bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline genetic testing for inherited prostate cancer in practice: Implications for genetic testing, precision therapy, and cascade testing
Authors: Giri Veda N. , Hegarty Sarah E. , Hyatt Colette , O'Leary Erin , Garcia John , Knudsen Karen E. , Kelly William K. , Gomella Leonard G. 
Published: November 2018

BackgroundGenetic testing capability and guidelines are rapidly expanding to assess inherited prostate cancer (PCA). Clinical genetic data from multigene testing can provide insights into the germline pathogenic variant (PV) spectrum and correlates in men with PCA unselected for metastatic disease to optimize identification of men for genetic evaluation and management.MethodsA retrospective cross‐sectional analysis was conducted of de‐identified clinical genetic testing data from a large commercial genetic testing laboratory in the US. ICD‐10 claims codes were used to identify men with PCA, along with family history data. Gleason score was abstracted from test request forms. Overall PV rate among men with PCA was estimated, along with PVs in DNA repair genes. Family history and Gleason score association to germline DNA repair PVs was assessed using Fisher's exact test with correction for false‐discovery.ResultsAs of August 2017, genetic results were available on 1328 men with PCA. Overall PV rate was 15.6%, with 10.9% of PV in DNA repair genes. PVs were most commonly identified in BRCA2 (4.5%), CHEK2 (2.2%), ATM (1.8%), and BRCA1 (1.1%). Breast cancer family history was significantly associated with germline DNA repair PVs (OR 1.89, [95%CI 1.33, 2.68], P = 0.003). Among men with Gleason score>= 6 (n = 706), Gleason> = 8 was significantly associated with DNA repair PVs (OR 1.85 [95%CI 1.22, 2.80], P = 0.004).ConclusionsA substantial proportion of men with PCA unselected for metastatic disease carry germline DNA repair PVs. Breast cancer family history and high Gleason score are important predictors to identify men with PCA who may carry germline DNA repair PVs. Our findings support current NCCN guidelines and have implications for genetic assessment, therapeutic management, and cascade testing for men with PCA and their families.
Integrated weed management (IWM): why are farmers reluctant to adopt non‐chemical alternatives to herbicides?
Authors: Moss Stephen 
Published: November 2018

AbstractImplementation of integrated weed management (IWM) has been poor, with little evidence of concomitant reductions in herbicide use. Non‐chemical methods are often adopted as a means of compensating for reduced herbicide efficacy, due to increasing resistance, rather than as alternatives to herbicides. Reluctance to adopt non‐chemical methods is not due to a lack of research or technology but to a lack of farmer motivation and action. Justifiably, herbicides are often seen as the easier option – their convenience outweighs the increased complexity, costs and management time associated with non‐chemical alternatives. Greater use of non‐chemical alternatives to herbicides will only occur if the following seven aspects are addressed: (i) better recognition of the reasons why farmers are reluctant to use non‐chemical alternatives; (ii) encouraging farmers to adopt a longer‐term approach to weed control; (iii) changing farmers' attitudes to pesticides; (iv) paying more attention to the individual farmer's perspective; (v). greater involvement of economists, social scientists and marketing professionals; (vi) re‐evaluating research and extension priorities; and (vii) changing the mindset of funders of research and extension. If ‘persuasion’ fails to deliver greater implementation of IWM, authorities may resort to greater use of financial and other incentives combined with tougher regulations. © 2018 Society of Chemical Industry
Aloysia citriodora Palau (lemon verbena) for insomnia patients: A randomized, double‐blind, placebo‐controlled clinical trial of efficacy and safety
Authors: Afrasiabian Farshid , Mirabzadeh Ardakani Mehran , Rahmani Khaled , Azadi Nammam Ali , Alemohammad Zahra Banafsheh , Bidaki Reza , Karimi Mehrdad , Emtiazy Majid , Hashempur Mohammad Hashem 
Published: November 2018

