bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prion neurotoxicity
Authors: Le Nhat T. T. , Wu Bei , Harris David A. 
Published: December 2018

AbstractAlthough the mechanisms underlying prion propagation and infectivity are now well established, the processes accounting for prion toxicity and pathogenesis have remained mysterious. These processes are of enormous clinical relevance as they hold the key to identification of new molecular targets for therapeutic intervention. In this review, we will discuss two broad areas of investigation relevant to understanding prion neurotoxicity. The first is the use of in vitro experimental systems that model key events in prion pathogenesis. In this context, we will describe a hippocampal neuronal culture system we developed that reproduces the earliest pathological alterations in synaptic morphology and function in response to PrPSc. This system has allowed us to define a core synaptotoxic signaling pathway involving the activation of NMDA and AMPA receptors, stimulation of p38 MAPK phosphorylation and collapse of the actin cytoskeleton in dendritic spines. The second area concerns a striking and unexpected phenomenon in which certain structural manipulations of the PrPC molecule itself, including introduction of N‐terminal deletion mutations or binding of antibodies to C‐terminal epitopes, unleash powerful toxic effects in cultured cells and transgenic mice. We will describe our studies of this phenomenon, which led to the recognition that it is related to the induction of large, abnormal ionic currents by the structurally altered PrP molecules. Our results suggest a model in which the flexible N‐terminal domain of PrPC serves as a toxic effector which is regulated by intramolecular interactions with the globular C‐terminal domain. Taken together, these two areas of study have provided important clues to underlying cellular and molecular mechanisms of prion neurotoxicity. Nevertheless, much remains to be done on this next frontier of prion science.
Platforms of in vivo genome editing with inducible Cas9 for advanced cancer modeling
Authors: Jo Norihide , Sogabe Yuko , Yamada Yosuke , Ukai Tomoyo , Kagawa Harunobu , Mitsunaga Kanae , Woltjen Knut , Yamada Yasuhiro 
Published: December 2018

The emergence of clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology has dramatically advanced how we manipulate the genome. Regarding in vivo experiments, Cas9‐transgenic animals could provide efficient and complex genome editing. However, this potential has not been fully realized partly due to a lack of convenient platforms and limited examples of successful disease modeling. Here, we devised two doxycycline (Dox)‐inducible Cas9 platforms that efficiently enable conditional genome editing at multiple loci in vitro and in vivo. In these platforms, we took advantage of a site‐specific multi‐segment cloning strategy for rapid and easy integration of multiple single guide (sg)RNAs. We found that a platform containing rtTA at the Rosa26 locus and TRE‐Cas9 together with multiple sgRNAs at the Col1a1 locus showed higher efficiency of inducible insertions and deletions (indels) with minimal leaky editing. Using this platform, we succeeded to model Wilms’ tumor and the progression of intestinal adenomas with multiple mutations including an activating mutation with a large genomic deletion. Collectively, the established platform should make complicated disease modeling in the mouse easily attainable, extending the range of in vivo experiments in various biological fields including cancer research.
Digital ITEMS Module 03: Nonparametric Item Response Theory
Authors: Wind Stefanie A. 
Published: December 2018

AbstractIn this digital ITEMS module, we introduce the framework of nonparametric item response theory (IRT), in particular Mokken scaling, which can be used to evaluate fundamental measurement properties with less strict assumptions than parametric IRT models. We walk through the key distinction between parametric and nonparametric models, introduce the two key nonparametric models under Mokken scaling – the monotone homogeneity and double monotonicity model – and discuss modern extensions of the basic models. We also describe how researchers and practitioners can use key nonparametric statistics and graphical visualization tools to evaluate the fundamental measurement properties of an assessment from a nonparametric perspective. Finally, we illustrate the key reasoning steps and associated best practices using video‐based worked examples completed with the mokken package in R.
Tree rings provide no evidence of a CO2 fertilization effect in old‐growth subalpine forests of western Canada
Authors: Hararuk Oleksandra , Campbell Elizabeth M. , Antos Joseph A. , Parish Roberta 
Published: December 2018

