bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatores Associados ao Atraso entre o Diagnóstico e o Início do Tratamento de Câncer de Mama: um Estudo de Coorte com 204.130 Casos no Brasil
Authors: Coutinho de Medeiros Giselle , Gomes Chagas Teodózio Clarice , Alves Nogueira Fabro Erica , Sales de Aguiar Suzana , Henrique Machado Lopes Artur , Cordeiro de Conte Bárbara , Vieira da Silva Erisvan , Pestana Coelho Lyssandra Luiza , Ferreira Muniz Nitza , Pimentel de Carvalho Schuab Sara Isabel , Bergmann Anke , Santos Thuler Luiz Claudio
Published: August 2020

Introdução: O câncer de mama e considerado um problema de saúde publica, tendo crescente incidência mundial. Diversos fatores contribuem para o diagnostico tardio e dificultam o inicio do tratamento, repercutindo em um pior prognostico. Objetivos: Analisar o intervalo de tempo entre o diagnostico e o inicio do primeiro tratamento oncológico na população brasileira, além de avaliar os fatores associados aos maiores intervalos. Método: Trata-se de um estudo de coorte retrospectivo com 540.529 pacientes cadastrados no Sistema de Registros Hospitalares de Câncer (SisRHC) no período de 2000 a 2017. Utilizou-se como desfecho o intervalo de tempo entre o diagnostico e o inicio do primeiro tratamento oncológico, considerando-se como atraso o intervalo maior do que 60 dias. Para analise das variáveis, foram realizadas analise descritiva e regressão logística simples (IC95%; p<0,05). Resultados: Foram analisados 204.130 casos que apresentaram media de idade de 55,8 anos (±13,24), sendo predominantemente do sexo feminino (99,1%), 55,1% eram da Região Sudeste e 71,4% residiam em cidades não capitais. A mediana do intervalo de tempo entre o diagnostico e o inicio do primeiro tratamento oncológico foi de 63 dias (variação interquartil = 36-109). As variáveis sociodemográficas, clinicas e relacionadas ao tratamento mostraram impacto no intervalo de tempo, com exceção da variável sexo. Conclusão: O tempo entre o diagnostico e o inicio do primeiro tratamento oncológico foi elevado. Fatores sociodemográficos, clínicos e relacionados ao tratamento influenciam nos intervalos de tempo. Identifica-los precocemente pode contribuir para o direcionamento de ações a esses grupos mais vulneráveis ao atraso.
Educating Gen-Z: Developing a Teaching and Learning Ecosystem in a 21st Century Learning
Authors: Chan Vincent , Binti Abdul Malik Nur Iylia Syafiqah , Ee Chun Cedric Choong
Published: August 2020

Fostering a teaching and learning ecosystem is vital in the 21st century teaching and learning process to determine student's positive impact on social academic outcomes. This paper proposed a teaching and learning ecosystem for Gen-Z students and the researchers developed RICES concept and Fish approach to support their ecosystem. This study will investigate and explore the implementation of RICES (Relationship & Role, Introduction, Communication, Educate and Structure) strategy to build and foster the teaching
and learning ecosystem. The ecosystem will ensure educating this generation will be more holistic whilst enabling the learning-centred approach to be effectively used. The paper is concluded with the approach and impact of RICES. A descriptive research method was conducted with the tertiary students. The result revealed that RICES strategy shows a significant relationship among of each element.
Usage of Mobile Application in Assisting Chemical Experiments
Authors: Sin Y.K.
Published: August 2020

ChemEx is a mobile application that is created to assist students in performing chemical experiments. Students who study Bachelor of Electronic Engineering majoring in Nanotechnology use chemical experiment to synthesise nanoparticles. Through observation, they lack of confidence during the nanoparticles synthesis because they were not involved in any chemistry activities after foundation. To overcome this issue, a mobile application called ChemEx is created using Android Studio. In ChemEx, the usage of apparatuses and instruments, lab safety, the concept molarity and dilution, as well as the data of chemicals are introduced. Pre and post-test are used to evaluate the effectiveness of ChemEx in helping the
students. Besides this, feedback form is used to evaluate the satisfaction of students after using ChemEx. The pre and post-test results show that the students have improved their understanding in apparatuses, safety, molarity and dilution. In the meantime, feedbacks show students are satisfied using ChemEx.
Effectiveness of Using Appropriate Blended Learning Tools for Teaching and Learning Computer Programming Related Courses
Authors: Joseph Emerson Raja , Hoseen Md Jakir , Salleh Fazly , Way Soong Lim
Published: August 2020

With the advent of technology there are plenty of blended learning tools available for us to use in teaching and training activity. Selecting appropriate tools for a particular category of students and the nature of the subject being taught is important to achieve better academic results. Hence, the objective of this research is to assess effectiveness of various blended learning tools and to find the appropriate tool for teaching a
computer -based campus in Malaysia. This subject was delivered using four selected blended learning digital tools; ED puzzle virtual classroom videos, Home works on MMLS, MMLS online Quiz and MMLS discussion board, at the beginning of Trimester 2, 2018/2019. They were asked in the middle of the trimester to rate the usefulness of the four selected blended learning digital tools in a 5-point scale using an online survey. The analysis
feedback shows that D puzzle virtual the trimester. The effectivenes when the achievements of the students in terms of their academic performance were compared with previous year. It clearly shows that the academic performance of the students of year 2019 is better than of students towards student centred learning.
Student’s Perception on Implementation of Blended Learning in UNITEN
Authors: Bin Abdul Wahida Rahmat Bin Abdul Wahida , Bin Abd. Aziz T. J. Iskandar , Bin Abd. Aziz Ahmad Ikhsan , Binti Azami Nur Hanani , Binti Aziz Nur Aimi Syaqilah
Published: August 2020

