bluuebunny/crossref_metadata_2025 huggingface dataset:
Apresentação: deslocando referências, propondo novas questões
Authors: Telles Vera Da Silva
Published: January 2020

Apresentacao ao Dossiê - Punição,  prisão e cidade: contextos transversais
On the Linguistic Representational Power of Neural Machine Translation Models
Authors: Belinkov Yonatan , Durrani Nadir , Dalvi Fahim , Sajjad Hassan , Glass James
Published: January 2020

Despite the recent success of deep neural networks in natural language processing and other spheres of artificial intelligence, their interpretability remains a challenge. We analyze the representations learned by neural machine translation (NMT) models at various levels of granularity and evaluate their quality through relevant extrinsic properties. In particular, we seek answers to the following questions: (i) How accurately is word structure captured within the learned representations, which is an important aspect in translating morphologically rich languages? (ii) Do the representations capture long-range dependencies, and effectively handle syntactically divergent languages? (iii) Do the representations capture lexical semantics? We conduct a thorough investigation along several parameters: (i) Which layers in the architecture capture each of these linguistic phenomena; (ii) How does the choice of translation unit (word, character, or subword unit) impact the linguistic properties captured by the underlying representations? (iii) Do the encoder and decoder learn differently and independently? (iv) Do the representations learned by multilingual NMT models capture the same amount of linguistic information as their bilingual counterparts? Our data-driven, quantitative evaluation illuminates important aspects in NMT models and their ability to capture various linguistic phenomena. We show that deep NMT models trained in an end-to-end fashion, without being provided any direct supervision during the training process, learn a non-trivial amount of linguistic information. Notable findings include the following observations: (i) Word morphology and part-of-speech information are captured at the lower layers of the model; (ii) In contrast, lexical semantics or non-local syntactic and semantic dependencies are better represented at the higher layers of the model; (iii) Representations learned using characters are more informed about word-morphology compared to those learned using subword units; and (iv) Representations learned by multilingual models are richer compared to bilingual models.
An Empirical Study on Crosslingual Transfer in Probabilistic Topic Models
Authors: Hao Shudong , Paul Michael J.
Published: January 2020

Probabilistic topic modeling is a common first step in crosslingual tasks to enable knowledge transfer and extract multilingual features. Although many multilingual topic models have been developed, their assumptions about the training corpus are quite varied, and it is not clear how well the different models can be utilized under various training conditions. In this article, the knowledge transfer mechanisms behind different multilingual topic models are systematically studied, and through a broad set of experiments with four models on ten languages, we provide empirical insights that can inform the selection and future development of multilingual topic models.
Nilotanypus Kieffer from China (Diptera: Chironomidae: Tanypodinae)
Authors: CHENG MING , WANG XINHUA
Published: January 2020

The genus Nilotanypus is recorded from the Oriental region for the first time. Two new species, N. polycanthus and N. quadratus, from Oriental China are described and figured as males. N. dubius (Meigen) is recorded from northern China. A key to the males of all known Nilotanypus is presented.
New subfamilies and a new genus and species of Melithaeidae (Coelenterata: Octocorallia: Alcyonacea) with comparative data on the structure of both melithaeid and subergorgiid axes
Authors: ALDERSLADE PHILIP
Published: January 2020

Asperaxis karenae, a new genus and new species of the gorgonian family Melithaeidae, is described. The coenenchymal sclerites of the new genus bear similarities to those of Acabaria, but the axis is quite different from that which is characteristic of the family. The axial sclerites are rods and sticks, often sinuous and branched, with simple, sparse, tubercles. The internodes may be whole or partial, and are not clearly delimited from the internodes. A new subfamily, Asperaxinae, is proposed to accommodate any taxa with the new axial characters, and the Melithaeinae for the existing nominal taxa. The structure of both axial forms and the subergorgiid axis are illustrated with scanning electron micrographs.
The understanding of the concept LANGUAGE among young people in Lithuania and Lithuanians living abroad
Authors: Smetona Marius , Smetonienė Irena
Published: January 2020

