bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex differences in the prevalence and determinants of HPV-related external genital lesions in young adults: a national cross-sectional survey in Brazil
Authors: Comerlato Juliana , Kops Natália Luiza , Bessel Marina , Horvath Jaqueline Driemeyer , Fernandes Bruna Vieira , Villa Luisa Lina , de Souza Flavia Moreno Alves , Pereira Gerson Fernando Mendes , Wendland Eliana Márcia
Published: September 2020

Background

External genital lesions (EGL) are the most common sexually transmitted infections (STIs). We aimed to evaluate the prevalence, determinants and sex differences in EGL among young adults from Brazil.

Methods

Overall, 7694 participants (aged 16 to 25 years) underwent an interview, genital examination and sampling for HPV genotyping.

Results

The prevalence of EGL was 4.08% (234) and is more frequent in men (5.72%) than women (2.31%) (p <  0.001). Genital lesions were significantly associated with male sex, infection by high-risk and multiple HPV types, having more than two sexual partners in the last year, smoking status and the presence of other STI. While alcohol use was associated with a higher prevalence of EGL in women, same-sex sexual relationship increase the prevalence in men. In the EGL group, 67.79% (p = 0.032) were positive for HPV infection and the types HPV6 and HPV11 were the most prevalent ones.

Conclusion

The prevalence of EGL in young adults was consistently high, and most cases were associated with genital HPV infection and STIs. Although men have a higher prevalence, both sexes share most genital lesion determinants. The promotion of sexual education and vaccination especially focus in young men, who are usually outside the targets of primary health care programmes, can prevent EGL in Brazilian young adults.
Contact tracing of syphilis-seropositive pregnant women and syphilis-infection among their male partners in Bao'an district, Shenzhen, China
Authors: Yan Ruilin , Deng Baoqing , Wen Guichun , Huang Licheng , Li Limei , Huang Zhiming
Published: September 2020

Background

Untreated male partners are a critical source of maternal re-infection. Contact tracing is a good way to identify infection among partners and reduce risk of mother-to-child transmission related to maternal re-infection. This study aimed to analyze the current situation and related factors of contact tracing of syphilis-seropositive pregnant women and syphilis-infection among their male partners.

Method

Data of syphilis-seropositive pregnant women and their male partners attending clinic for syphilis-screening were obtained from the Shenzhen Program for Prevention of Congenital Syphilis. Contact tracing rate of syphilis-seropositive pregnant women and syphilis prevalence among male partners were counted, and related factors were also analyzed using a random-effects logistic regression model.

Result

Of the 1299 syphilis-seropositive pregnant women, 74.1% (963/1299) had their male partners receiving syphilis-screening and 19.1% (184/963) of male partners were syphilis-infected. For pregnant women, being divorced (adjusted odds ratio [AOR] =0.39; 95%CI: 0.17–0.87), seeking for emergency services at their first antenatal clinics visits (AOR = 0.58; 95%CI: 0.44–0.77), reporting willingness to notify partner(AOR = 7.65; 95%CI: 4.69–12.49), multi-partners (AOR = 1.38; 95%CI:1.03–1.86) and having a history of drug abuse (AOR = 0.37; 95%CI: 0.14–1.00)were independently associated with successful contact tracing. For male partners, of minority ethnicity (AOR = 4.15; 95%CI: 1.66–10.34), age at first sex>20(AOR = 0.57; 95%CI: 0.37–0.87), reporting multi-partners (AOR = 1.60; 95%CI: 1.04–2.46), having a history of drug abuse (AOR = 4.07; 95%CI: 1.31–12.64) were independently associated with syphilis-infection. In addition, pregnant women with TRUST titer ≥1:8 (AOR = 2.81; 95%CI: 1.87–4.21), having a history of adverse pregnancy outcomes (AOR = 1.70; 95%CI: 1.14–2.53), reporting multi-partners (AOR = 0.43; 95%CI: 0.29–0.64) and reporting the current partner as the source of syphilis (AOR = 5.05; 95%CI: 2.82–9.03) were independently associated with partners’ syphilis-infection.

Conclusion

Contact tracing is feasible and effective in identifying syphilis-infected partners among syphilis-seropositive pregnant women. Contact tracing is associated with many factors such as women’s marital status, services at their first antenatal clinics visit and willingness of partner notification. Partners’ ethnicity, age at first sex, multi-partners and history of drug abuse as well as women’s levels of TRUST titer were associated with partners’ syphilis-infection.
FUT4siRNA augments the chemosensitivity of non-small cell lung cancer to cisplatin through activation of FOXO1-induced apoptosis
Authors: Gao Wei , Liang Jinxiao , Ye Yiru , Lu Jinlan , Lin Tongtong , Wang Na , Dong Jingyin , Pan Jianping
Published: September 2020

Background

Increased fucosylation is associated with the chemoresistance phenotype. Meanwhile, fucosyltransferase IV (FUT4) amounts are frequently elevated in lung cancer and may be related to increased chemoresistance.

Methods

In the present work, FUT4’s role in cisplatin-induced apoptosis was assessed in A549 and H1975 cells, respectively. To clarify whether the FUT4 gene attenuates chemosensitivity in tumor cells, we constructed FUT4siRNA and evaluated its effects on cisplatin-induced apoptosis and cell growth inhibition. Cell viability, apoptosis, migration and invasion assay were conducted to investigate cisplatin sensitivity. The activation of EGFR/AKT/FOXO1 signaling were measured by western blot. The translocation of FOXO1 was assessed by IFC using Laser Scanning Confocal Microscope.

