bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying Balanced Chromosomal Translocations in Human Embryos by Oxford Nanopore Sequencing and Breakpoints Region Analysis
Authors: Pei Zhenle , Deng Ke , Lei Caixai , Du Danfeng , Yu Guoliang , Sun Xiaoxi , Xu Congjian , Zhang Shuo 
Published: January 2022

Background: Balanced chromosomal aberrations, especially balanced translocations, can cause infertility, recurrent miscarriage or having chromosomally defective offspring. Preimplantation genetic testing for structural rearrangement (PGT-SR) has been widely implemented to improve the clinical outcomes by selecting euploid embryos for transfer, whereas embryos with balanced translocation karyotype were difficult to be distinguished by routine genetic techniques from those with a normal karyotype.Method: In this present study, we developed a clinically applicable method for reciprocal translocation carriers to reduce the risk of pregnancy loss. In the preclinical phase, we identified reciprocal translocation breakpoints in blood of translocation carriers by long-read Oxford Nanopore sequencing, followed by junction-spanning polymerase chain reaction (PCR) and Sanger sequencing. In the clinical phase of embryo diagnosis, aneuploidies and unbalanced translocations were screened by comprehensive chromosomal screening (CCS) with single nucleotide polymorphism (SNP) microarray, carrier embryos were diagnosed by junction-spanning PCR and family haplotype linkage analysis of the breakpoints region. Amniocentesis and cytogenetic analysis of fetuses in the second trimester were performed after embryo transfer to conform the results diagnosed by the presented method.Results: All the accurate reciprocal translocation breakpoints were effectively identified by Nanopore sequencing and confirmed by Sanger sequencing. Twelve embryos were biopsied and detected, the results of junction-spanning PCR and haplotype linkage analysis were consistent. In total, 12 biopsied blastocysts diagnosed to be euploid, in which 6 were aneuploid or unbalanced, three blastocysts were identified to be balanced translocation carriers and three to be normal karyotypes. Two euploid embryos were subsequently transferred back to patients and late prenatal karyotype analysis of amniotic fluid cells was performed. The outcomes diagnosed by the current approach were totally consistent with the fetal karyotypes.Conclusions: In summary, these investigations in our study illustrated that chromosomal reciprocal translocations in embryos can be accurately diagnosed. Long-read Nanopore sequencing and breakpoint analysis contributes to precisely evaluate the genetic risk of disrupted genes, and provides a way of selecting embryos with normal karyotype, especially for couples those without a reference.
Identification of Inflammation-Related Biomarker Pro-ADM for Male Patients With Gout by Comprehensive Analysis
Authors: Qiu Kangli , Zeng Tianshu , Liao Yunfei , Min Jie , Zhang Nan , Peng Miaomiao , Kong Wen , Chen Lu-lu 
Published: January 2022

ObjectiveGout is a local inflammatory disease caused by the deposition of monosodium urate (MSU) crystals in joints or adjacent tissues. When some gout occurs without hyperuricemia, or its clinical symptoms and signs are not typical, the diagnosis of gout will be delayed, so there is an urgent need to find a new biomarker to predict and diagnose of gout flare. Our research attempts to find the key genes and potential molecular mechanisms of gout through bioinformatics analysis, and collected general data and blood biochemical samples of patients with gout and healthy, then analyzed and compared the expression of factors regulated by key genes.MethodGSE160170 were downloaded from GEO database for analysis. The data were normalized to identify the differentially expressed genes (DEGs), then GO and KEGG enrichment analysis were applied. Protein-protein interaction (PPI) networks and hub genes between DEGs were identified. Then collect general information and blood samples from male patients with acute gout, hyperuricemia and healthy. ELISA method was used to detect pro-ADM levels of different groups, and the data was input into SPSS statistical software for analysis.ResultWe identified 266 DEGs (179 up-regulated and 87 down-regulated) between gout patients and healthy controls. GO analysis results show that DEGs are mostly enriched in inflammatory response, growth factor activity, cytokine activity, chemokine activity, S100 protein binding and CXCR chemokine receptor binding. KEGG pathway analysis showed that DEGs are mainly related to Chemokine signaling pathway and Cytokine-cytokine receptor interaction. ADM, CXCR1, CXCR6, CXCL3, CCL3, CCL18, CCL3L3, CCL4L1, CD69, CD83, AREG, EREG, B7RP1, HBEGF, NAMPT and S100B are the most important hub genes in the PPI network. We found that the expression of pro-ADM in the gout group and hyperuricemia group was higher than that in the healthy group, and the difference was statistically significant.ConclusionIn this study, a series of bioinformatics analyses were performed on DEGs to identify key genes and pathways related to gout. Through clinical verification, we found that pro-ADM can be used as an inflammation-related biomarker for acute attacks of gout, providing new ideas for the diagnosis and treatment of gout.
Rituximab in the Treatment of Interstitial Lung Diseases Related to Anti-Melanoma Differentiation-Associated Gene 5 Dermatomyositis: A Systematic Review
Authors: He Chenjia , Li Wenyu , Xie Qibing , Yin Geng 
Published: January 2022

