bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learning improves the ability of sgRNA off-target propensity prediction
Authors: Liu Qiaoyue , Cheng Xiang , Liu Gan , Li Bohao , Liu Xiuqin 
Published: January 2020

Abstract
Background CRISPR/Cas9 system, as the third-generation genome editing technology, has been widely applied in target gene repair and gene expression regulation. Selection of appropriate sgRNA can improve the on-target knockout efficacy of CRISPR/Cas9 system with high sensitivity and specificity. However, when CRISPR/Cas9 system is operating, unexpected cleavage may occur at some sites, known as off-target. Presently, a number of prediction methods have been developed to predict the off-target propensity of sgRNA at specific DNA fragment. Most of them use artificial feature extraction operations and machine learning techniques to obtain off-target scores. With the rapid expansion of off-target data and the rapid development of deep learning theory, the existing prediction methods can no longer satisfy the prediction accuracy at the clinical level. Results Here, we propose a prediction method named CnnCrispr to predict the off-target propensity of sgRNA at specific DNA fragments. CnnCrispr automatically trains the sequence features of sgRNA-DNA pairs with GloVe model, and embeds the trained word vector matrix into the deep learning model including biLSTM and CNN with five hidden layers. We conducted performance verification on the data set provided by DeepCrispr, and found that the auROC and auPRC in the "leave-one-sgRNA-out" cross validation could reach 0.957 and 0.429 respectively (the pearson value and spearman value could reach 0.495 and 0.151 respectively under the same settings). Conclusion Our results show that CnnCrispr has better classification and regression performance than the existing states-of-art models. The code of CnnCrispr can be freely downloaded from https://github.com/LQYoLH/CnnCrispr.
Development and outcomes of a comprehensive multidisciplinary incidental lung nodule and lung cancer screening program
Authors: LeMense Gregory , Waller Ernest A. , Campbell Cheryl , Bowen Tyler 
Published: January 2020

Abstract
Background: Appropriate management of lung nodules detected incidentally or through lung cancer screening can increase the rate of early-stage diagnoses and potentially improve treatment outcomes. However, the implementation and management of comprehensive lung nodule programs is challenging. Methods: This single-center, retrospective report describes the development and outcomes of a comprehensive lung nodule program at a community practice in Tennessee. Computed tomography (CT) scans potentially revealing incidental lung nodules were identified by a computerized search. Incidental or screening-identified lung nodules that were enlarging or not seen in prior scans were entered into a nodule database and guideline-based review determined whether to conduct a diagnostic intervention or radiologic follow-up. Referral rates, diagnosis methods, stage distribution, treatment modalities, and days to treatment are reported. Results: The number of patients with lung nodules referred to the program increased over 2 years, from 665 patients in Year 1 to 745 patients in Year 2. Most nodules were incidental (62%-65%). Nodules identified with symptoms (15.2% in Year 1) or through screening (12.6% in Year 1) were less common. In Year 1, 27% (182/665) of nodules required a diagnostic intervention and 18% (121/665) were malignant. Most diagnostic interventions were image-guided bronchoscopy (88%) or percutaneous biopsy (9%). The proportion of Stage I-II cancer diagnoses increased from 23% prior to program implementation to 36% in Year 1 and 38% in Year 2. In screening cases, 71% of patients completed follow-up scans within 18 months. Only 2% of Year 1 patients under watchful waiting required a diagnostic intervention, of which 1% received a cancer diagnosis. Conclusions: The current study reports outcomes over the first two years of a lung cancer screening and incidental nodule program. The results show that the program was successful, given the appropriate level of data management and oversight. Comprehensive lung nodule programs have the potential to benefit the patient, physician, and hospital system.
Maternal pre-pregnancy body mass index, gestational weight gain and breastfeeding outcomes
Authors: Martin Hayley , Thevenet-Morrison Kelly , Dozier Ann 
Published: January 2020

