bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence, Risk Factors, and Outcomes of Patients with COVID‑19‑Associated Pulmonary Aspergillosis (CAPA) in Intensive Care Units: A Systematic Review and Meta-Analysis Of 29 Cohort Studies
Authors: Chen Wensen , Yin Cheng , Zhong Ming , Hu Bijie , Gao Xiaodong , Zhang Kai , Liu Yun , Zhuang Guihua
Published: June 2021

Background Patients with Coronavirus disease 2019 (COVID-19) admitted to an intensive care unit (ICU) might develop COVID-19-related pulmonary Aspergillosis (CAPA). We aimed to identify studies systematically that describe the incidence and risks factors of CAPA, and to assess its outcome. Methods Two authors independently searched ScienceDirect, PubMed, CNKI, MEDLINE (OVID), and MedRXIV from December 31, 2019 to Feb 27, 2021. We included observational cohort studies that investigated patients with CAPA admitted to an ICU. We assessed the quality of all included studies using the Newcastle–Ottawa Scale). The meta-analysis was registered with PROSPERO (CRD42021242179).ResultsTwenty-nine cohort studies with 2095 patients with COVID-19 admitted to an ICU and 264 patients who developed to CAPA were included (Pooled incidence: 0.14, 95% confidence interval [CI] = 0.11–0.17). The overall mortality and case fatality rate of CAPA were 0.07 (0.05–0.09) and 0.51 (0.44–0.58), respectively. Patients with COVID‑19 would develop CAPA at 7.28 days after mechanical ventilation (range, 5.48–9.08). Compared with patients without CAPA, those with CAPA had a significantly lower median body mass index (27.32 vs. 28.97 kg/m2, P = 0.034), higher median creatinine level (127.94 vs. 88.23 µmol/L, P = 014), and were more likely to receive corticosteroids therapy (41.0% vs. 38.0%, risk ratio [RR] = 1.98, 95% CI=1.08–3.63) and renal replacement therapy (42.0% vs. 28.2%, RR = 1.61, 95% CI=1.04–2.50) during admission. Remarkably, patients with CAPA were associated significantly with a 1.66‑fold higher mortality (RR = 1.66, 95% CI=1.31–2.12) without significant heterogeneity and publication bias. ConclusionsPatients with COVID-19 admitted to an ICU might develop CAPA and have higher all‑cause mortality. We recommend conducting prospective screening for CAPA among patients with severe COVID-19, especially for those who receive mechanical ventilation over 7 days.
An Efficient and Sustainable Approach to Prepare Carboxylated Cellulose Nanocrystals for Rubber Reinforcement Featuring Dual Crosslinking Networks
Authors: Hu Jie , Kong Zhengqing , Liu Ke , Qin Jinli , Tao Yuhong , Zhou Lijuan , Yuan Yuan , Jiang Min , Duan Yongxin , Zhang Jianming
Published: June 2021

The surface functionalization of CNCs and the construction of strong interfacial adhesion between CNCs and rubber matrix are effective way to achieve high performance rubber/CNCs nanocomposites. Herein, carboxylation of sulphated cellulose nanocrystals (CNC-OSO3H) was conducted in aqueous medium by using citric acid as modifier. Large amount of carboxyl groups was successfully grafted on the surface of CNC-OSO3H, which endows the carboxylated CNC-OSO3H (abbreviate as CNC-CA) with higher chemical reactivity and thermal stability. Subsequently, carboxylated styrene butadiene rubber (XSBR)/CNC-CA nanocomposites with dual crosslinking design were prepared by using polyethylene glycol diglycidyl ether (PEGDE) as the crosslinking agent and CNC-CA as the reinforcing fillers. FTIR investigation found that in the obtained nanocomposites, the carboxyl groups on CNC-CA and XSBR formed hydrogen bonds (physical crosslinking) with each other, and the carboxyl groups formed covalent bond with the epoxy group on PEGDE simultaneously. The coexistence of physical and chemical crosslinking improved the interface compatibility between CNC-CA and XSBR matrix, accelerated the homogenous dispersion of CNC-CA and realized the crosslinking of the matrix itself. As expected, XSBR/CNC-CA nanocomposites with dual crosslinking network showed remarkable enhancement in tensile strength (up to 500%), modulus (up to 151%), work of fracture (up to 348%). This work provides both a facile and green approach to obtain carboxylated CNCs and a convenient method for the preparation of high-performance rubber nanocomposites with multiple interactions.
Determining the Prevalence of RET/PTC Mutation in Cases Where Thyroid Nodules in American Thyroid Association (ATA) Ultrasonography (USG) Guidance According to Risk Category is Determined and investigating the Relation of Malignancy
Authors: Erdogan Mehmet , Karadeniz Muammer , Ertan Yesim , Ozgen Ahmet Gokhan , Tamsel Sadık , Kose Timur , Berdeli Afig , Ozdemir Murat
Published: June 2021