Results

We found that FUT4 knockdown dose-dependently increased cisplatin-associated cytotoxicity. Furthermore, FUT4 silencing induced apoptosis and inhibited proliferation in A549 and H1975 cells by suppressing Akt and FOXO1 phosphorylation induced by cisplatin administration, which resulted in nuclear translocation of FOXO1.

Conclusion

These results suggested FUT4 might control chemoresistance to cisplatin in lung cancer by suppressing FOXO1-induced apoptosis.
Tourniquet use in routine primary total knee arthroplasty is associated with a higher transfusion rate and longer postoperative length of stay: a real-world study
Authors: Xu Hong , Yang Jingli , Xie Jinwei , Huang Zeyu , Huang Qiang , Cao Guorui , Pei Fuxing
Published: September 2020

Background

In an enhanced recovery after surgery program, a growing number of orthopedists are reconsidering the necessity of tourniquet use in total knee arthroplasty (TKA). However, the impact of tourniquet use on transfusion rate and postoperative length of stay (PLOS) in TKA remains controversial. Therefore, we carried out a study to investigate the effect of tourniquet application in routine primary TKA on transfusion rate and PLOS.

Methods

We analyzed data from 6325 patients who underwent primary unilateral TKA and divided them into two groups according to whether a tourniquet was applied during the procedure, and a tourniquet was used in 4902 and not used in 1423. The information for transfusion and PLOS was extracted from patients’ electronic health records, and the data were analyzed with logistic and linear regression analyses.

Results

Following TKA, the transfusion rate and PLOS were 14.52% and 7.72 ± 3.54 days, respectively, in the tourniquet group, and 6.47% and 6.44 ± 3.48 days, respectively, in the no-tourniquet group. After adjusting for the different related variables, tourniquet use was significantly correlated with a higher transfusion rate (risk ratio = 1.888, 95% confidence interval (CI) 1.449–2.461, P < 0.001) and a longer PLOS (partial regression coefficient (B) = 0.923, 95%CI 0.690–1.156, P < 0.001).

Conclusions

Our findings suggested that tourniquet use in routine primary TKA was related to a higher transfusion rate and a longer PLOS. The impact of tourniquet use on transfusion rate and PLOS should be taken into account in clinical practice.
Percutaneous-perventricular device closure of ventricular septal defect: mid-term follow-up
Authors: Wang Long , Xie Lin , Ruan Weiqiang , Li Tao , Gan Changping , Lin Ke
Published: September 2020

Background

This report presents updated data and mid-term follow-up information to a former study introducing the novel technique of percutaneous-perventricular device closure of doubly committed subarterial ventricular septal defect.

Methods

Thirty-eight patients were added to the former series. There were 54 patients in total who had isolated doubly committed subarterial ventricular septal defects and underwent percutaneous-perventricular device closure. Closure outcomes and possible complications were measured in the hospital and during the 2.5-year follow-up.

Results

Surgery was successful in 53 patients (98.1%). There was no death, residual shunt, new valve regurgitation or arrhythmia either perioperatively or during the entire follow-up period. Only one patient developed pericardial effusion and tamponade in the former series. The mean hospital stay was 3.2 ± 0.6 days (range, 3.0 to 6.0 days), and only one unsuccessful case needed blood transfusion (1.9%).

Conclusions

The percutaneous-perventricular device closure of isolated doubly committed subarterial ventricular septal defects appeared to be safe. Close monitoring for bleeding is essential postoperatively, especially in younger patients. This technique is generally safe with acceptable mid-term follow-up.
Minimum volume standards in day surgery: a systematic review
Authors: Stanak Michal , Strohmaier Christoph
Published: September 2020

Background

The aim was to find out if and for what indications are minimum volume standards (MVS) applied in the day surgery setting and whether the application of MVS improves patient relevant outcomes.

Methods

We conducted a comprehensive systematic literature search in seven databases on July 12th, 2019. Concerning effectiveness and safety, the data retrieved from the selected studies were systematically extracted into data-extraction tables. Two independent researchers (MS, CS) systematically assessed the quality of evidence using the quality assessment tool for individual studies of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) called Task Force Checklist for Quality Assessment of Retrospective Database Studies. No instances of disagreement occurred. No further data processing was applied.

Results

The systematic literature search, together with hand search, yielded 595 hits. No prospective or controlled studies were found. Data from eight retrospective studies were used in the analysis of clinical effectiveness and safety on seven indications: anterior cruciate ligament reconstruction, cataract surgery, meniscectomy, thyroidectomy, primary hip arthroscopy, open carpal tunnel release, and rotator cuff repair. All interventions (except for carpal tunnel release and thyroidectomy) confirmed a volume-outcome relationship (VOR) with relation to surgeon/hospital volume, however, none established MVS for the respective interventions. Safety related data were reported without its relationship to surgeon/hospital volume.

