bluuebunny/crossref_metadata_2025 huggingface dataset:
Benchmarking variant identification tools for plant diversity discovery
Authors: Wu Xing , Heffelfinger Christopher , Zhao Hongyu , Dellaporta Stephen L.
Published: September 2019

Background

The ability to accurately and comprehensively identify genomic variations is critical for plant studies utilizing high-throughput sequencing. Most bioinformatics tools for processing next-generation sequencing data were originally developed and tested in human studies, raising questions as to their efficacy for plant research. A detailed evaluation of the entire variant calling pipeline, including alignment, variant calling, variant filtering, and imputation was performed on different programs using both simulated and real plant genomic datasets.

Results

A comparison of SOAP2, Bowtie2, and BWA-MEM found that BWA-MEM was consistently able to align the most reads with high accuracy, whereas Bowtie2 had the highest overall accuracy. Comparative results of GATK HaplotypCaller versus SAMtools mpileup indicated that the choice of variant caller affected precision and recall differentially depending on the levels of diversity, sequence coverage and genome complexity. A cross-reference experiment of S. lycopersicum and S. pennellii reference genomes revealed the inadequacy of single reference genome for variant discovery that includes distantly-related plant individuals. Machine-learning-based variant filtering strategy outperformed the traditional hard-cutoff strategy resulting in higher number of true positive variants and fewer false positive variants. A 2-step imputation method, which utilized a set of high-confidence SNPs as the reference panel, showed up to 60% higher accuracy than direct LD-based imputation.

Conclusions

Programs in the variant discovery pipeline have different performance on plant genomic dataset. Choice of the programs is subjected to the goal of the study and available resources. This study serves as an important guiding information for plant biologists utilizing next-generation sequencing data for diversity characterization and crop improvement.
Forecasting maldistribution of human resources for healthcare and patients in Japan: a utilization-based approach
Authors: Ishikawa Tomoki , Nakao Yuji , Fujiwara Kensuke , Suzuki Teppei , Tsuji Shintaro , Ogasawara Katsuhiko
Published: September 2019

Background

Hokkaido’s demographic trend of population decrease with aging population is remarkable even in Japan. Although healthcare policy decision-makers need to appropriately allocate resources while grasping regional demands, not much is available on whether medical demand would increase or not for future. In addition, little is known about what impact will current situation have on future demand-supply balance and equality by regions. This study aims to support decision-making in human resource planning for coping with changing population structure by forecasting future demand, and evaluation those regional maldistributions.

Method

We set patients with acute myocardial infarction or cerebral stroke, and all medical care as study subjects and analyzed for 2015, 2025, and 2035 in Hokkaido and each Secondary Medical Care Area. We used a utilization-based approach to estimate the healthcare supply–demand balance in the future. Moreover, we evaluated the regional maldistribution of demand-supply balance by calculating Herfindahl-Hirschman Index, Gini Coefficients, the number of physicians/specialists per patient. Moreover, we conducted sensitivity analysis to evaluation impact on aspects of demand-supply balance by uncertainty of utilization for future.

Results

Our results displayed that concentration of patients will progress, while regional distribution will shrink in all subject. However, from comparison based on all medical care, Gini Coefficients of acute myocardial infarction and cerebral stroke has always been high. This suggest that the resource allocation of them has room for improvement. In addition, our analysis showed the change in this balance will differ in each region in the future. Moreover, demographic change will not consistent with the number of patient change from 2015 to 2035.

Conclusion

These results suggest policy planners should use the number of patient by disease, by region as indicator of demand, instead of provider-to-population ratios being in use today. The result of our sensitivity analysis show two findings. First, the range of each indicator have possible for future. Second, increase of utilization, for instance lowing barrier in the use by development operation of patient transportation in AMI/CS, would improve maldistribution of opportunity for resident to get emergency medical services.
Correction to: Nutraceutical approach for the management of cardiovascular risk – a combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: results from a randomized, double-blind, placebo-controlled study
Authors: Ruscica Massimiliano , Pavanello Chiara , Gandini Sara , Macchi Chiara , Botta Margherita , Dall’Orto Daria , Del Puppo Marina , Bertolotti Marco , Bosisio Raffaella , Mombelli Giuliana , Sirtori Cesare R. , Calabresi Laura , Magni Paolo
Published: September 2019

Following publication of the original article [1], the authors reported an error in the affiliation of the third author, Sara Gandini. The correct affiliation should read: Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Ventricular Zone Expressed PH Domain Containing 1 (VEPH1): an adaptor protein capable of modulating multiple signaling transduction pathways during normal and pathological development
Authors: Brown Theodore J. , Kollara Alexandra , Shathasivam Premalatha , Ringuette Maurice J.
Published: September 2019

Ventricular Zone Expressed PH Domain-Containing 1 (VEPH1) is an 833-amino acid protein encoded by an evolutionarily conserved single-copy gene that emerged with pseudocoelomates. This gene has no paralog in any species identified to date and few studies have investigated the function of its encoded protein. Loss of expression of its ortholog, melted, inDrosophilaresults in a severe neural phenotype and impacts TOR, FoxO, and Hippo signaling. Studies in mammals indicate a role for VEPH1 in modulating TGFβ signaling and AKT activation, while numerous studies indicate VEPH1 expression is altered in several pathological conditions, including cancer. Although often referred to as an uncharacterized protein, available evidence supports VEPH1 as an adaptor protein capable of modulating multiple signal transduction networks. Further studies are required to define these adaptor functions and the role of VEPH1 in development and disease progression.
Evaluation of median urinary iodine concentration cut-off for defining iodine deficiency in pregnant women after a long term USI in China
Authors: Zhang Huidi , Wu Meng , Yang Lichen , Wu Jinghuan , Hu Yichun , Han Jianhua , Gu Yunyou , Li Xiuwei , Wang Haiyan , Ma Liangkun , Yang Xiaoguang
Published: September 2019

