bluuebunny/crossref_metadata_2025 huggingface dataset:
Pauwels screw combined inverted triangle cannulated screws for the treatment of Pauwels type-III femoral neck fracture:- a new surgical method based on the morphology of the fracture
Authors: Xue Gang , Chen Siting , Zhou Maosheng , Wang Zhengyu , Wan Liangliang , Xie JiaBing , Yang Min
Published: July 2020

Background: Femoral neck fracture is a serious injury in adults with significant functional consequences.Internal fixtion is an established treatment for femoral neck fractures in young adult patients .However, the risk of complications following fixation has plague orthopedists for decades.In all femoral neck fracture ,Pauwels type-III femoral neck fractures with a large vertical shear force were more likely to cause clinical failure.The aim of this study is to intruduce a new surgical technique for the treatment of this fracture according to the morphology of the fracture using the combination of Pauwels screw and inverted triangle cannulated screws(PSTCS)，and report the clinical effects in a prospective cohort of 14 patients.Methods: From June 2017 to June 2019, a total of 14 patients (8 males and 6 females ) with Pauwels type-III femoral neck fracture underwent the surgical treatment of PSTCS according to the morphologyical types of fracture in clinical operation in our department. Patients were allowed to perform contraction exercises of quadriceps femoris on postoperative day1, passive flexion and extension exercises postoperative day 2 onwards, and active flexion and extension exercises postoperative day 7 onwards. Patients were allowed for partial-weight bearing walking postoperative 1month onwards with axillary crutches. After one month AP and lateral radiograph were taken. Full ambulation was permitted until the presence of radiological consolidation.Intraoperative (Operative duration,Blood loss),postoperation(Fracture union time,The Harris Hip Score,Visual analog score) were record for comparison.Results: All patients were followed up for at least 12 months.In the end point of the follow up ,12 of the 14 patients (85.7%)with pauwels type-III femoral neck fractures had achieved satisfactory hip function. Operative duration was a mean of 49.5 ±10.4 minutes.Intraoperative blood loss was between 26 and 110 ml (mean, 44.4±20.6ml) and without intraoperative blood transfusion . The Harris Hip Score was between 64 and 95(mean,87.6±8.9).Fracture healing was observed in all patients according to the X-ray . No internal fixation was loosened or screw cut-out in the follow-up period.The femoral head necrosis was observed in 1 patient in this study. In addition, there was no obvious fracture displacement, femoral neck shortening, or hip varus. Conclusions: The study showed that PSTCS can provide a satisfactory clinical outcomes for treatment of pauwels type-III femoral neck fractures.Most patients (85.7%) achieved good or excellent results with the use of PSTCS,which appears to be a reliable method and provides another choice for this problematic fracture.The new internal fixation method of PSTCS can provide mechanical stability and promote fracture healing
Connective tissue remodelling is differently modulated by Tocilizumab versus Methotrexate monotherapy in patients with early Rheumatoid Arthritis: the AMBITION study
Authors: Drobinski Patryk J. , Bay-Jensen Anne C. , Karsdal Morten A. , Siebuhr Anne S. , Sardar Samra
Published: July 2020

Objective: Associations between Rheumatoid Arthritis (RA) and effect of treatment at the tissue levels are poorly understood. We investigated the scope of released extracellular matrix (ECM) metabolites as a consequence of tissue remodeling in patients treated with Methotrexate (MTX) and Tocilizumab (TCZ) compared to placebo.Methods: Tissue metabolites from 387 RA patients treated with either TCZ (8 mg/kg) or MTX monotherapy (7.5–20 mg/kg) were measured at baseline and 8-weeks sera by validated ELISA assays. The levels of collagen biomarkers (C1M, C2M, C3M and C4M) together with C-reactive protein (CRP) and CRP metabolite (CRPM) were investigated. Baseline levels of biomarkers have been compared with 72 age and gender matched healthy controls. Comparison between treatment and response groups were done by ANCOVA, Spearman’s correlation and Logistic regression adjusted for age, gender, BMI and disease duration.Results: C1M and C3M, were significantly (P < 0.05) inhibited by TCZ and C3M by MTX (P < 0.01) compared to placebo. C1M and C3M inhibition with TCZ was respectively 23% and 16% greater than that of MTX (P < 0.01 and P < 0.0001). C4M was inhibited by TCZ and MTX, but the effect of TCZ was 22% greater than MTX (P < 0.0001). TCZ and MTX had minimal effect on C2M levels. MTX had no effect on CRP and CRPM, whereas TCZ reduced their levels to 69% and 27% from baseline. Investigated biomarkers revealed a significant (P < 0.05) differences in biomarker profiles of MTX ACR50 treatment responders and non-responders. Change to week 8 in levels of C3M, C4M, CRP and CRPM in MTX patients correlated significantly (rho = 0.41 to 0.18, P < 0.0001 to 0.039) with change in disease activity (DAS28) at week 8, 16 and 24, whereas only CRP in TCZ patients (rho = 0.32 to 0.21, P < 0.0001 to 0.01).Conclusion: Patients receiving TCZ treatment for 8 weeks had higher suppression of tissue remodeling and inflammatory biomarkers over patients treated with MTX. Measured biomarkers enabled for a discrimination of biomarker profiles of ACR50 treatment responding patients and identification of those who benefit at the early time-point. Week 8 change in levels of C3M, C4M, CRP and CRPM significantly predicted clinical response to treatment and correlated with DAS28 at all time-points.
Independent and interactive effect of sitting time and physical activity on prevalence of hyperuricemia: the Henan Rural Cohort Study
Authors: Dong Xiaokang , Li Yuqian , Zhang Lulu , Liu Xiaotian , Tu Runqi , Wang Yikang , Li Ruiying , Li Linlin , Hou Jian , Mao Zhenxing , Huo Wenqian , Wang Chongjian
Published: July 2020