The understanding of the concept LANGUAGE among young people in Lithuania and Lithuanians living abroadThis article applies the methodology developed by the Ethnolinguistic School of Lublin to analyse how the concept LANGUAGE (Lith. KALBA) is understood by young people in Lithuania and how its understanding changes when a person lives far away from their homeland. A comparison of replies from the two groups indicates that the social aspect has the most weight in both of them, as the difference in the percentage of mentions of this aspect was quite small. Lithuanians living abroad tend to stress the cultural and the psychosocial aspects much more; they find the connection with other Lithuanians very important. The survey of young people in Lithuania reveals a more distinct ideological aspect of LANGUAGE, and the historical and political aspects, even though they occur rarely, are still present, while the replies from the respondents living abroad lack the latter two. However, the survey of Lithuanian emigrants has uncovered a locative aspect, which is not present among the respondents living in the country. Young people in Lithuania have a somewhat broader understanding of the concept: when they think about language, they are already beginning to look for other possibilities of linguistic expression, noting that language is more than just sounds or words, but also includes gestures; they also mention programming languages. Rozumienie pojęcia JĘZYK wśród litewskiej młodzieży i Litwinów za granicąNiniejszy artykuł, oparty na metodologii lubelskiej szkoły etnolingwistycznej, ukazuje, jak pojęcie JĘZYK (lit. KALBA) jest rozumiane przez współczesnych młodych mieszkańców Litwy i jak zmienia się jego konceptualizacja, gdy osoby przebywają przez dłuższy czas z dala od ojczyzny. Porównanie odpowiedzi obu grup respondentów uwidoczniło, że badani najliczniej przypisują językowi aspekt społeczny i  różnica procentowa w wyborze tego kryterium w obu grupach nie jest duża. Emigranci litewscy mocniej natomiast wyróżniają aspekt kulturowy i  psychospołeczny języka, dla nich relacje z innymi Litwinami są bardzo ważne. W odpowiedziach studentów mieszkających na Litwie często występuje aspekt ideologiczny języka, rzadziej – historyczny i polityczny, a w odpowiedziach emigrantów takich aspektów nie ma, chociaż można tu z kolei wyróżnić aspekt lokatywny, który nie zaznaczył się w ankietach respondentów z Litwy. Młodzież z Litwy język rozumie nieco szerzej: stara się szukać innych możliwości ekspresji językowej, uważa, że pojęcie JĘZYK obejmuje nie tylko dźwięki lub słowa, ale i gesty, a nawet języki programowania.
miR-125a-5p Inhibits Oxidized Low-Density Lipoprotein-Induced Proliferation and Migration of Vascular Smooth Muscle Cells Through PI3K/AKT Signaling
Authors: Xu Xiangmei , Li Dongbin , Chen Hao , Wei Xiaogang , Wang Xiaoyan
Published: January 2020

Certain microRNAs (miRNA/miRs) serve important roles in the progression of atherosclerosis (AS); however, the exact regulatory mechanisms of miRNAs in AS remain to be fully elucidated. The present study aimed to investigate the effects of miR-125a-5p in AS and the underlying mechanisms.
Oxidized low-density lipoprotein (ox-LDL) was employed to stimulate human aortic vascular smooth muscle cells (HAVSMCs) to establish a cell model of AS. Reverse transcription-quantitative PCR was used to determine the expression levels of miR-125a-5p. Cell proliferation was evaluated using
a Cell Counting Kit-8 (CCK-8) and migration was detected using a Transwell assay. In addition, the levels of the VSMC-specific marker gene α-smooth muscle actin, the cell cycleregulatory proteins cyclin-dependent kinase (CDK)2, cyclin D1, cyclin E and p27, as well as the migration-associated
proteins matrix metalloproteinase-2 (MMP2) and MMP9, and phosphorylated phosphoinositide 3-kinase (p-PI3K) and p-AKT were determined by western blot analysis. The results revealed that transfection of miR-125a-5p mimics inhibited the ox-LDL-induced proliferation of HSVSMCs, accompanied by
decreased expression of CDK-2, cyclin D1 and cyclin E, and increased expression of p27. Furthermore, miR-125a-5p mimics attenuated the ox-LDL-induced migration of HAVSMCs in parallel with downregulation of the expression of MMP2 and MMP9. Furthermore, the effect of ox-LDL to increase p-PI3K
and p-AKT levels was significantly blunted by miR-125a-5p mimics. In conclusion, the present results suggested that miR-125a-5p mimics inhibited ox-LDL-induced proliferation and migration of HAVSMCs through inhibition of PI3K/AKT signaling, providing a potential novel therapeutic strategy
for AS.
The Effect and Mechanism of Continuous Passive Exercise Combined with Platelet-Rich Plasma on Rabbit Knee Osteoarthritis Model
Authors: Zuo Bingguang , Zhang Lei , Wang Zhipei , Diao Li , Han Sukun
Published: January 2020

Osteoarthritis (OA) is a disease in orthopedics. Continuous passive exercise (CPM) and intraarticular injection of platelet-rich plasma (PRP) have certain effects on OA. However, the effect of these two combination on OA remains unclear. The present study aims to evaluate the treatment
efficacy of this combination on OA. 50 New Zealand white rabbits were randomly divided into control group, OA group, CPM group, PRP group and CPM + PRP group followed by analysis of the pathological changes of chondrocyte by H&E staining and Mankin's score, level of IL-1 and TNF-α
by ELISA, as well as MMP-1 and MMP-13 protein expression by western blot. Compared with control group, the Mankin's score of OA group was significantly increased (P < 0.05), along with increased expressions of MMP-1 and MMP-13 in the joint fluid, levels of IL-1 and TNF-α
(P < 0.05). CPM group and PRP group presented significantly lower Mankin's scores, reduced IL-1 and TNF-α levels in synovial fluid as well as decreased MMP-1 and MMP-13 protein expression in articular cartilage compared with OA group (P < 0.05). Compared with
CPM group and PRP group, the Mankin's score of CPM + PRP group was significantly decreased (P < 0.05), along with reduced IL-1 and TNF-α levels in joint fluid, and decreased expression of MMP-1 and MMP-13 protein in articular cartilage (P < 0.05). The efficacy
of CPM combined with PRP in treating OA is better than that of CPM or PRP alone, which may be related to the decreased expression of IL-1, TNF-α , MMP-1 and MMP-13.
Evaluation of Structural and Biomechanical Characterization of Implant for Cranial Restoration
Authors: Tsai Fu-Hui , Cheng Han-Yi
Published: January 2020