Background

The WHO/UNICEF/ICCIDD define iodine deficiency during pregnancy as median urinary iodine concentration (MUIC) ≤ 150 μg/L. China implemented universal salt iodization (USI) in 1995, and recent surveillance showed nationwide elimination of iodine deficiency disorders (IDD). Data from 2014 showed that the MUIC in 19,500 pregnant women was 154.6 μg/L and 145 μg/L in 9000 pregnant women in 2015. However, symptoms of iodine deficiency were absent. Our study sought to evaluate whether MUIC below 150 μg/L affects thyroid function of Chinese pregnant women and their newborns in Chinese context.

Methods

We screened 103 women with normal thyroid function and MUIC lower than 150 μg/L during week 6 of pregnancy at Peking Union Medical College Hospital. Patient demographics and dietary salt intake were recorded. Subjects were followed at 12, 24, and 32 gestational weeks. At each visit, a 3-day dietary record, drinking water samples, and edible salt samples were collected and analyzed for total dietary iodine intake. Additionally, 24-h urine iodine and creatinine were measured. Blood tests assessed thyroid function in both mothers and newborns.

Results

Of 103 pregnant women enrolled, 79 completed all follow-up visits. Most subjects maintained normal thyroid function throughout pregnancy. However, 19 had thyroid dysfunction based on thyroid stimulating hormone and free thyroxine levels. The median serum iodine was 71 μg/L (95% CI: 44, 109). The median thyroglobulin was < 13 μg/L. values above this level indicate iodine deficiency in pregnant women. The median dietary iodine intake during pregnancy, derived from the 3-day record and measures of water and salt, was 231.17 μg/d. Assuming 90% urinary iodine excretion (UIE), 200.11 μg/d UIE means the 222.34 μg iodine loss per day, suggesting that subjects had a positive iodine balance throughout pregnancy. All neonatal blood samples showed TSH levels lower than 10 mIU/L, indicating normal thyroid function. No significant difference was found among gestational weeks for urinary iodine, and the MUIC in subjects who completed 3 follow-up visits was 107.41 μg/L.

Conclusion

Twenty years after implementing USI, expectant Chinese mothers with MUIC of 107.4 μg/L, less than the WHO’s 150 μg/L benchmark, maintained thyroid function in both themselves and their newborn babies.
Correction to: Inter and intra cultural variations of millet (Pennisetum glaucum (L.) R. Br) uses in Niger (West Africa)
Authors: Moussa Hamadou , Kindomihou Valentin , Houehanou Thierry D. , Soumana Idrissa , Souleymane Oumarou , Chaibou Mahamadou
Published: September 2019

Please note that following publication of the original article [1], Figs. 4, 5 and 6 in the article have been updated to remove oblique lines that were erroneously rendered in the figures.
Cancer-associated adipocytes: key players in breast cancer progression
Authors: Wu Qi , Li Bei , Li Zhiyu , Li Juanjuan , Sun Si , Sun Shengrong
Published: September 2019

Adipocytes are one of the primary stromal cells in many tissues, and they are considered to play an active role in the tumor microenvironment. Cancer-associated adipocytes (CAAs) are not only found adjacent to cancer cells, but also communicate with cancer cells through releasing various factors that can mediate local and systemic effects. The adipocyte-cancer cell crosstalk leads to phenotypical and functional changes of both cell types, which can further enhance tumor progression. Indeed, obesity, which is associated with an increase in adipose mass and an alteration of adipose tissue, is becoming pandemic in some countries and it is now considered to be an independent risk factor for cancer progression. In this review, we focus on the potential mechanisms involved with special attention to the adipocyte-cancer cell circle in breast cancer. We envisage that besides having a direct impact on tumor cells, CAAs systemically preconditions the tumor microenvironment by favoring anti-tumor immunity. A better understanding of cancer-associated adipocytes and the key molecular events in the adipocyte-cancer cell crosstalk will provide insights into tumor biology and permit the optimization of therapeutic strategies.
Antibody-drug conjugates in clinical trials for lymphoid malignancies and multiple myeloma
Authors: Yu Bo , Liu Delong
Published: September 2019

Antibody-drug conjugates (ADC) represent a distinct family of chemoimmunotherapy agents. ADCs are composed of monoclonal antibodies conjugated to cytotoxic payloads via specialized chemical linkers. ADCs therefore combine the immune therapy with targeted chemotherapy. Due to the distinct biomarkers associated with lymphocytes and plasma cells, ADCs have emerged as a promising treatment option for lymphoid malignancies and multiple myeloma. Several ADCs have been approved for clinical applications: brentuximab vedotin, inotuzumab ozogamicin, moxetumomab pasudotox, and polatuzumab vedotin. More novel ADCs are under clinical development. In this article, we summarized the general principles for ADC design, and updated novel ADCs under various stages of clinical trials for lymphoid malignancies and multiple myeloma.
Comparative outcomes of foot cast and short leg cast in pseudo‐Jones avulsion fracture: a single blinded randomized controlled trial
Authors: Piyapittayanun Peerapong , Mutthakalin Kanakij , Arirachakaran Alisara , Kongtharvonskul Jatupon
Published: September 2019

Background

Fractures of the metatarsal bones account for 35% of all foot fractures. Conservative management of fractures proximal to the metaphyseal‐diaphyseal junction of the fifth metatarsal bone (pseudo‐Jones) is by protected weight bearing. The methods of protected weight bearing include short‐leg casting and splinting (boot cast, Jones's bandage and elastic bandage). However, currently there is no consensus as to which method is the most suitable.

