of oval root canals.MethodologyThe micro‐CT of a mandibular molar with an oval root canal with an apical ramification was used for computational analysis after preparation and geometric reconstruction. Geometries with the needles in two positions (1 and 3 mm from WL) were created to run the simulations. Key parameters of irrigation were displayed with CFD and compared.ResultsThe penetration depth of the needle in the root canal strongly influenced shear stress and apical pressure. The three needles revealed that the highest shear stress, velocity and apical pressure were 1 mm from the WL and generated medium velocities. In N simulations, the fluid flow did not reach the apical ramification and the lowest shear stress values for positive pressure needles were found. The predominant axial component for FV revealed a different pattern of irrigation with high shear stress values and higher apical pressures than those exerted by other needles. SV simulations had generalized fluid flow in most of the main canal, the highest shear stress values and lower apical pressure than the threshold determined for risk of extrusion. MiC was associated with low velocity, shear stress and apical pressure.ConclusionThe SV needle demonstrated a combination of low positive pressure and high shear stress; while N had the lowest shear stress and FV the highest apical pressure. MiC generated fluid flow in part of the apical ramification with negative apical pressure values but low shear stress and velocity.
Highly precise risk prediction model for new‐onset hypertension using artificial intelligence techniques
Authors: Kanegae Hiroshi , Suzuki Kenji , Fukatani Kyohei , Ito Tetsuya , Harada Nakahiro , Kario Kazuomi 
Published: December 2019

AbstractHypertension is a significant public health issue. The ability to predict the risk of developing hypertension could contribute to disease prevention strategies. This study used machine learning techniques to develop and validate a new risk prediction model for new‐onset hypertension. In Japan, Industrial Safety and Health Law requires employers to provide annual health checkups to their employees. We used 2005‐2016 health checkup data from 18 258 individuals, at the time of hypertension diagnosis [Year (0)] and in the two previous annual visits [Year (−1) and Year (−2)]. Data were entered into models based on machine learning methods (XGBoost and ensemble) or traditional statistical methods (logistic regression). Data were randomly split into a derivation set (75%, n = 13 694) used for model construction and development, and a validation set (25%, n = 4564) used to test performance of the derived models. The best predictor in the XGBoost model was systolic blood pressure during cardio‐ankle vascular index measurement at Year (−1). Area under the receiver operator characteristic curve values in the validation cohort were 0.877, 0.881, and 0.859 for the XGBoost, ensemble, and logistic regression models, respectively. We have developed a highly precise prediction model for future hypertension using machine learning methods in a general normotensive population. This could be used to identify at‐risk individuals and facilitate earlier non‐pharmacological intervention to prevent the future development of hypertension.
Effect of c‐Ski on atrial remodelling in a rapid atrial pacing canine model
Authors: Wang Juan , Han Min , Han Su‐xia , Zhi Cuiju , Gao Suli , Li Yao 
Published: December 2019

AbstractAtrial fibrosis is an important factor in the initiation and maintenance of atrial fibrillation (AF); therefore, understanding the pathogenesis of atrial fibrosis may reveal promising therapeutic targets for AF. In this study, we successfully established a rapid atrial pacing canine model and found that the inducibility and duration of AF were significantly reduced by the overexpression of c‐Ski, suggesting that this approach may have therapeutic effects. c‐Ski was found to be down‐regulated in the atrial tissues of the rapid atrial pacing canine model. We artificially up‐regulated c‐Ski expression with a c‐Ski–overexpressing adenovirus. Haematoxylin and eosin, Masson's trichrome and picrosirius red staining showed that c‐Ski overexpression alleviated atrial fibrosis. Furthermore, we found that the expression levels of collagen III and α‐SMA were higher in the groups of dogs subjected to right‐atrial pacing, and this increase was attenuated by c‐Ski overexpression. In addition, c‐Ski overexpression decreased the phosphorylation of smad2, smad3 and p38 MAPK (p38α and p38β) as well as the expression of TGF‐β1 in atrial tissues, as shown by a comparison of the right‐atrial pacing + c‐Ski‐overexpression group to the control group with right‐atrial pacing only. These results suggest that c‐Ski overexpression improves atrial remodelling in a rapid atrial pacing canine model by suppressing TGF‐β1–Smad signalling and p38 MAPK activation.
Colposcopic scoring indexes in the evaluation of cervical lesions with the cytological result of atypical squamous cells, cannot exclude high‐grade lesion
Authors: Kudela Erik , Laucekova Zuzana , Nachajova Marcela , Visnovsky Jozef , Bielik Tibor , Krivus Stefan , Biringer Kamil , Balharek Tomas , Zubor Pavol 
Published: December 2019