Abstract
Background: It is well established that mothers with above-normal pre-pregnancy BMI are at increased risk of breastfeeding cessation; however, the impact of pregnancy weight-gain (PWG) is less well-defined. Excess PWG may alter the hormonal preparation of breast tissue for lactation, increase the risk of complications that negatively impact breastfeeding (e.g. Cesarean-section, gestational diabetes), and may make effective latch more difficult to achieve. Methods: Our objective was to determine the impact of PWG and pre-pregnancy BMI on the risk of breastfeeding cessation utilizing the Institute of Medicine’s 2009 recommendations. Cox proportional hazards models were utilized to estimate the risk of cessation of exclusive breastfeeding, and cessation of any breastfeeding among women who initiated exclusive and any breastfeeding, respectively, in a cross sectional sample of survey respondents from a New York county (N=1207). PWG category was interacted with pre-pregnancy BMI (3 levels of pre-pregnancy BMI, 3 levels of PWG). Confounders of the relationship of interest were evaluated using directed acyclic graphs and bivariate analyses; variables not on the proposed causal pathway and associated with the exposure and outcome were included in multivariate models. Results: After adjustment, women of normal and obese pre-pregnancy BMI with greater-than-recommended PWG had 1.39 (1.03-1.86) and 1.48 (1.06-2.07) times the risk of any breastfeeding cessation within the first 3 months postpartum compared to women with normal pre-pregnancy BMI who gained within PWG recommendations. Overweight women with greater-than-recommended PWG were at increased risk of cessation, although not significantly (aHR[95% CI]: 1.29 [0.95 – 1.75]). No significant relationship was observed for exclusive breastfeeding cessation. Conclusions: Pre-pregnancy BMI and PWG may be modifiable risk factors for early breastfeeding cessation. Understanding the mechanism behind this risk should be ascertained by additional studies aimed at understanding the physiological, social, logistical (positioning) and other issues that may lead to early breastfeeding cessation.
Metaphase spread of mouse oocytes
Authors: SANKAR ADITYA 
Published: January 2020

Abstract
this protocol briefly described the procedure of performing metaphase spreads on single mouse MII (metaphase-II) oocytes. This will allow the user to count the chromosomes as well as perform additional immunofluorescence based stains for protein localization on fixed samples. the assay is however prone to false positive whole chromosome aneuploidies due to the nature of dropping the oocytes onto the etched glass slides. Hence, some skill development by repetition is required to ensure consistent outcomes. The whole procedure from obtaining oocytes to imaging happens over two days.
Effects of Ultrasound-Guided Paravertebral Block on MMP-9 and Postoperative Pain in Patients Undergoing VATS Lobectomy: A Randomized, Controlled Clinical Trial
Authors: Chu Haichen , Dong He , Wang Yongjie , Niu Zejun 
Published: January 2020

Abstract
Background: Local anesthesia can reduce the response to surgical stress and decrease the consumption of opioids, which may reduce immunosuppression and potentially delay postoperative tumor recurrence. We compared paravertebral block(PVB) combined with general anesthesia(GA) and general anesthesia regarding their effects on matrix metalloproteinase-9 (MMP-9) and postoperative pain after video-assisted thoracoscopic surgery(VATS) lobectomy.
Methods: 54 patients undergoing elective VATS lobectomy at a single tertiary care, teaching hospital located in Qingdao between May 2 2018 and Sep 28 2018 were randomised by computer to either paravertebral block combined with general anesthesia or general anesthesia. The primary outcome was pain scores during postoperative 48h. The secondary outcome were plasma concentrations of MMP-9, complications, and duration of postoperative hospital stay.
Results: 75 were enrolled to the study, of whom 21 were excluded before surgery. We analyzed lobectomy patients undergoing paravertebral block combined with general anesthesia (n=25) or general anesthesia (n=24). Both groups were similar regarding baseline characteristics. Pain scores were lower at 4h and 24h in PVB/GA group, compared with GA group (2.53±0.83 vs 3.4±0.91; 2.2±0.94 vs 3.0±0.93, respectively, P <0.05). There were no difference at 1h and 48h between groups. Patients in the PVB/GA group showed a greater decrease in plasma MMP-9 level at T1 and T2 after VATS lobectomy ( P <0.05). Postoperative complications and length of stay did not differ by anesthetic technique.
Conclusions: The paravertebral block/general anesthesia can provide statistically better pain relief and attenuate MMP-9 response to surgery and after VATS lobectomy. This technique may be beneficial for patients to recover rapidly after lung surgery and reduce postoperative tumor recurrence.
Antibiotic treatment regimens for bone infection after debridement: a study of 902 cases
Authors: Author) Xiaohua Wang(Former Corresponding , Fang Li , Chen Yueqi , Wang Shulin , Ma Huan , Zhao Hongwen , Author) Zhao Xie(New Corresponding 
Published: January 2020

