bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Teacher-Student Writing Conferences on Frequency and Accuracy of Using Cohesive Devices in EFL Students’ Writing
Authors: Alfalagg Abdullah Rajab
Published: June 2020

While the bulk of feedback studies have focused on written corrective feedback, oral feedback in teacher-student writing conferences in EFL context has been underexplored. This article investigated teacher oral feedback based on the tenets of sociocultural theory. It examined the impact of teacher-student writing conferences on students’ accuracy and frequency of cohesive devices employment. The study followed a quasi-experimental design with a pre-test, intervention and post-test. Data were collected from an intensive writing course for intermediate students at the college level. Based on guided-free writing prompts, the students had to write argumentative paragraphs of about 150-180 words followed by individual conference sessions to offer them oral feedback. The findings showed that oral feedback in writing conferences statistically impacted the students’ writing performance with huge effect size (Cohen’s d = 2.19). Moreover, the results demonstrated empirical evidence that writing conferences positively impacted the students’ frequency of employing referential markers (t value = -3.011; p= 0.006 < 0.05) and conjunctions (t value=-2.200; p= 0.039 < 0.05). Further, oral feedback statistically impacted the students’ accuracy of utilizing referential markers (t value= -6.874; p= 0.000 < 0.05) and conjunctions (t value= -7.253; p= 0.000 < 0.05). Writing conferences provided mediated learning experience for the students. The oral feedback assisted the students to decrease the overuse of the first, second person pronouns and the definite article ‘the’ with generic meaning in their writing. Instead, they depended on noun phrases and the third person pronouns which contributed to the text overall cohesion by creating explicit chains of references to the antecedents within the textual environment. Also, oral feedback helped the students to use conjunctions appropriately and accurately, so their texts were written densely cohesive. Pedagogical implications were discussed at the end of the article.
Key words: Teacher-student writing conferences; oral feedback; cohesion; referential markers; conjunctions; EFL students
Therapeutic potential of CKD-506, a novel selective histone deacetylase 6 inhibitor, in a murine model of rheumatoid arthritis
Authors: Park Jin Kyun , Jang Yu Jin , Oh Bo Ram , Shin Jieun , Bae Daekwon , Ha Nina , Choi Young Il , Youn Gi Soo , Park Jinseu , Lee Eun Young , Lee Eun Bong , Song Yeong-Wook
Published: June 2020

Objectives

Histone deacetylase (HDAC) 6 promotes inflammation. We investigated the anti-arthritic effects of CKD-506, a novel HDAC6 inhibitor, in vitro and in a murine model of arthritis as a novel treatment option for rheumatoid arthritis (RA).

Methods

HDAC6 was overexpressed in mouse peritoneal macrophages and RAW 264.7 cells and the effects of a HDAC6 inhibitor CKD-506 on cytokine production and activity of NF-κB and AP-1 signaling were examined. Peripheral blood mononuclear cells (PBMCs) from RA patients and fibroblast-like synoviocytes (FLS) were activated in the presence of CKD-506. Next, regulatory T cells (Treg) were induced from RA patients and co-cultured with healthy effector T cells (Teff) and cell proliferation was analyzed by flow cytometry. Finally, the effects of the inhibitor on the severity of arthritis was assessed in a murine model of adjuvant-induced arthritis (AIA).

Results

Overexpression of HDAC6 induced in macrophages to produce TNF-α and IL-6. The inhibitory effect of CKD-506 was mediated via blockade of NF-κB and AP-1 activation. HDAC6 inhibition reduced TNF-α and IL-6 production by activated RA-PBMCs. Also, CKD-506 inhibited production of MMP-1, MMP-3, IL-6 and IL-8 by activated FLS. In addition, CKD-506 inhibited proliferation of Teffs directly and indirectly by improving iTreg function. In AIA rats, oral CKD-506 improved clinical arthritis in a dose-dependent manner. A combination of sub-therapeutic CKD-506 and methotrexate exerted a synergistic effect.

Conclusion

The novel HDAC6 inhibitor CKD-506 induces regulatory immune responses in monocytes/macrophages, improves Treg function, and ameliorates arthritis severity in a murine model of RA. Thus, CKD-506 might be a novel and effective treatment option for RA.
Bioinformatic analysis reveals MIR502 as a potential tumour suppressor in ovarian cancer
Authors: Li Yan , Wang Qi , Ning Ning , Tang Fanglan , Wang Yan
Published: June 2020

Background: Ovarian cancer (OC) is a major cause of death among women due to the lack of early screening methods and its complex pathological progression. Increasing evidence has indicated that microRNAs regulate gene expression in tumours by interacting with mRNAs. Although the research regarding OC and microRNAs is extensive, the vital role of MIR502 in OC remains unclear.Methods: We integrated two microRNA expression arrays from GEO to identify differentially expressed genes. The Kaplan–Meier method was used to screen for miRNAs that had an influence on survival outcome. Upstream regulators of MIR502 were predicted by JASPAR and verified by ChIP-seq data. The LinkedOmics database was used to study genes that were correlated with MIR502. Gene Set Enrichment Analysis (GSEA) was conducted for functional annotation with GO and KEGG pathway enrichment analyses by using the open access WebGestalt tool. We constructed a PPI network by using STRING to further explore the core proteins.Results: We found that the expression level of MIR502 was significantly downregulated in OC, which was related to poor overall survival. NRF1, as an upstream regulator of MIR502, was predicted by JASPAR and verified by ChIP-seq data. In addition, anti-apoptosis and pro-proliferation genes in the Hippo signalling pathway, including CCND1, MYC, FGF1 and GLI2, were negatively regulated by MIR502, as shown in the GO and KEGG pathway enrichment results. The PPI network further demonstrated that CCND1 and MYCN were at core positions in the development of ovarian cancer. Conclusions: MIR502, which is regulated by NRF1, acts as a tumour suppressor gene to accelerate apoptosis and suppress proliferation by targeting the Hippo signalling pathway in ovarian cancer.
Moxibustion therapy on Myofascial Pain Syndrome: an evidence-based clinical practice guideline protocol
Authors: wu zenan , Xu Guixing , Xiong Jun , Zuo Zhengyun , Xie Qiongshan , Yu Xinyu
Published: June 2020

