bluuebunny/crossref_metadata_2025 huggingface dataset:
LipoDDx: a mobile application for identification of rare lipodystrophy syndromes
Authors: Araujo-Vilar David , Fernández-Pombo Antia , Rodríguez-Carnero Gemma , Martínez-Olmos Miguel Angel , Cantón Ana , Villar-Taibo Rocio , Hermida-Ameijeiras Alvaro , Santamaría-Nieto Alicia , Díaz-Ortega Carmen , Martínez-Rey Carmen , Antela Antonio , Losada Elena , Muy-Pérez Andrés , González-Méndez Blanca , Sánchez-Iglesias Sofía
Published: March 2020

Background: Lipodystrophy syndromes are a group of disorders characterized by a loss of adipose tissue once other situations of nutritional deprivation or exacerbated catabolism have been ruled out. With the exception of the HIV-associated lipodystrophy, they have a very low prevalence, which together with their large phenotypic heterogeneity makes their identification difficult, even for endocrinologists and pediatricians. This leads to significant delays in diagnosis or even to misdiagnosis. Our group has developed an algorithm that identifies the more than 40 rare lipodystrophy subtypes described to date. This algorithm has been implemented in a free mobile application, LipoDDx®. Our aim was to establish the effectiveness of LipoDDx®.40 clinical records of patients with a diagnosis of certainty of most lipodystrophy subtypes were analyzed, including subjects without lipodystrophy. The medical records, blinded for diagnosis, were evaluated by 13 physicians, 1 biochemist and 1 dentist. Each evaluator first gave his/her results based on his/her own criteria. Then, a second diagnosis was given using LipoDDx®. The results were analysed based on a score table according to the complexity of each case and the prevalence of the disease.Results: LipoDDx® provides a user-friendly environment, based on usually dichotomous questions or choice of clinical signs from drop-down menus. The final result provided by this app for a particular case can be a low/high probability of suffering a particular lipodystrophy subtype. Without using LipoDDx® the success rate was 17 ± 20%, while with LipoDDx® the success rate was 79 ± 20% (p <0.01).Conclusions: LipoDDx® is a free app that enables the identification of subtypes of rare lipodystrophies, which in this small cohort has around 80% effectiveness, which will be of help to doctors who are not experts in this field. However, it will be necessary to analyze more cases in order to obtain a more accurate efficiency value.
Feasibility of Heavy Slow Resistance Training in patients with subacromial shoulder pain. A single-blind, randomized pilot study.
Authors: Kvalvaag Elisabeth , Høiland Hans Hugo Fredriksen , Johnsen Marianne Bakke , Brox Jens Ivar , Engebretsen Kaia Beck , Røe Cecilie
Published: March 2020

Background: Subacromial shoulder pain is the most common shoulder diagnosis, and should preferably be treated non-operatively. Previous studies have shown promising results of Heavy Slow Resistance training (HSR) in patellar and Achilles tendinopathy, but few studies have evaluated the effect of HSR for shoulder pain. The purpose of this pilot trial was to evaluate if HSR training is feasible for patients with subacromial shoulder pain, and to compare HSR to traditional supervised exercises.
Methods: Twenty-two patients with subacromial shoulder pain lasting at least three months were recruited and randomized to HSR (n=11) or traditional supervised exercises (n=11) by computer-generated randomization in blocks of four. Patients received HSR once a week, in addition to home-training twice a week, or supervised exercises twice a week for 12 weeks, in addition to daily home-training. The primary outcome measure was the Shoulder Pain and Disability Index (SPADI). Linear regression analysis was applied to evaluate the between group differences after 12 weeks. Outcome assessors were masked.
Results: After 12 weeks, patients in both groups had improved significantly from baseline in SPADI score (P=0.001) but no group difference was found (mean difference 1.3; 95% CI, -21.9 to 24.5, P=0.91). Similar non-significant results between groups were seen for pain in activity and rest, and the DASH score.
Conclusion: This pilot-study observed similar results of HSR compared to supervised exercises for patients with subacromial shoulder pain and both groups improved significantly from baseline. Only one patient changed from HSR to supervised exercises due to increased pain. Based on this, HSR appears to be a feasible treatment for this patient group, but due to small sample size there is a risk of type II error and studies with larger sample size are required.
Mitochondrial tRNA methylation in Alzheimer’s disease and progressive supranuclear palsy
Authors: Silzer Talisa K. , Pathak Gita A. , Phillips Nicole
Published: March 2020

Background

Methylation of mitochondrial tRNAs (mt-tRNA) at the 9 th position (“p9 site”) is known to impact translational efficiency and downstream mitochondrial function; however, direct assessment of mt-RNA methylation is challenging. Recent RNA sequence-based methods have been developed to reliably identify post-transcriptional methylation. Though p9 methylation has been studied in healthy human populations and in the context of cancer, it has not yet been analyzed in neurodegenerative disease, where mitochondrial dysfunction is a prominent and early hallmark of disease progression.

Results

Here we show variable methylation at 11 p9 sites in post-mortem cerebellar tissue of elderly subjects who were either healthy or diagnosed with Alzheimer’s disease (AD), progressive supranuclear palsy (PSP) or pathological aging (PA). Similarities in degree of methylation were observed between AD and PSP. Expression of 5300 genes was significantly correlated with p9 methylation, with AD and PSP subjects exhibiting similar expression profiles. The top 100 transcripts were found to be enriched for mitochondrial-related toxicity. Overrepresentation testing using the top 1000 transcripts revealed enrichment for a number of molecular processes and terms including some which were mitochondrial-related.

