bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and cardiovascular safety of the new estrogen-free contraceptive pill containing 4 mg drospirenone alone in a 24/4 regime.
Authors: Palacios Santiago , Colli Enrico , REGIDOR PEDRO ANTONIO
Published: September 2020

Background: A new estrogen-free contraceptive has been approved by both the FDA and more than 15 European authorities. It is composed of drospirenone (DRSP) at a dosage of 4 mg in a regimen 24/4. The molecule is known to have anti-gonadotropic, anti-mineralocorticoid, anti-estrogenic, and antiandrogenic properties. The purpose of these clinical trials with a new estrogen-free contraceptive was to introduce a contraceptive method with high efficacy and showing a profile with low cardiovascular risks.Methods: Three European and American multicenter clinical trials have been conducted in more than 2,500 patients and more than 25,000 cycles, not only demonstrating an excellent efficacy (Pearl Index of 0.73) but also investigating possible cardiovascular risks. In the USA study, 422 participants (41.9 %) had a risk factor for VTE, while in the European studies, 261 patients (16.6 %) had at least one VTE risk factor. Amount of arterial and venous thromboembolic events, hemostasiological data, blood pressure development, and ECG data were evaluated. Results: No single case of VTE was documented, no changes in hemastosiological parameters were observed, a small decrease in RR in patients with pretreatment values between 130 and 140 and/or 85 to 90 mm HG and no influence on ECG parameters were observed.Conclusions: The introduction of a new estrogen-free contraceptive with 4 mg of non-micronized drospirenone in a 24/4-day regimen expands contraception options for women as not only a high efficacy could be demonstrated during clinical trials but also a very high cardiovascular safety profile was observed even in women with cardiovascular risk factors.EudraCT registration numbers: 2010-021787-15 & 2011-002396-42. Clincaltrials.gov: NCT02269241
Transcriptome analysis reveals underlying immune response mechanism of fungal (Penicillium oxalicum) disease in Gastrodia elata Bl. f. glauca S. Chow (Orchidaceae)
Authors: Wang Yanhua , Gao Yugang , Zang Pu , Xu Yue
Published: September 2020

Background: Gastrodia elata Bl. f. glauca S. Chow is a medicinal plant. G. elata f. glauca is unavoidably infected by pathogens in their growth process. In previous work, we have successfully isolated and identified Penicillium oxalicum from fungal diseased tubers of G. elata f. glauca. As a widespread epidemic, this fungal disease seriously affected the yield and quality of G. elata f. glauca. We speculate that the healthy G. elata f. glauca might carry resistance genes, which can resist against fungal disease. In this study, healthy and fungal diseased mature tubers of G. elata f. glauca from Changbai Mountain area were used as experimental materials to help us find the potential resistance genes against fungal disease.Results: A total of 7540 differentially expressed Unigenes (DEGs) were identified (FDR<0.01, log2FC>2). The current study screened 10 potential resistance genes. They were attached to transcription factors (TFs) in plant hormone signal transduction pathway and plant pathogen interaction pathway, including WRKY22, GH3, TIFY/JAZ, ERF1, WRKY33, TGA. In addition, four of these genes were closely related to jasmonic acid signaling pathway.Conclusions: The immune response mechanism of fungal disease in G. elata f. glauca is a complex biological process, involving plant hormones such as ethylene, jasmonic acid, salicylic acid and disease-resistant transcription factors such as WRKY, TGA.
Changes in treatment strategy over time for arteriovenous malformation in a Japanese high-volume center
Authors: Komatsu Katsuya , Takagi Yasushi , Ishii Akira , Kikuchi Takayuki , Yamao Yukihiro , Yoshida Kazumichi , Miyamoto Susumu
Published: September 2020

Background: Despite rapid developments in devices used to treat arteriovenous malformation (AVM), a randomised trial of Unruptured Brain Arteriovenous malformations published in 2014 recommended conservative treatment for nonhemorrhagic AVM.Objective: The purpose of the current retrospective study was to confirm how AVM treatment in Japan has changed and to assess the safety of treatment for hemorrhagic and nonhemorrhagic AVMs.Methods: We enrolled 242 consecutive patients with AVM; each patient’s treatment was selected and performed at our hospital. The type of onset, Spetzler–Martin (S–M) grade, age, sex, selected treatment, mortality, and morbidity were compared between the first and second periods of our study.Results: In patients with grade I–III AVM, the selected treatment changed between the first and second periods; however, in grade IV and V patients, the selected treatment did not change. Overall, interventions by microsurgery alone decreased (p < 0.001), the proportion of total treatments including microsurgery decreased (p = 0.005), interventions using stereotactic radiosurgery (SRS) alone increased (p = 0.009), and interventions including SRS increased (p = 0.002). Morbidity associated with intervention was 0.92% in the first period and 0% in the second period, and mortality was 0.92% in the first period and 1.67% in the second.Conclusions: With the development of new devices, the selected treatment was changed in patients with S–M grade I–III AVM, but was not changed in patients with grade IV and V. The complication rate was low and did not change throughout the periods. These findings suggest that the safety of treatment depends on a full understanding of device development and the selection of proper treatment, not on hemorrhagic onset. Further treatment innovations are expected to change the treatment for grade IV and V AVMs.
More fuel to the fire: Some patients with non-celiac self-reported wheat sensitivity exhibit adaptive immunological responses in duodenal mucosa.
Authors: Castillo-Rodal Antonia Isabel , Furuzawa-Carballeda Janette , Pelaez-Luna Mario , Castro-Gomez Jose , Lopez-Vidal Yolanda , Uscanga Luis Federico
Published: September 2020