Background

Myofascial Pain syndrome (MPS) is a chronic systemic Pain disorder. Among the common treatments, moxibustion has an irreplaceable therapeutic effect and is an effective Traditional Chinese Medicine(TCM) therapy for MPS. However, the lack of clinical practice guidelines (CPGs) has prompted the publication of guidelines on the use of moxibustion in the treatment of MPS
Methods

The CPG will base on the Institute of Medicine (IOM), the World Health Organization(WHO) guideline handbook, the Grade of Recommendations Assessment, Development and Evaluation (GRADE),the Appraisal of Guidelines for Research & EvaluationⅡ (AGREEⅡ), Reporting Items for practice Guideline in Health care (RIGHT), and recommendations thereof will be made on the basis of systematic reviews. We will establish a guidelines development team that will draft clinical questions in the form of population, intervention, comparison, results (PICO) and conduct a literature search and quality of evidence assessment. The Experts will make recommendations after two or three rounds of Delphi investigations We will carefully consider the patient's values and preferences and conduct a peer review.
Ethics and dissemination:

The guidelines will not contain any personal data and will not prejudice individual rights, so no ethical approval will be required. The guidelines will be subject to rigorous peer review and may be published in a journal or circulated at relevant conferences.
Results

The guidelines will be published in relevant peer-reviewed journals.
Conclusion

This guide will make it easier for clinicians to treat MPS in the clinical setting and improve the effectiveness of treatment for MPS
Study registration:

The study is registered with the International Practice Guideline Registry Platform(IPGRP) :IPGRP-2020CN030
Modelling Community Participatory Systems to Improve Health Care interventions for Adolescents in Latin America
Authors: Cordova-Pozo Kathya Lorena , Hagens Arnold , Sojo-Milano Mayira , Auquilla Nancy , Cruz Francisca
Published: June 2020

BackgroundCommunity participation is a systematic process where a group of people unites with the intention to solve a common problem. Although it is not new, every project adopts their own vision of participation which could impact differently to the outcomes of the project and may not lead to improve their original situation. The goal of this study was to model the interrelationship of Participatory Action Research (PAR) with the improvement of health that adds up to Community Development (CD) and describe the implementation in recent projects in Latin America.MethodsThe approach of this research is qualitative and intends to construct a framework that displays the relationshipbetweenPAR-CDtolater assess the implementation of seven Latin American projects. Group Model Building (GMB) and document assessment were used as methods.ResultsAdynamic system model is presented.The target variable is CD while control variables are the situation analysis, stakeholders, policy, bidirectional contribution, context-based for cultural-social-ethical, evidence-based and availability of resources.In the document assessment some missing elements were identified like dynamics of time, evidence base, cost-effectiveness, availability of resources, feasibility, replicability, sustainability, and scalability.ConclusionsThis research demonstrates that success of PAR-CD depends on a complex and dynamic system that contains causal loops and control factors. It alsoevidences the gap between an ideal model and what is implemented of PAR-CDgivingopportunities for improvement.Trial registration: Permission to conduct this study was granted by a research ethics committee at Colegio Medico de Cochabamba, Bolivia.
Application of Digital Subtraction Angiography in Canine Hindlimb Arteriography
Authors: Chen Tiannan , Wang Xue , Wang Chengwei , Zhang Shiyong , Wang Jie
Published: June 2020

BACKGROUND: Research in the field of lower extremity vascular disease has increased in popularity over the years. In order to properly characterize and validate the effectiveness of interventions, in vivo experimentation in large animals is required. Thus, it is necessary to find a method to detect the shape and density of blood vessels in the lower extremities, which can evaluate and verify the effectiveness of the treatment measures, and has high feasibility and repeatability. This experiment is to characterize the influencing factors and determine both the feasibility and overall value of digital subtraction angiography in lower limb arteriography in a canine animal model.METHODS: Six Beagle dogs were immobilized on a working bed after administration of anesthesia. Percutaneous access was achieved via the femoral artery using an indwelling needle. A bolus of contrast agent was injected into the access site and digital subtraction angiography bolus chase technology was used to collect contrast images for analysis of this method.At the end of our procedure, the Beagles was anesthetized,veterinary injected excess potassium chloride.After confirming the loss of vital signs of beagles, the carcasses were handed over to the animal experimental center of Xinjiang Medical University,handled by qualified institutions.RESULT: The final arteriographic images of the hind limbs from all six canines were clear, and the branches of small vessels could be distinguished without any visible artifacts.CONCLUSION: These results suggest that arteriography using digital subtraction angiography can clearly reveal the shape and density of blood vessels in canine animal models. This method has great potential to significantly improve research related to limb ischemia, due to its simple and reproducible results.
Electrocardiographic findings of methanol toxicity: A cross-sectional study of 356 cases in Iran.
Authors: Nikoo Mohammad Hossein , Arjangzadeh Alireza , Pakfetrat Maryam , Boogar Shahrokh Sadeghi , Mohammadkarimi Vahid , Ostovan Vahid Reza , Khodamoradi Zohre , Roozbeh Jamshid , Khalili Mohammadreza , Shirazi Farnaz Kamali Haghighi , Kouhi Paryia , Heydari Seyyed Taghi
Published: June 2020