AbstractAtmospheric CO2 concentrations are now 1.7 times higher than the preindustrial values. Although photosynthetic rates are hypothesized to increase in response to rising atmospheric CO2 concentrations, results from in situ experiments are inconsistent in supporting a CO2 fertilization effect of tree growth. Tree‐ring data provide a historical record of tree‐level productivity that can be used to evaluate long‐term responses of tree growth. We use tree‐ring data from old‐growth, subalpine forests of western Canada that have not had a stand‐replacing disturbance for hundreds of years to determine if growth has increased over 19th and 20th centuries. Our sample consisted of 5,858 trees belonging to five species distributed over two sites in the coastal zone and two in the continental climate of the interior. We calculated annual increments in tree basal area, adjusted these increments for tree size and age, and tested whether there was a detectable temporal trend in tree growth over the 19th and 20th centuries. We found a similar pattern in 20th century growth trends among all species at all sites. Growth during the 19th century was mostly stable or increasing, with the exception of one of the coastal sites, where tree growth was slightly decreasing; whereas growth during the 20th century consistently decreased. The unexpected decrease in growth during the 20th century indicates that there was no CO2 fertilization effect on photosynthesis. We compared the growth trends from our four sites to the trends simulated by seven Earth System Models, and saw that most of the models did not predict these growth declines. Overall, our results indicate that these old‐growth forests are unlikely to increase their carbon storage capacity in response to rising atmospheric CO2, and thus are unlikely to contribute substantially to offsetting future carbon emissions.
Habitation environment suitability and population density patterns in China: A regionalization approach
Authors: Liu Cuiling , Wang Fahui , Xu Yaping 
Published: December 2018

AbstractThe stunning disparity in population density between the southeast and northwest in China is highlighted by the “Hu Line,” a famous population demarcation line proposed by Huanyong Hu in 1935. This research seeks to uncover the underlying physical environment factors that shape such a contrast. Specifically, we propose a habitation environment suitability index (HESI) model to integrate topographic factors, climatic suitability, and hydrological condition into one comprehensive index, and then use a GIS‐automated regionalization method termed REDCAP (Regionalization with Dynamically Constrained Agglomerative Clustering and Partitioning) to derive two demarcation lines based on the HESI and population density values, respectively. The two lines that divide China into two regions are largely consistent with each other. The result indicates that the population distribution disparity between the southeast and northwest is largely attributable to the difference in physical environments, and the barrier defined by the Hu Line is here to stay. In addition, the research also explores the (in)consistency between population density and HESI distribution patterns in various regions.
Inactivation mechanisms of electron beam irradiation on Listeria innocua through the integrity of cell membrane, genomic DNA and protein structures
Authors: Shi Feifei , Zhao Hongwei , Wang Li , Cui Xiaorui , Guo Weiling , Zhang Weidong , Song Hongbo , Li Shurong 
Published: December 2018

SummaryAs a non‐thermal sterilisation technology, electron beam irradiation (EBI) has attracted great interest for microbial inactivation in food preservation. This study aims to investigate the effects of EBI on membrane permeability, physiological status, morphological structure, genome integrity and protein structures of Listeria innocua irradiated at doses of 0.75, 1.50, 2.25, 3.00, 3.75 and 5.00 kGy. The results showed that EBI noticeably reduced the total microbial counts of L. innocua by more than 7 log CFU mL−1 with 5.00 kGy treatment. The cell membrane permeability increased, resulting in the leakage of intracellular substances and changes in cell physiological status, which was proven by the cell staining and electron microscopy (EM) observations. Moreover, the integrity of genomic DNA and protein secondary structure, but not the protein primary structure were also disrupted. These findings provide the intrinsic mechanisms for the inactivation of L. innocua affected by EBI, which could serve as a theoretical basis for a better application of EBI in food sterilisation.
Risk‐adjusted proposal for >60 months follow up after surgical treatment of organ‐confined renal cell carcinoma according to life expectancy
Authors: Frees Sebastian K , Kamal Mohammed M , Nestler Sebastian , Levien Patrick MF , Bidnur Samir , Brenner Walburgis , Thomas Christian , Jaeger Wolfgang , Thüroff Joachim W , Roos Frederik C 
Published: December 2018