ObjectiveThe effectiveness of rituximab in anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM) with interstitial lung disease (ILD) has been explored only in isolated case reports and small series. This paper aims to review the current evidence regarding rituximab (RTX) use in the treatment of ILD related to anti-MDA5 DM (anti-MDA5 DM-ILD).MethodsWe conducted a review by searching PubMed, Web of Science, Embase, and Cochrane for articles with information on patients with anti-MDA5 DM and RTX treatment, published until August 2021, in English language. The selected studies listed variation in chest high-resolution computed tomography (HRCT) and/or pulmonary function test (PFT) as a primary outcome, in patients with anti-MDA5 DM-related ILD after using RTX.ResultsOf the 145 potentially eligible articles, 17 were selected. The information gathered from a total of 35 patients with anti-MDA5 DM-ILD was reviewed, including 13 men and 22 women. Patient age at onset was 47.60 ± 13.72 years old. A total of 11.43% (4/35) of the patients were found to have chronic ILD (C-ILD) and 88.57% (31/30) exhibited rapidly progressive ILD (RP-ILD). Most patients (29/30) had typical DM rashes. Prior to RTX administration, the majority of patients (27/35) were treated with medium- or high-dose glucocorticoids and at least one additional immunotherapeutic agent. With regard to RTX efficacy for ILD in anti-MDA5 DM, 71.43% (25/35) of the patients responded to treatment. Skin rash also improved in more than half of the patients after RTX treatment. The most common side effects were infections, reported by 37.14% (13/35) of the patients after using RTX.ConclusionAs a CD20 targeting drug, RTX is a promising therapeutic tool for anti-MDA5 DM-ILD, although the risk of infections should be considered before treatment. Further prospective controlled studies are required to evaluate the optimal RTX treatment regimen.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289714, identifier CRD42021289714.
Seasonality and Annual Utilization Patterns of Antibacterials at Muhimbili National Hospital, Dar es Salaam, Tanzania: A 2015 Monthly Survey
Authors: Sangeda Raphael Zozimus , Urassa Mariki I. , Buma Deus , Musiba George Nyamanda , Chiwanga Faraja S. , Chambuso Mhina , Horumpende Pius Gerald 
Published: January 2022

IntroductionAntibacterial utilization studies can help identify areas of intervention of antimicrobial stewardship programs (ASP) to facilitate rational use and prevent the emergence of antimicrobial resistance (AMR). Assessment and comparison of antibacterial utilization depend on the Anatomical Therapeutic Chemical (ATC) classification system and Defined Daily Dose (DDD) recommended by the World Health Organization (WHO) collaborative center for international drug monitoring. This study aimed to determine the DDD of each prescribed antibacterial group and the proportions of wide-spectrum antibacterials used at Muhimbili National Hospital (MNH) in Tanzania to allow baseline data for hospital ASPs.MethodsA retrospective analytical study using data collected from 1st January 2015 to 31st December 2015 was undertaken at MNH. Data on antibacterials prescribed and dispensed were obtained from the MNH database. The ATC/DDD system was used to classify and quantify the antibacterial utilization patterns.ResultsA total of 10,643.1 DDDs were used in thirteen ward units at the Kibasila, Mwaisela and Sewahaji blocks of the MNH. Eighteen different antibacterials were prescribed and dispensed to 1496 patients. Capsules were the most dispensed dosage form. The drug ciprofloxacin was the leading antibacterial prescribed, with a DDD of about 3780 (35.5%) per year. This was followed by metronidazole and amoxicillin. The proportion of wide-spectrum antibacterials was as high as 66%. Utilization peaks were noted in April, July and September. There was a significant monthly increase in antibacterials utilization between January and December 2015 (p-value = 0.002, R-square = 0.64). The trends forecasted increased through June 2016.ConclusionsUtilization trends indicated a significant monthly increase in 2015 at MNH wards in Tanzania. The use of wide-spectrum antibacterials was widespread. This calls for continued antibacterial utilization surveillance and implementation of hospital-based ASP to mitigate the rapidly rising global threat of AMR.
Long-Term Outcomes and Prognostic Factors of Superficial Esophageal Cancer in Patients Aged ≥ 65 Years
Authors: Chang Jin Won , Jung Da Hyun , Huh Cheal Wung , Park Jun Chul , Shin Sung Kwan , Lee Sang Kil , Lee Yong Chan 
Published: January 2022