BackgroundThere are few studies on the hyperuricemia (HUA) and moderate to vigorous intensity physical activity (PA) and also hardly regarding sitting time (ST). The purpose of this study was to examine the independent and interactive association of PA and ST with HUA.MethodsA cross-sectional analysis was performed on 38,855 participants (aged 18-79) enrolled from the Henan Rural Cohort Study at baseline (2015 to 2017). PA and ST levels were assessed by using the International Physical Activity Questionnaire (IPAQ). HUA was defined as a serum uric acid level of >7.0 mg/dL for males and >6.0 mg/dL for females. Multivariable logistic regression and linear regression models were applied to examine the independent association between PA or ST and HUA and serum uric acid level. Interaction plots were used to visualize the interaction effects of PA and ST on HUA.ResultsPA level was inversely related with serum uric acid level (β: -0.09, 95% confidence interval (CI): -0.16, -0.02), but ST was positively related with uric acid level (β: 2.04, 95% CI:1.82, 2.26). Metabolic equivalent (MET-hour/day) was associated with decreased prevalence of HUA (odds ratio (OR): 0.98, 95% CI: 0.96, 0.99), while per hour increased for ST was associated with increased HUA (OR:1.05, 95% CI: 1.04, 1.06). The interaction of PA and ST was significant (P<0.001).ConclusionExposure to higher ST was independently related to increased prevalence of HUA, while vigorous PA with a decreased HUA prevalence. Meanwhile, higher daily ST might attenuate the protective effect of PA on HUA.Clinical Trial RegistrationThe Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). http://www.chictr.org.cn/showproj.aspx?proj=11375
Seed Set Patterns in East African Cooking Bananas (Musa spp.) are Dependent on Weather Before, During, and After Pollination
Authors: Waniale Allan , Mukasa Settumba B. , Tugume Arthur K. , Tumuhimbise Robooni , Kubiriba Jerome , Tushemereirwe Wilberforce K. , Batte Michael , Brown Allan , Swennen Rony
Published: July 2020

Background: Seed set in banana (Musa spp.) is influenced by weather but the most critical weather attribute(s) and the critical period are unknown. Such information is of paramount importance to increase seed set for banana breeding programs. Three female fertile East African cooking bananas (EACBs), ‘Enzirabahima’ (AAA), ‘Mshale’ (AA), and ‘Nshonowa’ (AA) were pollinated with the highly male fertile wild banana ‘Calcutta 4’ (AA). At full maturity, bunches were harvested and ripened and seeds extracted from ripe fruit pulp. Seed set was then correlated with weather before, during, and after pollination.Results: Seed set was positively correlated with high temperatures (r=0.172 – 0.488), solar radiation (r=0.181 – 0.282) and negatively correlated with rainfall (r=-0.214 – -0.238) and relative humidity (RH) (r=-0.158 – -0.438) between 75 and 15 days before pollination (DBP). The pattern of weather association was cultivar-dependent with ‘Nshonowa’ having the strongest significant associations. At the time of pollination, high average temperatures were critical for seed set in ‘Enzirabahima’ (r=0.214, P<0.01) while high morning RH was critical for ‘Mshale’ (r=0.299, P<0.01). After pollination, high morning temperatures were associated with seed set (r=0.150 – 0.429) between 15 days to 90 days after pollination (DAP). High average temperatures were negatively correlated with seed set in ‘Mshale’ and ‘Nshonowa’ from 45 DAP to time of harvest (r=-0.208 – -0.344). Coefficients of correlation were generally highest 15 DBP especially for ‘Mshale’ and ‘Nshonowa.’ Principle component analysis showed that average and maximum temperature are the most important variables in the entire data set. Conclusion: Coefficients of correlation were generally less than 0.5 partly as a result of weather involvement in seed set at several floral development stages; before, during, and after pollination. The most critical developmental stage is 15 DBP especially for ‘Mshale’ and ‘Nshonowa’ as they had the high correlation coefficients. Average temperature should be the main focus for seed set increase in banana.
Use of Machine Learning to Rapidly Predict Positivity to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) Using Basic Clinical Data
Authors: Langer Thomas , Favarato Martina , Giudici Riccardo , Bassi Gabriele , Garberi Roberta , Villa Fabiana , Gay Hedwige , Zeduri Anna , Bragagnolo Sara , Molteni Alberto , Beretta Andrea , Corradin Matteo , Moreno Mauro , Vismara Chiara , Perno Carlo Federico , Buscema Massimo , Grossi Enzo , Fumagalli Roberto
Published: July 2020