Background: In contrast to the well characterized Celiac Disease (CD), the clinical scenarios encompassed by non-celiac self-reported wheat sensitivity might be related to different antigens that trigger distinct immune-inflammatory reactions. Although an increased number of intestinal intraepithelial lymphocytes (IEL) is observed at the inception of both diseases, subsequent immunopathogenic pathways seem to be different. We aimed to describe the cytokine profile showcased by the duodenal mucosa of patients with self-reported wheat intolerance.Methods: In a blind, cross-sectional study, we included duodenal biopsies from 15 consecutive untreated patients with active CD, 9 individuals with self-reported NCSRWS and 10 subjects with dyspepsia without CD and food intolerances. Using Immunohistochemistry and flow- cytometry we determined the presence of pro-inflammatory cytokine expressing monocytes and monocyte-derived dendritic cells involved in innate immune activation, cytokine-driven polarization and maintenance of Th1 and Th17/Th22, and anti-inflammatory/profibrogenic cytokines. Results: The percentage of cells expressing all tested cytokines in lamina propria and epithelium was higher in CD patients than control group. Cytokines that induce and maintain Th1 and Th17 polarization were higher in CD than in NCSRWS and controls; and higher in NCSRWS compared to controls. Similar differences were detected in the expression of IL-4 and TGF- β1, while IL-10-expressing cells were lower in NCSRWS patients than in controls and CD subjects. Conclusions : NCSRWS patients exhibit components of both, innate and adaptive immune mechanisms but to a lesser extent compared to CD.
Clinical practice and postoperative rehabilitation after knee arthroscopy vary according to surgeons’ expertise: a survey among Polish Arthroscopy Society members.
Authors: Bąkowski Paweł , Bąkowska-Żywicka Kamilla , Piontek Tomasz
Published: September 2020

Background: Meniscus repair is a challenging task in knee arthroscopy. Currently, there are a variety of arthroscopic methods available for meniscus repair. The purpose of this study was to determine a consensus in meniscus tear treatment in the environment of Polish orthopaedists.Methods: A total of 205 registered orthopaedic surgeons participated in the surveys. The survey consisted of 35 questions regarding general arthroscopy and postoperative management, including physicians’ level of expertise, anaesthesia, postoperative treatment, rehabilitation and procedures performed. Comparisons were made between knee arthroscopy experts (> 100 arthroscopies performed per year) and non-experts (≤ 100 cases) on aspects of patient care.Results: The most important finding of this study was the agreement among almost all aspects of the knee arthroscopy approach. Consensus among Polish surgeons was noticed in choosing regional anaesthesia for knee arthroscopy, the lack of need for knee braces and knee medications, the of use of LMW heparin for thromboprophylaxis, 1-2 days of hospitalization, the recommendation of rehabilitation and the use of magnetic resonance as a diagnostic test for meniscus damage. Surgical expertise was significantly associated with the performance of meniscus suture procedures (p = 0.009). Experts recommended starting rehabilitation on the day of surgery (p=0.007) and were more likely to use objective physical tests (p=0.003). Non-expert surgeons recommended a longer period from meniscus suture to full-range knee motion (p=0.001) and admitted that patient age does matter for meniscus repair qualification (p=0.002).Conclusions: There is consensus among almost all issues of meniscus tear treatment in the environment of Polish orthopaedists; however, the issues of rehabilitation and the use of advanced meniscus repair techniques are associated with surgical expertise.
Influence of Severity of Infection on the Effect of Appropriate Antimicrobial Therapy for Acinetobacter baumannii Bacteremic Pneumonia
Authors: Kang Fang-Yu , How Chorng-Kuang , Wang Yung-Chih , Cheng Aristine , Yang Ya-Sung , Kuo Shu-Chen , Liu Chang-Pan , Liu Yuag-Meng , Chen Te-Li , Lee Yi-Tzu
Published: September 2020

Background The impact of appropriate antimicrobial therapy for A. baumannii bacteremic pneumonia has not been well established due to the inclusion of the three phenotypically indistinguishable Acinetobacter species and confounding factors including underlying diseases and severity of infection. This retrospective study aimed to evaluate the impact of appropriate antimicrobial therapy on 14-day mortality in A. baumannii bacteremic pneumonia patients after adjusting for risk factors. Methods This study was conducted at five medical centers in Taiwan between July 2012 and June 2016. A. baumannii species identification was performed using reference molecular methods. Risk factors for 14-day mortality were analyzed via logistic regression. The interaction between the Acute Physiology and Chronic Health Evaluation (APACHE) II score and appropriate antimicrobial therapy was assessed using the logistic model. Results A total of 336 patients with monomicrobial A. baumannii bacteremic pneumonia were included in this study. The overall 14-day mortality rate was 47.3%. The crude mortality of appropriate antimicrobial therapy was 35.9% (57 of 151 patients). Appropriate antimicrobial therapy was associated with a lower mortality after multivariate adjustment (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.34-0.97; p = 0.04), and the effect was influenced by APACHE II score (OR for interaction term, 0.0098; 95% CI, 0.0005-0.1885; p = 0.002). Further analysis demonstrated that appropriate antimicrobial therapy significantly reduced 14-day mortality among the patients with an APACHE II score >35 (OR 0.0098; 95% CI 0.0005-0.1885). Conclusion Appropriate antimicrobial therapy decreases 14-day mortality of the most severely ill patients with A. baumannii bacteremic pneumonia.
Gastrointestinal symptoms and fecal nucleic acid testing of children with 2019 coronavirus disease: a systematic review and meta-analysis
Authors: Wang Ji-Gan , Cui Hairong , Tang Huabo , Deng Xiu-li
Published: September 2020