Blended learning (BL) can be regarded as a teaching approach that combines online and face-to-face method of instructions in which it integrates the conventional classroom teaching with a combination of media, tools and teaching methods in web-based environment settings. Universiti Tenaga Nasional (UNITEN) has been implementing blended learning since 2016 on selected courses offered. The implementation of blended learning was carried out in four levels comprising of information dissemination, online assessment, flipped teaching and adaptive learning. The objectives of this study are to investigate students' awareness towards blended learning implementation and to measure their level of satisfaction on the courses they registered.
Factors Associated with Use of Maternal Health Services in Nepal: Analysis of the 2016 Nepal Demographic and Health Survey
Authors: Bhattarai Prithutam
Published: August 2020

Background: Timely access and use of health services are critical for improving maternal health services. The objective of present study is to identify key factors related to antenatal care and institutional delivery services in Nepal.Methods: Data from the Nepal Demographic Health Survey 2016 was analyzed. Women who have taken four or more antenatal checkup (ANC4+), and who delivered at a health Institution were considered outcome variables. Logistic regression analysis was used to compute odds ratio. Women (15-49) having most recent birth in 5 years preceding the survey were included in the study.Results: 69.4% women had taken four or more ANC and 60.6 % had given delivery at a health institution. Age of mother at birth of child, birth order, residence, and ethnicity were significantly associated with use of maternal health service. Educated were 3.79(CI2.83-5.08) times likely to take ANC4+ and 2.71 (CI 2.05-3.57) times likely to give birth at health institution. Richest women were 2.25(CI2.83-5.08) times likely to utilize the ANC4+ service and 9.48(CI6.46-13.91) times likely to give birth at health institution. Women in Province 7 were 3.16(CI2.14-4.67) times likely to utilize ANC4+ service and 2.71(CI 1.83-4.05) times likely to give delivery in health institution compared to women in Province 6.Conclusions: Higher educated and richest women were using antenatal care and institutional delivery compared to less educated. The finding reinforces importance of empowering women with education and improving economic situation.Keywords: Antenatal care; demographic and health survey; institutional delivery; maternal health; Nepal.
A Review of eHealth Initiatives: Implications for Improving Health Service Delivery in Nepal
Authors: KC Ashish , Sunny Avinash K , Poudel Rajendra Prasad , Basnet Omkar
Published: August 2020

The aim of this paper is to take stock of the use of information and communication technologies in delivering health services in Nepal and identify bottlenecks in implementation for improving delivery of health services. A descriptive review was conducted from May to September 2016. Data were collected from organizations working on the different thematic areas in health where information and communication technologies was used. Fifteen ongoing eHealth projects were identified in the areas of monitoring and surveillance, electronic health records/electronic medical records, health information system, and telemedicine. Common challenges were addressed, including a lack of funding, infrastructure, electricity and network, and national capacity. Most eHealth projects were not integrated into the national system. Working at a national level to address the challenges, centralizing eHealth projects and developing national policies would ensure to adopt eHealth at a right place and to accelerate eHealth initiatives.Keywords: eHealth; health service delivery;information and communication technologies (ICT); Nepal.
Severity of Hyperemesis Gravidarum and Associated Maternal factors
Authors: Thakur Murari , Gautam Jageshwor , Dangal Ganesh
Published: August 2020

Background: Hyperemesis gravidarum is the most severe form of nausea and vomiting in pregnancy. It is one of the most common cause of early pregnancy admissions and associated with various maternal risk factors . Very few studies have been conducted among Nepalese women with hyperemesis gravidarum. This study aims to identify various maternal risk factors among Nepalese women and its severity using pregnancy unique quantification of emesis scoring. Methods: This is a cross sectional observational study conducted at Paropakar Maternity and Women’s Hospital. Total duration of the study period was for one year from February 2018 to Janurary 2019. A total of 144 patients meeting the inclusion criteria were included in the study.The severity of the hyperemesis gravidarum was assessed and classified using pregnancy unique quantification of emesis scoring. Various maternal demographic, obstetric and personal factors were studied in relation to the incidence and severity of hyperemesis gravidarum.Results: Moderate (49.30%) to severe(50.69%) hyperemesis gravidarum were admitted in the hospital. Most women were nulliparous from 20-24 years age group. Among all categories of BMI, underweight had more severe hyperemesis gravidarum (63.63%) and overweight patient had increased incidence of moderate hyperemesis gravidarum (66.66%). Women with previous dysmenorrhea had severe hyperemesis gravidarum (54.05%) and non-smoker had severe hyperemesis gravidarum (52.03%) while smoker had moderate hyperemesis gravidarum (57.14%).Conclusions: Pregnant women of age group of 20-24 years, nulliparity and underweight were associated with severe hyperemesis gravidarum. Keywords: Hyperemesis gravidarum; maternal factors ; pregnancy unique quantification of emesis.
Investigating the Availability and Usage of Seatbelts in Malawi for Policy Review and Formulation
Authors: Ngwira Gibson Mpokonyoka , Bolaane Benjamin , Parida Bhagabat P.
Published: August 2020