Method

We have conducted a randomized controlled trial to compare outcomes of foot casting (FC) and short leg casting (SLC) to assess pain, function and complication outcomes for the treatment of pseudo‐jones metatarsal fractures. This single‐center, single blind, randomized controlled trial was conducted between 1 June 2016–1 July 2018 at Police General Hospital, Bangkok, Thailand.

Result

A total of 72 pseudo‐jones metatarsal fracture participants were randomly allocated to treatment by foot cast or short leg cast. The primary outcomes were pain VAS, AOFAS and complications measured at 2, 4, 6 and 8 weeks after receiving the treatment. Seventy‐two patients (36 paticipants per group) were enrolled to receive either FC or SLC. The mean VAS measured at baseline, 2 weeks, 4 weeks, 6 weeks and 8 weeks were 7.36, 1.97, 0.58, 0.17 and 0.08 respectively in the FC group; and 6.09, 2.91, 1.23, 0.37 and 0.11 respectively in the SLC group. The mean AOFAS at baseline, 2, 4, 6 and 8 weeks were 33.60, 68.22, 82.72, 91.75 and 98.11 respectively in the FC group; and 32.60, 60.20, 70.20, 92.24 and 99.13 in the SLC group. The estimated mean difference of pain VAS and AOFAS at 2 weeks and 4 weeks were − 0.94 (95% CI: − 1.53, − 0.34), − 0.65 (95%CI: − 1.24, − 0.05), 8.02 (95%CI: 3.74, 12.10) and 12.52 (95%CI: 8.27, 16.78), which were statistically significantly better in the FC groups when compared to the SLC groups. However, there were no statistically significant difference between the two groups at 6 and 8 weeks.

Conclusion

This study demonstrated that the application of foot casting can improve pain VAS and AOFAS function at 2 and 4 weeks in the treatment of pseudo‐jones metatarsal fractures when compared to short leg casting. However, at 6 and 8 weeks, there were no statistically significantly different between the two groups.
A family pedigree of malignancies associated with BRCA1 pathogenic variants: a reflection of the state of art in China
Authors: Li Wenhui , Li Lei , Wu Ming
Published: September 2019

Background

Little is known about the status of genetic counseling for ovarian cancer in China.

Case presentation

We report a four-generation Chinese family with several types of cancer. The proband was a patient with high-grade serous ovarian cancer (HGSOC) who was found to harbor a pathogenic BRCA1 variant. Cosegregation analysis identified 7 of 9 relatives with the same deleterious variant. One month after the genetic test, one female carrier 54 years of age was diagnosed with stage IVB HGSOC, and another female 55 years of age accepted risk-reducing salpingo-oophorectomy, which revealed occult cancer of the fallopian tube (Stage IA).

Conclusions

Genetic counseling and testing for ovarian cancer in China have fallen behind international trends. Innovative studies and practices are urgently needed to establish models for cancer screening, prevention and treatment.
Modular pathway engineering of key precursor supply pathways for lacto-N-neotetraose production in Bacillus subtilis
Authors: Dong Xiaomin , Li Nan , Liu Zhenmin , Lv Xueqin , Li Jianghua , Du Guocheng , Wang Miao , Liu Long
Published: September 2019

Background

Lacto-N-neotetraose (LNnT) is one of the important ingredients of human milk oligosaccharides, which can enhance immunity, regulate intestinal bacteria and promote cell maturation.

Results

In this study, the synthetic pathway of LNnT was constructed by co-expressing the lactose permease (LacY) β-1,3-N-acetylglucosaminyltransferase (LgtA) and β-1,4-galactostltransferase (LgtB) in Bacillus subtilis, resulting in an LNnT titer of 0.61 g/L. Then, by fine-tuning the expression level of LgtB, the growth inhibition was reduced and the LNnT titer was increased to 1.31 g/L. In addition, by modular pathway engineering, the positive-acting enzymes of the UDP-GlcNAc and UDP-Gal pathways were strengthened to balance the two key precursors supply, and the LNnT titer was improved to 1.95 g/L. Finally, the LNnT titer reached 4.52 g/L in a 3-L bioreactor with an optimal glucose and lactose feeding strategy.

Conclusions

In general, this study showed that the LNnT biosynthesis could be significantly increased by optimizing enzymes expression levels and modular pathway engineering for balancing the precursors supply in B. subtilis.
Asymptomatic pharyngeal carriage rate of Streptococcus pyogenes, its associated factors and antibiotic susceptibility pattern among school children in Hawassa town, southern Ethiopia
Authors: Anja Asrat , Beyene Getenet , S/Mariam Zewdineh , Daka Deresse
Published: September 2019

Objectives

The aim of this study was to determine the asymptomatic pharyngeal carriage rate ofS. pyogenes, antimicrobial pattern and related risk factors among school children in Hawassa, southern Ethiopia.