OBJECTIVE

RET/PTC in FNA (Fine needle aspiration) biopsy smears could improve the FNA diagnosis. The aim of study determining the prevalence of RET/PTC mutation in cases where thyroid nodules in ATA USG according to risk catogory is determined and investigating the relation of malignancy.
METHODS

RNA was extracted from 60 routine FNA. RET/PTC rearrangements were detected by real-time quantitative polymerase chain reaction, and, in parallel, RT-PCR is used to detect the chimeric RET/PTC1, RET/PTC2 and RET/PTC3 transcripts in RNA extracted from FNA.
RESULTS

A total of 75% FNA RET rearrangements were detected in the 20 PTC patients. RET/PTC positive was detected in 35% of cases without cancer (sensitivity 75%, specificity 65%) (p = 0,003). Significant correlation was found between A-high suspicion USG group (80%), B- intermediate suspicion USG group (45%) and C- low suspicion USG group (20%) in of RET/PTC rearrangements (p = 0.001). A significant correlation was found between the USG groups and the PTC (respectively group A,B,C: 60%, 30%, 10%)(p = 0.003). There was a statistical difference related to in the USG groups frequency between Classic type PTC (70%) and Follicular type PTC (30%)(p = 0.019). There was a statistical difference related to between RET/PTC and PTC types in the USG groups (p = 0.012). There was a statistical difference related to between usg groups tumor diameter A and C (P = 0.010).
CONCLUSİON

Molecular testing of FNA samples improves presurgical diagnosis. RET/PTC was found to be significantly higher in the diagnoses of the PTC with 75% sensitivity and 65% specificity
Effects of Different Land Use Types Managed By Smallholder Farmers on Soil Properties in Central Ethiopia
Authors: Haile Getahun , Lemenih Mulugeta , Itanna Fisseha , Teklu Beyene , Agegnehu Getachew
Published: June 2021

Background Aim: Land use change causes a remarkable change in soil properties. The nature of change depends on multiple factors such as soil type, type and intensity of land use, climate, and the like. This study investigated the variation in soil physicochemical properties across five common land use practices i.e., enset system, farmland, and grazing-land (closed and open), and Eucalyptus woodlots practiced on originally same soil type and comparable topographic and climatic settings.Methods: A total of 105 disturbed and undisturbed soil samples [5 treatments (land use types) *7 replications (household)* 3 soil depth layers: 0–15cm, 15–30 cm, 30–45cm] were collected for selected soil chemical and physical analyses. Standard soil analytical procedures were followed in carrying out soil analysis. To meet the assumptions of normal distribution and homogeneity of variances, soil data on available phosphors were log-transformed before statistical analysis was undertaken and reported after back transformation. Two way analysis of variable were used to investigate the effects of land use and soil depth and their interaction on soil properties and when the analysis showed a significant difference (p <0.05) among land use and soil depth men separation were made using Turkey’s pairwise comparisons.Results: There were significant differences in physical and chemical properties of soil across land use and soil depth categories. Enset system had significantly higher pH, available phosphorus (P), exchangeable potassium (K+), soil organic carbon (SOC), and total nitrogen (TN) and their stocks than other land use types. Enset fields had higher SOC (78.4%) and soil TN (75%), and SOC and TN stocks of (66%) and (58%), respectively than cereal farmland. This study had also revealed a less expected finding of higher soil organic carbon and total nitrogen under Eucalyptus wood than farm land. Soil carbon and total nitrogen stocks showed a decreasing trend of enset system> closed grazing-land > eucalyptus woodlot > open grazing-land > farmland 0-45cm.Conclusion: Overall, some land use systems (e. g. enset agroforestry) improve the soil biophysical and chemical properties, while others such as cereal production degrade the soil. Hence appropriate land and soil management intervention should be promptly adapted to mitigating the continuous loss of nutrient from the dominantly practiced cereal farm land through maintaining crop residues, manure, crop rotation and scaling up agro-forestry system.
Relative Performance of Cluster Algorithms and Validation Indices in Maize Genome-wide Structure Patterns
Authors: Videla María Eugenia , Iglesias Juliana , Bruno Cecilia
Published: June 2021

