bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of STAT3 signaling pathway in breast cancer
Authors: Ma Jia-hui , Qin Li , Li Xia
Published: February 2020

Breast cancer has grown to be the second leading cause of cancer-related deaths in women. Only a few treatment options are available for breast cancer due to the widespread occurrence of chemoresistance, which emphasizes the need to discover and develop new methods to treat this disease. Signal transducer and activator of transcription 3 (STAT3) is an early tumor diagnostic marker and is known to promote breast cancer malignancy. Recent clinical and preclinical data indicate the involvement of overexpressed and constitutively activated STAT3 in the progression, proliferation, metastasis and chemoresistance of breast cancer. Moreover, new pathways comprised of upstream regulators and downstream targets of STAT3 have been discovered. In addition, small molecule inhibitors targeting STAT3 activation have been found to be efficient for therapeutic treatment of breast cancer. This systematic review discusses the advances in the discovery of the STAT3 pathways and drugs targeting STAT3 in breast cancer.
Correction to: Effects of probiotics on type II diabetes mellitus: a meta-analysis
Authors: Tao Yun-Wen , Gu Ying-Luo , Mao Xin-Qi , Zhang Lei , Pei Yu-Fang
Published: February 2020

Following publication of the original article [1], the authors reported an error in one of the author names. In this Correction the incorrect and correct author names are listed.
NoncoRNA: a database of experimentally supported non-coding RNAs and drug targets in cancer
Authors: Li Lulu , Wu Pengfei , Wang Zhenyu , Meng Xiangqi , Zha Caijun , Li Ziwei , Qi Tengfei , Zhang Yangong , Han Bo , Li Shupeng , Jiang Chuanlu , Zhao Zheng , Cai Jinquan
Published: February 2020

NoncoRNA (http://www.ncdtcdb.cn:8080/NoncoRNA/) is a manually curated database of experimentally supported non-coding RNAs (ncRNAs) and drug target associations that aim to potentially provide a high-quality data resource for exploring drug sensitivity/resistance-related ncRNAs in various human cancers. ncRNA are RNA molecular that do not encode proteins, but are involved in gene regulation and cellular functions in variety of human diseases, including neurodegenerative diseases and cancers. Here, we developed NoncoRNA which contained 8233 entries between 5568 ncRNAs and 154 drugs in 134 cancers. Each entry in the NoncoRNA contains detailed information on the ncRNAs, drugs, and cancers, the ncRNA expression pattern and experimental detection techniques, drug response and other targets, literature references, and other information. NoncoRNA offers a user-friendly, open access web interface to easily browse, search, and download data. NoncoRNA also provides a submission page for researchers to submit newly validated ncRNA-drug-cancer associations. NoncoRNA might serve as an immeasurable resource for understanding the roles of ncRNAs in cancer therapy.
Chronic whipworm infection exacerbates Schistosoma mansoni egg-induced hepatopathology in non-human primates
Authors: Le Loc , Khatoon Sabiha , Jiménez Paola , Peterson Christopher , Kernen Rebecca , Zhang Weidong , Molehin Adebayo J. , Lazarus Samra , Sudduth Justin , May Jordan , Karmakar Souvik , Rojo Juan U. , Ahmad Gul , Torben Workineh , Carey David , Wolf Roman F. , Papin James F. , Siddiqui Afzal A.
Published: February 2020

Background

Schistosomiasis continues to inflict significant morbidity and mortality in the tropical and subtropical regions of the world. The disease endemicity overlaps with the transmission of other parasitic diseases. Despite the ubiquity of polyparasitism in tropical regions, particularly in rural communities, little is known about the impact of multiple helminth infections on disease progression. In this pilot study, we describe the influence of chronic Trichuris trichiura infection on Schistosoma mansoni egg-induced hepatopathology in infected baboons.

Methods

Baboons with or without underlying whipworm infection were challenged with S. mansoni cercariae to establish schistosomiasis. Adult S. mansoni worms were recovered by perfusion and enumerated, hepatic granulomas were quantified via light microscopy, and transcriptional profiling of tissues were completed using RNA sequencing technologies.

Results

Co-infection with both S. mansoni and T. trichiura resulted in higher female schistosome worm burden and significantly larger liver granuloma sizes. Systems biology analyses of peripheral blood mononuclear cells (PBMC) revealed pathways associated with increased liver damage in co-infected baboons.

Conclusions

Underlying chronic whipworm infection intensified schistosome egg-induced liver pathology in infected baboons. RNA-Seq analysis provided insight into pathways associated with increased liver damage, corroborating histological findings.
Single-cell transcriptome analysis reveals TOX as a promoting factor for T cell exhaustion and a predictor for anti-PD-1 responses in human cancer
Authors: Kim Kyungsoo , Park Seyeon , Park Seong Yong , Kim Gamin , Park Su Myeong , Cho Jae-Won , Kim Da Hee , Park Young Min , Koh Yoon Woo , Kim Hye Ryun , Ha Sang-Jun , Lee Insuk
Published: February 2020

Background

T cells exhibit heterogeneous functional states in the tumor microenvironment. Immune checkpoint inhibitors (ICIs) can reinvigorate only the stem cell-like progenitor exhausted T cells, which suggests that inhibiting the exhaustion progress will improve the efficacy of immunotherapy. Thus, regulatory factors promoting T cell exhaustion could serve as potential targets for delaying the process and improving ICI efficacy.

