bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGARUH PEMBERIAN EKSTRAK RUMPUT KEBAR (Biophytum petersianum) TERHADAP DIAMETER DAN TEBAL EPITEL TUBULUS SEMINIFERUS MENCIT (Mus musculus) YANG DIPAPAR 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN
Authors: Rusyawardani Aldis Ingrid , Widjiati Widjiati , Utama Suzanita , Anwar Chairul , Luqman Epy Muhammad , Maslachah Lilik
Published: June 2020

The aim of this research is to analyze the effect of kebar grass on the diameter and epithelium thickness of seminiferous tubules. Twenty male mice of BALB/C strain with an average weight of 25 gram were used in this research. Total five experimental groups (4 mice each group) were treated with combination of TCDD and kebar grass extract designed as follows: (C-) 0mg/g BW/day dan 0µg/kg BW, (C+) 0mg/g BW/day and 7µg/kg BW, (T1) 0,045mg/g BW/day and 7µg/kg BW, (T2) 0,080mg/g BW/day and 7µg/kg BW, (T3) 0,1350mg/g BW/day and 7µg/kg BW. The TCDD was injected peritoneally in single dose while kebar grass extract was given orally everyday for 53 days. The results showed a significant difference (p<0,05) on group which is treated with kebar grass extract 0,135mg/ g BW/ day is proven could maintain the diameter of seminiferous tubules in T3 group (170,5μmb ± 0,65μm) compared with C+ group (129,50μma ± 8,42μm). Significant difference of epithelial thickness were also found between the control and treatment groups (p<0,05). The C+ group (33,57μmb ± 1,61μm) was different from the T1 group (43,80μmc ± 1,46μm), T2 (48,49μmd ± 1,08μm), T3 (52,15μme ± 0,86μm) and C- (56,17μma ± 1,35μm). This findings might suggest TCDD has the potential to decrease the epithelium thickness and the diameter of seminiferous tubules, while kebar grass extract in various dose were proven to be able maintain the epithelium thickness of seminiferous tubules but could not maintain the diameter of seminiferous tubules.
DAMPAK PEMBERIAN ROTI AFKIR TERHADAP EFISIENSI REPRODUKSI SAPI PERAH Friesian Holstein DI WILAYAH KERJA KPSP SETIA KAWAN NONGKOJAJAR, PASURUAN
Authors: Nurdianto S. Ricko , Hidanah Sri , Madyawati Sri Pantja , Samik Abdul , Wurlina Wurlina , Suprayogi Tri Wahyu
Published: June 2020

The purpose of this research is to know the impact of bread waste to efficiency reproduction of Friesian Holstein cow in regional working KPSP Setia Kawan Nongkojajar, Pasuruan by value Service per Conception (S/C), Conception Rate (CR), Days Open (DO). Method in this research is the dependent variable observed is the reproductive efficiency, the dependent variable as a supporter is the cow has given birth, the healthy dairy cow, the feed volume given. The data obtained is processed by using descriptive analysis to get the reproduction efficiency figure. The result of the research indicate that the value of Service per Conception (S/C) = 1.5 ± 0.69 times, Days Open (DO) = 95.6 ± 11.32 days and Conception Rate (CR) = 65% and Fertility Status (FS) = 72,4%. Results of this study can be concluded that bread waste provided by the breeder as an additional feed for dairy cow has no significant effect.
CONCEPTION RATE DAN SERVICE PER CONCEPTION PADA SAPI BALI HASIL INSEMINASI BUATAN DI KABUPATEN SUMBAWA BARAT TAHUN 2017
Authors: Deskayanti Asih , Sardjito Trilas , Sunarso Agus , Srianto Pudji , Suprayogi Tri Wahyu , Hermadi Herry Agoes
Published: June 2020

The study was conducted to know Conception Rate and Service per Conception of  Bali cattle acceptors in west Sumbaw district. Data were collected fot the periode of January to September 2017 from inseminator in west Sumbawa district. The data were taken by primary and secondary data. Primary data retrieval is done by direct observation, which includes several variables, where the variable include the identitiy of the breeder, the cages, feeding, drinking and knowladge of breeders. The secondary data were obtained by recording of the officer insemination. All data was analyzed to find a percentage of Conception Rate and find number of Service per Conception (S/C) by analyzed descriptive of SPSS. Risults of this research showed that Conception Rate and Service per Conception’s average of Bali Cattle is 60 % and 1,7. The conculusion of this research showed that Conception Rate is lower than normal value and Service per Conception of Bali cattle in West Sumbawa district is better. This research was expected to be a reference for the next artificial insemination programmed by the government.
HUBUNGAN ANTARA BODY CONDITION SCORE (BCS) DENGAN PRODUKSI SUSU SAPI PERAH FRIESIAN HOLSTEIN (FH)
Authors: Netika Melsa , Darsono Roesno , Utomo Budi , Mustofa Imam , Ismudiono Ismudiono , Suprayogi Tri Wahyu
Published: June 2020

The aim of this research was to observe the Body Condition Score (BCS) and milk production of Friesian Holstein (FH) dairy cattles. 144 of dairy cattles divided into 3 groups based on BCS 1-9 scale. The results showed that Y = 6.62 + 5.54X - 5.78X2. Coefficient of determination (R2) of 20.6 this mean any increase in milk production by 20.6% is affected by BCS. It can be concluded that there is a correlation between Body Condition Score (BCS) and milk production. The higher BCS (BCS 7-8) the lower milk production, while in ideal BCS production (5-6) the production of milk is optimize.
The Effect of Health Education Course Review Horay Method and Video Media on Improvement of Personal Hygiene Ability in Children Age School
Authors: Riya Novita , Sufyanti Arief Yuni , Dwi Kurnia Iqlima
Published: June 2020

