bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different effects of Wnt/β‐catenin activation and parathyroid hormone on diaphyseal and metaphyseal in the early phase of femur bone healing of mice
Authors: Liu Daocheng , He Sihao , Chen Sixu , Yang Lei , Yang Jiazhi , Bao Quanwei , Qin Hao , Zhao Yufeng , Zong Zhaowen 
Published: March 2019

SummaryParathyroid hormone (PTH) and agents related to the manipulation of Wnt/β‐catenin signalling are two promising anabolic anti‐osteoporotic therapies that have been shown to promote the healing of bone fractures. Now, it is widely accepted that cortical bone and trabecular bone are two different compartments, and should be treated as separate compartments in pathological processes, such as fracture healing. It is currently unknown whether PTH and the activation of β‐catenin signalling would demonstrate different effects on cortical bone and trabecular bone healing. In the current study, single 0.6‐mm cortex holes were made in the femur metaphysis and diaphysis of mice, and then, PTH application and β‐catenin activation were used to observe the promoting effect on bone healing. The effects of β‐catenin and PTH signalling on fracture healing were observed by X‐ray and CT at 3, 6, and 14 days after fracture, and the levels of β‐catenin were detected by RT‐PCR assay, and the number of specific antigen‐positive cells of BRDU, OCN, RUNX2 was counted by immunohistochemical staining. While β‐catenin activation and PTH were found to demonstrate similar effects on accelerating metaphyseal bone healing, activation of β‐catenin showed a more striking effect than PTH on promoting diaphyseal bone healing. These findings might be helpful for selecting proper medication to accelerate fracture healing of different bone compartments.
Time, expertise and status: barriers faced by mainstream primary school SENCos in the pursuit of providing effective provision for children with SEND
Authors: Smith Mia D. , Broomhead Karen E. 
Published: March 2019

AbstractThe inclusion ‘ideal’ is one which has been both celebrated and maligned. It paved the way for equality; but also, out of its diversity sprang many misconceptions and concerns for children with Special Educational Needs and Disabilities (SEND). It is within this maelstrom of difficulty that the Special Educational Needs Co‐ordinator (SENCo) role is placed, so that those undertaking the position of SENCo face numerous barriers in the pursuit of providing effectively for children with SEND. Semi‐structured interviews were conducted with fifteen SENCos employed at mainstream primary schools within the North West of England. Findings revealed conflict between how SENCos viewed their role and responsibilities, and the expectations that they perceived to be placed on them by parents of children with SEND and mainstream colleagues. This study brings to the fore the complexities of the role of the SENCo, and the continuing demands placed on these practitioners.
CCTV surveillance for crime prevention
Authors: Piza Eric L. , Welsh Brandon C. , Farrington David P. , Thomas Amanda L. 
Published: March 2019

Research SummaryWe report on the findings of an updated systematic review and meta‐analysis of the effects of closed‐circuit television (CCTV) surveillance cameras on crime. The findings show that CCTV is associated with a significant and modest decrease in crime. The largest and most consistent effects of CCTV were observed in car parks. The results of the analysis also demonstrated evidence of significant crime reductions within other settings, particularly residential areas. CCTV schemes incorporating active monitoring generated larger effect sizes than did passive systems. Schemes deploying multiple interventions alongside CCTV generated larger effect sizes than did schemes deploying single or no other interventions alongside CCTV.Policy ImplicationsThe results of this systematic review—based on 40 years of evaluation research—lend support for the continued use of CCTV to prevent crime as well as reveal a greater understanding of some of the key mechanisms of effective use. Of particular salience is the continued need for CCTV to be narrowly targeted on vehicle crimes and property crime and not be deployed as a “stand‐alone” crime prevention measure. As CCTV surveillance continues to expand its reach in both public and private space and evolve with new technology, policy will benefit from high‐quality evaluations of outcomes and implementation.
Microwave‐Assisted Degradation of Polysaccharide from Polygonatum sibiricum and Antioxidant Activity
Authors: Zhang Hui , Cai Xiu‐ting , Tian Qing‐hua , Xiao Lin‐xia , Zeng Zhen , Cai Xin‐tong , Yan Ji‐zhong , Li Qing‐yong 
Published: March 2019