Methods

We analyzed the single-cell transcriptome data derived from human melanoma and non-small cell lung cancer (NSCLC) samples and classified the tumor-infiltrating (TI) CD8+ T cell population based on PDCD1 (PD-1) levels, i.e., PDCD1-high and PDCD1-low cells. Additionally, we identified differentially expressed genes as candidate factors regulating intra-tumoral T cell exhaustion. The co-expression of candidate genes with immune checkpoint (IC) molecules in the TI CD8+ T cells was confirmed by single-cell trajectory and flow cytometry analyses. The loss-of-function effect of the candidate regulator was examined by a cell-based knockdown assay. The clinical effect of the candidate regulator was evaluated based on the overall survival and anti-PD-1 responses.

Results

We retrieved many known factors for regulating T cell exhaustion among the differentially expressed genes between PDCD1-high and PDCD1-low subsets of the TI CD8+ T cells in human melanoma and NSCLC. TOX was the only transcription factor (TF) predicted in both tumor types. TOX levels tend to increase as CD8+ T cells become more exhausted. Flow cytometry analysis revealed a correlation between TOX expression and severity of intra-tumoral T cell exhaustion. TOX knockdown in the human TI CD8+ T cells resulted in downregulation of PD-1, TIM-3, TIGIT, and CTLA-4, which suggests that TOX promotes intra-tumoral T cell exhaustion by upregulating IC proteins in cancer. Finally, the TOX level in the TI T cells was found to be highly predictive of overall survival and anti-PD-1 efficacy in melanoma and NSCLC.

Conclusions

We predicted the regulatory factors involved in T cell exhaustion using single-cell transcriptome profiles of human TI lymphocytes. TOX promoted intra-tumoral CD8+ T cell exhaustion via upregulation of IC molecules. This suggested that TOX inhibition can potentially impede T cell exhaustion and improve ICI efficacy. Additionally, TOX expression in the TI T cells can be used for patient stratification during anti-tumor treatments, including anti-PD-1 immunotherapy.
Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors
Authors: Smith Christopher G. , Moser Tina , Mouliere Florent , Field-Rayner Johanna , Eldridge Matthew , Riediger Anja L. , Chandrananda Dineika , Heider Katrin , Wan Jonathan C. M. , Warren Anne Y. , Morris James , Hudecova Irena , Cooper Wendy N. , Mitchell Thomas J. , Gale Davina , Ruiz-Valdepenas Andrea , Klatte Tobias , Ursprung Stephan , Sala Evis , Riddick Antony C. P. , Aho Tevita F. , Armitage James N. , Perakis Samantha , Pichler Martin , Seles Maximilian , Wcislo Gabriel , Welsh Sarah J. , Matakidou Athena , Eisen Tim , Massie Charles E. , Rosenfeld Nitzan , Heitzer Ellen , Stewart Grant D.
Published: February 2020

Background

Cell-free tumor-derived DNA (ctDNA) allows non-invasive monitoring of cancers, but its utility in renal cell cancer (RCC) has not been established.

Methods

Here, a combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n = 91) with various renal tumor subtypes, were used to determine ctDNA content in plasma and urine.

Results

Our data revealed lower plasma ctDNA levels in RCC relative to other cancers of similar size and stage, with untargeted detection in 27.5% of patients from both cohorts. A sensitive personalized approach, applied to plasma and urine from select patients (n = 22) improved detection to ~ 50%, including in patients with early-stage disease and even benign lesions. Detection in plasma, but not urine, was more frequent amongst patients with larger tumors and in those patients with venous tumor thrombus.

With data from one extensively characterized patient, we observed that plasma and, for the first time, urine ctDNA may better represent tumor heterogeneity than a single tissue biopsy. Furthermore, in a subset of patients (n = 16), longitudinal sampling revealed that ctDNA can track disease course and may pre-empt radiological identification of minimal residual disease or disease progression on systemic therapy. Additional datasets will be required to validate these findings.

Conclusions

These data highlight RCC as a ctDNA-low malignancy. The biological reasons for this are yet to be determined. Nonetheless, our findings indicate potential clinical utility in the management of patients with renal tumors, provided improvement in isolation and detection approaches.
Perspectives in fluid biomarkers in neurodegeneration from the 2019 biomarkers in neurodegenerative diseases course—a joint PhD student course at University College London and University of Gothenburg
Authors: Obrocki Pawel , Khatun Ayesha , Ness Deborah , Senkevich Konstantin , Hanrieder Jörg , Capraro Federica , Mattsson Niklas , Andreasson Ulf , Portelius Erik , Ashton Nicholas J. , Blennow Kaj , Schöll Michael , Paterson Ross W. , Schott Jonathan M. , Zetterberg Henrik
Published: February 2020

Until relatively recently, a diagnosis of probable Alzheimer’s disease (AD) and other neurodegenerative disorders was principally based on clinical presentation, with post-mortem examination remaining a gold standard for disease confirmation. This is in sharp contrast to other areas of medicine, where fluid biomarkers, such as troponin levels in myocardial infarction, form an integral part of the diagnostic and treatment criteria. There is a pressing need for such quantifiable and easily accessible tools in neurodegenerative diseases.

In this paper, based on lectures given at the 2019 Biomarkers in Neurodegenerative Diseases Course, we provide an overview of a range of cerebrospinal fluid (CSF) and blood biomarkers in neurodegenerative disorders, including the ‘core’ AD biomarkers amyloid β (Aβ) and tau, as well as other disease-specific and general markers of neuroaxonal injury. We then highlight the main challenges in the field, and how those could be overcome with the aid of new methodological advances, such as assay automation, mass spectrometry and ultrasensitive immunoassays.

