bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic anticipation to reduce emergency department length of stay: a retrospective cohort study in Ferrara University hospital, Italy
Authors: Strada Andrea , Bolognesi Niccolò , Manzoli Lamberto , Valpiani Giorgia , Morotti Chiara , Bravi Francesca , Bentivegna Roberto , Forini Elena , Pesci Antonella , Stefanati Armando , Di Ruscio Eugenio , Carradori Tiziano 
Published: July 2020

Abstract
Background
Emergency Department (ED) crowding reduces staff satisfaction and healthcare quality and safety, which in turn increase costs. Despite a number of proposed solutions, ED length of stay (LOS) - a main cause of overcrowding - remains a major issue worldwide.
This retrospective cohort study was aimed at evaluating the effectiveness on ED LOS of a procedure called “Diagnostic Anticipation” (DA), which consisted in anticipating the ordering of blood tests by nurses, at triage, following a diagnostic algorithm approved by physicians.

Methods
In the second half of 2019, the ED of the University Hospital of Ferrara, Italy, adopted the DA protocol on alternate weeks for all patients with chest pain, abdominal pain, and non-traumatic bleeding. A retrospective cohort study on DA impact was conducted. Using ED electronic data, LOS independent predictors (age, sex, NEDOCS and Priority Color Code, imaging tests, specialistic consultations, hospital admission) were evaluated through multiple regression.

Results
During the weeks when DA was adopted, as compared to control weeks, the mean LOS was shorter by 18.2 min for chest pain, but longer by 15.7 min for abdominal pain, and 33.3 for non-traumatic bleeding. At multivariate analysis, adjusting for age, gender, triage priority, specialist consultations, imaging test, hospitalization and ED crowding, the difference in visit time was significant for chest pain only (p < 0.001).

Conclusions
The impact of DA varied by patients’ condition, being significant for chest pain only. Further research is needed before the implementation, estimating the potential proportion of inappropriate blood tests and ED crowding status.
An application of analytic network process model in supporting decision making to address pharmaceutical shortage
Authors: Zarei Leila , Moradi Najmeh , Peiravian Farzad , Mehralian Gholamhosein 
Published: July 2020

Abstract
Background
The present study aimed to develop an Analytic Network Process (ANP) model to assist policymakers in identifying and prioritizing allocation indicators, which are being used or should be used to distribute drugs in short supply among different provinces.

Methods
The model encompasses the interactions between various indicators and efficiency, equity, and effectiveness paradigms. Accordingly, a set of clusters and elements, which were associated with the allocation of drugs in short supply in Iran’s pharmaceutical system, were detected to develop the model and were then compared in pairs in terms of a specified factor to show the priorities.

Results
Equity had the highest priority (0.459) following by Efficiency (0.37), and Effectiveness (0.171). The 4 most important allocation indicator were “number of prescriptions” (0.26) and “total bed occupancy rate” (0.19) related to equity, “total population” (0.21) in efficiency and “the burden of rare and incurable disease” (0.07) in effectiveness paradigm.

Conclusions
The capability to overcome inefficient resource allocation patterns caused by both oversupply and undersupply derived from historic resource allocation may be highly limited in the absence of the need indicators. The quality of the decision is related to a careful balancing act of the three paradigms which represents roughly the triple aim of public healthcare systems: clinical improvement (effectiveness), population health improvement (equity and access), and reducing cost (economic aspects -efficiency).
Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis
Authors: Jin Tian , Wu Di , Liu Xiao-Ming , Xu Jiang-Tao , Ma Bing-Jie , Ji Yun , Jin Yu-Ying , Wu Si-Yin , Wu Tao , Ma Ke 
Published: July 2020

Abstract
Background
Celastrol has been proven effective in anti-inflammatory but was limited in the clinic due to the poor solubility and side effects induced by low bioavailability. Osteoarthritis has acidic and inflammatory environment. Our aim was to load celastrol into HMSNs and capped with chitosan to construct a pH-responsive nanoparticle medicine (CSL@HMSNs-Cs), which is of high solubility for osteoarthritis intra-articular injection treatment.

Methods
The CSL@HMSNs-Cs were assembled and the characteristics were measured. The CSL@HMSNs-Cs was applied in vitro in the chondrocytes collected from rats cartilage tissue and in vivo in the MIA induced knee osteoarthritis rats via intra-articular injection. Cytotoxicity assay, pH-responsive release, pain behavior, MRI, safranin o fast green staining, ELISA and western blot analysis were applied to evaluate the bioavailability and therapeutic effect of CSL@HMSNs-Cs.