A number of clustering algorithms are available to depict population genetic structure (PGS) with genomic data; however, there is no consensus on which methods are the best performing ones. We conducted a simulation study of three PGS scenarios with subpopulations k=2, 5 and 10, recreating several maize genomes as a model to: (i) compare three well-known clustering methods: UPGMA, k-means and, Bayesian method (BM), (ii) asses four internal validation indices: CH, Connectivity, Dunn and Silhouette, to determine the reliable number of groups defining a PGS, and (iii) estimate the misclassification rate for each validation index. Moreover, a publicly available maize dataset was used to illustrate the outcomes of our simulation. BM was the best method to classify individuals in all tested scenarios, without assignment errors. Conversely, UPGMA was the method with the highest misclassification rate. In scenarios with 5 and 10 subpopulations, CH and Connectivity indices had the maximum underestimation of group number for all cluster algorithms. Dunn and Silhouette indices showed the best performance with BM. Nevertheless, since Silhouette measures the degree of confidence in cluster assignment, and BM measures the probability of cluster membership, these results should be considered with caution. In this study we found that BM showed to be efficient to depict the PGS in both simulated and real maize datasets. This study offers a robust alternative to unveil the existing PGS, thereby facilitating population studies and breeding strategies in maize programs. Moreover, the present findings may have implications for other crop species.
IL-17 Upregulates MCP-1 Expression via Act1 / TRAF6 / TAK1 in Experimental Autoimmune Myocarditis
Authors: huang xiao , Li Zhuolun , Shen Xinhe , nie na , shen yan
Published: June 2021

Myocarditis is a myocardial inflammatory infiltration heterogeneous disease. At present, various interventions are not effective in the treatment of myocarditis. IL-17, an important pro‐inflammatory factor secreted mainly by Th17 cells, can promote the expression of multiple cytokines. MCP-1 is an important cytokine that mediates mononuclear cell infiltration. Studies have found that IL-17 could stimulate the expression of MCP-1 to mediate inflammatory infiltration. But the mechanism by which IL-17 induces MCP-1 expression in experimental autoimmune myocarditis (EAM) remains unclear. The purpose of this study is to establish an EAM model to explore the role of Act1/TRAF6/TAK1 cascade in the induction of MCP-1 by IL-17. In the present study, we found that in EAM, IL-17 could stimulate the expression of MCP-1 by activating Act1/TRAF6/TAK1 cascade. After interfering TAK1 with si-TAK1, myocardial tissue inflammation was greatly alleviated, and both MCP-1 mRNA and protein expression were downregulated. In conclusion, IL-17 can activate AP-1, NF-κB via Act1/TRAF6/TAK1 upregulation of MCP-1 expression in EAM.
Phase I Trial of Copanlisib, a Selective Pi3k Inhibitor, in Combination With Cetuximab in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma
Authors: Marret Grégoire , Isambert Nicolas , Rezai Keyvan , Gal Jocelyn , Saada-Bouzid Esma , Rolland Frédéric , Chausson Maggy , Borcoman Edith , Alt Marie , Klijanienko Jerzy , Vansteene Damien , Guigay Joël , Kamal Maud , Bièche Ivan , LeTourneau Christophe
Published: June 2021

BackgroundThe phosphatidylinositol-3 kinase pathway is often altered in head and neck squamous cell carcinoma (HNSCC), and is involved in the resistance to EGFR inhibitors. ObjectiveWe investigated the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetics, and preliminary efficacy of the combination of copanlisib, an intravenous, pan-class I PI3K inhibitor, with the anti-EGFR monoclonal antibody cetuximab in recurrent and/or metastatic HNSCC patients in a phase I dose-escalation trial. Patients and methodsCopanlisib was given intravenously on days 1, 8, and 15 of 28-day cycles at the dose of 45 mg and 30 mg, in combination with standard doses of weekly cetuximab (400 mg/m² loading dose followed by 250 mg/m² on days 8, 15, and 22, and weekly thereafter). ResultsThree patients received copanlisib 45 mg, of whom two experienced grade 3 hyperglycemia during Cycle 1 that met the DLT criteria. Eight patients were then treated with copanlisib at the dose of 30 mg. Because of the occurrence of hyperglycemia, a premedication with metformine was introduced on the day of the injections. No DLTs were reported at this dose level. The trial was stopped early because of the unfavourable toxicity profile of the combination. Among eight evaluable patients for response, four patients (50%) had disease stabilization according to RECIST1.1 as best response.ConclusionCopanlisib combined with cetuximab demonstrated unfavorable toxicity and limited efficacy in heavily pretreated recurrent and/or metastatic HNSCC patients. NCT02822482, Date of registration: June 2016.
An Improved Blockchain-Based Secure Data Deduplication using Attribute-Based Role Key Generation with Efficient Cryptographic Methods
Authors: S Ruba , Kalpana A.M.
Published: June 2021