The objective this research was to investigate the biomechanical properties of various structures and thicknesses of implants for cranial restoration. A three-dimensional (3D) printing (3DP) technique has been applied in factories for several decades, but it was only recently introduced
to the dental field less than 10 years ago. The structures of pre-shaped cranial mesh implants are critical factors for clinical applications. Many previous studies used finite element models to investigate for implants, but few examined a 3D model for pre-shaped cranial mesh implants with
different structures and thicknesses. 3D cranial models were reconstructed using computer tomography to simulate preshaped cranial mesh implants under physical impacts. Data indicated that the stress significantly decreased when implants with greater thicknesses were used. Moreover, the implant
with a circular structure created a relatively smaller stress that was approximately 7% lower compared to the implant with a triangular structure. As described above, the results of the present study demonstrate that 3DP-Ti is a reliable material of implants for cranial restoration.
Biological Characteristics and Multilineage Differentiation of Kidney Mesenchymal Stem Cells Derived from the Tibetan Mastiff
Authors: Yan Bing , Liang Ruining , Ji Meng , Wuyun Qi-Qige , Guan Weijun , Tian Xiuzhi
Published: January 2020

Of all the significant researches that have taken place in isolation, culture and characterization of mesenchymal stem cells (MSCs), the field of kidney-derived mesenchymal stem cells (KMSCs) in Tibetan mastiff is still a blank. Therefore, the purpose of this study is to isolate, culture
and characterize the Tibetan mastiff KMSCs. The KMSCs were successfully isolated from one-day year old Tibetan mastiff kidney, cultured for 16 passages and distinguished by two methods: immunofluorescence staining and RT-PCR. The Tibetan mastiff KMSCs expressed specific surface marker genes
(VIM, CD44, FN1, CD90, CD109, CD73, FN1) and kidney marker gene PAX2. The proliferation ability of Tibetan mastiff KMSCs was measured through cell count and clonality. Furthermore, cells differentiated into different cell types (hepatocellular cells, osteogenic cells, adipogenic cells and
chondrogenic cells) under special induced medium, and the marker genes of induced cells were identified with Immunofluorescence staining and RT-PCR. All of these results indicated that the Tibetan mastiff KMSCs were obtained successfully, which possessed certain characteristics of multipotent
stem cells. Therefore, MSCs in Tibetan mastiff kidney hold potential for clinical applications for regenerative therapy and their further studies are waiting to be required to investigate their functions.
Designing and Fast 3D Printing of Continuous Carbon Fibers for Biomedical Applications
Authors: Zhang Haiguang , Qi BaoQuan , Hu Qingxi , Yan Biao , Liu Dali , Ramalingam Murugan
Published: January 2020

Carbon fibers are excellent materials for engineering biomedical materials and devices owing to their functional properties of low weight, high strength, high chemical and thermal stability, and blood and cell compatibility. Recent studies have demonstrated that the carbon fibers could
be used as a scaffolding system for bone repair and regenerative application. However, carbon fiber-based composite products lack the long-term retention of their biological property upon implantation, which greatly affects their wider biomedical applications. In this study, design and fabrication
of carbon fibers composite scaffolds using a fast 3D printing technology has been successfully realized, which provides a new direction for the biomedical application of carbon fiber composite materials.
Systematic Review of Household Water Conservation Interventions Using the Information–Motivation–Behavioral Skills Model
Authors: Ehret Phillip J. , Hodges Heather E. , Kuehl Colin , Brick Cameron , Mueller Sean , Anderson Sarah E.
Published: January 2020

Increasing droughts and water shortages are intensifying the need for residential water conservation. We identify and classify 24 water conservation studies using the information–motivation–behavioral skills (IMB) model by categorizing interventions based on content and water conservation effectiveness. This synthesis revealed several insights. First, all of the interventions used information, motivation, and/or behavioral skills, suggesting that water conservation interventions can be interpreted within the IMB framework. Second, interventions with two or more IMB components led to reductions in water usage, but the average effect sizes between different types of interventions were similar and there was a considerable range around these averages. To the extent that intervention effectiveness is driven by populations lacking specific IMB components, more elicitation research to identify gaps in specific populations could support greater effectiveness. Designing interventions explicitly with the IMB model would facilitate comparability across studies and could support a better understanding of water conservation interventions.
Neoliberal co-optation, power relations and informality in the Balkan International Relations profession
Authors: Džuverović Nemanja , Tepšić Goran
Published: January 2020