Results
CSL@HMSNs-Cs was stable due to the protection of the chitosan layers in alkaline environment (pH = 7.7) but revealed good solubility and therapeutic effect in acidic environment (pH = 6.0). The cytotoxicity assay showed no cytotoxicity at relatively low concentration (200 μg/mL) and the cell viability of chondrocytes stimulated by IL-1β was increased in CSL@HMSNs-Cs group. Paw withdrawal threshold in CSL@HMSNs-Cs group is increased, and MRI and Safranin O Fast Green staining showed improvements in articular surface erosion and joint effusion. The upregulated expression levels of IL-1β, TNF-α, IL-6, MMP-3 and MMP-13 and NF-κB signaling pathway of chondrocytes were inhibited in CSL@HMSNs-Cs group.

Conclusion
Hollow mesoporous silica nanoparticles were an ideal carrier for natural drugs with poor solubility and were of high biocompatibility for intra-articular injection. These intra-articular injectable CSL@HMSNs-Cs with improved solubility, present a pH-responsive therapeutic strategy against osteoarthritis.
Identification of six candidate genes for endometrial carcinoma by bioinformatics analysis
Authors: Zhu Yiming , Shi Liang , Chen Ping , Zhang Yingli , Zhu Tao 
Published: July 2020

Abstract
Background
Endometrial carcinoma (EC) is the most common gynecological malignant tumors which poses a serious threat to women health. This study aimed to screen the candidate genes differentially expressed in EC by bioinformatics analysis.

Methods
GEO database and GEO2R online tool were applied to screen the differentially expressed genes (DEGs) of EC from the microarray datasets. Protein-protein interaction (PPI) network for the DEGs was constructed to further explore the relationships among these genes and identify hub DEGs. Gene ontology and KEGG enrichment analyses were performed to investigate the biological role of DEGs. Besides, correlation analysis, genetic alteration, expression profile, and survival analysis of these hub DEGs were also investigated to further explore the roles of these hub gene in mechanism of EC tumorigenesis. qRT-PCR analysis was also performed to verify the expression of identified hub DEGs.

Results
A total of 40 DEGs were screened out as the DEGs with 3 upregulated and 37 downregulated in EC. The gene ontology analysis showed that these genes were significantly enriched in cell adhesion, response to estradiol, and growth factor activity, etc. The KEGG pathway analysis showed that DEGs were enriched in focal adhesion, leukocyte transendothelial migration, PI3K-Akt signaling pathway, and ECM-receptor interaction pathway. More importantly, COL1A1, IGF1, COL5A1, CXCL12, PTEN, and SPP1 were identified as the hub genes of EC. The genetic alteration analysis showed that hub genes were mainly altered in mutation and deep deletion. Expression validation by bioinformatic analysis and qRT-PCR also proved the expression of these six hub genes were differentially expressed in EC. Additionally, significantly better overall survival and disease-free survival were observed with six hub genes altered, and survival outcome in high expression of COL1A1, IGF1, and PTEN patients was also significantly better than low expression patients.

Conclusions
COL1A1, IGF1, COL5A1, CXCL12, PTEN, and SPP1 involved in the pathogenesis of EC and might be candidate genes for diagnosis of EC.
Predictive factors for pleural drainage volume after uniportal video-assisted thoracic surgery lobectomy for non-small cell lung cancer: a single-institution retrospective study
Authors: Tang Ming-bo , Li Jia-lin , Tian Su-yan , Gao Xin-liang , Liu Wei 
Published: July 2020

Abstract
Objective
To identify the predictive factors associated with pleural drainage volume (PDV) after uniportal video-assisted thoracic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC).

Methods
A total of 440 consecutive NSCLC patients who underwent uniportal VATS lobectomy were enrolled in this study between November 2016 and July 2019. Thirty-four parameters, including patients’ clinicopathological characteristics and other potential predictors were collected. Daily drainage volume was summed up as PDV. Univariate analysis and multivariate regression models were fitted to identify independent predictive factors for PDV.