AbstractFour polysaccharide fractions (P‐1: 71.40%, P‐2: 1.95%, P‐3: 1.14%, P‐4: 1.64%) were isolated from crude Polygonatum sibiricum polysaccharide (PSP), processed by water extraction, ethanol precipitation, and further separated with diethylaminoethyl cellulose‐52 anion‐exchange chromatography. Their molecular weights and monosaccharide compositions were characterized by high performance gel chromatography with evaporative light scattering detector and ultraviolet–visible detector. The antioxidant activity of four polysaccharides fractions were assessed by the electron transfer menchanism (DPPH, ferric reducing power, and ABST assays) and chelation of transition metals (Fe2+ and Cu2+ chelation ability). The highest content fraction P‐1 exhibited the lowest antioxidant activity, and the ranking of antioxidant capacity was P‐4 > P‐3 > P‐2 > PSP > P‐1. After processed by microwave‐assisted degradation, the molecular weight of P‐1 was decreased from 2.99 × 105 to 2.33 × 103 Da, while the antioxidant activity of degraded P‐1 was about eightfold higher than natural P‐1. These results indicated that the proposed microwave‐assisted degradation approach was an efficacious methodology to improve their bioactivity by lower the molecular weight of polysaccharides.Practical ApplicationThis study provided an environmentally friendly, convenient and efficient microwave‐assisted degradation technology to process the neutral polysaccharides from Polygonatum sibiricum. The results could be used for the development and utilization of various plant polysaccharides as a kind of food supplement in our daily life.
High dose rate brachytherapy boost for prostate cancer: Biochemical control and the impact of transurethral resection of the prostate and hydrogel spacer insertion on toxicity outcomes
Authors: Chao Michael , Bolton Damien , Lim Joon Daryl , Chan Yee , Lawrentschuk Nathan , Ho Huong , Spencer Sandra , Wasiak Jason , Guerrieri Mario , Ow Darren , Troy Andrew , Pham Trung , Sengupta Shomik , Tan Alwin , McMillan Kevin , Koufogiannis George , Foroudi Farshad , Ng Michael , Khoo Vincent 
Published: March 2019

AbstractIntroductionTo examine the long‐term outcomes of high dose rate brachytherapy boost (HDR‐BT) combined with external beam radiotherapy (EBRT) for intermediate and high‐risk prostate cancer patients.MethodsData from 95 patients who underwent combined EBRT (50.4 Gy) and HDR‐BT to the prostate between 2010 and 2017 were retrospectively analysed. Biochemical progression free survival (bPFS), local recurrence free survival (LRFS), metastatic free survival (MFS) and overall survival (OS) were estimated using Kaplan–Meier method. Regression analysis was conducted to identify important predictors of outcomes.ResultsA total of 24 patients received an initial HDR‐BT dose of 18 Gy in three fractions, with the remaining 71 patients receiving 16 Gy in two fractions as per departmental protocol changes. Most patients (88%) received androgen deprivation therapy. A transurethral resection of the prostate (TURP) was performed in 14 patients and hydrogel spacers (HS) were used in 30 patients. Median follow‐up was 58 months. The 5‐year bPFS, LRFS, MFS and OS were 92%, 100%, 92% and 88%. Univariate regression revealed no statistical association between patient characteristics and time to relapse (all P > 0.1). Late > grade 2 genitourinary (GU) toxicity was 6.3%. The use of HS or prior TURP had no impact on late GU toxicity. Late Grade 1 gastrointestinal (GI) toxicity was 5.3%.ConclusionThe combined HDR‐BT with EBRT resulted in excellent bPFS. The cumulative risk of late GU and GI toxicity was low and can be further improved with preventative strategies such as a pre‐emptive TURP and/or HS insertion.
Targeting senescent cells alleviates obesity‐induced metabolic dysfunction
Authors: Palmer Allyson K. , Xu Ming , Zhu Yi , Pirtskhalava Tamar , Weivoda Megan M. , Hachfeld Christine M. , Prata Larissa G. , van Dijk Theo H. , Verkade Esther , Casaclang‐Verzosa Grace , Johnson Kurt O. , Cubro Hajrunisa , Doornebal Ewald J. , Ogrodnik Mikolaj , Jurk Diana , Jensen Michael D. , Chini Eduardo N. , Miller Jordan D. , Matveyenko Aleksey , Stout Michael B. , Schafer Marissa J. , White Thomas A. , Hickson LaTonya J. , Demaria Marco , Garovic Vesna , Grande Joseph , Arriaga Edgar A. , Kuipers Folkert , von Zglinicki Thomas , LeBrasseur Nathan K. , Campisi Judith , Tchkonia Tamar , Kirkland James L. 
Published: March 2019