The article attempts to assess the importance of informal networks in achieving internationally recognised academic standards set in four Balkan countries by the reform of higher education institutions and the International Relations (IR) profession in particular. Starting from the core-periphery division of the Global IR, the authors are examining the results of these reforms by focusing on the neoliberalisation of the university and the professional subordination of peripheral IR communities to the Western-dominated epistemic community (including ‘brain drain’ and recruitment of ‘organic’ intellectuals). Based on the interviews conducted with Balkan IR scholars, the authors conclude that informality is viewed as social capital, that is, a means of acquiring benefits by virtue of personal ties with the ‘gatekeepers’ of core IR. In that respect, interviewees suggest three possible solutions for overcoming the epistemic dependence of the Balkan IR community: development of local standards, stimulation of critical approach and better preparation for international standards, while the authors of the article also propose the fourth possibility: abandoning the core-periphery division, and thinking beyond geopolitical and geocultural divisions – the main idea behind the Global IR project.
Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Chronic Rhinosinusitis With Nasal Polyps: Etiopathogenesis and Recurrence
Authors: Guerra Germano , Testa Domenico , Salzano Francesco Antonio , Tafuri Domenico , Hay Eleonora , Schettino Antonetta , Iovine Renata , Marcuccio Giuseppina , Motta Gaetano
Published: January 2020

Chronic rhinosinusitis with nasal polyps is a multifactorial disease of the nasal and paranasal sinus mucosa and it includes, as comorbidities, anatomic and morphologic alterations, allergic rhinitis, and immunologic diseases. We investigated matrix metalloproteinases (MMP-2, MMP-7, and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) concentration in different etiopathogenetical groups of patients with nasal polyposis (NP) in relation to recurrence after sinonasal surgery. The study group consisted of 45 patients with NP (those with allergic rhinitis, nonallergic rhinitis and asthma or nonallergic rhinitis, and obstruction of osteomeatal complex [OMC]) who underwent endonasal sinus surgery. We also collected 10 patients who underwent septoplasty as control. Immunohistochemistry of nasal mucosa fragments, Western blotting, and polymerase chain reaction analysis showed increased MMPs levels (MMP-9 more than MMP-2 and MMP-7) and decreased tissue inhibitors of MMPs levels (TIMP-1 less than TIMP-2), in patients with chronic rhinosinusitis with nasal polyps compared with control group, in particular in patients with nonallergic rhinitis and asthma compared to those with allergic rhinitis and nonallergic rhinitis and obstruction of OMC. We observed a higher risk of recurrence in patients with nonallergic rhinitis and asthma than in those with allergic rhinitis and nonallergic rhinitis and obstruction of OMC after 36 months from surgery. In this research, we evaluated pathogenesis of NP related to MMPs and their inhibitors concentrations in polypoid tissue.
Factors Affecting the Behavior and Duration of Breastfeeding Among Physician Mothers
Authors: Ersen Gamze , Kasim Ismail , Agadayi Ezgi , Demir Alsancak Aybuke , Sengezer Tijen , Ozkara Adem
Published: January 2020

Background

Increasing breastfeeding duration may help physician mothers better counsel their patients. To improve the breastfeeding duration of physician mothers, the factors that may influence their breastfeeding duration should be known.

Research Aim

To investigate the breastfeeding behavior and duration among physician mothers and to determine the factors that influence breastfeeding practices.

Methods

This was an online prospective cross-sectional self-report survey. A 26-item author-created data-collecting tool inquiring sociodemographic and work characteristics, medical history of delivery, and breastfeeding history was sent to female physicians who had infants between 12 and 60 months of age via an online social group, “Physician Mothers,” with 11,632 members. Participants ( N = 615) responded, and descriptive statistics were analyzed.

Results

Participants’ mean duration of exclusive breastfeeding was 4.8 months ( SD = 1.9). The total breastfeeding length was a mean 15.8 months ( SD = 7.6). The rate of breastfeeding duration for at least 24 months was 17.8% ( n = 75). The most common reason for weaning from breastfeeding was workplace-related conditions (23.6%, n = 145). Participants reported that the mean time of resuming night shifts after delivery was 8.6 months ( SD = 4.7). The rate of participants who were unable to use their breastfeeding leave rights partially or completely was 43.6% ( n = 268).

Conclusion

Although legislation is in place to allow working mothers to breastfeed their infants, these legal rights were not used properly. Physician mothers should be fully supported in using their breastfeeding leave rights, and workplace conditions should be improved to enable physician mothers to breastfeed their infants for extended periods.
Parents’ Perceptions of Access to Services for Their Adult Children Diagnosed With Autism Spectrum Disorder
Authors: Marsack-Topolewski Christina N. , Weisz Arlene N.
Published: January 2020

The purpose of this phenomenological study was to investigate parents’ perceptions of service access for their adult children with autism spectrum disorder (ASD). Access includes accommodation, acceptability, availability, and affordability (4 As) of services. This study examined which of the 4 As presented the biggest challenges across multiple types of services needed. Fifty-one parents of adult children with ASD participated in semistructured interviews sharing perceptions of support services available for their adult children. Parents discussed eight types of services (case management, educational programs, employment and employment supports, physical/mental health care, housing, day program or respite care, social life and recreation, and transportation). Based on parent perceptions, services were inconsistently accessible, difficult to obtain, and inadequate. Trained social workers and health care professionals are needed to provide and coordinate services for adults with ASD.
Application of transesophageal echocardiography, left atrial appendage angiography, cardiac computed tomography angiography, and three-dimensional reconstruction model in left atrial appendage occlusion
Authors: Lei Huang Hao , Kang Li Hua , Yuan Song Zhi , Chen Wan , Qing Yao
Published: January 2020