Objective: Reverse Transcription-Polymerase Chain Reaction (RT-PCR) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) diagnosis currently requires quite a long time span. A quicker and more efficient diagnostic tool in emergency departments could improve management during this global crisis. Our maingoal was assessing the accuracy of artificial intelligence in forecasting the resultsof RT-PCR for SARS-COV-2, using basic information at hand in all emergencydepartments.Methods: This is a retrospective study carried out between February 22 and March 16 2020 in one of the main hospitals in Milan, Italy. We screened for eligibility all patients admitted with influenza-like symptoms tested for SARS-COV-2.Patients under 12 years old, with no leukocyte formula performed in the ED,were excluded. Input data through artificial intelligence were made up of a combination of clinical, radiological and routine laboratory data upon hospital admission.Results: Among 199 patients subject to study (median [interquartile range] age 65 [46-78] years; 127 [63.8%] men), 124 [62.3%] resulted positive to SARS-COV-2. The best Machine Learning System reached an accuracy of 91.4% with 94.1% sensitivity and 88.7% specificity.Conclusion: Our study suggests that properly trained artificial intelligence algorithms may be able to predict correct results in RT-PCR for SARS-COV-2, using basic clinical data. If confirmed,on a larger-scale study, this approach could have important clinical and organizational implications.
Integrated Analysis of Long Non-Coding RNAs and mRNAs Associated With Malignant Transformation of Gastrointestinal Stromal Tumors
Authors: Yin Xiaonan , Yin Yuan , Dai Lei , Shen Chaoyong , Chen Na , Li Junshu , Cai Zhaolun , Jiang Zhiyuan , Wang Jian , Zhao Zhou , Chen Xin , Deng Hongxin , Zhang Bo
Published: July 2020

Background: Malignant transformation of gastrointestinal stromal tumors (GISTs) is correlated with poor prognosis; however, the underlying biological mechanism is not well understood. Methods: In the present study, low-risk (LR) GISTs, GISTs categorized as high-risk based on tumor size (HBS), and on mitotic rate (HBM) were collected for RNA sequencing. Candidate hub lncRNAs were selected by Oncomine analysis. Expression of a selected hub lncRNA, DNM3OS, and its correlation with patients’ prognosis were analyzed using FISH staining, followed with the determination of function and underlying mechanism. Results: Our results revealed a series of key pathways and hub lncRNAs involved in the malignant transformation of GISTs. Oncomine analysis revealed a tight association between clinical signatures and DNM3OS and suggested that DNM3OS is a hub lncRNA that is involved in the Hippo signaling pathway. In addition, DNM3OS was upregulated in HBS, HBM, and HBS/M GIST and correlated with worse prognosis in patients with GISTs. In addition, DNM3OS promoted GIST cell proliferation and mitosis by regulating the expression of GLUT4 and CD36. Conclusions: These results improve our understanding of the malignant transformation of GISTs and unveil a series of hub lncRNAs in GISTs.
Lycorine Hydrochloride Inhibits Cell Proliferation and Induces Apoptosis Through Promoting FBXW7-MCL1 Axis in Gastric Cancer
Authors: Li Chongyang , Deng Chaowei , Wang Xue , Pan Guangzhao , Zhang Kui , Dong Zhen , Zhao Gaichao , Tan Mengqin , Hu Xiaosong , Shi Shaomin , Du Juan , Ji Haoyan , Wang Xiaowen , Yang Liqun , Cui Hongjuan
Published: July 2020

Background: Lycorine hydrochloride (LH), an alkaloid extracted from the bulb of the lycorisaceae plant, is considered to have anti-viral, anti-malarial，and anti-tumorous effects. At present, the underlying mechanisms of LH in gastric cancer remain unclear. MCL1, an anti-apoptotic protein of BCL2 family, is closely related to drug resistance of tumor. Therefore, MCL1 is considered as a potential target for cancer treatment. Methods: The effect of LH on gastric cancer was assessed in vitro (by MTT, BrdU, western blotting…) and in vivo (by immunohistochemistry，H&E).Results: In this study, we showed that LH has an anti-tumorous property by down-regulating MCL1 in gastric cancer. Besides, we unveiled that LH reduced the protein stability of MCL1 by up-regulating ubiquitin E3 ligase FBXW7, which induced S-phase cell cycle arrest and triggered apoptosis of gastric cancer cells. Meanwhile, the results also showed that LH could induce apoptosis of the BCL2-drug-resistant-cell-lines. Moreover, PDX (Patient-Derived tumor xenograft) model experiment showed that LH combined with HA14-1 (inhibitor of BCL2), had a more significant therapeutic effect for gastric cancer. Conclusions: Together, the efficacy shown in our data suggests that lycorine hydrochloride is a promising anti-tumorous compound for gastric cancer.
Perceptions of syringe services programs and supervised use sites among a sample of registered voters in a U.S. state
Authors: Brooks-Russell Ashley , Brandspigel Sara , Franco Carol Y , Alishahi Musheng L. , Lee-Winn Angela E.
Published: July 2020

BackgroundThe decision to initiate a syringe service program or expand to a supervised use site is often influenced by local public support or opposition. The purpose of this study was to better understand public attitudes to local syringe service programs to inform the possibility of expanding services.Methods.We surveyed a sample of registered voters (n = 690) in the eight counties in the state of Colorado, United States, with existing syringe service programs about their awareness of and attitudes towards syringe service programs and supervised use sites.Results.Over three-quarters of respondents reported they were familiar with syringe service programs but only quarter knew they were legal, despite all survey respondents living near an operating program. Nearly 1 in 3 respondents thought a syringe service program or a supervised use site makes a community better and a majority (57%) thought supervised use sites should be legal in their state. There were significant differences in attitudes towards the benefits and risks of syringe service programs by political party affiliation.ConclusionUnderstanding the level of community knowledge and support for syringe service programs, as well as the reasons for opposition, can be helpful in addressing community concerns when seeking to initiate or expand services.
Feasibility study: Spot-scanning Proton Arc therapy (SPArc) for left-sided breast irradiation
Authors: Chang Sheng , Liu Gang , Zhao Lewei , Dilworth Joshua T , Zheng Weili , Jawad Saada , Yan Di , Chen Peter , Stevens Craig , Kabolizadeh Peyman , Li Xiaoqiang , Ding Xuanfeng
Published: July 2020

