bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery and Development of Safe-in-Man Broad-Spectrum Antiviral Agents
Authors: Andersen Petter I. , Ianevski Aleksandr , Lysvand Hilde , Vitkauskiene Astra , Oksenych Valentyn , Bjoras Magnar , Telling Kaidi , Lutsar Irja , Dumpis Uga , Irie Yasuhiko , Tenson Tanel , Kantele Anu , Kainov Denis E.
Published: February 2020

Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 120 safe-in-man agents in freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.
KEEFEKTIFAN MODUL ELEKTRONIK BERBASIS KONSERVASI UNTUK MENINGKATKAN KREATIFITAS PEMBELAJARAN MATA KULIAH PANGKAS DISAIN
Authors: Setyowati Erna
Published: February 2020

The conventional methods still used in practical learning of hairdressing subject and its gave the less optimal learning results. Its requires some creativity, extensive innovation and an electronic module containing materials, images and video tutorials, therefore self-learning stimulus could be provided optimally. Paperless method is one implementation of conservation policy of environmental efficiency and prevention of environmental pollution, beside that it could optimizing the information technology based system on the learning process. Conservation-based electronic module using C56 adobe flash software and flipbook application. The objective of this research is to know the effectiveness of electronic module based on conservation and improvement of learning creativity of hairdressing. The research used the pre-experiment design, observation data collection method, questionnaire, test and documentation with descriptive percentage analysis and validity module test. The result of module validity test is declared a feasible and effective equaled to 84,20 %, while the result of learning using electronic module was increasing student creativity equaled to 22,85 % which obtained from pre-test, post test and process based on aspect of science, affective, and skills assessment.
Assessment of Short-Term Patient Outcomes Following Overlapping Orthopaedic Surgery at a Large Academic Medical Center
Authors: Glauser Gregory , Osiemo Benjamin , Goodrich Stephen , McClintock Scott D. , Weber Kristy L. , Levin L. Scott , Malhotra Neil R.
Published: February 2020

Background:

Overlapping surgery is a long-standing practice that has not been well studied. The aim of this study was to assess whether overlapping surgery is associated with untoward outcomes for orthopaedic patients.

Methods:

Coarsened exact matching was used to assess the impact of overlap on outcomes among elective orthopaedic surgical interventions (n = 18,316) over 2 years (2014 and 2015) at 1 health-care system. Overlap was categorized as any overlap, and subcategories of exclusively beginning overlap and exclusively end overlap. Study subjects were matched on the Charlson comorbidity index score, duration of surgery, surgical costs, body mass index, length of stay, payer, and race, among others. Serious unanticipated events were studied.

Results:

A total of 3,395 patients had any overlap and were matched (a match rate of 90.8% of 3,738). For beginning and end overlap, matched groups were created, with a match rate of 95.2% of 1043 and 94.7% of 863, respectively. Among matched patients, any overlap did not predict an unanticipated return to surgery at 30 days (8.2% for any overlap and 8.3% for no overlap; p = 0.922) or 90 days (14.1% and 14.1%, respectively; p = 1.000). Patients who had surgery with any overlap demonstrated no difference compared with controls with respect to reoperation, readmission, or emergency room (ER) visits at 30 or 90 days (a reoperation rate of 3.1% and 3.2%, respectively [p = 0.884] at 30 days and 4.2% and 3.5% [p = 0.173] at 90 days; a readmission rate of 10.3% and 11.0% [p = 0.352] at 30 days and 5.5% and 5.2% [p = 0.570] at 90 days; and an ER visit rate of 5.2% and 4.6% [p = 0.276] at 30 days and 4.8% and 4.3% [p = 0.304] at 90 days). Patients with surgical overlap showed reduced mortality compared with controls during follow-up (1.8% and 2.6%, respectively; p = 0.029). Patients with beginning and/or end overlap had a similar lack of association with serious unanticipated events; however, patients with end overlap showed an increased unexpected rate of return to the operating room after reoperation at 90 days (13.3% versus 9.7%; p = 0.015).

Conclusions:

Nonconcurrent overlapping surgery was not associated with adverse outcomes in a large, matched orthopaedic surgery population across 1 academic health system.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Pre- and post-sequencing recommendations for functional annotation of human fecal metagenomes
Authors: Treiber Michelle L. , Taft Diana H. , Korf Ian , Mills David A. , Lemay Danielle G.
Published: February 2020