Objective: The objective was to evaluate the application of transesophageal echocardiography, left atrial appendage angiography, cardiac computed tomography angiography, and three-dimensional reconstruction model in the left atrial appendage occlusion. Methods: A total of 53 patients with persistent atrial fibrillation hospitalized from January 2015 to February 2019 were selected. Transesophageal echocardiography and cardiac computed tomography angiography were performed simultaneously before operation, and three-dimensional reconstruction of the left atrial appendage model was performed based on the cardiac computed tomography angiography findings. The morphology and size of the left atrial appendage were displayed by the left atrial appendage angiography during the operation. Results: Cardiac computed tomography angiography revealed filling defects in the left atrial appendage in four patients, whereas transesophageal echocardiography revealed thrombosis in two patients of the four patients. According to the cardiac computed tomography angiography results, the morphology of the left atrial appendage was classified into chicken wing–like, cauliflower-like, wind vane–like, and cactus-like. The diameters and depths of the left atrial appendage measured by cardiac computed tomography angiography and three-dimensional reconstruction model were found to be the greatest, and the orifice sizes and depths of the left atrial appendage measured by the left atrial appendage angiography were the smallest. Conclusion: Transesophageal echocardiography, left atrial appendage angiography, cardiac computed tomography angiography, and three-dimensional reconstruction model can evaluate the morphology and size of the left atrial appendage. The cardiac computed tomography angiography and three-dimensional reconstruction model could demonstrate the internal structure of the left atrial appendage more clearly.
PPMS onset upon adalimumab treatment extends the spectrum of anti-TNF-α therapy-associated demyelinating disorders
Authors: Engel Sinah , Luessi Felix , Mueller Aneka , Schopf Rudolf E. , Zipp Frauke , Bittner Stefan
Published: January 2020

Since their introduction in 1999, anti-tumour necrosis factor-α (anti-TNF-α) therapies have been suspected repeatedly to be associated with the occurrence of central nervous system (CNS) demyelinating disorders, including multiple sclerosis (MS). However, recent publications were restricted to descriptions of monophasic demyelinating events or cases of relapsing–remitting MS (RRMS). We here provide the first case report of primary progressive MS (PPMS) onset upon anti-TNF-α therapy as well as a literature review of previously published cases of anti-TNF-α therapy-associated MS onset. The 51-year old male patient was treated with adalimumab due to psoriasis arthritis. About 18 months after treatment initiation, he developed slowly progressing neurological deficits including gait impairment, paraesthesia of the lower limbs, strangury and visual impairment, which led to the discontinuation of adalimumab therapy. Magnetic resonance imaging of the brain and the spinal cord revealed multiple inflammatory lesions and cerebrospinal fluid examination showed slight pleocytosis and positive oligoclonal bands. Thus, PPMS was diagnosed according to the 2017 revision of the McDonald criteria. As PPMS often causes only subtle symptoms in the beginning and early treatment discontinuation of anti-TNF-α therapy seems essential to improve the patient’s outcome, we think that it is important to increase the awareness of slowly progressing neurological deficits as a potential adverse event of anti-TNF-α therapy among all clinicians involved in the initiation and monitoring of these drugs. In addition, the occurrence of both RRMS and progressive MS upon anti-TNF-α therapy might suggest a shared TNF-α-mediated pathophysiological mechanism in the evolution of all MS subtypes.
Formalin Versus Bouin Solution for Testis Biopsies: Which Is the Better Fixative?
Authors: Ellenburg James L , Kolettis Peter , Drwiega Joseph C , Posey Anna M , Goldberg Matthew , Mehrad Mitra , Giannico Giovanna , Gordetsky Jennifer
Published: January 2020

Purpose:

Some resources recommended Bouin solution for the fixation of testis biopsy specimens. We compared the histologic quality of rat testicular tissue using buffered formalin and Bouin solution as fixatives.

Methods:

We prospectively compared the histologic quality of rat testicular tissue fixed in Bouin solution versus formalin. Testicular tissue was harvested post-mortem from six rats. Each testis was removed and sectioned in half; one half was fixed in formalin and one half in Bouin solution. Testicular tissue histology (nuclear membrane detail, nuclear granularity, cytoplasmic granularity, cytoplasmic membrane detail, and basement membrane detail) was graded as high quality (2) or low quality (1). Sloughing of cells into the lumens of the seminiferous tubules was graded on a 0-3 scale (0=none, 1=mild, 2=moderate, 3=extensive).

Results:

All slides regardless of fixative were of appropriate quality for the histologic evaluation of spermatogenesis. The average sloughing score for formalin cases was 1.4 and for Bouin cases 1.6. Formalin fixed tissue was found to have high quality nuclear membrane detail (2), nuclear granularity (1.9), and basement membrane detail (2). Cytoplasmic granularity was of lesser but adequate quality (1.4). Cytoplasmic membrane detail was poor, (1). Tissue fixed with Bouin solution had high quality basement membrane detail (2) and adequate cytoplasmic granularity (1.5), nuclear membrane detail (1.3) and nuclear granularity (1.4). Cytoplasmic membrane detail was poor (1).