Background
This study investigated the feasibility and potential clinical benefit of utilizing a new proton treatment technique: Spot-scanning Proton Arc (SPArc) therapy for left-sided breast cancer irradiation to further reduce radiation dose to healthy tissue and mitigate the probability of normal tissue complications compared to conventional Intensity Modulated Proton Therapy(IMPT).
Methods
Eight patients diagnosed with left-sided breast cancer and treated with breast-preserving surgery followed by whole breast irradiation without regional nodal irradiation were included in this retrospective planning. Two proton treatment plans were generated for each patient: vertical intensity-modulated proton therapy used for clinical treatment (vIMPT, gantry angle 10°-30°) and SPArc for comparison purpose. Both SPArc and vIMPT plans were optimized using the robust optimization of ± 3.5% range and 5 mm setup uncertainties. Root-mean-square deviation dose (RMSD) volume histograms were used for plan robustness evaluation. All dosimetric results were evaluated based on dose-volume histograms (DVH), and the interplay effect was evaluated based on the accumulation of single-fraction 4D dynamic dose on CT50. The treatment beam delivery time was simulated based on a gantry rotation with energy-layer-switching-time (ELST) from 0.2 to 5 s.
Results
The average D1 to the heart and LAD were reduced to 53.63 cGy and 82.25 cGy compared with vIMPT 110.38 cGy (p = 0.001) and 170.38 cGy (p = 0.001), respectively. The average V5Gy and V20Gy of ipsilateral lung was reduced to 16.77% and 3.07% compared to vIMPT 25.56% (p = 0.001) and 4.68% (p = 0.003). Skin3mm mean and maximum dose was reduced to 3999.38 cGy and 4395.63 cGy compared to vIMPT 4104.25 cGy (p = 0.039) and 4411.63 cGy (p = 0.043), respectively. A significant relative risk reduction (RNTCP = NTCPSPArc / NTCPvIMPT) for organs at risk (OARs) was obtained with SPArc ranging from 0.61 to 0.86 depending on the clinical endpoint. The RMSD Volume Histogram(RVH) analysis shows SPArc provided better plan robustness in OARs sparing, including the heart, LAD, ipsilateral lung, and skin. The average estimated treatment beam delivery times were comparable to vIMPT plans when the ELST is about 0.5 s.
Conclusion
SPArc technique can further reduce dose delivered to OARs and the probability of normal tissue complications in patients treated for left-sided breast cancer.
Factors Associated With the Recruitment of Foreign Nurses in Japan: A Nationwide Survey of Hospitals
Authors: Hirano Yuko , Tsubota Kunio , Ohno Shun
Published: July 2020

Background: Recruiting foreign nurses is now a global concernto combatnursing shortages.Japan has officially opened its labor market to foreign nurses, through aneconomic partnership agreement with three other Asian countries. However, fewhospitalsemploy foreign nurses. Weinvestigatedthe waysto expand the number of hospitals employing foreign nurses in Japan by exploring the perceptions of hospital managerswho have notpreviously employedforeign nurses.Method:An anonymous questionnairewas developed and distributed to hospitalsthat had not previously employed foreign nurses;itrequestedthe staff’s opinions on Japan’s policy on recruitment of foreign nurses and their intentions to hire foreign nurses. We randomly selected 1,879 hospitals, or 22% of the hospitals in Japan (n=8,540) with more than 20 beds.We used descriptive statistics, a Chi-square test, and a logistic regression analysis to identify the predictors and developed a model to predict the likelihood of their intention to recruit foreign nurses in the future.Results: In total, 432hospitalswere eligible for further analysis (response rate:22.9%).Half (50%) of the hospital managerswere very/quiteinterested in Japan’s policy on recruiting foreign nurses, though only 20% intended to recruit under the economic partnership agreement in the future. The likelihood of foreign nurse recruitment under the partnership agreement was associated with the degree of interest in the policy (OR 9.38;95%CI 4.42–19.90) and managers’ perception of foreign nurses (OR 5.32, 95% CI 2.38–11.89).Conclusion:The strongest factor associated with the intention to recruit foreign nurses byhospitals thathadnot previously employed themwas the degree of interest in the government’s economic partnership agreement, followed by managers’ perceptionof foreign nurses, measured by “image score”. Foreign nurses contribute to the workplace byworking together inmulticultural teams;therefore,the Japanese government shouldfosterinitiatives to raise interest among Japanese hospitalstorecruit foreign nursesand improve perceptions among hospital staff.
“I Need to Be the First One With a Different Approach and to Make a Difference to the People” - Transforming Pediatric Training for Non-physician Clinicians in Malawi: A Mixed-method Study
Authors: Yasmin Farzana , Schultz Andreas , Phiri Ajib , Weigel Ralf
Published: July 2020