Bakground: Methanol is used widely in industry but methanol poisoning is not common; however, a number of outbreaks have been recently reported due to inappropriate processing of alcoholic beverages. Shiraz which is located in the southern part of Iran faced one of these in 2020 during COVID-19 pandemic. There is scarce literature on the electrocardiographic findings in methanol toxicity. The aim of this study is to address this gap in the literature. Method: A total of 356 cases with methanol toxicity were referred to Shiraz University of Medical Science Tertiary Hospitals (Faghihi and Namazi) in March and April 2020. The clinical findings such as blindness and impaired level of consciousness, lab data such as arterial blood gas, electrolytes, and creatinine, and the most common findings from ECGs were collected. Results: The most common ECG findings were J point elevation (68.8%), presence of U wave (59.2%), QTc prolongation (53.2% in males and 28.6% in females), and fragmented QRS (33.7%). An outstanding finding in this study was the presence of myocardial infarction in 5.3% of the cases, a finding which, to our knowledge, has only been reported in in a few case reports. Brugada pattern (8.1%) and Osborn wave (3.7%) were other interesting findings. In multivariate analysis, when confounding factors faded, myocardial infarction, atrioventricular conduction disturbances, sinus tachycardia and a prolonged QTC of more than 500 msecond were four independent correlates of methanol toxicity severity measured with arterial blood PH on arterial blood gas measurements, with p values and odds ratios of < 0.001 (12.386), 0.012 (5.981), 0.018(2.262) and 0.001(3.247), respectively. Conclusion: Electrocardiographic changes during methanol intoxication are remarkable and correlate well with the severity of poisoning. Myocardial infarction was an egregious yet concerningly common finding in this sample, which need to be ruled out in methanol toxicity.
Progesterone levels on the human chorionic gonadotropin trigger day affect the pregnancy rates for embryos transferred at different stages of development in both general and selected IVF/ICSI populations
Authors: Merviel Philippe , Bouée Sarah , Jacamon Anne-Solenn , Chabaud Jean-Jacques , Martelot Marie-Thérèse Le , Roche Sylvie , Rince Camille , Drapier Hortense , Perrin Aurore , Beauvillard Damien
Published: June 2020

Background
Two meta-analyses have shown that pregnancy and birth rates are significantly higher after blastocyst transfer than after cleaved embryo transfer. Other studies have revealed that a serum progesterone level > 1.5 ng/ml on the trigger day is responsible for premature luteinization and is associated with a low pregnancy rate. The objectives of the present study were to determine whether blastocyst transfer gave higher pregnancy rates than cleaved embryo transfer at day 3 in both the general and selected IVF/ICSI populations, and whether the serum progesterone level influenced the pregnancy rate.
Method
: We studied IVF/ICSI cycles with GnRH antagonist - FSH/hMG protocols in a general population (n = 1210) and a selected “top cycle” population (n = 677), after blastocyst transfer on D5 or cleaved embryo transfer on D3. The selected cycles had to meet the following criteria: female age < 35, first or second cycle, and one or two embryos transferred. We recorded predictive factors for pregnancy and calculated the serum progesterone to oocyte ratio (P/Ooc), the serum progesterone to serum estradiol ratio (P/E2), and the serum progesterone to follicle (> 14 mm) index (PFI).
Results
In the general population, the clinical pregnancy rate was significantly higher after blastocyst transfer (33.3%) than after cleaved embryo transfer (25.3%; p < 0.01). The differences between blastocyst and embryo transfer groups were not significant in the selected population (respectively 35.7% vs. 35.8% for the clinical pregnancy rate). The only predictive factors common to the general and selected populations were the serum progesterone levels on the eve of the trigger day and on the day itself, which were significantly lower in the subgroups of women who became pregnant (p < 0.01). We found a serum progesterone threshold of 0.9 ng/ml, as also reported by other studies. The P/Ooc ratio and the PFI appear to have predictive value for cleaved embryos transfers.
Conclusions
Blastocyst transfers were associated with higher clinical pregnancy rate than cleaved embryo transfers in a general population but not in a selected population. The serum progesterone levels on the eve of the trigger day and on the day itself predicted the likelihood of pregnancy.
Health-Related Behaviors and Health Insurance Status among US Adults: Findings from the 2017 Behavioral Risk Factor Surveillance System
Authors: Zhao Guixiang , Hsia Jason , Town Machell
Published: June 2020