ObjectivesTo determine the long‐term oncological outcome of organ‐confined (<pT3) renal cell carcinoma.MethodsWe identified 889 patients with complete long‐term follow‐up data, who had been surgically treated for renal cell carcinoma (<T3) at our institution between 1976 and 2009. Kaplan–Meier analysis was used to assess the incidence and time interval of recurrence defined as local recurrences or metastases. We further compared patients who had tumor progression before or after 60 months.ResultsAfter a median follow‐up period of 74.33 months (range 3–329 months), 44 patients (4.9%) had disease recurrence. A total of 38.6% of the recurrences occurred after 60 months; 76.2% of patients had distant metastases and 23.8% of patients had local recurrences. In patients with low‐grade (G1) and low‐stage (pT1a) tumors, there was a trend to develop recurrence or metastases after longer intervals. Patients with lung metastasis and patients with multiple metastatic locations developed these metastases earlier than patients with bone metastasis. The risk of dying of other causes correlated with age, but the time interval to metastases did not.ConclusionsCurrent guidelines recommend a follow‐up period of 60 months after surgical treatment of organ‐confined renal cell carcinoma. Our data shows that one‐third of recurrences of <pT3 renal cell carcinoma occur after 60 months. According to our oncological analysis, we suggest an age‐adjusted strategy of follow‐up balancing the risk of tumor recurrence and the life expectancy of the patient.
Clinical performance of one‐piece zirconia dental implants: A systematic review
Authors: ArRejaie Aws S. , Al‐Hamdan Rana S. , Basunbul Ghadeer I. , Abduljabbar Tariq , Al‐Aali Khulud A. , Labban Nawaf 
Published: December 2018

AbstractThe aim of the present review was to evaluate the clinical and radiographic performance of one‐piece zirconia implants (O‐PZI). This review followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta‐Analysis) guidelines that addressed the following focused question: What is the overall clinical and radiographic performance of O‐PZI? The MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Oral Health Group Trials Register databases were searched. Six clinical studies were included. For studies evaluating O‐PZI compared with one‐piece titanium implants, zirconia implants showed higher crestal bone loss (CBL) in both the studies. However, one study demonstrated a high failure rate compared to titanium dental implants, while one study demonstrated comparable survival rates between zirconia and titanium dental implants. For studies evaluating O‐PZI for the restoration of single crown and fixed dental prostheses, O‐PZI showed comparable bone loss and survival rates for single crowns and fixed dental prostheses. Two studies were included that compared O‐PZI with two‐piece zirconia (T‐PZI). One study showed a higher CBL and low survival rate for O‐PZI compared to T‐PZI, whereas the other study demonstrated comparable CBL and survival rates between O‐PZI and T‐PZI. It is still debatable whether O‐PZI demonstrate better clinical performance when compared with titanium implants or two‐piece design.
Mechanical regulation of oligodendrocyte morphology and maturation by the mechanosensor p130Cas
Authors: Shimizu Takeshi , Osanai Yasuyuki , Tanaka Kenji F. , Thai Truc Quynh , Abe Manabu , Natsume Rie , Sakimura Kenji , Ikenaka Kazuhiro 
Published: December 2018

AbstractOligodendrocytes (OLs) are myelinating cells of the central nervous system. Recent studies have shown that mechanical factors influence various cell properties. Mechanical stimulation can be transduced into intracellular biochemical signals through mechanosensors, such as integrin, p130Cas, talin and vinculin. However, the molecular mechanisms underlying the mechanical regulation of OLs by mechanosensors remain largely unknown. We found that morphology of OL was affected by knockdown of the mechanosensors p130Cas or talin1. Stretching of OL precursor cells induced the phosphorylation of p130Cas and talin‐associated assembly of vinculin. Shear stress decreased the number of OL processes, whereas these effects were mechanically suppressed by dominant‐negative (DN) p130Cas, but not by DN‐talin1. To investigate the roles of p130Cas in post‐natal OLs in vivo, we constructed a novel p130Cas knock‐in mouse and found overexpression of p130Cas in vivo affected the number of mature OLs in the cortex. These results indicate that the mechanosensor p130Cas controls both OL morphogenesis and maturation.
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Exploring bowel dysfunction of patients following colorectal surgery: A cohort study
Authors: Tan Shu‐Hwa , Liao Yuan‐Mei , Lee Kwo‐Chen , Ko Yi‐Li , Lin Pi‐Chu 
Published: December 2018

