bluuebunny/crossref_metadata_2025 huggingface dataset:
Symptomatic Features of 932 Hospitalized Patients with COVID-19 in Wuhan
Authors: Sun Liang-Liang , Wang Jian , Wang Yu-Sheng , Hu Ping-Fang , Zhao Zheng-Qing , Chen Wei , Ning Bei-Fang , Yin Chuan , Hao Yu-Shi , Wang Qiong , Wang Chen , Liu Ya-Long , Chen Cheng , Yin Ji-Zhong , Huang Hai , Xie Wei-Fen
Published: January 2021

BackgroundMuch remains unknown about COVID-19 onset and rehabilitation's symptomatic features, especially the long-term health consequences of patients with COVID-19 who have been discharged from the hospital.MethodsIn this cohort study, we collected the first pandemic data of hospitalized patients in Wuhan from February 20 to March 31, 2020. All patients completed a 3-month follow-up after discharge. We carefully analyzed the detailed symptomatic characteristics of severe COVID-19 at illness onset and three months after discharge, compared it with non-severe patients, and used multiple logistic regression to determine potential symptomatic risk factors for severe COVID-19.ResultsA total of 932 hospitalized patients with COVID-19 were enrolled, including 52 severe cases and 880 non-severe cases. Fever (60%), cough (50.8%), and fatigue (36.4%) were the most common symptoms, followed by anorexia (21.8%) and dyspnea (19.2%). The median duration of fever was seven days, which was characterized by persistent low fever. The median duration of cough was 17 days, characterized by dry cough without sputum. Most dyspnea occurred on the fourth day after symptom onset, with a median duration of 16 days. The incidences of taste loss and olfactory disturbance were only 6.2% and 3.1%, respectively. Multivariate logistic regression analysis showed that age over 65 years old (OR 6.52, 95% CI 3.27-13.02, P<0.0001), male sex (3.71, 1.90-7.26, P = 0.0001), fever lasting for more than five days (1.90, 1.00-3.62, P=0.0498), anorexia at onset (2.61, 1.26-5.40, P=0.0096), and modified Medical Research Council level above grade 2 when dyspnea occurred (14.19,7.01-28.71, P<0.0001) were symptomatic risk factors for severe COVID-19. Three months after discharge from the hospital, 6.2% of patients still cough, 7.2% of patients still dyspnea, and 1.8% still fatigue, and 1.5% of patients had olfactory or taste disorders.ConclusionsCOVID-19 caused clusters of symptoms, with multiple systems involved. Specific symptomatic features at the onset of illness have predictive value for severe COVID-19. Persistent legacy symptoms are more frequent in severe COVID-19 patients.
Platelets and Pro-Angiogenic Circulating Cells Accelerate Skin Wound Healing
Authors: Erratico Silvia , Belicchi Marzia , Meregalli Mirella , Silvestre Dario Di , Tripodi Luana , Palma Antonella De , Jones Rebecca , Ferrari Emanuele , Porretti Lura , Trombetta Elena , Merlo Giorgio R. , Mauri Pierluigi , Torrente Yvan
Published: January 2021

BackgroundDelayed wound healing and chronic skin lesions represent a major health problem. Over the past years, growth factors mediated by platelet-rich plasma (PRP) and cell-based therapies were developed as effective and affordable treatment able to improve wound healing capacity. However, the precise molecular mechanism through which PRP exhibits its beneficial effects remains unrevealed. Herein we show that a combination of PRP and pro-angiogenic cells (AngioPRP) could exert a synergistic positive effect on keratinocyte proliferation and angiogenesis accelerating wound healing.MethodWe designed a sterile and closed class IIa device (NovySep) for single use only to collect blood-derived mononucleated cells and the plasma phase after centrifugation without opening the system. We performed in vitro and in vivo wound healing experiments to assess the angiogenic potential of AngioPRP; we evaluated the extracellular matrix remodeling and the physical properties of treated wounds through mechanical (stress-strain test) and proteomics analysis.ResultAngioPRP enhanced wound healing by promoting uniform regeneration of the basal and granular layers and vessel remodeling. We coupled this effect with normalization of mechanical properties of rescued mouse wounds, which is sustained by a correct arrangement of elastin and collagen fibers. The network analysis-based protein–protein interactions of AngioPRP-treated wounds demonstrated a fingerprint of AngioPRP-related proteins that may provide the signal for a faster wound healing response which include Caveolin and EGFR/TGFβ/β-catenin pathways.ConclusionA combined treatment composed of PRP and a pool of pro-angiogenic/keratogenic cells (AngioPRP) may provide a more integrated method to supports wound healing, by promoting a cascade of events leading to the reduction of TGFβ1/β-catenin up-downstream signaling pathways. The molecular mechanism undergoing the support of AngioPRP to wound healing opens new perspectives in the treatment of skin injuries.
MicroRNA-21 Promotes Allergic Airway Inflammation and AHR and Inhibits Mesenchymal Stem Cell Migration in Cockroach Allergen Induced Asthma Model
Authors: Cheng Tianli , heng jianfu , Mei Quanhui , Chen Lijun , Zeng Feng
Published: January 2021