Conclusion:

Compared to Bouin solution, formalin fixation of rat testicular tissue produced adequate histology for the evaluation of spermatogenesis and may be superior to Bouin solution for certain cytologic features.
Achieving complete remission in CLL patients treated with ibrutinib: clinical significance and predictive factors
Authors: Strati Paolo , Schlette Ellen J. , Solis Soto Luisa M. , Duenas Daniela E. , Sivina Mariela , Kim Ekaterina , Keating Michael J. , Wierda William G. , Ferrajoli Alessandra , Kantarjian Hagop , Estrov Zeev , Jain Nitin , Thompson Philip A. , Wistuba Ignacio I. , Burger Jan A.
Published: January 2020

In this Letter to Blood, Strati and colleagues report that depth of response is associated with durability of benefit in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib. Patients who achieve a complete remission have longer durations of response than those with partial response. The authors provide preliminary evidence associating tumor-associated macrophages with depth of treatment response.
How I treat anemia in heart failure
Authors: Anand Inder , Gupta Pankaj
Published: January 2020

Anemia is a very common comorbidity in patients with heart failure (HF), affecting ∼30% of stable ambulatory patients and 50% patients with acute decompensated HF. Absolute or functional iron deficiency (ID) is seen in ∼50% patients with HF. Both of these comorbidities often coexist and are independently associated with increased mortality and hospitalizations. These findings led several investigators to test the hypotheses that treatment of anemia and ID in HF would improve symptoms and long-term outcomes. Small studies showed that erythropoiesis-stimulating agents (ESAs) improve subjective measures of HF. However, a large pivotal outcome trial found that the ESA darbepoetin alfa did not improve long-term outcomes in patients with HF with reduced ejection fraction and instead was associated with adverse effects. Studies using IV iron have had somewhat greater success, showing improvements in subjective and some objective measures of HF. However, more research is needed to establish the best treatment options for these high-risk patients. We present 5 common scenarios of patients with HF and anemia and describe our personal approach on how we might treat them based on objective evidence where available. An algorithm that offers guidance in regard to personalized therapy for such patients is also presented.
Spatial-temporal distribution of human brucellosis in mainland China from 2004 to 2017 and an analysis of social and environmental factors
Authors: Peng Cheng , Li Yan-Jun , Huang De-Sheng , Guan Peng
Published: January 2020

Background

This study aimed to describe the changing distribution of human brucellosis between 2004 and 2017 in mainland China and seek scientific evidence of the relationship between socio-economic, environmental, and ecological factors and human brucellosis incidence.

Methods

The annual numbers of brucellosis cases and incidence rates from 31 provinces in mainland China between 2004 and 2017 were obtained from the Data-Center for China Public Health Science. The number of monthly brucellosis cases in 2018 was obtained from the Chinese Center for Disease Control and Prevention. The electronic map of the People’s Republic of China was downloaded from the National Earth System Science Data Sharing Platform. Human population density, gross domestic product (GDP), and an inventory of cattle and sheep at the end of each year from 2004 to 2017 were obtained from the National Bureau of Statistics of China. Annual rainfall data from 31 provinces in the People’s Republic of China from 2004 to 2017 were collected from the China Meteorological Data Service Center. The risk distribution and changing trends of human brucellosis were mapped with ArcGIS. A cluster analysis was employed to identify geographical areas and periods with statistically significant incidence rates. Multivariate linear regression was used to determine possible factors that were significantly correlated with the presence of human brucellosis cases.

Results

Human brucellosis cases have spread throughout the whole country. Human brucellosis cases occurred mostly from March to August and were concentrated from April to July. The inventory of sheep, GDP, and climate were significantly correlated with the presence of brucellosis cases in mainland China.

Conclusions

The geographical expansion of human brucellosis in mainland China was observed, so did the high-incidence clusters between 2004 and 2017. Most of the cases were reported during the early spring to early summer (February–August). Results from the multivariate linear regression suggested that the inventory of sheep, GDP, and climate were significantly associated with the incidence of human brucellosis in mainland China.
Bayesian mixture regression analysis for regulation of Pluripotency in ES cells
Authors: Aflakparast Mehran , Geeven Geert , de Gunst Mathisca C.M.
Published: January 2020

Background

Observed levels of gene expression strongly depend on both activity of DNA binding transcription factors (TFs) and chromatin state through different histone modifications (HMs). In order to recover the functional relationship between local chromatin state, TF binding and observed levels of gene expression, regression methods have proven to be useful tools. They have been successfully applied to predict mRNA levels from genome-wide experimental data and they provide insight into context-dependent gene regulatory mechanisms. However, heterogeneity arising from gene-set specific regulatory interactions is often overlooked.

Results

We show that regression models that predict gene expression by using experimentally derived ChIP-seq profiles of TFs can be significantly improved by mixture modelling. In order to find biologically relevant gene clusters, we employ a Bayesian allocation procedure which allows us to integrate additional biological information such as three-dimensional nuclear organization of chromosomes and gene function. The data integration procedure involves transforming the additional data into gene similarity values. We propose a generic similarity measure that is especially suitable for situations where the additional data are of both continuous and discrete type, and compare its performance with similar measures in the context of mixture modelling.