AbstractAimColposcopic indexes including Reid index and Swede score were developed to make the colposcopy more objective. The aim of our study was to evaluate the significance of colposcopic indexes in the evaluation of ASC‐H cervical lesions.MethodsWe carried out a cross‐sectional study in the Clinic of Obstetrics and Gynecology between January 2013 and December 2018. The study included 535 women, from which 66 women had a cytological result ASC‐H. Scoring of all colposcopic findings was assessed according to Reid modified index and Swede score and a composite score was determined. Frequency distributions were compared using χ2/Fisher exact test. Spearman rank correlation coefficient was computed between RCI and Swede score.ResultsSensitivity, specificity, positive and negative predictive value and positive likelihood ratio of modified Reid colposcopic index at a cutoff of ≥4 for the detection of HSIL+ lesions were: 86.11% (95% CI: 70.5–95.3), 83.33% (95% CI: 65.3–94.4), 86.11% (95% CI: 69.7–94.8), 83.33% (95% CI: 64.5–93.7) and 5.17 (95% CI: 2.3–11.6). Swede score with the cutoff value ≥5 showed comparable results to modified Reid index with the increased sensitivity: 94.44% (95% CI: 81.3–99.3).ConclusionASC‐H category represents the trickiest cytological diagnosis as it is underlined with the high risk of severe cervical dysplasia. Evaluating the cervical lesion by the use of colposcopic indices helps the gynecologist to objectively evaluate all the pathologies of uterine cervix. Swede score with the cutoff value 8 also enables a ‘see and treat’ option in management of atypical squamous cells, cannot exclude high‐grade lesions.
Combination methotrexate and gefitinib: A potential medical treatment for inoperable nontubal ectopic pregnancy
Authors: Italiano Stella , Tong Stephen , Readman Emma , Tassone Meredith , Hastie Roxanne , Pritchard Natasha 
Published: December 2019

AbstractNontubal ectopic pregnancies present as a therapeutic challenge. A 35‐year‐old primigravida at 7 weeks gestation had a live interstitial ectopic pregnancy and contraindications to surgery. The patient was treated with a multidose methotrexate regimen combined with oral gefitinib (250 mg daily for 7 days). The peak human chorionic gonadotropin (hCG) of the patient was recorded at 19 510 IU/L and began declining from day 4 of combination therapy (day 6 of initial treatment). Successful resolution of the ectopic was demonstrated by cessation of the fetal heart by day 15 and hCG falling to 23 IU/L by day 42. A 10‐year review of all nontubal ectopic pregnancies treated with methotrexate identified 46 cases, which had a comparable time to resolution to combination therapy. However, for cases where cardiac activity was present, the median time to resolution following methotrexate treatment was 64 days (47–87 days), 22 days longer than combination therapy. Combination therapy may provide a safe medical treatment for inoperable nontubal ectopic pregnancy.
Adolescents' Weight Management Goals: Healthy and Unhealthy Associations with Eating Habits and Physical Activity
Authors: Durocher Elyse , Gauvin Lise 
Published: December 2019

ABSTRACTBACKGROUNDThis study aims to quantify associations between one's weight management goal and eating behaviors and physical activity among teenagers.METHODSWeighted logistic regressions were performed predicting healthy behaviors from weight goal separately for boys and girls while controlling for age, body mass index, socioeconomic indicators, school type, and region using data from the 2010 to 2011 Enquête québécoise sur la santé des jeunes du secondaire, a survey of a representative sample of Quebec adolescents (N = 32,040).RESULTSAbout 18%, 31%, 19%, and 34% of boys and 32%, 34%, 5%, and 25% of girls were respectively trying to lose weight, maintain their weight, gain weight, and not trying to do anything about their weight. Trying to lose weight was associated with lower likelihood of eating breakfast daily (boys: odds ratio [OR] = 0.72; 95% confidence interval [CI] = 0.61, 0.84 girls: OR = 0.61; 95% CI = 0.54, 0.70). Among girls, trying to lose weight was also associated with higher likelihood of consuming at least 5 portions of fruits and vegetables (OR = 1.20; 95% CI = 1.04, 1.37), lower likelihood of drinking sugar‐sweetened beverages daily (OR = 0.77; 95% CI = 0.66, 0.90). Each weight‐related goal was associated with unhealthy behaviors but most of them were also associated with adoption of healthier ones.CONCLUSIONHaving a weight related goal cannot inherently be thought of as health promoting goal.
Content and Quality of Motor Initiatives in the Support of People With Profound Intellectual and Multiple Disabilities
Authors: van Alphen Helena J. M. , Waninge Aly , Minnaert Alexander E. M. G. , van der Putten Annette A. J. 
Published: December 2019

