bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of Bone Remodeling Compartments in BMP-2-Injected Knees Supports a Local Vascular Mechanism for Arthritis-Related Bone Changes
Authors: Seeherman Howard J. , Li X. Jian , Wozney John M.
Published: December 2020

Background:

Synovial membrane-derived factors are implicated in arthritis-related bone changes. The route that synovial factors use to access subchondral bone and the mechanisms responsible for these bone changes remain unclear. A safety study involving intra-articular injection of bone morphogenetic protein-2 (BMP-2)/calcium phosphate matrix (CPM) or CPM addresses these issues.

Methods:

Knee joints in 21 monkeys were injected with CPM or 1.5 or 4.5 mg/mL BMP-2/CPM and were evaluated at 1 and 8 weeks. Contralateral joints were injected with saline solution. Knee joints in 4 animals each were injected with 1.5 or 4.5 mg/mL BMP-2/CPM. Contralateral joints were injected with corresponding treatments at 8 weeks. Both joints were evaluated at 16 weeks. Harvested joints were evaluated grossly and with histomorphometry. Knee joints in 3 animals were injected with 125I-labeled BMP-2/CPM and evaluated with scintigraphy and autoradiography at 2 weeks to determine BMP-2 distribution.

Results:

All treatments induced transient synovitis and increased capsular vascularization, observed to anastomose with metaphyseal venous sinusoids, but did not damage articular cartilage. Both treatments induced unanticipated activation of vascular-associated trabecular bone remodeling compartments (BRCs) restricted to injected knees. Bone volume increased in BMP-2/CPM-injected knees at 8 and 16 weeks. Scintigraphy demonstrated metaphyseal 125I-labeled BMP-2 localization restricted to injected knees, confirming local rather than systemic BMP-2 release. Autoradiography demonstrated that BMP-2 diffusion through articular cartilage into the metaphysis was blocked by the tidemark. The lack of marrow activation or de novo bone formation, previously reported following metaphyseal BMP-2/CPM administration, confirmed BMP-2 and synovial-derived factors were not free in the marrow. The 125I-labeled BMP-2/CPM, observed within venous sinusoids of injected knees, confirmed the potential for capsular and metaphyseal venous portal communication.

Conclusions:

This study identifies a synovitis-induced venous portal circulation between the joint capsule and the metaphysis as an alternative to systemic circulation and local diffusion for synovial membrane-derived factors to reach subchondral bone. This study also identifies vascular-associated BRCs as a mechanism for arthritis-associated subchondral bone changes and provides additional support for their role in physiological trabecular bone remodeling and/or modeling.

Clinical Relevance:

Inhibition of synovitis and accompanying abnormal vascularization may limit bone changes associated with arthritis.
The effects of biocrusts on soil parameters in a semi-arid pediment at north-eastern Iran
Authors: Sepehr Adel , Gholamhosseinian Atoosa , Emadodin Iraj
Published: December 2020

The biocrusts are organized by soil-surface communities of biota that live within or on the very top of soil surface and play an important role in soil conservation. They include lichens, mosses, fungi, cyanobacteria, eukaryotic algae, and other heterotrophic bacteria. The interaction between biocrusts and soil is very important and good awareness from that help to better manage soil specially in arid and semi-arid areas. The linkage between cyanobacteria species and soil physicochemical parameters and mineralogy in two geomorphic zones in the northeastern Iran was studied. Samples were collected in summer along a linear transect by using 50 x 50 cm quadrates for each study zone. Individual mineral soil particles were analyzed by a scanning electron microscopy (SEM). The amounts of Na, K, Ca, and Mg contents as well as EC and SOC altered significantly between two study zones. Biocrusts increased levels of organic carbon, pH, calcium carbonate, exchangeable sodium and potassium percentages. The main soil properties of SOC, CaCO3 and amount of clay changed among biocrust sand bare soils.
Investigating land surface deformation using InSAR and GIS techniques in Cluj–Napoca city’s most affected sector by urban sprawl (Romania)
Authors: Kerekes Anna Hajnalka , Poszet Szilárd Lehel , Baciu Laurențiu Călin
Published: December 2020

The last three decades have marked an unprecedented urban expansion of the city of Cluj-Napoca, leading to strong anthropogenic influences on the natural environment and important changes in the land-use. Due to the specific morphology of Cluj area, characterized by limited available plane surfaces which are insufficient to support the urban expansion, more and more territories with slopes between 5°-26° are used for constructions. These areas are marked by high risks of mass movements due to their specific geological and geomorphological characteristics, therefore the present study proposes a more detailed and complex GIS and remote sensing analysis of the western urban part of Cluj-Napoca, in order to highlight the main changes of the city and the consequences of the human actions. One of the most used radar interferometry (InSAR) technique was applied in order to detect land deformations that can threaten the infrastructure and the population. Sentinel-1B SAR imagery were processed by the DInSAR methodology, resulting in a land deformation map, which represents an important support in generating the vulnerability assessment. Based upon this evaluation, we concluded that the most vulnerable neighbourhoods to land deformations from the western part of the city are the peripheral ones, as following: Dâmbul Rotund, Bună Ziua, Europa, Mănăștur, West Iris and Făget, proving that human activity and the geological setting are the main triggering factors of the discussed phenomenon.
ZAKAT AND POVERTY ALLEVIATION IN INDONESIA: A PANEL ANALYSIS AT PROVINCIAL LEVEL
Authors: Choiriyah Evi Aninatin Nimatul , Kafi Abdul , Hikmah Irma Faikhotul , Indrawan Imam Wahyudi
Published: December 2020