BackgroundMesenchymal stem cells (MSCs) have been used to treat asthma in a mouse model. However, the efficacy and mechanism of MSCs are not elucidated. MicroRNAs (miRNAs) play a key rolein asthma and related to the aim of this study was to illustrate the role of miR21 and its influence on MSC migration in asthma model. MethodsA mouse model of asthma was established using cockroach extract (CRE), and miR-21 expression was examined. A miR-21 lentivirus construct was used to investigate the role of miR-21 in vivo and in vitro in mouse bone marrow-derived (BM-) MSCs. A TOPFlash reporter gene assay was used to study the signaling downstream of miR-21. IL-4, IL-5, IL-13, IgE, and IgG1 levels in bronchoalveolar lavage fluids were determined by enzyme-linked immunosorbent assays.ResultsMiR-21 was upregulated in CRE-induced asthmatic mice. MiR-21 promoted allergic airway inflammation and airway hyperreactivity by inhibiting BM-MSC migration. β-Catenin was found to act downstream of miR-21 as a negative regulator of miR-21. Rescue experiments verified that miR-21 inhibited BM-MSC migration by suppressing Wnt/β-catenin signaling.ConclusionMiR-21 promotes allergic airway inflammation and AHR and inhibits BM-MSC migration through Wnt/β-catenin signaling, which may serve as an effective therapeutic target for asthma.
Construction and Validation of a Nomogram for The Prediction of Overall Survival in Intrahepatic Cholangiocarcinoma
Authors: Yang Yong-jing , Cao Ling , Yan Ling , Zhu Jing , Li Qiang , Wu Chun-jiao
Published: January 2021

Objective: This study aimed to establishand validates a nomogram to predict the overall survival (OS) of patients with intrahepatic cholangiocarcinoma (ICC).Patients and methods: The ICC patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Then, the independent prognosis-related factors were obtained from the training set using the Cox regression model for the establishment of a nomogram.Results: We identified 3675 eligible patients with a median survival time of 9 months (0–153 months). According to multivariate analysis, age, sex, marital status, grade, T stage, N stage, M stage, surgery, chemotherapy and radiotherapy were identified as the factors to independently predictthe prognosis for ICC (all P<0.05). Thereafter, the above factors were incorporated for the construction of a nomogram. In comparison with the AJCC 8th TNM classification system and the SEER summary stage system, our constructed nomogram showed higher ability in discrimination, as revealed by the C-index (all P<0.001).Besides, the internal as well as external calibration curve analysis demonstrated that the predicted results were highly consistent with the actual ones. On the other hand, our nomogram outperformed the AJCC 8th TNM classification system and the SEER summary stage system in predicting the 3- and 5-year OS, as suggested by time-independent area under the curve (tAUC) values.Conclusion: Our constructed nomogram performs well, indicating its potential as an efficient approach to evaluate the prognosis of ICC patients.
Refractive Outcomes of Table-Mounted and HandheldAuto-Refractometers in Children: An Observational Cross-Sectional Study
Authors: karab müjdat , karabulut sinem , karalezli Aylin
Published: January 2021

Background: To compare the refractive results of two autorefractors.Methods: We designed this study as an observational, cross-sectional study. We compared the mean spheric and cylinder power, spherical equivalent, Jackson cross-cylinder values, determined the limits of agreement (LoA), and evaluated reliability.Results: Nidek HandyRef-K autorefractor measured more astigmatism and myopia in terms of the mean cylindrical power (P<.001) and spherical equivalent (P=.024). Nidek HandyRef-K showed significantly more myopic results in subgroups with spherical power more than +1.50 Diopters (D) hyperopia and -3.00 D myopia (P=.031; P=.045; P=.026; respectively) and higher astigmatism in the subgroup with the cylindric power less than -1.00 D (P<.001). The mean differences and 95% LoA were 0.06 D ± 0.47 D (-0.82 D to 0.98 D) in spherical power, 0.08 D ± 0.28 D (-0.47 D to 0.64 D) in cylindrical power, 0.11 D ± 0.47 D (-0.81 D to 1.01 D) in spherical equivalent, 0.02 D ± 0.36 D (-0.73 D to 0.69 D) in Jackson cross-cylinder power at 0°, 0.005 D ± 0.54 D (-1.07 D to 1.06 D) in Jackson cross-cylinder power at 45°. There was a strong correlation for spherical power (Spearman’s rho=0.99, P<.001), cylindrical power (Spearman’s rho=0.88, P<.001), spherical equivalent (Spearman’s rho=0.98, P<.001).Conclusion: Nidek HandyRef-K showed more myopic results regarding spherical equivalent and cylindrical power. Nidek HandyRef-K showed significantly more myopia in spherical power more than +1.50 D hyperopia, -3.00 D myopia, and more prominent astigmatism in cylindrical power less than -1.00 D subgroups.
Identification of a 10-Gene Signature Model to Predict Efficacy of Neoadjuvant Therapy in Patients With HER2 Positive Breast Cancer.
Authors: Wang Yusong , Wang Mozhi , Sun Xiangyu , Yao Litong , Wang Mengshen , Dong Haoran , Li Xinyan , He Mingcong , Xu Yingying
Published: January 2021