BackgroundThe number of elderly patients with superficial esophageal cancer (SEC) is increasing. We aimed to evaluate the clinical outcomes and prognostic factors of overall survival (OS) in elderly patients undergoing endoscopic submucosal dissection (ESD) or surgical resection for SEC.MethodsBetween January 2001 and May 2020, 290 patients aged ≥65 years who underwent ESD or surgical resection for SEC were evaluated. Their clinical outcomes and prognosis were assessed, and independent risk factors for OS were identified.ResultsThe mean patient age (269 men and 21 women) was 70.9 years (range 65–90 years). En bloc, R0, and curative resections were achieved in 94.5%, 90.0%, and 73.4% of the patients, respectively. During the follow-up [mean: 54.6 months (range: 1–210 months)], 79 patients died. The 3-, 5-, and 10-year OS rates were 82.5, 73.1, and 59.7%, respectively. In multivariate analysis, cancer history of the other organs, American Society of Anesthesiologists performance status, and presence of lymphovascular involvement (hazard ratio = 1.852, 1.656, and 1.943, respectively; all P &lt; 0.05) were independent risk factors for poor OS. The high-risk group (≥2 risk factors) showed a significantly lower OS than the low-risk group (≤ 1 risk factor) (P &lt; 0.001).ConclusionsThe three risk factors could be useful in predicting the long-term prognosis of elderly patients with SEC.
Application of Machine Learning Algorithms to Predict Lymph Node Metastasis in Early Gastric Cancer
Authors: Tian HuaKai , Ning ZhiKun , Zong Zhen , Liu Jiang , Hu CeGui , Ying HouQun , Li Hui 
Published: January 2022

ObjectiveThis study aimed to establish the best early gastric cancer lymph node metastasis (LNM) prediction model through machine learning (ML) to better guide clinical diagnosis and treatment decisions.MethodsWe screened gastric cancer patients with T1a and T1b stages from 2010 to 2015 in the Surveillance, Epidemiology and End Results (SEER) database and collected the clinicopathological data of patients with early gastric cancer who were treated with surgery at the Second Affiliated Hospital of Nanchang University from January 2014 to December 2016. At the same time, we applied 7 ML algorithms—the generalized linear model (GLM), RPART, random forest (RF), gradient boosting machine (GBM), support vector machine (SVM), regularized dual averaging (RDA), and the neural network (NNET)—and combined them with patient pathological information to develop the best prediction model for early gastric cancer lymph node metastasis. Among the SEER set, 80% were randomly selected to train the models, while the remaining 20% were used for testing. The data from the Second Affiliated Hospital were considered as the external verification set. Finally, we used the AUROC, F1-score value, sensitivity, and specificity to evaluate the performance of the model.ResultsThe tumour size, tumour grade, and depth of tumour invasion were independent risk factors for early gastric cancer LNM. Comprehensive comparison of the prediction model performance of the training set and test set showed that the RDA model had the best prediction performance (F1-score = 0.773; AUROC = 0.742). The AUROC of the external validation set was 0.73.ConclusionsTumour size, tumour grade, and depth of tumour invasion were independent risk factors for early gastric cancer LNM. ML predicted LNM risk more accurately, and the RDA model had the best predictive performance and could better guide clinical diagnosis and treatment decisions.
Protective Effects of Appropriate Amount of Nuts Intake on Childhood Blood Pressure Level: A Cross-Sectional Study
Authors: Feng Ye , Bi Yang , Tang Xian , Zhang Ping , Tong Jishuang , Peng Xin , Tian Jie , Liang Xiaohua 
Published: January 2022