As a pillar of Islam and an instrument for poverty alleviation, zakat is perceived as aneffective tool for tackling the problem of poverty in the Muslim world. However,whether zakat is effective in improving indicators of both quantity and quality ofpoverty is still a question requiring empirical investigation. This study is aims toempirically investigate the role of impactful zakat in poverty alleviation as indicated bythe BAZNAS prosperity index (Indeks Kesejahteraan BAZNAS or IKB), at provinciallevel in Indonesia. This study covers annual data from 28 provinces in Indonesia forthe years 2017 and 2018. Data analysis uses a panel-data approach, with threeindicators of poverty – the poverty headcount ratio (P0), poverty gap index (P1), andpoverty severity index (P2) – as dependent variables. The study finds that higherBAZNAS IKB, used as a sign of impactful zakat, significantly reduces P0 but hasinsignificant effect on P1 and P2. The results of this study imply that zakat managersshould put emphasis on the poorest section of the poor population to enableimprovements in poverty indicators through zakat utilization.
ONLINE PAYMENT, INDIVIDUAL CHARACTERISTICS, AND DIGITAL FINANCIAL INCLUSION IN OIC COUNTRIES
Authors: Al Hashfi Rizqi Umar , Zusryn Alyta Shabrina , Khoirunnisa Novi Lailatul , Listyowati Ammelia Rizza Fitri Ayu
Published: December 2020

Digital financial inclusion (DFI) is a prominent issue in the digital era, since it focuseson the use of technology to serve unbanked people at low cost. The adoption ofmobile money platforms that allow users to make efficient peer-to-peer and real-timetransactions is one aspect of the DFI agenda. This study aims to investigate thedeterminants of mobile money usage using data derived from the 2017 GlobalFinancial Inclusion survey conducted by the World Bank and Gallup and applyingprobit regression and the Heckman selection model to check robustness. Eventhough access to a financial institution is relatively low, the percentage of mobilemoney usage in Organisation of Islamic Cooperation (OIC) countries is slightly higherthan in non-OIC countries and worldwide. The rate of adoption of mobile money ishigher for individuals making online transactions, with more educated and moreprosperous males tending to be more included in the use of digital financial services.The U-shape hypothesis for the relationship between age and the use of mobilemoney is not supported. Our research contributes to the theoretical development ofthe Unified Theory of Acceptance and Use of Technology 2 in illustrating the use ofmobile technology. The empirical results are recommended for use by practitioners,regulators and policymakers in creating and fostering a sound ecosystem for digitalfinance development.
„Domorodci“ ne/známého „domova“. Cesty německých vyhnanců a vysídlenců do Československa a jejich percepce místního obyvatelstva ve vysídleneckých periodikách
Authors: Kreisslová Sandra , Nosková Jana
Published: December 2020

The study focuses on a specific type of tourism (the so-called Heimattourismus) whose main aim is to visit countries, or better said, localities, which expelled and displaced Germans had to abandon after the end of World War II due to forced migration and which they consider(ed) as one of their ‘homes’. After the first unofficial trips, it is possible to observe a gradual increase in organised and individual tourism of displaced Germans to Czechoslovakia since the second half of the 1950s. In this article, we focus on one of the many topics related to Heimattourism, namely reflections of the local population in the former homeland and the stereotypes constructed about locals by Sudeten German tourists. We examine the topic by analysing ‘travel reports’ published by displaced persons and expellees in their journals since these trips had begun until mid-1960s.
“Past Future Concrete” revisited: Ex-Yugoslav monuments shaped as destinations via online image practices
Authors: Baumann Uwe
Published: December 2020

Spomenik is the Serbo-Croatian word for monument. Internationally, the term is used for the partisan monuments that were erected throughout the former Yugoslavia to commemorate events of the Second World War. With the wars in the 1990s that led to the disintegration of Yugoslavia, many of these objects became detached from their original function, and thus became a dissonant heritage between differing nationalist narratives of the past. With their modernist architecture, the Spomeniks have become, since the late 2000s, popular internet motifs, and tourists are now showing growing interest in visiting the monuments. In order to capitalize on and institutionalize this increasing attention, a cultural route for tourists has recently been established. In this process of valorization, presenting the condition and decay of the monuments and characterizing them as “lost” places, which has become a decisive aesthetic in their circulation online, plays a large role in the constitution of these sites of memory (lieux de mémoire). This picturesque image practice as a phenomenon of cosmopolitanism will be exemplified by online representations of the Tjentište Monument in Bosnia-Herzegovina.
Smart Flow Steering Agent for End-to-End Delay Improvement in Software-Defined Networks
Authors: Hussain Omar F. , Al-Kaseem Bilal R. , Akif Omar Z.
Published: December 2020