Conclusion

With mitochondrial dysfunction being an established hallmark of neurodegenerative disease pathophysiology, this work sheds light on the potential molecular underpinnings of this dysfunction. Here we show overlap in cerebellar pathophysiology between common tauopathies such as Alzheimer’s disease and progressive supranuclear palsy. Whether p9 hypermethylation is a cause or consequence of pathology remains an area of focus.
Percutaneous endoscopic posterior lumbar interbody fusion(PEPLIF): technical note
Authors: He Liming , Feng Haoyu , Ma Xun , Chang Qiang , Chang Jianjun , Sun Lin
Published: March 2020

Background: Endoscopic lumbar interbody fusion is based on endoscopic lumbar discectomy, a well-established and widely used clinical procedure. Endoscopic lumbar interbody fusion has several key advantages over other types of procedures, including that it is minimally invasive, more precise, safer, and provides better visualization. Most surgeons use the transforaminal approach for this surgery. Here, we report the first percutaneous endoscopic posterior lumbar interbody fusion (PEPLIF). Methods: The authors introduce the PEPLIF technique with step by step instructions and describe key procedures in detail. Tips for controlling hemorrhages and avoiding complications during the procedure are presented. The authors also discuss the indications and advantages of applying the PEPLIF technique.Results: PEPLIF is a repeatable lumbar fusion technique.Conclusions: PEPLIF is a feasible and effective technique for the fusion of L4-5 and L5-S1 (especially L5-S1). All procedures are completed in full using endoscopy without replacing the cannula. The endoscopic view is similar to that of an open posterior lumbar interbody fusion, thus reducing the learning curve.
Human breast tumour cells viability effect of African Dioscorea Rotundata Tuber extracts in MCF-7 and MDA-MB231 cell lines
Authors: Odimegwu Joy Ifunanya , Odukoya Olukemi Abiodun , Español Alejandro , Sales Maria Elena
Published: March 2020

Background : Several Dioscorea species are used in Chinese medicine for tumours and Dioscorea species grown in Africa are yet to be tested to the best of knowledge for efficacy as cytotoxic agents. In Nigeria, the greatest producer of edible yams in the world, Dioscorea is the king of plants. Its tubers feeds millions of people and also function as ethnomedicine for diverse diseases. We aim to test the efficacy of edible Dioscorea species grown and consumed in Nigeria on two breast cancer cell lines; MCF-7 and MDA-MB231 derived from a luminal and a triple-negative breast cancer (TNBC) respectively and to confirm safety in non-tumour cells MCF-10A (normal breast cell lines) using a well established cytotoxic compound paclitaxel as a standard. Metastatic breast cancer is a prevalent cause of mortality in women around the world. Breast cancer therapies have greatly advanced in recent years, leading to the statement that cancer is not a death sentence but many patients develop cancer re-occurrence and metastasis and subsequently yield to the disease because of chemoresistance. Methods : Ethanolic extracts of Dioscorea rotundata boiled and raw (DiosB and DiosR) respectively were chemically analysed for the presence of diosgenin using HPLC and their cytotoxic activity was tested on MCF-7, MDA-MB-231 and MCF-10A cells I n vitro by MTT assay.Results : DiosB and DiosR extracts were more effective on MCF-7 than on MDA-MB231 cells showing a higher maximal effect on MCF-7 cells than on MDA-MB231 after 24 h and 48 h treatments (p<0.0001 and p<0.05 respectively). DiosR, if applied at a range between 50-70 g/ml, can be effective to reduce breast tumor cell viability without affecting non tumorigenic MCF-10A cells either at 24 h or at 48 h. African yams contain cytotoxic principles. DiosB showed an IC 50 of 38.83µg/ml while DiosR showed an IC 50 of 41.80µg/ml. Discussion : The results have shown that Dioscorea rotundata tubers could be used effectively to treat breast cancer tumors and this is in sync with its diosgenin content, a known cytotoxic compound and the use of other Dioscorea species for similar treatments in Asia etc. A major limitation will be in creating higher demand for the tuber which is consumed as a staple and at the moment affordable to all.Conclusion : There will be need to make consumers aware of the significant anticancer importance of D. rotundat a and a great need to increase its cultivation in order to make it sufficient as food and as medicine.
A differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human
Authors: Zhang Wandong , Liu Qing Yan , Haqqani Arsalan S. , Leclerc Sonia , Lei Joy , Fauteux Francois , Baumann Ewa , Delaney Christie E. , Ly Dao , Star Alexandra T. , Brunette Eric , Sodja Caroline , Hewitt Melissa , Sandhu Jagdeep K. , Stanimirovic Danica B.
Published: March 2020