Road fatalities remain a major public health concern as over 1.3 million people across the world die in road accidents annually, and another 20-50 million sustain injuries. Malawi, with vehicle ownership about 437,416, has not been an exception to this, with reported fatality rates of 35 crash deaths per 100,000 population, possibly due to limited understanding of factors that contribute to such high road fatality rates. This may have resulted in implementing inappropriate and ineffective mitigation measures. Thus, the overall objective of this study was to investigate the availability, including their functionality and usage of seatbelts in motor vehicles, which could possibly be one of the major factors for increase in road fatalities. To establish the rates of availability, ncluding their functionality and usage of seatbelts in motor vehicles, primary data through survey for a sample of 1,200 vehicles were investigated. The independent ariables of data were cross tabulated with the dependent variables to establish these rates. Chi-square test was also performed to establish the significance of associations between the cross tabulated variables. The analysis found that Malawi’s drivers and assengers poorly comply with seatbelt laws. The overall seatbelt usage rate was 35.8%. In this regard, where over 90% of motor vehicles in Malawi have functional seatbelts, poor enforcement of existing seatbelt laws and awareness on the dangers of not using eatbelts could account for the low usage.
Examining the relationship between road safety outcomes and the built environment in Bogotá, Colombia
Authors: Vergel-Tovar Erik , López Segundo , Lleras Natalia , Hidalgo Darío , Rincón Maryfely , Orjuela Sebastián , Vega Juliana
Published: August 2020

The study of the relationship between the built environment and road safety suggests that density and urban design features may be associated with traffic incidents. In this study, quantitative data analysis using generalized ordinal logit models, and linear and log-linear regressions was conducted to estimate the influence of the built environment on road safety in Bogotá, focusing on road crash outcomes by estimating the influence of built environment attributes on fatalities and injured victims. The analysis was performed using georeferenced road crash data from 2012 to 2016 provided by Bogotá’s Department of Mobility. The quantitative data analysis focused on arterial roads, considering crash severity and types of road users involved, as well as Bus Rapid Transit System corridors. This analysis was complemented with on-site interviews. The results suggest that the presence of pedestrian bridges is positively associated with the number of road crashes for all road users. Other urban variables such as density and distance to intersections showed significant correlations with safety.
A Qualitative Study of the Context of Speed Management in Cambodia
Authors: King Mark , Pen Sakony
Published: August 2020

Cambodia has one of the highest road crash rates amongst low-and middle-income countries (LMICs), with speeding a major contributor. Best practice speed management has been promoted internationally, and transfer of knowledge and best practices from high income countries (HICs) to LMICs has been recommended. However there is a need to take account of the physical, social and political environment of the LMIC concerned. The aims of this study were to analyse the context of speed management in Cambodia using the Road Safety Space Model (RSSM), and to recommend how best practice speed management could be implemented. Secondary sources were reviewed, and semi-structured interviews were conducted with 13 key informants with professional experience in speed management and enforcement in Cambodia. The interviews were recorded, transcribed, translated and thematic analysis was undertaken. The findings were interpreted using RSSM, within the categories of economic, institutional and social/cultural factors. Although there are Cambodian government initiatives to address speeding issues, many challenges were revealed. Recommendations are made, aligned with best practice recommendations for speed management. They include establishment of a functional road hierarchy and a review of provisions for different road users; a move away from the current complex vehicle-based speed limit scheme; improved databases to support enforcement, monitoring and evaluation; a review of current legislation and practices around fines and implementation of the licence points system; improvement of the spatial and temporal coverage of enforcement; public education to support enforcement; workplace safety measures to address speeding; and better coordination and funding across government agencies.
Features of Low-Income and Middle-Income Countries making Road Safety more Challenging
Authors: Job Soames , Wambulwa William M
Published: August 2020

Low- and Middle-Income Countries suffer the large majority (93%) of global road crash deaths and face particular challenges in managing this crisis. This paper presents global data and trends revealing underlying features of the problem for LMICs. LMICs are commonly grouped and described together in road safety commentaries, yet appreciation of the substantial differences between LICs and MICs is vital. While global deaths per 100,000 people have stabilized during the UN Decade of Road Safety, the population rate has increased in LICs (by 8.2%), while decreasing in HIC and MIC. LICs have less resources to address road safety and younger populations adding to risk. Wide variations on road safety performance exist within country income groups, with some of this variance occurring systematically between regions. Absolute numbers of
deaths are increasing due to increasing population and increasing vehicle fleets in LMICs compared with HICs. The capacity of MICs, and especially LICs, to manage road safety is hampered by poor crash data to guide action as well less available funding and resources to achieve safer road engineering, safer vehicles, and protect the large
proportions of vulnerable road users. Road crash deaths and injuries are retarding the economic growth of LMICs and investing road safety is a costeffective means by which LMICs can move towards becoming HICs. Vital opportunities for cost-effective savings of lives and debilitating injuries in LMICs include better management of speed (especially through infrastructure), improving safety infrastructure for pedestrians, increasing seatbelt use, and shifting travel from motorcycles to buses through provision of Bus Rapid Transit systems.
Exploring oxygen dynamics and depletion in an intensive bivalve production area in the coastal sea off Rushan Bay, China
Authors: Wu W , Liu J , Bouwman AF , Wang J , Yin X , Zang J , Ran X
Published: August 2020