Background
Shotgun metagenomes are often assembled prior to annotation of genes which biases the functional capacity of a community towards its most abundant members. For an unbiased assessment of community function, short reads need to be mapped directly to a gene or protein database. The ability to detect genes in short read sequences is dependent on pre- and post-sequencing decisions. The objective of the current study was to determine how library size selection, read length and format, protein database, e-value threshold, and sequencing depth impact gene-centric analysis of human fecal microbiomes when using DIAMOND, an alignment tool that is up to 20,000 times faster than BLASTX.
Results
Using metagenomes simulated from a database of experimentally verified protein sequences, we find that read length, e-value threshold, and the choice of protein database dramatically impact detection of a known target, with best performance achieved with longer reads, stricter e-value thresholds, and a custom database. Using publicly available metagenomes, we evaluated library size selection, paired end read strategy, and sequencing depth. Longer read lengths were acheivable by merging paired ends when the sequencing library was size-selected to enable overlaps. When paired ends could not be merged, a congruent strategy in which both ends are independently mapped was acceptable. Sequencing depths of 5 million merged reads minimized the error of abundance estimates of specific target genes, including an antimicrobial resistance gene.
Conclusions
Shotgun metagenomes of DNA extracted from human fecal samples sequenced using the Illumina platform should be size-selected to enable merging of paired end reads and should be sequenced in the PE150 format with a minimum sequencing depth of 5 million merge-able reads to enable detection of specific target genes. Expecting the merged reads to be 180-250bp in length, the appropriate e-value threshold for DIAMOND would then need to be more strict than the default. Accurate and interpretable results for specific hypotheses will be best obtained using small databases customized for the research question.
Compliance with spectacle use in children with refractive errors- a systematic review and meta-analysis
Authors: Dhirar Nonita , Dudeja Sankalp , Duggal Mona , Gupta Parul Chawla , Jaiswal Nishant , Singh Meenu , Ram Jagat
Published: February 2020

Background Primary objective of this review was to measure compliance with spectacle use in children with refractive errors. Secondary objective was to understand the reasons for non-compliance.Methods The databases searched were Ovid, EMBASE, CINAHL and Pubmed. All studies up to March, 2018 were included. The search terms were- ((((((Compliance [Title/Abstract]) OR Adherence[Title/Abstract]) OR Compliant[Title/Abstract]) OR Adherent[Title/Abstract])) AND (((Spectacle[Title/Abstract]) OR Spectacles[Title/Abstract]) OR Eye Glasses[Title/Abstract])) AND ((((Child[Title/Abstract]) OR Children[Title/Abstract]) OR Adolescent[Title/Abstract]) OR Adolescents[Title/Abstract]). Two researchers independently searched the databases and initial screening obtained 33 articles. The PRISMA guidelines were followed for conducting and writing the systematic review. Two reviewers assessed data quality independently using the Quality Assessment tool for systematic reviews of observational studies (QATSO). Poor quality studies were those, which had a score of less than 33% on the QATSO tool. Sensitivity analysis was done to determine if poor quality studies effected compliance. Galbraith plot was used to investigate statistical heterogeneity amongst studies. A random effects model was used to pool compliance.Results Twenty-three studies were included in the review, of which 20 were included in the quantitative analysis. All the studies were cross sectional. The overall compliance with spectacle use was 40.14% (95% CI- 32.78-47.50). The compliance varied from 9.84% (95% CI=2.36-17.31) to 78.57% (95% CI=68.96-88.18). The compliance derived in sensitivity analysis was 40.09%. Reasons for non-compliance were broken/lost spectacles, forgetfulness, and parental disapproval.Conclusion Appropriate remedial measures such as health education and strengthening vision care services will be required to address poor compliance with spectacle use among children.
Evolution of PHAS Loci in the Young Spike of Allohexaploid Wheat
Authors: Zhang Rongzhi , Huang Siyuan , Li Shiming , Song Guoqi , Li Yulian , Li Wei , Li Jihu , Gao Jie , Gu Tiantian , Li Dandan , Zhang Shujuan , Li Genying
Published: February 2020

Background: PhasiRNAs (phased secondary siRNAs) play important regulatory roles in the development processes and biotic or abiotic stresses in plants. Some of phasiRNAs involve in the reproductive development in grasses, which include two categories, 21-nt (nucleotide) and 24-nt phasiRNAs. They are triggered by miR2118 and miR2275 respectively, in premeiotic and meiotic anthers of rice, maize and other grass species. Wheat ( Triticum aestivum ) with three closely related subgenomes (subA, subB and subD), is a model of allopolyploid in plants. Knowledge about the role of phasiRNAs in the inflorescence development of wheat is absent until now, and the evolution of PHAS loci in polyploid plants is also unavailable. Results : Using 261 small RNA expression datasets from various tissues, a batch of PHAS (phasiRNA precursors) loci were identified in the young spike of wheat, most of which were regulated by miR2118 and miR2275 in their target site regions. Dissection of PHAS and their trigger miRNAs among the diploid (AA and DD), tetraploid (AABB) and hexaploid (AABBDD) genomes of Triticum indicated that distribution of PHAS loci were dominant randomly in local chromosomes, while miR2118 was dominant only in the subB genome. The diversity of PHAS loci in the three subgenomes of wheat and their progenitor genomes (AA, DD and AABB) suggested that they originated or diverged at least before the occurrence of the tetraploid AABB genome. The positive correlation between the PHAS loci or the trigger miRNAs and the ploidy of genome indicated the expansion of genome was the major drive force for the increase of PHAS loci and their trigger miRNAs in Triticum . In addition, the expression profiles of the PHAS transcripts suggested they responded to abiotic stresses such as cold stress in wheat. Conclusions: Altogether, non-coding phasiRNAs are conserved transcriptional regulators that display quick plasticity in Triticum genome. They may be involved in reproductive development and abiotic stress in wheat. It could be referred to molecular research on male reproductive development in Triticum .
Long-Lasting Insecticidal Nets retain bio-efficacy after five years of storage: implications for malaria control programmes
Authors: Musa Jeremiah John , Moore Sarah , Moore Jason , Mbuba Emmanuel , Mbeyela Edgar , Kobe Dickson , Swai Johnson K. , Odufuwa Olukayode G.
Published: February 2020