BackgroundPatients with human epidermal growth factor receptor 2 (HER2) positive breast cancer represent a poor prognosis, which are recommended to be treated with neoadjuvant therapy (NAT). Tumor immune microenvironment, especially tumor infiltrating cells (TILs), are proved to predict the efficacy of NAT. However, validated immune-related multi-gene signatures for HER2-positive BC are still lacking.MethodsWe collected gene expression arrays of pre-NAT samples from the National Center for Biotechnology Information Gene Expression Omnibus. Totally 4 studies are included in our study (n=295, no. of train =207, no. of validation=95) to construct the signature. Single Sample Gene Set Enrichment Analysis (ssGSEA)and weighted gene co-expression network analysis (WGCNA)were used to quantify immune-infiltrating components in tumor environment and to identify immune related modules. We used spline regression to evaluate non-linear effect of genes and to construct the signature.ResultsImmune infiltration status was significantly related to pathological complete response (pCR) (p=0.02). We filtered 80 differential expression genes according to immune infiltration status, and identified two gene modules correlated to pCR and immune infiltration status. CCL5, CD72, PTGDS, CYTIP, PAX5, and estrogen receptor (ER)status were significantly related with pCR in linear multivariate analysis. In spline regression, non-linear aspects of MAP7, IL2RB, CD3G, PTPRC, TRAC were relevant to pCR. We constructed a signature concerning both linear and non-linear effect of genes, which was validated in 5-fold cross validation (AUC=0.81) and an external validation cohort (n=88) (AUC=0.797).ConclusionsIn HER2 positive BC, immune infiltration status should be involved into consideration to make optimal regimens. A ten-gene generalized non-linear signature including ER status could predict the efficacy of NAT.
microRNA-1915-3p Promotes Cell Metastasis and Progression by Targeting Bcl2L11 in Hepatocellular Carcinoma
Authors: Huang Wenjie , Li Sufen , Chen Xianhua , Sun Lin , Pan Gangxi , Chen Jianlin , Sun Xiujuan , Shen Yongqi , Lu Yonggang , Sun Yifan
Published: January 2021

BackgroundIncreasing evidence suggests that miR-1915-3p plays vital regulatory roles in metastasis and progression of several types of cancer. However, the roles and underlying mechanism of miR-1915-3p in hepatocellular carcinoma (HCC) remains largely unclear. MethodsWe carried out a bioinformatic meta-analysis to investigate a possible role of miR-1915-3p as prognostic biomarkers. In vitro cellular models of HCC were used for functional studies exploring the role of miR-1915-3p in HCC development and progression. Finally, in vivo studies were performed to demonstrate that miR-1915-3p is a viable therapeutic target.ResultsThis study showed that miR-1915-3p was significantly increased in HCC tissue samples and cell lines, and high miR-1915-3p expression was associated with a poor overall survival (OS) and disease-free survival (DFS) time of HCC patients. Overexpression or ablation of miR-1915-3p expression resulted in accelerated or inhibited cell proliferation, migration, and invasion respectively in HCC cells. In addition, miR-1915-3p induced downregulation of proapoptotic factors, including caspase3, caspase8, BAD, Bcl2L11, and P53. It also induced upregulation of antiapoptotic Bcl-2, protecting HCC cells from apoptosis. A biological analysis indicated that miR-1915-3p could be directly targeted to Bcl2L11 to regulate the proliferation, invasion, and migration of HCC cells. Furthermore, in vivo studies confirmed that treatment with miR-1915-3p retarded the growth of tumor in nude mice. Conclusionour study provided the evidence for the regulatory role of miR-1915-3p in HCC, which was causally linked to targeting of Bcl2L11. Medications that abrogate excessively expressed miR-1915-3p may offer novel targets for the management of HCC.
Use of Vasopressors Increases the Risk of Mortality in Severe Traumatic Brain Injury: A Nationwide Retrospective Cohort Study in Japan
Authors: Hosomi Sanae , Sobue Tomotaka , Kitamura Tetsuhisa , Hirayama Atsushi , Ogura Hiroshi , Shimazu Takeshi
Published: January 2021

BackgroundPharmacological elevation of blood pressure is frequently incorporated in severe traumatic brain injury management algorithms. However, there is limited evidence on prevalent clinical practices regarding resuscitation for severe traumatic brain injury using vasopressors. We conducted a nationwide retrospective cohort study to determine the association between the use of vasopressors and mortality following hospital discharge in patients with severe traumatic brain injury, and to determine whether the use of vasopressors affects emergency department mortality or the occurrence of cognitive dysfunction.MethodsData were collected between January 2004 and December 2018 from the Japanese Trauma Data Bank, which includes data from 272 emergency hospitals in Japan. Adults aged ≥16 years with severe traumatic brain injury, without other major injuries, were examined. A severe traumatic brain injury was defined based on the Abbreviated Injury Scale code and a Glasgow Coma Scale score of 3–8 on admission. Multivariable analysis and propensity score matching were performed. Statistical significance was assessed using 95% confidence intervals (CIs).ResultsIn total, 10 284 patients were eligible for analysis, with 650 patients (6.32%) included in the vasopressor group and 9634 patients (93.68%) included in the non-vasopressor group. The proportion of deaths on hospital discharge was higher in the vasopressor group than in the non-vasopressor group (81.69% [531/650] vs. 40.21% [3,874/9,634]). This finding was confirmed by multivariable logistic regression analysis (adjusted odds ratio [OR], 5.71; 95% CI: 4.56–7.16). Regarding propensity score-matched patients, the proportion of deaths on hospital discharge remained higher in the vasopressor group than in the non-vasopressor group (81.66% [530/649] vs. 50.69% [329/649]) (OR, 4.33; 95% CI: 3.37–5.57). The vasopressor group had a higher emergency department mortality rate than the non-vasopressor group (8.01% [52/649] vs. 2.77% [18/649]) (OR, 3.05; 95% CI: 1.77–5.28). There was no reduction in complications of cognitive disorders in the vasopressor group (5.39% [35/649] vs. 5.55% [36/649]) (OR, 0.97; 95% CI: 0.60–1.57).ConclusionsIn this population, the use of vasopressors for severe traumatic brain injury was associated with higher mortality on hospital discharge. Our results suggest that vasopressors should be avoided in most cases of severe traumatic brain injury.
The management and outcome of paediatric splenic injuries in the Netherlands
Authors: Grootenhaar Maike , Lamers Dominique , Ulzen Karin Kamphuis-van , de Blaauw Ivo , Tan Edward C
Published: January 2021