Results

Out of 287 school children’s screened, 35 (12.2%) were colonized withS. pyogenes. The carriage rate was significantly associated with factors such as sex (female p = 0.013) occupational status of mother (p = 0.002), lower income source (500–900 ETB, 1000–1500 ETB) (p = 0.001, and p = 0.042), history of hospitalization (p = 0.00) and residence of the children (p = 0.002). High level resistant to tetracycline and low level to vancomycin were observed, while penicillin, amoxicillin, erythromycin, chloramphenicol, and ceftriaxone were found to be effective.
Stochastic bifurcation analysis in Brusselator system with white noise
Authors: Li Changzhao , Zhang Juan
Published: September 2019

In this paper, we mainly study the stochastic stability and stochastic bifurcation of Brusselator system with multiplicative white noise. Firstly, by a polar coordinate transformation and a stochastic averaging method, the original system is transformed into an Itô averaging diffusion system. Secondly, we apply the largest Lyapunov exponent and the singular boundary theory to analyze the stochastic local and global stability. Thirdly, by means of the properties of invariant measures, the stochastic dynamical bifurcations of stochastic averaging Itô diffusion equation associated with the original system is considered. And we investigate the phenomenological bifurcation by analyzing the associated Fokker–Planck equation. We will show that, from the view point of random dynamical systems, the noise “destroys” the deterministic stability. Finally, an example is given to illustrate the effectiveness of our analyzing procedure.
An effective computational approach based on Gegenbauer wavelets for solving the time-fractional Kdv-Burgers-Kuramoto equation
Authors: Secer Aydin , Ozdemir Neslihan
Published: September 2019

In this paper, our purpose is to present a wavelet Galerkin method for solving the time-fractional KdV-Burgers-Kuramoto (KBK) equation, which describes nonlinear physical phenomena and involves instability, dissipation, and dispersion parameters. The presented computational method in this paper is based on Gegenbauer wavelets. Gegenbauer wavelets have useful properties. Gegenbauer wavelets and the operational matrix of integration, together with the Galerkin method, were used to transform the time-fractional KBK equation into the corresponding nonlinear system of algebraic equations, which can be solved numerically with Newton’s method. Our aim is to show that the Gegenbauer wavelets-based method is efficient and powerful tool for solving the KBK equation with time-fractional derivative. In order to compare the obtained numerical results of the wavelet Galerkin method with exact solutions, two test problems were chosen. The obtained results prove the performance and efficiency of the presented method.
Treatment-Free Survival: A Novel Outcome Measure of the Effects of Immune Checkpoint Inhibition—A Pooled Analysis of Patients With Advanced Melanoma
Authors: Regan Meredith M. , Werner Lillian , Rao Sumati , Gupte-Singh Komal , Hodi F. Stephen , Kirkwood John M. , Kluger Harriet M. , Larkin James , Postow Michael A. , Ritchings Corey , Sznol Mario , Tarhini Ahmad A. , Wolchok Jedd D. , Atkins Michael B. , McDermott David F.
Published: September 2019

PURPOSE

Outcome measures that comprehensively capture attributes of immuno-oncology agents, including prolonged treatment-free time and persistent treatment-related adverse events (TRAEs), are needed to complement conventional survival end points.

METHODS

We pooled data from the CheckMate 067 and 069 clinical trials of nivolumab and ipilimumab, as monotherapies or in combination, for patients with advanced melanoma. Treatment-free survival (TFS) was defined as the area between Kaplan-Meier curves for two conventional time-to-event end points, each defined from random assignment: time to immune checkpoint inhibitor (ICI) protocol therapy cessation and time to subsequent systemic therapy initiation or death. TFS was partitioned as time with and without toxicity by a third end point, time to cessation of both ICI therapy and toxicity. Toxicity included persistent and late-onset grade 3 or higher TRAEs. The area under each Kaplan-Meier curve was estimated by the 36-month restricted mean time.

RESULTS

At 36 months, many of the 1,077 patients who initiated ICI therapy were surviving free of subsequent therapy initiation (47% nivolumab plus ipilimumab, 37% nivolumab, 15% ipilimumab). The restricted mean TFS was longer for nivolumab plus ipilimumab (11.1 months) compared with nivolumab (4.6 months; difference, 6.5 months; 95% CI, 5.0 to 8.0 months) or ipilimumab (8.7 months; difference, 2.4 months; 95% CI, 0.8 to 4.1 months); restricted mean TFS represented 31% (3% with and 28% without toxicity), 13% (1% and 11%), and 24% (less than 1% and 23%) of the 36-month period, respectively, in the three treatment groups. TFS without toxicity was longer for nivolumab plus ipilimumab than nivolumab (difference, 6.0 months) or ipilimumab (difference, 1.7 months).

CONCLUSION

The analysis of TFS between ICI cessation and subsequent therapy initiation revealed longer TFS without toxicity for patients with advanced melanoma who received nivolumab plus ipilimumab compared with nivolumab or ipilimumab. Regardless of treatment, a small proportion of the TFS involved grade 3 or higher TRAEs.
Morphology-dependent random binary fragmentation of in silico fractal-like agglomerates
Authors: Drossinos Y. , Melas A. D. , Kostoglou M. , Isella L.
Published: September 2019

Linear binary fragmentation of synthetic fractal-like agglomerates composed of spherical, equal-size, touching monomers is numerically investigated. Agglomerates of different morphologies are fragmented via random bond removal. The fragmentation algorithm relies on mapping each agglomerate onto an adjacency matrix. The numerically determined fragment size distributions are U-shaped, clusters break predominantly into two largely dissimilar fragments, becoming more uniform as the fractal dimension decreases. A symmetric beta distribution reproduces the fragment distribution rather accurately. Its exponent depends on the structure (fractal dimension) and number of monomers of the initial agglomerate. A universal fragment distribution, a function only of the initial fractal dimension, is derived by requiring that it satisfy the fragmentation conversation laws and the straight-chain limit. We argue that the fragmentation rate is proportional to the initial agglomerate size.
Text as Data
Authors: Gentzkow Matthew , Kelly Bryan , Taddy Matt
Published: September 2019