Introduction: Personal hygiene problems that often occur in school-age children are related to hand hygiene and dental hygiene. This study aims to explain the effect of health education methods review horay courses and videos media on improving personal hygiene abilities.Methods: Quasy-experimental pretest-posttest design with control group design. A population of 150 students in Elementary School (ES) A of Surabaya and 123 students in ES B of Surabaya. The sample size was proportional to stratified cluster random sampling. A total of 72 respondents in ES A of Surabaya and ES B of Surabaya with 36 treatment groups and 36 control groups. The instrument used a questionnaire and an observation sheet (checklist). The analysis uses the Wilcoxon Signed Ranks Test and the Mann-Whitney U Test.Results: Wilcoxon Signed Ranks Test showed knowledge (p = 0.000), attitude (p = 0.000), hand hygiene practice (p = 0.000) and tooth brushing practice (p = 0.000). The value of p <0.05 then there was the effect of intervention courses review horay method and video to increase the ability of personal hygiene in school-age children. Mann-Whitney U Test results showed knowledge (p = 0.000), attitude (p = 0.000), hand hygiene practices (p = 0.000) and tooth brushing practice (p = 0.000). The value of p <0.05 then there was a mean difference in the level of personal hygiene ability between the treatment and control groups.Conclusion: Health education horay review course method and video media to improve the ability of personal hygiene in school-age children to increase knowledge, attitudes and actions in the form of hand hygiene and tooth brushing properly and correctly in the elementary school.
Icterícia neonatal e seus fatores perinatais associados: perfil dos recém-nascidos internados em uma unidade de terapia intensiva neonatal de maternidade de referência terciária no município de Fortaleza – Ceará
Authors: Carvalho Rafaela Loiola de , Lavor Maria Francielze Holanda
Published: June 2020

Objetivos: conhecer o perfil de recém-nascidos (RN) internados em unidade de terapia intensiva (UTIN), no Serviço de Neonatologia de uma maternidade pública terciária do município de Fortaleza, que apresentaram icterícia. Metodologia: estudo transversal, prospectivo, sendo os dados coletados nos prontuários de 01 de fevereiro a 31 de julho de 2018, utilizando questionário simples. As análises estatísticas foram realizadas no programa software R 3.3.1 e Microsoft Excel® 2016. Resultados: os dados revelaram que 70,7% dos RN apresentaram icterícia significativa e 84,5% tinham idade gestacional menor que 35 semanas. O sexo masculino apresentou-se em 58,2% dos casos. Em 65,3% o tempo de clampeamento do cordão umbilical foi menor que 1 minuto. A taxa de sepse precoce foi de 68% e a de sepse tardia de 35,9%. A hemorragia peri-intraventricular (HPIV) esteve presente em 37,4% da amostra. O índice de policitemia foi de 1%. Pré-eclâmpsia foi fator protetor para icterícia significativa. Fototerapia foi realizada em todos os RN e 5,1% necessitaram de exsanguíneotransfusão. Conclusões: a prematuridade abaixo de 35 semanas foi o principal fator associado a icterícia de alto risco e esforços obstétricos e neonatais voltados para a sua prevenção são necessários no sentido de melhorar esse quadro e seus fatores relacionados.
Violencia de género, custodia compartida y mediación familiar en España. Discursos profesionales
Authors: Gómez Gómez Francisco , Esteban Raúl Soto
Published: June 2020

Los profesionales de los juzgados de familia entre los que se encuentran jueces y trabajadores sociales actúan en las familias en las que aparecen diferentes relaciones interpersonales conflictivas. Estos profesionales abordan la violencia de género, la custodia compartida y la mediación familiar en su práctica profesional diaria.

Este artículo, basado en una investigación doctoral más amplia sobre el trabajo social judicial como ayuda en las crisis conyugales analiza cualitativamente los discursos obtenidos en entrevistas realizadas a jueces y trabajadores sociales de los juzgados de familia de Madrid y Barcelona.

Se reflejan las opiniones más comunes de la actuación pericial y judicial, realizando una prospección anónima para alcanzar la expresión libre de los profesionales.

Los significativos resultados que se ofrecen indican la necesidad de continuar estudiando las problemáticas abordadas en los juzgados de familia, en lugar de profundizar en una polarización del pensamiento sobre cuestiones trascendentales para la organización de las familias en crisis.
How Rational Is the Greek Plan for Opening up Tourism?
Authors: Lazaridis Emmanuel , Clark Estelle
Published: June 2020

The issue of when and how to return to business following COVID-19 lockdown is occupying the minds of policymakers, C-Suite executives and managers the world over. We are concerned by the extent to which it appears that these decisions are being taken on a wing and a prayer, while being pitched to the public as though they shouldn’t be questioned. In this paper, we compare the likely impact of COVID-19 infections from travellers coming from the main countries that visit Greece, to the revenues they generate for the Greek economy. We find that arrivals from some countries should be excluded but aren't, while arrivals from other countries that are excluded perhaps shouldn't be. We show that a rational choice around limitations on the reopening of tourist markets depends on the demand for travel to Greece. We conclude that the current policy is largely economically rational, with some exceptions, but also speculate that Greece may not be ready to handle the resulting infection load.
What Makes the UK Recovery Trial More Pragmatic than the European Discovery Trial?
Authors: Han Ru , Liang Shuyao , Biernikiewicz Malgorzata , Wang Yitong , Toumi Mondher
Published: June 2020