Background: Non-operative management (NOM) is generally accepted as a treatment method of traumatic paediatric splenic rupture. However, considerable variations in management exist. This study analyses local trends in aetiology and management of paediatric splenic injuries and evaluates the implementation of the guidelines proposed by the American Paediatric Surgical Association (APSA) in a level 1 trauma centre. Methods: The charts of paediatric patients with blunt splenic injury (BSI) who were admitted or transferred to a level 1 trauma centre between 2003 and 2020 were retrospectively assessed. Information pertaining to demographics, mechanism of injury, injury description, associated injuries, intervention and outcomes were analysed and compared to international literature.Results: There were 130 patients with BSI identified (63.1% male), with a mean age of 11.3 ± 4.0 and a mean injury severity score (ISS) of 21.6 ± 13.7. Bicycle accidents were the most common trauma mechanism (23.1%). Sixty-four percent were multi-trauma patients, 25% received blood transfusions, and 31% were hemodynamically unstable. Mean injury grade was 3.0, with 30% of patients having a high-grade injury. In total, 75% of patients underwent NOM with a 100% efficacy rate. Total splenectomy rate was 6.2%. Four patients died due to brain damage. Patients with a high-grade BSI (grade IV-V) had a significantly higher ISS and longer bedrest and more often presented with an active blush on computed tomography (CT) scans than patients with a low-grade BSI (grade I-III). Non-operative management was mainly the choice of treatment in both groups (76.6% and 79.5%, respectively). Hemodynamic instability was a predictor for operative management (OM) (p=0.001). Predictors for a longer length of stay (LOS) included concomitant injuries, hemodynamic instability and OM (all p < 0.02). Interobserver agreement in the grading of BSI is moderate, with a Cohens Kappa coefficient of 0.493.Conclusion: Non-operative management has proven to be a realistic management approach in both low- and high-grade splenic injuries. Consideration for operative management should be based on hemodynamic instability. Compared to the anticipated length of bedrest and hospital stay outlined in the APSA guidelines, the Netherlands can reduce the length of bedrest and hospital stay through their non-operative management.Level of evidence: Therapeutic study, level III
Alterations in The Gut Microbiota and Metabolite Profiles in The Context of Neuropathic Pain
Authors: Chen Peng , Wang Chen , Ren Yan-na , Ye Zeng-jie , Jiang Chao , Wu Zhi-bing
Published: January 2021

The aim of this study was to explore the relationships among gut microbiota disturbances and serum and spinal cord metabolic disorders in neuropathic pain. 16S rDNA amplicon sequencing and serum and spinal cord metabolomics were used to identify alterations in the microbiota and metabolite profiles in the sham rats and the chronic constriction injury (CCI) model rats. Correlations between the abundances of gut microbiota components at the genus level, the levels of serum metabolites, and pain-related behavioural parameters were analysed. Ingenuity pathway analysis (IPA) was applied to analyse the interaction networks of the differentially expressed serum metabolites. First, we found that the composition of the gut microbiota was different between rats with CCI-induced neuropathic pain and sham controls. At the genus level, the abundances of Helicobacter, Phascolarctobacterium, Christensenella, Blautia, Streptococcus, Rothia and Lactobacillus were significantly increased, whereas the abundances of Ignatzschineria, Butyricimonas, Escherichia, AF12, and Corynebacterium were significantly decreased. Additionally, 72 significantly differentially expressed serum metabolites and 17 significantly differentially expressed spinal cord metabolites were identified between the CCI rats and the sham rats. Finally, correlation analysis showed that changes in the gut microbiota was significantly correlated with changes in serum metabolite levels, suggesting that dysbiosis of the gut microbiota is an important factor in modulating metabolic disturbances in the context of neuropathic pain. In conclusion, our research provides a novel perspective on the potential roles of the gut microbiota and related metabolites in neuropathic pain.
Association of Different Interventions to Increase Leukocyte Testing During Treatment With Dimethyl Fumarate
Authors: Heidenreich Paul , Sahay Anju , Lin Shoutzu , Gholami Parisa , Goldstein Mary , Moore Von , Burk Muriel , Glassman Peter , Cunningham Francesca
Published: January 2021

Background: Dimethyl fumarate (DMF), a treatment for multiple sclerosis, may cause leukopenia and infection. Accordingly, periodic white blood cell (WBC) monitoring is recommended. We sought to evaluate the VA Medication Use Evaluation Tracker (MUET) initiative which provides VA facilities with a list of patients prescribed DMF therapy without a documented white blood cell count (WBC).Methods: We identified 118 VA facilities with patients treated with DMF from 1/1/2016 through 9/30/2016. We determined WBC measurements within three months of the first filled prescription. The lead pharmacist at each facility was surveyed asking if any of seven intervention types were used to improve WBC monitoring (academic detailing, provider education without academic detailing, electronic clinical reminders, request for provider action plan, draft orders for WBC monitoring, patient mailings, and patient calls).Results: The facility response rate for the survey was 78% (92 of 118 facilities). For the 92 included facilities (1,115 patients) the mean rate of WBC monitoring was 54%. Use of the at-risk patient lists was noted in 55% (51/92) of facilities. In multivariate analysis, only academic detailing and provider education remained significantly associated with higher WBC monitoring. From a base WBC monitoring rate of 46%, academic detailing increased the rate by 17% (95% CI 4 to 30%, p=0.011) and provider education increased the rate by 9% (95% CI 0.6 to 18%, p=0.037). The WBC monitoring rate increased by 3.8% for each additional intervention used (95% CI 1.2%-6.4%, p=0.005).Conclusions: Interventions focused on the physician, including academic detailing, were associated with improved WBC monitoring for patients at risk for leukopenia from dimethyl fumarate treatment.
Characterization of Tau ELISAs for Evaluating Tau Accumulation in the Brains With Alzheimer’s Disease
Authors: Shinohara Mitsuru , Hirokawa Junko , Shimodaira Akemi , Tashiro Yoshitaka , Suzuki Kaoru , Fukumori Akio , Matsubara Tomoyasu , Morishima Maho , Saito Yuko , Murayama Shigeo , Sato Naoyuki
Published: January 2021