Aloysia citriodora (A. citriodora) has a long history of traditional use for sedation and treatment of insomnia in different societies. This study was carried out to assess the efficacy of A. citriodora in patients with insomnia. One hundred patients were randomly divided into two groups of A. citriodora (total essential oil 1.66 mg/10 ml and total amount of flavonoid in terms of quercetin 3.22 mg/10 ml of the syrup) and placebo. They were advised to use 10 cc of the syrups; an hour before the bedtime for a period of 4 weeks. Participants were assessed using Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) questionnaires at the baseline and then 2 and 4 weeks after the enrollment. Mean scores of global PSQI and its four components including sleep latency, habitual sleep efficiency, daytime dysfunction, and subjective sleep quality and also ISI score in the A. citriodora group improved significantly after 4 weeks of treatment when compared with the placebo group (p < 0.001, for all of them). Also, improvement of global score of PSQI and ISI was observed in the intervention group as compared with the placebo group, 2 weeks after the enrollment (p < 0.001). The results of this study showed that oral intake of A. citriodora can be suggested as a complementary treatment for patients with insomnia.
Exploiting Nanomaterial‐Mediated Autophagy for Cancer Therapy
Authors: Wei Weijun , Rosenkrans Zachary T. , Luo Quan‐Yong , Lan Xiaoli , Cai Weibo 
Published: November 2018

AbstractAutophagy is a conserved process that is critical for sequestering and degrading proteins, damaged or aged organelles, and for maintaining cellular homeostasis under stress conditions. Despite its dichotomous role in health and diseases, autophagy usually promotes growth and progression of advanced cancers. In this context, clinical trials using chloroquine and hydroxychloroquine as autophagy inhibitors have suggested that autophagy inhibition is a promising approach for treating advanced malignancies and/or overcoming drug resistance of small molecule therapeutics (i.e., chemotherapy and molecularly targeted therapy). Efficient delivery of autophagy inhibitors may further enhance the therapeutic effect, reduce systemic toxicity, and prevent drug resistance. As such, nanocarrier‐based drug delivery systems have several distinct advantages over free autophagy inhibitors that include increased circulation of the drugs, reduced off‐target systemic toxicity, increased drug delivery efficiency, and increased solubility and stability of the encapsulated drugs. With their versatile drug encapsulation and surface‐functionalization capabilities, nanocarriers can be engineered to deliver autophagy inhibitors to tumor sites in a context‐specific and/or tissue‐specific manner. This review focuses on the role of nanomaterials utilizing autophagy inhibitors for cancer therapy, with a focus on their applications in different cancer types.
A whole systems approach to education redesign: A case study on the need for intergenerational perspectives and inclusion
Authors: Laszlo Kahlia , Laszlo Alexander 
Published: November 2018

AbstractThis study was commissioned by the Global Education Futures forum for presentation at its fourth International Conference in Moscow, Russia, from February 29 to March 2, 2016 (http://edu2035.org/#program). The objective was to conduct field research with a special focus on the vision of the future of education held by young people. This report presents some views and perspectives of my generation regarding what they want education to be like in the future. In northern California, my teachers Ms. B and Mr. Wahanik used the framework of questions and activities that my father and I developed to gather this kind of information by running a sort of “focus group” with my 10th Grade class and to find out what their views, perspective, opinions, ideas, hopes, and concerns are regarding this theme. A similar process was run with a group of young people in Buenos Aires, Argentina.
A Reciprocal Role of the Smad4-Taz Axis in Osteogenesis and Adipogenesis of Mesenchymal Stem Cells
Authors: Park Jin Seok , Kim Minbeom , Song No-Joon , Kim Jun-Hyeong , Seo Dongyeob , Lee Ji-Hyung , Jung Su Myung , Lee Jae Young , Lee Jaewon , Lee Youn Sook , Park Kye Won , Park Seok Hee 
Published: November 2018