In order to understand the clinical manifestations and incidence of gastrointestinal symptoms of coronavirus disease (COVID-19) in children and discuss the importance of fecal nucleic acid testing.We retrospectively analyzed studies on gastrointestinal symptoms and fecal nucleic acid detection in pediatric COVID-19 patients from January 1, 2020 to August 10, 2020, including prospective clinical studies and case reports. The results of fecal nucleic acid detection were analyzed systematically. Stata12.0 software was used for meta-analysis.The results showed that the most common gastrointestinal symptoms in children with COVID-19 were vomiting and diarrhea, with a total incidence of 17.7% (95% Cl: 13.9%-21.5%). However, the prevalence of gastrointestinal symptoms in other countries (21.1%, 95% CI: 16.5%-25.7%) was higher compared to China (12.9%, 95% CI: 8%-17.7%). In Wuhan, the pooled prevalence was much higher (41.3%, 95 % CI: 3.2%-79.4%) compared to areas outside Wuhan in China (7.1%, 95 % CI: 4.0%-10.3%).The positive rate of fecal nucleic acid testing in COVID-19 children was relatively high at 85.8% (91/106). Additionally, 71.2% (52/73) were still positive for fecal nucleic acid after respiratory tract specimens turned negative. One and two weeks after the respiratory tract specimens turned nucleic acid-negative, 45.2% (33/73) and 34.2% (25/73) patients, respectively, remained fecal nucleic acid-positive. The longest interval between the respiratory tract specimens turning negative and fecal specimens turning negative exceeded 70 days.Conclusions and Relevance:Gastrointestinal symptoms in pediatric COVID-19 are relatively common. Attention should be paid to the detection of fecal nucleic acids in children. Fecal nucleic acid-negative status should be considered as one of the desegregation standards.
Analyses of the Local Control of Pulmonary Oligometastases after Stereotactic Body Radiotherapy and the Impact of Local Control on Survival
Authors: Yamamoto Takaya , Niibe Yuzuru , Aoki Masahiko , Shintani Takashi , Yamada Kazunari , Kobayashi Mitsuru , Yamashita Hideomi , Ozaki Masatoki , Manabe Yoshihiko , Onishi Hiroshi , Yahara Katsuya , Nishikawa Atsushi , Katsui Kuniaki , Oh Ryoong-Jin , Terahara Atsuro , Jingu Keiichi
Published: September 2020

Background: Successful local therapy for oligometastases may lead to longer survival. The purpose of this multicentre retrospective study was to investigate factors affecting the local control (LC) of pulmonary oligometastases treated by stereotactic body radiotherapy (SBRT) and to investigate the impact of LC on survival.Methods: The inclusion criteria included 1 to 5 metastases, the primary lesion and other extrathoracic metastases were controlled before SBRT, and the biological effective dose (BED10) of the SBRT was 75 Gy or more. The Cox proportional hazards model was used for analyses.Results: Data of 1378 patients with 1547 tumours from 68 institutions were analysed. The median follow-up period was 24.2 months. The one-year, 3-year and 5-year LC rates were 92.1%, 81.3% and 78.6%, respectively, and the 1-year, 3-year and 5-year overall survival rates were 90.1%, 60.3% and 45.5%, respectively. Multivariate analysis for LC showed that increased maximum tumour diameter (p=0.011), type A dose calculation algorithm (p=0.005), shorter overall treatment time of SBRT (p=0.035) and colorectal primary origin (p<0.001 excluding oesophagus origin) were significantly associated with a lower LC rate. In the survival analysis, local failure (p<0.001), worse performance status (1 vs. 0, p=0.013; 2–3 vs. 0, p<0.001), oesophageal primary origin (vs. colorectal origin, p=0.038), squamous cell carcinoma (vs. adenocarcinoma, p=0.006) and increased maximum tumour diameter (p<0.001) showed significant relationships with shorter survival.Conclusions: Several factors of oligometastases and SBRT affected LC. LC of pulmonary oligometastases by SBRT showed a significant survival benefit compared to patients with local failure.
Design and Optimization for UAV-Enabled Two-Way Relaying System with SWIPT
Authors: Wang Jinlong , Wang Gang , Chen Guanyi , Li Bo , Zhou Ruofei , Zhang Ruoyu
Published: September 2020

In this paper, we investigate the resource allocation scheme for an unmanned-aerial-vehicle-enable (UAV-enabled) two-way relaying system with simultaneous wireless information and power transfer (SWIPT), where two userequipment exchange information with the help of UAV relay and harvest energythrough power splitting (PS) scheme. Under the transmission power constraintsat UEs and UAV relay, a non-convex intractable optimization problem isformulated which maximizes the sum retained energy of two UEs while satisfying the minimum signal-to-noise ratio requirement. We decouple the complicated beamforming and PS factors optimization problem into three solvable subproblems and propose an efficient alternating optimization scheme. Subsequently, in order to reduce the complexity, a robust scheme based on generalized singular value decomposition (GSVD) is designed. Finally, numerical results verify the robustness and effectiveness of two proposed schemes.
Accessibility of Urban Green Infrastructure in Addis Ababa City, Ethiopia: Current Status and Future Challenge
Authors: Azagew Sileshi , Worku Hailu
Published: September 2020