Conclusions

We applied the proposed method on a data from mouse embryonic stem cells (ESC). We find that including additional data results in mixture components that exhibit biologically meaningful gene clusters, and provides valuable insight into the heterogeneity of the regulatory interactions.
Comparison of the molecular and cellular phenotypes of common mouse syngeneic models with human tumors
Authors: Zhong Wenyan , Myers Jeremy S. , Wang Fang , Wang Kai , Lucas Justin , Rosfjord Edward , Lucas Judy , Hooper Andrea T. , Yang Sharon , Lemon Lu Anna , Guffroy Magali , May Chad , Bienkowska Jadwiga R. , Rejto Paul A.
Published: January 2020

Background

The clinical success of immune checkpoint inhibitors demonstrates that reactivation of the human immune system delivers durable responses for some patients and represents an exciting approach for cancer treatment. An important class of preclinical in vivo models for immuno-oncology is immunocompetent mice bearing mouse syngeneic tumors. To facilitate translation of preclinical studies into human, we characterized the genomic, transcriptomic, and protein expression of a panel of ten commonly used mouse tumor cell lines grown in vitro culture as well as in vivo tumors.

Results

Our studies identified a number of genetic and cellular phenotypic differences that distinguish commonly used mouse syngeneic models in our study from human cancers. Only a fraction of the somatic single nucleotide variants (SNVs) in these common mouse cell lines directly match SNVs in human actionable cancer genes. Some models derived from epithelial tumors have a more mesenchymal phenotype with relatively low T-lymphocyte infiltration compared to the corresponding human cancers. CT26, a colon tumor model, had the highest immunogenicity and was the model most responsive to CTLA4 inhibitor treatment, by contrast to the relatively low immunogenicity and response rate to checkpoint inhibitor therapies in human colon cancers.

Conclusions

The relative immunogenicity of these ten syngeneic tumors does not resemble typical human tumors derived from the same tissue of origin. By characterizing the mouse syngeneic models and comparing with their human tumor counterparts, this study contributes to a framework that may help investigators select the model most relevant to study a particular immune-oncology mechanism, and may rationalize some of the challenges associated with translating preclinical findings to clinical studies.
The complete genome sequence of the nitrile biocatalyst Rhodococcus rhodochrous ATCC BAA-870
Authors: Frederick Joni , Hennessy Fritha , Horn Uli , de la Torre Cortés Pilar , van den Broek Marcel , Strych Ulrich , Willson Richard , Hefer Charles A. , Daran Jean-Marc G. , Sewell Trevor , Otten Linda G. , Brady Dean
Published: January 2020

Background

Rhodococci are industrially important soil-dwelling Gram-positive bacteria that are well known for both nitrile hydrolysis and oxidative metabolism of aromatics.Rhodococcus rhodochrousATCC BAA-870 is capable of metabolising a wide range of aliphatic and aromatic nitriles and amides. The genome of the organism was sequenced and analysed in order to better understand this whole cell biocatalyst.

Results

The genome ofR. rhodochrousATCC BAA-870 is the firstRhodococcusgenome fully sequenced using Nanopore sequencing. The circular genome contains 5.9 megabase pairs (Mbp) and includes a 0.53 Mbp linear plasmid, that together encode 7548 predicted protein sequences according to BASys annotation, and 5535 predicted protein sequences according to RAST annotation. The genome contains numerous oxidoreductases, 15 identified antibiotic and secondary metabolite gene clusters, several terpene and nonribosomal peptide synthetase clusters, as well as 6 putative clusters of unknown type. The 0.53 Mbp plasmid encodes 677 predicted genes and contains the nitrile converting gene cluster, including a nitrilase, a low molecular weight nitrile hydratase, and an enantioselective amidase.

Although there are fewer biotechnologically relevant enzymes compared to those found in rhodococci with larger genomes, such as the well-knownRhodococcus jostiiRHA1, the abundance of transporters in combination with the myriad of enzymes found in strain BAA-870 might make it more suitable for use in industrially relevant processes than other rhodococci.

Conclusions

The sequence and comprehensive description of theR. rhodochrousATCC BAA-870 genome will facilitate the additional exploitation of rhodococci for biotechnological applications, as well as enable further characterisation of this model organism. The genome encodes a wide range of enzymes, many with unknown substrate specificities supporting potential applications in biotechnology, including nitrilases, nitrile hydratase, monooxygenases, cytochrome P450s, reductases, proteases, lipases, and transaminases.
The advantages of the Matthews correlation coefficient (MCC) over F1 score and accuracy in binary classification evaluation
Authors: Chicco Davide , Jurman Giuseppe
Published: January 2020

Background

To evaluate binary classifications and their confusion matrices, scientific researchers can employ several statistical rates, accordingly to the goal of the experiment they are investigating. Despite being a crucial issue in machine learning, no widespread consensus has been reached on a unified elective chosen measure yet. Accuracy and F1score computed on confusion matrices have been (and still are) among the most popular adopted metrics in binary classification tasks. However, these statistical measures can dangerously show overoptimistic inflated results, especially on imbalanced datasets.

Results

The Matthews correlation coefficient (MCC), instead, is a more reliable statistical rate which produces a high score only if the prediction obtained good results in all of the four confusion matrix categories (true positives, false negatives, true negatives, and false positives), proportionally both to the size of positive elements and the size of negative elements in the dataset.