Background: Malawi has a critical shortage of skilled health workers limiting its ability to achieve its outlined national health goals. To address this, in 2012, theMinistry of Health and the College of Medicine introduced a three-year specialist Bachelor of Science (BSc) degree in Paediatric and Child Health (PCH) for Clinical Officers, a non-physician clinician cadre. In this training program, learning occurs through supervised ward rounds, bloc courses, and a research project. The German Society of Paediatrics and International Child Health, with funding from the German government, provided support between 09/2017 and 08/2019. This study aims to evaluate this support project to model the training for the coming cohorts of BSc PCHCO students.Methods:All 17 currently enrolled students took partin this study. Quantitative data was collected between 01/2018 using the Research Self-Efficacy Scale (RSES, ten-point scale), Stages of Change (SOC, four-point scale), and the post-self-assessment survey of bloc courses (five-point scale). In addition, three focus group discussions and five in-depth interviews with students and key informants were conductedduring April 1-10, 2019.Results:The mean (SD) scores for RSES and SOC model were 9.10 (0.91) and 3.54 (0.40) respectively; for the bloc course post-self-assessment it was 3.26 (0.48). Students found the program well-paced, felt that their clinical knowledge and skills had improved, and valued the acquired holistic approach of disease management which included the social determinants of health. They reported increased confidence and being more prepared for leadership roles at their facility and community. The involvement of international lecturers enriched their global perspectives. Students had concerns about theirrecognition in the government system and continued support after graduation. The shortage ofsupervising and teaching staff was perceived as a key barrier to continuing the program. Conclusion: Studentsimproved theirclinical expertise, developed self-efficacy, andnew attitudes towards research. Application of various educational strategies through this project and the involvement of teachers from diverse backgrounds may enable them to build their professional networks. Continuous professional development and alumni mentoring are recommended to sustain the achieved results.
Pattern-mixture model in network meta-analysis of binary missing outcome data: one-stage or two-stage approach?
Authors: Spineli Loukia Maria , Papadimitropoulou Katerina , Kalyvas Chrysostomos
Published: July 2020

Background
Trials with binary outcomes can be synthesised using within-trial exact likelihood or approximate normal likelihood in one-stage or two-stage approaches, respectively. The advantages of the one-stage over the two-stage approach have been documented extensively in the literature. Little is known how these approaches behave in the presence of missing outcome data (MOD) which are ubiquitous in trials. In this work, we compare the one-stage versus two-stage approach via a pattern-mixture model in the network meta-analysis Bayesian framework to handle MOD appropriately.
Methods
We used 29 published networks to empirically compare the two approaches with respect to the relative treatment effects of several competing interventions and the between-trial variance (

{\tau }^{2}
). We categorised the networks according to the extent and balance of MOD in the included trials. To complement the empirical study, we conducted a simulation study to compare the competing approaches regarding bias and width of the 95% credible interval of the (summary) log odds ratios (OR) and

{\tau }^{2}
in the presence of moderate and large MOD.
Results
The empirical study did not reveal any systematic bias between the compared approaches regarding the log OR, but showed systematically larger uncertainty around the log OR under the one-stage approach for networks with at least one small trial or low event risk and moderate MOD. For these networks, the simulation study revealed that the bias in log OR for comparisons with the reference intervention in the network was relatively higher in the two-stage approach. Contrariwise, the bias in log OR for the remaining comparisons was relatively higher in the one-stage approach. Overall, bias increased for large MOD. Furthermore, in these networks, the empirical results revealed slightly higher

{\tau }^{2}
estimates under the one-stage approach irrespective of the extent of MOD. The one-stage approach also led to less precise log OR and

{\tau }^{2}
when compared with the two-stage approach for large MOD.
Conclusions
Due to considerable bias in the log ORs overall, especially for large MOD, none of the competing approaches was superior. Until a more competent model is developed, the researchers may prefer the one-stage approach to handle MOD, while acknowledging its limitations.
Application of NOSES Combined with ERAS in the Treatment of Rectal Cancer
Authors: Li Sheng , Wen Bo , Yao Wei , Wang Xiongyu , Ma Kanggui , Liu Senlin , Yao Xueqing
Published: July 2020

Background: In recent years, Natural Orifice Specimen Extraction Surgery (NOSES) has been developed rapidly, and the feasibility and advantages of Enhance Recovery after Surgery (ERAS) also have been recognized in colorectal cancer. How about combining NOSES with ERAS? In this article, we are trying to answer this question. Methods: The 120 cases of rectal cancer patients who met the inclusion criteria from January 2018 to December 2019 were divided into three groups using the random number table method: traditional care control group (laparoscopic assisted surgery + traditional care), ERAS control group (laparoscopic adjuvant surgery + ERAS) and experimental group (NOSE + ERAS), 40 cases in each group, randomized controlled study was performed. Results: There were no significant differences in surgical time, bleeding volume, number of detected lymph nodes, incidence of venous thrombosis in the lower extremities, anastomotic leakage, and abdominal infection among the three groups (P> 0.05). The total complication rate, incidence of incision-related complications, incidence of pulmonary and urinary tract infections, and postoperative pain NRS score in the NOSES+ERAS group cases were significantly lower than those in the other two control groups. Patients in the NOSES + ERAS group had higher satisfaction rates and shorter postoperative hospital stay than those in the other two control groups. The feeding time and exhaust time after surgery in NOSES+ERAS group and ERAS control group were earlier than those in traditional care control group. The above differences are statistically significant (P <0.05). Conclusion: The NOSES radical resection of rectal cancer under the guidance of ERAS achieved more minimally invasive cosmetic and functional, individualized treatment effect in laparoscopic surgery. There is a greater advantage that ERAS combined with the NOSES radical resection of rectal cancer which is worthy of popularization and with good application prospect.
Alterations of RNA Splicing Patterns in Esophagus Squamous Cell Carcinoma
Authors: Ding Jiyu , Li Chunquan , Cheng Yinwei , Du Zepeng , Wang Qiuyu , Tang Zhidong , Song Chao , Xia Qiaoxi , Bai Wenjing , Lin Ling , Liu Wei , Xu Liyan , Li Enmin , Wu Bingli
Published: July 2020