Background
Health insurance coverage has increased overtime. However, little is known on the associations between health insurance status and adoption of health-related behaviors among US adults.
Methods
The 2017 Behavioral Risk Factor Surveillance System collected data on health insurance coverage in 50 states and the District of Columbia (DC), and on type of insurance in 5 states and DC. We examined four health-related behaviors: no tobacco use, nondrinking or moderate drinking, meeting aerobic physical activity recommendations, and having a healthy body weight. We conducted log-linear regression analyses to assess the associations between health-related behaviors and insurance status, while adjusting for potential confounders. Data analyses were conducted in 2019.
Results
The percentages of adults who reported no tobacco use or meeting physical activity recommendations were significantly higher, and the percentages of adults with a healthy body weight were significantly lower among those who were insured versus uninsured, or among adults with private insurance versus uninsured. Adults with health insurance also had a higher prevalence of reporting all 4 health-related behaviors than those uninsured. These patterns persisted after multivariable adjustment for potential confounders including sociodemographics, routine checkup, and number of chronic diseases. Adults with public insurance were 7% more likely to report no tobacco use than adults who were uninsured. Additionally, adults with private insurance were 8% and 7% more likely to report no tobacco use and meeting physical activity recommendations, respectively, but 10% less likely to report nondrinking or moderate drinking than adults with public insurance.
Conclusions
Significant associations existed between having health insurance coverage and engaging in some health-related behaviors among US adults.
Modified culture system and combination of FICTION could increase the detection rate of abnormalities in multiple myeloma
Authors: Fu Qiang , Xie Shanzhen , Chen Jiadi , Ye Changjiang , Huang Huifang
Published: June 2020

Background

Conventional karyotyping of multiple myeloma (MM) is hampered by the low mitotic index of plasma cells (PCs). Furthermore, low proportions of PCs in some specimens may lead to false negative results in fluorescence in situ hybridisation (FISH) detection. The detection rate of cytogenetic abnormalities in MM must therefore be improved.
Methods

Bone marrow cells were cultured in an ordinary medium for 24 h or in a medium containing 10 ng/mL IL-6 and 40 ng/mL GM-CSF for 6 d. Fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms (FICTION) was also conducted, which combines fluorescence immunophenotyping (using CD138) and FISH.
Results

Under modified culture conditions, the successful rate of culture and abnormality rate during karyotype analysis increased to 86.4% and 40.9%, respectively. The abnormality rate of FICTION (89.5%) was significantly higher than that of FISH (60.0%). The genetic abnormality rate increased to 92.3% when FICTION and karyotyping were conducted under modified culture conditions.
Conclusion

The established modified culture system could improve karyotyping quality in MM. Owing to its obvious advantages compared with FISH, FICTION is recommended for detecting genetic abnormalities in MM. Combining modified culture system and FICTION could improve the sensitivity of cytogenetic risk stratification in MM patients.
Analysis of Normal Ankle Radiographic Angles
Authors: Zheng Weixin , Du Junhua , Lu Yao , Liang Jingqi , Zhang Yan , Liang Xiaojun , Zhao Hongmou
Published: June 2020

Background

Understanding the position of the normal ankle is the key before every successfully surgical planning. The aims of our study were to quantify the normal ankle angles, measures and reference points systematically on ankle radiographs.
Methods

A total of 900 angles and 300 basic information were measured on 100 healthy ankles. The radiographic measurements were performed on standard weight-bearing anteroposterior (AP) and lateral view of the ankle. A total of 6 angles were made from the AP view, 3 angles from the lateral view. All angles were measured by 2 foot and ankle surgeons, independent of each other. For intraobserver reliability, after six weeks, the same angles were measured by each observer.
Results

A total of 900 angles and 300 basic information were measured on 100 healthy ankles. The mean age of the subjects was 33.0 ± 9.1years, with 57 females(57%) and 43 males(43%), with 44 left feet(44%) and 56 right feet(56%). Intraobserver is reliability greater than 0.8 and the interobserver reliability greater than 0.8. The following angles were measured from the AP of ankle: TAS’s angle, TT’s angle, TC’s angle, TMM’s angle, TLM’s angle, MA’s angle. The following angles were measured from the lateral view: TLS’s angle, Kite angle, TTA’s angle.
Conclusions

Our study will provide a set of standard angle measures. The range of angles can be used as a reference for preoperative design and intraoperative and postoperative evaluations.
Patient Characteristics and Medical Provider Factors Are Associated With Length of Stay in Total Hip Arthroplasty Patients: a Retrospective Chinese Cohort Study
Authors: Zeng Hui , Li Guoqing , Yu Fei , Weng Jian , Xiong Ao , Fu Qiang , Zeng Yucong , Wang Fangxi , Xu Chang , Wang Deli
Published: June 2020

Background

Total hip arthroplasty (THA) is a successful treatment in the improvement of quality of life. Diagnosis-related groups (DRGs) payment has a significant impact on the hospital market in China and length of stay (LOS) is one of its crucial manifestations. Patient characteristics and medical provider factors can affect LOS but the relationship is uncertain. We intent to explore the relationship between patient characteristics and medical provider factors and LOS of primary THA patients.
Methods

We reviewed the database containing 461 patients who underwent primary THA between January 2014 to January 2019 and regressed the LOS against a variety of perioperative factors. A multivariable linear regression model was performed to assess the difference.
Results

For parts of patient characteristics, multivariable linear regression analysis revealed that comorbidities, pre-operation albumin < 30 g/L, and pre-operation CRP ≥ 5 mg/L were all significantly associated with LOS (p < 0.05). For parts of medical provider factors, multivariable linear regression analysis revealed that date of surgery, urinary catheter, and incision drainage were all significantly associated with LOS (p < 0.05).
Conclusions