Background: Many studies have been conducted on the challenges underpinning the depletion and inaccessibility of urban green infrastructures (UGI) in cities of developed countries. Contrary to this, similar studies in rapidly urbanizing cities of Africa are scant. In this study, we assessed the status, accessibility and constraints of UGI in rapidly urbanizing city Addis Ababa, Ethiopia. We first mapped and calculated the status of UGI from 2003 to 2016 based on the land use data in Arch GIS. We then analyzed UGI access such as recreational parks based on proximate and per capita green indicators by using the land use maps, road network and gridded population data. Finally, we examined the challenges behind the current states of UGI based on document review, expert interview and field observation.
Results: Our study disclosed that the land use of UGI from 2003 to 2016 is decreased by 9.2%. The land use of urban agriculture decreased significantly (by 11.9%) followed by urban forest (by 3.7%). The accessibility indicators also revealed that the city residents have no sufficient recreational UGI. The city’s park per capita was very small (0.37m 2 ) compared to Ethiopian UGI standards (15m 2 ) and the large portion of the city’s population (above 90%) has no access to existing parks within the minimum walking distance thresholds. Expansion of built up environment, density, weak implementation of policies and plans, and lack of priority for UGI development were identified as the major constraints behind the current state of UGI in the city.
Conclusion: we conclude that UGI is degrading and insufficiently accessible for the city residents due to weak enforcement of development plans, density, built up area expansion, and lack of priority for UGI. Thus, strict adherence to the development plans and regulations is of paramount importance to maintain UGI in the city. Moreover, developing small to median size parks in already proposed areas, new expansion and renewal parts of the city is vital to enhance recreational park access. We hope that this study serves as a benchmark for policy and planning to ensure accessible and adequate UGI in rapidly urbanizing city Addis Ababa and beyond.
Little Akaki River Sediment Enrichment with Heavy Metals, Pollution Load and Potential Ecological Risks in Downstream, Central Ethiopia
Authors: Mekuria Deshu Mamo , Kassegne Alemnew Berhanu Berhanu , Asfaw Seyoum Leta Leta
Published: September 2020

Background: Addis Ababa City’s river ecosystem is under extreme pressure as a result of inappropriate practices of dumping domestic and industrial wastes; thus, threatening its ability to maintain basic ecological, social and economic functions. Little Akaki River which drains through Addis Ababa City receives inorganic and organic pollutants from various anthropogenic sources. Most of inorganic pollutants such as toxic heavy metals released into the river are eventually adsorbed and settle in the sediment. The objective of this study was to evaluate the enrichment levels, pollution load and ecological risks of selected heavy metals (Zn, Cr, Cd and Pb) using various indices.Results: The mean concentrations of heavy metals in Little Akaki River sediment were: Zn (78.96 ± 0.021 - 235.2 ± 0.001mg/kg); Cr (2.19 ± 0.014 - 440.8 ± 0.003 mg/kg); Cd (2.09 ± 0.001-4.16 ± 0.0001mg/kg) and Pb (30.92 ± 0.018 -596.4 ± 0.066 mg/kg). Enrichment factor values indicated that sediments were moderate to significantly enriched with Zn and Cr; moderate to very highly enriched with Pb, and very highly enriched in all sampled sites with Cd. Geo-accumulation index and contamination factor values indicated that the sediments were moderate to very highly contaminated with toxic Cd and Pb. The decreasing order of pollution load index (PLI) in downstream was: (S9) > (S4) > (S8) > (S3)> (S6) > (S10) > (S5) > (S2)> (S7) > (S1). PLI and hierarchical cluster analysis revealed that the highest pollution load occurred in the lower course of the river (S9) which may be due to metals inputs from anthropogenic sources. The ecological risk (RI =350.62) suggested that the contaminated Little Akaki River sediment can pose considerable ecological risks of pollution.Conclusions: The concentrations of Zn, Cr, Cd and Pb in Little Akaki River sediment surpassed eco-toxicological guideline limits of USEPA (threshold effect concentration) and CCME (Interim Sediment Quality Guidelines). Thus, the contaminated sediments can pose adverse biological effects on sediment dwelling organisms.
A rare presentation of superficial, inter-muscular, cystic, extra-spinal schwannoma over upper back.
Authors: Saha Srinjoy
Published: September 2020

Schwannomas are rare tumours arising from peripheral nerve sheath and are usually related to the spinal cord and spinal nerves. Contrast magnetic resonance imaging (MRI) usually helps in establishing a pre-operative diagnosis. Rarely, their manifestation may be surprisingly new. Here, a 44-year-old lady came to our clinic with a painless asymptomatic progressively enlarging swelling over her upper back. It was fluctuant, with absent neural signs and symptoms. MRI showed a benign, purely-cystic, superficial-intermuscular, extra-spinal swelling near the upper thoracic vertebrae. However, classical diagnostic signs of schwannoma were absent. Complete surgical excision was performed with smooth dissection through a well-defined plane between the lesion and surrounding muscles. A 6.5x5.0x2.5 cm oval lesion with a glistening whitish-grey capsule was excised, and the deep wound was reconstructed in multiple layers. Interestingly, it was not attached to any identifiable nerves. Histopathology showed typical hallmarks like Antoni A regions and Verocay bodies. Positive S-100 staining during immunohistochemistry established its diagnosis as schwannoma. The postoperative one-and-half-year follow-up period was uneventful. Cystic schwannomas can surprise and confuse clinicians by arising anywhere in the body and with atypical manifestations. Surgeons need to consider it in the differential diagnoses of any undiagnosed slowly-growing swelling, including purely-cystic ones and perform careful surgical dissection to avoid any inadvertent nerve damage.
Genome-wide characterization and expression analysis of the heat shock transcription factor family in pumpkin (Cucurbita moschata)
Authors: Shen Changwei , Yuan Jingping
Published: September 2020