Alternative splicing (AS) is an important biological process for regulating the expression of various isoforms from a single gene and thus to promote proteome diversity. In this study, RNA-seq data from 15 pairs of esophageal squamous cell carcinoma (ESCC) tissue samples and two cell lines were analyzed. AS events with significant differences between ESCC and matched normal tissues were re-annotated to find protein coding genes or non-coding RNAs. A total of 45,439 AS events was found. Of these, 6,019 (13.25%) significant differentially AS events were identified. Exon skipping (SE) events occupied the largest proportion of abnormal splicing events. Fifteen differential splicing events with the same trends of ΔΨ values in ESCC tissues and cell lines were found. Four pathways and 20 biological processes related to cell junction and migration were significantly enriched. The upregulated splicing factor SF3B4, which regulates 92 gene splicing events, could be a potential prognostic factor of ESCC. Sashimi plotting was applied to show the differentially-spliced genes, including HNRNPC, VCL, ZNF207, KIAA1217, TPM1 and CALD1. These results suggest that cell junction- and migration-related biological processes and KEGG pathways are affected by the AS abnormalities, and aberrant splicing events can be affected by changed expression of splicing factors. In summary, we identified significant differentially AS events which might be related to the development of ESCC.
Accelerated Fetal Growth in Early Pregnancy and Risk of Preterm Birth: A Prospective Cohort Study
Authors: Elenis Evangelia , Wikström Anna-Karin , Simic Marija
Published: July 2020

Background: Preterm birth (occurring before 37 completed weeks of gestation) affects 15 million infants annually, 7.5% of which die due to related complications. The detection and early diagnosis are therefore paramount in order to prevent the development of prematurity and its consequences. So far, focus has been laid on the association between reduced intrauterine fetal growth during late gestation and prematurity. The aim of the current study was to investigate the association between accelerated fetal growth in early pregnancy and the risk of preterm birth. Methods: This prospective cohort study included 69 617 singleton pregnancies without congenital malformations and with available biometric measurements during the first and second trimester. Estimation of fetal growth was based on measurements of biparietal diameter (BPD) at first and second trimester scan. We investigated the association between accelerated fetal growth and preterm birth prior to 37 weeks of gestation. The outcome was further stratified into very preterm birth (before 32 weeks of gestation) or moderate preterm birth (between 32 and 37 weeks of gestation) and medically induced or spontaneous preterm birth and was further explored. Results: The odds of prematurity were increased among fetuses with accelerated BPD growth (> 90th centile) estimated between first and second ultrasound scan, even after adjustment for possible confounders (aOR 1.36; 95% CI 1.20-1.54). The findings remained significant what regards moderate preterm births but not earlier births. Regarding medically induced preterm birth, the odds were found to be elevated in the group of fetuses with accelerated growth in early pregnancy (aOR 1.34; 95% CI 1.11-1.63). On the contrary, fetuses with delayed fetal growth exhibited lower risk for both overall and spontaneous preterm birth.Conclusions: Fetuses with accelerated BPD growth in early pregnancy, detected by ultrasound examination during the second trimester, exhibited increased risk of being born preterm. The findings of the current study suggest that fetal growth in early pregnancy should be taken into account when assessing the likelihood for preterm birth.
Comparison of Curettage and Hysteroscopy Plus Curettage After Uterine Arterial Embolization in the Treatment of Cesarean Scar Pregnancy
Authors: Cao Lili , Qian Zhida , Huang Lili
Published: July 2020

Background: Caesarean scar pregnancy (CSP) stands for the advanced stage severe complication secondary to cesarean section, and its incidence shows an increasing trend recently. However, no consensus has been reached about the optimal CSP treatment. Methods: The childbearing CSP patients with a cesarean section history were evaluated by ultrasonography, with a gestational age of less than 10 weeks. 34 patients receiving dilation and curettage (D&C) and uterine artery embolization (UAE) were enrolled into the D&C group, while 46 undergoing hysteroscopy (H/S) and D&C after UAE were enrolled into the H/S+D&C group. Results: Differences in success rate and decrease in the β-hCG level in serum on the second day of surgery were not significant between D&C and H/S+D&C groups (P>0.05). Also, differences in side effect rate, intraoperative blood loss amount, postoperative bleeding time, and total length of stay were not significant between both groups (P>0.05). Compared with D&C group, H/S+D&C group had decreased postoperative length of stay (P<0.05), increased hospitalization cost (P<0.05), and significantly elevated time of CSP mass disappearance (P<0.05). In addition, 8 (18.19%) patients in H/S+D&C group developed anesthesia-related side effects.Conclusions:This study reveals no obvious difference between UAE+D&C and H/S+D&C in terms of the clinical efficacy and safety, except for the time of CSP mass disappearance. The hospitalization cost is more expensive for H/S+D&C, but the postoperative length of stay is shorter for H/S+D&C. Besides, H/S+D&C is associated with the risk of anesthesia-associated side effects. All these will affect the selection of patients for the two methods.
Longitudinal Change in Arterial Stiffness After Delivery in Women With Preeclampsia and Normotension: a Prospective Cohort Study
Authors: KIM Sehun , LIM Hyun Ja , KIM Jeung-Ran , OH Kung Joon , HONG Joon-Seok , Suh Jung-Won
Published: July 2020