An ever-increasing share of human interaction, communication, and culture is recorded as digital text. We provide an introduction to the use of text as an input to economic research. We discuss the features that make text different from other forms of data, offer a practical overview of relevant statistical methods, and survey a variety of applications. (JEL C38, C55, L82, Z13)
What Can Be Learned from Spatial Economics?
Authors: Proost Stef , Thisse Jacques-François
Published: September 2019

Spatial economics aims to explain why there are peaks and troughs in the spatial distribution of wealth and people, from the international and regional to the urban and local. The main task is to identify the microeconomic underpinnings of centripetal forces, which lead to the concentration of economic activities, and centrifugal forces, which bring about the dispersion of economic activities at the regional and urban levels. Transportation matters at both scales, but in a different way. The emphasis is on the interregional flows of goods and passenger trips at the regional level and on individual commuting at the urban level. ( JEL F12, L13, R12, R23, R30, R40)
Society and Economy: Frameworks and Principles: A Book Review
Authors: Goyal Sanjeev
Published: September 2019

Mark Granovetter has written a deep and wide-ranging book on economy and society entitled Society and Economy: Frameworks and Principles. Economists, in particular, will find his discussion on the role of social networks in understanding the problem of aggregation—from micro foundations to large-scale institutional phenomena—especially relevant. And they will find much to ponder over the ways in which overlapping structures—of networks and institutions—shape human behavior and determine aggregate economic outcomes. The high-level and parsimonious style of this book is distinctive and sets it apart from much of contemporary social science. This style and the apparent unwillingness to engage closely with research developments over the past two decades may, however, mean that the book will have limited influence on ongoing and future research. (JEL D02, D90, Z13)
An illustration of how responsive feedback in a social marketing tobacco control intervention in Ghana enabled managers to make decisions that increased intervention effectiveness
Authors: Agha Sohail , Paullin Jean
Published: September 2019

This report illustrates how a feedback loop, set up to provide data and insights to a donor and designers/implementers of a social marketing tobacco prevention intervention in Ghana, helped adapt the original design of the intervention to one that was more suited to the social and media contexts of Ghana. The designers/implementers had previously, successfully implemented a tobacco control intervention with adolescents in Botswana. This experience had informed the initial intervention design in Ghana. As the feedback generated by evaluators started demonstrating just how different the Ghanaian social and media contexts were from the Botswanan one, implementers started making changes to their selection of channels, resulting in a design which was quite different from the original one. The close involvement of the donor in this process enabled implementers to make rapid changes to the design of the intervention. This illustration adds to a small but growing literature establishing the importance of feedback loops to improve the design and implementation of development interventions.
Pathogenic FAM83G palmoplantar keratoderma mutations inhibit the PAWS1:CK1α association and attenuate Wnt signalling.
Authors: Wu Kevin Z.L. , Jones Rebecca A. , Tachie-Menson Theresa , Macartney Thomas J. , Wood Nicola T. , Varghese Joby , Gourlay Robert , Soares Renata F. , Smith James C. , Sapkota Gopal P.
Published: September 2019

Background: Two recessive mutations in the FAM83G gene, causing A34E and R52P amino acid substitutions in the DUF1669 domain of the PAWS1 protein, are associated with palmoplantar keratoderma (PPK) in humans and dogs respectively. We have previously reported that PAWS1 associates with the Ser/Thr protein kinase CK1α through the DUF1669 domain to mediate canonical Wnt signalling.

Methods: Co-immunoprecipitation was used to investigate possible changes to PAWS1 interactors caused by the mutations. We also compared the stability of wild-type and mutant PAWS1 in cycloheximide-treated cells. Effects on Wnt signalling were determined using the TOPflash luciferase reporter assay in U2OS cells expressing PAWS1 mutant proteins. The ability of PAWS1 to induce axis duplication in Xenopus embryos was also tested. Finally, we knocked-in the A34E mutation at the native gene locus and measured Wnt-induced AXIN2 gene expression by RT-qPCR.

Results: We show that these PAWS1A34E and PAWS1R52P mutants fail to interact with CK1α but, like the wild-type protein, do interact with CD2AP and SMAD1. Like cells carrying a PAWS1F296A mutation, which also abolishes CK1α binding, cells carrying the A34E and R52P mutants respond poorly to Wnt signalling to an extent resembling that observed in FAM83G gene knockout cells. Consistent with this observation, these mutants, in contrast to the wild-type protein, fail to induce axis duplication in Xenopus embryos. We also found that the A34E and R52P mutant proteins are less abundant than the native protein and appear to be less stable, both when overexpressed in FAM83G-knockout cells and when knocked-in at the native FAM83G locus. Ala34 of PAWS1 is conserved in all FAM83 proteins and mutating the equivalent residue in FAM83H (A31E) also abolishes interaction with CK1 isoforms.