Background: Long Lasting Insecticidal Nets (LLINs) are the most sustainable and effective malaria control tool currently available. Global targets are for 80% of the population living in malaria endemic areas to have access to (own) and use a LLIN. However, current access to LLINs in endemic areas is 56% due to system inefficiencies and budget limitations. Thus, cost-effective approaches to maximize access to effective LLINs in endemic areas are required. This study evaluated whether LLINs that had been stored for five years under manufacturer’s recommended conditions may be optimally effective against Anopheles mosquitoes, to inform malaria control programmes and governments on the periods over which LLINs may be stored between distributions, in an effort to maximise use of available LLINs. Methods: Standard World Health Organization (WHO) bioassays (cone and tunnel test) were used to evaluate the bio-efficacy and wash resistance of Olyset ® and DawaPlus ® 2.0 (rebranded Tsara ® Soft) LLINs after five years of storage at 25°C - 33.4°C and 40% - 100% relative humidity. In addition, a small scale Ifakara Ambient Chamber test (I-ACT) was conducted to compare the bio-efficacy of one long stored LLINs to one new LLIN of the same brand, washed or unwashed. LLINs were evaluated using laboratory reared fully susceptible Anopheles gambiae s.s (Ifakara strain) and pyrethroid resistant Anopheles arabiensis (Kingani strain). Results: After five years of storage, both unwashed and washed, Olyset ® and DawaPlus ® 2.0 (Tsara ® Soft) LLINs passed WHO bio-efficacy criteria on knockdown (KD60) ≥95%, 24-hour mortality ≥80% and ≥90% blood-feeding inhibition in WHO assays against susceptible An. gambiae s.s. DawaPlus ® 2.0 LLINs also passed combined WHO bioassay criteria against resistant An. arabiensis. Confirmatory I-ACT tests using whole nets demonstrated that long-stored LLINs showed higher efficacy than new LLINs on both feeding inhibition and mortality endpoints against resistant strains. Conclusions: Even after long-term storage of around 5 years, both Olyset ® and DawaPlus ® 2.0 LLINs remain efficacious against susceptible Anopheles mosquitoes at optimal storage range of 25°C - 33.4°C for temperature and 40% - 100% relative humidity measured by standard WHO methods. DawaPlus ® 2.0 (Tsara ® Soft) remained efficacious against resistant strain.
Incidence, Clinical Profile, and Risk Factors for Serious Bacterial Infections in Children Hospitalized With Fever in Ujjain, India
Authors: Pathak Ashish , Upadhayay Radika , Mathur Aditya , Rathi Sunil , Lundborg Cecilia Stålsby
Published: February 2020

Background Fever is a cause for concern for both parents and the treating pediatrician and a common reason for antibiotic overuse. However, the proportion of children hospitalized for fever with serious bacterial infection (SBI) is uncertain. We aimed to evaluate the epidemiological, clinical, hematological, and biochemical risks for SBI among the children admitted with fever. Method This prospective study was conducted in a rural teaching hospital in India on consecutive children, aged 3 months–12 years, presenting with fever 100°F (37.7°C) or higher. The presence of SBI was confirmed with one of the following criteria: (a) a positive blood culture; (b) roentgenographically confirmed pneumonia with high titres of C-reactive protein; (c) a culture-confirmed urinary tract infection; (d) enteric fever diagnosed clinically in addition to either a positive blood culture or high Widal titers; and (e) meningitis diagnosed clinically in addition to either a positive blood culture or cerebrospinal fluid culture. A predefined questionnaire was filled. Results A total of 302 children were included in the study, out of which 47% (95% CI 41.4%-52.7%) presented with SBI. The factors associated with confirmed SBI in bivariate analysis were history of previous hospitalization, history of chronic illness, history of medication in the previous one week, a partially immunized child, history of common cold, moderate-grade fever, toxic look, significant lymphadenopathy, absence of BCG scar, delayed development, irritability, breathlessness, respiratory distress, poor feeding, significant weight loss, suspected urinary tract infection, hyponatremia, hypokalemia, and abnormal leucocyte count. The final generalized logistic regression model revealed partially immunized child (RR 4.26), breathlessness (RR 1.80), weight loss (RR 2.28), and suspected urinary tract infection (RR 1.95) as risk factors for the increased risk of SBI. Conclusion The study identified multiple risk factors for SBI. Pediatricians can be made aware of these risk factors. Further studies are warranted to identify age-specific risk factors for SBI because most clinicians depend on clinical signs and symptoms to identify SBI.
Camelina sativa meal hydrolysate as sustainable biomass for the production of carotenoids by Rhodosporidium toruloides
Authors: Bertacchi Stefano , Bettiga Maurizio , Porro Danilo , Branduardi Paola
Published: February 2020