AbstractAdipose tissue inflammation and dysfunction are associated with obesity‐related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug‐inducible “suicide” genes driven by the p16Ink4a promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating inflammatory mediators, and promoted adipogenesis in obese mice. Elimination of senescent cells also prevented the migration of transplanted monocytes into intra‐abdominal adipose tissue and reduced the number of macrophages in this tissue. In addition, microalbuminuria, renal podocyte function, and cardiac diastolic function improved with senolytic therapy. Our results implicate cellular senescence as a causal factor in obesity‐related inflammation and metabolic derangements and show that emerging senolytic agents hold promise for treating obesity‐related metabolic dysfunction and its complications.
Combination of Clinically Utilized Kappa‐Opioid Receptor Agonist Nalfurafine With Low‐Dose Naltrexone Reduces Excessive Alcohol Drinking in Male and Female Mice
Authors: Zhou Yan , Kreek Mary Jeanne 
Published: March 2019

BackgroundNalfurafine is the first clinically approved kappa‐opioid receptor (KOP‐r) agonist as an antipruritus drug with few side effects in humans (e.g., sedation, depression, and dysphoria). No study, however, has been done using nalfurafine on alcohol drinking in rodents or humans.MethodsWe investigated whether nalfurafine alone or in combination with mu‐opioid receptor (MOP‐r) antagonist naltrexone changed excessive alcohol drinking in male and female C57BL/6J (B6) mice subjected to a chronic intermittent‐access drinking paradigm (2‐bottle choice, 24‐hour access every other day) for 3 weeks. Neuronal proopiomelanocortin enhancer (nPE) knockout mice with brain‐specific deficiency of beta‐endorphin (endogenous ligand of MOP‐r) were used as a genetic control for the naltrexone effects.ResultsSingle administration of nalfurafine decreased alcohol intake and preference in both male and female B6 mice in a dose‐dependent manner. Pretreatment with nor‐BNI (a selective KOP‐r antagonist) blocked the nalfurafine effect on alcohol drinking, indicating a KOP‐r‐mediated mechanism. Pharmacological effects of a 5‐dosing nalfurafine regimen were further evaluated: The repeated nalfurafine administrations decreased alcohol consumption without showing any blunted effects, suggesting nalfurafine did not develop a tolerance after the multidosing regimen tested. Nalfurafine did not produce any sedation (spontaneous locomotor activity), anhedonia‐like (sucrose preference test), anxiety‐like (elevated plus maze test), or dysphoria‐like (conditioned place aversion test) behaviors, suggesting that nalfurafine had few side effects. Investigating synergistic effects between low‐dose naltrexone and nalfurafine, we found that single combinations of nalfurafine and naltrexone, at doses lower than individual effective dose, profoundly decreased excessive alcohol intake in both sexes. The effect of nalfurafine on decreasing alcohol consumption was confirmed in nPE−/− mice, suggesting independent mechanisms by which nalfurafine and naltrexone reduced alcohol drinking.ConclusionThe clinically utilized KOP‐r agonist nalfurafine in combination with low‐dose naltrexone has potential in alcoholism treatment.
Protective Effects of Facilitated Removal of Blood Alcohol and Acetaldehyde Against Liver Injury in Animal Models Fed Alcohol and Anti‐HIV Drugs
Authors: Han Hui , He Yuxin , Johnson Heather , Mishra Pratibha , Lee Harrison , Ji Cheng 
Published: March 2019