BACKGROUND: Preeclampsia is associated with increased arterial stiffness during pregnancy. However, data on the longitudinal change in arterial stiffness after delivery in women with preeclampsia are lacking. We aimed to examine the longitudinal change in arterial stiffness after delivery in women with preeclamptic and normotensive pregnancies, using the cardio-ankle vascular index for assessment of arterial stiffness. METHODS: Pregnant women with preeclampsia (n=37) and normotension (n=36) who gave birth at Seoul National University Bundang Hospital between March 2013, and May 2016, were enrolled and followed up at day 1, 6 months, and 12 months after delivery. The longitudinal change in the cardio-ankle vascular index and other variables including blood pressure, lipid profiles, serum creatinine, liver enzymes were compared between the two groups using mixed-effect model, and interactions among the main predictors were examined. RESULTS: The longitudinal change in the cardio-ankle vascular index did not significantly differ between the two groups (β=0.11, 95% CI: -0.31 – 0.54, p=0.60). Predictors of the longitudinal change in the cardio-ankle vascular index included age, time since delivery, body mass index, and diabetes mellitus. Women with preeclampsia showed significantly elevated blood pressure, lipid profiles, serum creatinine, and liver enzymes compared to women with normotension over the course of one year of follow up. CONCLUSION: Preeclampsia is associated with unfavorable blood pressure and metabolic indices after delivery. However, there was no difference in the longitudinal change in arterial stiffness between women with preeclampsia and normotension over the course of one year after delivery.
Large Retrospective Cohort Study of the Association Between Maternal 25-Hydroxyvitamin D Status and Birth Weight of Neonate
Authors: Yu Li , Ke Hai-Jin , Che Di , Guo Yong , Wu Jie-Ling
Published: July 2020

Background: The effect of maternal vitamin D status on the birth weight of offspring is controversial as the results are inconsistent between different populations. This large retrospective cohort study aimed to assess the relationship between maternal vitamin D levels and birth weight of neonate. Methods: Serum samples were collected from 10,586 Chinese women in the 2 nd trimester of pregnancy, and the 25-hydroxyvitamin D [25(OH)D] level of the participants was assessed. Using the INTERGROWTH-21st standards, the offsprings were classified into three groups based on their gestational age and birth weight, which were as follows: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Results: The average maternal vitamin D concentration was 61.1 nmol/L. The 25(OH)D concentrations were <75.0, <50.0, and <25.0 nmol/L in 76.6%, 31.1%, and 1.6% of the participants, respectively. Approximately 6.4%, 86.4%, and 7.2% of women delivered SGA, AGA, and LGA infants, respectively. No significant differences were observed in vitamin D levels between the three groups (P = 0.562). With the increase in 25(OH)D levels, the risk of SGA and LGA tended to increase and decrease, respectively. However, the results were not precise. AGA was not affected by 25(OH)D levels. The results of the curve fitting and threshold effect analyses did not support the correlation between vitamin D levels and SGA or LGA. Based on the univariate prediction model and the model that adjusted for the risk factors, the area under the curve was extremely small. Thus, 25(OH)D level is not an effective predictor of SGA and LGA. Conclusions: Low maternal vitamin D levels were not associated with SGA or LGA.
A Consensus Time for Performing Quality Control of 225Ac-Labeled Radiopharmaceuticals
Authors: Kelly James M. , Amor-Coarasa Alejandro , Sweeney Elizabeth , Babich John
Published: July 2020

Background: As 225Ac-labeled radiopharmaceuticals continue to show promise as targeted alpha therapeutics, there is a growing need to standardize quality control (QC) testing procedures. The determination of radiochemical purity (RCP) is an essential QC test. A significant obstacle to RCP testing is the disruption of the secular equilibrium between actinium-225 and its daughter radionuclides during labeling and analysis. In order to accelerate translation of actinium-225 targeted alpha therapy, we aimed to determine the earliest time point at which the RCP of an 225Ac-labeled radiopharmaceutical can be accurately calculated.Results: Six ligands were conjugated to macrocyclic metal chelators and labeled with actinium-225 under conditions designed to generate diverse incorporation yields. RCP was determined by radio thin layer chromatography (radioTLC) followed by exposure of the TLC plate on a phosphor screen either 0.5, 2, 3.5, 5, 6.5, or 26 h after the plate was developed. The dataset was used to create models for predicting the true RCP using pre-equilibrium measurements at early time points. The 585 TLC measurements span RCP values of 1.8% to 99.5%. The statistical model created from these data predicted an independent data set with high accuracy. Predictions made at 0.5 h are more uncertain than predictions made at later time points. This is primarily due to the decay of bismuth-213. At 2 h the mean average error is < 3%. A measurement of RCP > 90% at this time point predicts a true RCP > 97%.Conclusions: RCP of 225Ac-labeled radiopharmaceuticals can be quantified with acceptable accuracy at least 2 h after radioTLC. This time point best balances the need to accurately quantify RCP with the need to safely release the batch as quickly as possible.
Autoantibody-negative insulin-dependent Diabetes after COVID-19
Authors: Hollstein Tim , Schulz Juliane , Glück Andreas , Schulte Dominik M , Schreiber Stefan , Bornstein Stefan R , Laudes Matthias
Published: July 2020