Background: As the circular economy advocates a near total waste reduction, the industry has shown an increased interest towards the exploitation of various residual biomasses. The origin and availability of biomass used as feedstock strongly affects the sustainability of biorefineries, where it is converted in energy and chemicals. Here, we explored the valorization of Camelina meal, the leftover residue from Camelina sativa oil extraction. In fact, in addition to Camelina meal use as animal feed, there is an increasing interest in further valorizing its macromolecular content or its nutritional value. Results: Camelina meal hydrolysates were used as nutrient and energy source for the fermentation of the carotenoid-producing yeast Rhodosporidium toruloides in shake flasks. Total acid hydrolysis revealed that carbohydrates accounted for a maximum of 31 ± 1.0% of Camelina meal. However, because acid hydrolysis is not optimal for subsequent microbial fermentation, an enzymatic hydrolysis protocol was assessed, yielding a maximum sugar recovery of 53.3%. Separate Hydrolysis and Fermentation, Simultaneous Saccharification and Fermentation, and SSF preceded by presaccharification of Camelina meal hydrolysate produced 5 ± 0.7, 16 ± 1.9, and 13 ± 2.6 mg/L of carotenoids, respectively. Importantly, the presence of water-insoluble solids, which normally inhibit microbial growth, correlated with a higher titer of carotenoids, suggesting that the latter could act as scavengers. Conclusions: This study paves the way for the exploitation of Camelina meal as feedstock in biorefinery processes. The process under development provides an example of how different final products can be obtained from this side stream, such as pure carotenoids and carotenoid-enriched Camelina meal can potentially increase the initial value of the source material. The obtained data will help assess the feasibility of using Camelina meal to generate high value-added products.
Association between subthreshold depression and self-care behaviours in people with type 2 diabetes: a systematic review of observational studies
Authors: Shrestha Monika , Ng Ashley , Al-Ghareeb Amal , Alenazi Fatimah , Gray Richard
Published: February 2020

Background: Self-care behaviours in people living with type 2 diabetes are important to achieving optimal glycemic control. Major depression in type 2 diabetes is associated with decreased adherence to self-care behaviours. The association between subthreshold depression and self-care behaviours, however, has not previously been systematically reviewed. The objective of this review is to determine the association between subthreshold depression and self-care behaviours. Methods: A systematic search was performed in five electronic databases that included MEDLINE, EMBASE, PsycINFO, Emcare, and CINAHL. Any observational studies in adults with type 2 diabetes, investigating the association between subthreshold depression and any self-care behaviours were included in the review. Qualitative studies, review articles and grey literature were excluded. Two reviewers independently completed title and abstract and full-text screening, appraised study quality, and extracted the data. A third reviewer resolved any discrepancies between the reviewers if needed. Included articles were critically appraised using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Meta-analyses were not conducted, because criteria for conducting such analyses were not met. Results: A total of 6,408 articles were identified through the database searching. After the abstract and full-text review, two articles met the inclusion criteria. One of the included study was cross-sectional while the other was a longitudinal study. Both studies showed inconsistent findings in the association between subthreshold depression and self-care behaviours. Important risks of bias were identified in the included studies. Discussion: The evidence from the two included studies on a possible association between subthreshold depression and self-care behaviours in adults with type 2 diabetes was not consistent and potentially biased. Our review established a gap in knowledge and suggests that further high-quality studies are needed to examine the association between subthreshold depression and self-care behaviours in people with type 2 diabetes. Systematic review registration: PROSPERO CRD42018116373
Antimicrobial resistance among pathogens that infect the bloodstream: a multicenter surveillance report for 1998–2017
Authors: tian lei , zhang zhen , sun ziyong
Published: February 2020

Background Bloodstream infections (BSIs) are a common consequence of infectious diseases and cause high morbidity and mortality. Appropriate antibiotic use is critical for patients’ treatment and prognosis. Long-term monitoring and analyzing of bacterial resistance are important for guiding physicians in choosing the appropriate antibiotics and understanding the changes in bacterial resistance and infection control. Here, we report a retrospective study on antimicrobial resistance in BSI-associated pathogens.Methods Data from the Hubei Province Antimicrobial Resistance Surveillance System (HBARSS) from 1998–2017 were retrospectively analyzed using WHONET 5.6 software. Results Data from HBARSS (1998–2017) revealed that 40,518 Gram-positive bacteria and 26,568 Gram-negative bacteria caused BSIs, the most common of which were Staphylococcus aureus and Escherichia coli. Drug susceptibility data showed that the resistance rates of E. coli and Klebsiella pneumoniae to cefotaxime were significantly higher than those to ceftazidime. Carbapenem-resistant (CR) E. coli and K. pneumoniae have also emerged. In 2013–2017, K. pneumoniae showed resistance levels reaching 15.8% and 17.5% to imipenem and meropenem, respectively, and Acinetobacter baumannii showed high resistance rates ranging from 60–80% to common antibiotics. Control of methicillin-resistant Staphylococcus aureus (MRSA) remains a major challenge, and in 2009–2017, the MRSA detection rate was 40–50%. Conclusions Prevalence of CR K. pneumoniae has increased significantly in recent years. Resistance rates of A. baumannii to common antimicrobial agents have increased exponentially, reaching high levels. MRSA remains a challenge to control.
Construction of immune human library and screening of neutralizing antibodies specific to glycoprotein of severe fever with thrombocytopenia syndrome virus
Authors: zhang wenshuai , Guo Xiling , Chi Ying , Jiao Yongjun
Published: February 2020