Conclusions

This present paper provides some evidence in favor of the VOR, however, it based on low quality retrospective data-analyses. The present results cannot offer any clear-cut MVS thresholds for the day surgery setting and so the simple transition from inpatient results (that support MVS) to the day surgery setting is questionable. Further quality assuring policy approaches should be considered.
What makes advocacy work? Stakeholders’ voices and insights from prioritisation of maternal and child health programme in Nigeria
Authors: Uzochukwu Benjamin , Onyedinma Chioma , Okeke Chinyere , Onwujekwe Obinna , Manzano Ana , Ebenso Bassey , Etiaba Enyi , Ezuma Nkoli , Mirzoev Tolib
Published: September 2020

Background

The Nigerian government introduced and implemented a health programme to improve maternal and child health (MCH) called Subsidy Reinvestment and Empowerment programme for MCH (SURE-P/MCH). It ran from 2012 and ended abruptly in 2015 and was followed by increased advocacy for sustaining the MCH (antenatal, delivery, postnatal and immunization) services as a policy priority. Advocacy is important in allowing social voice, facilitating prioritization, and bringing different forces/actors together. Therefore, the study set out to understand how advocacy works - through understanding what effective advocacy implementation processes comprise and what mechanisms are triggered by which contexts to produce the intended outcomes.

Methods

The study used a Realist Evaluation design through a mixed quantitative and qualitative methods case study approach. The programme theory (PT) was developed from three substantive social theories (power politics, media influence communication theory, and the three-streams theory of agenda-setting), data and programme design documentation, and subsequently tested. We report information from 22 key informant interviews including national and State policy and law makers, policy implementers, CSOs, Development partners, NGOs, health professional groups, and media practitioners and review of relevant documents on advocacy events post-SURE-P.

Results

Key advocacy organizations and individuals including health professional groups, the media, civil society organizations, powerful individuals, and policymakers were involved in advocacy activities. The nature of their engagement included organizing workshops, symposiums, town hall meetings, individual meetings, press conferences, demonstrations, and engagements with media. Effective advocacy mechanism involved alliance brokering to increase influence, the media supporting and engaging in advocacy, and the use of champions, influencers, and spouses (Leadership and Elite Gendered Power Dynamics). The key contextual influences which determined the effectiveness of advocacy measures for MCH included the political cycle, availability of evidence on the issue, networking with powerful and interested champions, and alliance building in advocacy. All these enhanced the entrenchment of MCH on the political and financial agenda at the State and Federal levels.

Conclusions

Our result suggest that advocacy can be a useful tool to bring together different forces by allowing expression of voices and ensuring accountability of different actors including policymakers. In the context of poor health outcomes, interest from policymakers and politicians in MCH, combined with advocacy from key policy actors armed with evidence, can improve prioritization and sustained implementation of MCH services.
Colon capsule endoscopy versus CT colonography in FIT-positive colorectal cancer screening subjects: a prospective randomised trial—the VICOCA study
Authors: González-Suárez Begoña , Pagés Mario , Araujo Isis Karina , Romero Cristina , Rodríguez de Miguel Cristina , Ayuso Juan Ramón , Pozo Àngels , Vila-Casadesús Maria , Serradesanferm Anna , Ginès Àngels , Fernández-Esparrach Glòria , Pellisé Maria , López-Cerón María , Flores David , Córdova Henry , Sendino Oriol , Grau Jaume , Llach Josep , Serra-Burriel Miquel , Cárdenas Andrés , Balaguer Francesc , Castells Antoni
Published: September 2020

Background

Colon capsule endoscopy (CCE) and CT colonography (CTC) are minimally invasive techniques for colorectal cancer (CRC) screening. Our objective is to compare CCE and CTC for the identification of patients with colorectal neoplasia among participants in a CRC screening programme with positive faecal immunochemical test (FIT). Primary outcome was to compare the performance of CCE and CTC in detecting patients with neoplastic lesions.

Methods

The VICOCA study is a prospective, single-centre, randomised trial conducted from March 2014 to May 2016; 662 individuals were invited and 349 were randomised to CCE or CTC before colonoscopy. Endoscopists were blinded to the results of CCE and CTC.

Results

Three hundred forty-nine individuals were included: 173 in the CCE group and 176 in the CTC group. Two hundred ninety individuals agreed to participate: 147 in the CCE group and 143 in the CTC group. In the intention-to-screen analysis, sensitivity, specificity and positive and negative predictive values for the identification of individuals with colorectal neoplasia were 98.1%, 76.6%, 93.7% and 92.0% in the CCE group and 64.9%, 95.7%, 96.8% and 57.7% in the CTC group. In terms of detecting significant neoplastic lesions, the sensitivity of CCE and CTC was 96.1% and 79.3%, respectively. Detection rate for advanced colorectal neoplasm was higher in the CCE group than in the CTC group (100% and 93.1%, respectively; RR = 1.07; p = 0.08). Both CCE and CTC identified all patients with cancer. CCE detected more patients with any lesion than CTC (98.6% and 81.0%, respectively; RR = 1.22; p = 0.002).

Conclusion

Although both techniques seem to be similar in detecting patients with advanced colorectal neoplasms, CCE is more sensitive for the detection of any neoplastic lesion.

Trial registration

ClinicalTrials.gov Identifier: NCT02081742. Registered: September 16, 2013.
Cepharanthine and Curcumin inhibited mitochondrial apoptosis induced by PCV2
Authors: Xu Yinlan , Zheng Jiangang , Sun Panpan , Guo Jianhua , Zheng Xiaozhong , Sun Yaogui , Fan Kuohai , Yin Wei , Li Hongquan , Sun Na
Published: September 2020

Background

Porcine circovirus type 2 (PCV2) is an immunosuppressive pathogen with high prevalence rate in pig farms. It has caused serious economic losses to the global pig industry. Due to the rapid mutation of PCV2 strain and co-infection of different genotypes, vaccination could not eradicate the infection of PCV2. It is necessary to screen and develop effective new compounds and explore their anti-apoptotic mechanism. The 13 natural compounds were purchased, with a clear plant origin, chemical structure and content and specific biological activities.