The objective of this study was to review the study design and preliminary results of the Recovery trial and analyze the implementability of the Recovery trial by comparing it with the European Discovery trial.Method: The study design of the Recovery trial in the latest version of protocol was described and deeply analyzed to address the issue of implementation of the trial. A comparative analysis of study design and implementation between the UK Recovery trial and the European Discovery trial was conducted following the description.Results: The Recovery trial is a pragmatic, randomized, controlled, adaptive, open-label clinical trial. The study design of the Recovery trial was reported in the ISRCTN registry, the EU Clinical Trials Register and the U.S. National Library of Medicine ClinicalTrials.gov registry. Initially published on the 13th March 2020, the study protocol of the Recovery trial has been updated five times at the time of this writing. More than 11,000 patients have been enrolled and 80% have completed the follow-up. Thousands of health care professionals at 175 Trusts in the UK have been involved. Conclusion: The Recovery trial applies a study design to address the issue of implementation in the context of the COVID-19 pandemic and emergency. It was conceptually pragmatic with a clear vision to address the top priority: the control of mortality and rational use of scarce resources. By contrast, the Discovery trial was designed as an intellectual exercise and consequently failed to address the issue of implementation in emergency.
Repurposing of FDA Approved Drugs as COVID-19 Therapeutics: Safety Concerns and Contraindications of Drugs in Clinical Trials
Authors: Dharavath Ravinder Naik , Dutt Meenu , Kumar Sunil , Badyal Priya , Rawat Nitin , Kaur Tanzeer , Sharma Shweta , Bishnoi Mahendra , Chopra Kanwaljit
Published: June 2020

Coronavirus disease (COVID-19) is the current global public health threat with no specific, effective, and approved treatment available till date. The outbreak of COVID-19 has led the world into an unimagined and uncertain situation by disrupting the economies, claiming human lives, and leaving many into secondary mental health problems. As per the latest WHO report, approximately 8.2 million people are infected, and nearly 0.44 million lives are lost to COVID. The infection has spread to over 200 countries and territories around the world. The world is in search of efficient diagnostics and therapeutics, including vaccines, biologics and drugs. With the rapid increase in rates of infection and time constraints, drug repurposing seems to be a potential and viable option to find the promising anti-COVID therapeutics. In the wake of a rapid increase in the number of clinical trials involving drugs for repurposing, we aim to provide information on the safety concerns related to the drugs currently investigated in trials. This review also highlights the possible mechanisms of actions, adverse drug reactions, and contraindications of the drugs under repurposing evaluation.
Probiotics Effect on the Immune System
Authors: Ng Jonathan Cho Kin
Published: June 2020

Background: Probiotics can provide health benefits to an individual by regulation of the immune system. Many clinical trials have found that probiotics can prevent upper respiratory tracts infections. Aim: To perform a systematic review and meta-analysis of available trials to investigate the effectiveness of probiotics in the prevention of upper respiratory tract infections in individuals of all ages. Conclusion: Probiotics were found to be better in reducing the number of participants who experienced acute URTI, the average duration per episode of acute URTI, use of antibiotics in URTI related cases and absence due to URTI. Side effects were found to be minor, making probiotics a good candidate for clinical use. This shows that probiotics are effective in preventing acute URTIs. However, due to limited studies and small sample size, the results are subjected to bias and should be interpreted with care.
CD44 Alternative Splice Variants v6 and v10
Authors: Aquib Ahmed , Yadav Ajay Kumar
Published: June 2020

CD44 glycoprotein is ubiqutously present and situated at the extracellular surface of cell. Its role as an adhesion recptor was modified depending upon the state of post addition of glycomoeties under varied microenvironment. Many alternative spliced variants of CD44 were expressed by human cells depending upon the attainment during mutifunctional signal disposition. The function of splice factors, and hnRNPA family (Heterogenous ribonucleoproteins A) were dicussed in context to CD44 alternative variants. Glioma cell cline U87 MG were used in this study to search more about the affect of hnRNPA1 and hnRNPA2/B1 knockdown in CD44 V6 and CD44V10 expression. We found in preliminary study that splice factor knock down reduces the alternative splice variants of CD44 such as V6 & V10. Therefore, potential of this study to elaborate further the mechanism in vivo model, to validate the alternative spliced variant in context to interaction with extracellular microenvironment.
Spectrophotometer Determination of Cefixime in pure form and pharmaceutical preparation by Using Cloud point Extraction
Authors: Kadhim et al. Esraa
Published: June 2020

Two simple methods spectrophotometric were suggested for the determination of Cefixime (CFX) in pure form and pharmaceutical preparation. The first method is based without cloud point (CPE) on diazotization of the Cefixime drug by sodium nitrite at 5Cº followed by coupling with ortho nitro phenol in basic medium to form orange colour. The product was stabilized and measured 400 nm. Beer’s law was obeyed in the concentration range of (10-160) μg∙mL-1 Sandell’s sensitivity was 0.0888μg∙cm-1, the detection limit was 0.07896μg∙mL-1, and the limit of Quantitation was 0.085389μg∙mL-1.The second method was cloud point extraction (CPE) with using  Trtion X-114 as surfactant. Beer’s law was obeyed in the concentration range of (10-160) μg∙mL-1. Sandell’s sensitivity was 0.1470μg∙cm-1, the detection limit was 0.06680μg∙mL-1, and the limit of quantitation was 0.07293μg∙mL-1. All variables including the reagent concentration, reaction time, colour stability period, and mole ratio were studied in order to optimize the reaction conditions. The composition of product (1:1). The methods were effectively useful to the determination of Cefixime in pharmaceutical dose form, and the attained results were in good agreement with the official result and other methods in literature .No interference was observed from the commonly encountered additives and excipients
Detection and Resistance of Staphylococcus aureus chiken meats to some antibiotics
Authors: Rastina Rastina , Abrar Mahdi , Erina Erina , Winaruddin Winaruddin , Suryani Suryani
Published: June 2020