To ensure fault tolerance and distributed management, distributed protocols are employed as one of the major architectural concepts underlying the Internet. However, inefficiency, instability and fragility could be potentially overcome with the help of the novel networking architecture called software-defined networking (SDN). The main property of this architecture is the separation of the control and data planes. To reduce congestion and thus improve latency and throughput, there must be homogeneous distribution of the traffic load over the different network paths. This paper presents a smart flow steering agent (SFSA) for data flow routing based on current network conditions. To enhance throughput and minimize latency, the SFSA distributes network traffic to suitable paths, in addition to supervising link and path loads. A scenario with a minimum spanning tree (MST) routing algorithm and another with open shortest path first (OSPF) routing algorithms were employed to assess the SFSA. By comparison, to these two routing algorithms, the suggested SFSA strategy determined a reduction of 2% in packets dropped ratio (PDR), a reduction of 15-45% in end-to-end delay according to the traffic produced, as well as a reduction of 23% in round trip time (RTT). The Mininet emulator and POX controller were employed to conduct the simulation. Another advantage of the SFSA over the MST and OSPF is that its implementation and recovery time do not exhibit fluctuations. The smart flow steering agent will open a new horizon for deploying new smart agents in SDN that enhance network programmability and management.
Detecting Textual Propaganda Using Machine Learning Techniques
Authors: Khanday Akib Mohi Ud Din , Khan Qamar Rayees , Rabani Syed Tanzeel
Published: December 2020

Social Networking has dominated the whole world by providing a platform of information dissemination. Usually people share information without knowing its truthfulness. Nowadays Social Networks are used for gaining influence in many fields like in elections, advertisements etc. It is not surprising that social media has become a weapon for manipulating sentiments by spreading disinformation.  Propaganda is one of the systematic and deliberate attempts used for influencing people for the political, religious gains. In this research paper, efforts were made to classify Propagandist text from Non-Propagandist text using supervised machine learning algorithms. Data was collected from the news sources from July 2018-August 2018. After annotating the text, feature engineering is performed using techniques like term frequency/inverse document frequency (TF/IDF) and Bag of words (BOW). The relevant features are supplied to support vector machine (SVM) and Multinomial Naïve Bayesian (MNB) classifiers. The fine tuning of SVM is being done by taking kernel Linear, Poly and RBF. SVM showed better results than MNB by having precision of 70%, recall of 76.5%, F1 Score of 69.5% and overall Accuracy of 69.2%.
Early Stuck Pipe Sign Detection with Depth-Domain 3D Convolutional Neural Network Using Actual Drilling Data
Authors: Tsuchihashi Naoki , Wada Ryota , Ozaki Masahiko , Inoue Tomoya , Mopuri Konda Reddy , Bilen Hakan , Nishiyama Tazuru , Fujita Kazuhiro , Kusanagi Kazuya
Published: December 2020

A real-time stuck pipe prediction using the deep-learning approach is studied in this paper. Early signs of stuck pipe, hereinafter called stuck, are assumed to show common patterns in the monitored data set, and designing a data clip that well captures these features is critical for efficient prediction. With the valuable input from drilling engineers, we propose a 3D-convolutional neural network (CNN) approach with depth-domain data clip. The clip illustrates depth-domain data in 2D-histogram images with unique abstraction of the time domain. Thirty field well data prepared in multivariate time series are used in this study—20 for training and 10 for validation. The validation data include six stuck incidents, and the 3D-CNN model has successfully detected early signs of stuck in three cases before the occurrence. The portion of the data clip contributing to anomaly detection is indicated by gradient-weighted class activation map (grad-CAM), providing physical explanation of the black box model. We consider such explanation inevitable for the drilling engineers to interpret the signs for rational decision-making.
The Role of Digital Clinical Decision Support Tool in Improving Quality of Intrapartum and Postpartum Care: Experiences From Two States of India.
Authors: Usmanova Gulnoza , Lalchandani Kamlesh , Srivast Ashish , Joshi Chandra , Bhatt Deepak , Bairagi Anand , Jain Yashpal , Afzal Mohammed , Dhoundiyal Rashmi , Benawari Jyoti , Chaudhary Tarun , Mishra Archana , Wadhwa Rajni , Srid Pompy , Bahl Nupur , Gaikwad Pratibha , Sood Bulbul
Published: December 2020

Background: Computerized clinical decision support (CDSS) –digital information systems designed to improve clinical decision making by providers – are a promising tool for improving quality of care. This study aims to understand the uptake of ASMAN application (defined as completeness of electronic case sheets), the role of CDSS in improving adherence to key clinical practices and delivery outcomes. Methods: We have conducted secondary analysis of program data (government data) collected from 81 public facilities across four districts each in two sates of Madhya Pradesh and Rajasthan. The data collected between August –October 2017 (baseline) and the data collected between December 2019 – March 2020 was analysed (latest). Results: The completeness of electronic case sheets was low at postpartum period (40.5%), and in facilities with more than 300 deliveries a month (20.9%). In multivariate logistic regression analysis, the introduction of technology yielded to significant improvement in adherence to key clinical practices. We have observed reduction in fresh still births rates and asphyxia, but these results were not statistically significant in interrupted time series analysis. However, our analysis showed that identification of maternal complications has increased over the period of program implementation and at the same time referral outs decreased. Conclusions: Our study indicates CDSS has a potential to improve quality of intrapartum care and delivery outcome. Future studies with rigorous study design is required to understand the impact of technology in improving quality of maternity care.
Ultrathin Dual-Mode Vortex Beam Generator Based on Anisotropic Coding Metasurface
Authors: Zhang Liang , Guo Jie , Ding Tongyu
Published: December 2020

In this paper, anisotropic coding metasurfaces is proposed to achieve dual-mode vortex beam generator by independently manipulating the orthogonally linearly polarized waves. The metasurface is composed of ultrathin single-layer ground-backed Jerusalem cross structure, which can provide complete and independent control of the orthogonally linearly polarized incident waves with greatly simplified design process. As proof of concept, a metasurface is design to generate vortex beams with different topological charges under orthogonal polarizations operating at 15 GHz. Experimental measurements performed on fabricated prototype reveal high quality, and show good agreements with theoretical designs and simulation results. Such ultrathin dual-mode vortex beam generator may find potential applications in wireless communication systems in microwave region.
Prevalence of Helicobacter Pylori Infection and Associated Factors Among Gastritis Patents in Yekatit 12 Teaching Hospital Addis Ababa Ethiopia
Authors: Hailu Awraris , Sileshi Bekureamanuel , Panari Hazaratali
Published: December 2020