Background: Crop quality and yield are affected by abiotic and biotic stresses, and heat shock transcription factors (Hsfs) are considered to play important roles in regulating plant tolerance under various stresses. To investigate the response of Cucurbita moschata to abiotic stress, we analyzed the genome of C. moschata. Results: In this research, a total of 36 C. moschata Hsf (CmHsf) members were identified and classified into three subfamilies (I, II, and III) according to their amino acid sequence identity. The Hsfs of the same subfamily usually exhibit a similar gene structure (intron-exon distribution) and conserved domains (DNA-binding and other functional domains). Chromosome localization analysis showed that the 36 CmHsfs were unevenly distributed on 18 of the 21 chromosomes (except for Cm_Chr00, Cm_Chr08 and Cm_Chr20), among which 18 genes formed 9 duplicated gene pairs that have undergone segmental duplication events. The Ka/Ks ratio showed that the duplicated CmHsfs have mainly experienced strong purifying selection. High-level synteny was observed between C. moschata and other Cucurbitaceae species. Conclusions: The expression profile of CmHsfs in the roots, stems, cotyledons and true leaves revealed that the CmHsfs exhibit tissue specificity. The analysis of cis-acting elements and quantitative real-time polymerase chain reaction (qRT-PCR) revealed that some key CmHsfs were activated by cold stress, heat stress, hormones and salicylic acid. This study lays the foundation for revealing the role of CmHsfs in resistance to various stresses, which is of great significance for the selection of stress-tolerant C. moschata.
Distinctive roles of syntaxin binding protein 4 and its action target, TP63, in lung squamous cell carcinoma: A theranostic study for the precision medicine
Authors: Bilguun Erkhem-Ochir , Kaira Kyoichi , Kawabata-Iwakawa Reika , Rokudai Susumu , Shimizu Kimihiro , Yokobori Takehiko , Oyama Tetsunari , Shirabe Ken , Nishiyama Masahiko
Published: September 2020

Background: Lung squamous cell carcinoma (LSCC) remains a challenging disease to treat, and further improvements in prognosis are dependent upon the identification of LSCC-specific therapeutic biomarkers and/or targets. We previously found that Syntaxin Binding Protein 4 (STXBP4) plays a crucial role in lesion growth and, therefore, clinical outcomes in LSCC patients through regulation of tumor protein p63 (TP63) ubiquitination. Methods: To clarify the impact of STXBP4 and TP63 for LSCC therapeutics, we assessed relevance of these proteins to outcome of 144 LSCC patients and examined whether its action pathway is distinct from those of currently used drugs in in vitro experiments including RNA-seq analysis through comparison with the other putative exploratory targets and/or markers.Results: Kaplan–Meier analysis revealed that, along with vascular endothelial growth factor receptor 2 (VEGFR2), STXBP4 expression signiﬁed a worse prognosis in LSCC patients, both in terms of overall survival (OS, p=0.002) and disease-free survival (DFS, p=0.041). These prognostic impacts of STXBP4 were confirmed in univariate Cox regression analysis, but not in the multivariate analysis. Whereas, TP63 (ΔNp63) closely related to OS (p=0.013), and shown to be an independent prognostic factor for poor OS in the multivariate analysis (p=0.0324). The action pathway of STXBP4 on suppression of TP63 (ΔNp63) was unique: Ingenuity pathway analysis using the knowledge database and our RNA-seq analysis in human LSCC cell lines indicated that 35 pathways were activated or inactivated in association with STXBP4, but the action pathway of STXBP4 was distinct from those of other current drug targets: STXBP4, TP63 and KDR (VEGFR2 gene) formed a cluster independent from other target genes of tumor protein p53 (TP53), tubulin beta 3 (TUBB3), stathmin 1 (STMN1) and cluster of differentiation 274 (CD274: programmed cell death 1 ligand 1, PD-L1). STXBP4 itself appeared not to be a potent predictive marker of individual drug response, but we found that TP63, main action target of STXBP4, might be involved in drug resistance mechanisms of LSCC. Conclusion: STXBP4 and the action target, TP63, could afford a key to the development of precision medicine for LSCC patients.
A sex/gender perspective on interventions to promote children’s and adolescents’ overall physical activity: Results from genEffects systematic review
Authors: Schulze Carolin , Demetriou Yolanda , Emmerling Sandra , Schlund Annegret , Phillips Susan P. , Puil Lorri , Coen Stephanie E. , Reimers Anne K.
Published: September 2020