Background: One main pathological hallmark of Alzheimer’s disease (AD) is tau accumulation as neurofibrillary tangles (NFTs) in the brain. Although sandwich enzyme-linked immunosorbent assays (ELISAs) are useful for quantifying tau levels, including those in CSF, plasma and brain, it has not yet been determined which antibody combination is the most appropriate for assessing the neuropathological accumulation of tau in the brain. Methods: We developed several sandwich tau ELISAs by introducing antibodies against several tau epitopes, including from its N-terminal and C-terminal regions, and evaluated tau levels depending on disease stage, brain areas, and other AD-related changes. Results: We observed that tau levels in insoluble brain fraction determined by each ELISAs differ depending on the epitopes of the antibodies: there is a trend that non-AD control samples yield relatively high signals when an antibody against the N-terminal region of tau is used. On the other hand, ELISAs combining two antibodies against the later-middle to C-terminal regions of tau produced substantially increased signals from AD samples, compared to those from non-AD controls. Such ELISAs better distinguish AD and non-AD controls, and the results are more closely associated with Braak NFT stage, Aβ accumulation, and neuroinflammatory markers. In addition, these ELISAs can reflect the pattern of tau spread across brain regions. Conclusions: Tau ELISAs that combine two antibodies against the later-middle to C-terminal regions of tau can better reflect neuropathological tau accumulation, which would enable to evaluate tau accumulation in the brain at a biochemical level.
Deepoxy-deoxynivalenol (DOM-1), a Derivate of Deoxynivalenol (DON), Exhibits Less Toxicity on Intestinal Barrier Function, Campylobacter Jejuni Colonization and Translocation in Broiler Chickens
Authors: Ruhnau Daniel , Hess Claudia , Doupovic Barbara , Grenier Bertrand , Schatzmayr Dian , Hess Michael , Awad Wageha
Published: January 2021

Background: Intestinal epithelial cells are challenged by mycotoxins and many bacterial pathogens. It was previously shown that the mycotoxin deoxynivalenol (DON) as well as Campylobacter (C.) jejuni have a negative impact on gut integrity. Recently it was demonstrated that DON increased the load of C. jejuni in the gut and inner organs. Based on this finding, it was hypothesized the DON metabolite (deepoxy-deoxynivalenol, DOM-1), which is produced during the biotransformation of DON and is less toxic than DON itself should be able to reduce the negative effects of DON on colonization and translocation of C. jejuni in broilers because it lacks the epoxide ring responsible for the toxicity of DON. Methods: A total of 180 broiler chickens were housed in floor pens on wood shavings with feed and water provided ad libitum. Birds were divided into six groups (n = 30 with 5 replicates/group): 1. Control, 2. DOM-1, 3. DON, 4. DOM-1 + C. jejuni, 5. DON + C. jejuni, 6. C. jejuni. At day 14, birds of groups 4, 5 and 6 were orally inoculated via feeding tube (gavage) with 1-ml of a PBS suspension containing 1x108 CFU of C. jejuni NCTC 12744. The performance parameters: body weight (BW), body weight gain (BWG), and feed intake of the birds were determined. At 7, 14, and 21 days post infection, samples from liver, spleen, duodenum, jejunum and cecum were aseptically collected and processed for bacteriological investigations. Finally, at each killing time point, segments of duodenum, jejunum and cecum were harvested and prepared for Ussing chamber studies to measure the paracellular mannitol fluxes. Results: A significant decrease in body weight was observed for chickens receiving the DON diet with or without C. jejuni compared to the other groups. Furthermore, it was found that the co-exposure of birds to DON and C. jejuni resulted in a higher C. jejuni load not only in the gut but also in liver and spleen due to increased paracellular permeability of the duodenum, jejunum and cecum. On the contrary, DOM-1 supplementation in the feed improved the birds’ performance and led to a better feed conversion ratio throughout the trial. Furthermore, DOM-1 did not negatively affect gut permeability and decreased the C. jejuni counts in the intestine and internal organs. Conclusion: Altogether, the dietary inclusion of DOM-1 had a positive effect on performance, did not negatively affect gut paracellular permeability and reduced the C. jejuni load in the intestine, indicating that this mycotoxin metabolite could exert beneficial effects on the gastrointestinal tract by biotransformation, including minimizing the Campylobacter burden in chickens and also the risk for human infection.
A Discrete Multi Objective Artificial Bee Colony Algorithm for a Real World Electronic Device Testing Machine Allocation Problem
Authors: Xie Jin , Li Xinyu , GAO Liang
Published: January 2021