Introduction: Helicobacter pylori colonize the stomach of about ~50% of the world’s human population and infection is more in clients with dyspeptic conditions and its associated with the severity of gastritis. The present study revealed that the magnitude of H. Pylori and burden of the bacterial infection as well as the contribution of H. Pylori for gastritis and also assesses the current prevalence of H. Pylori infection.Objective: To evaluate the prevalence of Helicobacter Pylori infection and associated factors among gastritis patents in Yekatit 12 Hospital.Methodology: An institutional based cross-sectional study was conducted in Yekatit 12 teaching hospital Addis Ababa city, Ethiopia. The participants were those patients come to the hospital for treatment of gastritis and send to the laboratory to confirm Helicobacter pylori infection in the data collection period. A total of 394 participants were interviewed by using a structured pre tested questionnaire. The data were coded and entered into Epi Data 3.1 version , cleaned and exported to version 20, SPSS. Multiple Logistic regression was used to estimate Adjusted (AORs) with a 95% confidence interval (CI) of positive responses to the different risk factors. P-value < 0.05 was considered as significant.Result: The total occurrence of H. Pylori in observers was 25.9%. Regarding income of family, those participants who have less income and living in rural areas were extra prone to be infected with H. Pylori (AOR=5.857, CI 95% = 1.389-24.686, P = 0.016 and AOR=3.663, CI 95% = 1.068-12.557, P =0.039) respectively. Further, the prevalence of study was significant association with participants who had experience of gastrointestinal illness, mouth to mouth kissing, unable to hand wash regularly before meal and after latrine used (AOR=4.270, 95%CI=1.785-10.21, P=0.01, AOR=53.085, 95%CI=16.185-174.114, P=0.000, AOR=7.316, 95%CI=1.944-27.536, P=0.003, AOR=3.374, 95%CI=1.024-11.114, P=0.046) respectively.Conclusion and recommendation: The finding shows that H. Pylori infection was significantly associated with occupational status,gender, smoking tobacco and hand washing regularly before meal and after toilet. I recommend making clean and saving the work place; regular hand wash, before food preparation, before feeding and after latrine. A health professional should give health education by using different media about the transition and health biro also should give emphases.
Development Dental Defects in Permanent Teeth Resulting From Primary Tooth Trauma. A Systematic Review.
Authors: Villasenín Lucía Caeiro , Muñoz Clara Serna , Silva Amparo Pérez , Vicente Ascensión , Pascual Andrea Poza , Ruiz Antonio José Ortiz
Published: December 2020

Children are vulnerable to dental trauma, especially in the first two year of life.The objective was to determine whether trauma in temporary teething causes alterations in the development of permanent teething. Searches were made in May 2020 using PubMed, MEDLINE, MEDES, Scopus, Lilacs, and Embase. Papers in English, German, and Spanish, without restrictions in the year of publication, were included. The quality of the studies was analyzed using the NOS Scale.The search retrieved 537 references, and 7 studies were included for a qualitative analysis. The results showed that trauma to a deciduous tooth can damage the bud of the permanent tooth. Enamel discoloration and/or hypoplasia were the most common sequelae in the permanent teeth after trauma to the primary predecessor. The type and severity of sequelae in the permanent tooth are associated with the development phase of the bud. Children with trauma of their primary teeth should receive check-ups until the eruption of the permanent teeth for the early diagnosis and treatment of possible sequelae. Intrusion of the primary tooth was the trauma that caused the most damage and enamel alterations the most frequent sequelae.
Identifying Hidden Patterns of Fatal Pedestrian Traffic Accidents in East Azerbaijan Province of Iran: Application of Categorical Principal Component Analysis (CATPCA)
Authors: Jamali-Dolatabad Milad , Sarbakhsh Parvin , Sadeghi-bazargani Homayoun
Published: December 2020

Background: Identifying patterns and hidden relationships among fatal pedestrian road traffic accident (FPRTA) features can be effective to reduce pedestrian fatalities. This study aimed to detect the patterns of FPRTA in the East Azerbaijan province of Iran.Methods: The present study is a descriptive-analytic study based on the data of all 1782 FPRTAs that occurred in East Azerbaijan province of Iran during the years 2010 to 2019 collected by the forensic organization. CATPCA (Categorical Principal Component Analysis) was performed to recognize hidden patterns in the data by extracting principal components from the set of 13 features of FPRTA. The importance of each component was assessed by using the variance accounted for (VAF) index. Results: The optimum number of components to fit the CATPCA model was six with a 71.09% explanation of the total variation. The first and most important component with VAF=22.04% contained the demographic and socioeconomic characteristics of the pedestrians. The second-ranked component with VAF=12.96% was about the injury. The third component with VAF=10.56% was about the severity of the accident. The fourth component with VAF=9.07% was somehow related to the knowledge and observance of the traffic rules. The fifth component with VAF=8.63% was about the quality of medical relief and finally, the sixth component with VAF=7.82% was about environmental conditions. Conclusion: CATPCA revealed hidden patterns of FPRTA data in the format of six components. The revealed patterns showed that some interactions between correlated features led to a higher mortality rate.
Proteomics and Metabonomics Analyses of Covid-19 Complications in Patients With Pulmonary Fibrosis
Authors: Yang Jianrong , Chen Chunxia , Chen Wan , Huang Luying , Fu Zhao , Ye Kun , Lv Liwen , Nong Zhihuang , Zhou Xing , Lu Wensheng , Zhong Mei
Published: December 2020