Receptor-mediated transcytosis (RMT) is a principal pathway for transport of macromolecules essential for brain function across the blood-brain barrier (BBB). Antibodies or peptide ligands which bind RMT receptors are often co-opted for brain delivery of biotherapeutics. A constitutively recycling transferrin receptor (TfR) is a prototype receptor utilized to shuttle therapeutic cargos across the BBB. Several other BBB-expressed receptors have been shown to mediate transcytosis of ligands including insulin receptor (INSR) and insulin-like growth factor-1 receptor (IGF1R), lipid transporters LRP1, LDLR, LRP8 and TMEM30A, solute carrier family transporter LAT1 (subunit CD98hc) and leptin receptor (LEPR). In this study, we analyzed expression patterns of genes encoding RMT receptors in isolated brain microvessels, the brain and peripheral organs of the mouse and the human using RNAseq approach. IGF1R, INSR and LRP8 were highly enriched in the mouse brain microvessels compared to peripheral tissues. In the human brain microvessels only INSR was enriched compared to either the brain or the lung. The expression levels of LRP1, IGF1R, LRP8 and TFRC were significantly higher in the mouse compared to the human brain microvessels. The protein expression of these receptors analyzed by quantitative Western blot and immunofluorescent staining of the brain microvessels correlated with their transcript abundance. This study provides a molecular transcriptomics map of key RMT receptors in mouse and human brain microvessels and peripheral tissues, important sot translational studies of biodistribution, efficacy and safety of antibodies developed against these receptors.
Interviews with experts in Rare Diseases for the development of Clinical Decision Support System software - a qualitative study
Authors: Schaaf Jannik , Prokosch Hans-Ulrich , Boeker Martin , Schaefer Johanna , Vasseur Jessica , Storf Holger , Sedlmayr Martin
Published: March 2020

Background Patients with a rare disease (RD) are often diagnosed too late or not at all. Clinical decision support systems (CDSSs) could support the diagnostic process in rare diseases (RDs). The MIRACUM (Medical Informatics in Research and Medicine) consortium, which is one of four funded consortia in the German Medical Informatics Initiative, will develop a CDSS for RDs based on distributed clinical data from ten university hospitals. This qualitative study aims to investigate (1) the relevant organizational conditions for the operation of a CDSS for RDs, (2) which data is necessary for decision support, and (3) the appropriate user group for such a CDSS. Methods Interviews were carried out with RDs experts. Participants were recruited from staff physicians at the Rare Disease Centers (RDCs) at the MIRACUM locations, which offer diagnosis and treatment of RDs. An interview guide was developed with a category-guided deductive approach. The interviews were recorded on an audio device and then transcribed into written form. We continued data collection until all interviews were completed. Afterwards, data analysis was performed using Mayring’s qualitative content analysis approach. Results A total of seven experts were included in the study, from seven of the eight MIRACUM locations which have established an RDC. The results show that administrative staff and physicians from RDC B-centers, representing different medical specialties, are involved in the diagnostic process. The experts cited various software programs used for diagnostic support and considered both physicians and experts from the B-centers to be potential users of a CDSS. Furthermore, the experts explained that RDs exist which cannot be fully differentiated, but rather described only by their overall symptoms or findings: diagnosis is dependent on the disease or disease group. At the end of the diagnostic process, most centers prepare a summary of the patient case. Conclusions This qualitative study is a first step towards establishing the requirements for the development of a CDSS for RDs. However, further research is necessary to create solutions by also including the experts on RDs.
Inferring the votes in a new political landscape. The case of the 2019 Spanish Presidential elections.
Authors: Grimaldi Didier , Diaz Javier , Arboleda Hugo
Published: March 2020

Electoral prediction from Twitter data is an appealing research topic. The article aims at inferring the results of 2019 Spanish Presidential elections analysing Tweets. It defines a specific political dictionnary to analyse the sentiment and the opinion of the messages posted during the campaign. Our predicting model compares the performance of 5 multi-linear regression algorithms and our results are compared to the ones delivered by the standard poll systems based on telephone survey. Our methodology correctly ranks the candidates and gives for the winner of the election (Sanchez) a better prediction of voting share than the national polls. This stream of studies is still in the early stage even if our findings look like very promising. Therefore, as a future line of research, we recommend to include more socio- and economic factors like sex, age, location, etc. in the objective to improve our model and results.
Prevalence and antimicrobial resistance of animal Salmonellosis in Ethiopia
Authors: Kahsay Atsebaha Gebrekidan
Published: March 2020

Background Salmonellosis remained the global public health problems of animals and humans. Consumption of animal food from infected animals or from the contamination of carcasses such as cattle, swine, and sheep and poultry are the main sources of non-Typhoidal Salmonella and the leading cause of zoonotic foodborne diseases. The eligibility criteria of this study has included publication in English, cross-sectional study, samples of food animal origin, antimicrobial sensitivity test methods. Google Scholar and PubMed have used to search the prevalence, incidence, distribution, antimicrobial resistance, animals and humans. Author, study area, study period, sample sources, number of animals, number of samples, positive isolates were used as search strategy. Results A total of 8.4% (564/6721) animal salmonellosis were identified from 11 studies in Ethiopia. The source of samples were pigs, cattle, poultry, and eggs. Five studies were selected for the analysis of prevalence and drug resistance of animal salmonellosis whereas six were found eligible for analysis of animal salmonellosis in serotype level and twenty nine serotypes were extracted having 354 isolates. Of the total 147(6.1%) isolates in five studies, ampicillin, streptomycin and tetracycline were resistant to 89 (60.5%), 70 (47.6%) and 64(43.5%) respectively. The resistant profile for ceftriaxone, gentamicin and ciprofloxacin were 20 (13.6%), 21 (12.9%) and 10 (6.8%), respectively. Twelve serotypes having 204 isolates have showed antimicrobial resistance. Six serotypes had multidrug resistance comprising 120 isolates. The predominant serotype that showed MDR (to three antibiotics) was S. Hadar 81 (67.5%) followed by S. Kentucky 22(18.3%). Conclusion The overall prevalence of animal salmonellosis in Ethiopia was 8.4% (564/6721).The source of samples for the assessment of the prevalence of animal salmonellosis in Ethiopia were pigs, cattle, poultry, and eggs. Of the total 147(6.1%) isolates in five studies, ampicillin, streptomycin and tetracycline were resistant to 89 (60.5%), 70 (47.6%) and 64(43.5%), respectively. A total of 29 serotypes comprising 354 isolates were revealed from six studies. Twelve serotypes having 204 isolates were showed antimicrobial resistance. Six serotypes showed multidrug resistance and the predominant serotype that showed MDR was S. Hadar 81 (67.5%) followed by S. Kentucky 22(18.3%)
The gut microbiome affects the responses of heart valve replacement patients to the anticoagulant warfarin
Authors: Wang Lin , Liu Linsheng , Liu Xiaoxue , Xiang Min , Zhou Ling , Huang Chenrong , Shen Zhenya , Miao Liyan
Published: March 2020