Abstract
IgE reactivity to fish allergens from Pacific cod (Gadus macrocephalus) in atopic dogs
Authors: Imanishi Ichiro , Uchiyama Jumpei , Mizukami Keijiro , Kamiie Junichi , Kurata Keigo , Iyori Keita , Fujimura Masato , Shimakura Kuniyoshi , Nishifuji Koji , Sakaguchi Masahiro
Published: June 2020

Background: IgE reactivity to fish allergens in atopic dogs, which are used as models for food allergy, has not been elucidated to date. We investigated IgE reactivity to crude extracts and purified allergens derived from the Pacific cod (Gadus macrocephalus) in atopic dogs to identify the allergenic proteins of cod.Results: The levels of specific IgE to crude cod extracts were measured in the sera of 179 atopic dogs, including 27 dogs with cod allergy, using enzyme-linked immunosorbent assay (ELISA). Specific IgE to crude cod extracts were present in 36 (20%) of the 179 atopic dogs and in 12 (44%) of the 27 dogs with cod allergy. The allergens in crude cod extracts were analyzed by ELISA, immunoblotting, and liquid chromatography-tandem mass spectrometry. In allergen component analysis, IgE reactivity to tropomyosin and enolase was observed in the sera of dogs with cod allergy. IgE reactivity to parvalbumin, collagen, and tropomyosin was evaluated using the sera of atopic dogs that tested positive for specific IgE to crude cod extracts. Among the 36 dogs with IgE reactivity to crude cod extracts, 9 (25%), 14 (39%), and 18 (50%) dogs tested positive for specific IgE to parvalbumin, collagen, and tropomyosin, respectively.Conclusions: The IgE reactivity to cod allergens observed in dogs was similar to that in humans, and this finding further supports the use of atopic dogs with fish allergy as a model for fish allergy in humans.
Transcriptome analysis reveals ethylene-mediated defense responses to Fusarium oxysporum f. sp. cucumerinum infection in Cucumis sativus L.
Authors: Dong Jingping , Wang Yuean , Xian Qianqian , Chen Xuehao , Xu Jun
Published: June 2020

Background: Fusarium wilt, caused by Fusarium oxysporum f. sp. cucumerinum (Foc), is a severe disease affecting cucumber (Cucumis sativus L.) production worldwide, but mechanisms underlying Fusarium wilt resistance in cucumber remain unknown. To better understand of the defense mechanisms elicited in response to Foc inoculation, RNA sequencing-based transcriptomic profiling of responses of the Fusarium wilt-resistant cucumber line ‘Rijiecheng’ at 0, 24, 48, 96, and 192 hours after Foc inoculation was performed.Results: We identified 4116 genes that were differentially expressed between 0 hour and other time points after inoculation. All ethylene-related and pathogenesis-related genes from the differentially expressed genes were filtered out. Real-time PCR analysis showed that ethylene-related genes were induced in response to Foc infection. Importantly, after Foc infection and exogenous application of ethephon, a donor of ethylene, the ethylene-related genes were highly expressed. In response to exogenous ethephon treatment in conjunction with Foc inoculation, the infection resistance of cucumber seedlings was enhanced and endogenous ethylene biosynthesis increased dramatically. Conclusion: Collectively, ethylene signaling pathways play a positive role in regulating the defense response of cucumber to Foc infection. The results provide insight into the cucumber Fusarium wilt defense mechanisms and provide valuable information for breeding new cucumber cultivars with enhanced Fusarium wilt tolerance.
Initiation into street, challenges, means of survival and perceived strategies to alleviate its plights among street children in Addis Ababa, Ethiopia 2019 A phenomenological study design
Authors: Chimdessa Ayana Fite
Published: June 2020

Background: There has been a major discrepancy in defining the term street children-where various stakeholders define in different ways. In spite of increasing in number, the life and health of street children is becoming a global concern. Even though a wide range of policies and strategies are available, they are poorly designed with helpless implementation. This made street children defenseless to harassments and denial of social protection services.Methods: A phenomenological study design was employed to explore difficulties of the street children and perceived strategies to prevent and alleviate plights. The study was conducted from January to March 2019. A Time-Space Sampling (TSS) was used to recruit participants. Pre-tested interview guide was used for data collection. Data was analyzed by using framework analysis software. Results: A total of 103 street children took part in the study. Complexity of push and pull factors pose to risk of flee into the street. Street children are facing widespread challenges i.e. social network fragmentation, child trafficking, harassments and shortage of coverage of basic needs. Furthermore, absences of comprehensive and contextualized strategies and less political value for this group worsening it. Thus, street children have been considered as felon, out laws and having a mentality of committing crime by both law keeping bodies and society. This in turn, affecting street children’s’ acceptance by their community and get legal protection under the law and made them more risk to denial of social protection services. To win street life struggles, they use different survival mechanisms by forming small group. Income Generating Activities (IGAs), shelter, community support, child protection, access to health education, health services, life coaching and by less extent reintegration are positively perceived strategies to address their problems. Conclusion: Lack/poorly designed policies and strategies targeting street children has made them prone to health and social problems. Furthermore, stigma by community, limited resources, lack of comprehensive standards and absence of political value of interventions exacerbating it. Therefore, call for different stakeholders in supporting to design and implement clear, case based and contextualized strategic policies to address and prevent plights; by considering positively perceived street children’s strategies.
Central venous pressure measurement is associated with improved outcomes in septic patients: an analysis of the MIMIC-III database
Authors: Chen Hui , Zhu Zhu , Zhao Chenyan , Guo Yanxia , Chen Dongyu , Wei Yao , Jin Jun
Published: June 2020