As we hopefully move towards an era of disease-modifying treatments, reliable biomarkers will be essential to increase diagnostic accuracy, allow for earlier diagnosis, better participant selection and disease activity and treatment effect monitoring.
Production of tailor-made enzymes to facilitate lipid extraction from the oleaginous yeast Schwanniomyces occidentalis
Authors: Heshof Ruud , Visscher Bram , van de Zilver Eric , van de Vondervoort Rick , van Keulen Femke , Delahaije Roy J. B. M. , Wind Richèle D.
Published: February 2020

Due to the depletion of fossil fuel resources and concern about increasing atmospheric CO2 levels, the production of microbial oil as source for energy and chemicals is considered as a sustainable alternative. A promising candidate strain for the production of microbial oil is the oleaginous yeast Schwanniomyces occidentalis CBS 2864. To compete with fossil resources, cultivation and processing of S. occidentalis requires improvement. Currently, different cell wall disruption techniques based on mechanical, chemical, physiological, and biological methods are being investigated using a variety of oil producing yeasts and microalgae. Most of these techniques are not suitable for upscaling because they are technically or energetically unfavorable. Therefore, new techniques have to be developed to overcome this challenge. Here, we demonstrate an effective mild enzymatic approach for cell disruption to facilitate lipid extraction from the oleaginous yeast S. occidentalis. Most oil was released by applying 187 mg L−1 tailor-made enzymes from Trichoderma harzianum CBS 146429 against the yeast cell wall of S. occidentalis at pH 5.0 and 40 °C with 4 h of incubation time after applying 1 M NaOH as a pretreatment step.
Long noncoding RNAs: new insights in modulating mammalian spermatogenesis
Authors: Sahlu Bahlibi Weldegebriall , Zhao Shanjiang , Wang Xiuge , Umer Saqib , Zou Huiying , Huang Jinming , Zhu Huabin
Published: February 2020

Spermatogenesis is a complex differentiating developmental process in which undifferentiated spermatogonial germ cells differentiate into spermatocytes, spermatids, and finally, to mature spermatozoa. This multistage developmental process of spermatogenesis involves the expression of many male germ cell-specific long noncoding RNAs (lncRNAs) and highly regulated and specific gene expression. LncRNAs are a recently discovered large class of noncoding cellular transcripts that are still relatively unexplored. Only a few of them have post-meiotic; however, lncRNAs are involved in many cellular biological processes. The expression of lncRNAs is biologically relevant in the highly dynamic and complex program of spermatogenesis and has become a research focus in recent genome studies. This review considers the important roles and novel regulatory functions whereby lncRNAs modulate mammalian spermatogenesis.
PI3K inhibitor treatment ameliorates the glucocorticoid insensitivity of PBMCs in severe asthma
Authors: Bi Jing , Min Zhihui , Yuan Honglei , Jiang Zhilong , Mao Ruolin , Zhu Tao , Liu Chunfang , Zeng Yuzhen , Song Juan , Du Chunling , Chen Zhihong
Published: February 2020

Background

Glucocorticoid (GC) insensitivity is an important feature of severe and fatal asthma. Oxidative stress can induce phosphoinositide‐3‐kinase (PI3K) activation, contributing to the development of GC insensitivity in chronic airway diseases. However, the underlying molecular mechanism of PI3K in the pathogenesis of severe asthma remains unknown.

Methods

We isolated peripheral blood mononuclear cells (PBMCs) from 34 participants (12 patients with mild/moderate asthma, 10 patients with severe asthma, and 12 control subjects). H2O2 was used to stimulate the human macrophage line U937 to mimic the oxidative stress status in severe asthma. The ability of candidate compounds, namely, azithromycin, PI3K inhibitors (BEZ235 and LY294002) and a p38 MAPK inhibitor (BIRB796), to ameliorate GC insensitivity in severe asthma was evaluated.

Results

PBMCs from patients with severe asthma exhibited dose‐dependent and time‐dependent GC insensitivity, which correlated with reduced activity of histone deacetylase 2 (HDAC2) (p < 0.05) and elevated expression of proinflammatory genes [nuclear factor‐κB (NF‐κB) and activator protein‐1 (AP‐1)] (p < 0.01) compared with these parameters in the control group. The PI3K inhibitors (BZE235 and LY294002) significantly restored the GC sensitivity of PBMCs from patients with severe asthma. In vitro, the PI3K inhibitors (BZE235 and LY294002) ameliorated GC insensitivity in H2O2/TNFα‐induced IL‐8 release from U937 cells by independently restoring the activity of HDAC2 or inhibiting the activation of transcription factors.

Conclusions

This study demonstrates that PI3K inhibitors ameliorate GC insensitivity in severe asthma by restoring HDAC2 activity and inhibiting the phosphorylation of nuclear signaling transcription factors.
Pregabalin induced visual hallucinations – a rare adverse reaction
Authors: Mousailidis Georgios , Papanna Basavaraja , Salmon Andrew , Sein Aung , Al-Hillawi Qutaiba
Published: February 2020

Background

Pregabalin is an anticonvulsive, analgesic and anxiolytic medication. The typical side effects include dizziness, somnolence and weight gain. Few studies or case reports have demonstrated psychiatric side effects resulting from its use.

Case presentation

We present a patient who suffered visual hallucinations and agitation associated with an increase in pregabalin dose, resolving completely after pregabalin discontinuation.