Hypoxia is a mounting problem affecting the world’s coastal waters, with severe consequences for marine ecosystems. Coastal oxygen consumption has been increasing, mainly owing to the continued spread nutrient discharges. Using field observations, incubation experiments and numerical modeling, we studied the spatial and temporal variability of dissolved oxygen (DO) in the coastal area off Rushan Bay, China, a typical coastal area influenced by intensive mariculture oyster production. Results show that summer DO is increasingly declining in bottom waters below the thermocline. Oxygen input from the air-sea interface exchange, primary production and net water exchange accounted for 70, 26 and 4% of the DO supply, respectively. Oxygen consumption by organic matter decomposition in the water column and sediment contributed, respectively, 79 and 21% to the total DO removal. In regions such as the coastal area off Rushan Bay where the algal biomass filtered by bivalves is imported from elsewhere by sea currents, the carbon and nutrient release by mariculture may lead to local oxygen depletion, which increased from a negligible contribution in 1984 to up to 24% of the total DO consumption in the water column in the period of June-September 2014. This phenomenon of oxygen depletion is a concern for other coastal areas with intensive bivalve and other shellfish production.
Reconstruction of temperature experienced by Pacific bluefin tuna Thunnus orientalis larvae using SIMS and microvolume CF-IRMS otolith oxygen isotope analyses
Authors: Hane Y , Kimura S , Yokoyama Y , Miyairi Y , Ushikubo T , Ishimura T , Ogawa N , Aono T , Nishida K
Published: August 2020

This study aimed to reconstruct temperatures experienced during the larval period by adult Pacific bluefin tuna Thunnus orientalis using high-resolution otolith stable oxygen isotope (δ18O) analysis. A novel otolith sample preparation protocol for secondary ion mass spectrometry (SIMS) analysis developed in this study reduced the background noise of SIMS measurements, enabling analyses of >10 times higher resolution around the otolith core compared to previous studies using conventional isotope ratio mass spectrometry (IRMS). The values obtained from SIMS were compared to those obtained by microvolume δ18Ootolith analysis using micromilling and conventional continuous-flow IRMS (CF-IRMS). There was a systematic offset (average 0.41‰ with SIMS resulting in lower values) most likely caused by matrix effects on SIMS δ18Ootolith values that can be calibrated using a strong linear relationship between SIMS and CF-IRMS measurements (r2 = 0.78, p < 0.001). The core-to-edge δ18Ootolith of 5 Pacific bluefin tuna revealed fine-scale seasonal variations in water temperature agreeing with known migration patterns. In addition, the ambient water temperature experienced during larval stages (about 10-20 d post hatch) estimated from otolith core δ18O ranged from 26.7 to 30.7°C, overlapping with temperatures associated with the occurrence of larval Pacific bluefin tuna. Combining SIMS and microvolume CF-IRMS δ18O otolith analyses offers a microscale examination of fish ecology that is not possible with conventional IRMS techniques. This novel method is particularly useful for understanding the early life history of fish that may be affected by climate change and reconstructing a well-resolved migration history for fish species that have small otoliths and/or narrow growth increments.
Does Obstructive Sleep Apnea Worsen During REM Sleep?
Authors: PEREGRIM I. , GREŠOVÁ S. , PALLAYOVÁ M. , FULTON B. L. , ŠTIMMELOVÁ J. , BAČOVÁ I. , MIKUĽAKOVÁ A. , TOMORI Z. , DONIČ V.
Published: August 2020

Although it is thought that obstructive sleep apnea (OSA) is worse during rapid eye movement (REM) sleep than in non-REM (NREM) sleep there are some uncertainties, especially about apnoe-hypopnoe-index (AHI). Several studies found no significant difference in AHI between both sleep stages. However, REM sleep is associated more with side sleeping compared to NREM sleep, which suggests that body position is a possible confounding factor. The main purpose of this study was to compare the AHI in REM and NREM sleep in both supine and lateral body position. A retrospective study was performed on 422 consecutive patients who underwent an overnight polysomnography. Women had higher AHI in REM sleep than NREM sleep in both supine (46.05±26.26 vs. 23.91±30.96, P<0.01) and lateral (18.16±27.68 vs. 11.30±21.09, P<0.01) body position. Men had higher AHI in REM sleep than NREM sleep in lateral body position (28.94±28.44 vs. 23.58±27.31, P<0.01), however, they did not reach statistical significance in supine position (49.12±32.03 in REM sleep vs. 45.78±34.02 in NREM sleep, P=0.50). In conclusion, our data suggest that REM sleep is a contributing factor for OSA in women as well as in men, at least in lateral position.
Gastrodin Ameliorates Anxiety-Like Behaviors and Inhibits IL-1β Level and p38 MAPK Phosphorylation of Hippocampus in the Rat Model of Posttraumatic Stress Disorder
Authors: PENG Z. , WANG H. , ZHANG R. , CHEN Y. , XUE F. , NIE H. , CHEN Y. , WU D. , WANG Y. , WANG H. , TAN Q.
Published: August 2020

Gastrodin, a main constituent of a Chinese herbal medicine, has been shown to be effective in treating various mood disorders. The purpose of the present study was to determine whether gastrodin could ameliorate stress-associated behavior in a rat model of enhanced single prolonged stress (ESPS)-induced posttraumatic stress disorder (PTSD). Following ESPS, rats were administered orally with gastrodin (50, 100, or 200 mg/kg daily) or vehicle for 2 weeks. Animals were then tested in the open field and elevated plus-maze, and the levels of IL-6 and IL-1β, the expression of iNOS, p38 and phospho-p38 (p-p38) in hippocampus were also tested. ESPS exposure resulted in pronounced anxiety-like behavior, elevated IL-6 and IL-1β levels, and the higher expression of iNOS and p-p38 in hippocampus. However, repeated treatment with gastrodin, particularly at higher doses, reversed the aforementioned changes, including anxiety-like behavior, levels of IL-6 and IL-1β, and the expression of iNOS and the p38 MAPK phosphorylation. These results indicate that gastrodin possesses anxiolytic effect and may be an effective herbal preparation for the treatment of PTSD.
Age and Heat Exposure-Dependent Changes in Antioxidant Enzymes Activities in Rat's Liver and Brain Mitochondria: Role of α-tocopherol
Authors: STOJKOVSKI V. , HADZI-PETRUSHEV N. , ILIESKI V. , SOPI R. , GJORGOSKI I. , MITROV D. , JANKULOVSKI N. , MLADENOV M.
Published: August 2020