Patient characteristics and medical provider factors are associated with LOS of THA patients. Evaluation and identification of risk factors are beneficial in patients' education, perioperative discussion and surgery decisions in the different primary THA patient populations.
Alteration of Screw-home Movement in Patients With Knee Osteoarthritis: A Cross-sectional Study
Authors: Jeon Jeongwoo , Lee Dongyeop , Yu Jaeho , Kim Jinseop , Lhee Sang Hoon , Chong Suri , Hong Jiheon
Published: June 2020

Background: Tibial rotation accompanying sagittal movement contains the phenomenon of screw-home movement of the knee, which plays an important role in knee stability during extension. This study aimed to investigate the alteration of screw-home movement in patients with knee osteoarthritis (OA).Methods: Participants (n =67) in this cross-sectional study were outpatients in the department of orthopedics of a general hospital and included patients with knee OA (n=31) and asymptomatic control subjects (n=36).Knee kinematic data were measured using an inertial measurement unit. The total tibial rotation was obtainedduring knee sagittal movement. The acquired angle of tibial rotation was divided into four periodseach extension and flexion. The total tibial rotation and the variation of each period were compared between the OA and control groups.Results: Significant differences arose between the OA and control groups in the total tibial rotation during knee extension and flexion(P< 0.001).The variation of tibial rotation was also significantly different between groups for all periods (P< 0.001; knee extensionat 70° to 45°,P = 0.014).Conclusions: We found a reduction in the total tibial rotation and loss of the screw-home movement in the unloaded OA knee. To normalize the screw-home movement, it is necessary to promote proper articular movement of the knee joint and suppress the hyperexcitability of the medial muscles.
Factors Associated with Failure of Bony Union After Conservative Treatment of Acute Cases of Unilateral Lumbar Spondylolysis
Authors: Tatsumura Masaki , Gamada Hisanori , Okuwaki Shun , Eto Fumihiko , Nagashima Katsuya , Ogawa Takeshi , Mammoto Takeo , Hirano Atsushi , Koda Masao , Yamazaki Masashi
Published: June 2020

Background: If bone union is expected, conservative treatment is generally selected for lumbar spondylolysis. However, sometimes conservative treatments are unsuccessful. We sought to determine the factors associated with failure of bony union in acute unilateral lumbar spondylolysis with bone marrow edema including contralateral pseudoarthrosis.Methods: This study targeted unilateral lumbar spondylolysis treated conservatively in high school or younger students. Conservative therapy was continued until the bone marrow edema disappeared on MRI and bone union was investigated by CT. We conducted a univariate analysis of sex, age, pathological stage, lesion level complicating the contralateral bone defect, lesion level, and intercurrent spina bifida occulta, and variables with p < 0.1 were considered in a logistic regression analysis. An item with p < 0.05 was defined as a factor associated with failure of bony union.Results: We found 92 cases of unilateral spondylolysis with bone marrow edema and 66 cases were successfully treated conservatively. Failure of bony union in unilateral lumbar spondylolysis with bone marrow edema was associated with advanced pathological stage (p = 0.004), contralateral pseudoarthrosis (p < 0.001), and L5 lesion level (p = 0.002). The odds ratio was 20.0 (95% CI 3.0–193.9) for advanced pathological stage, 78.8 (95% CI 13–846) for contralateral pseudoarthrosis, and 175 (95% CI 8.5–8192) for L5 lesion level.Conclusions: Conservative therapy aiming at bony union is contraindicated in cases of acute unilateral spondylolysis when the pathological stage is advanced, the lesion level is L5, or there is contralateral pseudoarthrotic spondylolysis.
Genomic surveillance of a resurgence of COVID-19 in Guangzhou, China
Authors: Zhang Zhou-Bin , Li Peng , Liu Hong-Jie , Zhong Jia-Yong , Zheng Yingfeng , Li Kui-Biao , Qin Peng-Zhe , Zeng Qing , Li Jin-Hui , Li Li-Zhong , Cao Lan , Wu Ji-Bin , Chen Yi-Yun , Jia Lei-Li , Song Hong-Bin , Wang Hua-Dong , Zhang Qi-Wei , Fan Jun , Di Biao , Jia Hong-Ling , Ni Ming , Xiao Chuan-Le
Published: June 2020

In the middle of March, the World Health Organization declared the outbreak of COVID-19 caused by SARS-CoV-2 infection a global pandemic. While China experienced a dramatic decline in daily growth rate of COVID-19, multiple importations of new cases from other countries and their related local infections caused a rapid rise. Between March 12 and April 15, we collected nasopharyngeal samples from 109 imported cases from 25 countries and 69 local cases in Guangzhou, China. In order to characterize the transmission patterns and genetic evolution of this virus among different populations, we sequenced the genome of SARS-CoV-2. The imported viral strains were assigned to lineages distributed in Europe (33.0%), America (17.4%), Africa (25.7%), or Southeast/West Asia (23.9%). Importantly, 10 imported cases from Africa formed two novel sub-lineages not identified in global tree previously. A detailed analysis showed that the imported viral strains from Philippines and Pakistan were closely related and within the same sub-lineage, whereas Ethiopia had varied lineages in the African phylogenetic tree. In spite of the diversity of imported SARS-CoV-2, 60 of 69 local infections could be traced back to two specific small lineages imported from Africa. A combined genetic and epidemiological analysis revealed a high-resolution transmission network of the imported SARS-CoV-2 in local communities, which might help inform the public health response and genomic surveillance in other cities and regions. Finally, we observed in-frame deletions on seven loci of SARS-CoV-2 genome, some of which were intra-host mutations, and they exhibited no enrichment on the S protein. Our findings provide new insight into the viral phylodynamics of SARS-CoV-2 and beta coronavirus.
MCL-1 plays an oncogenic role in breast cancer by modulating chemoresistance and stemness properties by activating Wnt/β-catenin
Authors: Zhang Yuzhu , Zhu Ling , Zhang Yanmei , Lu Hai , Wei Xiaoqing , Xu Rui , Ren Liping , Chen Qianjun
Published: June 2020