Purpose: Measurement of central venous pressure (CVP) can be a useful clinical tool. However, the formal utility of CVP measurement in preventing mortality in septic patients has never been proven.Methods: The Medical Information Mart for Intensive Care III (MIMIC-III) database was searched to identify septic patients with and without CVP measurements. The primary outcome was 28-day mortality. Multivariate regression was used to elucidate the relationship between CVP measurement and 28-day mortality, and propensity score matching (PSM) and an inverse probability of treatment weighing (IPTW) were employed to validate our findings. Results: A total of 10275 patients were included in our study, of which 4516 patients (44%) underwent CVP measurement within 24 h of intensive care unit (ICU) admission. The risk of 28-day mortality was reduced in the CVP group (OR 0.60 (95% CI 0.51-0.70; p<0.001)). Patients in the CVP group received more fluid on day 1, and had a shorter duration of mechanical ventilation and vasopressor use, and the reduction in serum lactate was greater than that in the no CVP group. The mediating effect of serum lactate reduction was significant for the whole cohort (p=0.04 for the average causal mediation effect (ACME)) and patients in the CVP group with an initial CVP level below 8 mmHg (p=0.04 for the ACME).Conclusion: CVP measurement was associated with decreased risk-adjusted 28-day mortality among patients with sepsis and was proportionally mediated through serum lactate reduction.
Renal Hemangioblastoma with Mixed Mullerian tumor of endometrium: A tale of two rare primary tumors
Authors: Setia Aparna , Kumar Devender , Bains Lovenish , Sharma Pallavi , Tempe Anjali , Mallaya Varuna
Published: June 2020

Introduction: Renal hemangioblastoma (RH) is a very rare benign tumor. Hemangioblastoma most commonly occur in the central nervous system (CNS) and only few cases of RH have been reported as they occur most commonly as asymptomatic masses found incidentally. Mixed Mullerian Tumor (MMT) of the uterus is a rarer and aggressive form of uterine malignancy. The detection of two primary rare tumors incidentally is a rare entity. Case presentation: A 50 years female presented with abnormal uterine bleeding which on endometrial sampling was diagnosed as a rare variety of endometrial cancer i.e., MMT or uterine carcinosarcoma. On preoperative imaging, a renal mass was also detected which was highly vascular and was mimicking Renal Cell Carcinoma (RCC). Fine needle aspiration cytology (FNAC) was done from the renal mass to differentiate between RCC and metastasis but it showed only blood cells. Patient underwent staging laparotomy for endometrial cancer and frozen section examination of the renal mass which was inconclusive with few atypical cells and thus patient underwent radical nephrectomy too. Histopathological examination revealed it to be a RH which is a very rare benign tumor. Discussion: RH is a rare benign tumor which doesn’t require any treatment in majority of the patients. Only 26 cases of RH outside the CNS have been reported till date. MMT is a rare aggressive uterine tumor with an incidence of 1-2 % of all uterine neoplasms, which metastasizes early and thus early identification and treatment is the key. RH needs to be differentiated from RCC to avoid over treatment. Morphological findings are similar in both, preoperative FNAC, PET scan and intraoperative frozen section can be utilized to differentiate in between two in well circumcised tumors and in high suspicion. Occurrence of renal mass as an incidental finding in the preoperative work up of uterine malignancy directed us to the differentials of metastasis or another histologically distinct primary tumor. The presence of two rare primary tumors i.e., RH and MMT in the same patient which are unrelated is a rare entity.
Investigation of molecular mechanisms using integrated analysis of transcriptomes and cytokinome in dermatomyositis
Authors: Bai Jingjing , Wu Chanyuan , Zhong Danli , Xu Dong , Wang Qian , Zeng Xiaofeng
Published: June 2020

Background Pathomechanism of dermatomyositis (DM) remains yet fully elucidated. While several cytokines have been proved to participate in the progress of DM, few studies provided a comprehensive analysis of cytokinome in different DM clinical-serological subgroups and correlation with disease activity as well as interaction with DM tissue lesions.Methods Transcriptome datasets of DM skin and muscle were obtained from public database. Hub genes and signaling pathways were filtered by bioinformatic software. Serum cytokinome was measured in DM patients with different clinical-serological subgroups and correlation with disease activity indicators was analyzed. Cytokine interaction network was constructed.Results 6 hub genes, including STAT1, MX1, ISG15, IFIT3, GBP1 and OAS2 were identified as IFN signature in DM. Differently expressed genes (DEGs) identified in the skin and muscle datasets were significantly enriched in the type I interferon signaling pathway, defense response to virus and chemotaxis. 11 cytokines were significantly elevated in patients positive for melanoma differentiation-associated protein (MDA5) antibody. IFN-α, IFN-γ, MIP-1α, IP-10, MCP1, GRO-α, IL-6, IL-18 and IL-1RA were correlated with disease activity. MCP1/MIP-1α/RANTES/MCP2/CCR1 axes were filtered from cytokine interaction network.Conclusions The complexity of DM immunopathogenesis is mediated through interactions of multiple cytokines and signaling pathways. Type I interferon is the core participant in DM tissue damage. Serum upregulation of IFN-α, IFN-γ, MIP-1α, IP-10, MCP1, GRO-α, IL-6, IL-18 and IL-1RA could be used for disease activity assessment in DM patients positive for MDA5 antibody. Finally, MCP1/MIP-1α/RANTES/MCP2/CCR1 axes mediated monocytes attraction might be novel therapeutic targets in DM by chemokine network analysis.
Clinical and molecular spectrum of 46,XY disorders of sex development that harbourMAMLD1 variations: Case series and review of literature
Authors: Lele Li , Su Chang , Fan Lijun , Gao Fenqi , Liang Xuejun , Gong Chunxiu
Published: June 2020