This paper studies the Electronic Device Testing Machine Allocation Problem (EDTMAP), aiming to improve the production of electronic devices and reduce the scheduling distance of testing machines through reasonable machine allocation. Firstly, a mathematical model is formulated for the EDTMAP to maximize both production and the opposite of the scheduling distance of testing machines. Secondly, we develop a Discrete Multi Objective Artificial Bee Colony (DMOABC) algorithm to solve the EDTMAP. A crossover operator and a local search operator are designed to improve the exploration and exploitation of the algorithm, respectively. Some numerical experiments are designed to evaluate the performance of the proposed algorithm. The experimental results demonstrate the superiority of the proposed algorithm compared with NSGA --Ⅱ and SPEA2. Finally, the mathematical model and the DMOABC algorithm areapplied to a real world factory that tests radio frequency modules. The result also verifies our method can significantly improve production and reduce the scheduling distance of testing machines.
Comparison of Two Surgical Methods in the Treatment of Acute Achilles Tendon Rupture: a Case-control Study
Authors: Yu Hao , Wang Fangyuan , Xie Jia , Zhan Junfeng , Yao Yunfeng , Jing Juehua , Li Jun
Published: January 2021

Background: The Achilles tendon is the strongest tendon in the human body but also prone to injury and rupture, thereby requiring early diagnosis and treatment to prevent the development of lower limb dysfunction. Currently, the best treatment method for acute Achilles tendon rupture remains controversial. As both traditional incision repair and minimally invasive repair have limitations, we propose a new surgical method: the modified Ma-Griffith method combined with minimally invasive small incision(M-G/MISI). This study aimed to compare the efficacy of M-G/MISI and the modified suture technique (MST) for the treatment of acute Achilles tendon rupture.Methods: We conducted a retrospective review of the medical records of all patients who underwent treatment for acute Achilles tendon rupture between January 2012 and January 2020 at our hospital. A total of 67 patients were included and divided into two groups: 34 males in the M-G/MISI treatment group and 33 patients (2 females and 31 males) in the MST group. Demographic characteristics, operative details, and postoperative complications were recorded, and data were statistically analysed using SPSS 24.0 for Windows (IBM Corp. Released 2016. IBM SPSS Statistics for Windows, Version 24.0) to compare the treatment efficacy of the two surgical methods.Results: Although there was no difference in demographic characteristics between the two groups, there were significant differences in the incision length, intra-operative blood loss, post-operative Achilles tendon total rupture score, and post-operative American Orthopedic Foot and Ankle Society score. Post-operatively, there was one case of traumatic Achilles tendon rupture in the M-G/MISI group and one case each of infection and deep vein thrombosis in the modified suture group.Conclusion: After follow-up, the post-operative recovery of acute Achilles tendon rupture treated with M-G/MISI is better than that with the MST.
Preliminary Establishment of a Spinal Stability Scoring System for Multiple Myeloma
Authors: Yao Xingchen , Shi Xiangjun , Xu Ziyu , Tan Jie , Wei Yanzhe , Qi Lei , Zhou Zihao , Li Lihong , Du Xinru
Published: January 2021

Background: Multiple myeloma is an incurable malignant plasma cell disorder that represents the most common primary malignant bone tumor. It commonly involves bone metastasis in multiple vertebral bodies, which SINS scoring system may not be fully applicable to MM patients. We designed a stability evaluation system to evaluate the spinal stability of patients with MM spinal involvement in order to guide clinical treatment.Methods: By using Delphi method, information was collected and extracted through a series of questionnaires and improved via feedback and we preliminary establishment of a spinal stability scoring system for multiple myeloma.Results: Fifteen clinicians completed a second round of questionnaires and compared their answers with those of the first round of questionnaires to identify significant comments or changes that required group discussions. As a result, no further feedback was used to improve the scoring system. After integrating the information from the expert consultation questionnaire, we established the initial scoring system for MM spine stability and used the scoring system to assess a series of representative clinical cases. The scoring system consisted of the following six components. The MM spinal stability scoring system was created by calculating the scores of the six separate components: Location, Pain, Number of segments, Physiological curvature, Comorbidities and Neurological function. The minimum value was ‘0’, and the maximum value was ‘24’. A score of ‘0-10’ indicated ‘spine stability’, a score of ‘11-17’ indicated ‘potential instability’, and a score of ‘18-24’ indicated ‘spine instability’. Patients with a score of ‘11-24’ need an intervention such as surgery.Conclusions: The initial establishment of the MM spine stability scoring system provides a vital theoretical basis for the evaluation of spine stability in individuals with MM. Trial registration: The conducted study contains a retrospective analysis of medical records of our hospital database. Beijing Chao-yang Hospital Human Research Ethics Committee classifies this as a retrospective audit. The ethics approval and consent was given for the conducted retrospective data analysis.
Optimization of Communication to Improve the Medication Process in Nursing Home Care – a Qualitative Evaluation
Authors: Nestler Nadja , Mahlknecht Angelika , Bauer Ulrike , Krisch Laura , Osterbrink Juergen , Flamm Maria
Published: January 2021

Background: Cooperation and communication are central factors for a safe medication process, especially residents of nursing homes, due to their multimorbidity, and hence, their need of numerous drugs. An interprofessional team is needed to handle potential problems of the medication process, but as several studies confirm, communication and cooperation within the medication process allow for improvement. This study aims to understand functioning and malfunctioning aspects of communication and cooperation within the medication process, to use these results to optimize the communication and coordination between the involved professional groups, and to examine changes after intervention.Methods: This qualitative study is part of an interventional study. Involved professional groups of the medication process were interviewed before and after an intervention to evaluate experiences regarding communication, cooperation, as well as with the intervention overall. Six group discussions and two expert interviews with general practitioners, nurses of nursing homes and pharmacists were recorded and transcribed. Data analysis was done via qualitative content analysis to examine communication and cooperation of the professional groups. A derived coding tree was developed, output from codes was used to sort data into themes, and quotations were selected that exemplified themes for inclusion in this manuscript.A combined intervention was implemented that included an education program concerning medication safety and an online communication tool.Results: Responsibility and availability are two central aspects for efficient cooperation and communication. Problems are mostly system-related due to the necessity to use traditional ways of communication. The usage of a new online communication platform enables a regular medication review and an independence from personal attendances of all professional groups.Conclusion: An interprofessional education program as well as the implementation of an online communication tool overcame barriers of communication and cooperation, systematized the medication process, and allowed for independent working routines of the professional groups.Trial registration: DRKS Data Management, ID: DRKS00007900
Effects of single transplantation and multiple transplantation of human umbilical cord mesenchymal stem cells on the recovery of ovarian function in the treatment of premature ovarian failure in mice
Authors: Lv Xiaodan , Guan Chunyi , Li Ying , Su Xing , Zhang lu , Wang Xueqin , Ma Xu , Xia hongfei
Published: January 2021