Background

Breast cancer is the most common malignant tumor and the leading cause of death in women. Chemotherapy is one of the most important treatments for breast cancer. However, the development of chemotherapy resistance is the main cause of 20–30% of breast cancer patients developing metastasis, leading to death. MCL-1, an anti-apoptotic protein, has not been found to contribute to chemotherapy resistance in breast cancer.
Methods

We used large gene panels to detect pathological sections of tumors in drug-resistant and sensitive patients. We validated protein profiling by IHC in a larger cohort of samples. We performed the function of MCL-1 by knockdown and overexpression in vitro and in vivo. Luciferase assay and CHIP assay were used to prove the regulatory network between MCL-1 and LRP6.
Result

We found that MCL-1 is more highly expressed in drug-resistant breast cancer tissues than it is in sensitive breast cancer tissues. Functional studies have revealed that MCL-1 plays an important role in drug resistance by regulating apoptosis in breast cancer cells. We found that overexpression of MCL-1 enhances the chemoresistance and stemness of breast cancer cells in vitro and in vivo, while silencing has the opposite effect. Mechanistically, by downregulating and upregulating MCL-1, we show that MCL-1 regulates LRP6 and activates the WNT/β-catenin signaling pathway in breast cancer cells. Finally, we found that a high level of MCL-1 expression predicts a poor prognosis in breast cancer.
Conclusion

Our work highlights the role of MCL-1 in chemoresistance and stemness. The MCL-1-WNT/β-catenin axis might be used as a new clinical target for breast cancer therapy.
Ethnic Disparities in Stillbirth Risk in Yunnan, China: A Prospective Cohort Study, 2010-2018
Authors: Wu Yanpeng , Pan Jianhong , Han Dong , Li Lixin , Wu Yanfei , Liao Rui , Liu Zijie , You Dingyun , Chen Pingyan , Wu Ying
Published: June 2020

Background: Racial and ethnic disparities in stillbirth risk had been documented in most western countries, but it remains unknown in China. This study was to determine whether exist ethnic disparities in stillbirth risk in mainland China. Methods: Data came from 217,070 pregnancies of Yunnan China during 2010-2018 year. The Han majority and other four main minorities including Yi, Dai, Miao, Hani were investigated in the analysis. The stillbirth hazards were estimated by life-table analysis. The excess stillbirth risk (ESR) was computed for Chinese minorities in multiple logistic regression. Results: Compared with other four minorities, women in Han majority were more likely to more educated, less multiparous, and less occupied in agriculture. The pattern of stillbirth hazard of Dai women across different gestation intervals were found to be different from other ethnic groups, especially in 20-23 weeks with 3.2 times higher than Han women. The ESR of the Dai, Hani, Miao, and Yi were 45.05%, 18.70%, -4.17% and 12.28%, respectively. Adjusted for maternal age, education, parity and other general risk factors, the ethnic disparity still persisted between Dai women and Han women. Adjusted for preterm birth further (gestation age <37 weeks) can reduce 19.39% ESR of Dai women and made the disparity insignificant. Maternal diseases and congenital anomalies explained little for ethnic disparities.Conclusions: We identified the ethnic disparity in stillbirth risk between Dai women and Han women. General risk factors including sociodemographic factors and maternal diseases explained little. Considerable ethnic disparities can be attributed to preterm birth.
Closed Reduction of Severely Angulation Rockwood and Wilkins’ Type C Thumb Metacarpal Base Fractures in Children
Authors: Qiao Fei , Jiang Fei
Published: June 2020

Background: Management of severely angulation Rockwood and Wilkins’ type C(RW-C) thumb metacarpal base fractures in children is challenging. We report experiences of leverage reduction and dual antegrade crossing Kirschner wires (DACK-wires) fixation in these fractures, aiming to assess the results using our technique.Methods: From October 2011 to September 2015, 17 children with severely angulation RW-C thumb metacarpal base fractures were treated at our institute. All patients underwent percutaneous leverage reduction and DACK-wires fixation in an average surgery time of 20 minutes (range 12 ~ 32minutes). The injured arm was immobilized of a thumb-spica cast including the entire first ray for 4-6 weeks, evaluated clinically and radiologically. The Cannon scoring system were used to evaluate the results. Percutaneous leverage and DACK-wires fixation were performed for 17 patients. No patients were treated with open reduction. 16 patients were followed up for a mean of 30 months (range 12-41 months). Results: There were 9 girls and 7 boys with ages ranging from 7.5 to 14.0 years and an average age of 10.8 years. Percutaneous leverage reduction and DACK-wires were successfully used in an average total surgery time of 20 minutes (range 12 ~ 32 minutes). Bone union was achieved in all patients within a mean time of 4.2 weeks (range 4~6 weeks). The average angulation (pre-operation; 50.5° (range 40.8°–67.0°) vs post-operation: 5.0° (range 0.0°–7.0°) was significantly different(P<0.05). The clinical results were evaluated by the Cannon scoring system, and there were 15 excellent results and one good result. There were no refractures and no incidences of nonunion, growth arrest in the proximal epiphysis. Only one patient suffered from superficial infection which was resolved after removal of k-wires and oral antibiotics. Cosmetic results were described as good and satisfactory by all patients.Conclusion: Our percutaneous leverage technique with DACK-wires fixation can be successfully used to these fractures. This technique is simple to learn and minimally invasive, and the results are excellent.
Diagnostic Accuracy of Hand Surgeons and Pain Specialists in Diagnosing CRPS Based on the Budapest Criteria
Authors: Jänsch Pattariya , Asmus Ariane , Pappa-Eisenschenk Sofia , Eisenschenk Andreas , Miillrose Michael , Diehl Joscha , Kim Simon
Published: June 2020