Conclusions

Acute visual hallucinations should be considered in the clinical spectrum of very rare side effects of pregabalin use, especially at higher doses. Tapered discontinuation of the medication can improve and resolve symptoms.
The in vivo role of Rev1 in mutagenesis and carcinogenesis
Authors: Sasatani Megumi , Zaharieva Elena Karamfilova , Kamiya Kenji
Published: February 2020

Translesion synthesis (TLS) is an error-prone pathway required to overcome replication blockage by DNA damage. Aberrant activation of TLS has been suggested to play a role in tumorigenesis by promoting genetic mutations. However, the precise molecular mechanisms underlying TLS-mediated tumorigenesis in vivo remain unclear. Rev1 is a member of the Y family polymerases and plays a key role in the TLS pathway. Here we introduce the existing to date Rev1-mutated mouse models, including the Rev1 transgenic (Tg) mouse model generated in our laboratory. We give an overview of the current knowledge on how different disruptions in Rev1 functions impact mutagenesis and the suggested molecular mechanisms underlying these effects. We summarize the available data from ours and others’ in vivo studies on the role of Rev1 in the initiation and promotion of cancer, emphasizing how Rev1-mutated mouse models can be used as complementary tools for future research.
Complementary feeding practices and nutrient intakes of children aged 6–24 months from Bangladeshi background living in Tower Hamlets, East London: a feasibility study
Authors: Jabri Laura , Rosenthal Diana Margot , Benton Lorna , Lakhanpaul Monica
Published: February 2020

Background

The aim of this study was to assess dietary intakes and complementary feeding practices of children aged 6–24 months who are from Bangladeshi ancestry and living in Tower Hamlets, London, and determine the feasibility of a larger, population-representative study.

Methods

Questionnaires for demographic variables and feeding practices, and 24-h dietary recalls were administered to 25 mothers to determine whether it would be feasible to conduct a similar study on a representative sample size of the same population. Data from both tools were used to determine adequacy of complementary feeding practices through the WHO indicators and an infant and child feeding index score as well as overall macronutrient and micronutrient intake.

Results

Four children had varying suboptimal complementary feeding practices: two children failed to achieve the minimum dietary diversity, one child was being fed cow’s milk before the age of 1 year, and one scored ‘poor’ on the infant and child feeding index. Most notably, the mean protein intake (39.7 g/day, SD 18.2) was higher than RNIs for all age groups (P = 0.001). Vitamin D intake was below recommendations (P = 0.006) for the 12–24-month age group. For the 10–12-month age group, zinc intake fell below recommendations (P = 0.028). For the 6–9-month combined age group, iron and zinc intakes were below recommendations (P = 0.021 and P = 0.002, respectively).

Conclusions

Given the feasibility of this study, the results obtained require a large-scale study to be conducted to confirm findings. Our initial results indicated that children from Bangladeshi heritage may not be meeting nutritional requirements; thus, a future intervention tailored to the needs of the Bangladeshi population may be required to improve aspects of complementary feeding practices and nutrient intakes of those children.
Reproducible and transparent research practices in published neurology research
Authors: Rauh Shelby , Torgerson Trevor , Johnson Austin L. , Pollard Jonathan , Tritz Daniel , Vassar Matt
Published: February 2020

Background

The objective of this study was to evaluate the nature and extent of reproducible and transparent research practices in neurology publications.

Methods

The NLM catalog was used to identify MEDLINE-indexed neurology journals. A PubMed search of these journals was conducted to retrieve publications over a 5-year period from 2014 to 2018. A random sample of publications was extracted. Two authors conducted data extraction in a blinded, duplicate fashion using a pilot-tested Google form. This form prompted data extractors to determine whether publications provided access to items such as study materials, raw data, analysis scripts, and protocols. In addition, we determined if the publication was included in a replication study or systematic review, was preregistered, had a conflict of interest declaration, specified funding sources, and was open access.

Results

Our search identified 223,932 publications meeting the inclusion criteria, from which 400 were randomly sampled. Only 389 articles were accessible, yielding 271 publications with empirical data for analysis. Our results indicate that 9.4% provided access to materials, 9.2% provided access to raw data, 0.7% provided access to the analysis scripts, 0.7% linked the protocol, and 3.7% were preregistered. A third of sampled publications lacked funding or conflict of interest statements. No publications from our sample were included in replication studies, but a fifth were cited in a systematic review or meta-analysis.

Conclusions

Currently, published neurology research does not consistently provide information needed for reproducibility. The implications of poor research reporting can both affect patient care and increase research waste. Collaborative intervention by authors, peer reviewers, journals, and funding sources is needed to mitigate this problem.
The Impact of High School Life Science Teachers’ Subject Matter Knowledge and Knowledge of Student Misconceptions on Students’ Learning
Authors: Chen Chen , Sonnert Gerhard , Sadler Philip M. , Sunbury Susan
Published: February 2020

One of the foundational assumptions in education is that greater teacher knowledge contributes to greater gains in student knowledge, but empirical evidence in support of this assumption is scarce. Using a U.S. sample of 79 biology teachers and their 2749 high school students, we investigate whether teachers’ subject matter knowledge (SMK) and knowledge of students’ misconceptions (KOSM) in high school life science are associated with students’ posttest performance on multiple-choice test items designed to reveal student misconceptions, after controlling for their pretest scores. We found that students were more likely to answer an item on the posttest correctly if their teachers could answer the question correctly, themselves (SMK). Teachers’ ability to predict students’ most common wrong answer (KOSM) for an item predicted even better student performance. Items for which a particular wrong answer rose above others in popularity saw an even greater benefit for teacher KOSM.
Crossing Boundaries: Steps Toward Measuring Undergraduates’ Interdisciplinary Science Understanding
Authors: Tripp Brie , Voronoff Sophia A. , Shortlidge Erin E.
Published: February 2020