Deduplication can be used as a data redundancy removal method that has been constructed to save system storage resources through redundant data reduction in cloud storage. Now a day, deduplication techniques are increasingly exploited to cloud data centers with the growth of cloud computing techniques. Therefore, many deduplication methods were presented by many researchers to eliminate redundant data in cloud storage. For secure deduplication, previous works typically have introduced third-party auditors for the data integrity verification, but it may be suffered from data leak by the third-party auditors. And also the customary methods could not face more difficulties in big data deduplication to correctly consider the two conflicting aims of high duplicate elimination ratio and deduplication throughput. In this paper, an improved blockchain-based secure data deduplication is presented with efficient cryptographic methods to save cloud storage securely. In the proposed method, an attribute-based role key generation (ARKG) method is constructed in a hierarchical tree manner to generate a role key when the data owners upload their data to cloud service provider (CSP) and to allow authorized users to download the data. In our system, the smart contract (agreement between the data owner and CSP) is done using SHA-256 (Secure Hash Algorithm-256) to generate a tamper-proofing ledger for data integrity, in which data is protected from illegal modifications, and duplication detection is executed through hash-tag that can be formed by SHA-256. Message Locked encryption (MLE) is employed to encrypt data for data uploading by the data owners to the CSP. The experimental results show that our proposed secure deduplication scheme can give higher throughput and a low duplicate elimination ratio.
An Innovative Framework for Real Time Monitoring of Pollutant Point Sources in River Networks
Authors: BaratiMoghaddam M. , Mazaheri Mehdi , Samani J. M. V. , Boano Fulvio
Published: June 2021

The simultaneous identification of location and source release history in complex river networks is a very complicated ill-posed problem, particularly in a case of multiple unknown pollutant sources with time-varying release pattern. This study presents an innovative method for simultaneous identification of the number, locations and release histories of multiple pollutant point sources in a river network using minimum observation data. Considering two different type of monitoring stations with an adaptive arrangement as well as real-time data collection at those stations and using a reliable numerical ﬂow and transport model, at first the number and suspected reach of presence of pollutant sources are determined. Then the source location and its intensity function is calculated by solving inverse source problem using a geostatistical approach. A case study with three different scenarios in terms of the number, release time and location of pollutant sources are discussed, concerning a river network with unsteady and non-uniform flow. Results showed the capability of the proposed method in identifying of sought source characteristics even in complicated cases with simultaneous activity of multiple pollutant sources.
Epidemiological Surveillance To Establish Thresholds For Influenza Among Children In Satellite Cities Of A metropolitan area of Tokyo, Japan
Authors: Matsuda Ayako , Asayama Kei , Obara Taku , Yagi Naoto , Ohkubo Takayoshi
Published: June 2021