Backgrounds: Numerous algorithms based on patient genetic variants have been established with the aim of reducing the risk of GI bleeding and thromboembolism during warfarin administration. However, approximately 35% of individual warfarin sensitivity remains unexplained. Gut microbiota composition related to the vitamin K generation should be taken into account. Methods : Faecal samples were collected from 200 inpatients undergoing heart valve replacement (HVR). Ultimately, faecal samples from 80 inpatients (27 low responders (LRs), 27 high responders (HRs) and 26 normal responders (NRs) were analyzed for microbiota composition through 16S rDNA sequencing. Fifteen samples (5 LRs, 5 HRs and 5 NRs) were also analyzed through metagenomic whole-genome shotgun (WGS) sequencing. We validated the results from 10 LRs, 10 HRs and 10 NRs. Results: Significant differences were observed in the diversity and composition of the gut microbiome among the three groups. The genera Bacteroides, Escherichia-Shigella and Klebsiella were enriched in the LRs, while the genus Enterococcus was enriched in the HRs. WGS sequencing indicated that the abundance of enzymes, modules and KO associated with bacterial vitamin K biosynthesis was significantly higher in LRs than in HRs or NRs. The 12 optimal microbial markers were identified through tenfold cross-validation with a random forest model. Conclusions: This study characterized gut microbiome in the different response to warfarin of HVR patients and suggested that gut microbiome might play an important role in the clinical warfarin anticoagulation therapy.
A new plasmid carrying mphA causes prevalence of azithromycin resistance in enterotoxigenic Escherichia coli serogroup O6
Authors: Xiang Ying , Wu Feng , Chai Yinghui , Yang Lang , Tian Sai , Zhang Haoran , Li Yinxia , Xu Xuebin , Yang Chaojie , Liu Hongbo , Qiu Shaofu , Song Hongbin , Sun Yansong
Published: March 2020

Background: At present, azithromycin has become an effective treatment for severe diarrhea caused by Enterotoxigenic Escherichia coli (ETEC) infection. However, enterobacteria have begun to develop resistance to azithromycin and have attracted attention in recent years. This study conducted to described the emergence of a high proportion of azithromycin-resistant ETEC serogroup O6 strains in Shanghai and to analyzed the mechanisms of azithromycin resistance.Results: Strains from adult diarrhea patients with ETEC serogroup O6 infections were collected by Shanghai Diarrhea Surveillance Network and the Foodborne Surveillance Network from 2016 to 2018. We tested 30 isolates of ETEC O6 serogroup, 26 of which were resistant to azithromycin. Phylogenetic analysis revealed that these ETEC serogroup O6 strains have formed an independent dominant clone. S1-PFGE and southern blotting revealed the presence of the mphA gene on the 103kb plasmid. Illumina and Nanopore sequencing and plasmid coverage analysis further confirmed that azithromycin-resistant strains carried a novel IncFII plasmid harboring mphA and blaTEM-1 resistance genes.Conclusions: This is the first study to report a high proportion of azithromycin resistance in a particular ETEC serogroup due to a specific plasmid carrying mphA. Our findings indicate the rapid spread of azithromycin resistance, highlighting the urgency of stringent surveillance and control measure.
The Multivariate Distributed Lag Non-Linear Model (MVDLNM) that Accommodates Cumulative Outcomes
Authors: Chen Yi-Hau , Huang Xing-Yi , Kuo Pei-Cheng , Guo Chao-Yu
Published: March 2020