Background To evaluate the effects of interventions on children’s and adolescents’ overall physical activity (PA) for boys and girls separately and to appraise the extent to which the studies haven taken sex/gender into account.Methods Systematic review and semi-quantitative analysis. Eleven electronic databases were searched to identify all relevant randomized and non-randomized controlled trials. Studies had to report overall PA as the main outcome to be eligible for inclusion in the review. The main outcomes of the studies is a quantified measure of overall PA. Additionally, all studies had to report sex/gender disaggregated overall PA at baseline and/or follow up and/or explain how they dealt with sex/gender during outcome analysis (i.e., sex/gender adjusted analyses) and/or report that there were no differences in the outcome when looking at sex/gender. PRISMA guidelines were followed. Two authors independently screened studies for eligibility and assessed the risk of bias. Semi-quantitative analyses were conducted to evaluate intervention effects, taking into account the extent to which studies have considered sex/gender aspects. To evaluate sex/gender considerations in primary studies, a newly developed sex/gender checklist was used. The study was registered previously (registration number CRD42018109528).Results In total, 97 articles reporting 94 unique studies with 164 outcomes for overall PA were included in the present review. Average sample size was 829 participants, ranging from five to 9,839. Participants’ ages ranged from three to 19 years. Our review shows that overall 35% of PA outcomes had significant effects in increasing overall PA of children and adolescents. Not including single sex/gender studies, 105 out of 120 PA outcomes resulted in same intervention effects for boys and girls. The interventions reported to have similar effects on PA outcomes for boys and girls showed higher quality of reporting sex/gender aspects of measurement instruments, participant flow and intervention content and materials than PA outcomes with effects only in boys or only in girls. Overall, consideration of sex/gender aspects in intervention studies is low.Conclusions There is still a need to address sufficient consideration of sex/gender aspects in developing and implementing interventions in the context of PA.
Gene expression dysregulated of Long Chain Non-coding RNA in patients with idiopathic achalasia: New Insight into Pathogenesis
Authors: Lu Chao , Zhang Hongtao , Wei Furong , Yao Xin , Yu Chaohui
Published: September 2020

The authors have requested that this preprint be withdrawn due to erroneous posting.
Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rheumatoid arthritis: a randomized controlled study
Authors: Kang Bing-xin , Xu Hui , Gao Chen-xin , Zhong Sheng , Zhang Jing , Xie Jun , Sun Song-tao , Ma Ying-hui , Xu Xi-rui , Zhao Chi , Zhai Wei-tao , Xiao Lian-bo
Published: September 2020

Background: To identify the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who have undergone primary unilateral total knee arthroplasty (TKA).Methods: For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants aged 50–75 years, with RA who underwent unilateral primary TKA were recruited. The patients received one dose of 1g IV-TXA was 10 min before skin incision, followed by articular injection 1.5 g TXA after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay.Results: Between September 2019 and May 2020, 104 participants were randomized, but 7 were lost to follow-up. The mean TBL, HBL, and maximum Hb decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. D-dimer level was lower in group B than in group A on postoperative day 1 (P < 0.001), and the incidence of thromboembolic events was similar between the two groups (P > 0.05). Conclusion: In patients with RA, three doses of postoperative IV-TXA further enabled HBL and Hb decrease without increasing the incidence of adverse events in a short period of time after TKA.Trial registration: The trial was registered in Chinese Clinical Trial Registry (ChiCTR1900025013).
Capsaicin analog supplementation is not effective to improve 10-km running time-trial performance in amateur athletes: a randomized, crossover, double-blind and placebo-controlled study
Authors: Morano Ana Elisa von Ah , Padilha Camila S. , Soares Vinicius Aparecido Matos , Machado Fabiana Andrade , Hofmann Peter , Rossi Fabrício E , Lira Fabio
Published: September 2020

Background: To investigate the acute effects of a capsaicin analogue supplement on 10-km time trial performance and physiological responses in amateur athletes. Methods: Twenty-one participants (age = 29.3 ± 5.5 years), completed two randomized, double-blind trials: capsaicin analogue condition [Capsiate (CAP) = 24 mg] or a placebo condition. The participants consumed two doses of 12 mg of capsaicin or placebo capsule 45 minutes before and immediately at the start of each trial. The time required to complete 10-km, lactate concentration, maximum heart rate (HRpeak), and rating of perceived exertion (RPE) were recorded. Results: 10-km time-trial performance (CAP = 45.07 ± 6.41 min vs. placebo = 45.13 ± 6.73, P = 0.828) was not statistically significant different between conditions. No statistically significant differences between conditions were detected for lactate concentration (P = 0.507), HRpeak (P = 0.897) and RPE (P = 0.517). Conclusion: Two doses of 12 mg Capsaicin analogue supplementation did not improve performance and physiological responses in a 10-km running time-trial in amateur athletes.
Clinical efficacy of short-term pre-operative halo-pelvic traction in the treatment of severe spinal deformities complicated with respiratory dysfunction
Authors: Qi Longtao , Xu Beiyu , Li Chunde , Wang Yu
Published: September 2020