A desired outcome of education reform efforts is for undergraduates to effectively integrate knowledge across disciplines in order to evaluate and address real-world issues. Yet there are few assessments designed to measure if and how students think interdisciplinarily. Here, a sample of science faculty were surveyed to understand how they currently assess students’ interdisciplinary science understanding. Results indicate that individual writing-intensive activities are the most frequently used assessment type (69%). To understand how writing assignments can accurately assess students’ ability to think interdisciplinarily, we used a preexisting rubric, designed to measure social science students’ interdisciplinary understanding, to assess writing assignments from 71 undergraduate science students. Semistructured interviews were conducted with 25 of those students to explore similarities and differences between assignment scores and verbal understanding of interdisciplinary science. Results suggest that certain constructs of the instrument did not fully capture this competency for our population, but instead, an interdisciplinary framework may be a better model to guide assessment development of interdisciplinary science. These data suggest that a new instrument designed through the lens of this model could more accurately characterize interdisciplinary science understanding for undergraduate students.
Moral injury in a context of trauma
Authors: Jones Edgar
Published: February 2020

Moral injury, characterised by guilt, shame and self-condemnation, is conceptualised either as an adjunct to post-traumatic stress disorder or as a new syndrome. Studies of symptoms and potentially morally injurious events have produced a possible definition and informed the design of rating scales. The current challenge remains the design of effective interventions. Because moral injury relates to ethical behaviour, the meaning attached to events and perceptions of the self, moral philosophy and spirituality could contribute to the design of treatments.
Surgical Trends in Breast Cancer in Turkey: An Increase in Breast-Conserving Surgery
Authors: Çakmak Güldeniz Karadeniz , Emiroğlu Selman , Sezer Atakan , Canturk Nuh Zafer , Yeniay Levent , Kuru Bekir , Karanlık Hasan , Soyder Aykut , Gökgöz Şehsuvar , Sakman Gürhan , Ucuncu Muhammed , Akcay Mufide Nuran , Girgin Sadullah , Gurdal Sibel Ozkan , Emiroglu Mustafa , Ozbas Serdar , Öz Abdullah Bahadir , Arici Cumhur , Toktas Osman , Demircan Orhan , Çalık Adnan , Polat Ayfer Kamali , Maralcan Gokturk , Demirer Seher , Ozmen Vahit
Published: February 2020

PURPOSE

Breast cancer is the most frequent cancer in women, and there is a great variability in surgical practice for treating that cancer in different countries. The aims of this study were to analyze the effect of guidelines from the Turkish Federation of Breast Diseases Societies on academic institutions that have breast centers and to evaluate surgical practice in Turkey in 2018.

PATIENTS AND METHODS

Between January and March 2019, a survey was sent to breast surgeons who were working in breast centers in academic institutions. The sampling frame included 24 academic institutions with breast centers in 18 cities in Turkey to evaluate interdisciplinary differences among breast centers and seven regions in Turkey regarding patients’ choices, surgical approaches, and academic institutions.

RESULTS

All surgeons responded to the survey, and all 4,381 patients were included. Most of the surgeons (73.9%) were working in a breast center. Multidisciplinary tumor boards were performed in 87% of the breast centers. The average time between clinical evaluation and initiation of treatment was 29 days; the longest time was in Southeast Anatolia (66 days). Only 6% of patients had ductal carcinoma in situ. Sentinel lymph node biopsy was available in every region across the country and was performed in 64.5% of the patients. In 2018, the overall breast-conserving surgery rate was 57.3% in Turkey, and it varied from 72.2% in the Black Sea region to 33.5% in Central Anatolia ( P < .001). Oncoplastic breast surgery options were available at all breast centers. However, 25% of the breast centers from the Black Sea region and half the breast centers from Eastern Anatolia and the Mediterranean region did not perform this type of surgery.

CONCLUSION

Increasing rates of nonpalpable breast cancer and decreasing rates of locoregional recurrences favored breast-conserving surgery, especially in developed countries. Guidelines from the Turkish Federation of Breast Diseases Societies resulted in more comprehensive breast centers and improved breast health in Turkey.
deBetti Dry Aged: maturado para expandir?
Authors: Morgado Maurício Gerbaudo , Do Prado Lucas Sciencia , Cardoso Tiago Casagrande
Published: February 2020

Neste caso buscam-se discutir as diferentes estratégias de crescimento de um varejista e o alinhamento com seus objetivos de longo prazo. O texto apresenta a história de um açougue (deBetti), que tem foco na comercialização de carnes premium (cortes e hambúrgueres) notadamente, o dry-aged beef. O fundador passa por dilemas sobre como crescer sem perder a qualidade. O caso proporciona aprendizado sobre temas conectados à estratégia mercadológica varejista, como: segmentação, mercado-alvo e posicionamento; estratégias de crescimento para o varejo; e decisões sobre o composto mercadológico varejista, frente ao posicionamento e a estratégias adotadas.
Αξιολόγηση της ορθογραφικής δεξιότητας και γνώσης σε μαθητές με ειδικές εκπαιδευτικές ανάγκες
Authors: Ξάνθη Στυλιανή Βασίλειος
Published: February 2020