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease circulated in eastern Asian countries including China, Japan and South Korea. Currently, there are no effective prophylactic or therapeutic measurements available in the clinical settings. Antibody-mediated prevention and treatment can be an effective complement to the clinical supporting strategies. Glycoprotein N (Gn) and Glycoprotein C (Gc) are two of the highly antigenic envelope proteins on the SFTS virus (SFTSV) surface and contain neutralizing epitopes that can induce neutralizing antibodies. Methods To obtain the neutralizing antibodies specific to glycoprotein of SFTSV, we used phage display technology to generate a human phage antibody library with ScFv format from the peripheral lymphocytes of 8 patients who had recovered from SFTS. The library was bio-panned against recombinant Gn and Gc proteins for four rounds to find their specific antibody clones. Finally, the selected clones were characterized by binding activity test, virus neutralization and Competitive ELISA.Results An immune human ScFv antibody library against SFTSV with high capacity and diversity was constructed. After 4 rounds of panning, 6 distinct clones were found. Of them, 5 were specific to Gn, whereas only 1 was specific to Gc. The immunofluorescence assay showed only three clones with Gn specificity called MAb 4A6, MAb 2B6 and MAb 1F2, respectively, could bind nature virion. All these clones showed broad neutralization activity against the SFTSV, and had different antigenic epitopes from MAb 4-5, a previous identified antibody clone. Conclusions Three new monoclonal antibodies described in our study could be used as potential agents in immunotherapy against SFTSV infection.
Autophagy modulation altered differentiation capacity of CD146+ cells toward endothelial cells, pericytes, and cardiomyocytes
Authors: Hassanpour Mehdi , Rezaie Jafar , Darabi Masoud , Hiradfar Amirataollah , Rahbarghazi Reza , Nouri Mohammad
Published: February 2020

Background: To date, many attempts are employed to increase the regenerative potential of stem cells. In this study, we evaluated the hypothesis whether an autophagy modulation could induce/reduce CD146+ cells differentiation into mature pericyte, endothelial and cardiomyocyte lineage. Methods In this study, CD146+ cells were enriched from human bone marrow aspirates and trans-differentiated into mature EC, PC and CM after exposure to autophagy stimulator (50 µM Met)/inhibitor (15 µM HCQ). The protein levels of autophagy proteins were monitored by western blotting. NO content was measured using the Griess assay. Using real-time PCR assay and western blotting, we monitored the lineage protein and gene levels. The fatty acid change was determined by gas chromatography. Pro-inflammatory cytokine and angiocrine factors were measured by ELISA. The exosome secretion capacity was assessed by AChE activity and real-time PCR assay. Result Data revealed the modulation of autophagy factors, Beclin-1, P62 and LC3 II/I ratio in differentiating CD146+ cells after exposure to Met and HCQ (p<0.05). The inhibition of autophagy increased released NO content and decreased intracellular NO content compared to the Met-treated cells (p<0.05). Real-time PCR analysis showed that the treatment of CD146+ cells with autophagy modulators altered the expression of VE-cadherin, cTnI and α-SMA. Our data demonstrated that the stimulation of autophagy signaling in CD146+ cells with Met increased the expression of VE-cadherin, α-SMA, and cTnI compared to HCQ-treated cells (p<0.05) while western blotting revealed the protein synthesis of all lineage-specific proteins in under the stimulation and inhibition of autophagy. Fatty acid profile analysis revealed the increase of unsaturated fatty acids after exposure to HCQ (p<0.05). None statistically significant differences were found in the levels of Tie-1, Tie-2, VEGFR-1 and VEGFR-2 after autophagy modulation. The treatment of cells with HCQ increased the levels of TNF-α and IL-6 compared to the Met-treated cells. Data revealed the increase of exosome biogenesis and secretion to the supernatant in cells treated with HCQ compared to the Met groups (p<0.05).ConclusionsIn summary, autophagy modulation could be altered differentiation potency of CD146+ cells and could be novel and applicable cardiac cell therapy in the cardiac regeneration field.
Circulating Tumor Cell Subtypes may Predict Responses to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer
Authors: Ma Ge , Wang Jingyi , Wang Xingmeng , Zeng Hanling , Li Minghui , Han Xu , Mao Xinrui , Jiang Yi , Xia Tiansong , Liu Xiaoan , wang shui
Published: February 2020

Background: Neoadjuvant chemotherapy (NCT) is the standard treatment for patients with locally advanced breast cancer (LABC). However, the predictive value of circulating tumor cells (CTCs) with different molecular subtypes in NCT response has not yet been determined, which was, therefore, the aim of this study.
Methods: All patients were staged as LABC and received an EC×4 –T×4 NCT regimen. Blood samples were collected from patients at the time of biopsy, and after the first and eighth NCT courses. Patients were divided into High responders (High-R) and Low responders (Low-R) according to Miller-Payne system and changes in Ki-67 levels after NCT treatment. A novel SE-i•FISH strategy was applied to detect CTCs. Subtypes were successfully analyzed in LABC patients undergoing NCT, for the first time.
Results: Total CTCs increased continuously and were higher for Low-R patients; while in the High-R group, total CTCs increased slightly during NCT before returning to baseline levels. Triploid and tetraploid chromosome 8 as well as the proportion of each, increased for Low-R but not High-R patients. The number of small CTCs in the Low-R group increased significantly until the last sample, however, remained constant in the High-R group. The patients with more CTCs had shorter PFS and OS than those with less CTCs after the 8th course of NCT.
Conclusions: Total CTCs as well as individual subtypes within peripheral blood following NCT were predictive of patient responses to NCT. More detailed characterization of CTC blood profiles may improve predictive capacity and lead to improved LABC treatments.
Proactive community case management in Senegal 2014-2016: a case study in maximizing the impact of community case management of malaria
Authors: Gaye Seynabou , Kibler Janelle , Ndiaye Jean Louis , Diouf Mame Birame , Linn Annē , Gueye Alioune Badara , Fall Fatou Ba , Ndiop Medoune , Diallo Ibrahima , Cisse Moustapha , Ba Mady , Thwing Julie
Published: February 2020