To investigate the role of mitochondrial antioxidant capacity during increased susceptibility to heat accompanied by the aging, young and aged Wistar rats were exposed on heat for 60 min. After heat exposure, hepatic and brain mitochondria were isolated. Our results revealed changes in antioxidant enzyme activities in liver and brain mitochondria from young and to a greater extent in aged rats. Our measurements of MnSOD, GPx and GR activity indicate greater reactive oxygen species production from the mitochondria of aged heat exposed in comparison to young heat exposed rats. Also in the aged rats, the effect of α-tocopherol treatment in the prevention of oxidative stress occurred as a result of heat exposure, is less pronounced. Taken together, our data suggest that mitochondria in aged rats are more vulnerable and less able to prevent oxidative changes that occur in response to acute heat exposure.
Plasma Membrane Density of GABAB-R1a, GABAB-R1b, GABA-R2 and Trimeric G-proteins in the Course of Postnatal Development of Rat Brain Cortex
Authors: DLOUHÁ K. , KAGAN D. , ROUBALOVÁ L. , UJČÍKOVÁ H. , SVOBODA P.
Published: August 2020

With the aim to understand the onset of expression and developmental profile of plasma membrane (PM) content /density of crucial components of GABAB-R signaling cascade, GABAB-R1a, GABAB-R1b, GABAB-R2, Gi1/Gi2α, Gi3α, Goα, Gzα and Gβ subunit proteins were determined by quantitative immunoblotting and compared in PM isolated from brain cortex of rats of different ages: between postnatal-day-1 (PD1) and 90 (PD90). PM density of GABAB-R1a, GABAB-R2, Gi1/Gi2α, Gi3α, Goα, Gzα and Gβ was high already at birth and further development was reflected in parallel decrease of both GABAB-R1a and GABAB-R2 subunits. The major decrease of GABAB-R1a and GABAB-R2 occurred between the birth and PD15: to 55 % (R1a, **) and 51 % (R2, **), respectively. Contrarily, PM level of the cognate G-proteins Gi1/Gi2α, Gi3α, Goα, Gzα and Gβ was unchanged in the course of the whole postnatal period of brain cortex development. Maturation of GABAB-R cascade was substantially different from ontogenetic profile of prototypical plasma membrane marker, Na, K-ATPase, which was low at birth and further development was reflected in continuous increase of PM density of this enzyme. Major change occurred between the birth and PD25. In adult rats, membrane content of Na, K-ATPase was 3-times higher than around the birth.
Treatment of Rats With Hypolipidemic Compound Pirinixic Acid Protects Their Hearts Against Ischemic Injury: Are Mitochondrial KATP Channels and Reactive Oxygen Species Involved?
Authors: NEMČEKOVÁ M. , ČARNICKÁ S. , FERKO M. , MURÁRIKOVÁ M. , LEDVÉNYIOVÁ V. , RAVINGEROVÁ T.
Published: August 2020

Hypolipidemic compound pirinixic acid (WY-14643, WY) is known to exert pleiotropic (other than primary) effects, such as activation of peroxisome proliferator-activated receptors (PPAR-α), transcription factors regulating different cardiac functions. Their role in ischemia-reperfusion (I/R) injury and cardioprotection is less clear, although protective effects of PPAR agonists have been documented. This study was designed to explore the effects of WY on the I/R injury in the rat heart and potential mechanisms involved, including mitochondrial KATP channels (mitoKATP) opening and production of reactive oxygen species (ROS). Langendorff-perfused hearts of rats intragastrally treated with WY (3 mg/kg/day) for 5 days and of control animals were subjected to 30-min global ischemia and 2-h reperfusion with or without 15-min perfusion with mitoKATP blocker 5-hydroxydecanoate (5-HD) prior to I/R. Evaluation of the infarct size (IS, TTC staining) served as the main end-point of protection. Lipid peroxidation (a marker of ROS production) was determined by measurement of myocardial concentration of conjugated dienes (CD), whereas protein expression of endothelial NO synthase was analysed by Western blotting. A 2-fold increase in the cardiac protein levels of eNOS after treatment with WY was accompanied by lower post-I/R levels of CD compared with those in the hearts of untreated controls, although WY itself enhanced ROS generation prior to ischemia. IS was reduced by 47 % in the hearts of WY-treated rats (P<0.05), and this effect was reversed by 5-HD. Results suggest that PPAR-α activation may confer protection against lethal I/R injury in the rat heart that involves up-regulation of eNOS, mitoKATP opening and reduced oxidative stress during I/R.
Application of Waveguide Invariant Theory to Analysis of Interference Phenomenon in Deep Ocean
Authors: Yao Yuan , Sun Chao , Liu Xionghou
Published: August 2020