Results

The maximum no-cytotoxic concentration (MNTC) and 50% cytotoxic concentration (CC50) of 13 tested compounds were obtained by the cytopathologic effect (CPE) assay and (3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method in PK-15 cells. The results of qPCR and Western blot showed that, compared with the PCV2 infected group, the expression of Cap in Paeonol (0.4 mg/mL and 0.2 mg/mL), Cepharanthine (0.003 mg/mL, 0.0015 mg/mL and 0.00075 mg/mL) and Curcumin (0.02 mg/mL, 0.001 mg/mL and 0.005 mg/mL) treated groups were significantly lowered in a dose-dependent manner. The results of Annexin V-FITC/PI, JC-1, Western blot and ROS analysis showed that the expression of cleaved caspase-3 and Bax were up-regulated Bcl-2 was down-regulated in Cepharanthine or Curcumin treated groups, while ROS and MMP value were decreased at different degrees and the apoptosis rate was reduced. In this study, Ribavirin was used as a positive control.

Conclusions

Paeonol, Cepharanthine and Curcumin have significant antiviral effect. And the PCV2-induced Mitochondrial apoptosis was mainly remitted by Cepharanthine and Curcumin.
Genome scale analysis of pathogenic variants targetable for single base editing
Authors: Lavrov Alexander V. , Varenikov Georgi G. , Skoblov Mikhail Yu
Published: September 2020

Background

Single nucleotide variants account for approximately 90% of all known pathogenic variants responsible for human diseases. Recently discovered CRISPR/Cas9 base editors can correct individual nucleotides without cutting DNA and inducing double-stranded breaks. We aimed to find all possible pathogenic variants which can be efficiently targeted by any of the currently described base editors and to present them for further selection and development of targeted therapies.

Methods

ClinVar database (GRCh37_clinvar_20171203) was used to search and select mutations available for current single-base editing systems. We included only pathogenic and likely pathogenic variants for further analysis. For every potentially editable mutation we checked the presence of PAM. If a PAM was found, we analyzed the sequence to find possibility to edit only one nucleotide without changing neighboring nucleotides. The code of the script to search Clinvar database and to analyze the sequences was written in R and is available in the appendix.

Results

We analyzed 21 editing system currently reported in 9 publications. Every system has different working characteristics such as the editing window and PAM sequence. C > T base editors can precisely target 3196 mutations (46% of all pathogenic T > C variants), and A > G editors – 6900 mutations (34% of all pathogenic G > A variants).

Conclusions

Protein engineering helps to develop new enzymes with a narrower window of base editors as well as using new Cas9 enzymes with different PAM sequences. But, even now the list of mutations which can be targeted with currently available systems is huge enough to choose and develop new targeted therapies.
Cancer gene expression profiles associated with clinical outcomes to chemotherapy treatments
Authors: Borisov Nicolas , Sorokin Maxim , Tkachev Victor , Garazha Andrew , Buzdin Anton
Published: September 2020

Background

Machine learning (ML) methods still have limited applicability in personalized oncology due to low numbers of available clinically annotated molecular profiles. This doesn’t allow sufficient training of ML classifiers that could be used for improving molecular diagnostics.

Methods

We reviewed published datasets of high throughput gene expression profiles corresponding to cancer patients with known responses on chemotherapy treatments. We browsed Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Tumor Alterations Relevant for GEnomics-driven Therapy (TARGET) repositories.

Results

We identified data collections suitable to build ML models for predicting responses on certain chemotherapeutic schemes. We identified 26 datasets, ranging from 41 till 508 cases per dataset. All the datasets identified were checked for ML applicability and robustness with leave-one-out cross validation. Twenty-three datasets were found suitable for using ML that had balanced numbers of treatment responder and non-responder cases.

Conclusions

We collected a database of gene expression profiles associated with clinical responses on chemotherapy for 2786 individual cancer cases. Among them seven datasets included RNA sequencing data (for 645 cases) and the others – microarray expression profiles. The cases represented breast cancer, lung cancer, low-grade glioma, endothelial carcinoma, multiple myeloma, adult leukemia, pediatric leukemia and kidney tumors. Chemotherapeutics included taxanes, bortezomib, vincristine, trastuzumab, letrozole, tipifarnib, temozolomide, busulfan and cyclophosphamide.
Circulating Receptor Activator of Nuclear Factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in type 2 diabetes: a prospective, observational cohort study
Authors: Bourron Olivier , Phan Franck , Diallo Mamadou Hassimiou , Hajage David , Aubert Carole-Elodie , Carlier Aurélie , Salem Joe-Elie , Funck-Brentano Christian , Kemel Salim , Cluzel Philippe , Redheuil Alban , Davaine Jean-Michel , Massy Ziad , Mentaverri Romuald , Bonnefont-Rousselot Dominique , Gillery Philippe , Jaisson Stéphane , Vermeer Cees , Lacorte Jean-Marc , Bouziri Nesrine , Laroche Suzanne , Amouyal Chloé , Hartemann Agnes
Published: September 2020

Background

Lower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes.

Methods

Lower limb arterial calcification scores were determined by computed tomography at baseline and after a mean follow up of 31.20 ± 3.86 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and metabolic parameters were measured at baseline. The predictive effect of these markers on calcification progression was analyzed by a multivariate linear regression model.