Results
The median PDV was 840 ml during the median drainage duration of 4 days. A strong correlation was observed between PDV and drainage duration (correlation coefficient = 0.936). On univariate analysis, age, forced expiratory volume in 1 s % predicted (FEV1%), left ventricular ejection fraction (LVEF), operation time, serum total protein (TP), and body mass index (BMI) showed a significant correlation with PDV (P value, < 0.001, < 0.001, 0.003, 0.008, 0.028, and 0.045, respectively). Patients with smoking history (P = 0.030) or who underwent lower lobectomy (P = 0.015) showed significantly increased PDV than never smokers or those who underwent upper or middle lobectomy, respectively. On multivariate regression analysis, older age (P< 0.001), lower FEV1% (P< 0.001), lower LVEF (P = 0.011), lower TP (P = 0.013), and lower lobectomy (P = 0.016) were independent predictors of increased PDV.

Conclusions
Predictive factors of PDV can be identified. Based on these predictors, patients can be treated with tailored individualized safe chest tube management.
Evaluating interventions to improve test, treat, and track (T3) malaria strategy among over-the-counter medicine sellers (OTCMS) in some rural communities of Fanteakwa North district, Ghana: study protocol for a cluster randomized controlled trial
Authors: Soniran Olajoju Temidayo , Abuaku Benjamin , Ahorlu Collins Stephen 
Published: July 2020

Abstract
Background
The World Health Organization initiated test, treat, and track (T3) malaria strategy to support malaria-endemic countries in their efforts to achieve universal coverage with diagnostic testing, antimalarial treatment, and strengthening surveillance systems. Unfortunately, T3 is not adopted by over-the-counter medicine sellers (OTCMS) where many patients with malaria-like symptoms first seek treatment. Sub-Saharan African countries are considering introducing and scaling up RDTs in these outlets to reduce malaria burden. In this context, this study is aimed at improving implementation of the T3 among OTCMS using a number of intervention tools that could be scaled-up easily at the national level.

Methods/design
The interventions will be evaluated using a two-arm, cluster randomized trial across 8 rural communities (4 clusters per arm), in two adjacent districts (Fanteakwa North and Fanteakwa South districts) of Ghana. A total of 8 OTCMS in the intervention arm and 5 OTCMS in the control arm in the selected communities will participate in the study. In the intervention arm only, subsidized malaria rapid diagnostic test (mRDT) kits will be introduced after the OTCMS have been trained on how to use the kit appropriately. Supervision, technical assistance, feedbacks, and collection of data will be provided on a regular basis at the participating medicine stores. The primary outcome is the proportion of children under 10 years with fever or suspected to have malaria visiting OTCMS and tested (using mRDT) before treatment. Secondary outcomes will include adherence to national malaria treatment guidelines and recommended mRDT retail price. Outcomes will be measured using mainly a household survey supplemented by mystery client survey and a surveillance register on malaria tests conducted by the OTCMS during patient consultations. Data collected will be double entered and verified using Microsoft Access 2010 (Microsoft Inc., Redmond, Washington) and analyzed using STATA version 11.0.

Discussion
The trial will provide evidence on the combined effectiveness of provider and community interventions in improving adherence to the T3 initiative among OTCMS in rural Ghana.

Ethical clearance
NMIMR-IRB CPN 086/18-19

Trial registration
ISRCTN registry ISRCTN77836926. Registered on 4 November 2019.
Protocol for a randomized controlled trial to assess two procedures of vaginal native tissue repair for pelvic organ prolapse at the time of the questioning on vaginal prosthesis: the TAPP trial
Authors: Lacorre A. , Vidal F. , Campagne-Loiseau S. , Marin B. , Aubard Y. , Siegerth F. , Mesnard C. , Chantalat E. , Hocke C. , Gauthier T. 
Published: July 2020

Abstract
Background
Native tissue cystocele repair has been the cornerstone of prolapse surgery, especially since the learned societies warned clinicians and patients about serious mesh-related complications. Surgical techniques mainly consist in anterior colporraphy and vaginal patch plastron. However, success rates of native tissue cystocele repair are heterogeneous, depending on the design of studies and definition of outcomes. To date, high-quality data comparing vaginal native tissue procedures are still lacking.