Η παρούσα μελέτη συνδυάζοντας ποσοτικές μεθόδους αξιολόγησης και ποιοτικές διαδικασίες ανάλυσης λαθών διερευνά την ικανότητα για ορθογραφημένη γραφή μαθητών Β΄ - ΣΤ΄ δημοτικού με ειδικές εκπαιδευτικές ανάγκες. Πιο συγκεκριμένα, η έρευνα εξετάζει το στάδιο ανάπτυξης της ορθογραφικής δεξιότητας μαθητών δημοτικού δευτέρας, τρίτης, τετάρτης, πέμπτης και έκτης τάξης, αξιολογώντας την ορθογραφημένη γραφή 20 μαθητών με ειδικές εκπαιδευτικές ανάγκες με μία σταθμισμένη δοκιμασία γραφής λέξεων καθ’ υπαγόρευση και συγκρίνοντας τις επιδόσεις τους με τον μέσο όρο των επιδόσεων του γενικού πληθυσμού της ίδιας ηλικιακής ομάδας. Από την ποιοτική ανάλυση των λαθών σε αντίστοιχες κατηγορίες που αφορούν τη φωνολογική, μορφολογική και την οπτικό-ορθογραφική επίγνωση, καθώς και τη χρήση των συμβάσεων του γραπτού λόγου, διαπιστώνονται οι διαβαθμίσεις στην ανάπτυξη της ορθογραφικής ικανότητας των μαθητών που βρίσκονται οι συγκεκριμένοι μαθητές και παρέχονται χρήσιμες πληροφορίες για τις γνωστικές τους διεργασίες και τις ατομικές τους ανάγκες. Τα αποτελέσματα της μελέτης αναδεικνύουν χαμηλότερες επιδόσεις των περισσότερων μαθητών σε σχέση με τον μέσο όρο του πληθυσμού των συνομηλίκων τους. Επίσης, καταδεικνύουν περιορισμούς και ελλείμματα σε δεξιότητες φωνολογικής και μορφοσυντακτικής επεξεργασίας καθώς και περιορισμένες οπτικό-ορθογραφικές  αναπαραστάσεις. Με βάση αυτά τα ευρήματα η εργασία πραγματεύεται το στάδιο ανάπτυξης της ορθογραφικής δεξιότητας των μαθητών, τους παράγοντες που επηρέασαν καθοριστικά την ορθογραφική τους επίδοση, τον βαθμό δυσκολίας του ορθογραφικού έργου και τον διαφορετικό ρυθμό ανάπτυξης της ορθογραφικής ικανότητας των μαθητών.
Η μετασχηματιστική ηγεσία στη δημόσια δευτεροβάθμια εκπαίδευση στην Ελλάδα: διερεύνηση των απόψεων των εκπαιδευτικών
Authors: Καλλιοντζή Βασιλική , Ιορδανίδης Γεώργιος
Published: February 2020

Η επιταγή της σύγχρονης εκπαιδευτικής πολιτικής για υψηλά σχολικά αποτελέσματα οδηγεί στην επιδίωξη μετασχηματισμού των σχολείων, μέσω της βελτίωσης της ποιότητας του παραγόμενου έργου. Προς αυτήν την κατεύθυνση, τις τελευταίες δεκαετίες, το ενδιαφέρον των ερευνητών στρέφεται σε μια δυναμική διαδικασία, την ηγεσία. Στόχος της συγκεκριμένης έρευνας είναι η διερεύνηση των απόψεων των εκπαιδευτικών της ελληνικής δημόσιας δευτεροβάθμιας εκπαίδευσης, ως προς το μοντέλο της ηγετικής συμπεριφοράς που υιοθετούν οι διευθυντές, στα πλαίσια του ελληνικού συγκεντρωτικού εκπαιδευτικού συστήματος. Για τη μέτρηση της πλήρους έκτασης των ηγετικών στυλ, από το μετασχηματιστικό και το συναλλακτικό έως το παθητικό, επιλέχθηκε ως ερευνητικό εργαλείο το Πολυπαραγοντικό Ερωτηματολόγιο Ηγεσίας (M.L.Q.-5x) των Avolio και Bass, το οποίο επικεντρώνεται στα χαρακτηριστικά και τις συμπεριφορές των ηγετών και στην έκβαση της ηγεσίας. Συλλέχθηκαν 470 απαντημένα ερωτηματολόγια από 357 σχολικές μονάδες της Ελλάδας. Τα αποτελέσματα έδειξαν, ως προς το στυλ ηγεσίας, την εμφάνιση της μετασχηματιστικής ηγεσίας ελαφρώς ισχυρότερη από αυτήν της συναλλακτικής, ενώ η παθητική παρουσιάστηκε με ιδιαίτερα χαμηλές τιμές. Οι μεγαλύτερες μέσες τιμές εντοπίστηκαν, αριθμητικά ίσες, στην «εξιδανικευμένη επιρροή από τη συμπεριφορά» των ηγετών, του μετασχηματιστικού μοντέλου και στην «έκτακτη ανταμοιβή», του συναλλακτικού. Ακολουθούν οι μεταβλητές της «εμπνευσμένης κινητοποίησης» και της «πνευματικής διέγερσης» του μετασχηματιστικού στυλ. Επίσης, προέκυψε ισχυρή θετική συσχέτιση μεταξύ της μετασχηματιστικής και συναλλακτικής ηγεσίας και πολύ ισχυρή μεταξύ της μετασχηματιστικής και των μεταβλητών της «επιπρόσθετης προσπάθειας» των εκπαιδευτικών, της «αποτελεσματικότητας» της ηγετικής συμπεριφοράς και της «ικανοποίησης» από την ηγεσία, που συνθέτουν την έκβαση της ηγεσίας. Από την ανάλυση πολλαπλής παλινδρόμησης προέκυψε ότι η μετασχηματιστική ηγεσία έχει την καλύτερη ερμηνευτική ικανότητα ως προς την πρόβλεψη των μεταβλητών της έκβασης της ηγεσίας. Η πρόκριση στην ελληνική εκπαίδευση της μετασχηματιστικής ηγεσίας, είναι ευοίωνο εύρημα. Δημιουργούνται ενδείξεις για μια μεταρρυθμιστική τάση στο πεδίο της ελληνικής δημόσιας δευτεροβάθμιας εκπαίδευσης, που δύναται να συνεισφέρει στην προοδευτική απομάκρυνση, των κυρίαρχων τάσεων των ελληνικών κοινωνικών δομών, από το συντηρητισμό και τη γραφειοκρατική αντίληψη. Τα αποτελέσματα μπορούν να χρησιμεύσουν στον τομέα της εκπαιδευτικής πολιτικής για τη δημιουργία κουλτούρας που οδηγεί στη βελτίωση της ποιότητας της δημόσιας εκπαίδευσης.
R package “QRISK3”: an unofficial research purposed implementation of ClinRisk’s QRISK3 algorithm into R
Authors: Li Yan , Sperrin Matthew , van Staa Tjeerd
Published: February 2020