Results

At baseline, mean ± SD and median lower limb arterial calcification scores were, 2364 ± 5613 and 527 respectively and at the end of the study, 3739 ± 6886 and 1355 respectively. Using multivariate analysis, the progression of lower limb arterial log calcification score was found to be associated with (β coefficient [slope], 95% CI, p-value) baseline log(calcification score) (1.02, 1.00–1.04, p < 0.001), triglycerides (0.11, 0.03–0.20, p = 0.007), log(RANKL) (0.07, 0.02–0.11, p = 0.016), previous ischemic cardiomyopathy (0.36, 0.15–0.57, p = 0.001), statin use (0.39, 0.06–0.72, p = 0.023) and duration of follow up (0.04, 0.01–0.06, p = 0.004).

Conclusion

In patients with type 2 diabetes, lower limb arterial calcification is frequent and can progress rapidly. Circulating RANKL and triglycerides are independently associated with this progression. These results open new therapeutic perspectives in peripheral diabetic calcifying arteriopathy.

Trial registrationNCT02431234
An analysis of the strategic plan development processes of major public organisations funding health research in nine high-income countries worldwide
Authors: Morciano Cristina , Errico Maria Cristina , Faralli Carla , Minghetti Luisa
Published: September 2020

Background

There have been claims that health research is not satisfactorily addressing healthcare challenges. A specific area of concern is the adequacy of the mechanisms used to plan investments in health research. However, the way organisations within countries devise research agendas has not been systematically reviewed. This study seeks to understand the legal basis, the actors and the processes involved in setting research agendas in major public health research funding organisations.

Methods

We reviewed information relating to the formulation of strategic plans by 11 public funders in nine high-income countries worldwide. Information was collected from official websites and strategic plan documents in English, French, Italian and Spanish between January 2019 and December 2019, by means of a conceptual framework and information abstraction form.

Results

We found that the formulation of a strategic plan is a common and well-established practice in shaping research agendas across international settings. Most of the organisations studied are legally required to present a multi-year strategic plan. In some cases, legal provisions may set rules for actors and processes and may establish areas of research and/or types of research to be funded. Commonly, the decision-making process involves both internal and external stakeholders, with the latter being generally government officials and experts, and few examples of the participation of civil society. The process also varies across organisations depending on whether there is a formal requirement to align to strategic priorities developed by an overarching entity at national level. We also found that, while actors and their interactions were traceable, information, sources of information, criteria and the mechanisms/tools used to shape decisions were made less explicit.

Conclusions

A complex picture emerges in which multiple interactive entities appear to shape research plans. Given the complexity of the influences of different parties and factors, the governance of the health research sector would benefit from a traceable and standardised knowledge-based process of health research strategic planning. This would provide an opportunity to demonstrate responsible budget stewardship and, more importantly, to make efforts to remain responsive to healthcare challenges, research gaps and opportunities.
Assessment of the quality of recommendations from 161 clinical practice guidelines using the Appraisal of Guidelines for Research and Evaluation–Recommendations Excellence (AGREE-REX) instrument shows there is room for improvement
Authors: Florez Ivan D. , Brouwers Melissa C. , Kerkvliet Kate , Spithoff Karen , Alonso-Coello Pablo , Burgers Jako , Cluzeau Francoise , Férvers Beatrice , Graham Ian , Grimshaw Jeremy , Hanna Steven , Kastner Monika , Kho Michelle , Qaseem Amir , Straus Sharon
Published: September 2020

Objective

To assess the quality of recommendations from 161 clinical practice guidelines (CPGs) using AGREE-REX-D (Appraisal of Guidelines REsearch and Evaluation-Recommendations Excellence Draft).

Design

Cross-sectional study

Setting

International CPG community.

Participants

Three hundred twenty-two international CPG developers, users, and researchers.

Intervention

Participants were assigned to appraise one of 161 CPGs selected for the study using the AGREE-REX-D tool

Main outcome measures

AGREE-REX-D scores of 161 CPGs (7-point scale, maximum 7).

Results

Recommendations from 161 CPGs were appraised by 322 participants using the AGREE-REX-D. CPGs were developed by 67 different organizations. The total overall average score of the CPG recommendations was 4.23 (standard deviation (SD) = 1.14). AGREE-REX-D items that scored the highest were (mean; SD): evidence (5.51; 1.14), clinical relevance (5.95; SD 0.8), and patients/population relevance (4.87; SD 1.33), while the lowest scores were observed for the policy values (3.44; SD 1.53), local applicability (3,56; SD 1.47), and resources, tools, and capacity (3.49; SD 1.44) items. CPGs developed by government-supported organizations and developed in the UK and Canada had significantly higher recommendation quality scores with the AGREE-REX-D tool (p < 0.05) than their comparators.

Conclusions

We found that there is significant room for improvement of some CPGs such as the considerations of patient/population values, policy values, local applicability and resources, tools, and capacity. These findings may be considered a baseline upon which to measure future improvements in the quality of CPGs.
Acceleration of bone union by in situ-formed hydrogel containing bone morphogenetic protein-2 in a mouse refractory fracture model
Authors: Shoji Shintaro , Uchida Kentaro , Satio Wataru , Sekiguchi Hiroyuki , Inoue Gen , Miyagi Masayuki , Takata Ken , Yokozeki Yuji , Takaso Masashi
Published: September 2020

Background

An enzymatic crosslinking strategy using hydrogen peroxide and horseradish peroxidase is receiving increasing attention for application with in situ-formed hydrogels (IFHs). Several studies have reported the application of IFHs in cell delivery and tissue engineering. IFHs may also be ideal carrier materials for bone repair, although their potential as a carrier for bone morphogenetic protein (BMP)-2 has yet to be examined. Here, we examined the effect of an IFH made of hyaluronic acid (IFH-HA) containing BMP-2 in promoting osteogenesis in a mouse refractory fracture model.