AbstractAims and objectivesTo examine changes in patients’ bowel function and to compare patients’ outcome among different operation and treatment after rectal resection.BackgroundAnal‐preserving surgery is the trend of treatment of colorectal cancer and bowel function after surgery needs to be concerned.DesignProspective cohort study.MethodsA total of 38 patients with convenience sampling were recruited from a teaching hospital. The low anterior resection syndrome (LARS) score was used to assess bowel function disturbances before discharge and at 1 week, 1 month and 3 months after discharge. We followed the STROBE checklist to ensure rigour in our study.ResultsApproximately half of the patients experienced major LARS, including daily stool frequency of more than seven times and stool clustering at least once a week. The LARS scores observed at 1 month after discharge were significantly higher than those observed before discharge. Patients who received intersphincteric resection had higher LARS scores compared with those who received other surgeries. Furthermore, patients who underwent concurrent chemoradiotherapy, operation (OP) and chemotherapy had the highest LARS scores compared with those who underwent only an OP.ConclusionThe patients experienced varied intestinal dysfunction after surgery based on their treatment plan and surgical method. Nurses should provide individualised health education for these patients.Relevance to clinical practiceA health education booklet is recommended to educate patients about LARS symptoms and the techniques to adapt in their daily lives after surgery.
Efficacy of Megasphaera elsdenii inoculation in subacute ruminal acidosis in cattle
Authors: Arik Huzur Derya , Gulsen Nurettin , Hayirli Armagan , Alatas Mustafa Selcuk 
Published: December 2018

AbstractTwo consecutive experiments were carried out to determine efficacy of Megasphaera elsdenii inoculation in alleviation of subacute ruminal acidosis (SARA). In the first experiment, SARA was induced by feeding corn‐ and wheat‐based diets (20%, 40%, 60% and 80% of TMR, DM basis) in six ruminally cannulated heifers. Continuous pH was obtained using data loggers embedded in rumen. In corn (80%)‐ and wheat (60%)‐based diets ruminal pH ranged from 5.2 to 5.6 for 7.77 and 5.93 hr. In the second experiment (5 day), M. elsdenii (200 ml; 2.4 x 1010 cfu/ml) was inoculated during the first two days. During the SARA induction period, M. elsdenii and S. bovis in rumen liquor were more abundant in wheat‐based feeding (7.97 and 8.77) than in corn‐based feeding (7.06 and 7.95 per ml, log basis; p < 0.0001 for both). M. elsdenii inoculation increased total volatile fatty acids (VFA) concentration when corn‐based diet was fed, whereas it decreased total VFA concentration when wheat‐based diet was fed (p < 0.004). There was a decrease in the propionic acid proportion (24.04%–19.08%; p < 0.002), whereas no alteration in lactate and ammonia concentrations was observed. M. elsdenii inoculation increased protozoa count (from 5.39 to 5.55 per ml, log basis; p < 0.009) and decreased S. bovis count (from 9.18 to 7.95 per ml, log basis; p < 0.0001). The results suggest that M. elsdenii inoculation may help prevent SARA depending on dietary grain through altering rumen flora as reflected by a decrease in S. bovis count and an increase in protozoa count.
The use of diffusion tractography to characterize a corpus callosum malformation in a dog
Authors: Johnson Philippa J. , Barry Erica F. , Luh Wen‐Ming , Davies Emma 
Published: December 2018

IntroductionThe pathogenesis of corpus callosum malformations (CCM) is not well defined in the dog because of inherent limitations of structural magnetic resonance imaging (MRI) to evaluate the white matter. We used the advanced neuroimaging technique of tractography to virtually dissect the white matter projections in a dog with a CCM and in a normal control dog.MethodsA 9‐month‐old male Coonhound that had a previous structural MRI diagnosis of CCM and a normal control dog underwent anesthesia and 3‐Tesla MRI. Diffusion‐tensor imaging and 3D T1‐weighted and 2D T2‐weighted sequences were acquired. Diffusion data were processed before tensor reconstruction and fiber tracking. Virtual dissections were performed to dissect out the major white matter projections in each dog.ResultsIn the dog with CCM, the corpus callosum exhibited interhemispheric crossing fibers at the level of the splenium and formed longitudinal callosal fasciculi (Probst bundles). In addition, the fornix was small and the cingula enlarged and exhibited increased dorsal connectivity relative to the normal control.Conclusions and Clinical ImportanceWe used tractography to describe a white matter malformation in a dog. The results suggest that, embryologically, formed axons fail to cross midline and instead create Probst bundles.
Liver disease related to alpha1‐antitrypsin deficiency in French children: The DEFI‐ALPHA cohort
Authors: Ruiz Mathias , Lacaille Florence , Berthiller Julien , Joly Philippe , Dumortier Jérôme , Aumar Madeleine , Bridoux‐Henno Laure , Jacquemin Emmanuel , Lamireau Thierry , Broué Pierre , Rivet Christine , Belmalih Abdelouahed , Restier Lioara , Chapuis‐Cellier Colette , Bouchecareilh Marion , Lachaux Alain ,   Groupe Francophone d’Hépatologie Gastroentérologie et Nutrition Pédiatriques
Published: December 2018