Abstract
Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into mature cells of various cell types. Although the differentiation process of MSCs requires lineage-specific transcription factors, the exact molecular mechanism that determines MSCs differentiation is not clearly addressed. Here, we demonstrate a Smad4-Taz axis as a new intrinsic regulator for adipo-osteogenic differentiation of MSCs and show that this function of Smad4 is independent of the transforming growth factor-β signal. Smad4 directly bound to the Taz protein and facilitated nuclear localization of Taz through its nuclear localization signal. Nuclear retention of Taz by direct binding to Smad4 increased expression of osteogenic genes through enhancing Taz-runt-related transcription factor 2 (Runx2) interactions in the C3H10T1/2 MSC cell line and preosteoblastic MC3T3-E1 cells, whereas it suppressed expression of adipogenic genes through promoting Taz-peroxisome proliferator-activated receptor-γ (PPARγ) interaction in C3H10T1/2 and preadipogenic 3T3-L1 cells. A reciprocal role of the Smad4 in osteogenic and adipogenic differentiation was also observed in human adipose tissue-derived stem cells (hASCs). Consequently, Smad4 depletion in C3H10T1/2 and hASCs reduced nuclear retention of Taz and thus caused the decreased interaction with Runx2 or PPARγ, resulting in delayed osteogenesis or enhanced adipogenesis of the MSC. Therefore, these findings provide insight into a novel function of Smad4 to regulate the balance of MSC lineage commitment through reciprocal targeting of the Taz protein in osteogenic and adipogenic differentiation pathways. Stem Cells 2019;37:368–381
Exploring high‐dimensional free energy landscapes of chemical reactions
Authors: Awasthi Shalini , Nair Nisanth N. 
Published: November 2018

Molecular dynamics (MD) techniques are widely used in computing free energy changes for conformational transitions and chemical reactions, mainly in condensed matter systems. Most of the MD‐based approaches employ biased sampling of a priori selected coarse‐grained coordinates or collective variables (CVs) and thereby accelerate otherwise infrequent transitions from one free energy basin to the other. A quick convergence in free energy estimations can be achieved by enhanced sampling of large number of CVs. Conventional enhanced sampling approaches become exponentially slower with increasing dimensionality of the CV space, and thus they turn out to be highly inefficient in sampling high‐dimensional free energy landscapes. Here, we focus on some of the novel methods that are designed to overcome this limitation. In particular, we discuss four methods: bias‐exchange metadynamics, parallel‐bias metadynamics, adiabatic free energy dynamics/temperature‐accelerated MD, and temperature‐accelerated sliced sampling. The basic idea behind these techniques is presented and applications using these techniques are illustrated. Advantages and disadvantages of these techniques are also delineated.This article is categorized under:
Structure and Mechanism > Reaction Mechanisms and Catalysis
Molecular and Statistical Mechanics > Free Energy Methods
Theoretical and Physical Chemistry > Statistical Mechanics
Deriving bonding concepts for molecules, surfaces, and solids with energy decomposition analysis for extended systems
Authors: Pecher Lisa , Tonner Ralf 
Published: November 2018

Chemical bonding concepts like covalency, ionicity, Pauli repulsion, shared‐electron, or donor–acceptor bonding are important tools to sort our vast knowledge in chemistry and predict new reactivity. Electronic structure analysis provides the basis for a detailed understanding of the origins of these concepts. Energy decomposition analysis (EDA) is an established method for molecules and has recently been implemented for application in extended systems, that is, surfaces and solids, where it is termed periodic EDA (pEDA). The foundations and applications of this method which enables the derivation of bonding concepts are outlined in this review. Embedded in key examples from molecular and solid‐state chemistry, the major part covers the adsorption and reactivity of molecules with surfaces with a focus on organic molecules interacting with semiconductor surfaces. Based on electronic structure analysis and supported by a quantitative methodology, we show that analogous bonding concepts can be applied in diverse chemical environments.This article is categorized under:Electronic Structure Theory > Ab Initio Electronic Structure MethodsStructure and Mechanism > Computational Materials Science
Extensional Petri net
Authors: Dong Xiaoju , Fu Yuxi , Varacca Daniele 
Published: November 2018

Abstract
Petri nets form a concurrent model for distributed and asynchronous systems. They are capable of modeling information flow in a closed system, but are generally not suitable for the study of compositionality. We address the issue of Petri net compositionality by introducing extensional Petri nets. In an extensional Petri net some places are external while others are internal. Every external place is labeled by a distinguished interface name. When composing two extensional Petri nets two places with a same label are coerced. An external place can be turned into an internal place by applying localization operator. The paper takes a look at bisimulation semantics and observational properties of the extensional Petri nets.
Heterologous expression-facilitated natural products’ discovery in actinomycetes
Authors: Xu Min , Wright Gerard D 
Published: November 2018