Methods

Immediately following a fracture procedure, animals either received no treatment (control) or an injection of IFH-HA/PBS or IFH-HA containing 2 μg BMP-2 (IFH-HA/BMP-2) into the fracture site (n = 16, each treatment).

Results

Fracture sites injected with IFH-HA/BMP-2 showed significantly greater bone volume, bone mineral content, and bone union compared with sites receiving no treatment or treated with IFH-HA/PBS alone (each n = 10). Gene expression levels of osteogenic markers, Alpl, Bglap, and Osx, were significantly raised in the IFH-HA/BMP-2 group compared to the IFH-HA/PBS and control groups (each n = 6).

Conclusion

IFH-HA/BMP-2 may contribute to the treatment of refractory fractures.
Promoting functions of microRNA-29a/199B in neurological recovery in rats with spinal cord injury through inhibition of the RGMA/STAT3 axis
Authors: Yang Weijie , Sun Ping
Published: September 2020

Background

The prognostic and therapeutic potential of microRNAs (miRNAs) in spinal cord injury (SCI) has aroused increasing concerns. This study aims to research the functions of miR-29a/199B in the neurological function recovery after SCI and the mechanical mechanism.

Methods

A rat model with SCI was induced with sham-operated ones as control. The locomotor function and coordination of rat hindlimbs were determined by a Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and a ladder-climbing test, respectively. Expression of a neurofilament protein NF-200 and synaptophysin in gray matter of rats was determined to evaluate neuronal recovery in a cellular perspective. Binding relationships between miR-29a/199B with RGMA were predicted and validated using luciferase assays. Altered expression of miR-29a/199B and RGMA was introduced to explore their functions in rat neurological functions. The protein level and phosphorylation of STAT3 in gray matter were measured by western blot analysis.

Results

miR-29a and miR-199B were poorly expressed, while RGMA was abundantly expressed in gray matter at injury sites. Either miR-29a or miR-199B could bind to RGMA. Overexpression of miR-29a/199B or silencing of RGMA led to an increase in BBB locomotor scores, hindlimb coordination ability, and the expression of NF-200 and synaptophysin in gray matter. Further inhibition in miR-29a/199B blocked the promoting roles of RGMA silencing in neurological recovery. Upregulation of miR-29a/199B or downregulation of RGMA suppressed the phosphorylation of STAT3.

Conclusion

This study evidenced that miR-29a and miR-199B negatively regulated RGMA to suppress STAT3 phosphorylation, therefore promoting the neurological function recovery in rats following SCI.
Incidence and risk factors associated with postoperative stroke in the elderly patients undergoing hip fracture surgery
Authors: Yu Lili , Zhu Yanbin , Chen Wei , Bu Hui , Zhang Yingze
Published: September 2020

Objectives

Stroke is one of the rare but devastating complications after hip fracture in the elderly. By far, there is still scarce data on postoperative stroke in elderly patients with hip fractures.

Methods

This was a retrospective study of prospectively collected data. Between October 2014 to December 2018, patients aged above 65 years who underwent operative treatment for hip fractures were included. Inpatient medical surveillance and scheduled telephone follow-up at 1, 3, 6, and 12 months after operation was conducted to identify who developed an incident stroke. Variables of interests were extracted from patients’ inpatient medical records. Univariate analysis and multivariate logistic regression analysis were used to identify the independent risk factors associated with stroke.

Results

During the study period, a total of 3743 patients were included, among whom 56 were found to have a stroke after operation, representing an incidence of 1.5% (95% CI, 1.1 to 1.9%). The multivariate analyses showed that advanced age (1-year increment; OR, 1.32; 95% CI, 1.08 to 1.48), history of previous stroke (OR, 4.79; 95% CI, 1.86 to 6.56), ASA III and above (OR, 2.62; 95% CI, 1.27 to 3.68), long-term use of aspirin (OR, 3.63; 95% CI, 1.41 to 4.78), and elevated RDW level (each increment of 1%, OR, 1.21; 95% CI, 1.02 to 1.36) were independently associated with postoperative stroke.

Conclusions

Although most are not modifiable, these risk factors help in counseling patients regarding the risk of postoperative stroke, individual risk stratification, and targeted optimization of medical conditions and should be firmly kept in treating surgeon’s mind.
microRNA-1271-5p/TIAM1 suppresses the progression of ovarian cancer through inactivating Notch signaling pathway
Authors: Han Feng-Juan , Li Jia , Shen Ying , Guo Ying , Liu Yi-Chao , Yu Yang , Xu Jia-Yue , Liu Shao-Xuan , Wang Yan-Hong
Published: September 2020

Objective

Ovarian cancer (OC) has been regarded as the most malignant gynecological neoplasm and often confers grave outcomes owing to the frequent metastasis and high recurrence. A previous study has demonstrated that miR-1271-5p is implicated in OC progression, however, the possible mechanism of it remains unknown. The purpose of this investigation was to explore how miR-1271-5p regulates the progression of OC.

