bluuebunny/crossref_metadata_2025_split huggingface dataset:
The contribution of Parkin, PINK1 and DJ‐1 genes to selective neuronal degeneration in Parkinson's disease
Authors: van der Vlag Marc , Havekes Robbert , Heckman Pim R. A. 
Published: January 2020

AbstractParkinson's disease (PD) is characterised by selective and severe degeneration of the substantia nigra pars compacta and the locus coeruleus (LC), which underlies the most prominent symptoms. Although α‐synuclein accumulation has long been established to play a causal role in the disease, it alone cannot explain the selective degenerative pattern. Recent evidence shows that the selective vulnerability could arise due to the large presence of cytosolic catecholamines and Ca2+ ions in the substantia nigra pars compacta and LC specifically that can be aberrantly affected by α‐synuclein accumulation. Moreover, each has its own toxic potential, and disturbance of one can exacerbate the toxic effects of the others. This presents a mechanism unique to these areas that can lead to a vicious degenerative cycle. Interestingly, in familial variants of PD, the exact same brain areas are affected, implying the underlying process is likely the same. However, the exact disease mechanisms of many of these genetic variants remain unclear. Here, we review the effects of the PD‐related genes Parkin, PINK1 and DJ‐1. We establish that these mutant varieties can set in motion the same degenerative process involving α‐synuclein, cytosolic catecholamines and Ca2+. Additionally, we show indications that model organisms might not accurately represent all components of this central mechanism, explaining why Parkin, PINK1 and DJ‐1 model organisms often lack a convincing PD‐like phenotype.
Metabolic rate is negatively linked to adult survival but does not explain latitudinal differences in songbirds
Authors: Boyce Andy J. , Mouton James C. , Lloyd Penn , Wolf Blair O. , Martin Thomas E. 
Published: January 2020

AbstractSurvival rates vary dramatically among species and predictably across latitudes, but causes of this variation are unclear. The rate‐of‐living hypothesis posits that physiological damage from metabolism causes species with faster metabolic rates to exhibit lower survival rates. However, whether increased survival commonly observed in tropical and south temperate latitudes is associated with slower metabolic rate remains unclear. We compared metabolic rates and annual survival rates that we measured across 46 species, and from literature data across 147 species of birds in northern, southern and tropical latitudes. High metabolic rates were associated with lower survival but survival varied substantially among latitudinal regions independent of metabolism. The inability of metabolic rate to explain latitudinal variation in survival suggests (1) species may evolve physiological mechanisms that mitigate physiological damage from cellular metabolism and (2) extrinsic rather than intrinsic sources of mortality are the primary causes of latitudinal differences in survival.
Effects of long‐term straw return on soil organic carbon storage and sequestration rate in North China upland crops: A meta‐analysis
Authors: Berhane Medhn , Xu Miao , Liang Zhiying , Shi Jianglan , Wei Gehong , Tian Xiaohong 
Published: January 2020

AbstractSoil organic carbon (SOC) is essential for soil fertility and climate change mitigation, and carbon can be sequestered in soil through proper soil management, including straw return. However, results of studies of long‐term straw return on SOC are contradictory and increasing SOC stocks in upland soils is challenging. This study of North China upland agricultural fields quantified the effects of several fertilizer and straw return treatments on SOC storage changes and crop yields, considering different cropping duration periods, soil types, and cropping systems to establish the relationships of SOC sequestration rates with initial SOC stocks and annual straw C inputs. Our meta‐analysis using long‐term field experiments showed that SOC stock responses to straw return were greater than that of mineral fertilizers alone. Black soils with higher initial SOC stocks also had lower SOC stock increases than did soils with lower initial SOC stocks (fluvo‐aquic and loessial soils) following applications of nitrogen‐phosphorous‐potassium (NPK) fertilizer and NPK+S (straw). Soil C stocks under the NPK and NPK+S treatments increased in the more‐than‐20‐year duration period, while significant SOC stock increases in the NP and NP+S treatment groups were limited to the 11‐ to 20‐year period. Annual crop productivity was higher in double‐cropped wheat and maize under all fertilization treatments, including control (no fertilization), than in the single‐crop systems (wheat or maize). Also, the annual soil sequestration rates and annual straw C inputs of the treatments with straw return (NP+S and NPK+S) were significantly positively related. Moreover, initial SOC stocks and SOC sequestration rates of those treatments were highly negatively correlated. Thus, long‐term straw return integrated with mineral fertilization in upland wheat and maize croplands leads to increased crop yields and SOC stocks. However, those effects of straw return are highly dependent on fertilizer management, cropping system, soil type, duration period, and the initial SOC content.
Screening for vulnerable older people: Is the Probability of Repeated Admission scale an accurate tool?
Authors: Perez Mariangela , Moreira Virgílio G , Lourenço Roberto A 
Published: January 2020