When a hydrophone is deployed under the critical depth in deep ocean, the interference pattern will be complex and variable. The waveguide invariant is no longer constant and is treated as a distribution. The interference pattern is impacted by refracted and surface reflected (RSR) modes, as well as surface reflected and bottom reflected (SRBR) modes together. This phenomenon is illustrated by numerical simulation and explained by the waveguide invariant theory in this paper. The theory demonstrates: (1) The interference pattern in zone-b corresponds to the waveguide invariant βRSR that varies quickly and leads to the slope change, which is contributed by RSR modes whose phase velocity is less than the sound velocity at seafloor; (2) The interference pattern in zone-a1 and zone-c1 is corresponding to the βSRBRWS that is the approximately 0.7 and leads to the stable slope, which is contributed by SRBR modes whose phase velocity is between the sound velocity at seafloor and sediment velocity; (3) The interference pattern in zone-a2 and zone-c2 is corresponding to the βSRBRSH which hardly varies at low frequency but varies fiercely with source frequency increasing, so the striations are complex with high frequency, which is contributed by SRBR modes whose phase speed is between sediment speed and half space speed.
Mitochondrial DNA Diversity in Large White Pigs in Russia
Authors: Getmantseva Lyubov , Bakoev Siroj , Bakoev Nekruz , Karpushkina Tatyana , Kostyunina Olga
Published: August 2020

The Large White pig is the most commonly raised commercial pig breed in the world. The aim of this work was to investigate D-loop mtDNA in Large White pigs (n = 402) of various selections bred in the Russian Federation from 2000 to 2019. The general sample consisted of three groups: Old (n = 78) (Russian selection, 2000–2010); Imp (n = 123) (imported to Russia in 2008–2014); New (n = 201) (2015–2019). The synthesized score (Fz) was calculated by analyzing the main PCA (principal component analysis components). An affiliation to Asian or European haplogroups was determined according to the NCBI (National Center for Biotechnology Information). In the study, we defined 46 polymorphic sites and 42 haplotypes. Significant distinctions between groups Old, Imp and New in frequencies of haplotypes and haplogroups were established. The distribution of Asian and European haplotypes in the groups was Old: 50%/50%, Imp: 43%/57%, New: 75%/25%, respectively. The variety of haplotypes and haplogroups in the pigs of the group New is related to the farms in which they breed. Haplotype frequencies significantly differ between the clusters Old_Center, Old_Siberia and Old_South. This study will provide information on the genetic diversity of Large White breed pigs. The results will be useful for the conservation and sustainable use of these resources.
Hybrid Siamese Network for Unconstrained Face Verification and Clustering under Limited Resources
Authors: Ahmed Nehal K. , Hemayed Elsayed E. , Fayek Magda B.
Published: August 2020

In this paper, we propose an unconstrained face verification approach that is dependent on Hybrid Siamese architecture under limited resources. The general face verification trend suggests that larger training datasets and/or complex architectures lead to higher accuracy. The proposed approach tends to achieve high accuracy while using a small dataset and a simple architecture by directly learn face’s similarity/dissimilarity from raw face pixels, which is critical for various applications. The proposed architecture has two branches; the first part of these branches is trained independently, while the other parts shared their parameters. A multi-batch algorithm is utilized for training. The training process takes a few hours on a single GPU. The proposed approach achieves near-human accuracy (98.9%) on the Labeled Faces in the Wild (LFW) benchmark, which is competitive with other techniques that are presented in the literature. It reaches 99.1% on the Arabian faces dataset. Moreover, features learned by the proposed architecture are used in building a face clustering system that is based on an updated version of the Density-Based Spatial Clustering of Applications with Noise (DBSCAN). To handle the cluster quality challenge, a novel post-clustering optimization procedure is proposed. It outperforms popular clustering approaches, like K-Means and spectral by 0.098 and up to 0.344 according to F1-measure.
Molecular and Immunological Characterization of Biliary Tract Cancers: A Paradigm Shift Towards a Personalized Medicine
Authors: Malenica Ines , Donadon Matteo , Lleo Ana
Published: August 2020

Biliary tract cancers (BTCs) are a group of rare cancers that account for up to 3–5% of cancer patients worldwide. BTCs include cholangiocarcinoma (CCA), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC). They are frequently diagnosed at an advanced stage when the disease is often found disseminated. A late diagnosis highly compromises surgery, the only potentially curative option. Current treatment regimens include a combination of chemotherapeutic drugs gemcitabine with cisplatin that have a limited efficiency since more than 50% of patients relapse in the first year. More recently, an inhibitor of fibroblast growth factor receptor 2 (FGFR2) was approved as a second-line treatment, based on the promising results from the NCT02924376 clinical trial. However, novel secondary treatment options are urgently needed. Recent molecular characterization of CCA and GBC highlighted the molecular heterogeneity, etiology, and epidemiology in BTC development and lead to the classification of the extrahepatic CCA into four types: metabolic, proliferating, mesenchymal, and immune type. Differences in the immune infiltration and tumor microenvironment (TME) have been described as well, showing that only a small subset of BTCs could be classified as an immune “hot” and targeted with the immunotherapeutic drugs. This recent evidence has opened a way to new clinical trials for BTCs, and new drug approvals are highly expected by the medical community.
First-Line Treatment for Primary Breast Diffuse Large B-Cell Lymphoma Using Immunochemotherapy and Central Nervous System Prophylaxis: A Multicenter Phase 2 Trial
Authors: Yhim Ho-Young , Yoon Dok Hyun , Kim Seok Jin , Yang Deok-Hwan , Eom Hyeon-Seok , Kim Kyoung Ha , Park Yong , Kim Jin Seok , Kim Hyo Jung , Suh Cheolwon , Kim Won Seog , Kwak Jae-Yong
Published: August 2020