Conclusions: We propose that mutations in PAWS1 cause PPK pathogenesis through disruption of the CK1α interaction and attenuation of Wnt signalling.
ω-Circularity of Yablo's Paradox
Authors: Çevik Ahmet
Published: September 2019

In this paper, we strengthen Hardy’s [1995] and Ketland’s [2005] arguments on the issues surrounding the self-referential nature of Yablo’s paradox [1993]. We first begin by observing that Priest’s [1997] construction of the binary satisfaction relation in revealing a fixed point relies on impredicative definitions. We then show that Yablo’s paradox is ‘ω-circular’, based on ω-inconsistent theories, by arguing that the paradox is not self-referential in the classical sense but rather admits circularity at the least transfinite countable ordinal. Hence, we both strengthen arguments for the ω-inconsistency of Yablo’s paradox and present a compromise solution of the problem emerged from Yablo’s and Priest’s conflicting theses.
A view from the acute hospital: managing patients with alcohol problems
Authors: Pang David , Duffield Pete , Day Ed
Published: September 2019

Regular heavy consumption of alcohol is associated with a wide range of physical, psychological and social problems. All health-care clinicians should be able to screen for and detect problematic levels of alcohol consumption in their patients, and deliver an effective brief intervention. When patients with alcohol dependence are admitted to hospital there must be an assessment of whether medication is required to prevent withdrawal symptoms and potential delirium tremens and withdrawal seizures. Medically assisted alcohol withdrawal using a long-acting benzodiazepine such as chlordiazepoxide should be carefully monitored and titrated to effect, and the clinician should be aware of the risk of Wernicke–Korsakoff syndrome and other complications. Abstinence from alcohol is usually only the first step in treatment, and effective linkage to community alcohol services is an important step.
Acute thrombocytopenia: picking a way through a paucity of platelets
Authors: Musson E Nuttall , Lomas O , Murphy MF
Published: September 2019

Thrombocytopenia is defined as a platelet count under 150x109/litre. It may be found as a bystander to other pathology or directly related to an underlying haematological condition. Apart from laboratory artefact, it should be treated seriously as it often reflects serious underlying disease. This review uses short case histories to illustrate how to approach thrombocytopenia during the initial presentation of an adult patient to hospital. This article guides the general hospital physician through the narrow but potentially confusing differential diagnoses related to thrombocytopenia, with particular focus on immune thrombocytopenia, disseminated intravascular coagulation and thrombotic thrombocytopenic purpura. Thrombocytopenia in pregnancy deserves special consideration and will not be discussed in this article.
Tuning of the Wavelet Filters for the IMU Data Based on the PDC Method and the GPS Solution in a Bi-Dimensional Navigation Application
Authors: ADOCHIEI Ioana Raluca , GRIGORIE Teodor Lucian , ADOCHIEI Felix Constantin
Published: September 2019

The degradation of navigation accuracy and integrity of GPS in the presence of radio frequency interference, hostile jamming and high dynamical situations, when the satellite signals may get lost due to signal blockage, led to the development of MEMS-INS/GPS integrated navigation systems for various applications of the positioning and navigation technologies. Unfortunately, the short-term advantages brought by the INS systems are overshadowed by their imprecise operation over the long term, mainly due to inertial sensor errors. A critical component of the inertial sensors errors is the noise. To improve the quality of the inertial sensors data, many denoising techniques have been used. Wavelet method has been proven as a useful tool for signal analysis, and it is widely used in signal processing and denoising applications. The here proposed technique is based on a time-frequency approach previously applied in bio-signals processing. In the proposed mechanism, the inertial sensors signals are processed analysed by using an extended version of the Wavelet transform. The optimal levels of decomposition are established for the wavelet filters, based on the evaluation of a parameter called coupling level (CL). It characterizes the coupling dynamics information between the reference signals, provided by a GPS, and the perturbed signal, which are the outputs of the inertial navigation system (INS). The proposed tuning method is experimentally tested in a bi-dimensional navigation application.
Assessment of Mechanical Properties of Biocomposite Material by using Sawdust and Rice Husk
Authors: SINGH Prabhat , SINGH Bhagel
Published: September 2019

This paper presents an experimental study on the development of biocomposite material by using sawdust (SD) and rice husk (RH). The use of composite in the present production has increased dramatically since the 1970’s. Traditional material like aluminum, steel, iron and copper etc. may be easily replaced by using this classical biocomposites. The tensile test, hardness and tear resistance test were conducted in a Universal testing machine as per ASTM D638, ASTM D2240 and ASTM D1004 standard, respectively. Although commercial industries have increasingly been concerned with the low cost, light weight and eco-friendly material, the biocomposite material has also a great potential for reduced production cost and low maintenance which have proven to be a main factor in a push towards recycled biocomposites. In this paper we have fabricated a biocomposite model from materials like sawdust, rice husk. The main reason to use biocomposites is that they are more economical and have high strength to weight ratio compared to glass fibers. Hence fabricated material can be used for various applications.
Evaluation of the metabolism properties of choline kinase alpha in neoplasms of the parathyroid glands. A pilot study
Authors: Mokrysheva Natalia G. , Voronkova Iya A. , Krupinova Julia A. , Dolgushin Mikhail B. , Gurevch Larisa E. , Odzharova Akgul A. , Kuznetsov Sergey N. , Kryukova Irina V.
Published: September 2019