Methods

Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were employed to analyze the differentially expressed miRNAs or genes as well as their corresponding prognostic values. miR-1271-5p expression in OC cells was examined by qRT-PCR. Cell counting kit 8 (CCK-8), colony formation, and transwell tests were conducted to evaluate the proliferation, migration and invasion potentials. Bioinformatics prediction and luciferase activity analysis were utilized to predict and verify the target gene of miR-1271-5p. Western blot assay was carried out to measure protein expression.

Results

miR-1271-5p was significantly decreased in OC and its down-regulation was associated with the grave outcome of OC patients. Upregulation of miR-1271-5p inhibited cell viability, but miR-1271-5p knockdown promoted the proliferation of OC cells. TIAM1 was a direct target gene of miR-1271-5p and expressed in OC tissues at higher level. High expression of TIAM1 induced the poorer prognosis of patients with OC. Further functional analyses showed that the suppressive role of miR-1271-5p on OC cell malignant behaviors was overturned by the upregulation of TIAM1. The protein levels of Cyclin D1, HES1, NOTCH and NUMB were remarkably changed due to the abnormal expression of miR-1271-5p and TIAM1.

Conclusion

To sum up, miR-1271-5p inhibits proliferation, invasion and migration of OC cells by directly repressing TIAM1 to inactivate the Notch signaling pathway, which provides an alternative therapeutic candidate for the advancement of OC treatment.
Sinc-Galerkin method for solving the time fractional convection–diffusion equation with variable coefficients
Authors: Chen Li Juan , Li MingZhu , Xu Qiang
Published: September 2020

In this paper, a new numerical algorithm for solving the time fractional convection–diffusion equation with variable coefficients is proposed. The time fractional derivative is estimated using the$L_{1}$L1formula, and the spatial derivative is discretized by the sinc-Galerkin method. The convergence analysis of this method is investigated in detail. The numerical solution is$2-\alpha$2−αorder accuracy in time and exponential rate of convergence in space. Finally, some numerical examples are given to show the effectiveness of the numerical scheme.
Design of nonstandard computational method for stochastic susceptible–infected–treated–recovered dynamics of coronavirus model
Authors: Shatanawi Wasfi , Raza Ali , Arif Muhammad Shoaib , Abodayeh Kamaledin , Rafiq Muhammad , Bibi Mairaj
Published: September 2020

The current effort is devoted to investigating and exploring the stochastic nonlinear mathematical pandemic model to describe the dynamics of the novel coronavirus. The model adopts the form of a nonlinear stochastic susceptible-infected-treated-recovered system, and we investigate the stochastic reproduction dynamics, both analytically and numerically. We applied different standard and nonstandard computational numerical methods for the solution of the stochastic system. The design of a nonstandard computation method for the stochastic system is innovative. Unfortunately, standard computation numerical methods are time-dependent and violate the structure properties of models, such as positivity, boundedness, and dynamical consistency of the stochastic system. To that end, convergence analysis of nonstandard computational methods and simulation with a comparison of standard computational methods are presented.
A de novo frameshift pathogenic variant in TBR1 identified in autism without intellectual disability
Authors: Sapey-Triomphe Laurie-Anne , Reversat Julie , Lesca Gaëtan , Chatron Nicolas , Bussa Marina , Mazoyer Sylvie , Schmitz Christina , Sonié Sandrine , Edery Patrick
Published: September 2020

Abstract

Background

In order to be able to provide accurate genetic counseling to patients with Autism Spectrum Disorder (ASD), it is crucial to identify correlations between heterogeneous phenotypes and genetic alterations. Among the hundreds of de novo pathogenic variants reported in ASD, single-nucleotide variations and small insertions/deletions were reported in TBR1. This gene encodes a transcription factor that plays a key role in brain development. Pathogenic variants in TBR1 are often associated with severe forms of ASD, including intellectual disability and language impairment.

Methods

Adults diagnosed with ASD but without intellectual disability (diagnosis of Asperger syndrome, according to the DSM-IV) took part in a genetic consultation encompassing metabolic assessments, a molecular karyotype and the screening of a panel of 268 genes involved in intellectual disability, ASD and epilepsy. In addition, the patient reported here went through a neuropsychological assessment, structural magnetic resonance imaging and magnetic resonance spectroscopy measurements.

Results

Here, we report the case of a young adult male who presents with a typical form of ASD. Importantly, this patient presents with no intellectual disability or language impairment, despite a de novo heterozygous frameshift pathogenic variant in TBR1, leading to an early premature termination codon (c.26del, p.(Pro9Leufs*12)).

Conclusion

Based on this case report, we discuss the role of TBR1 in general brain development, language development, intellectual disability and other symptoms of ASD. Providing a detailed clinical description of the individuals with such pathogenic variants should help to understand the genotype-phenotype relationships in ASD.
Retraction Note: Evaluation of obstructed defecation syndrome (ODS) using magnetic resonance defecography (MRD)
Authors: Parry Arshed Hussain , Wani Abdul Haseeb
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
Mitochondrial Dysfunction in Obesity and Reproduction
Authors: Das Manasi , Sauceda Consuelo , Webster Nicholas J G
Published: September 2020