There are limited data from prospective controlled trials regarding optimal treatment strategies in patients with primary breast diffuse large B-cell lymphoma (DLBCL). In this phase 2 study (NCT01448096), we examined the efficacy and safety of standard immunochemotherapy and central nervous system (CNS) prophylaxis using intrathecal methotrexate (IT-MTX). Thirty-three patients with newly diagnosed primary breast DLBCL received six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and four fixed doses of IT-MTX (12 mg). The median age was 50 years (range, 29–75), and all patients were females. According to the CNS-International Prognostic Index, most patients (n = 28) were categorized as the low-risk group. Among the 33 patients, 32 completed R-CHOP, and 31 completed IT-MTX as planned. With a median follow-up of 46.1 months (interquartile range (IQR), 31.1–66.8), the 2-year progression-free and overall survival rates were 81.3% and 93.5%, respectively. Six patients experienced treatment failures, which included the CNS in four patients (two parenchyma and two leptomeninges) and breast in two patients (one ipsilateral and one contralateral). The 2-year cumulative incidence of CNS relapse was 12.5%. Although standard R-CHOP and IT-MTX without routine radiotherapy show clinically meaningful survival outcomes, this strategy may not be optimal for reducing CNS relapse and warrants further investigation.
Menopausal Hormone Therapy and Risk of Endometrial Cancer: A Systematic Review
Authors: Tempfer Clemens B. , Hilal Ziad , Kern Peter , Juhasz-Boess Ingolf , Rezniczek Günther A.
Published: August 2020

Background: Menopausal hormone therapy (MHT) is an appropriate treatment for women with the climacteric syndrome. The estrogen component of MHT effectively alleviates climacteric symptoms but also stimulates the endometrium and thus may increase the risk of endometrial cancer (EC). Materials and Methods: We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify controlled and uncontrolled clinical trials reporting on the prevalence and/or incidence of EC among women using MHT. Results: 31 publications reporting on 21,306 women with EC diagnosed during or after MHT were identified. A significantly reduced risk of EC among continuous-combined (cc)MHT users with synthetic progestins (SPs) was demonstrated in 10/19 studies with odds ratios (ORs)/hazard ratios (HRs) between 0.24 and 0.71. Only one study documented an increased risk of EC among long-term users (≥10 years), not confirmed in three other sub-group analyses of women with ≥6, ≥5, and >10 years of ccMHT use. A significantly increased risk of EC among users of sequential-combined (sc)MHT with SPs was demonstrated in 6/12 studies with ORs/HRs between 1.38 and 4.35. Number of days of progestin per month was a significant modulator of EC risk. A decreased risk of EC was seen in obese women. Two studies documented an increased risk of EC among users of cc/scMHT with micronized progesterone. A significantly increased risk of EC among estrogen-only MHT users was demonstrated in 9/12 studies with ORs/HRs between 1.45 and 4.46. The adverse effect of estrogen-only MHT was greatest among obese women. Conclusion: ccMHT with SPs reduces the risk of EC, whereas estrogen-only MHT increases the risk. scMHT with SPs and cc/scMHT with micronized progesterone increase the risk of EC depending on type of progestin, progestin dosage, and duration of MHT use.
Two Antagonistic Microtubule Targeting Drugs Act Synergistically to Kill Cancer Cells
Authors: Peronne Lauralie , Denarier Eric , Rai Ankit , Prudent Renaud , Vernet Audrey , Suzanne Peggy , Ramirez-Rios Sacnicté , Michallet Sophie , Guidetti Mélanie , Vollaire Julien , Lucena-Agell Daniel , Ribba Anne-Sophie , Josserand Véronique , Coll Jean-Luc , Dallemagne Patrick , Díaz J. Fernando , Oliva María Ángela , Sadoul Karin , Akhmanova Anna , Andrieux Annie , Lafanechère Laurence
Published: August 2020

Paclitaxel is a microtubule stabilizing agent and a successful drug for cancer chemotherapy inducing, however, adverse effects. To reduce the effective dose of paclitaxel, we searched for pharmaceutics which could potentiate its therapeutic effect. We screened a chemical library and selected Carba1, a carbazole, which exerts synergistic cytotoxic effects on tumor cells grown in vitro, when co-administrated with a low dose of paclitaxel. Carba1 targets the colchicine binding-site of tubulin and is a microtubule-destabilizing agent. Catastrophe induction by Carba1 promotes paclitaxel binding to microtubule ends, providing a mechanistic explanation of the observed synergy. The synergistic effect of Carba1 with paclitaxel on tumor cell viability was also observed in vivo in xenografted mice. Thus, a new mechanism favoring paclitaxel binding to dynamic microtubules can be transposed to in vivo mouse cancer treatments, paving the way for new therapeutic strategies combining low doses of microtubule targeting agents with opposite mechanisms of action.
Extracellular Glutathione Peroxidase GPx3 and Its Role in Cancer
Authors: Chang Caroline , Worley Beth L. , Phaëton Rébécca , Hempel Nadine
Published: August 2020

Mammalian cells possess a multifaceted antioxidant enzyme system, which includes superoxide dismutases, catalase, the peroxiredoxin/thioredoxin and the glutathione peroxidase systems. The dichotomous role of reactive oxygen species and antioxidant enzymes in tumorigenesis and cancer progression complicates the use of small molecule antioxidants, pro-oxidants, and targeting of antioxidant enzymes as therapeutic approaches for cancer treatment. It also highlights the need for additional studies to investigate the role and regulation of these antioxidant enzymes in cancer. The focus of this review is on glutathione peroxidase 3 (GPx3), a selenoprotein, and the only extracellular GPx of a family of oxidoreductases that catalyze the detoxification of hydro- and soluble lipid hydroperoxides by reduced glutathione. In addition to summarizing the biochemical function, regulation, and disease associations of GPx3, we specifically discuss the role and regulation of systemic and tumor cell expressed GPx3 in cancer. From this it is evident that GPx3 has a dichotomous role in different tumor types, acting as both a tumor suppressor and pro-survival protein. Further studies are needed to examine how loss or gain of GPx3 specifically affects oxidant scavenging and redox signaling in the extracellular tumor microenvironment, and how GPx3 might be targeted for therapeutic intervention.
Tumor Budding and Poorly Differentiated Clusters in Small Intestinal Adenocarcinoma
Authors: Jun Sun-Young , Chung Joon-Yong , Yoon Nara , Jung Eun Sun , Oh Young-Ha , Hong Seung-Mo
Published: August 2020