Pulmonary fibrosis is a devastating disease, and the pathogenesis of this disease is not completely clear. Here, the medical records of 85 Covid-19 cases were collected, among which fibrosis and progression of fibrosis were analyzed in detail. Next, data independent acquisition (DIA) quantification proteomics and untargeted metabolomics were used to screen disease-related signaling pathways through clustering and enrichment analysis of the differential expression of proteins and metabolites. The main imaging features were lesions located in the bilateral lower lobes and involvement in five lobes. The closed association pathways were FcγR-mediated phagocytosis, PPAR signaling, TRP-inflammatory pathways, and the urea cycle. Our results provide evidence for the detection of serum biomarkers and targeted therapy in patients with Covid-19.
A Global Genome-wide Scan With Optimal Cutoff Mining for Emerging Biomarkers in Head and Neck Squamous Cell Carcinoma
Authors: Chi Li-Hsing , Wu Alexander TH , Hsiao Michael , Li Yu-Chuan (Jack)
Published: December 2020

Background: The survival analysis of the Cancer Genome Atlas (TCGA) dataset is a well-known method to discover the gene expression-based prognostic biomarkers of head and neck squamous cell carcinoma (HNSCC). In order to utilize a continuous gene expression for survival analysis, it is necessary to determine a cutoff point by the dichotomization of the patients. There is some optimization software for cutoff determination. However, those predetermined cutoffs by software usually set at the median, 1/4 quantile, or 3/4 quantile of RNA sequencing (RNA -Seq) value to nd a significant P-value of the Kaplan-Meier curve. There are few clinicopathological features available on their pre-processed data sets.Methods: We developed a comprehensive work flow by R script, running on the Rstudio platform. It includes data retrieving and pre-processing, feature selection, cutoff mining engine, Kaplan-Meier survival analysis, Cox proportional hazard modeling, and biomarker discovery.Results: Using this work flow on the TCGA HNSCC cohort, we scanned human protein-coding genes (20,500) programmatically. After adjustment with other confounders, we found that the clinical tumor stage and the surgical margin involvement are independent risk factors in patient survival. According to the resulting tables with Bonferroni adjusted P-value under optimal cutoff as well as hazard ratio (>= 1:5), there were ten candidate biomarkers, named as DKK1, CAMK2N1, STC2, PGK1, SURF4, USP10, NDFIP1, FOXA2, STIP1, and DKC1, which are significantly associated with the poor prognosis of overall survival (OS). At the same time, the other ten genes were over-expressed in the better survival patients (with hazard ratio <= 0:5), named as ZNF557, ZNF266, IL19, MYO1H, FCGBP, LOC148709, EVPLL, PNMA5, IQCN (previous name as KIAA1683), and NPB. Further validations are warranted.Conclusions: We suggested this analysis tool equipped with an optimal cutoff finder will help with biomarker discovery of protein-coding genes, in terms of tumor-agnostic therapy.
Multi - Bacillary Leprosy Under Chinese Leprosy Elimination Program
Authors: Zhang Qingping , Ge Li , Zhang Hong , Chen Ping , Lin Zhaoxing , Wang Yaofei , Yang Xiaodong
Published: December 2020

Background: Objectives: To analyze the sociodemographic and clinical factors associated with multi-bacillary(MB) leprosy in elimination planning areas in Northwest China.Design: Retrospective observational study.Setting: Three specialized hospitals were included.Participants : The medical records of leprosy in Shaanxi Province from 2004 to 2020 were collected from the leprosy management information system (LEPMIS).Primary and secondary outcome measures: The basic situation of leprosy treatment and follow-up were investigated.Results : 305 new cases of leprosy were included in the study. 272 cases (89.18%) were MB leprosy, and 33 (10.82%) were pauci-bacillary (PB) leprosy. Male patients were more likely to have neurological injury ( P <0.001; OR:0.35; 95%CI:0.194-0.630). Patients over 60 years old were more likely to have leprosy deformity ( P <0.001; OR:0.113; 95%CI:0.027-0.478) and nerve injury ( P =0.035; OR:0.333; 95%CI:0.115-0.965). Patients with marriage histories were more likely to have leprosy deformities ( P =0.018; OR:0.842; 95%CI: 0.718-0.987). Patients with passive detection had a lower probability of leprosy reaction ( P =0.011; OR:4.268; 95%CI:1.276-14.272); Patients with nerve damage, positive skin smear test or level I or level II disability were more likely to be classified as MB leprosy.Conclusions : MB leprosy is related to social and demographic factors (with or without marriage history, age at diagnosis, discovery mode) and clinical factors (such as the number of skin lesions and nerve lesions).
Effect of Hypoglycemia on Measures of Myocardial Blood Flow and Myocardial Injury in Adults With and Without Type 1 Diabetes: A Prospective, Randomized, Open-Label, Blinded Endpoint, Cross-Over Study
Authors: Noh Radzi M , Graveling Alex J , Lang Ninian N , White AC , Lee Kuan Ken , Mills Nicholas L , Newby David E , Lang Chim C , Frier Brian M
Published: December 2020