AbstractMotor activation is rarely integrated into the support of people with profound intellectual and multiple disabilities (PIMD), which might be the result of the limited evidence‐based knowledge in this field. Practitioners have recently been developing several motor initiatives for people with PIMD, but it remains unclear about what core elements the motor initiatives actually consist of and to what level of quality it is implemented in practice. This study aims to offer an overview and analysis of the content and quality of motor initiatives actually in use for people with PIMD. Motor initiatives were explored by asking practitioners to complete an online inventory form. Documents, expert knowledge, and observations were used to collect data about the characteristics of the motor initiatives. The quality of the motor initiatives which met our eligibility criteria, was analyzed on the basis of the level of evidence for their effectiveness. The inventory yielded 118 motor initiatives of which 17 met the eligibility criteria. We identified four motor initiatives reflecting an approach to motorically activate people with PIMD within various activities, three including power‐assisted exercises, three with aquatic exercises, two frameworks which integrated motor activities into their daily programs, two methods which included small‐scale activities, two rhythmic movement therapies, and one program including gross motor activities. We found limited indications for descriptive evidence from 17 initiatives, limited or no indications for theoretical evidence from 12 and five initiatives respectively, and none of the initiatives provided a causal level of evidence for effectiveness. A wide variety of motor initiatives is used in current practice to activate persons with PIMD, although their effectiveness is actually unproven. Science and practice should cooperate to develop an evidence‐based understanding to ensure more evidence‐based support for the motor activation of people with PIMD in the future.
Characterization of gastrointestinal pathologies in the dystonia musculorum mouse model for hereditary sensory and autonomic neuropathy type VI
Authors: Lynch‐Godrei Anisha , De Repentigny Yves , Yaworski Rebecca A. , Gagnon Sabrina , Butcher James , Manoogian Juliana , Stintzi Alain , Kothary Rashmi 
Published: December 2019

AbstractBackgroundDystonia musculorum (Dstdt) is a murine disease caused by recessive mutations in the dystonin (Dst) gene. Loss of dorsal root ganglion (DRG) sensory neurons, ataxia, and dystonic postures before death by postnatal day 18 (P18) is a hallmark feature. Recently we observed gas accumulation and discoloration in the small intestine and cecum in Dstdt mice by P15. The human disease resulting from dystonin loss‐of‐function, known as hereditary sensory and autonomic neuropathy type VI (HSAN‐VI), has also been associated with gastrointestinal (GI) symptoms including chronic diarrhea and abdominal pain. As neuronal dystonin isoforms are expressed in the GI tract, we hypothesized that dystonin loss‐of‐function in Dstdt‐27J enteric nervous system (ENS) neurons resulted in neurodegeneration associated with the GI abnormalities.MethodsWe characterized the nature of the GI abnormalities observed in Dstdt mice through histological analysis of the gut, assessing the ENS for signs of neurodegeneration, evaluation of GI motility and absorption, and by profiling the microbiome.Key resultsThough gut histology, ENS viability, and GI absorption were normal, slowed GI motility, thinning of the colon mucous layer, and reduced microbial richness/evenness were apparent in Dstdt‐27J mice by P15. Parasympathetic GI input showed signs of neurodegeneration, while sympathetic did not.Conclusions & InferencesDstdt‐27J GI defects are not linked to ENS neurodegeneration, but are likely a result of an imbalance in autonomic control over the gut. Further characterization of HSAN‐VI patient GI symptoms is necessary to determine potential treatments targeting symptom relief.
Chinese wheat mosaic virus‐derived vsiRNA‐20 can regulate virus infection in wheat through inhibition of vacuolar‐ (H+)‐PPase induced cell death
Authors: Yang Jian , Zhang Tianye , Li Juan , Wu Ne , Wu Guanwei , Yang Jin , Chen Xuan , He Long , Chen Jianping 
Published: December 2019

Summary

Vacuolar (H+)‐PPases (VPs), are key regulators of active proton (H+) transport across membranes using the energy generated from PPi hydrolysis. The VPs also play vital roles in plant responses to various abiotic stresses. Their functions in plant responses to pathogen infections are unknown.