Background Mastermind-like domain-containing 1 (MAMLD1) has previously been identified as a causative gene for "46,XY Disorders of Sex Development (DSD)". Recently, there has been some controversy regarding the causative role of MAMLD1 variations in DSDs. Here we describe a clinical series and review the reported cases to evaluate the role of MAMLD1 variants in children with 46,XY DSD. Cases of 46,XY DSD harbouring MAMLD1 variants from unrelated families were recruited from the Beijing Children’s Hospital in China (N = 10) or identified through a literature search (N = 26). The clinical manifestations and genetic variants of all the patients were evaluated.Results Hypospadias was the most prevalent phenotype among our 10 cases (8 out of 10 cases) and in all the previously reported ones. Central precocious puberty and isolated micropenis were observed for the first time. Among the 10 cases, nine variants were identified, including three nonsense (p.R356X, p.Q152X, and p.Q124X) and six missense (p.P334S, p.S662R, p.A421P,p.T992I, p.P542S, and p.R927L) variants. In silico analysis showed that the variants p.P334S, p.P542S, p.S662R, and p.R927Lmight lead to drastic changes in the interaction force of the amino acid chain and the flexibility of the spatial structure, and such changes may affect protein function.Conclusion Patients with 46,XY DSD harbouring MAMLD1variants manifest a broad spectrum of phenotypes and mostly present with hypospadias. The six novel variants reported here enrich the mutation database and contribute to our understanding of the pathogenesis of 46,XY DSD.
Prognostic factors of patients with pulmonary large-cell neuroendocrine carcinoma after surgery: a competing risk analysis
Authors: Huang Qian , Liu Jie , Cai Huifang , Zhang Qi , Wang Lina
Published: June 2020

Background: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare primary malignant tumor with a poor prognosis. Our aim was to determine the prognostic factors of patients with pulmonary LCNEC after surgery based on competing risk model. Methods: Patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database. For single outcome events, Kaplan-Meier method and Cox proportional risk model were used for analysis. Competing risk model was used in the analysis of multiple outcome events to adjust potential confounding factors. Competing risk model was used to calculate the cumulative incidence function of LCNEC-specific death. The Fine-Gray model was used for multivariate analysis to determine independent prognostic factors.Results: We finally screened 614 patients with pulmonary LCNEC who underwent surgery. The univariate analysis showed that T stage, N stage, M stage, regional nodes positive (RNP), and radiotherapy were significantly associated with the cumulative incidence of LCSD (P < 0.05). The Fine-Gray model showed that age, T stage, M stage, RNP, radiotherapy, and chemotherapy were independent prognostic factors for patients with pulmonary LCNEC after surgery (P < 0.05). Conclusion: Based on the competing risk model, we estimated a more accurate cumulative incidence of LCNEC-specific death and prognostic factors for patients with pulmonary LCNEC after surgery.
Using Osmotic Stress to Stabilize Mannitol Production in Synechocystis sp. PCC6803
Authors: Wu Wenyang , Du Wei , Gallego Ruth Perez , Hellingwerf Klaas J. , Woude Aniek D. van der , Santos Filipe Branco dos
Published: June 2020

Background

Mannitol is a C(6) polyol that is used in the food and medical sector as a sweetener and antioxidant, respectively. The sustainable production of mannitol, especially via the direct conversion of CO2 by photosynthetic cyanobacteria, has become increasingly appealing. However, previous work aiming to achieve mannitol production in the marine Synechococcus sp. PCC 7002 via heterologous expression of mannitol-1-phosphate-5-dehydrogenase (mtlD) and mannitol-1-phosphatase (m1p, in short: a ‘mannitol cassette’), proved to be genetically unstable. In this study, we aim to overcome this genetic instability by conceiving a strategy to stabilize mannitol production using Synechocystis sp. PCC 6803 as a model cyanobacterium.

Results

Here, we explore the stabilizing effect that mannitol production may have on cells faced with osmotic stress, in the freshwater cyanobacterium Synechocystis sp. PCC 6803. We first validated that mannitol can function as a compatible solute in Synechocystis sp. PCC 6803, and in derivative strains in which the ability to produce one or both of the native compatible solutes was impaired. Wild type Synechocystis, complemented with a mannitol cassette, indeed showed increased salt tolerance, which was even more evident in Synechocystis strains in which the ability to synthesize the endogenous compatible solutes was impaired. Next we tested the genetic stability of all these strains with respect to their mannitol productivity, with and without salt stress, during prolonged turbidostat cultivations. The obtained results show that mannitol production under salt stress conditions in the Synechocystis strain that cannot synthesize its endogenous compatible solutes is remarkably stable, while the control strain completely loses this ability in only 6 days. DNA sequencing results of the control groups that lost the ability to synthesize mannitol revealed that multiple types of mutation occurred in the mtlD gene that can explain the disruption of mannitol production.