Aims: Hypoglycemia provokes a profound autonomic response in humans including cardiovascular effects. This study examined the effect of experimentally-induced hypoglycemia on measures of myocardial blood flow and myocardial injury in adults with, and without, type 1 diabetes.Methods and Results: In a prospective, randomized, open-label, blinded, endpoint cross-over study, 17 young adults with type 1 diabetes with no cardiovascular risk factors, and 10 healthy non-diabetic volunteers, underwent hyperinsulinemic euglycemic (blood glucose 4.5-5.5 mmol/L) and hypoglycemic (2.2-2.5 mmol/L) clamps. Myocardial blood flow was assessed using transthoracic echocardiography Doppler coronary flow reserve (CFR) and myocardial injury using plasma high-sensitivity cardiac troponin I (hs-cTnI) concentration. During euglycemia, a non-significant trend for lower CFR was observed in participants with type 1 diabetes than in those without type 1 diabetes (3.66±0.47 versus 3.92±0.85), and a non-significant lower trend also occurred during hypoglycemia (type 1 diabetes: 3.54±0.58 versus non-diabetes: 3.80±0.84). A generalized linear mixed-model analysis was performed, with diabetes status and euglycemia or hypoglycemia as factors affecting CFR. No significant statistical difference in CFR was observed for diabetes status (p=0.23) or between euglycemia and hypoglycemia (p=0.31). No changes in hs-cTnI occurred during hypoglycemia or in the recovery period (p=0.86).Conclusions: While the observed reduction in coronary flow reserve did not achieve significance during exposure to insulin-induced hypoglycemia in healthy young men with type 1 diabetes, with no evidence of myocardial injury, adverse cardiovascular effects of hypoglycemia cannot be excluded in older people who have coronary disease. Further studies are required to investigate this putative problem.
HIV Prevention at Drug Shops: Awareness and Attitudes among Shop Dispensers and Young women about Oral Pre-exposure Prophylaxis and the Dapivirine Ring in Shinyanga, Tanzania
Authors: Tubert Julia , Packel Laura , Hunter Lauren A. , Mfaume Rashid , Njau Prosper , Ramadhani Angela A. , Liu Jenny X. , McCoy Sandra I.
Published: December 2020

Background: HIV risk remains high among adolescent girls and young women (AGYW, ages 15-24) in Tanzania. Many AGYW experience stigma and provider bias at health facilities, deterring their use of HIV prevention services. Privately-owned drug shops, ubiquitous in many communities, may be an effective and accessible channel to deliver HIV prevention products to AGYW, including oral pre-exposure prophylaxis (PrEP) and the dapivirine vaginal ring. Methods: In July-August 2019, we enrolled 26 drug shops in Shinyanga, Tanzania in an ongoing study to create “girl-friendly” drug shops where AGYW can access HIV self-testing and contraception. At baseline, all shop dispensers were given basic information about oral PrEP and the dapivirine ring and were asked about their interest in stocking each. During the next 3-5 months, we surveyed AGYW (n=56) customers about their interest in oral PrEP and the ring. Results: Among dispensers, the median age was 42 years and 77% were female. Overall, 42% of dispensers had heard of a medication for HIV prevention. Almost all dispensers reported some interest in stocking oral PrEP (92%) and the dapivirine ring (96%). Most (85%) reported they would provide oral PrEP to AGYW who requested it. Among AGYW customers, the median age was 17 years; 18% of AGYW were married and 7% had children. Only 20% of AGYW had heard of a medication to prevent HIV, yet 64% and 43% expressed some interest in using oral PrEP and the dapivirine ring, respectively, after receiving information about the products. PrEP interest was higher among AGYW who were partnered and had children.Conclusions: Despite low prior awareness of PrEP among shop dispensers and AGYW, we found high levels of interest in oral PrEP and the dapivirine ring in both groups. Community-based drug shops represent a promising strategy to make HIV prevention more accessible to AGYW.
Corrosion and Transformation of Solution Combustion Synthesized Co, Ni and CoNi Nanoparticles in Synthetic Freshwater with and without Natural Organic Matter
Authors: Khort Alexander , Hedberg Jonas , Mei Nanxuan , Romanovski Valentin , Blomberg Eva , Wallinder Inger Odnevall
Published: December 2020

Pure metallic Co, Ni, and their bimetallic compositions of Co3Ni, CoNi, and CoNi3 nanomaterials were prepared by solution combustion synthesis. Microstructure, phase composition, and crystalline structure of these nanoparticles (NPs) were characterized along with studies of their corrosion and dissolution properties in synthetic freshwater with and without natural organic matter (NOM). The nanomaterials consisted of aggregates of fine NPs (3–30 nm) of almost pure metallic and bimetallic crystal phases with thin surface oxide covered by a thin carbon shell. The nanomaterials were characterized by BET surface areas ranging from ~ 1 to 8 m2/g for the Ni and Co NPs, to 22.93 m2/g, 14.86 m2/g, and 10.53 m2/g for the Co3Ni, CoNi, CoNi3 NPs, respectively. More Co and Ni were released from the bimetallic NPs compared with the pure metals although their corrosion current densities were lower. In contrast to findings for the pure metal NPs, the presence of NOM increased the release of Co and Ni from the bimetallic NPs in freshwater compared to freshwater only even though its presence reduced the corrosion rate (current density). It was shown that the properties of the bimetallic nanomaterials were influenced by multiple factors such as their composition, including carbon shell, type of surface oxides, and the entropy of mixing.
Clinically Inapparent Right Heart Dysfunction is Associated with Reduced Myofilament Force Development in Coronary Artery Disease
Authors: Bening Constanze , Sales Virna , Alhussini Khaled , Radakovic Dejan , Benitez Rodolfo , Madrahimov Nodir , Keller Daniel , Leyh Rainer
Published: December 2020