Cardiovascular disease has been the leading cause of death for decades. Risk prediction models are used to identify high risk patients; the most common model used in the UK is ClinRisk’s QRISK3. In this paper we describe the implementation of the QRISK3 algorithm into an R package. The package was successfully validated by the open sourced QRISK3 algorithm and QRISK3 SAS program. We provide detailed examples of the use of the package, including assigning QRISK3 scores for a large cohort of patients. This R package could help the research community to better understand risk prediction scores and improve future risk prediction models. The package is available from CRAN: https://cran.r-project.org/web/packages/QRISK3/index.html.
Cost per insertion and couple year of protection for postpartum intrauterine devices and implants provided during service scale-up in Kigali, Rwanda
Authors: Wall Kristin M. , Ingabire Rosine , Allen Susan , Karita Etienne
Published: February 2020

Introduction: In two high-volume government hospitals, their two affiliated health facilities, and two additional health facilities, we developed and implemented postpartum intrauterine device (PPIUD) and postpartum (PP) implant promotional counseling and service delivery procedures between May-July 2017 in Kigali, Rwanda. Between August 2017 and July 2018, 9,073 pregnant women received PPIUD/PP implant promotions who later delivered in one of our selected facilities. Of those, 2,633 had PPIUDs inserted, and 955 had PP implants inserted. The goal of the present analysis is to detail implementation expenditures and estimate incremental costs per insertion and couple years of protection (CYP) for PPIUD and PP implant users.

Methods: We detail the incremental costs during the implementation from the health system perspective (including both the implementation costs and the cost of contraceptive methods) and use of standard methods to estimate the cost per insertion and CYP for PPIUD and PP implant users. In addition to the incremental costs of labor and supplies, the costs of promotional activities are included. Research costs for formative work were excluded.

Results: A total of $74,147 USD was spent on the implementation between August 2017 and July 2018. The largest expense (34% of total expenses) went toward personnel, including doctoral-level, administrative, data management and nurse counseling staff. Training for PPIUD and implant providers and promoters comprised 8% of total expenses. Recruitment and reimbursements comprised 6% of expenses. Costs of implants to the government comprised 12% of the expenses, much higher than the cost of IUDs (1%). Costs per insertion were $25/PPIUDs and $77/PP implant. Costs per CYP were $6/PPIUDs and $21/PP implant. 

Conclusion: Understanding the cost per PPIUD/PP implant inserted and CYP can help to inform the cost of scaling up PPIUD/PP implant service implementation activities and resource allocation decision-making by the Rwandan Ministry of Health.
The Use of Project Design Technology in Professionally-Oriented Educational Space
Authors: Miroshin Dmitriy , Michurova Natal'ya , Shterenzon Vera
Published: February 2020

The subject of the research is the process of organizing and implementing the design and technological training of university students in the course of studying educational modules in a professionally-oriented educational space created on the basis of social partnership between the university and the enterprise-customer of trained personnel. The object of research is the technology of project-based training of students in the design of assemblies, parts and technological processes for their manufacture, implemented in a professionally-oriented educational space. The authors consider in detail such aspects of the topic as options for organizing a professionally-oriented educational space in the framework of social partnership through the use of real-life projects and simulation modeling of a specialist’s professional activity in students ’project activities. The authors consider a phased methodology for the implementation of project-based learning technology during the technological preparation of students, focused on the formation of professional competencies and labor functions of professional standards. The results of a pedagogical experiment on the formation of technological competencies during the implementation of project training in a professionally-oriented educational space are presented. The main research methods: theoretical analysis of the experience of organizing project training, the synthesis of didactic tools and teaching methods, a comparative pedagogical experiment. The main conclusions of the study are to justify the high pedagogical eff ectiveness of organized project training in a professionally-oriented educational space created on the basis of a social partnership between a university and an enterprise. The scientifi c novelty of the study lies in the application of technology for project training in the conditions of quasi-professional activity when students perform real projects. A special contribution of the authors to the study is the development of a model for the joint implementation of project-based learning technology in preparing students for a professionally-oriented educational environment.
The best route determination using nearest neighbor approach
Authors: Rahma Nafia , Purwani Annie , Febriyanto Dwi Nita
Published: February 2020

This research constitutes an application of heuristic optimization using the nearest neighbor (NN) method. It is a method used to design a route based on the next closest distance. The case here is the garbage freight of Yogyakarta City which becomes one of the Environmental Services Department duties. The sector of this research object is Malioboro-Kranggan because it has the highest number of TPS locations. There are 34 TPS locations, and 2 depots with an average volume of total garbage are 197 m3/day. Several alternative routes have resulted because the same distance was found when deciding the next distance (TPS 26 and TPS 31). The best alternative was determined based on the best scenario parameter of total mileage and operational time. The first scenario chose the garbage volume that is close to the remaining capacity, meanwhile, the second scenario chose the smallest garbage volume. At TPS 27, an alternative with the same closest distance appeared again (TPS 15 and TPS 18). Hence, the whole algorithm results in four alternative decisions. The first alternative results 13.59 hours as the total time and 40.092 km as the total distance, the second results 13.50 hours with 40.315 km, the third results 13.57 hours with 41.393 km, and the fourth results 13.803 hours with 40.41 km. The best alternative goes to the first alternative based on the parameter set before. It means that the scenario taken is by choosing the TPS with the closest remaining volume of the vehicle.
Central place theory and tax revenue from tourism
Authors: Gmeiner Robert J.
Published: February 2020