The Senegal National Malaria Control Program (NMCP) introduced home-based malaria management for all ages, with diagnosis by rapid diagnostic test (RDT) and treatment with artemisinin-based combination therapy (ACT) in 2008, expanding to over 2000 villages nationwide by 2014. With prise en charge à domicile (PECADOM), community health workers (CHWs) were available for community members to seek care, but did not actively visit households to find cases. A trial of a proactive model (PECADOM Plus), in which CHWs visited all households in their village weekly during transmission season to identify fever cases and offer case management, in addition to availability during the week for home-based management, found that CHWs detected and treated more cases in intervention villages, while the number of cases detected weekly decreased over the transmission season. The NMCP scaled PECADOM Plus to three districts in 2014 (132 villages), to a total of six districts in 2015 (246 villages), and to a total of 16 districts in 2016 (708 villages). A narrative case study with programmatic results is presented. During active sweeps over approximately 20 weeks, CHWs tested a mean of 77 patients per CHW in 2014, 89 patients per CHW in 2015, and 90 patients per CHW in 2016, and diagnosed a mean of 61, 61, and 43 patients with malaria per CHW in 2014, 2015, and 2016, respectively. The number of patients who sought care between sweeps increased, with a 104% increase in the number of RDTs performed and a 77% increase in the number of positive tests and patients treated with ACT during passive case detection. While the number of CHWs increased 7%, the number of patients receiving an RDT increased by 307% and the number of malaria cases detected and treated by CHWs increased 274%, from the year prior to PECADOM Plus introduction to its first year of implementation. Based on these results, approximately 700 additional CHWs in 24 new districts were added in 2017. This case study describes the process, results, and lessons learned from Senegal’s implementation of PECADOM Plus, as well as guidance for other programs considering introduction of this innovative strategy.
A Family of Fuchs Endothelial Corneal Dystrophy and Anterior Polar Cataract with An Analysis of Whole Exome Sequencing
Authors: Jiang Xue , Jin Xin , Zhang Nan , Zhang Hong
Published: February 2020

Background Our aim was to introduce a family affected by this rare phenotype, and perform the whole exome sequencing (WES) to explore the potential candidate genes causing the disorders.Methods A five-generation family including 5 patients affected by FECD with APC, and 9 patients suffered from only FECD was recruited from the First Affiliated Hospital of Harbin Medical University. All participants received ophthalmic examinations. 8 family members were selected to perform WES with a bioinformatics analysis.Results Patients in this family had FECD as the common feature. The proband (a 65-year-old female) was affected by FECD and APC in both eyes, with epithelial bullae in the left eye of the. Slit-lamp, specular and confocal microscope and OCT images showed guttae more serious in the central cornea than the peripheral area, confirming the diagnosis of FECD. In this family, most corneal guttae were bilateral with almost equal degree of progression in Descemet membrane, APC was found around the age of 10, perhaps even earlier. Bioinformatics analysis showed that 83 potential candidate genes in total may cause this condition in this family. No known causative gene of this phenotype or FECD was found by WES.Conclusion We introduced a family of FECD with APC, with no known causative gene found by WES, inferring that there may be a novel gene-locus associated with this condition. Further study will be engaged on candidate gene screening and variants validation with corresponding functional aspects to clarify the relationship between genotype and phenotype.
Impact on Early Discharge After Emergency Department-Based Treatment Pathway in Nonperforated Appendicitis: A Retrospective Study
Authors: Ojakäär Artur , Purdy Martin , Kechagias Aristotelis , Järvelin Ulla , Palomäki Ari
Published: February 2020

Background Acute appendicitis is a global disease and a very common indication for emergency surgery worldwide. The need for hospital resources is therefore constantly high. The administration in Kanta-Häme Central Hospital, southern Finland, called for an urgent reorganisation due to shortage of hospital beds at the department of general surgery. Treatment pathway of nonperforated acute appendicitis was moved into Emergency Department (ED). The aim of this study was to assess whether it affected the length of in-hospital stay (LOS) and the 30-day complication rate.MethodsThis is a retrospective pre- and post- intervention analysis. After the reorganisation, most postoperative patients with nonperforated appendicitis were followed at the 24-hour observation unit of the ED instead of the surgical ward. Patients operated during the first three months after the reorganisation were compared to those operated during the three months before it. A case met inclusion criteria if there were no signs of appendiceal perforation during surgery. Exclusion criteria comprised age <18 years and perforated disease. ResultsDuring the study period, appendicectomy was performed on 112 patients, of whom 62 were adults with nonperforated appendicitis. Twenty-seven of the included patients were treated before the reorganisation, and 35 after it. Twenty of the latter were followed only at the ED. LOS decreased significantly after the reorganisation. Median postoperative time till discharge was 15.67 hrs for all patients after the reorganisation and 13.13 hrs for those exclusively followed at the ED, compared to 24.42 hrs before the reorganisation (standard error 6.2 hrs, 95% confidence interval 2.3–15.2 hrs, p < 0.01). There were no more complications in the group treated postoperatively in the ED. ConclusionsEarly discharge from the ED observation unit after appendicectomy for nonperforated appendicitis in adults is safe and feasible. Shifting the postoperative monitoring and the discharge policy of such patients to the ED – instead of the surgical ward – occurred in the majority of the cases after the reorganisation. This change may spare resources as in this series it resulted in a significantly shorter LOS without any increase in the 30-day complication rate.
HDAC6 inhibition enhances the anti-tumor effect of eribulin through tubulin acetylation in triple negative breast cancer cells
Authors: Oba Takaaki , Ono Mayu , Matoba Hisanori , Uehara Takeshi , Hasegawa Yoshie , Ito Ken-ichi
Published: February 2020