Here we report the manifestation of insulin dependent diabetes after a COVID-19 infection in the absence of typical autoantibodies for type 1 diabetes. A 19-year-old Caucasian male subject presented to our emergency department with diabetic ketoacidosis (DKA). C-peptide levels accounted to 0.62µg/L in the presence of blood glucose concentrations of 30.6 mmol/L (552 mg/dL). The patient´s case history revealed a COVID-19 disease 6-8 weeks prior to admission. This is of interest, since COVID-19 internalization into host cells is mediated via Angiotensin-converting enzyme 2 (ACE2) [1], a transmembrane glycoprotein which amongst others is crucial for β-cell homeostasis and function [2,3,4]. Detailed laboratory testing was performed, revealing no serum-antibodies against islet-cells (ICA), glutamic acid decarboxylase (GAD65-AA), tyrosine phosphatase (IA-2-AA), insulin (IAA) and zinc-transport-8 (ZnT8-AA), but against COVID-19. Hence, this is a presentation of an insulin-dependent diabetes mellitus in the absence of markers of autoimmunity, which might suggest direct cytolytic effects of COVID-19 on pancreatic β-cells presumably mediated via ACE2.
Ease and equity of access to free DR-TB services in Nigeria- a qualitative analysis of policies, structures and processes
Authors: Oga-Omenka Charity , Bada Florence , Agbaje Aderonke , Dakum Patrick , Menzies Dick , Zarowsky Christina
Published: July 2020

Introduction:
Persistent low rates of case notification and treatment coverage reflect that accessing diagnosis and treatment for drug-resistant tuberculosis (DR-TB) in Nigeria remains a challenge, even though it is provided free of charge to patients. Equity in health access requires availability of comparable, appropriate services to all, based on needs, and irrespective of socio-demographic characteristics. Our study analyzed elements that facilitate or hinder equitable access for different groups of patients within the current health system to support DR-TB management in Nigeria.
Methods:
We conducted documentary review of guidelines and workers manuals, as well as 29 qualitative interviews, including 5 focus group discussions, with a total of 86 participants, in Nigeria. Between August and November 2017, we interviewed patients who were on treatment, their treatment supporter, and providers in Ogun and Plateau States, as well as program managers in Benue and Abuja. We adapted and used Levesque’s patient-centered access to care framework to analyze DR-TB policy documents and interview data.
Results:
Thematic analysis revealed inequitable access to DR-TB care for some patient socio-demographic groups. While patients were mostly treated equally at the facility level, some patients experienced more difficulty accessing care based on their gender, age, occupation, educational level and religion. Health system factors including positive provider attitudes and financial support provided to the patients facilitated equity and ease of access. However, limited coverage and the absence of patients’ access rights protection and considerations in the treatment guidelines and workers manuals likely hampered access.
Conclusion:
In the context of Nigeria’s low case-finding and treatment coverage, applying an equity of access framework was necessary to highlight gaps in care. Differing social contexts of patients adversely affected their access to DR-TB care. We identified several strengths in DR-TB care delivery, including the current financial support that should be sustained. Our findings highlight the need for government’s commitment and continued interventions.
Development and Validation of Nomograms for Predicting Overall Survival and Cancer-Specific Survival in Patients with Ovarian Clear Cell Carcinoma
Authors: Chen Qian , Wang Shu , Lang Jing-he
Published: July 2020

Background
Ovarian clear cell carcinoma (OCCC) is a rare histologic type of ovarian cancer. There is a lack of useful prognostic predictive tool for OCCC in clinical work. This study aimed to construct and validate nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with OCCC.
Methods
Data of patients with primary diagnosed OCCC in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016 was extracted. Prognostic factors were evaluated with LASSO COX regression and multivariate Cox regression analysis, which were applied to construct nomograms. The performance of the nomogram models was assessed by concordance index (C-index), calibration plots, decision curve analysis (DCA) and risk subgroup classification. The Kaplan-Meier curves were plotted to compare survival outcomes between subgroups.
Results
A total of 1541 patients from SEER registries were randomly divided into a training cohort (n = 1079) and a validation cohort (n = 462). Age, laterality, stage, lymph node (LN) dissected, organ metastasis and chemotherapy were independently and significantly associated with OS, while laterality, stage, LN dissected, organ metastasis and chemotherapy were independent risk factors for CSS. Nomograms were developed for prediction of 3- and 5‐year OS and CSS. The C-indexes for OS and CSS were 0.802[95% confidence interval (CI) 0.773–0.831] and 0.802 (0.769–0.835), respectively, in the training cohort, while 0.746 (0.691–0.801) and 0.770 (0.721–0.819), respectively, in the validation cohort. Calibration plots illustrated favorable consistency between the nomogram predicted and actual survival. C-index and DCA curves also indicated better performance of nomogram than the AJCC staging system. Significant differences were observed in survival curves of different risk subgroups.
Conclusions
We constructed predictive nomograms and a risk classification system to evaluate the OS and CSS of OCCC patients. They were validated to be of satisfactory predictive value, and could aid in future clinical practice.