Conclusions

Mannitol production in freshwater Synechocsytis sp. PCC6803 confers it with increased salt tolerance. Under this strategy, genetically instability which was the major challenge for mannitol production in cyanobacteria is tackled. This paper marks the first report of utilization of the response to salt stress as a factor that can increase the stability of mannitol production in a cyanobacterial cell factory.
Construction of a sensitive and specific lead biosensor using a genetically engineered bacterial system with a luciferase gene reporter controlled by pbr and cadA promoters
Authors: Nourmohammadi Esmail , Hosseinkhani Saman , Nedaeinia Reza , Khoshdel-Sarkarizi Hoda , Nedaeinia Mozhdeh , Ranjbar Maryam , Ebrahimi Neshat , Farjami Zahra , Nourmohammadi Mohammad , Mahmoudi Ali , Goli Mohammad , A.Ferns Gordon , Sadeghizadeh Majid
Published: June 2020

Background: A bacterial biosensor refers to genetically engineered bacteria that produce an assessable signal in the presence of a physical or chemical agent in the environment. Methods: We have designed and evaluated a bacterial biosensor expressing a luciferase-reporter gene controlled by pbr and cadA promoters in Cupriavidus metallidurans (previously termed Ralstonia metallidurans) containing the CH34 and pI258 plasmids of Staphylococcus aureus, respectively, and that can be used for the detection of heavy metals. In the present study, we have produced and evaluated biosensor plasmids designated pGL3-luc/pbr-biosensor and pGL3-luc/cad-biosensor, that were based on the expression of luc+ under the control of the cad promoter and the cadC gene of S. aureus plasmid pI258 and pbr promoter and pbrR gene from plasmid pMOL30 of Cupriavidus metallidurans. Results: We found that the pGL3-luc/pbr-biosensor may be used to measure lead concentrations between 1-100 μM in the presence of other metals, including: zinc, cadmium, tin and nickel. The latter metals did not result in any significant signal. The pGL3-luc/cad-biosensor could detect lead concentrations between 10 nM to 10 μM. Conclusions: This biosensor was found to be a specific for measuring lead ions in both environmental and biological samples.
Exosomal miR-380 derived from alveolar macrophages in COPD is involved in enhanced proliferation of human bronchial epithelial cells
Authors: Fan Yunxin , Feng Xiumin , Zhang Jingxi , Bai Chong
Published: June 2020

Background Chronic obstructive pulmonary disease (COPD) is closely related to the occurrence of lung cancer. Both diseases involve changes in the biological function and structure of bronchial epithelial cells. Recently, the role of exosomes in intercellular communication has attracted increasing attention from researchers. As an important molecule carried by exosomes, the role of exosomal miRNAs in diseases such as COPD and lung cancer has also been gradually confirmed. The aim of this study is to investigate the effect of exosomal miRNA derived from macrophages on the proliferation of bronchial epithelial cells. Results After co-culture with alveolar macrophages from COPD, the proliferative activity and migration capacity of 16HBE was significantly enhanced compared with those from healthy controls. Alveolar macrophages from COPD promoted the production of MUC5AC, MUC5B and MUC2 as well as TNF - α and IL-6 in 16HBE. MiR-380 was up-regulated miRNA in exosomes derived from alveolar macrophages through miRNA array analysis. Exosomal miR-380 enhanced the proliferation and migration of 16HBE, promoted the expression of mucins such as MUC5AC, MUC5B and MUC2 of 16HBE, but inhibited the expression of CFTR protein. The target gene of miR-380 was CFTR. The proliferative activity and migration ability of 16HBE was enhanced by blocking CFTR. Conclusions Alveolar macrophages from COPD can enhance the proliferation and migration of 16HBE and promote the expression of mucin and proinflammatory mediators such as IL-6 and TNF-α. Exosomal miR-380 derived from macrophages in COPD was significantly up-regulated. The enhancement of proliferation and migration may be related to the down regulation of CFTR by exosomes delivering miR-380 to bronchial epithelial cells, opening a new way for the therapy and prevention in COPD and its complication.
CircRNA TADA2A relieves idiopathic pulmonary fibrosis by inhibiting proliferation and activation of fibroblasts
Authors: Li Juan , Li Ping , Zhang Guojun , Qin Pan , Zhang Da , Zhao Wei
Published: June 2020

The excessive activation and proliferation of lung fibroblasts are responsible for the abundant deposition of extracellular matrix (ECM) in idiopathic pulmonary fibrosis (IPF), while its specific mechanism is still unknown. This study focuses on the role of circRNA (circ) TADA2A in functional abnormalities of lung fibroblasts and aims to elaborate its regulatory mechanism. In the present study, circTADA2A was down-regulated in both IPF primary human lung fibroblasts and human IPF fibroblastic cell lines. Functionally, the overexpression of circTADA2A repressed the activation and proliferation of normal human fibroblastic cell line induced by several fibrogenic growth factors. Using fluorescence in situ hybridization (FISH), luciferase reporter assays, and RNA pull-down, circTADA2A was confirmed to function as sponges of miR-526b and miR-203, thus releasing the expression of Caveolin (Cav)-1 and Cav-2. The overexpression of circTADA2A suppressed lung fibroblasts activation via Cav-1 and reduced lung fibroblasts proliferation via Cav-2. In vivo experiments also confirmed that the overexpression of circTADA2A decreased fibrogenic responses induced by bleomycin in lung fibrosis mice. Collectively, circTADA2A repressed lung fibroblasts activation via miR-526b/Cav-1 and reduced lung fibroblasts proliferation via miR-203/Cav-2, thus inhibiting the excessive deposition of ECM and relieving IPF.
Identifying the Biomarkers of Spinal Cord Injury and the effects of Neurotrophin-3 Based on MicroRNA and mRNA Signature
Authors: Qi Shuang , Li Zinan , Yu Shanshan
Published: June 2020