Abstract
Purpose: Our aim was to investigate the clinical efficacy and complications of antibiotics treatment duration for the patients of bone infection. Methods: We retrospectively analyzed the patients with bone infection admitted to our hospital between March 2013 and October 2018. The surgical debridement was performed and the patients were divided into three groups: IV group (Intravenous antibiotics for 2 weeks); Oral group (Intravenous antibiotics for 2 weeks followed by oral antibiotics for 4 weeks); Rifampicin group (Intravenous antibiotics for 2 weeks followed by oral antibiotics plus rifampicin for 4 weeks). The infection control rate and complications were compared. Results ： A total of 902 patients were enrolled, the infection sites included 509 tibias, 228 femurs, 32 humeri, 23 radii and ulnae, 40 calcanei, 23 multiple-site infections and the other sites 47 cases. After at least 6 months of follow-up, 148 (16.4%) patients had recurrence of infection. The recurrence rate of IV group was 17.9%, which was no significant higher than that of Oral group (10.1%) or Rifampicin group (10.5%). The abnormal rate of Glutamic-pyruvic transaminase(ALT) in IV group was 15.1%, which was lower than that of Oral group (18.0%) and Rifampicin group (27.4%), P=0.026. The positive rates of proteinuria in the three groups were 3.2%, 4.5%, and 9.3%, respectively, P=0.020. Conclusion: After debridement of bone infection, the additional oral antibiotic treatment may increase the damage of liver and kidney, and can not significantly reduce the infection recurrence rate. Therefore, it is recommended to adopt short-term systemic antibiotic treatment after debridement.
Exposure to Baby-Friendly Hospital Practices and Mothers’ Achievement of their Planned Duration of Breastfeeding.
Authors: Lok Kris Y.W. , Chow Charlotte L.Y. , Fan Heidi S.L. , Chan Vincci H.S. , Tarrant Marie 
Published: January 2020

Abstract
Background: Both breastfeeding intentions and exposure to baby-friendly hospital practices have been associated with a longer duration of breastfeeding. This study aims to examine the effect of exposure to baby-friendly hospital practices on mothers’ achievement of their planned duration of breastfeeding.
Methods: A total of 1011 mother-newborn pairs from the postnatal units of four public hospitals in Hong Kong were recruited. Sociodemographic data and breastfeeding intention data were collected via self-report questionnaires during the postnatal hospitalization and exposure to Baby-Friendly hospital practices were assessed through hospital records and maternal self-report. Breastfeeding status after hospital discharge was assessed through telephone follow-up for up to 12 months postnatal, or until participants were no longer breastfeeding.
Results: Only 55% (n=552) of study participants achieved their intended duration of breastfeeding. Participants with higher socioeconomic status, previous breastfeeding experience, and those who had lived in Hong Kong for less than 5 years, were more likely to achieve their planned duration of breastfeeding. Among baby-friendly hospital practices, feeding only breast milk during the hospitalization and providing information about breastfeeding support on discharge were associated with participants’ achieving their individual breastfeeding intentions. After adjustment, when compared with women who experienced one baby-friendly practice, participants who experienced six baby-friendly hospital practices were significantly more likely to achieve their planned duration of breastfeeding (adjusted odds ratio=8.45, 95% confidence interval 3.03 – 23.6).
Conclusions : Nearly half of participants did not achieve their planned breastfeeding duration. Exposure to baby-friendly hospital practices, especially in-hospital exclusive breastfeeding and providing breastfeeding support information upon hospital discharge may help more mothers to achieve their individual breastfeeding goals.
Immunofluorescence of mouse zygotes and preimplantation embryos
Authors: SANKAR ADITYA 
Published: January 2020