Abstract
Actinomycetes produce many of the drugs essential for human and animal health as well as crop protection. Genome sequencing projects launched over the past two decades reveal dozens of cryptic natural product biosynthetic gene clusters in each actinomycete genome that are not expressed under regular laboratory conditions. This so-called ‘chemical dark matter’ represents a potentially rich untapped resource for drug discovery in the genomic era. Through improved understanding of natural product biosynthetic logic coupled with the development of bioinformatic and genetic tools, we are increasingly able to access this ‘dark matter’ using a wide variety of strategies with downstream potential application in drug development. In this review, we discuss recent research progress in the field of cloning of natural product biosynthetic gene clusters and their heterologous expression in validating the potential of this methodology to drive next-generation drug discovery.
Outcomes of pelvic resection from malignant pelvic tumors. A case series
Authors: Kamal Achmad Fauzi , Wahyudi Muhammad , Prabowo Yogi 
Published: November 2018

ABSTRACT

Introduction:
Malignant pelvic tumors also tend to present late and therefore pose a major challenge for orthopedic oncologists because of the large tumor size, local extension, and complex anatomy with proximity to major neurovascular structures and intestinal and urinary tracts.

Method:
We evaluated the oncologic, functional outcome and complications following internal hemipelvectomy in a consecutive series of patients with malignant muculoskeletal tumors of the pelvis at our hospital between January 2012 and December 2017. The follow-up period was defined as the length of time elapsed from the date of surgery until the death or last date of review following operation. We analyzed survival rate using Kaplan Meier method and it relation with tumor site, tumor size, and type of histology.

Result:
Our clinical series of patients were composed of 4 males and 5 females. Of 9 patients, 6 cases were primary malignant bone tumor (3 cases of chondrosarcoma, 2 cases of osteosarcoma, and 1 case of Ewing's sarcoma), 2 cases of metastatic bone disease from thyroid carcinoma, 1 case from breast adenocarcinoma. The Kaplan Meier analysis showed 1 year and 2 years survival rate were 88.9% and 66.7% respectively. The functional outcomes showed the mean MSTS score 16.5 point. The lowest score was 9, which was pelvis resection type I + II on osteosarcoma case. The highest score was 25, which was pelvic resection type II + III and reconstruted with iliofemoral arthrodesis. There was 1 case intraoperative bleeding and 2 cases post operative infections.

Conclusions:
The majority of pelvic tumor underwent pelvic resection is chondrosarcoma. Functional outcome MSTS score was still comparable with previous study. Complications of pelvic surgeries were bleeding and infection. In our small case series, pelvic resection with wide margin and reconstruction of bone defect may give good local control and clinical outcome.

Highlights:
The Raigorodok stockwork gold–sulfide–quartz deposit in the North Kazakhstan gold ore province
Authors: Kovalev K.R. , Syzdykov S.O. , Kalinin Yu.A. , Naumov E.A. , Baranov V.V. , Sukhorukov V.P. , Gladkov A.S. , Zhimulev F.I. 
Published: November 2018

Abstract
The Raigorodok stockwork gold–sulfide–quartz deposit is located in the contact zone of a monzogabbro–diorite intrusion belonging to the Stepnyak complex (442 Ma). Two main ore formation stages have been established: early, with disseminated gold-bearing pyrite–chalcopyrite mineralization related to skarn, propylite, and K-feldspar formation, and late, with productive mineralization. The late stage was accompanied by the formation of beresite, sericite, and quartz and comprised two substages: (1) quartz–gold–pyrite–chalcopyrite mineralization and (2) quartz–carbonate–gold–polysulfide mineralization. The 40Ar/39Ar ages of beresites and sericites are 422.9 ± 4.3 Ma and 416.7 ± 4.3 Ma, respectively, which is 19–22 Myr younger than the age of the host intrusion. The deposit ores formed stepwise, at temperatures of 112–335 °C and fluid salinity of 0.7–21.2 wt.% NaCl equiv. Sulfur for skarns, propylites, beresites, and ores might have been provided by a deep magma chamber, and the carbonaceous shales of the Vendian Sharyk Formation might have been the source of gold. The isotope and geochemical data and the results of fluid inclusion study suggest that Raigorodok is an intrusion-related deposit. At the same time, the deposit has a number of signs of porphyry-epithermal ore-magmatic systems.
Inherent thermal convection in a granular gas inside a box under a gravity field
Authors: Vega Reyes Francisco , Puglisi Andrea , Pontuale Giorgio , Gnoli Andrea 
Published: November 2018