BackgroundAt present, there is no effective treatment for premature ovarian failure (POF), and stem cell therapy is considered the most promising treatment. Human umbilical cord blood mesenchymal stem cells (hUC-MSCs) have shown good regenerative ability in a variety of diseases including POI, but the method and dosage of hUC-MSCs to treat POI are not clear. This study aims to explore the treatment options of hUC-MSCs for POF by comparing single injection and multiple injections of hUC-MSCs on the ovarian function repair of POF caused by chemotherapy drugs.MethodsFemale mice were injected intraperitoneally with 30 mg/kg of busulfan and 120 mg/kg of cyclophosphamide to induce POF. In the single hUC-MSCs injection group, 7 days after the mice were injected with cyclophosphamide and busulfan, hUC-MSCs were transplanted into these mice. In the multiple injection group, hUC-MSCs were transplanted 7 days, 14 days and 21 days after the mice were injected with cyclophosphamide and busulfan. We evaluated ovarian morphology, fertility, follicle stimulating hormone and estradiol concentration, and follicle count, evaluated POF model and cell transplantation. In addition, real-time PCR, immunohistochemistry, miRNA chip and mRNA chip are used to evaluate the effect of cell therapy.ResultsCompared with the POF group, the ovarian size and primordial follicle count in the hUC-MSC group were significantly improved, and the fertility was also significantly improved. Immunohistochemistry showed that compared with the POF group, the anti-Mullerian hormone and Ki-67 in the ovary of the hUC-MSC group increased significantly, and ovulation was significantly restored. Real-time PCR showed that the expression of follicle stimulating hormone receptor, inhibin and inhibin in the hUC-MSCs group was significantly restored compared with the POF group. The results of mRNA and miRNA chips also showed that hUC-MSC restored ovarian function at the gene level. long-term treatment effect shows that the multiple transplantation hUC-MSCs group is better than the single transplantation hUC-MSCs group. 60 days after the mice were injected with cyclophosphamide and busulfan, the organ coefficient of multiple transplantation of hUC-MSCs increased compared with the POF group, the number of primary follicles increased, and hormone secretion increased. ConclusionThe results show that multiple trasplantation of hUC-MSCs can promote the recovery of ovarian function in POF mice more than a single transplantation. This study provides a basis for the therapeutic dose and therapeutic effect of hUC-MSCs on POF.
Comparison of Choroidal Thickness Measurements between Spectral-domain Optical Coherence Tomography and Swept-source Optical Coherence Tomography in Children
Authors: Lee Chun On , Zhang Xiujuan , Tang Shumin , Chen Li Jia , Cheung Carol , Yam Jason
Published: January 2021

PURPOSE: Choroidal thickness is associated with many ocular conditions, interchangeability among different generations of optical coherence tomography is therefore important for both research purpose and clinical application. Hence, we compared choroidal thickness measurements between spectral-domain optical coherence tomography (SD-OCT) and swept-source optical coherence tomography (SS-OCT) in healthy pediatric eyes.METHODS: Children from the population–based Hong Kong Children Eye Study were recruited. Choroidal thickness was measured by both devices. Intra-class correlation coefficient (ICC) was used to compare the measurements.RESULTS: A total of 114 children with mean age of 7.38±0.82 years were included. The central foveal choroidal thickness (CFCT) measured by SD-OCT and SS-OCT was 273.24±54.29μm and 251.84±47.12μm respectively. Inter-device correlation coefficient was 0.840 (95%CI: 0.616-0.918). However, choroidal thickness obtained by SD-OCT was significantly thicker than that measured by SS-OCT with a mean difference of 21.40±33.13μm (P<0.001). Bland-Altman limit of agreement on the relative difference scale for SD-OCT/SS-OCT was 86.33μm. Validated conversion equation for translating SD-OCT CFCT measurement into SS-OCT was SS-OCT = 35.261 + 0.810 x SD-OCT. CONCLUSIONS: ICC shows an acceptable agreement between SD-OCT and SS-OCT, however, there was a significant inter-device difference of choroidal thickness measurements in normal children eyes. Therefore, the measurements are not interchangeable.
Glutamine, Glutamate, and Aspartate Improves Morphology and Energy Production of Small Intestine in Piglets with Different Energy Levels Diets
Authors: Wang Jing , Wang Nan , Qi Ming , Li Jianjun , Tan Bie , Yin Yulong
Published: January 2021