Abstract
This protocol is based on previously published work and described the procedure of immunofluorescence of mouse zygotes and preimplantation embryos. The procedure takes 2 days from recovery of gametes/embryos from the mouse to imaging of samples in a confocal microscope. The procedure uses bent capillaries and a mouth pipette with a filter, allowing for movement of the samples between solutions following necessary incubation times. This simple procedure works quite efficiently and is an easy skill to master with the availability of the necessary tools.
Simulation-based low-dose, high-frequency plus mobile mentoring versus traditional group-based trainings among health workers in Ebonyi and Kogi States, Nigeria; a cluster randomized controlled trial
Authors: UGWA EMMANUEL , Kabue Mark , Otolorin Emmanuel , Yenokyan Gayane , Oniyire Adetiloye , Orji Bright , Okoli Ugo , Enne Joseph , Alobo Gabriel , Olisaekee Gladys , Oluwatobi Adebayo , Oduenyi Chioma , Aledare Adekunle , Onwe Boniface , Ishola Gbenga 
Published: January 2020

Abstract
Background: There are few studies from low- and middle-income countries on learning outcomes among health workers trained on day of birth care using onsite, simulation-based, low-dose, high frequency (LDHF) training plus mobile (m) mentoring. The aim of this study was to compare their knowledge and skills competencies with those of health workers trained using the traditional offsite, group-based training (TRAD) approach in Kogi and Ebonyi states, Nigeria, over a 12-month period.

Methods: We conducted a prospective cluster randomized controlled trial, enrolling 299 health workers in 60 health facilities in Kogi and Ebonyi states, randomized to either LDHF/m-mentoring (intervention, n=30 facilities) or traditional group-based training (TRAD, n=30 facilities) control arm. Health workers in both arms received basic emergency obstetric and newborn care training with simulated practice using anatomic models and role-plays. The control arm participants were trained offsite while the intervention arm were trained onsite where they work. Mentorship was done through telephone calls and reminder text messages. The multiple choice questions and objective structured clinical examinations mean scores were compared; p-value <0.05 was considered statistically significant. Qualitative data were collected and analyzed along themes of interest.

Results: The mean knowledge scores between the two arms at months 3 and 12 post-training were equally high; no statistically significant differences. Both arms showed improvements in composite scores for assessed BEmONC clinical skills from around 30% at baseline to 75% and above at endline (p <0.05). Overall, the observed improvement and retention of skills was higher in intervention arm compared to the control arm at 12 months post-training, (p<0.05). Some LDHF/m-mentoring approach trainees reported that mentors’ support improved their acquisition and maintenance of knowledge and skills, which may have led to reductions in maternal and newborn deaths in their facilities.

Conclusion: The LDHF/m-mentoring intervention is more effective than TRAD approach in improving health workers’ skills acquisition and retention. Health care managers should have the option to select the LDHF/m-mentoring learning approach, depending on their country’s priorities or context, as it ensures health workers remain in their place of work during training events thus less disruption to service delivery.
IgG anti-hinge antibody against IgG4 F(ab’)2 generated by not matrix metalloproteinase-3 but pepsin is a useful diagnostic marker for rheumatoid arthritis, even seronegative rheumatoid arthritis.
Authors: Ota Toshiyuki , Ota Shun-ichiro , Uchino Ayumi , Nagano Shuji 
Published: January 2020