Background Halo traction has been used as an adjunctive method in the treatment of severe spinal deformities. But there are few reports on the clinical efficacy of halo-pelvic traction (HPT) in the treatment of severe spinal deformities complicated with respiratory dysfunction. This study was to evaluate the clinical efficacy and complications associated with pre-operative HPT in the treatment of severe spinal deformities with respiratory dysfunction.Methods Thirty patients with severe spinal deformities complicated with respiratory dysfunction treated with short-term pre-operative HPT were retrospectively reviewed. Inclusion criteria were: (1) patients with severe kyphoscoliosis (coronal Cobb angle or kyphosis angle ≥100°) and respiratory failure, (2) patients undergoing HPT until posterior fusion surgery. All patients underwent general anesthesia for HPT application, which the pelvic ring used in this study was a half-ring, and the rods were all placed on the anterolateral side of the truck. Results The major coronal curve scoliosis averaged 116.00 ± 16.70° and was reduced to 63.23 ± 14.00° after HPT, 46.33 ± 10.70° after surgery. The major kyphosis was 102.40 ± 27.67° and was reduced to 52.23 ± 14.16° after HPT, 42.0 ± 11.92° after surgery. A signiﬁcantly increased FVC was observed after HPT (p<0.001), with a signiﬁcantly improved FVC% (p<0.001). Similarly, a signiﬁcantly increased FEV1 was also observed (p <0.001), with a signiﬁcantly improved FEV1% (p<0.001).Conclusion This study indicated that the modified HPT could be used to help patients with severe spinal deformities complicated with respiratory dysfunction achieve significant correction in both the coronal and sagittal deformities during the pre-operative treatment period along with improved respiratory function and in the absence of severe complications.
Are preoperative high soluble programmed death ligand 1 levels responsible for patients’ poor prognoses in hepato-biliary-pancreatic cancer?
Authors: Okada Rei , Otsuka Yuichiro , Tsuchiya Masaru , Maeda Tetsuya , Ishii Jun , Kubota Yoshihisa , Funahashi Kimihiko , Kaneko Hironori , Shimada Hideaki
Published: September 2020

Background: Several reports showed that high soluble programmed death-ligand 1(sPD-L1) level was a risk factor for poor prognosis in various tumors. To date, the clinicopathologic and prognostic impact of sPD-L1 level in patients with hepato-biliary-pancreatic cancer have not been determined. Methods: A total of 119 patients (66 patients with hepatocellular carcinoma, 23 patients with cholangiocarcinoma, 30 patients with pancreatic cancer) who were treated at the Toho University Omori Hospital (Tokyo, Japan) from 2008 to 2016 were retrospectively analyzed. sPD-L1 levels were measured using an enzyme-linked immunosorbent assay for PD-L1 to evaluate clinicopathologic and prognostic impact. Results: sPD-L1 levels were significantly higher in low-albumin group than normal albumin group. According to stages in hepatocellular carcinoma and cholangiocarcinoma, there were no significant differences in sPD-L1 levels, which gradually increased according to stage in pancreatic cancer. Using a cut-off value of 81.6pg/ml for sPD-L1level, the high sPD-L1 group showed significantly worse prognosis than the low sPD-L1 group in patients with pancreatic cancer. Multivariate analysis identified sPD-L1 level ≥ 81.6 mg/dl ( p = 0.047) as an independent predictor of poor overall survival in patients with pancreatic cancer.Conclusion: Using a cut-off value of 81.6pg/ml for sPD-L1level, high sPD-L1 levels were independently associated with poor prognosis in patients with pancreatic cancer. However, this association in hepatocellular carcinoma or cholangiocarcinoma was not clear.
Bioretention As A Control To Urban Drainage System With An Ecohydrological Base: GIS As A Tool On Decision Making
Authors: Rosa Altair , Procopiuck Mario , Macedo Marina Batalini de , Lago César Ambrogi Ferreira do , Sample David , Souza Vladimir Caramori de , Mendiondo Mario Eduardo
Published: September 2020

The occupation and use of increasingly impermeable urban land have made it difficult to infiltrate water and, consequently, increase the volume of runoff in different cities, which has required the development of bioretention techniques in the field of hydrology. The aim of this article is to define and apply criteria for the identification of areas for the construction of Bioretention systems for evaluations based on Geographic Information System indicators, considering the aspects of quantity and quality in urban drainage . The developed method allows to verify and compare changes in the surface of urban areas and their interference in the local environment , the mapping of land use and occupation to simplify procedures to define and prioritize areas for the construction of Bioretention systems, the use of resources from georeferenced bases to resolve eco-hydrological issues. The study develops technical bases for the use of a georeferencing tool to analyze areas with speed and consistency as a basis for decisions on the implementation of Bioretention systems
Fine structure of the intercalated disc and cardiac junctions in the black widow spider Latrodectus mactans
Authors: SUN Yan , LEE Seung-Min , KU Bon-Jin , Moon Myung-Jin
Published: September 2020

Arthropods have an open circulatory system with a simple tubular heart, so it has been estimated that the contractile pumping structure of the cardiac muscle will be less efficient than that of vertebrates. Nevertheless, certain arthropods are known to have far superior properties and characteristics than vertebrates, so we investigated the fine structural features of intercalated discs and cardiac junctions of cardiac muscle cells in the black widow spider Latrodectus mactans. Characteristically, the spider cardiac muscle has typical striated features and represents a functional syncytium that supports multiple connections to adjacent cells by intercalated discs. Histologically, the boundary lamina of each sarcolemma connects to the basement membrane to form an elastic sheath, and the extracellular matrix allows the cells to be anchored to other tissues. Since the intercalated disc is also part of sarcolemma, it contains gap junctions for depolarization and desmosomes that keep the fibers together during cardiac muscle contraction. Furthermore, fascia adherens and macula adherens (desmosomes) were also identified as cell junctions in both sarcolemma and intercalated discs. To enable the coordinated heartbeat of the cardiac muscle, the muscle fibers have neuronal innervations by multiple axons from the motor ganglion.
Differential kynurenine pathway metabolism in highly-metastatic aggressive breast cancer subtypes: beyond IDO1-induced immunosuppression
Authors: Heng Benjamin , Bilgin Ayse A. , Lovejoy David B , Tan Vanessa X , Milioli Heloisa Helena , Gluch Laurence , Busamante Sonia , Sabaretnam Tharani , Moscato Pablo , Lim Chai K , Guillemin Gilles J
Published: September 2020