Background: Weaning-stress may cause reduced energy intake for maintenance of mucosal structure. Glutamine (Gln), glutamate (Glu), and aspartate (Asp) are major energy sources for small intestine. This study investigated whether Gln, Glu, and Asp improve the intestinal morphology via regulating the energy metabolism in weaning-piglet. A total of 198 weaned-piglets were assigned to the following treatments: Control (Basal diet + 1.59% L-Alanine); T1 (Basal diet + 1% L-Gln + 0.5% L-Glu + 0.1% L-Asp); T2 (Low energy diet + 1% L-Gln + 0.5% L-Glu + 0.1% L-Asp). Jejunum and ileum were obtained on d-5 or d-21 post-weaning. Results: Improved growth performance on d-21 post-weaning were observed in T1 treatment. Both T1 and T2 treatments improved small intestinal morphology by increasing villus height, goblet cell number and decreasing crypt depth on d 5 or d-21 post-weaning. Gln, Glu, and Asp could restore the small intestinal energy homeostasis via replenishing the Krebs’ cycle and down-regulate the AMPK pathway. However, when piglets fed by a low energy diet, Gln, Glu, and Asp are not sufficient to maintain the intestinal energy balance on d-5 post-weaning so that the AMPK, beta-oxidation, and mitochondrial biogenesis are activated to meet the high energy demand of enterocytes. Conclusion: These data indicated that Gln, Glu, and Asp could restore the energy homeostasis of intestinal mucosa of piglets. And the mucosal energy metabolism showed different responses to the intervention of Gln, Glu, and Asp in piglets with a low energy diet between d5 and d21 post-weaning. These findings provide new information on the nutritional intervention for the insufficient energy intake in weaning-piglet.
A critical role of AREG for bleomycin-induced skin fibrosis
Authors: zhang Mary Yinghua , Fang Shuyi , Gao Hongyu , zhang xiaoli , Gu Dongsheng , Liu Yunlong , Wan Jun , Xie jingwu
Published: January 2021

We report our discovery of an important player in the development of skin fibrosis, a hallmark of scleroderma. Scleroderma is a fibrotic disease, affecting 70,000 to 150,000 Americans. Fibrosis is a pathological wound healing process that produces an excessive extracellular matrix to interfere with normal organ function. Fibrosis contributes to nearly half of human mortality. Scleroderma has heterogeneous phenotypes, unpredictable outcomes, no validated biomarkers, and no effective treatment. Thus, strategies to slow down scleroderma progression represent an urgent medical need. While a pathological wound healing process like fibrosis leaves scars and weakens organ function, oral mucosa wound healing is a scarless process. After re-analyses of gene expression datasets from oral mucosa wound healing and skin fibrosis, we discovered that several pathways constitutively activated in skin fibrosis are transiently induced during oral mucosa wound healing process, particularly the amphiregulin (Areg) gene. Areg expression is upregulated ~ 10 folds 24hrs after oral mucosa wound but reduced to the basal level 3 days later. During bleomycin-induced skin fibrosis, a commonly used mouse model for skin fibrosis, Areg is up-regulated throughout the fibrogenesis and is associated with elevated cell proliferation in the dermis. To demonstrate the role of Areg for skin fibrosis, we used mice with Areg knockout, and found that Areg deficiency essentially prevents bleomycin-induced skin fibrosis. We further determined that bleomycin-induced cell proliferation in the dermis was not observed in the Areg null mice. Furthermore, we found that inhibiting MEK, a downstream signaling effector of Areg, by selumetinib also effectively blocked bleomycin-based skin fibrosis model. Based on these results, we concluded that the Areg-EGFR-MEK signaling axis is critical for skin fibrosis development. Blocking this signaling axis may be effective in treating scleroderma.
Association between somatic RET mutations and clinical and genetic characteristics in patients with metastatic colorectal cancer
Authors: Yang Yuan-Zhong , Hu Wan-Ming , Xia Liang-Ping , He wen-zhuo
Published: January 2021

Background
Rearranged during transfection (RET) is a targetable oncogene. RET fusions have been reported in patients with metastatic colorectal cancer (mCRC). However, RET mutations in mCRC are less studied. Here, we aimed to characterize the clinical, pathological, and molecular landscape of RET-mutated mCRC.
Methods
Five hundred and eighty-two patients were included in this study. Next-generation sequencing was performed to detect RET mutations and calculate tumor mutation burden (TMB). We compared the clinical, pathological, and molecular characteristics of mCRC cases with tumors that harbored somatic RET mutations (N = 16, 2.7%) or had wild-type RET (N = 566, 97.3%).
Results
Males comprised the absolute majority of cases with RET mutations (15/16 [93.8%]) compared to their fraction among cases with wild-type RET (339/566 [59.9%]). Furthermore, all patients with RET mutations were younger than 60 years (16/16 [100%]), whereas such patients were less predominant in the group with wild-type RET (379/566 [67.0%]). Individuals with tumors positive for RET mutations more frequently exhibited mucinous histology (5/16 [31.2%] versus 55/566 [9.7%]), exhibited a lower incidence of liver metastasis (4/16 [25.0%] versus 335/566 [59.2%]) and higher incidence of peritoneal metastasis (9/16 [56.2%] versus 161/566 [28.4%]), expressed wild-type TP53 (8/16 [50.0%] versus 120/566 [21.2%]), and showed an increased frequency of MSI-high (6/16 [37.5%] versus 18/566 [3.2%]). In those with microsatellite-stable mCRC, patients with RET mutations had a higher median TMB than patients with wild-type RET (9.4 versus 6.7 mutations/Mb, respectively, P = 0.001). The median progression-free survival was similar in individuals with mutated and wild-type RET on the oxaliplatin-based regimen (7.1 versus 8.7 months, P = 0.516).
Conclusions
Our study suggests that cases with RET mutations represent a separate mCRC subtype. Further studies are needed to evaluate the efficacy of RET inhibitors in mCRC patients with RET mutations.