AimTo evaluate the Probability of Repeated Admission (Pra) scale performance in predicting healthcare utilization and death in a community sample of Rio de Janeiro city, Brazil.MethodsThis was a prospective longitudinal study. The sample was composed of community‐dwelling older people who participated in the research network Frailty in Brazilian Older People Study, Rio de Janeiro section. It analyzed data from the baseline and the follow up. At the baseline, 764 older adults were stratified by the Pra, and, 3 years later, data on health services utilization and survival status were collected. The Pra accuracy, obtained by the area under the curve, the sensitivity and the specificity to predict hospitalization in 3 years; visits to the emergency department; and death were determined. Cox regression estimated the survival curves, according to the risk strata.ResultsThe accuracy, the sensitivity and the specificity of Pra were 62% (95% CI 57–68%), 8.8% and 95.4% for hospitalization in 3 years; 59% (95% CI 53–64%), 8.3% and 94.8% for emergency room visits; 66% (95% CI 59–74%) and 68% (95% CI 63–73%), 15.0% and 96.0% for death. Survival curves showed that high‐risk individuals were more likely to die compared with the low‐risk individuals, adjusted to covariables (P < 0.001).ConclusionsThe Pra presented low accuracy, low sensitivity and high specificity for all outcomes observed, indicating a poor performance to screen vulnerable older adults in Brazil. Therefore, this tool should not be used alone, as a case‐finding instrument. Geriatr Gerontol Int 2020; 20: 360–365.
Lagrangian bounds for large‐scale multicommodity network design: a comparison between Volume and Bundle methods
Authors: Shibasaki Rui S. , Baiou Mourad , Barahona Francisco , Mahey Philippe , de Souza Mauricio C. 
Published: January 2020

AbstractThe Bundle Method and the Volume Algorithm are among the most efficient techniques to obtain accurate Lagrangian dual bounds for hard combinatorial optimization problems. We propose here to compare their performance on very large scale Fixed‐Charge Multicommodity Capacitated Network Design problems. The motivation is not only the quality of the approximation of these bounds as a function of the computational time but also the ability to produce feasible primal solutions and thus to reduce the gap for very large instances for which optimal solutions are out of reach. Feasible solutions are obtained through the use of Lagrangian information in constructive and improving heuristic schemes. We show in particular that, if the Bundle implementation has provided great quality bounds in fewer iterations, the Volume Algorithm is able to reduce the gaps of the largest instances, taking profit of the low computational cost per iteration compared to the Bundle Method.
Heuristic approaches for the family traveling salesman problem
Authors: Bernardino Raquel , Paias Ana 
Published: January 2020

AbstractIn this article, we address the family traveling salesman problem (FTSP), an NP‐hard problem that may be seen as a generalization of the traveling salesman problem. In the FTSP, the set of cities is partitioned into several families and one wants to find the minimum cost route that visits a given number of cities in each family. We propose two metaheuristics, a population‐based method and a local search method, and a hybrid algorithm, which combines a branch‐and‐cut algorithm with a local search procedure. All the proposed methods improve the best known upper bounds from the literature. The local search method and the hybrid algorithm improve the best known upper bounds for all the benchmark instances with unknown optimal value, while the population‐based method improves the best known upper bounds for all instances, except two. Furthermore, we developed an instance generator to create additional test instances with different visit patterns. These newly generated instances were considered in the computational experiment and, thus, we provide optimal values or upper bounds for each instance. Additionally, we created a website dedicated to the FTSP, where this information is made available to the scientific community (http://familytsp.rd.ciencias.ulisboa.pt/).
Microstructural evolution of 3YSZ flash‐sintered with current ramp control
Authors: R. Lavagnini Isabela , Campos João V. , Ferreira Julieta A. , A. Pallone Eliria M. J. 
Published: January 2020