Background: Right ventricular dysfunction after CABG is associated with poor peri- and postoperative outcomes. We hypothesized that inapparent RV dysfunction in these patients is already associated with pathological changes at the level of myofilaments in concert with altered biomarkers of myocardial remodeling and endothelial dysfunction.Methods: From 08/2016 to 02/2018, 218 patients scheduled for CABG were divided into two groups (TAPSE ≥20mm, n=178;TAPSE<20mm,n=40). Baseline serum samples for biomarkers (Galectin,TGFß1,N Acyl-SDMA, Arginine, ADMA and Pentraxin-3), clinical laboratory and transthoracic echocardiographic parameters were evaluated. To examine the myocardial apparatus of the right ventricle intraoperative right auricular tissue was harvested for stepwise skinned fiber force measurements.Results: Patients with TAPSE <20mm had a higher incidence of DM (55vs34%,p=0.018), preoperative AFib (43vs16%,p=0.000), reduced GFR (67±18vs77±24 ml/min/1.73m2,p=0.013), larger LA area (22±6vs20±5cm2,p=0.005) and reduced LVEF (50vs55 %,p=0.008). Furthermore, higher serum ADMA (0.70±0.13vs0.65±0.15µmol/l, p=0.046) and higher serum Pentraxin-3 levels (3371±1068vs2681±1353pg/dl,p=0.004) were observed in these Patients. Skinned fibre force measurements showed significant lower values at almost every step of calcium concentration (pCa 4.52 to pCa 5.5,p<0.01 and pCa 5.75 to 6.0,p< 0.05). Multivariable analysis revealed DM (OR 2.53 CI1.12-5.73, Euro Score II (OR1.34 CI 1.02-1.78), preoperative AF (OR4.86 CI2.06-11.47), GFR (OR7.72 CI 1.87-31.96), albumin (OR1.56 CI 0.52-2.60), Pentraxin-3 (OR19.68 CI14.13-25.24), depressed LVEF (OR8.61 CI 6.37-10.86), lower force values: (pCa 5.4; OR2.34 CI 0.40-4.29 and pCa 5.2; OR2.00 CI 0.39-3.60) as predictors for clinical inapparent right heart dysfunction. Conclusions: These preliminary data showed that inapparent right heart dysfunction in CAD is already associated with reduced force development of the contractile apparatus.
High Cytoplasmic FOXO3 Expression Associated with Poor Prognosis in Rectal Cancer Patients Received Preoperative Radiotherapy: A Study from Swedish Clinical Trial of Preoperative Radiotherapy to Big Database Analysis
Authors: Cui Weiyingqi , Xie Ning , Lam Eric. W.-F. , Hahn-Stromberg Victoria , Liu Na , Zhang Hong , Sun Xiao-Feng
Published: December 2020

Background: Accumulating evidence has implicated a pivotal role for FOXO3, FOXM1 and SIRT6 in cancer progression and metastasis. The majority of researches have focused on the functions of these proteins in drug resistance, but their relationships with radiotherapy (RT) response remain unclear. In this study, we examined the protein expression of FOXO3, FOXM1 and SIRT6 and their clinical significance in a Swedish rectal cancer trial of preoperative RT.Methods: Protein expression of FOXO3, FOXM1 and SIRT6 protein was examined by immunohistochemistry in tissue microarray (n =145). Genetic analysis of FOXO3, FOXM1 and SIRT6 were performed by cBioportal and MEXPRESS database. Gene-gene network analysis was conducted using GeneMANIA. Further functional enrichment analysis was performed based on LinkedOmics and Metascape online software.Results: The results showed that the FOXO3 and FOXM1 proteins were mainly expressed in the cytoplasm in both the normal and tumour tissues, and SIRT6 in both the cytoplasm and nucleus of the normal and tumour tissues. The FOXO3 and FOXM1 protein levels increased from the normal mucosa to the primary cancer (P < 0.001), while the SIRT6 protein decreased from the normal mucosa to the primary cancer (P < 0.001). High FOXO3 expression correlated with late TNM stage (P = 0.040) and distant metastasis (P = 0.032), as well as independently with disease free survival (RFS) in RT patients (HR = 7.948; P = 0.049; 95% CI = 1.002-63.032) but not in non-RT patients (P > 0.05). Furthermore, genetic analysis indicated that DNA methylation status contributes to the FOXO3 overexpression. Functional enrichment analysis demonstrated that FOXO3 is closely related to metabolism-related signalling pathway which is in turn associated with cancer radioresistance. Moreover, there were strong gene–gene interactions between FOXO3 and genes in metabolism-related signalling.Conclusions: Our findings suggest that FOXO3 may be a key predictive biomarker to optimise RT for rectal cancer patients to improve prognosis.Trial registration: Radiotherapy; 86151; Registered 17 November 1986; NCT00904813; https://clinicaltrials.gov/ct2/show/NCT00904813?term=Preoperative+Radiotherapy&cntry=SE&draw=3&rank=3.
Argininosuccinate Synthase 1 Suppresses Tumor Progression Through Activation of PERK/eIF2α/ATF4/CHOP Axis in Hepatocellular Carcinoma
Authors: Kim Sanghwa , Lee Minji , Song Yeonhwa , Lee Su-Yeon , Choi Inhee , Park I-Seul , Kim jiho , Kim Jin-sun , Kim Kang mo , Seo Haengran
Published: December 2020