ObjectiveIncreased blood pressure (BP) is a major risk factor for cardiovascular disease (CVD) in adults. Regular consumption of nuts may improve some BP in adults whereas evidence in children is relatively lacking. This study aimed to determine the efficacy of nuts intake on BP in children.MethodsStratified cluster sampling was performed to include a total of 15,268 primary school children aged 6–12 years in urban and rural areas in Southwest China. The daily nuts intake dosage was collected by questionnaires, and generalized linear model (GLM) and logistic regression were used to analyze the relationship between nuts intake and BP.ResultsFor the total subjects, 11,130 (72.9%) participants consumed &lt;35 g/day of nuts, 1,145 (7.5%) participants consumed 35 g/day ≤ nut &lt;50 g/day of nuts, 2,053 (13.4%) participants consumed 50~100 g/day of nuts, and 940 (6.2%) participants consumed over 100 g/day of nut. For sex subgroup, 1,074 (13.53%) boys and 979 (13.35%) girls consumed 50~100 g/day of nuts. Compared with the 50~100 g/day of nuts intake group, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were significantly different in &lt;35 g/day, 35g/day ≤ nut &lt;50 g/day, and &gt;100 g/day nuts intake groups (all p &lt; 0.001). The logistic regression showed that compared with the 50~100 g/day group, the other three groups are more likely associated with childhood hypertension (all p &lt; 0.001). Therefore, a U-shaped relationship between nuts intake and BP level was identified.ConclusionsThe finding suggests that intake of 50~100 g/day nuts is the recommended dose of nuts intake to control childhood hypertension, as well as for cardioprotection purposes.
Relationship Between Peripheral Refraction in Different Retinal Regions and Myopia Development of Young Chinese People
Authors: Zheng Xiangyue , Cheng Dejin , Lu Xiaoli , Yu Xiaoyi , Huang Yuting , Xia Yujie , Lin Chuni , Wang Zhao 
Published: January 2022

ObjectiveTo observe the associations between regional peripheral refraction and myopia development in young Chinese people.MethodsTwo hundred and forty-one young adult subjects (21 emmetropes, 88 low myopes, 94 moderate myopes, and 38 high myopes) aged 18–28 years were included, and only the right eyes were tested. Eye biometrics were measured before pupil dilation using the Lenstar. Relative peripheral refractive errors (RPRE) were measured after pupil dilation using multispectral refractive topography (MRT), at nine retinal eccentricities: 0–5, 5–10, 10–15, 15–20, 20–25, 25–30, 30–35, 35–40, and 40–45 degrees.ResultsIn this study, RPRE increased with eccentricity, and it shows a growing trend with the increase of the degree of myopia among emmetropia, low myopia and moderate myopia groups, and RPRE varied with myopia severity at eccentricities between 20 and 35 degrees only. In addition, axial length (AL) and RPRE were positively correlated between 20 and 45 degrees, and AL was an independent risk factor for RPRE between 20 and 35 degrees.ConclusionThese findings indicate that the eccentricities between 20 and 35 degrees RPRE may be closely related to refractive development and eye growth in young Chinese people.
Development and Electromyographic Validation of a Compliant Human-Robot Interaction Controller for Cooperative and Personalized Neurorehabilitation
Authors: Dalla Gasperina Stefano , Longatelli Valeria , Braghin Francesco , Pedrocchi Alessandra , Gandolla Marta 
Published: January 2022