AbstractThe effect of a controlled current ramp during flash sintering (FS) on the densification and microstructural evolution of 3 mol% yttria‐stabilized zirconia was investigated. The samples were flash sintered using a current ramp control with six different current ramp rates and compared with samples sintered by FS without current ramp control. In both cases, maximum electric current densities of 100 and 200 mA mm−2 were used. The microstructure of cylindrical samples was observed, showing grain size heterogeneity between the curved surface and the core for the flash‐sintered (FSed) samples regardless of the maximum current density used. By contrast, the current ramp FSed samples exhibited a homogeneous grain size when the electric current density of 100 mA mm−2 was applied. Thus, controlling a current ramp during FS can be an alternative for avoiding grain size heterogeneity on ceramics sintered by this technique.
Dihydrotestosterone potentiates insulin to up‐regulate prokineticin‐1 in decidualizing human endometrial stromal cells
Authors: Ujvari Dorina , Graells Brugalla Carlota , Hirschberg Angelica Lindén 
Published: January 2020

AbstractProkineticin 1 (PROK1) is a key regulator of embryo implantation and placentation, and its dysregulation is associated with pregnancy complications, such as pre‐eclampsia and foetal growth restriction. We have previously shown that insulin strongly enhances the expression of PROK1 in human decidualizing stromal cells. Here, we demonstrate that dihydrotestosterone (DHT), but not testosterone, potentiates insulin to up‐regulate PROK1 in these cells. However, the androgens alone do not influence the expression of PROK1. Our findings suggest that insulin and androgens both are involved in the regulation of PROK1 that could have implications for normal and pathological pregnancies.
Pre‐treatment systemic immune‐inflammation index is a useful prognostic indicator in patients with breast cancer undergoing neoadjuvant chemotherapy
Authors: Chen Li , Kong Xiangyi , Wang Zhongzhao , Wang Xiangyu , Fang Yi , Wang Jing 
Published: January 2020

AbstractThe systemic immune‐inflammation index (SII = N × P/L) based on neutrophil (N), platelet (P) and lymphocyte (L) counts is used to predict the survival of patients with malignant tumours and can fully reflect the balance between host inflammatory and immune status. This study is conducted to explore the potential prognostic significance of SII in patients with breast cancer undergoing neoadjuvant chemotherapy (NACT). A total of 262 patients with breast cancer received NACT were enrolled in this study. According to the receiver operating characteristic curve, the optimal cut‐off value of SII was divided into two groups: low SII group (<602 × 109/L) and high SII group (≥602 × 109/L). The associations between breast cancer and clinicopathological variables by SII were determined by chi‐squared test or Fisher's exact test. The Kaplan‐Meier plots and log‐rank test were used to determine clinical outcomes of disease‐free survival (DFS) and overall survival (OS). The prognostic value of SII was analysed by univariate and multivariate Cox proportional hazards regression models. The toxicity of NACT was accessed by National Cancer Institute Common Toxicity Criteria (NCICTC). According to univariate and multivariate Cox regression survival analyses, the results showed that the value of SII had prognostic significance for DFS and OS. The patients with low SII value had longer DFS and OS than those with high SII value (31.11 vs 40.76 months, HR: 1.075, 95% CI: 0.718‐1.610, P = .006; 44.47 vs 53.68 months, HR: 1.051, 95% CI: 0.707‐1.564, P = .005, respectively). The incidence of DFS and OS in breast cancer patients with low SII value was higher than that in those patients with high SII value in 3‐, 5‐ and 10‐year rates. The common toxicities after NACT were haematological and gastrointestinal reaction, and there were no differences by SII for the assessment of side effects of neoadjuvant chemotherapy. Meanwhile, the results also proved that breast cancer patients with low SII value and high Miller and Payne grade (MPG) survived longer than those breast cancer with high SII value and low MPG grade. In patients without lymph vessel invasion, these breast cancer patients with low SII value had better prognosis and lower recurrence rates than those with high SII value. Pre‐treatment SII with the advantage of reproducible, convenient and non‐invasive was a useful prognostic indicator for breast cancer patients undergoing neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.
Lobetyolin induces apoptosis of colon cancer cells by inhibiting glutamine metabolism
Authors: He Wei , Tao Weiwei , Zhang Feng , Jie Qian , He Yun , Zhu Wei , Tan Jiani , Shen Weixing , Li Liu , Yang Ye , Cheng Haibo , Sun Dongdong 
Published: January 2020