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide, and liver cancer has increased in mortality due to liver cancer because it was detected at an advanced stages in patients with liver dysfunction, making HCC a lethal cancer. Accordingly, we aim to new targets for HCC drug discovery using HCC tumor spheroids.Methods: Our comparative proteomic analysis of HCC cells grown in culture as monolayers (2D) and spheroids (3D) revealed that argininosuccinate synthase 1 (ASS1) expression was higher in 3D cells than in 2D cells due to upregulated endoplasmic reticulum (ER) stress responses. We investigated the clinical value of ASS1 in Korean patients with HCC. The mechanism underlying ASS1-mediated tumor suppression was investigated in HCC spheroids. ASS1-mediated improvement of chemotherapy efficiency was observed using high content screening in an HCC xenograft mouse model.Results: Studies of tumor tissue from Korean HCC patients showed that, although ASS1 expression was low in most samples, high levels of ASS1 were associated with favorable overall survival of patients. Here, we found that bidirectional interactions between ASS1 ER stress responses in HCC-derived multicellular tumor spheroids can limit HCC progression. ASS1 overexpression effectively inhibited tumor growth and enhanced the efficacy of in vitro and in vivo anti-HCC combination chemotherapy via activation of the PERK/eIF2α/ATF4/CHOP axis, but was not dependent on the status of p53 and arginine metabolism.Conclusion: These results demonstrate the critical functional roles for the arginine-metabolism–independent tumor suppressor activity of ASS1 in HCC and suggest that upregulating ASS1 in these tumors is a potential strategy in HCC cells with low ASS1 expression.
Efficacy and Mechanism of the Combination of PARP and CDK4/6 Inhibitors in the Treatment of Triple-negative Breast Cancer
Authors: ZHU XIUZHI , CHEN LI , Huang Binhao , Li Xiaoguang , Liu Yang , Hu Xin , Shao Zhimin , wang zhonghua
Published: December 2020

Background: PARP inhibitors (PARPi) benefit only a fraction of breast cancer patients with BRCA mutations and their efficacy is even more limited in triple-negative breast cancer (TNBC) due to clinical primary and acquired resistance. Here, we found that the efficacy of PARPi in TNBC can be improved with CDK4/6 inhibitors (CDK4/6i).Methods: We screened primary PARPi-sensitive and resistant cell lines from existing BRCAmut/TNBC cell lines and generated cells with acquired PARPi resistance by gradually increasing the concentration. The effects of the PARPi olaparib and the CDK4/6i palbociclib on BRCAmut/TNBC cell lines were examined in both sensitive and resistant cells in vitro and in vivo. Pathway and gene alterations were assessed mechanistically and pharmacologically.Results: We demonstrated for the first time that the combination of PARPi and CDK4/6i has synergistic effects against BRCAmut/TNBC both in vitro and in vivo. In the PARPi-sensitive MB436 cells, the single agent olaparib significantly inhibited cell viability and affected cell growth due to severe DNA damage. In the PARPi-resistant HCC1937 and SUM149 cells, single-agent olaparib was ineffective due to potential homologous recombination (HR) repair, and the combination of PARPi and CDK4/6i greatly inhibited HR during the G2 phase, increased DNA damage and inhibited tumor growth. Inadequate DNA damage caused by PARPi activated the Wnt signaling pathway and upregulated MYC. Further experiments indicated that the overexpression of β-catenin, especially its hyperphosphorylation at the Ser675 site activated the Wnt signaling pathway and mediated PARPi resistance, which could be strongly inhibited by the combined treatment with CDK4/6i.Conclusions: Our data provide a rationale for the clinical evaluation of the therapeutic synergy of PARPi and CDK4/6i in BRCAmut/TNBCs with high Wnt signaling activation, high MYC expression and do not respond to PARPi monotherapy.
The Effect of Learning Module Program on the Mothers’ Ability to Adapt New Foods, Feeding Styles, and Self-Efficacy to Their Children with Avoidant Restrictive Food Intake Disorder (ARFID)
Authors: prasetyo yoyok bekti , Nursalam Nursalam , Hargono Rahmat , Ahsan Ahsan
Published: December 2020

Purpose: This study is to examine the effects of learning module program on the mothers’ ability to adapt new foods, feeding styles, and self-efficacy to their children with Avoidant Restrictive Food Intake Disorder (ARFID).Methods: Quasi-experimental design without random sampling is used to evaluate the effectiveness of learning module program. There are 15 mothers take care of children with ARFID as experimental group given learning module program. The experimental group is conducted four meetings in four weeks. Each meeting has an effective 50 minutes. Fifteen mothers of control group are conducted home-visit by presenting the education of health to them. The control group intervention is performed two meetings. Meanwhile, the experimental group conducts pre-test and post-test. The data are analyzed by means of descriptive statistics, Chi-square test, Fisher’s exact test, Mann-Whitney U test and SPSS/WIN 22.0. Results: The participants of experimental group have showed bigger surge of new foods adaptation (t = -2.973, p < 0.003), feeding style (t = -4.646, p < 0.001), self-efficacy (t = -3.652, p = 0.001) than control group has.Conclusion: The findings indicated that the learning module program is deemed effective to improve mothers’ ability to adapt new foods, feeding styles, and self-efficacy to their children with ARFID.