Conclusions

In this article, we show how MCC produces a more informative and truthful score in evaluating binary classifications than accuracy and F1score, by first explaining the mathematical properties, and then the asset of MCC in six synthetic use cases and in a real genomics scenario. We believe that the Matthews correlation coefficient should be preferred to accuracy and F1score in evaluating binary classification tasks by all scientific communities.
A detailed in silico analysis of secondary metabolite biosynthesis clusters in the genome of the broad host range plant pathogenic fungus Sclerotinia sclerotiorum
Authors: Graham-Taylor Carolyn , Kamphuis Lars G. , Derbyshire Mark C.
Published: January 2020

Background

The broad host range pathogenSclerotinia sclerotioruminfects over 400 plant species and causes substantial yield losses in crops worldwide. Secondary metabolites are known to play important roles in the virulence of plant pathogens, but little is known about the secondary metabolite repertoire ofS. sclerotiorum. In this study, we predicted secondary metabolite biosynthetic gene clusters in the genome ofS. sclerotiorumand analysed their expression during infection ofBrassica napususing an existing transcriptome data set. We also investigated their sequence diversity among a panel of 25 previously publishedS. sclerotiorumisolate genomes.

Results

We identified 80 putative secondary metabolite clusters. Over half of the clusters contained at least three transcriptionally coregulated genes. Comparative genomics revealed clusters homologous to clusters in the closely related plant pathogenBotrytis cinereafor production of carotenoids, hydroxamate siderophores, DHN melanin and botcinic acid. We also identified putative phytotoxin clusters that can potentially produce the polyketide sclerin and an epipolythiodioxopiperazine. Secondary metabolite clusters were enriched in subtelomeric genomic regions, and those containing paralogues showed a particularly strong association with repeats. The positional bias we identified was borne out by intraspecific comparisons that revealed putative secondary metabolite genes suffered more presence / absence polymorphisms and exhibited a significantly higher sequence diversity than other genes.

Conclusions

These data suggest thatS. sclerotiorumproduces numerous secondary metabolites during plant infection and that their gene clusters undergo enhanced rates of mutation, duplication and recombination in subtelomeric regions. The microevolutionary regimes leading toS. sclerotiorumsecondary metabolite diversity have yet to be elucidated. Several potential phytotoxins documented in this study provide the basis for future functional analyses.
A software package for immunologists to learn simulation modeling
Authors: Handel Andreas
Published: January 2020

Background

As immunology continues to become more quantitative, increasingly sophisticated computational tools are commonly used. One useful toolset are simulation models. Becoming familiar with such models and their uses generally requires writing computer code early in the learning process. This poses a barrier for individuals who do not have prior coding experience.

Results

To help reduce this barrier, I wrote software that teaches the use of mechanistic simulation models to study infection and immune response dynamics, without the need to read or write computer code. The software, called Dynamical Systems Approach to Immune Response Modeling (DSAIRM), is implemented as a freely available package for the R programming language. The target audience are immunologists and other scientists with no or little coding experience. DSAIRM provides a hands-on introduction to simulation models, teaches the basics of those models and what they can be used for. Here, I describe the DSAIRM R package, explain the different ways the package can be used, and provide a few introductory examples.

Conclusions

Working through DSAIRM will equip individuals with the knowledge needed to critically assess studies using simulation models in the published literature and will help them understand when such a modeling approach might be suitable for their own research. DSAIRM also provides users a potential starting point towards development and use of simulation models in their own research.
Method comparison for the direct enumeration of bacterial species using a chemostat model of the human colon
Authors: Moura Ines B. , Normington Charmaine , Ewin Duncan , Clark Emma , Wilcox Mark H. , Buckley Anthony M. , Chilton Caroline H.
Published: January 2020

Background

Clostridioides difficileinfection (CDI) has a high recurrent infection rate. Faecal microbiota transplantation (FMT) has been used successfully to treat recurrent CDI, but much remains unknown about the human gut microbiota response to replacement therapies. In this study, antibiotic-mediated dysbiosis of gut microbiota and bacterial growth dynamics were investigated by two quantitative methods: real-time quantitative PCR (qPCR) and direct culture enumeration, in triple-stage chemostat models of the human colon. Threein vitromodels were exposed to clindamycin to induce simulated CDI. All models were treated with vancomycin, and two received an FMT. Populations of total bacteria,Bacteroidesspp.,Lactobacillusspp.,Enterococcusspp.,Bifidobacteriumspp.,C. difficile,and Enterobacteriaceae were monitored using both methods. Total clostridia were monitored by selective culture. Using qPCR analysis, we additionally monitored populations ofPrevotellaspp.,Clostridium coccoidesgroup, andClostridium leptumgroup.

Results

Both methods showed an exacerbation of disruption of the colonic microbiota following vancomycin (and earlier clindamycin) exposure, and a quicker recovery (within 4 days) of the bacterial populations in the models that received the FMT.C. difficileproliferation, consistent with CDI, was also observed by both qPCR and culture. Pearson correlation coefficient showed an association between results varying from 98% forBacteroidesspp., to 62% for Enterobacteriaceae.

Conclusions

Generally, a good correlation was observed between qPCR and bacterial culture. Overall, the molecular assays offer results in real-time, important for treatment efficacy, and allow the monitoring of additional microbiota groups. However, individual quantification of some genera (e.g. clostridia) might not be possible without selective culture.