AbstractThe purpose of the present study was to evaluate the anti‐cancer property of Lobetyolin on colorectal cancer and explore its potential mechanism. Lobetyolin was incubated with HCT‐116 cells in the absence or presence of ASCT2 inhibitor Benser or p53 inhibitor Pifithrin‐α. The levels of glutamine, glutamic acid, α‐ketoglutarate, ATP and GSH were determined to measure the glutamine metabolism. Annexin V‐FITC/PI staining and TUNEL assay were applied to estimate the apoptotic condition. The levels of ASCT2 were examined by RT‐qPCR, Western blot and immunofluorescence staining. The expressions of cleaved‐caspase‐3, caspase‐3, cleaved‐caspase‐7, caspase‐7, cleaved‐PARP, PARP, p53, p21, bax and survivin were detected using Western blot analysis. As a result, the treatment with Lobetyolin effectively induced apoptosis and glutamine metabolism in HCT‐116 cells through ASCT2 signalling. The inhibition of ASCT2 reduced the glutamine‐related biomarkers and augmented the apoptotic process. We further found that the effect of Lobetyolin on HCT‐116 was related to the expressions of p21 and bax, and transportation of p53 to nucleus. The inhibition of p53 by Pifithrin‐α promoted the inhibitory effect of Lobetyolin on ASCT2‐mediated apoptosis. Lobetyolin also exerted anti‐cancer property in nude mice. In conclusion, the present work suggested that Lobetyolin could induce the apoptosis via the inhibition of ASCT2‐mediated glutamine metabolism, which was possibly governed by p53.
Adrenomedullin has a cytoprotective role against endoplasmic reticulum stress for pancreatic β‐cells in autocrine and paracrine manners
Authors: Suetomi Risa , Ohta Yasuharu , Akiyama Masaru , Matsumura Takuro , Taguchi Akihiko , Yamamoto Kaoru , Kamatani Takashi , Tanizawa Yukio 
Published: January 2020

AbstractAims/IntroductionPancreatic β‐cells are sensitive to endoplasmic reticulum (ER) stress, which has a major role in the context of β‐cell death. Adrenomedullin (ADM) has been shown to exert a cytoprotective effect under various pathophysiological conditions. Several studies have suggested that thiazolidinediones have protective effects on β‐cells. During the course to elucidate the molecular mechanisms by which pioglitazone prevents β‐cell death, ADM emerged as a candidate. Here, we studied the regulation of ADM expression, including the effects of pioglitazone, and its role in pancreatic islets.Materials and MethodsWe analyzed ADM expression in islet cell lines treated with pioglitazone. The effects of ER stress on ADM and ADM receptor expressions were investigated by analyzing thapsigargin‐treated MIN6 cells and islets isolated from Wfs1−/− and db/db mice. To study the anti‐apoptotic effect of ADM, ER stress‐exposed MIN6 cells were treated with ADM peptides or transfected with ADM expression plasmid.ResultsPioglitazone increased the production and secretion of ADM in islets through peroxisome‐proliferator activated receptor‐γ‐dependent mechanisms. Thapsigargin treatment increased expressions of both ADM and ADM receptor, composed of Ramp2, Ramp3 and Crlr, in MIN6 cells. ADM and ADM receptor expressions were also increased in isolated islets from Wfs1−/− and db/db mice. ADM peptides and ADM overexpression protected MIN6 cells from thapsigargin‐induced apoptosis.ConclusionsER stress stimulates ADM production and secretion in islets. ADM signaling might protect β‐cells from ER stress‐induced apoptosis, and might be one of the self‐protective mechanisms. β‐Cell protection by pioglitazone is partly through induction of ADM. ADM‐based therapy could be a novel strategy for treating diabetes.
Clinical characteristics including cardiovascular and metabolic risk factors in adolescents with psoriasis
Authors: Blegvad C. , Nybo Andersen A.‐M. , Groot J. , Zachariae C. , Barker J. , Skov L. 
Published: January 2020