BackgroundWe previously developed enzyme nanoparticles (ENP) of alcohol metabolism. This study was to evaluate protective effects of facilitated removal of blood alcohol and/or acetaldehyde on anti‐HIV drugs and alcohol‐induced liver injuries.MethodsENP were prepared for degrading alcohol completely (ENP1) or partially into acetaldehyde (ENP2), which were applied to mice of acute binge or chronic‐binge alcohol feeding in the presence of antivirals (ritonavir and lopinavir). Liver pathologies were examined to assess the protective effects of ENP.ResultsIn the acute model, ENP1 and ENP2 reduced the blood alcohol concentration (BAC) by 41 and 32%, respectively, within 4 hr, whereas in control without ENP, BAC was reduced only by 15%. Blood acetaldehyde concentration (BADC) was increased by 39% in alcohol‐fed mice treated with ENP2 comparing to control. No significant effects of the anti‐HIV drugs on BAC or BADC were observed. Plasma alanine aminotransferase (ALT) and expression of liver TNF‐α were both significantly increased in the alcohol‐fed mice, which were normalized by ENP1. In the presence of the antivirals, ALT was partially reduced by ENP1 or ENP2. In the chronic model, inflammation, fatty liver, and ALT were increased, which were deteriorated by the antivirals. ENP1 partially reduced BAC, BADC, ALT, and expression of inflammation markers of TNF‐α, F4/80, and IL‐6 and lipogenic factors of ACC, LXRα, and SREBP1. ENP2 reduced BAC without significant effects on ALT, inflammation, or lipogenesis. Antivirals and alcohol synergistically increased expression of organelle stress markers of CHOP, sXBP‐1, ATF6, and GCP60. ENP1 reduced BAC, CHOP, and sXbp‐1. However, no effects of ENP1 were found on ATF6 or GCP60.ConclusionsRemoval of blood alcohol and acetaldehyde by the ENP protects the liver against alcoholic injuries, and the protection is less effective in chronic alcohol and antiviral feeding due to additional drug‐induced organelle stresses.
Incidence of medically treated depression in Denmark among individuals 15–44 years old: a comprehensive overview based on population registers
Authors: Musliner K. L. , Liu X. , Gasse C. , Christensen K. S. , Wimberley T. , Munk‐Olsen T. 
Published: March 2019

ObjectiveExamine the overall incidence of medically treated depression in Denmark among individuals 15–44 years old, and estimate the 5‐year cumulative incidence of psychiatric hospital care among individuals treated first in non‐hospital‐based care.MethodsWe followed all individuals born in Denmark between 1969 and 1998 from age 15 or 2006 (whichever came first) until first depression treatment; death; emigration; or December 31, 2013. Incidence rates were estimated using Poisson regression. Cumulative incidence of hospital care following treatment in non‐hospital care was estimated using Kaplan–Meier curves.ResultsIn this sample of 2 014 760 individuals, incidence rates of depression in non‐hospital and hospital‐based care in 2012–2013 were 6.6 (95% Confidence Interval: 6.5–6.7) per 1000 person‐years and 1.5 (95% CI: 1.5–1.6) per 1000 person‐years, respectively. Overall, 85–90% of first medical treatment for depression took place outside of psychiatric hospitals, but a quarter (26.3%) of individuals treated for depression received hospital care initially or within 5 years. Incidence of hospital care was higher in women and younger individuals.ConclusionsMost medical treatment for depression in Denmark takes place in non‐hospital settings. Women and younger individuals are more likely to receive hospital care both initially and within 5 years after first antidepressant treatment.
A risk model for addictive behaviors in adolescents: interactions between personality and learning
Authors: D'Agostino Alexandra R. , Peterson Sarah J. , Smith Gregory T. 
Published: March 2019

ABSTRACTBackground and AimsTo determine whether transdiagnostic risk, represented as elevations in one high‐risk personality trait, interacts with behavior‐specific risk, represented as elevated expectancies for reinforcement from either drinking or smoking, to account partly for early adolescent drinking and smoking behavior.DesignMultiple regression analysis.SettingTwenty‐three public schools in two school systems in the United States.ParticipantsA sample of 1897 adolescents tested in the spring of 5th, 6th, 7th, 8th and 9th grades.MeasurementsTransdiagnostic risk was measured as negative urgency, the tendency to act rashly when distressed, using the UPPS‐P child version. Drinking‐specific and smoking‐specific risk were measured as expectancies for reinforcement from drinking and smoking, using the Memory Model‐Based Expectancy Questionnaire (alcohol) and the Adolescent Smoking Consequences Questionnaire (smoking).FindingsThere was consistent concurrent prediction from the interactions of (a) negative urgency and alcohol reinforcement expectancies to early adolescent drinking and (b) negative urgency and smoking reinforcement expectancies to early adolescent smoking, above and beyond prediction from the main effects of those variables. In each case, expectancies were more predictive at higher levels of negative urgency. Incremental R2 values for main effects ranged from 0.07 to 0.26, and for interactions ranged from 0.01 to 0.03. Prospectively, the main effects predicted subsequent behavior but the interaction effects did not, except in one case.ConclusionsAmong elementary and high school students in the United States, the joint effects of negative urgency and behavior‐specific expectancies help to explain drinking and smoking behavior. Joint elevations on the trait and the learning variable account for drinking and smoking behavior beyond the main effects of each predictor. However, there is reason to doubt whether the joint effects predict subsequent increases in drinking and smoking beyond the main effects of those variables.
Clinical relevance of genome‐wide polygenic score may be less than claimed
Authors: Curtis David 
Published: March 2019