BackgroundThe clinical presentation of complex regional pain syndrome is heterogenous. The Budapest criteria give a list of symptoms and signs for the diagnosis. But the physician will often set the diagnosis clinically from the collection of symptoms and his or her experience. This study examines the accuracy of hand surgeons and pain specialists for diagnosing CRPS using the Budapest criteria as reference.MethodsWe included 124 patients of which 120 were diagnosed CRPS either by a clinician or by Budapest criteria. We analysed epidemiologic data, the number of patients with CRPS and mode of diagnosis and determined the CRPS severity score. Sensitivity, specificity, accuracy, and predictive values were calculated for hand surgeon and pain specialist. The number of CRPS-NOS was determined. We calculated the agreement between hand surgeon and pain specialist for the diagnosis CRPS.ResultsThe Budapest criteria were met in 108 cases with a mean CSS of 10.41 points. Sensitivity of hand surgeons for the diagnosis CRPS was 92 %, specificity 31 % and accuracy 90 %. The pain specialists had a sensitivity of 74 %, specificity of 71 % and accuracy of 74 %. Prevalence of CRPS-NOS was 9 %. In cases where hand surgeon and pain specialist agreed on CRPS, the Budapest criteria were met in 96 %, in all other combinations they were met in around 70 %. The agreement of hand surgeon and pain specialist was fair.ConclusionThe Budapest criteria can support the diagnosis CRPS in clinically ambiguous cases as they were most often met in cases with agreement of both clinicians. Care must be taken not to miss patients with CRPS-NOS.Trial registrationThe study was registered in the German Clinical Trials Register: DRKS00020348Universal Trial Number (UTN): U1111-1245-4109
A metabolic modeling approach reveals promising therapeutic targets and antiviral drugs to combat COVID-19
Authors: Santos-Beneit Fernando , Raškevičius Vytautas , Skeberdis Vytenis A. , Bordel Sergio
Published: June 2020

In this study we have developed a metabolic modeling approach to identify human metabolic enzymes which can be targeted for therapeutic intervention against COVID-19. A literature search was carried out in order to identify suitable inhibitors of these enzymes, which were confirmed by docking calculations. In total, 10 targets and 12 bioactive molecules have been predicted. Among the most promising molecules we identified Triacsin C, which inhibits ACSL3, and which has been shown to be very effective against different viruses, including positive-sense single-stranded RNA viruses. Similarly, we also identified the drug Celgosivir, which has been successfully tested in cells infected with different types of viruses such as Dengue, Zika, Hepatitis C and Influenza. Finally, other drugs targeting enzymes of lipid metabolism, carbohydrate metabolism or protein palmitoylation (such as propylthiouracil, 2-bromopalmitate, lipofermata, tunicamycin, benzyl isothiocyanate, tipifarnib and lonafarnib) are also proposed.
proDA: Probabilistic Dropout Analysis for Identifying Differentially Abundant Proteins in Label-Free Mass Spectrometry
Authors: Ahlmann-Eltze Constantin , Anders Simon
Published: June 2020

Protein mass spectrometry with label-free quantification (LFQ) is widely used for quantitative proteomics studies. Nevertheless, well-principled statistical inference procedures are still lacking, and most practitioners adopt methods from transcriptomics. These, however, cannot properly treat the principal complication of label-free proteomics, namely many non-randomly missing values.

We present proDA, a method to perform statistical tests for differential abundance of proteins. It models missing values in an intensity-dependent probabilistic manner. proDA is based on linear models and thus suitable for complex experimental designs, and boosts statistical power for small sample sizes by using variance moderation. We show that the currently widely used methods based on ad hoc imputation schemes can report excessive false positives, and that proDA not only overcomes this serious issue but also offers high sensitivity. Thus, proDA fills a crucial gap in the toolbox of quantitative proteomics.
D-dimer level elevation can aid in detection of asymptomatic COVID-19 presenting with acute cerebral infarction
Authors: Umemura Takeru , Kondo Hirohisa , Ohta Hirotsugu , Futatsuya Koichiro , Mizobe Takamitsu
Published: June 2020