Many governments, both state and local, attempt to promote tourism as a way of raising revenue and encouraging economic development. This is especially prevalent in Florida, where tourism revenue constitutes a major source of revenue through the sales tax. However, some areas in Florida are considerably more popular as tourist destinations than others. In this article, I use central place theory to provide a theoretical framework for dividing metropolitan areas into categories with similar characteristics and similar levels of tourism in order to provide policy recommendations specific to each category. I conclude that a uniform approach to tourism promotion will have far less meaningful overall effects compared to policies targeted based on this division of tourism destinations.
Simplified retrieval method for Edge Illumination X-ray phase contrast imaging allowing multi-modal imaging with fewer input frames
Authors: Buchanan Ian , Mittone Alberto , Bravin Alberto , Diemoz Paul , Endrizzi Marco , Olivo Alessandro
Published: February 2020

We present data from an implementation of Edge Illumination (EI) that uses a detector aperture designed for increasing dynamic range, suitable for clinically relevant X-ray energies and demonstrated here using synchrotron radiation. By utilising a sufficiently large crosstalk between pixels, this implementation enables single-scan imaging for phase and absorption, and double-scan for phase, absorption and dark field imaging. The presence of the detector mask enables a direct comparison between conventional EI and beam tracking (BT), which we conduct through Monte Carlo and analytical modelling in the case of a single-scan being used for the retrieval of all three contrasts. In the present case, where the X-ray beam width is comparable to the pixel size, we provide an analysis on best-positioning of the beam on the detector for accurate signal retrieval. Further, we demonstrate an application of this method by distinguishing different concentrations of microbubbles via their dark field signals at high energy using an EI system.
Photonics-based multi-band linearly frequency modulated signal generation and anti-chromatic dispersion transmission
Authors: Zhang Kun , Zhao Shanghong , Wen Aijun , Zhai Weile , Lin Tao , Li Xuan , Wang Guodong , Li He
Published: February 2020

A photonics-based anti-chromatic dispersion transmission scheme for multi-band linearly frequency modulated (LFM) signals is proposed and experimentally demonstrated. In the central station (CS), the key component is an integrated dual-polarization quadrature phase shift keying (DP-QPSK) modulator, of which the up-arm and down-arm are driven by a microwave reference signal and an intermediate-frequency (IF) LFM signal respectively. By properly adjusting the DP-QPSK modulator, optical frequency comb (OFC) and frequency shift lightwave are generated. After polarization coupling and remote transmission, the orthogonal-polarization optical signals are introduced into balanced photodetector for heterodyne detection. Thence, multi-band LFM signals are generated and transmitted to remote base stations (BS) with the largest power for the anti-chromatic dispersion ability. Experiments are conducted to verify the analysis. Multi-band LFM signals at L (1.5 GHz), C (7 GHz), X (10 GHz), Ku (15.5 GHz) and K (18.5 GHz) bands with flatness of 1.9 dB are simultaneously obtained in the CS after 50 km fiber transmission, while the normally double-sideband modulation approach experiences a significant power fading for the fiber dispersion. Tunability of the system is evaluated, and detection performances of the generated signals are also analyzed.
Generation and manipulation of oil-in-water micro-droplets by confined thermocapillary microvortices
Authors: Chen Yilin , Yang Jianxin , Wu Jiayin , Li Zongbao , Liu Shaojing , Zhong Huiqing , Zhou Ruixue , Luo Aiping , Ho Ho-Pui , He Sailing , Xing Xiaobo , Shui Lingling
Published: February 2020

Optofluidic manipulation of droplets is critical in droplet-based microfluidic systems for chemistry, biology, and medicine. Here, we reported a thermocapillary microvortices-based manipulation platform for controlling oil-in-water droplets through integrating a photothermal waveguide into a microfluidic chip. The sizes and shapes of the droplets can be controlled by adjusting optical power or positions of the water–oil interface. Here, teardrop-shaped droplets, which can encapsulate and accumulate mesoscopic matters easily, were generated when the water–oil interface and the channel boundaries approached the photothermal waveguide center simultaneously. The results showed that the thermocapillary microvortices have good controllability of droplet positions, droplet volumes, and encapsulated-particle distribution and thus it will be a powerful droplet manipulation strategy for microreactors and microcapsules.
Effective nonlinearity of the new quaternary chalcogenide crystal BaGa2GeSe6
Authors: Kato Kiyoshi , Badikov Valeriy V. , Wang Li , Panyutin Vladimir L. , Mitin Konstantin V. , Miyata Kentaro , Petrov Valentin
Published: February 2020

The unknown magnitude and relative signs of the trigonal crystal

B
a
G
a

2

G
e
S
e

6

nonlinear coefficients have hindered defining an optimum orientation for maximum frequency conversion efficiency. This issue is resolved in the present work, obtaining

d

11

=
+

23.6

,

d

22

=
−

18.5

, and

d

31

=
+

18.3

p
m

/

V

for frequency doubling of the 10.591 µm radiation.
High extinction ratio terahertz broadband polarizer based on the aligned Ni nanowire arrays
Authors: Xiang Wenfeng , Huang Xiaowei , Li Dong , Zhou Qingli , Guo Haizhong , Li Junjian
Published: February 2020

We present a broadband terahertz (THz) polarizer based on the stacks of aligned Ni nanowire (NW) arrays. We demonstrated that the polarizer has an extinction ratio of 58.8 dB and an average extinction ratio of 46.6 dB throughout a frequency range of 0.3–2.3 THz. Compared to carbon-nanotube and metallic wire-grid polarizers, our Ni-NW polarizers with rapid, reliable, low-cost fabrication processes are ideal candidates for emerging THz technologies.