Background: Immunotherapy has recently been proposed as a promising treatment to stop breast cancer (BrCa) progression and metastasis. However, there has been limited success in the treatment of BrCa with immune checkpoint inhibitors. This implies that BrCa tumors have other mechanism(s) to escape immune surveillance. While the kynurenine pathway (KP) is known to be a key player mediating tumor immune evasion and while there are several studies on the roles of the KP in cancer, little is known about KP involvement in BrCa.Methods: To understand how KP is regulated in BrCa, we examined the KP profile in BrCa cell lines and clinical samples (n = 1,997) that represent major subtypes of BrCa (luminal, HER2-enriched, and triple-negative (TN)). We carried out qPCR, western blot/immunohistochemistry and ultra-high pressure liquid chromatography on these samples to quantify KP enzyme gene, protein and activity respectively.Results: We revealed that the KP is highly dysregulated in the HER2-enriched and TN BrCa subtype. Gene, protein expression and KP metabolomic profiling have shown that the downstream KP enzymes KMO and KYNU are highly upregulated in the HER2-enriched and TN BrCa subtypes, leading to increased production of the potent immunosuppressive metabolites anthranilic acid (AA) and 3-hydroxylanthranilic acid (3HAA).Conclusions: Our findings suggest that KMO and KYNU inhibitors may represent new promising therapeutic targets for BrCa. We also showed that KP metabolite profiling can be used as an accurate biomarker for BrCa subtyping, as we successfully discriminated TN BrCa from other BrCa subtypes.
Improving Retention of Community-recruited Participants in HIV Prevention Research Through Saturday Household Visits; Findings from the HPTN 071 (PopART) Study in South Africa.
Authors: Bell-Mandla Nomtha Fundiswa , Sloot Rosa , Maarman Gerald , Griffith Sam , Moore Ayana , Floyd Sian , Hayes Richard , Fidler Sarah , Ayles Helen , Bock Peter
Published: September 2020

BackgroundIdentifying successful strategies to improve participant retention in longitudinal studies remains a challenge. In this study we evaluated whether non-traditional fieldworker shifts (after hours during the week and weekends) enhanced participant retention when compared to retention during traditional weekday shifts in the HPTN 071 (PopART) population cohort (PC). MethodsHPTN 071 (PopART) PC participants were recruited and followed up in their homes on an annual basis by research fieldworkers over a 3-4 year period. The average number of successful follow-up visits, where a PC participant was found and retained in the study, was calculated for each of 3 visit schedules (early weekday shift, late weekday shift, and Saturday shift), and standardized to account for variation in fieldwork shift duration. We used one-way univariate analysis of variance (ANOVA) to describe differences in mean-successful visits and 95% confidence intervals between the shift types.ResultsData on 16651 successful visits were included. Successful visit rates were higher when conducting Saturday visits (14.0; 95% CI: 11.3-16.6) compared to both regular (4.5; 95% CI: 3.7-5.3) and late weekday shifts (5.3; 95% CI: 4.7-5.8) overall and in all subgroup analyses (P<0.001). The successful visit rate was higher amongst women than men were during all shift types (3.2 vs. 1.3, p<0.001). Successful visit rates by shift type did not differ significantly by age, over time, by PC round or by community triplet. ConclusionThe number of people living with HIV continues to increase annually. High quality evidence from longitudinal studies remains critical for evaluating HIV prevention and treatment strategies. This study showed a significant benefit on participant retention through introduction of Saturday shifts for home visits and these data can make an important contribution to the emerging body of evidence for improving retention in longitudinal research. Trial registrationPopART was approved by the Stellenbosch University Health Research Ethics Committees (N12/11/074), London School of Hygiene and Tropical Medicine (6326) ethics committee and the Division of AIDS (DAIDS) (Protocol ID 11865). PopART was registered with ClinicalTrials.gov (registration number NCT01900977).
Designing a Permissioned Blockchain Network for the Halal Industry Using Hyperledger Fabric with Multiple Channels and the Raft Consensus Mechanism
Authors: Surjandari Isti , Yusuf Harman , Laoh Enrico , Maulida Rayi
Published: September 2020

Blockchain is an alternative solution that can improve the performance of the halal supply chain. Blockchain can address all the issues in the halal supply chain, such as the contamination of halal products and the disobedience of halal processes among all parties in the chain, including end customers. The type of technology suitable for this case is permissioned blockchain, in which administrators can determine the rights of each halal supply chain participant category. The determination of these rights must be done by consensus so that no party feels aggrieved. This study uses a blockchain network with three channels and the Raft consensus algorithm to design a web interface and test its capabilities. With regard to the web interface, there were no validity failures during the invoke and query tests. In addition, the web interface was also successful in thwarting the formation of a block in the case of data input errors from the user. Additionally, the server can act as a provider of information and validator of the web interface. The results of simulations conducted on the blockchain network show that the system’s transaction speed is fast, and all the transactions are successfully transferred to other peers. Thus, permissioned blockchain is useful for the halal supply chain not just because it can secure transactions while addressing halal issues but also because the transaction speed and rate of transfer data are very effective.