AbstractObjectivesA recent study claimed that genome‐wide polygenic scores (GPSs) for five common diseases could identify individuals with risk equivalent to monogenic mutations. Receiver operator curve analyses were reported to have areas under the curve (AUCs) ranging from 0.63 for inflammatory bowel disease up to 0.81 for coronary artery disease (CAD), but these models also included age and sex, themselves strong predictors of risk. The GPS for CAD identified 8% of the population at threefold increased risk, which was claimed to be comparable to the excess risk from monogenic mutations.MethodsIn the present study, attempts were made to model the distribution of the GPS for CAD to match the information provided. These models were based on the reported distribution of prevalence by centile of GPS and on the distribution of GPS in controls and cases, and were fitted to the reported results using linear approximations to the distributions and using simulations of a liability‐threshold model.ResultsIt was impossible to produce a compatible model in which the GPS produced an AUC as high as 0.81 and the most plausible estimate was that the true AUC was only 0.65. The reported distributions of the GPS in cases and controls overlap so much that they are not compatible with an AUC of 0.7 or higher.ConclusionsThe AUC of the GPS for these diseases is modest. Furthermore, the literature robustly demonstrates that the true CAD risk associated with monogenic mutations is much higher than the threefold increase that is predicted by the GPS. Together, these findings cast doubt on the clinical utility of the GPS.
Assessing edge effect on the spatial distribution of selected forest biochemical properties derived using the Worldview data in Dukuduku forests, South Africa
Authors: Mutanga Onisimo , Dube Timothy , Omer Galal 
Published: March 2019

AbstractThis work explores the potential of the high‐resolution WorldView‐2 sensor in quantifying edge effects on the spatial distribution of selected forest biochemical properties in fragmented Dukuduku forest in KwaZulu‐Natal, South Africa. Specifically, we sought to map fragmented patches within forested areas in Dukuduku area, using very high spatial resolution WorldView‐2 remotely sensed data and to statistically determine the effect of these fragmented patches on the spatial distribution of selected forest biochemical properties. Edge effects on carbon, LAI and foliar nitrogen were quantified based on the models derived by Omer et al. (IEEE Journal of Selected Topics in Applied Earth Observations and Remote Sensing, 2015, 8, 4825). Edge effect statistical results on the spatial distribution of carbon, LAI and nitrogen showed significant (α = 0.05) variations with change in distance from fragmented patches (>150 m2). Forest foliar carbon concentrations significantly (p‐value = 0.016) increased from 44.8% to 45.3% with increasing distance (25–375 m) from fragmented patches. A similar trend was observed for LAI. Nevertheless, for nitrogen the results show that its concentration significantly (p = 0.016) decreased with increase in distance from the fragmented patches. Overall, the findings of this work underscore the invaluable potential and strength of WorldView‐2 data set in assessing edge effect on the spatial distribution of selected forest biochemical properties.
Translated Justice? The Ixil Maya and the 2013 Trial of José Efraín Ríos Montt for Genocide in Guatemala
Authors: García María Luz 
Published: March 2019

ABSTRACTThis article takes an ethnographically engaged, discourse‐centered approach to questions of representation and cultural difference in democratic process in postwar Guatemala. When José Efraín Ríos Montt became the first former head of state convicted of genocide within his own country, in 2013, Ixil Maya witnesses who testified against him became international human rights icons. However, the trial was marked by difficulties in communication between Ixil witnesses and non‐Ixil lawyers, judges, and observers. “Miscommunications” resulted from diverging forms of speech that are deeply connected to different identities and ways of experiencing and understanding history. Discursive expectations within the courtroom limited recognition of Ixil ways of speaking and, consequently, of Ixil subjects. These expectations also obscured Ixil contestations to systems of power both inside and outside the courtroom. This analysis calls attention to the central role of language in processes of justice and political activism in solidarity with marginalized populations. [discourse‐centered approach, genocide trial, Ixil, Maya, Guatemala]