Mounting evidence suggests a role for mitochondrial dysfunction in the pathogenesis of many diseases, including type 2 diabetes, aging, and ovarian failure. Because of the central role of mitochondria in energy production, heme biosynthesis, calcium buffering, steroidogenesis, and apoptosis signaling within cells, understanding the molecular mechanisms behind mitochondrial dysregulation and its potential implications in disease is critical. This review will take a journey through the past and summarize what is known about mitochondrial dysfunction in various disorders, focusing on metabolic alterations and reproductive abnormalities. Evidence is presented from studies in different human populations, and rodents with genetic manipulations of pathways known to affect mitochondrial function.
Carbon Dioxide Absorption During Inhalation Anesthesia: A Modern Practice
Authors: Feldman Jeffrey M. , Hendrickx Jan , Kennedy R. Ross
Published: September 2020

CO2 absorbents were introduced into anesthesia practice in 1924 and are essential when using a circle system to minimize waste by reducing fresh gas flow to allow exhaled anesthetic agents to be rebreathed. For many years, absorbent formulations consisted of calcium hydroxide combined with strong bases like sodium and potassium hydroxide. When Sevoflurane and Desflurane were introduced, the potential for toxicity (compound A and CO, respectively) due to the interaction of these agents with absorbents became apparent. Studies demonstrated that strong bases added to calcium hydroxide were the cause of the toxicity, but that by eliminating potassium hydroxide and reducing the concentration of sodium hydroxide to <2%, compound A and CO production is no longer a concern. As a result, CO2 absorbents have been developed that contain little or no sodium hydroxide. These CO2 absorbent formulations can be used safely to minimize anesthetic waste by reducing fresh gas flow to approach closed-circuit conditions. Although absorbent formulations have been improved, practices persist that result in unnecessary waste of both anesthetic agents and absorbents. While CO2 absorbents may seem like a commodity item, differences in CO2 absorbent formulations can translate into significant performance differences, and the choice of absorbent should not be based on unit price alone. A modern practice of inhalation anesthesia utilizing a circle system to greatest effect requires reducing fresh gas flow to approach closed-circuit conditions, thoughtful selection of CO2 absorbent, and changing absorbents based on inspired CO2.
Intraoperative Intravascular Effect of Lactated Ringer’s Solution and Hyperoncotic Albumin During Hemorrhage in Cystectomy Patients
Authors: Löffel Lukas M. , Hahn Robert G. , Engel Dominique , Wuethrich Patrick Y
Published: September 2020

BACKGROUND:

The intraoperative effect of 20% albumin on plasma volume during surgery involving major blood loss has not been explored extensively due to methodological difficulties. Crystalloids poorly expand the plasma volume, and using a colloid might then be a way to avoid fluid overload. As doubts have been raised about synthetic colloids, albumin solutions are currently used more extensively. This study presents a methodological development showing how plasma volume expansion can be studied in surgical settings with the coinfusion of 20% albumin and lactated Ringer’s solution.

METHODS:

In this single-arm, single-center feasibility study, an intravenous (i.v.) infusion of 3 mL·kg·BW−1 of 20% albumin was administered over 30 minutes to 23 cystectomy patients during the bleeding phase in addition to lactated Ringer’s solution to correct blood loss. Blood samples were measured at regular intervals over a period of 300 minutes to estimate the blood volume expansion resulting from simultaneous infusions of lactated Ringer’s and 20% albumin solutions, using a regression equation and the area under the volume–time curve method.

RESULTS:

Mean hemorrhage was 974 mL (standard deviation [SD] ± 381). The regression method showed strong correlation (r
2 = 0.58) between blood loss minus blood volume expansion and the independent effects of the infused volume of lactated Ringer’s and 20% albumin solutions. The mean plasma volume expansion attributable to the infusion of lactated Ringer’s solution amounted to 0.38 (95% confidence interval [CI], 0.31–0.49) of the infused volume; for the 20% albumin, it was 1.94 mL/mL (95% CI, 1.41–2.46 mL/mL) over 5 hours on average (regression method). The mean within-patient change was 0.20 mL/mL (± 0.06 mL/mL) for the lactated Ringer’s solution and 2.20 mL/mL (±1.31 mL/mL) for the 20% albumin using the area under the volume–time curve method.

CONCLUSIONS:

Blood volume expansion averaged 1.9–2.2 times the infused volume of 20% albumin during surgery associated with hemorrhage of around 1000 mL. This effect was long standing and approximately 5 times stronger than for the lactated Ringer’s solution. Twenty percent albumin boosts the plasma volume expansion of lactated Ringer’s solution to as high as 40% of the infused volume on the average, which is an effect that lasts at least 5 hours.
Methemoglobinemia Unmasked by Use of Sodium Nitroprusside and Hypothermia in a Case of Chronic Thromboembolic Pulmonary Hypertension During Pulmonary Endarterectomy: A Case Report
Authors: Nair Hema C. , Jeyabalan Salome , Punnen Julius , Shetty Devi Prasad
Published: September 2020

In performing pulmonary endarterectomy (PEA) for a patient with chronic thromboembolic pulmonary hypertension (CTEPH), we encountered methemoglobinemia that was unmasked by hypothermia while on cardiopulmonary bypass (CPB). The patient on dapsone therapy for antiphospholipid antibody syndrome had developed acquired methemoglobinemia that went undiagnosed because her cyanosis was believed to be due to CTEPH and the resulting ventilation-perfusion (V/Q) mismatch. Although pharmacological triggers for methemoglobin are well known, causation by hypothermia is not described. Monitoring saturation while on CPB was challenging because of nonpulsatile blood flow but was overcome using cerebral oximetry.