Background: Improved prognosis for triple-negative breast cancer (TNBC) has currently plateaued and the development of novel therapeutic strategies is required. This study aimed to explore the anti-tumor effect of combined eribulin and HDAC inhibitor (vorinostat: VOR, pan-HDAC inhibitor and ricolinostat: RICO, selective HDAC6 inhibitor) treatment for TNBC. Methods: The effect of eribulin in combination with VOR or RICO was tested based on both concurrent and sequential administration to three TNBC cell lines (MDA-MB-231, Hs578T, and MDA-MB-157) and their eribulin-resistant derivatives. The expression of acetylated α-tubulin was analyzed by western blotting. Immunohistochemical analyses of clinical specimens obtained from breast cancer patients who underwent neoadjuvant chemotherapy with eribulin were also examined. Results: The simultaneous administration of low concentrations of VOR (0.2 μM) or RICO (0.2 μM) enhanced the anti-tumor effect of eribulin in MDA-MB-231 and Hs578T cells but not in MDA-MB-157 cells. Meanwhile, pre-treatment with 5 μM of VOR or RICO enhanced sensitivity to eribulin in MDA-MB-231, Hs578T, and MDA-MB-157 cells. VOR or RICO increased acetylated α-tubulin expression in MDA-MB-231 and Hs578T cells in a dose-dependent manner (0.2 μM to 5 μM). In contrast, whereas 5 μM of VOR or RICO increased the expression of acetylated α-tubulin in MDA-MB-157 cells, low concentrations (0.2 μM or 0.5 μM) did not. Treatment with eribulin also increased the expression of acetylated α-tubulin in MDA-MB-231 and Hs578T cells but not in MDA-MB-157 cells. These phenomena were also observed in eribulin-resistant cells. Based on immunohistochemical analyses of clinical specimens, the expression of acetylated α-tubulin was increased after eribulin treatment in TNBC. Conclusions: HDAC6 inhibition enhances the anti-tumor effect of eribulin through the acetylation of α-tubulin. This combination therapy could represent a novel therapeutic strategy for TNBC.
MYB44 competitively inhibits the formation of the MYB340-bHLH2-NAC56 complex to regulate anthocyanin biosynthesis in purple-fleshed sweet potato
Authors: Wei Zeng-Zheng , Hu Kang-Di , Zhao Dong-Lan , Tang Jun , Huang Zhong-Qin , Jin Peng , Li Yan-Hong , Han Zhuo , Hu Lan-Ying , Yao Gai-Fang , Zhang Hua
Published: February 2020

Background: Anthocyanins, which have important biological functions and have a beneficial effect on human health, notably account for pigmentation in purple-fleshed sweet potato tuberous roots. Individual regulatory factors of anthocyanin biosynthesis have been identified; however, the regulatory network of anthocyanin biosynthesis in purple-fleshed sweet potato is unclear. Results: We functionally determined that IbMYB340 cotransformed with IbbHLH2 in tobacco and strawberry receptacles induced anthocyanin accumulation, and the addition of IbNAC56a or IbNAC56b caused increased pigmentation. Furthermore, we confirmed the interaction of IbMYB340 with IbbHLH2 and IbNAC56a or IbNAC56b via yeast two-hybrid and firefly luciferase complementation assays; these proteins could form a MYB340-bHLH2-NAC56a or MYB340-bHLH2-NAC56b transcriptional complex to regulate anthocyanin biosynthesis by binding to the IbANS promoter rather than the IbUFGT promoter. Furthermore, it was found by a transient expression system in tobacco leaves that IbMYB44 could decrease anthocyanin accumulation. Moreover, the interaction of IbMYB44 with IbMYB340 and IbNAC56a or IbNAC56b was verified. This result suggested that IbMYB44 acts as a repressor of anthocyanin in sweet potato.Conclusions: The repressor IbMYB44 affected anthocyanin biosynthesis by competitively inhibiting the IbMYB340-IbbHLH2-IbNAC56a or IbMYB340-IbbHLH2-IbNAC56b regulatory complex formation. Overall, the present study proposed a novel regulatory network whereby several vital TFs play key roles in regulating anthocyanin biosynthesis, and it provides strong insight into the potential mechanism underlying anthocyanin biosynthesis in sweet potato tuberous roots with purple color.
Ambient sulfur dioxide could have an impact on testicular volume from an observational study on a population of infertile male
Authors: Chen Yuan , Chang Yi-Kai , Su Yann-Rong , Chang Hong Chiang
Published: February 2020