Background: The effects of meteorological factors on health outcomes have gained popularity due to climate change, which not only results in a general rise in temperature but also the abnormal climatic extremes. Instead of the conventional cross-sectional analysis that focuses on the association between a predictor and the single dependent variable, the distributed lag non-linear model (DLNM) has been widely adopted to examine the effect of multiple lagged environmental factors on the health outcome. In this research, we further investigate a more complex association structure between the lagged temperature exposures and the lagged mortality. Method: Derived by various statistical concepts, such as summation, autoregressive, principal component analysis, baseline adjustment, and offset in the DLNM, five strategies are newly proposed and evaluated by a simulation study based on permutation techniques. The longitudinal climate and daily mortality data in Taipei Taiwan from 2012 to 2016 were implemented to generate the null distribution. Results: According to simulation results, only one strategy, named as MV DLNM , could yield valid Type-I errors, while the other 4 strategies demonstrated much more inflated type-I errors. With an illustration using the real data, the MV DLNM that incorporates both the current and lagged mortalities demonstrates a more significant association comparing to the conventional DLNM that only relies on the current mortality. Conclusions: In public health research, not only the exposure may post a delayed effect, but also the outcome of interest could provide the lagged association signals. The joint modeling of the lagged exposure and the lagged outcome would discover such complex association structure.
Informing urban climate planning with high resolution data: the Hestia fossil fuel CO2 emissions for Baltimore, Maryland
Authors: Roest Geoffrey Scott , Gurney Kevin R , Miller Scot M , Liang Jianming
Published: March 2020

Background Cities contribute more than 70% of global anthropogenic carbon dioxide (CO2) emissions and are leading the effort to reduce GHG emissions through sustainable planning and development. However, urban greenhouse gas mitigation often relies on self-reported emissions estimates that may be incomplete and unverifiable via atmospheric monitoring. We present the Hestia Scope 1 fossil fuel CO2 emissions for the city of Baltimore, Maryland – a gridded annual and hourly emissions data product for 2010 through 2015.Results The emissions in the base year of 2011 totaled 1431.5 kt C, with the largest emissions coming from onroad (35.0% of total city emissions), commercial (18.3%), residential (16.7%), and industrial (12.6%) sectors. Scope 1 electricity production and marine shipping were each generally less than 10% of the city’s total emissions. Baltimore’s self-reported Scope 1 emissions of 1,182.6 kt C were 22.8% lower than Hestia-Baltimore emission in 2014, largely due to the omission of petroleum consumption in buildings and several sectors that largely fall outside the city’s regulatory purview – industrial point sources, marine shipping, nonroad vehicles, rail, and aircraft.Conclusions We emphasize the need for comprehensive, Scope 1-only emissions estimates for emissions verification and measuring progress towards greenhouse gas mitigation goals using atmospheric monitoring, but we also acknowledge that city planners may desire a greater mix of scope 1, 2, and 3 emissions with an emphasis on activities under local policy control.
Wild environment and diet structure shape gut microbiome and functional composition in semi-feral Tibetan goats
Authors: Zhang Ke , He Chong , Zhang Chenguang , Xu Yangbin , Li Chao , Jing Xu , Yang Yuxin , Ba Gui , Suo Langda , De Ji , Ci Deji , Zhang Li , Kalds Peter , Song Jiuzhou , Wang Xiaolong , Wu Yujiang , Chen Yulin
Published: March 2020

Background :The gut microbiota composition is influenced by diet as well as the environment in both wild and domestic animals. Although the rumen microbiome in herbivorous ruminants has been studied, the gut metagenome and the underlying ecological mechanisms of different feeding systems in extreme environment have not been elucidated. Here, the influence of two feeding systems, grazing and drylot, on the gut microbiome composition of Tibetan goats was investigated. These goats are a semi-feral highland breed that lives at an altitude of ~4800 m. 16S rRNA gene sequencing and metagenomic analysis was conducted using the gastrointestinal tract lumen and mucosa (rumen, cecum, and colon) samples obtained from yearling animals. Results: We observed distinct microbiome functions potential in the rumen and hindgut (cecum and colon). The peptidases, arginine and proline metabolism, oxidative phosphorylation, cysteine and methionine metabolism were highly enriched in the rumen microbiome. We demonstrated the proportion of Methanobrevibacter was significantly higher in the drylot group, thereby resulted in a higher abundance of enzymes involved in hydrogenotrophic methanogenesis. The core genera of Clostridium, Prevotella were observed in significantly different proportions between the two groups, these differences were reflective of the different nutrition metabolism between free-range and drylot animals. Although antimicrobial resistance in bacteria has been attributed to feeding conditions, the pasturing system did not affect the abundance of antibiotic resistance genes.Conclusions: Together, these results highlight the importance of hindgut microbiota in the process of nutrient metabolism, and provide ecological insights into establishment of the GIT microbiome in ruminants under a unique environmental system.
Estimating the Nationwide Transmission Risk of Measles in US Schools and Impacts of Vaccination and Supplemental Infection Control Strategies
Authors: Azimi Parham , Keshavarz Zahra , Laurent Jose Guillermo Cedeno , Allen Joseph Gardner
Published: March 2020