Methods
Herein we aimed to describe the design of the first randomized controlled trial (TAPP) comparing anterior colporraphy (plication of the muscularis and adventitial layers of the vaginal wall) and vaginal patch plastron (bladder support anchored on the tendinous arch of the pelvic fascia by lateral sutures) techniques.
Our aim is to assess the effectiveness of vaginal native tissue repair at 1 year for cystocele with a combined definition of success—anatomic and functional. The primary endpoint will be the success rate 1 year after surgery with a composite of objective and subjective measures (Aa and Ba points < 0 from POP-Q (Pelvic Organ Prolapse Quantification System) and a negative answer to question 3 of Pelvic Floor Distress Inventory and no need for additional treatment).

Discussion
A prospective study has found a success rate at 35% for anterior colporraphy based on a combined definition, both anatomic and functional, as recently recommended. However, the definition of anatomic was strict (POP-Q< 2), while it seems that the best definition of anatomic success is “no prolapse among the hymen”, that is to say Aa and Ba points from the POP-Q classification < 0. We hypothesize that vaginal patch plastron will have a better anatomic and functional success comparatively to anterior colporraphy because native tissue is added, as it corrects both median and lateral cystoceles thanks to bilateral paravaginal suspension.

Trial registration
CHU LIMOGES is the sponsor of this research (n°87RI18_0013).
This research is supported by the French Department of Health (PHRC 2018-A03476-49) and will be conducted with the support of DGOS (PHRC interregional – GIRCI SOHO).
The study protocol was approved by the Human Subjects Protection Review Board (Comité de Protection des Personnes) on May 16, 2019.
The trial is registered in the ClinicalTrials.gov registry (NCT03875989).
A network-wide view-based detection and mitigation of a sophisticated Interest Flooding Attack
Authors: Cheng Guang , Zhao Lixia , Hu Xiaoyan , Zheng Shaoqi , Wu Hua , Fan Chengyu 
Published: July 2020

AbstractInterest Flooding Attack (IFA) is one of the main security threats for the Named Data Networking (NDN). Most of its existing countermeasures enable intermediate routers near the attackers to independently detect the attack and consider the typical attack scenario in which attackers directly send malicious Interests at a constant and relatively high rate after the attack starts. Moreover, they may also throttle legitimate Interests when enforcing the existing defense measures at intermediate routers as it is still difficult for them to distinguish the Interests issued by attackers from those issued by legitimate consumers. Instead, this work aims at a more sophisticated attack scenario in which attackers start the attack at a relatively lower rate but gradually speed up to keep the Pending Interest Tables (PITs) of the victims increasing to finally deplete the PIT resources for legitimate consumers. It is relatively difficult for intermediate routers to independently and timely detect such a sophisticated IFA. To solve this problem, we propose a mechanism to detect and mitigate the sophisticated IFA from the network-wide view, dubbed as DMNWV. In DMNWV, a central controller monitors the network and makes a comprehensive and prompt decision on whether there is an ongoing IFA based on the overall state of the whole network collected from the abnormity information reports sent by the first-hop routers of attackers. Attack sources can be directly located after an IFA is determined, and then the routers directly connected to attackers (i.e., access routers) can take targeted measures based on the located attackers to prevent malicious Interest from entering the network without throttling legitimate Interests. We conduct an experimental study to evaluate the performance of DMNWV, explore the parameter settings of the attack detection algorithm at access routers, and measure the communication overhead of the central controller. The experimental results validate that DMNWV can timely detect and mitigate the sophisticated IFA without throttling requests from legitimate consumers with significantly low communication overhead of the central controller, which will not bring about too much burden to the network.
Exponential mean-square stability of numerical solutions for stochastic delay integro-differential equations with Poisson jump
Authors: Ahmadian Davood , Farkhondeh Rouz Omid 
Published: July 2020

AbstractIn this paper, we investigate the exponential mean-square stability for both the solution of n-dimensional stochastic delay integro-differential equations (SDIDEs) with Poisson jump, as well for the split-step θ-Milstein (SSTM) scheme implemented of the proposed model. First, by virtue of Lyapunov function and continuous semi-martingale convergence theorem, we prove that the considered model has the property of exponential mean-square stability. Moreover, it is shown that the SSTM scheme can inherit the exponential mean-square stability by using the delayed difference inequality established in the paper. Eventually, three numerical examples are provided to show the effectiveness of the theoretical results.
The controllability of damped fractional differential system with impulses and state delay
Authors: Nawaz Musarrat , Wei Jiang , Sheng Jiale , Khan Azmat Ullaha 
Published: July 2020