Background

To gain a better understanding of the molecular mechanisms of spinal cord injury and the effects of Neurotrophin-3, differentially expressed microRNAs (DEmiRNAs) and genes (DEGs) were analyzed.
Methods

The miRNA transcription profile of GSE82195 and the mRNA transcription profile of GSE82196 were downloaded from the Gene Expression Omnibus (GEO). Then, DERs were identified using limma. The noise-robust soft clustering of the intersection DERs was performed using Mfuzz package. Additionally, the integrated miRNAs–targets regulatory network was constructed using Cytoscape. Finally, the Comparative Toxicogenomics Database 2019 update was used to search the central nervous system injury related pathway.
Results

A total of 444 DERs including 382 DEGs and 62 DEmiRNAs were screened between group injury and group none whlie 576 DERs including 523 DEGs and 55 DEmiRNAs were screened between group NT-3 and group injury. Moreover, 80 intersections DERs were identified. DREs in cluster 1 were firstly significantly down-regulated in group injury and subsequently were significantly up-regulated in group NT-3. DERs in cluster 2 were firstly up-regulated in group injury and subsequently down-regulated in group NT-3. OPRL1 and GHSR were enriched in the KEGG pathway of Neuroactive ligand-receptor interaction. OPRL1 was involved in the chemical homeostasis and ion homeostasis while GHSR was related to the regulation of fatty acid metabolic process and regulation of cellular ketone metabolic process.
Conclusion

rno-miR-3072 and rno-miR-667-5p and OPRL1 and GHSR might participate in the pathogenesis of neurological injury and the neurotrophin-3 treatment.
Natural compounds as potential inhibitors of novel coronavirus (COVID-19) main protease: An in silico study
Authors: Mishra Amaresh , Pathak Yamini , Choudhir Gourav , Kumar Anuj , Mishra Surabhi Kirti , Tripathi Vishwas
Published: June 2020

COVID-19 pandemic has now expanded over 213 nations across the world. To date, there is no specific medication available for SARS CoV-2 infection. The main protease (Mpro) of SARS CoV-2 plays a crucial role in viral replication and transcription and thereby considered as an attractive drug target for the inhibition of COVID-19,. Natural compounds are widely recognised as valuabe source of antiviral drugs due to their structural diversity and safety. In the current study, we have screened twenty natural compounds having antiviral properties to discover the potential inhibitor molecules against Mpro of COVID-19. Systematic molecular docking analysis was conducted using AuroDock 4.2 to determine the binding affinities and interactions between natural compounds and the Mpro. Out of twenty molecules, four natural metabolites namely, amentoflavone, guggulsterone, puerarin, and piperine were found to have strong interaction with Mpro of COVID-19 based on the docking analysis. These selected natural compounds were further validated using combination of molecular dynamic simulations and molecular mechanic/generalized/Born/Poisson-Boltzmann surface area (MM/G/P/BSA) free energy calculations. During MD simulations, all four natural compounds bound to Mpro on 50ns and MM/G/P/BSA free energy calculations showed that all four shortlisted ligands have stable and favourable energies causing strong binding with binding site of Mpro protein. These four natural compounds have passed the Absorption, Distribution, Metabolism, and Excretion (ADME) property as well as Lipinski’s rule of five. Our promising findings based on in-silico studies warrant further clinical trials in order to use these natural compounds as potential inhibitors of Mpro protein of COVID.
Autophagy in spinal ligament fibroblasts: evidence and possible implications for ossification of the posterior longitudinal ligament
Authors: yang yuehua , Lin zunwen , Chen Jiangwei , Ding Sheng , Mao Weiwei , shi sheng , Liang Bi-Ru
Published: June 2020

Background: The molecular mechanisms of ossification of the posterior longitudinal ligament (OPLL) remains to be elucidated. The aim of the present study was to investigate the autophagy of spinal ligament fibroblasts derived from patients with OPLL and to examine whether autophagy associated gene expression was correlated with the expression of osteogenic differentiation genes. Methods: Expression of autophagy associated genes was detected in 37 samples from 21 OPLL patients and 16 non-OPLL patients. The correlation of autophagy associated gene expression and the expression of osteogenic differentiation genes was analyzed by Pearson’s correlation. The expression of autophagy associated genes of ligament fibroblasts was assessed by reverse transcription-quantitative Polymerase Chain Reaction (RT-qPCR), western blotting and immunofluorescence. The incidence of autophagy was assessed by flow cytometry. After knockdown using small interfering RNA targeting Beclin1, the expression of osteogenic differentiation genes were compared in spinal ligament fibroblasts. Results: In clinical specimens, mRNA expression levels of microtubule-associated protein 1 light chain 3 and Beclin1 were higher in the OPLL group compared with the non-OPLL group. Pearson correlation analysis demonstrated that Beclin1 expression was positively correlated with expression of osteocalcin (OCN) (r=0.8233, P<0.001), alkaline phosphatase, biomineralization associated (ALP) (r=0.7821, P<0.001) and collagen type 1 (COL 1) (r=0.6078, P=0.001). Consistently, the upregulation of autophagy associated genes in ligament fibroblasts from patients with OPLL were further confirmed by western blotting and immunofluorescence. The incidence of autophagy was also increased in ligament fibroblasts from patients with OPLL. Furthermore, knockdown of Beclin1 led to a decrease in the expression of OCN, ALP and COL 1 by 63.2% (P<0.01), 52% (P<0.01) and 53.2% (P<0.01) in ligament fibroblasts from patients with OPLL, respectively. Conclusions: Beclin1-mediated autophagy was involved in the osteogenic differentiation of ligament fibroblasts, and promoted the development of OPLL.