Background: The spread of airborne infectious diseases such as measles is a critical public health concern. The U.S. was certified measles-free in 2000, but the number of measles cases has increased in recent years breaking the record of the nationwide annual number of cases since 1992. Although the characteristics of schools have made them one of the most vulnerable environments during infection outbreaks, the transmission risk of measles among students is not completely understood. We aimed to evaluate how three factors influence measles transmission in schools: personal (vaccination), social (compartmentalizing), and building systems (ventilation, purification, and filtration).Methods: We used a combination of a newly developed multi-zone transient Wells-Riley approach, a nationwide representative School Building Archetype (SBA) model, and a Monte-Carlo simulation to estimate measles risk among U.S. students. We compared our risk results with the range of reported transmission rates of measles in school outbreaks to validate the risk model. We also investigated the effectiveness of vaccination and ten supplemental infection control scenarios for reducing the risk of measles transmission among students.Results: Our best nationwide estimate of measles transmission risk in U.S. schools were 3.5% and 32% among all (both unvaccinated and immunized) and unvaccinated students, respectively. The results showed the transmission risk of measles among unvaccinated students is >70 times higher than properly immunized ones. We also demonstrated that the transmission risk of measles in primary schools (assuming teacher self-contained classrooms) is less than secondary schools (assuming departmentalized systems). For building-level interventions, schools with ductless-with-air-filter and ductless-without-air-filter systems have the lowest and highest transmission risks of measles, respectively. Finally, our simulation showed infection control strategies could cut the average number of infected cases among all students in half when a combination of advanced air filtration, ventilation, and purification was adopted in the modeled schools. Conclusions: Our results highlight the primary importance of vaccination for reducing the risk of measles transmission among students. Yet, additional and significant risk reduction can be achieved through compartmentalizing students and enhancing building ventilation and filtration systems.
Cost-Effectiveness of guideline-based stepped and collaborative care versus treatment as usual for patients with depression – a cluster-randomized trial
Authors: Brettschneider Christian , Heddaeus Daniela , Steinmann Maya , Härter Martin , Watzke Birgit , König Hans-Helmut
Published: March 2020

Objective Depression is associated with major patient burden. Its treatment requires complex and collaborative approaches. A stepped-care model based on the German National Clinical Practice Guideline “Unipolar Depression” has been shown to be effective. In this study we assess the cost-effectiveness of this guideline based stepped care model versus standard care in depression. Methods This prospective cluster-randomized controlled trial included 737 depressive adult patients. Primary care practices were randomized to an intervention (IG) or a control group (CG). The intervention consisted of a four-level stepped care model. The CG received treatment as usual. A cost-utility analysis from the societal perspective with a time horizon of 12 months was performed. We used quality-adjusted life years (QALY) based on the EQ-5D as effect measure. Resource utilization was assessed by patient questionnaires. We calculated adjusted group differences in costs and effects, incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. The complete sample and subgroups based on depression severity were considered. Results In the IG, adjusted mean total costs (+5,016; SE: €2,691) and effects (+0.008 QALY; SE: 0.02) were higher than in the CG; yet, differences were not statistically significant. Significantly increased costs were found in the IG for outpatient physician services and psychiatrist services. Significantly increased total and indirect costs in the IG were found in the group with severe depression. Incremental cost-effectiveness ratios were unfavourable and the probability of cost-effectiveness was low, except for the group with moderate depression (70% for willingness-to-pay threshold of €50,000/QALY). Conclusions We found no evidence for cost-effectiveness of the intervention. However, we identified indicators that the intervention works according to the aims of the National Treatment Guideline.
Increases in depressive anhedonia predict psychopathology symptoms in adolescents
Authors: yang xinhua , Liu Sixun , Liu Guangya , Harrison Phillippa
Published: March 2020

Background: Recent works have s uggested changes in anhedonia may be a stronger predictor of psychological disorders than trait and state anhedonia. However, whether the distinction between different types of anhedonia occurs in adolescents remains unclear. Methods: A total of 543 adolescents aged 14-16 years completed measures of anhedonia at two time points one year apart. State anhedonia was assessed using the Snaith Hamilton Pleasure Scale while trait social anhedonia was assessed using the Adolescent Anticipatory and Consummatory Interpersonal Pleasure Scale and depressive anhedonia was assessed using the anhedonia subscale from the Child Mood and Feelings Questionnaire. Results: State, trait social and depressive anhedonia significantly increased over time. Increases in depressive anhedonia predicted all psychopathology symptoms, and increases in state anhedonia predicted suicidal ideation and anxiety, but increases in trait social anhedonia did not predict any psychopathology symptoms. Negative schizotypy predicted increases in state or trait social anhedonia whereas disorganizated schizotypy, depression, generalized anxiety, suicidal ideation, academic and bereavement stressful events predicted increases in depressive anhedonia after controlling for baseline anhedonia. Conclusions: This finding suggests changes in depressive anhedonia, in contrast to state and trait anhedonia, is a major contributing factor to psychopathology in adolescence.
Association between serotonin - related gene polymorphisms and e arly effects of sertraline in Chinese Han patients with panic disorder
Authors: Zou Zhili , Huang Yulan , Wang Jinyu , Min Wenjiao , Zhou Bo
Published: March 2020

Objective The aim of the present study was to examine the association of serotonin -related gene polymorphisms with PD risk. Then, we analyzed the correlation between these gene polymorphisms and response to sertraline drug. Methods 230 patients with PD and 231 healthy controls were enrolled in the study. Panic Disorder Severity Scale (PDSS) were administered to all subjects, and all patients in the study were also assessed after 4 weeks of treatment. The SLC6A4(rs140701, rs3813034, 5-HTTLPR and STin2), HTRA1 rs6295, HTR2A rs6313 and COMT rs4680 genes were genotyped and assessed for allele. Results The allelic model showed that the SLC6A4 rs140701 variant was significantly associated with increased risk of PD(OR = 0.624, 95% CI 0.450-0.864, p <0.05), and significant results was found in the dominant model(OR = 0.546; 95% CI, 0.371-0.804, p <0.05). There was a significant difference in allele and genotype frequency between responders and nonresponders in the 5-HTTLPR polymorphism (OR = 0.205, 95% CI 0.128-0.328; OR = 0.249, 95% CI 0.155-0.401, both p <0.001), and indicated the PD patients with S-allele had a poorer response to sertraline than L-allele carriers. Conclusions The present study suggest that the SLC6A4 rs140701 variant may be associated with susceptibility to PD, and 5-HTTLPR polymorphism may be a predictor of response to sertralines in the treatment of PD.
Associations of Quality, Quantity, and Structural Characteristics of Individual Social Network on Depressive Symptoms
Authors: Heo Ji Eun , Jung Sun Wook , Youm Yoosik , Kim Hyeon Chang , Jung Sun Jae
Published: March 2020