AbstractBackgroundClinical studies on psoriasis in adolescents have mainly been performed in patients with severe psoriasis. Population‐based studies of clinical characteristics and risk factors for later cardiovascular and metabolic disease in children and adolescents are lacking.ObjectivesTo examine the clinical characteristics of adolescents with psoriasis nested in a general population cohort. Furthermore, to investigate cardiovascular and metabolic risk factors in the adolescents with psoriasis compared to parentally predisposed and non‐predisposed adolescents without psoriasis from the same birth cohort.MethodsWe identified adolescents with and without psoriasis using a nationwide general population birth cohort in Denmark. A clinical examination included skin inspection and scoring of psoriasis severity, completion of a questionnaire on psoriasis and comorbidities, physical measurements, and blood sampling. Participants also completed self‐administered questionnaires on quality of life and mental health.ResultsWe included 81 adolescents with psoriasis and 234 controls (110 with genetic predisposition for psoriasis and 124 without predisposition). Median age was 15.6 (13.5–18.5) years, and in those with active psoriasis, median Psoriasis Area and Severity Index score was 1.2 (0.1–11.4). The scalp was the most common site of psoriasis, both at debut and at time of examination. Diaper rash in infancy was more frequent in the psoriasis group. No significant differences regarding quality of life, anxiety and depression were found. More adolescents with psoriasis were obese (8.6% vs. 1.7%, P = 0.008), and physical measures of abdominal obesity were also significantly higher. HbA1c was significantly higher (31.55 vs. 30.81 mmol/mol, P = 0.048), while no differences were found for blood pressure, lipids or high‐sensitivity C‐reactive protein. In a subgroup analysis, this was evident in the non‐predisposed psoriasis‐free controls only.ConclusionsOverall, adolescents with psoriasis from this general population had mild disease. Still, early markers of cardiovascular and metabolic disease were elevated.
Sonidegib and vismodegib in the treatment of patients with locally advanced basal cell carcinoma: a joint expert opinion
Authors: Dummer R. , Ascierto P.A. , Basset‐Seguin N. , Dréno B. , Garbe C. , Gutzmer R. , Hauschild A. , Krattinger R. , Lear J.T. , Malvehy J. , Schadendorf D. , Grob J.J. 
Published: January 2020

AbstractSonidegib and vismodegib are hedgehog pathway inhibitors (HhIs) approved for the treatment of advanced basal cell carcinoma (BCC). Until recently, vismodegib was the only targeted treatment available for patients with locally advanced BCC (laBCC) in cases where surgery and radiotherapy are inappropriate. Sonidegib has recently been approved and now presents an alternative treatment option. The clinical differences between the two HhIs in patients with laBCC are unclear, as no head‐to‐head randomized controlled trials are or will be initiated. Moreover, there were important differences in the designs of their pivotal studies, BOLT (sonidegib) and ERIVANCE (vismodegib), and these differences complicate evidence‐based analysis of their relative efficacy and safety profiles. In this paper, a group of clinical experts in the management of laBCC summarizes the clinical and pharmacological profiles of sonidegib and vismodegib based on published data and their own clinical experience. One key difference between the two pivotal studies was the criteria used to assess BCC severity. ERIVANCE (a single‐arm phase II trial) used the conventional Response Evaluation Criteria in Solid Tumors (RECIST), while the more recent double‐blind randomized BOLT trial used the stringent modified RECIST. A preplanned analysis adjusted the outcomes from BOLT with RECIST‐like criteria, and this enabled the experts to discuss relative efficacy outcomes for the two treatments. Centrally reviewed objective response rate (ORR) for vismodegib was 47.6% (95% CI: 35.5–60.6) at 21‐month follow‐up using RECIST. After adjusting with RECIST‐like criteria, the ORR for sonidegib according to central review at 18‐month follow‐up was 60.6% (95% CI: 47.8–72.4). Both treatments were associated with similar patterns of adverse events. Sonidegib and vismodegib share the same efficacy and tolerability profiles, but their pharmacokinetic profiles show several differences, such as volume of distribution and half‐life. Further studies are needed to understand how these differences may impact clinical practice.