BACKGROUND: Primary hyperparathyroidism (PHPT) is a widespread endocrine disease characterized by excessive production of parathyroid hormone (PTH) due to parathyroid gland hyperplasia (PGH) or tumor lesions (adenoma or cancer of the parathyroid gland (PG) in 80% and 15% of cases respectively). Choline kinase alpha (XK) overexpression is described in tumors of different localization, but there is no data on its expression in PG tumors.
AIMS: To study the character of XK expression in PG neoplasms and its relationship with clinical, laboratory, and visualization characteristics (positron emission tomography combined with computed tomography (PET/CT) with 18Ffluorocholine (18FFC)).
MATERIALS AND METHODS: The material for the study was based on tissue samples from 10 patients of 3470 years old (Me = 61.5; [48; 66]), with a laboratoryconfirmed diagnosis of PHT. An immunohistochemical study (IHC) was carried out on materials from 2 patients with hyperplasia of the main cells, from 5 patients with adenoma of PG, from 1 patient with atypical adenoma and 1 with carcinoma of PG; in 1 case the metastasis of cancer of the neck with lymph node was examined.
RESULTS: The expression of XK is spotted in all types of PG cells (chief cells: active and inactive forms), transitional forms between the chief cells and oxyphil; oxyphil cells, but it was most intense in active chief cells. The expression of XK was observed in neoplasms of PG of various degrees of malignancy. In the most numerous group of PG formations with a favorable prognosis (11 samples from 7 patients), no statistically significant correlation (p 0.05) was obtained between the intensity expression of the XK, of the PTH and the proliferative activity index Ki67, the level of radiopharmaceutical accumulation in PET/CT with 18FFC (SUVmax) and laboratory data (PTH, Ca, Ca++).
CONCLUSIONS: In the majority of investigated cases, moderate and intensive expression of the XK was detected in PG cells. A small amount of studied cases does not allow us to identify the connection between the intensity of XK expression and the malignant potential for the formation of PG.
Conhecimento tradicional dos pescadores sobre o comportamento reprodutivo dos peixes em um lago de inundação no Oeste do Pará, Brasil
Authors: Serrão Elizabete de Matos , Braga Tony Marcos Porto , Côelho Yana Karine Silva , Campos Diego Patrick Fróes , Santos Anderson Araújo , Imbiriba Luan Campos , Zacardi Diego Maia
Published: September 2019

O conhecimento tradicional refere-se ao conhecimento acumulado de práticas, experiências e crenças de grupos ou indivíduos sobre seu ambiente natural. No presente trabalho foi analisado o conhecimento tradicional que os pescadores possuem sobre o comportamento reprodutivo de dez principais espécies de peixes capturadas na região do Maicá, Santarém-Pará. Foram entrevistados 88 pescadores que possuíam dez ou mais anos de experiência de pesca na região, utilizando para isso formulários padronizados e semiestruturados, entre os meses de março e dezembro de 2017. O conhecimento dos pescadores da região do Maicá se mostrou consistente, detalhado e condizente com a literatura científica. Informações descritas e para as quais não foram encontradas referenciais teóricos ou que diferiram da literatura científica, podem gerar hipóteses para futuros estudos científicos locais. Com isso é aconselhável que os gestores dos recursos pesqueiros reconheçam e levem em consideração o Conhecimento tradicional desses pescadores e o incorporem em estudos futuros que possam contribuir na elaboração do plano de manejo e na gestão pesqueira da APA-Maicá após sua regulamentação.
Kapasitas Kelembagaan Dalam Pembinaan Usaha Mikro Kecil Dan Menengah Di Kota Surakarta
Authors: Sukoco Johan Bhimo
Published: September 2019

Micro-, Small-, and Medium-Scale Enterprises (SMEs) building is often due to the weak institutional capacity. Limited capital ownership, poor business knowledge, and narrow business network make SME performers less powerful in improving their business. This research studied the SMEs building in Surakarta City, viewed from indicator of empowerment according to Mardikanto (2013), Institutional Building. This research employed a descriptive qualitative method. Data collection was carried out using interview, observation, and document analysis. Technique of analyzing data used was purposive sampling, data validation was carried out using method triangulation, and data analysis was conducted using an interactive model of analysis. The result of research showed that institutional capacity of SMEs in Surakarta City was still weak. SMEs performers (actors) still understood poorly the procedure and requirement of business licensing. This made them dealing with business licensing reluctantly, leading to the weak business institution.  Pembinaan Usaha Mikro Kecil dan Menengah (UMKM) seringkali dikarenakan lemahnya kapasitas kelembagaan. Kepemilikan modal yang minim, pengetahuan usaha yang rendah, serta kurang luasnya jejaring usaha membuat pelaku UMKM menjadi kurang berdaya dalam meningkatkan usahanya. Penelitian ini mengkaji pembinaan UMKM di Kota Surakarta dilihat dari indikator pemberdayaan menurut Mardikanto (2010), yaitu Bina Kelembagaan. Penelitian ini menggunakan metode deskriptif kualitatif. Pengumpulan data menggunakan wawancara, observasi, dan analisis dokumen. Teknik pengumpulan data menggunakan purposive sampling, validitas data menggunakan triangulasi metode, dan analisis data menggunakan analisis interaktif. Hasil penelitian menunjukkan kapasitas kelembagaan UMKM di Kota Surakarta masih lemah. Pelaku UMKM masih kurang memahami prosedur dan persyaratan perizinan usaha. Hal ini mengakibatkan pelaku UMKM enggan melakukan pengurusan perizinan usaha yang berakibat lemahnya kelembagaan usaha.
Analisis Faktor-Faktor Yang Memengaruhi Kepuasan Pengguna Layanan Go-Ride (Studi Pada Mahasiswa Fakultas Ilmu Sosial Dan Ilmu Politik Universitas Diponegoro)
Authors: Puspitasari Septi , Widayanto Widayanto
Published: September 2019