Background This study explores the association between the size and intimacy of an individual’s social network with depressive symptoms, considering age diversity and age difference in the general adult population in South Korea. Methods We utilized data from a population of 2,363 in the Cardiovascular and Metabolic Disease Etiology Research Center cohort. Each participant’s social network properties and social support status were measured using the egocentric social network analysis tool. Depressive symptoms were assessed using the Beck Depression Inventory-II. Multivariable logistic regression was used to compute odds ratios (ORs) for depression by different social network characteristics. Results Overall, network size and mean intimacy were both associated with depressive symptoms; however, the combination of the two showed different association patterns with depressive symptoms by gender. Compared to those with both a larger network size and higher average intimacy in the network, only women showed significantly increased ORs for depression with decreases in either the size or the intimacy of the network. This tendency was prominent in women whose social networks had high age diversity or members mainly older than themselves. Limitations Depressive symptoms were measured according to self-assessed levels of depressive symptoms during the previous two weeks, which do not necessarily indicate depressive disorder. Conclusion The social network characteristics of size and intimacy associated differently with depressive symptoms by gender. In women whose social networks had high age diversity, smaller-sized and less intimate networks increased the likelihood of depression.
Prognostic nomograms for predicting overall survival of Paget ’s disease
Authors: Li Wei , Fang Kun , Huang Guo , Wang You-quan , Cao Hong , Long Lin , Li Dan , Zhu Tian , Tang Kang-yun , Su Li-zhi
Published: March 2020

Background The death rate of metastatic breast cancer in patients with mammary Paget's disease and underlying cancer is 61.3%, with a 10-year cumulative survival rate of 33%. The aim of this investigation was to develop a reliable nomogram to predict Female Paget’s Disease patient, thus helping clinical diagnosis and treatment. Methods Date of patients diagnosed with Paget’s Disease between 2004 to 2014 were downloaded from the Surveillance, Epidemiology, and End Results (SEER)database. Univariate and multivariate cox analysis were used to identify independent prognostic factors, which were used to construct nomograms to predict the probabilities of OS. The performance of the nomogram was assessed by C-indexes, receiver operating characteristic (ROC) curves and calibration curve. Decision curve analysis (DCA) was used to compare clinical usage between the nomogram and Adjusted AJCC staging system.Results Based on the univariate and multivariate cox analysis, features that correlated with survival outcomes were used to establish nomograms for OS prediction. The nomograms showed favorable sensitivity at predicting 1-,3-, and 5-year OS, with a C-index of 0.795(95% confidence interval (CI) 0.773-0.818) for OS. Calibration curves and ROC curves revealed excellent predictive accuracy. Finally, the 3- and 5-year DCA curves yielded larger net benefits than the Adjusted AJCC stage. Conclusions In conclusion, we have successfully established an effective nomogram to predict OS in Paget’s Disease patient, which can help clinicians in determining the appropriate therapy strategies for individual PD patients.
miR-138-5p inhibits the metastasis of prostate cancer by targeting FOXC1
Authors: Zhang Dapeng , Liu Xiaodong , Zhang Qingwei , Chen Xin
Published: March 2020

Background: This study aimed to uncover the regulatory effect of miR-138-5p on the metastasis of PCa cells, and further explore the potential regulatory mechanisms via regulating FOXC1.
Methods: 60 pairs tumor specimens from PCa patients were collected to determine the expression level of miR-138-5p by qRT-PCR. Subsequently, over-expression of miR-138-5p were established to explore the proliferation and metastasis of miR-138-5p in PCa cell lines was analyzed by CCK-8, Tranwell assay and Wounding healing assay, respectively. Bioinformatics analysis and luciferase reporter gene assay were performed to search for the target genes of miR-138-5p, and FOXC1 was selected. Finally, the biological role of miR-138-5p and FOXC1 in the progression of PCa was clarified by a series of rescue experiments.
Results: The results of qRT-PCR revealed that miR-138-5p was lowly expressed in PCa tissues and cell lines. Besdies, these PCa patients with low-miR-138-5p had a higher Gleason score, lymph node metastasis, bone metastasis and poor prognosis of PCa, compared with the patients with high-miR-138-5p. Over-expression of miR-138-5p inhibited the viability, migratory and invasive capacities of PC-3 and DU-145 cells. Bioinformatics analysis and luciferase reporter gene assay suggested that FOXC1 was predicted to be the target of miR-138-5p. Moreover, FOXC1 level was negatively correlated to that of miR-138-5p in PCa tissues. Importantly, FOXC1 could reverse miR-138-5p mimic induced-inhibition of PCa malignant progression.
Conclusions: Downregulated miR-138-5p was closely associated with Gleason score, distant metastasis and poor prognosis of PCa patients. In addition, miR-138-5p alleviated the malignant progression of PCa by targeting and downregulating FOXC1.
Impact of Spinal Muscular Atrophy on Caregivers’ Daily Activities and Health-related Quality of Life
Authors: Chen Er , Bawa Komal , Noone Josh M. , Whitmire Sarah M. , Buchenberger J. Daniel , Arnold W. David , Mills Rosalina , Dixon Stacy
Published: March 2020