AbstractBackground & AimsTo identify prognostic factors for liver disease in children with alpha‐1 antitrypsin deficiency, irrespective of phenotype, using the DEFI‐ALPHA cohort.MethodsRetrospective, then prospective from 2010, multicentre study including children known to have alpha‐1 antitrypsin blood concentration below 0.8 g/L, born in France since 1989. Clinical and biological data were collected. Liver disease was classified as “severe” (portal hypertension, liver failure, liver transplantation or death); “moderate” (persistent abnormal liver biology without portal hypertension); and “mild/none” (normal or almost normal liver biology and native liver). Prognostic factors for severe liver disease were evaluated using a Cox semiparametric model.ResultsIn January 2017, 153 patients from 19 centres had been included; genotypes were PIZZ in 81.9%, PISZ in 8.1%, other in 10.0%. Mean ± SD follow‐up was 4.7 ± 2.1 years. Half of patients had moderate liver disease. Twenty‐eight children (18.3%) had severe liver disease (mean age 2.5 years, range: 0‐11.6): diagnosis of alpha‐1 antitrypsin deficiency was made before two months of age in 65.4%, genotypes were PIZZ in 25 (89.3%), PISZ in 2, PIMlikeZ in 1, 15 children underwent liver transplantation, 1 child died at 3 years of age. Neonatal cholestasis was significantly associated with severe liver disease (P = 0.007).ConclusionAlpha‐1 antitrypsin‐deficient patients presenting with neonatal cholestasis were likely to develop severe liver disease. Some patients with non‐homozygous ZZ genotype can develop severe liver disease, such as PISZ and M variants, when associated with predisposing factors. Further genetic studies will help to identify other factors involved in the development of liver complications.
Anaphylaxis admissions in pediatric intensive care units: Follow‐up and risk of recurrence
Authors: Pouessel Guillaume , Cerbelle Valentine , Lejeune Stephanie , Leteurtre Stephane , Ramdane Nassima , Deschildre Antoine ,   the French Group for Pediatric Intensive Care Emergencies (GFRUP)
Published: December 2018

AbstractBackgroundData about the risk of anaphylaxis recurrence in children are lacking. We assessed anaphylaxis recurrence and medical follow‐up in a cohort of children previously hospitalized in a French pediatric intensive care unit (PICU) for anaphylaxis.MethodsWe conducted a telephone survey of 166 children (≤18 years) hospitalized from 2003 to 2013.ResultsIn all, 106 (64%) completed the survey (boys, 59%; mean age [SD]: 15.3 years [5.5]). The main index triggers were drugs (45%) and foods (37%). The mean duration follow‐up was of 7.7 years (SD: 2.4). Thirty‐eight (36%) children experienced 399 new allergic reactions during a follow‐up period of 282 patient‐years (incidence rate: 1.4/100 patients/y; 95% CI: 0.64‐2.04). Twelve children experienced 19 anaphylaxis reactions including five requiring PICU admission (anaphylaxis recurrence rate: 0.20/100 patients/y; 95% CI non‐calculable). Food was the trigger for 79% of recurrent reactions and drugs for 8%. The food trigger was previously known in 83%, the same as the index trigger in 69%. Overall, 1.5% of the recurrent reactions were treated with adrenaline injection and 8% an emergency hospital admission. Patients with recurrence had more likely a history of food allergy (P < 10−4), asthma (P < 0.005), atopic dermatitis (P < 0.05) than those without. 31% of the 50 children with food allergy did not see an allergist, 23% had no adrenaline auto‐injector, and 26% lacked a school individual healthcare plan.ConclusionsFollowing a PICU admission for anaphylaxis, recurrence is high in children with food allergy compared with drug allergy. Allergic comorbidities increase the risk. Medical follow‐up has to be improved for these at‐risk children.