This research aims to determine factor which the biggest contribution to satisfaction Go-Ride service users. Satisfaction was measured by five initial factors, service quality, price, perceived ease, perceived usefulness and online servicescape. This type research is explanatory research. The sampling technique non probability sampling with purposive sampling and accidental sampling. Samples taken 100 respondents using Go-Ride services in Undip FISIP. The results showed form five variables with 65 indicators only 24 indicators met the value KMO MSA and can be factor analysis, total variance explaned and rotated component matrix forms three components, hereinafter referred service quality, perceived ease and perceived usefulness, regression test stages shows service quality, perceived ease, perceived usefulness partially and simultaneously have positive and significant influence user satisfaction, perceived usefulness was dominant influence user satisfaction. Researcher suggestions to improve service quality, especially responsiveness service, implementation the most effective route selection according user's wishes, implementation reference coupon strategy.
Variasi Sifat Kimia Tanah Pada Sistem Agroforestri di Kawasan Hutan Tanaman Kayu Putih
Authors: Sadono Ronggo , Soeprijadi Djoko , Wirabuana Pandu Yudha Adi Putra
Published: September 2019

Sifat kimia tanah berperan penting dalam mendukung pertumbuhan dan perkembangan tanaman. Sifat kimia tanah dipengaruhi oleh tipe penggunaan lahan dan jenis vegetasi di atasnya. Perbedaan sifat kimia tanah dapat berpengaruh terhadap laju pertumbuhan tanaman sehingga menghasilkan variasi tingkat produktivitas. Penelitian ini mengkaji variasi sifat kimia tanah sebagai dampak pengembangan sistem agroforestri di hutan tanaman kayu putih. Lokasi penelitian terletak di Resort Pengelolaan Hutan Gubugrubuh, Kabupaten Gunungkidul. Sampel tanah dikumpulkan dari 3 petak yang menjadi prioritas penanaman kayu putih yaitu petak 75, petak 78, dan petak 80. Sampel tanah diambil dari lapisan permukaan pada kedalaman 0-15 cm. Indikator sifat kimia tanah yang diuji meliputi pH tanah, C-organik, N-total, P-tersedia, K-total, dan kapasitas pertukaran kation (KPK). Perbandingan sifat kimia tanah dari setiap petak dianalisis menggunakan metode One Way ANOVA (α=0,05) dan dilanjutkan HSD Tukey (α=0,05). Hasil penelitian menunjukkan kemasaman tanah pada setiap petak termasuk kategori agak masam dengan pH 6,00-6,50. Kandungan C-organik bervariasi antara 1,67-3,30%. Nilai N-total berkisar antara 0,13-0,18% sedangkan P-tersedia mencapai 1,50-6,50 ppm. Kadar K-total dan KPK termasuk kategori rendah dengan rentang nilai masing-masing 0,07-0,38 cmolc/kg dan 6,89-13,66 cmolc/kg. Penelitian ini menemukan bahwa N-total merupakan parameter sifat kimia tanah yang berbeda secara signifikan dari setiap petak (p<0,05).
Multikriteria Analisis dalam Pemilihan Alat Pengumpul Sampah dengan Pembobotan Kombinasi Hasil Analysis Hierarchy Process (AHP) dan Time Motion Study (TMS)
Authors: Chaerul Mochammad , Rahmania Syiffa
Published: September 2019

Pengumpulan sampah merupakan salahsatu tahapan dalam suatu sistem pengelolaan sampah suatu kota. Efektifitas dan efisiensi pengumpulan sampah dipengaruhi oleh jenis alat yang digunakan. Pemilihan alat pengumpul sampah dipengaruhi oleh berbagai macam kriteria. Salahsatu metode multikriteria analisis yang paling sering digunakan adalah Analysis Hierarchy Process (AHP).  Multikriteria tersebut bukan saja terbatas pada aspek teknis dan non-teknis semata tetapi juga aspek operasional masing-masing alat yang dapat didekati dengan metode Time Motion Study (TMS). Di banyak kasus, kedua metode multikriteria tersebut digunakan secara terpisah dan berdiri sendiri. Paper ini mencoba menggabungkan kedua metode tersebut untuk memilih 3 (tiga) alternatif alat pengumpul sampah, yaitu: gerobak, becak motor, dan truk yang digunakan di Kota Payakumbuh, Sumatera Barat sebagai studi kasus. Untuk aplikasi metode AHP, dipilih kelompok responden masyarakat, petugas pengumpul sampah, pemerintah dan akademisi dengan mempertimbangkan kriteria teknis, sosial, ekonomi, dan lingkungan. Penilaian rerata global dari seluruh kelompok responden menempatkan gerobak sebagai alat terbaik dengan nilai 0,381, dibandingkan becak motor (0,356) dan truk (0,263). Sedangkan dengan metode TMS, yang mempertimbangkan keseluruhan tahapan operasional masing-masing alat pengumpul sampah didapat nilai kecepatan dan efisiensi pengumpulan sampah tertinggi adalah untuk becak motor, yaitu masing-masing sebesar 56,32 m/menit dan 49,53 kg/menit, dibandingkan untuk truk dan gerobak. Penggabungan metode AHP dan TMS dilakukan dengan cara memberikan bobot untuk masing-masing parameter dari hasil kedua metode tersebut yang telah dinormalisasi. Urutan prioritas alat pengumpul yang terbaik bisa saja berbeda ketika bobot masing-masing parameter tersebut dirubah. Penggabungan kedua metode tersebut menghasilkan pilihan yang lebih baik dan dapat dijadikan sebagai pertimbangan bagi pengambil keputusan sehingga dapat diperoleh alat pengumpul sampah yang dianggap lebih efektif dan efisien, terutama dalam mendukung tercapainya universal akses di sektor persampahan.