Coronavirus disease 2019 (COVID-19) mainly manifests as a respiratory syndrome, besides causing other complications. Severe COVID-19 may also present with coagulopathy, leading to venous thrombosis and cerebral infarction. Stroke is one of the complications associated with severe COVID-19. Generally, acute stroke is the second complication in patients with respiratory syndrome. Here, we present a case of COVID-19 in an 84-year-old female patient who did not manifest any respiratory symptoms; however, she presented with acute stroke. The patient had no cough or fever before the stroke onset, but the COVID-19 PCR was positive. The patient also had markedly elevated D-dimer levels. Our findings suggest that coagulopathy can occur, even in a patient with asymptomatic COVID-19 infection. To our knowledge, this is the first case of asymptomatic COVID-19 in a patient presenting with cerebral infarction. We concluded that elevation of D-dimer levels is one of the tools to ascertain COVID-19 infection in such patients.
A Case Report: Gitelman Syndrome or Bartter Syndrome?
Authors: WU YuanBin , Hu Jingjing , Wang Bo , Yang Dongxin , Zheng Han , Tan Qiqi , Su Haihao
Published: June 2020

Background: Gitelman syndrome (GS) is a rare autosomal recessive inherited tubular disease which is caused by mutation in the SLC12A3 gene. It is characterized by hypokalemic alkalosis with hypomagnesemia and hypocalciuria, and can cause serious complications such as arrhythmia, syncope, sudden death, etc. Bartter syndrome (BS) is similar to Gitelman syndrome in clinical and laboratory examinations. If lack of sufficient understanding of the disease, it is easy to cause misdiagnosis and missed diagnosis. Case presentation: A 6-year-old Chinese girl presented with history of hand and foot spasms and was diagnosed with hypokalemia. Although multiple symptomatic treatments of potassium supplementation was given, is the concentration of potassium was still at a low level. Gene analysis revealed that the presence of two heterozygous mutations, i.e. a missense mutation c.248G> A and a frameshift mutation c.2875_2876del, in the SLC12A3 gene.The child was diagnosed with Gitelman syndrome(GS) due to SLC12A3 compound heterozygous mutation. Through treatment, the level of ion metabolism in children remains stable. Conclusions: By reviewing its clinical characteristics and diagnosis and treatment ideas, we can help improve clinicians' understanding of children's GS.
Poly(I:c)-priming Improved the Therapeutic Efficacy of Mesenchymal Stromal Cells on Experimental Colitis by Promoting the Expression of Indoleamine 2,3-dioxygenase
Authors: Lim Ji-Young , Kim Byung-Su , Ryu Da-Bin , Kim Tae Woo , Park Gyeongsin , Min Chang-Ki
Published: June 2020

Background:Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSC) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods:To compare the therapeutic effects between the naïve MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfatein drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were significantly improved after injection of the primed MSCs. Results:Mice receiving the poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 up-regulation in colon tissue and diminished the protective effects of the primed MSC. Conclusions: The priming of MSCs with poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.
Genetic relatedness of multidrug resistant Escherichia coli isolated from humans, chickens and poultry environments
Authors: Aworh Mabel Kamweli , Kwaga Jacob K. P. , Hendriksen Rene S. , Okolocha Emmanuel C. , Thakur Siddhartha
Published: June 2020

Background: Inappropriate use of antimicrobial agents in animal production has led to the development of antimicrobial resistance (AMR) in foodborne pathogens. Transmission of AMR foodborne pathogens from reservoirs, particularly chickens to the human population do occur. Recently, we reported that occupational exposure was a risk factor for multidrug-resistant (MDR) Escherichia coli (E. coli) among poultry-workers. Here we determined the prevalence and genetic relatedness among MDR E. coli isolated from poultry-workers, chickens, and poultry environments in Abuja, Nigeria. This study was conducted to address the gaps identified by the Nigerian AMR situation analysis.Methods: We conducted a cross-sectional study among poultry-workers, chickens, and poultry farm/live bird market (LBM) environments. The isolates were tested phenotypically for their antimicrobial susceptibility profiles, genotypically characterized using whole-genome sequencing (WGS) and in silico multilocus sequence types (MLST). We conducted a phylogenetic single nucleotide polymorphism (SNPs) analysis to determine relatedness and clonality among the isolates.Results: A total of 115 (26.8%) out of 429 samples were positive for E. coli. Of these, 110 isolates were viable for phenotypic and genotypic characterization. The selection comprised 47 (42.7%) isolates from poultry-workers, 36 (32.7%) from chickens, and 27 (24.5%) from poultry-farm or LBM environments. Overall, 101 (91.8%) isolates were determined MDR conferring resistance to at least three drug classes. High frequency of resistance were observed for tetracycline (n = 102; 92.7%), trimethoprim/sulfamethoxazole (n = 93; 84.5%), streptomycin (n = 87; 79.1%) and ampicillin (n = 88; 80%). Two plasmid-mediated colistin genes – mcr-1.1 harboured on IncX4 plasmids were detected in environmental isolates. The most prevalent sequence types (ST) were ST-155 (n = 8), ST-48 (n = 8) and ST-10 (n = 6). Two isolates of human and environmental sources with a SNPs difference of 6161 originating from the same farm shared a novel ST. The isolates had similar AMR genes and plasmid replicons.Conclusion: MDR E.coli isolates were prevalent amongst poultry-workers, poultry, and the poultry farm/LBM environment. The emergence of MDR E. coli with novel ST in two isolates may be plasmid-mediated. Competent authorities should enforce AMR regulations to ensure prudent use of antimicrobials to limit the risk of transmission along the food chain.