AbstractWe discuss the controllability for a damped fractional differential system with impulses and state delay, which involves Caputo fractional derivatives. Deriving the condition based on the Gramian matrix defined by the Mittag-Leffler matrix function and Laplace transformation, we establish necessary and sufficient conditions of controllability criteria. Finally, we construct two numerical examples to support the result.
Theoretical analysis of the delay on the p53 micronetwork
Authors: Wang Danni , Liu Nan , Yang Hongli , Yang Liangui 
Published: July 2020

AbstractTime delay plays a crucial role in p53 dynamic. However, the theoretical understanding is still lower. Thus we construct a micro-differential equation model and introduce the time delay τ based on the regulation process. Firstly, we linearize the system and analyze the associated characteristic equation. We can conclude that there exists the delay threshold $\tau _{0}$

τ
0

such that when the delay τ is less than $\tau _{0}$

τ
0

, the system is asymptotically stable and otherwise stable oscillations occur. Secondly, we use the normal form method and the center manifold theorem to derive the direction and stability of the Hopf bifurcation. Finally, by numerical simulations we verify our theoretical results. We also find that the effect of noise on the amplitude is more severe than that of the period, which well agrees with the experimental results.
High level MYCN amplification and distinct methylation signature define an aggressive subtype of spinal cord ependymoma
Authors: Raffeld Mark , Abdullaev Zied , Pack Svetlana D. , Xi Liqiang , Nagaraj Sushma , Briceno Nicole , Vera Elizabeth , Pittaluga Stefania , Lopes Abath Neto Osorio , Quezado Martha , Aldape Kenneth , Armstrong Terri S. , Gilbert Mark R. 
Published: July 2020

AbstractWe report a novel group of clinically aggressive spinal cord ependymomas characterized by Grade III histology, MYCN amplification, an absence of NF2 alterations or other recurrent pathogenic mutations, and a unique methylation classifier profile. Seven cases were found to have MYCN amplification in the course of routine mutational profiling of 552 patients with central nervous system tumors between December 2016 and July of 2019 and an eighth patient was identified from an unrelated set of cases. Methylation array analysis revealed that none of the 8 cases clustered with any of the nine previously described ependymoma methylation subgroups, and 7 of 8 formed their own tight unique cluster. Histologically all cases showed grade III features, and all demonstrated aggressive clinical behavior. These findings are presented in the context of data from three other studies describing similar cases. Therefore, a combined total of 27 MYCN amplified spinal cord ependymoma cases have now been reported in the literature, warranting their consideration as a distinctive subtype of spinal cord ependymoma (SP-EPN-MYCN) with their unique molecular characteristics and aggressive clinical behavior.
Erythrocytic α-synuclein contained in microvesicles regulates astrocytic glutamate homeostasis: a new perspective on Parkinson’s disease pathogenesis
Authors: Sheng Lifu , Stewart Tessandra , Yang Dishun , Thorland Eric , Soltys David , Aro Patrick , Khrisat Tarek , Xie Zhiying , Li Na , Liu Zongran , Tian Chen , Bercow Matthew , Matsumoto Junichi , Zabetian Cyrus P. , Peskind Elaine , Quinn Joseph F. , Shi Min , Zhang Jing 
Published: July 2020

AbstractParkinson’s disease is a neurodegenerative disorder characterized by the transmission and accumulation of toxic species of α-synuclein (α-syn). Extracellular vesicles (EVs) are believed to play a vital role in the spread of toxic α-syn species. Recently, peripheral α-syn pathology has been investigated, but little attention has been devoted to erythrocytes, which contain abundant α-syn. In this study, we first demonstrated that erythrocyte-derived EVs isolated from Parkinson’s disease patients carried elevated levels of oligomeric α-syn, compared to those from healthy controls. Moreover, human erythrocyte-derived EVs, when injected into peripheral blood in a mouse model of Parkinson’s disease, were found to readily cross the blood-brain barrier (BBB). These EVs accumulated in astrocyte endfeet, a component of the BBB, where they impaired glutamate uptake, likely via interaction between excitatory amino acid transporter 2 (EAAT2) and oligomeric α-syn. These data suggest that erythrocyte-derived EVs and the oligomeric α-syn carried in them may play critical roles in the progression or even initiation of Parkinson’s disease. Additionally, the mechanisms involved are attributable at least in part to dysfunction of astrocytes induced by these EVs. These observations provide new insight into the understanding of the mechanisms involved in Parkinson’s disease.