Background The present retrospective study investigates the effect of environmental pollutants on male reproductive health. Methods Male patients with primary infertility (n = 282) from a single center (National Taiwan University Hospital, Taipei, Taiwan), between January 2016 and December 2017, were identified. Patients were physically examined for the presence of varicocele, and the volume of both testicles. Semen quality was measured in terms of total sperm count (millions), sperm concentration (millions/ml), and the percentage of motile sperm cells and the sperm cells with normal morphology. Data on the concentration of SO 2 (ppb), O3 (ppb), NO and NO 2 (ppb), and PM2.5 concentrations (μg/m3), measured on daily and hourly basis, were acquired from the Environmental Protection Administration Executive Yuan, Taiwan. Individual exposure to pollutants was estimated based on the reported residential address of patients. Statistical analysis indicated the impact of each pollutant on the testicular volume and semen parameters. Results Mean ± SD of age was 36.7 ± 7.3 years. The average sperm count and concentration was 41.9 million/ml and 34.1 million/ml, respectively. Except for PM2.5, the mean concentration of all the particulate matters were within the reference value. NO2 and SO2 exposure were negatively associated with the sperm concentration and motility, and testicular volume, respectively. Conclusions NO2 and SO 2 exposure were negatively associated with the sperm concentration and motility, and testicular volume, respectively, in a population of infertile male. Nevertheless, studies are needed to ascertain the impact of different exposure levels of pollutants on the semen parameters.
Detection and Dynamics of Circulating Tumor Cells in Patients with High-Risk Prostate Cancer Treated with Radiotherapy and Hormones: A Prospective Phase II Study
Authors: Zapatero Almudena , Gómez-Caamaño Antonio , Rodriguez María Ángeles Cabeza , Muinelo-Romay Laura , de Vidales Carmen Martin , Abalo Alicia , Crespo Patricia Calvo , Mateos Luis León , Olivier Carlos , Piris Lorena Vega
Published: February 2020

Background: Circulating tumor cells (CTCs) are an established prognostic marker in castration-resistant prostate cancer but have received little attention in localized high-risk disease. We studied the detection rate of CTCs in patients with high-risk prostate cancer before and after androgen deprivation therapy and radiotherapy to assess its value as a prognostic and monitoring marker.Patients and Methods: We performed a prospective analysis of CTCs in the peripheral blood of 65 treatment-naïve patients with high-risk prostate cancer. EpCAM-positive CTCs were enumerated using the CELLSEARCH system at 4 timepoints. A cut off of 0 vs ≥ 1 CTC/7.5 ml blood was defined as a threshold for negative versus positive CTCs status.Results: CTCs were detected in 5/65 patients (7.5%) at diagnosis, 8/62 (12.9%) following neoadjuvant AD, and 11/59 (18.6%) at the end of radiotherapy, with a median CTC count/7.5 ml of 1 (range, 1-136). Only 1 patient presented a positive CTC result 9 months after radiotherapy. Positive CTC status was not significantly associated with any clinicopathologic factors. However, a significant association was observed between conversion of CTCs and stages T3 ( P = 0.044) and N1 ( P = 0.002). Detection of CTCs was not significantly associated with overall survival ( P > 0.40).Conclusions: We found a low detection rate for CTCs. De novo positive CTC counts after treatment are probably due to a passive mechanism associated with destruction of the tumor. Further studies with larger samples and more accurate assessment methods are needed to determine the prognostic and therapeutic potential of CTC detection.Trial registration: ClinicalTrials.gov ID: NCT01800058
Advanced glycation end products increased placental vascular permeability of human BeWo cells via RAGE/NF-kB signaling pathway
Authors: Shi Yuehua , Qian Jie , Zhang Qinfen , Hu Yan , Sun Dongdong , Jiang Li
Published: February 2020

Background: The placental barrier plays an important role in protecting the fetus from the maternal environment. Gestational diabetes mellitus (GDM), caused by placental permeability, is a serious pregnancy complication with a high incidence worldwide. This study aimed to investigate the effects of advanced glycation end products (AGEs) on cell tight conjunction, and explore underlying mechanisms of the dys-regulation of placental vascular permeability in BeWo cells. Methods: Monolayer permeability assay was employed to reveal the transformation of the placental vascular permeability in BeWo cells under different administrations. Transmission electron microscopy was utilized to evaluate cell tight conjunction of BeWo cells. Immunofluorescence, wetern blot and RT-qPCR were adopted to determine the protein and mRNA levels of ZO-1, Occludin, RAGE and NF-kB. In addition, anti-RAGE and NF-kB inhibitor (PDTC) were used to inactivate the RAGE/NF-kB signaling pathway. Results: AGEs significantly decreased trans-epithelial electrical resistance (TEER), while increased paracellular permeability (P < 0.05). TEM results showed that AGEs made the cell junction loose. Immunofluorescence, wetern blot and RT-qPCR analyses showed that AGEs significantly inhibited the expressions of ZO-1 and Occludin, while anti-RAGE or PDTC partially restored their levels. Besides, AGEs also significantly increased the expressions of mRNA RAGE and NF-kB in BeWo cells (P < 0.05), and their expressions were inhibited by anti-RAGEy or PDTC. Conclusion: AGEs could reduce the expressions of ZO-1 and Occludin by activating RAGE/NF-kB signaling pathway, thus increasing placental vascular permeability of BeWos cells. These findings would provide a novel sight for improving the development and prognosis of GDM.