We theoretically prove the existence in granular fluids of a thermal convection that is inherent in the sense that it is always present and has no thermal gradient threshold (convection occurs for all finite values of the Rayleigh number). More specifically, we study a gas of inelastic smooth hard disks enclosed in a rectangular region under a constant gravity field. The vertical walls act as energy sinks (i.e. inelastic walls that are parallel to gravity), whereas the other two walls are perpendicular to gravity and act as energy sources. We show that this convection is due to the combined action of dissipative lateral walls and a volume force (in this case, gravitation). Hence, we call it dissipative lateral walls convection (DLWC). Our theory, which also describes the limit case of elastic collisions, shows that inelastic particle collisions enhance the DLWC. We perform our study via numerical solutions (volume-element method) of the corresponding hydrodynamic equations in an extended Boussinesq approximation. We show that our theory describes the essentials of the results for similar (but more complex) laboratory experiments.
Geoarchaeological Study of Szálka and Vajda Kurgans (Great Hungarian Plain) Based on Radiocarbon and Geophysical Analyses
Authors: Tóth Csaba Albert , Prónay Zsolt , Braun Mihály , Nagy Péter , Pethe Mihály , Tildy Péter , Buró Botond , Kertész Titanilla , McIntosh Richard W , Molnár Mihály 
Published: November 2018

ABSTRACTTwo archaeologically unexplored mounds were studied in the area of the central Great Hungarian Plain. The age of the construction of the mounds was clarified on the basis of radiocarbon (14C) age determination of buried soil layers. Different, later-building phases of the mounds were detected by pedological and geo-electric analyses of the human-made layers. The age of the buried soils was corrected for the reservoir age of the recent soils found in the surroundings of the mounds. Radiocarbon ages of the carbon extracted from the soils at temperatures 400 and 800ºC were almost completely the same. Based on the calibrated ages of cal BP 4830–5270 (Szálka Mound) and cal BP 4880–5290 (Vajda Mound) of the buried soil layers, the identified kurgans were built by people of the Copper Age Yamnaya Culture. On the basis of the pedological and geophysical analysis of the layers, Szálka Mound and Vajda Mound were built in two and in three phases respectively from the chernozem-like humus-rich topsoil layers of the surrounding area. The former shallow quarry sites have been almost completely filled and cannot be identified at the foot of the mounds even using geodetic methods.
The development of a measure of root awareness to account for reading performance in the Arabic language: A development and validation study
Authors: TIBI SANA , TOCK JAMIE L. , KIRBY JOHN R. 
Published: November 2018

ABSTRACTMorphological awareness (MA) is an important predictor of reading outcomes in different languages. The consonantal root is a salient feature of Arabic lexical structure and critical to MA. The goals of this study were to (a) develop a measure of root awareness (RA) as one dimension of MA in Arabic, and (b) validate the RA measure by predicting reading outcomes in an Arabic population. A set of RA items was administered to 194 Arabic-speaking third-grade children. A one-factor model was specified using confirmatory factor analysis to examine the model fit of the RA measure. A structural equation model was then developed to examine the relation between the RA measure and important reading outcome measures including word reading, reading fluency, and reading comprehension. The results of these analyses indicated good model fit, and the RA measure accounted for a substantial portion of the variance in the outcomes. The establishment of the RA measure is an important preliminary step to efficiently assessing MA in Arabic and could serve as an integral tool for studying reading development.