Abstract
Background The pepsin agglutinator, discovered over 50 years ago, has recently referred to be an anti-hinge antibody (AHA) because of main reacting with the IgG hinge epitope. AHA shows different reactivity for each hinge epitope generated by each protease that cleaves the hinge region at different sites. Moreover, AHA shows different reactivity against different hinge epitopes derived from each IgG subclass even when the same protease is used. Since production of matrix metalloproteinase-3 (MMP-3) is enhanced in rheumatoid arthritis (RA), the specific AHA might be increasingly produced. The purpose of this study is to determine whether AHA against IgG hinge epitopes produced by MMP-3 is specifically elevated in RA. Methods Serum IgG or IgA class of AHA against the IgG1- or IgG4 F(ab’) 2 generated by either matrix metalloproteinase 3 (MMP-3) or pepsin was measured by ELISA in 81 healthy controls (HC) and 111 patients with RA. Receiver operating characteristic (ROC) analysis was used for obtaining optimal cutoff values and cutoff values indicating high specificity (>95%) of the AHA. Targeted epitope of the AHA was investigated by inhibition ELISA. Results Seven AHAs were statistically higher in RA than HC, except IgG AHA against IgG1 F(ab’) 2 generated by proteolytic cleavage of MMP-3. The areas under the curve of ROC curve were 0.66-0.80, although the sensitivities at high specificity were low (5.4-24.3%). The cumulative number of positive AHA in each individual was statistically higher in RA than HC, suggesting the extreme extent of AHA repertoires in RA. Inhibition studies revealed that IgG AHA against IgG4 F(ab’) 2 generated by pepsin cross-reacted with IgG1 F(ab’) 2 generated by pepsin. Although development of IgA AHAs in RA seems to be remarkable and specific, multivariate logistic regression analysis identified IgG AHA against IgG4 F(ab’) 2 generated by pepsin as an independent variable for RA diagnosis, even in RA patients who were negative for both RF and ACPA [odds ratio 1.18 (95% confidence interval 1.06-1.32); P =0.003]. Conclusion In RA, we observed diversification and amplification of AHA repertoires and diagnostic utility of the specific AHA against IgG4 F(ab’) 2 generated by pepsin, but not MMP-3.
Bioinformatics approach for potential genes associated with osteoarthritis
Authors: Chai Yi , Mai Cong-Ying , Zhang Ming-Yue , Xu Dao-Ming , Tan Feng , Li Xing , Fan Qiaoling 
Published: January 2020

Abstract
Background: Osteoarthritis is the main cause of disability and pain. Due to limited understanding of the disease mechanism, it is generally difficult to diagnose early and eliminate sequelae. The aim of this study was to identify novel biomarkers for osteoarthritis (OA) using a bioinformatics approach.

Method: The gene expression dataset GSE82107 were obtained from the Gene Expression Omnibus (GEO) database. Matrix quality assessment was performed using corrplot packages and principal component analysis. The differentially expressed genes (DEGs) picked out using GEO2R tool. Enrichment analyses were performed using The Database for Annotation, Visualization and Integrated Discovery and Gene Set Enrichment Analysis (GSEA). Weighted correlation network analysis (WGCNA) was used to find gene modules highly associated with OA. Cytoscape with Molecular Complex Detection (MCODE) plug-in was utilized to analyze protein-protein interaction of these DEGs. Receiver operator characteristic curve analysis was used to evaluate the diagnostic effectiveness of genes.

Results: Samples with different conditions (HC and OA) are obviously distinguished, and the distance between biological replicates is relatively close. In total, 1676 DEGs were identified. Enrichment analysis showed that there were some gene sets related to OA pathology, such as chondrocyte development. The results of WGCNA analysis showed that 298 genes were most positive associated with OA. 10 common genes obtained were selected as candidate core genes. ROC results showed that 5 of these genes had the greatest diagnostic value.

Conclusion: This is the first study to identify biomarkers related to OA by combining multiple algorithms such as GSEA, WGCNA, MCODE and ROC. We suggest that GLG1, PAPSS2, CTSK, TIMP1 and SDC1 could serve as valuable biomarkers. Further studies are needed to examine the precise role and mechanism of these genes in OA.