BackgroundAppropriate training modalities for post-stroke upper-limb rehabilitation are key features for effective recovery after the acute event. This study presents a cooperative control framework that promotes compliant motion and implements a variety of high-level rehabilitation modalities with a unified low-level explicit impedance control law. The core idea is that we can change the haptic behavior perceived by a human when interacting with the rehabilitation robot by tuning three impedance control parameters.MethodsThe presented control law is based on an impedance controller with direct torque measurement, provided with positive-feedback compensation terms for disturbances rejection and gravity compensation. We developed an elbow flexion-extension experimental setup as a platform to validate the performance of the proposed controller to promote the desired high-level behavior. The controller was first characterized through experimental trials regarding joint transparency, torque, and impedance tracking accuracy. Then, to validate if the controller could effectively render different physical human-robot interaction according to the selected rehabilitation modalities, we conducted tests on 14 healthy volunteers and measured their muscular voluntary effort through surface electromyography (sEMG). The experiments consisted of one degree-of-freedom elbow flexion/extension movements, executed under six high-level modalities, characterized by different levels of (i) corrective assistance, (ii) weight counterbalance assistance, and (iii) resistance.ResultsThe unified controller demonstrated suitability to promote good transparency and render both compliant and stiff behavior at the joint. We demonstrated through electromyographic monitoring that a proper combination of stiffness, damping, and weight assistance could induce different user participation levels, render different physical human-robot interaction, and potentially promote different rehabilitation training modalities.ConclusionWe proved that the proposed control framework could render a wide variety of physical human-robot interaction, helping the user to accomplish the task while exploiting physiological muscular activation patterns. The reported results confirmed that the control scheme could induce different levels of the subject's participation, potentially applicable to the clinical practice to adapt the rehabilitation treatment to the subject's progress. Further investigation is needed to validate the presented approach to neurological patients.
Synergies of Multiple Zeitgebers Tune Entrainment
Authors: Grabe Saskia , Mahammadov Elmir , Olmo Marta Del , Herzel Hanspeter 
Published: January 2022

Circadian rhythms are biological rhythms with a period close to 24 h. They become entrained to the Earth’s solar day via different periodic cues, so-called zeitgebers. The entrainment of circadian rhythms to a single zeitgeber was investigated in many mathematical clock models of different levels of complexity, ranging from the Poincaré oscillator and the Goodwin model to biologically more detailed models of multiple transcriptional translational feedback loops. However, circadian rhythms are exposed to multiple coexisting zeitgebers in nature. Therefore, we study synergistic effects of two coexisting zeitgebers on different components of the circadian clock. We investigate the induction of period genes by light together with modulations of nuclear receptor activities by drugs and metabolism. Our results show that the entrainment of a circadian rhythm to two coexisting zeitgebers depends strongly on the phase difference between the two zeitgebers. Synergistic interactions of zeitgebers can strengthen diurnal rhythms to reduce detrimental effects of shift-work and jet lag. Medical treatment strategies which aim for stable circadian rhythms should consider interactions of multiple zeitgebers.
High Level of the Fibrin Degradation Products at Admission Predicts Parenchymal Hematoma and Unfavorable Outcome of Ischemic Stroke After Intravenous Thrombolysis
Authors: Liu Chang , Zhang Yun , Niu Lingchuan , Li Jiani 
Published: January 2022

Background and PurposeWe aim to investigate whether the higher admission fibrin degradation products (FDPs) levels are associated with parenchymal hematomas (PHs) and unfavorable outcome after intravenous thrombolysis (IVT).MethodsConsecutive patients with acute ischemic stroke treated with IVT were studied. The FDP level was obtained on admission. PH was evaluated 24 h after treatment. The unfavorable outcome was defined as a 90-day modified Rankin Scale &gt;2. The multivariable linear stepwise regression was used to assess independent factors associated with the log-transformed FDP (lgFDP). The receiver operating characteristics (ROCs) curve analysis was used to determine the predictive value of the FDP level for PH and unfavorable outcome. The logistic regression was used to identify independent predictors for PH and unfavorable outcome. The mediation analyses were performed to investigate associations among the FDP level, PH, and outcome.ResultsA total of 181 patients were included in the final analyses [median age, 73 (63–79) years; 102 (56.4%) males; and the median baseline National Institutes of Health Stroke Scale (NIHSS) score, 8 (5–15)]. The lgFDP was independently associated with age (B = 0.011, 95% CI 0.006–0.015, p &lt; 0.001) and the baseline NIHSS score (B = 0.016, 95% CI 0.008–0.025, p &lt; 0.001). The FDP was positively associated with PH [odds ratio (OR) 1.034, 95% CI 1.000–1.069; p = 0.047]. According to the ROC analysis, the best discriminating factor for unfavorable outcome was the FDP ≥3.085 μg/ml. The FDP ≥3.085 μg/ml was an independent predictor of unfavorable outcome (OR 7.086, 95% CI 2.818–17.822; p &lt; 0.001). Mediation analysis revealed that the association of the FDP ≥3.085 μg/ml with unfavorable outcome was not mediated by PH (p = 0.161).ConclusionThe admission FDP levels can predict PH and unfavorable outcome in patients with acute ischemic stroke after IVT. PH does not mediate the effect of the FDP level on the outcome.