The clinicopathologic and prognostic significances of tumor budding (TB) and poorly-differentiated clusters (PDC) have not been investigated in small intestinal adenocarcinomas (SIACs). In 236 surgically-resected SIACs, we counted TB (single cells or clusters ≤4 tumor cells) and PDC (clusters ≥5 tumor cells) at the peritumoral-invasive front (p) and in the intratumoral area (i) independently to classify as grade-1 (≤4), grade-2 (5–9), or grade-3 (≥10). Consequently, grades-2 and -3 were considered high-grade. High-pTB, -iTB, -pPDC, and -iPDC were observed in 174 (73.7%), 129 (54.7%), 118 (50.0%), and 85 (36.0%) cases, respectively. High-TB/PDCs were more frequently observed in tumors with high-grade, higher T- and N-categories and stage grouping, and perineural or lymphovascular invasion. Patients with high-TB/PDC had a shorter survival than those with low-TB/PDC. In a multivariate analysis, high-pTB, nonintestinal type, high N-category, retroperitoneal seeding, and microsatellite-stable were worse independent-prognostic predictors. Subgroup analysis demonstrated that patients with high-pTB showed worse survival (median: 42.5 months) than those with low-pTB (133.7 months; p = 0.007) in the lower stage (stages I–II) group. High-TB/PDC, both in peritumoral and intratumoral localizations, were associated with aggressive behaviors in SIACs. High-pTB can be used as an adverse prognostic indicator in SIAC patients, especially when patients are in early disease stages.
Combination of Peri-Tumoral and Intra-Tumoral Radiomic Features on Bi-Parametric MRI Accurately Stratifies Prostate Cancer Risk: A Multi-Site Study
Authors: Algohary Ahmad , Shiradkar Rakesh , Pahwa Shivani , Purysko Andrei , Verma Sadhna , Moses Daniel , Shnier Ronald , Haynes Anne-Maree , Delprado Warick , Thompson James , Tirumani Sreeharsha , Mahran Amr , Rastinehad Ardeshir R , Ponsky Lee , Stricker Phillip D. , Madabhushi Anant
Published: August 2020

Background: Prostate cancer (PCa) influences its surrounding habitat, which tends to manifest as different phenotypic appearances on magnetic resonance imaging (MRI). This region surrounding the PCa lesion, or the peri-tumoral region, may encode useful information that can complement intra-tumoral information to enable better risk stratification. Purpose: To evaluate the role of peri-tumoral radiomic features on bi-parametric MRI (T2-weighted and Diffusion-weighted) to distinguish PCa risk categories as defined by D’Amico Risk Classification System. Materials and Methods: We studied a retrospective, HIPAA-compliant, 4-institution cohort of 231 PCa patients (n = 301 lesions) who underwent 3T multi-parametric MRI prior to biopsy. PCa regions of interest (ROIs) were delineated on MRI by experienced radiologists following which peri-tumoral ROIs were defined. Radiomic features were extracted within the intra- and peri-tumoral ROIs. Radiomic features differentiating low-risk from: (1) high-risk (L-vs.-H), and (2) (intermediate- and high-risk (L-vs.-I + H)) lesions were identified. Using a multi-institutional training cohort of 151 lesions (D1, N = 116 patients), machine learning classifiers were trained using peri- and intra-tumoral features individually and in combination. The remaining 150 lesions (D2, N = 115 patients) were used for independent hold-out validation and were evaluated using Receiver Operating Characteristic (ROC) analysis and compared with PI-RADS v2 scores. Results: Validation on D2 using peri-tumoral radiomics alone resulted in areas under the ROC curve (AUCs) of 0.84 and 0.73 for the L-vs.-H and L-vs.-I + H classifications, respectively. The best combination of intra- and peri-tumoral features resulted in AUCs of 0.87 and 0.75 for the L-vs.-H and L-vs.-I + H classifications, respectively. This combination improved the risk stratification results by 3–6% compared to intra-tumoral features alone. Our radiomics-based model resulted in a 53% accuracy in differentiating L-vs.-H compared to PI-RADS v2 (48%), on the validation set. Conclusion: Our findings suggest that peri-tumoral radiomic features derived from prostate bi-parametric MRI add independent predictive value to intra-tumoral radiomic features for PCa risk assessment.
Targeting NF-κB Signaling for Multiple Myeloma
Authors: Wong Ada Hang-Heng , Shin Eun Myoung , Tergaonkar Vinay , Chng Wee-Joo
Published: August 2020

Multiple myeloma (MM) is the second most common hematologic malignancy in the world. Even though survival rates have significantly risen over the past years, MM remains incurable, and is also far from reaching the point of being managed as a chronic disease. This paper reviews the evolution of MM therapies, focusing on anti-MM drugs that target the molecular mechanisms of nuclear factor kappa B (NF-κB) signaling. We also provide our perspectives on contemporary research findings and insights for future drug development.