Here, we show that TaVP, a VP of wheat (Triticum aestivum) is important for wheat resistance to Chinese wheat mosaic virus (CWMV) infection. Furthermore, overexpression of TaVP in plants induces the activity of PPi hydrolysis, leading to plants cell death.

A virus‐derived small interfering RNA (vsiRNA‐20) generated from CWMV RNA1 can regulate the mRNA accumulation of TaVP in wheat. The accumulation of vsiRNA‐20 can suppress cell death induced by TaVP in a dosage‐dependent manner. Moreover, we show that the accumulation of vsiRNA‐20 can affect PPi hydrolysis and the concentration of H+ in CWMV‐infected wheat cells to create a more favorable cellular environment for CWMV replication.

We propose that vsiRNA‐20 regulates TaVP expression to prevent cell death and to maintain a weak alkaline environment in cytoplasm to enhance CWMV infection in wheat. This finding may be used as a novel strategy to minimize virus pathogenicity and to develop new antiviral stratagems.
Roles of RIN and ethylene in tomato fruit ripening and ripening‐associated traits
Authors: Li Shan , Zhu Benzhong , Pirrello Julien , Xu Changjie , Zhang Bo , Bouzayen Mondher , Chen Kunsong , Grierson Donald 
Published: December 2019

Summary

RIPENING INHIBITOR (RIN)‐deficient fruits generated by CRISPR/Cas9 initiated partial ripening at a similar time to wild‐type (WT) fruits but only 10% WT concentrations of carotenoids and ethylene (ET) were synthesized. RIN‐deficient fruit never ripened completely, even when supplied with exogenous ET. The low amount of endogenous ET that they did produce was sufficient to enable ripening initiation and this could be suppressed by the ET perception inhibitor 1‐MCP.
The reduced ET production by RIN‐deficient tomatoes was due to an inability to induce autocatalytic system‐2 ET synthesis, a characteristic feature of climacteric ripening. Production of volatiles and transcripts of key volatile biosynthetic genes also were greatly reduced in the absence of RIN.
By contrast, the initial extent and rates of softening in the absence of RIN were similar to WT fruits, although detailed analysis showed that the expression of some cell wall‐modifying enzymes was delayed and others increased in the absence of RIN.
These results support a model where RIN and ET, via ERFs, are required for full expression of ripening genes. Ethylene initiates ripening of mature green fruit, upregulates RIN expression and other changes, including system‐2 ET production. RIN, ET and other factors are required for completion of the full fruit‐ripening programme.
Pathophysiological connections between gallstone disease, insulin resistance, and obesity
Authors: Cortés Víctor A. , Barrera Francisco , Nervi Flavio 
Published: December 2019

SummaryObesity and cholesterol gallstone disease (GSD) are frequently coexisting diseases; therefore and considering the current worldwide obesity epidemics, a precise understanding of the pathophysiological relationships between GSD and insulin resistance (IR) is important. Classically, obesity has been understood as a risk factor for GSD and the gallbladder (GB) viewed as a simple bile reservoir, with no metabolic roles whatsoever. However, consistent evidence has showed that both GSD and cholecystectomy associates with fatty liver and IR, raising the possibility that the GB is indeed an organ with metabolic regulatory roles. Herein, we review the pathophysiological mechanisms by which GSD, IR, and obesity are interconnected, with emphasis in the actions of the GB as a regulator of bile acids kinetics and a hormone secreting organ, with metabolic actions at the systemic level. We also examine the relationships between increased hepatic lipogenic in IR states and GSD pathogenesis. We propose a model in which GSD and hepatic IR mutually interact to determine a state of dysregulated lipid and energy metabolism that potentiate the metabolic dysregulation of obesity.