Background Spinal muscular atrophy (SMA) is a genetic debilitating disease affecting approximately 10,000 individuals in the United States. Individuals with SMA frequently require caregiver support and care. Through a partnership with a large patient organization, we surveyed caregivers of individuals with SMA below 18 years of age to understand the impact of SMA on caregivers with respect to their daily activities and health-related quality of life (HRQoL). In addition to structured questions, a standardized HRQoL instrument, the EQ-5D-5L and visual analogue scale, were administered. Results The caregiver sample consisted of 45 unpaid caregivers of individuals with SMA. Of them, 22% reported that they were sole caregivers that received no additional caregiving support and 98% were parents of an affected individual. The majority of caregivers cared for individuals with type 2 (58%), followed by type 1 (38%) and type 3 (4%) SMA. Sixty-four percent of the individuals with SMA were able to sit without support or better, while 31% had some motor function and 5% reported no motor function. On average, caregivers reported spending 136 hours/month managing the overall treatment, care, and support for the affected individual. Most of the individuals (91%) were reported to have received nusinersen; caregivers reported spending 29 hours managing treatment in a typical month. Caregiver time investment correlated directly with disease severity measured by both SMA type and patient motor function level. On average, caregivers rated their overall health as 76 on a scale of 0-100 using the EQ-5D-5L HRQoL visual analogue scale. Specifically, 42% of caregivers reported any inability to do their usual activities and 73% reported any anxiety or depression. Conclusions SMA negatively affects caregiver’s daily activities and HRQoL and represents a substantial burden. Disease severity is associated with an increasing amount of time required for care and support for patients with SMA and caregiver’s own HRQoL. As treatments become available, economic evaluation of these treatments should include effects on the family as well.
Overexpression of TGFβ1 in murine mesenchymal stem cells improve the lung inflammation via impacting Treg/Th17 balance in LPS-induced ARDS mice
Authors: Chen Jianxiao , Zhang Xiwen , Xie Jianfeng , Xue Ming , Liu Ling , Yang Yi , Qiu Haibo
Published: March 2020

Background: T helper 17 cells (Th17)/ regulatory T cells (Treg), as subtypes of CD4+T cells, played an important role in the inflammatory response of acute respiratory distress syndrome (ARDS). However, there is still a lack of effective methods to regulate the differentiation balance of Th17/Treg. It was proved that mesenchymal stem cells (MSCs) could regulate the differentiation of CD4+T cells, but the mechanism was still unclear. TGFβ1, as one of the paracrine cytokines of MSCs, could also regulate the differentiation of Th17/Treg but possess low expression in MSCs. Therefore, mouse MSCs (mMSCs)overexpressing TGFβ1 was constructed by lentivirus transfection and intratracheally transplanted into LPS-induced ARDS mice in our study. And the aim of which was to evaluate the therapeutic effects of mMSCs overexpressing TGFβ1 on inflammation and immunoregulationvia impacting Th17/Treg balance inLPS-induced ARDS mice. Methods: mMSCs with TGFβ1 overexpression were constructed using lentiviral vectors. Then mBM-MSCs and mBM-MSC-TGFβ1 (mMSCs overexpressing TGFβ1) were transplanted intratracheally into the ARDS mice induced by lipopolysaccharide. At 3d and 7d after transplantation, mice were sacrificed and the histopathology of lungs was assessed by hematoxylins and eosin staining and lung injury scoring. Homing of the mMSCs were assayed by ex vivooptical imaging. The relative number of Th17 and Treg in the lungs and spleens in mice were detected by FCM. IL-17A and IL-10 in the lungs of mice were analyzed by western blot. Permeability was evaluated by analysing the protein concentration of BALF using ELISA. Alveolar Lung fibrosis was assessed by Masson’s trichrome staining and Ashcroft scoring. The mortality of ARDS mice was followed until 7 days after transplantation. Results: The transduction efficiencies mediated by the lentiviral vectors were 82.3-88.6%. Overexpressing TGF-β1 inhibited the proliferation of mMSCs during day 5-7 (p<0.05), but made no effects on their differentiation or migration (p>0.05). Compared to the LPS+mBM-MSC-NC group, mMSCs overexpressing TGFβ1 engraftment led to improved histopathology of lung tissue in ARDS mice (p<0.05), much more differentiation of mMSCs into Th17 or Treg (p<0.05) and improved permeability of injured lungs (p<0.05). Moreover, IL-17A was also decreased while IL-10 increased in the LPS+mBM-MSC-TGFβ1 group than in the LPS+mBM-MSC-NC group respectively (p<0.05).Finally, mMSCs overexpressing TGFβ1 did not aggravate the fibrosis of lungs in ARDS mice (p>0.05). Conclusion: MSCs overexpressing TGFβ1 could regulate lung inflammation and attenuated lung injuries via modulating the imbalance of Th17/Treg in the lungs of ARDS mice.