Background: Few reports have longitudinally investigated seasonal influenza epidemiological surveillance data of pediatric populations in the metropolitan areas of Japan. We aimed to provide descriptive characteristics of circulating influenza and to investigate the usefulness of setting thresholds for influenza in children (0–15 years old) in two satellite cities of a metropolitan area of Tokyo, Japan, for five consecutive seasons of the influenza epidemic.Methods: The survey was conducted annually during the influenza season, from 2014 to 2018 (ending March 2019), at preschools (kindergartens and nursery schools), elementary schools, and junior high schools located in Toda and Warabi cities, Saitama prefecture. We investigated the epidemiological characteristics and established thresholds using the World Health Organization method.Results: Of the 108,362 children (21,024 to 22,088 throughout five seasons) who received the questionnaire, 76,753 (70.8%; 14,652 to 15,808) responded. After exclusion of responses without basic information, 64,586 children were included in the analysis, of which 13,754 (21.3%) had tested positive for influenza. Influenza type A was generally dominant, whereas type B was responsible for a substantial share of all influenza cases (>40% in seasons 2015 and 2017, when type A circulated with low incidence). The weeks when the influenza epidemic peaked had no clear seasonal pattern among the surveyed years, i.e., the peaks appeared at week 51 (mid-December) or later, whereas the World Health Organization methods reported that the median period when a peak was observed was at 3 weeks (mid-January), regardless of school age group.Conclusions: The present information obtained from the epidemiological survey regarding seasonal influenza in children would be useful for general practitioners, health policymakers, and planners who establish prevention and control methods against influenza.
A fully automatic deep learning system for L3 slice selection and body composition assessment on abdominal computed tomography.
Authors: Ha Jiyeon , Park Taeyong , Kim Hong-Kyu , Shin Youngbin , Ko Yousun , Kim Dong Wook , Sung Yu Sub , Lee Jiwoo , Ham Su Jung , Khang Seungwoo , Jeong Heeryeol , Koo Kyoyeong , Lee Jeongjin , Kim Kyung Won
Published: June 2021

Background and aims: As sarcopenia research has been gaining emphasis, the need for quantification of abdominal muscle on computed tomography (CT) is increasing. Thus, a fully automated system to select L3 slice and segment muscle in an end-to-end manner is demanded. We aimed to develop a deep learning model (DLM) to select the L3 slice with consideration of anatomic variations and to segment cross-sectional areas (CSAs) of abdominal muscle and fat. Methods: Our DLM, named L3SEG-net, was composed of a YOLOv3-based algorithm for selecting the L3 slice and a fully convolutional network (FCN)-based algorithm for segmentation. The YOLOv3-based algorithm was developed via supervised learning using a training dataset (n=922), and the FCN-based algorithm was transferred from prior work. Our L3SEG-net was validated with internal (n=496) and external validation (n=586) datasets. L3 slice selection accuracy was evaluated by the distance difference between ground truths and DLM-derived results. Technical success for L3 slice selection was defined when the distance difference was <10 mm. Overall segmentation accuracy was evaluated by CSA error. The influence of anatomic variations on DLM performance was evaluated.Results: In the internal and external validation datasets, the accuracy of automatic L3 slice selection was high, with mean distance differences of 3.7±8.4 mm and 4.1±8.3 mm, respectively, and with technical success rates of 93.1% and 92.3%, respectively. However, in the subgroup analysis of anatomic variations, the L3 slice selection accuracy decreased, with distance differences of 12.4±15.4 mm and 12.1±14.6 mm, respectively, and with technical success rates of 67.2% and 67.9%, respectively. The overall segmentation accuracy of abdominal muscle areas was excellent regardless of anatomic variation, with the CSA errors of 1.38–3.10 cm2.Conclusions: A fully automatic system was developed for the selection of an exact axial CT slice at the L3 vertebral level and the segmentation of abdominal muscle areas.
A Cross-sectional Analysis of Kogi State Residents' Knowledge and Perceptions on COVID-19 Pandemic
Authors: Mofolorunsho Taiye Babatunde , Mofolorunsho Kehinde Charles , Owoyemi Julius Olugbenga , Oloruntoba Olowonibi Olabisi , Onoja Joseph Ajogwu
Published: June 2021

Coupled with the outbreak of Covid-19 in Nigeria, there has been a controversial trailing of the Covid-19 incidence in Kogi State involving the state authorities and the Nigeria Centre for Disease Control (NCDC). Giving the importance of appropriate awareness and the perceptions to curbing the spread of the disease, this study aimed at assessing the knowledge, perception and precautionary measures of Kogi state residents in response to the outbreak of Covid-19. An online cross-sectional survey was conducted among 401 residents in Kogi State Nigeria, with a structured questionnaire. Data collected were analyzed using descriptive statistics of frequencies and Simple percentage in tables. Findings revealed that all the participants were aware of and had basic knowledge about Covid-19. The study participants had ample knowledge about the required preventive measures and how to protect themselves from Covid-19. It was also revealed that 45.2% of the respondents were conversant with the practice of three to more of the precautionary guidelines for preventing Covid-19. The study also found that a significant number of the respondents held a very low risk perception of Covid-19 by expressing an unlikely probability of getting infected by the virus. As regards skepticism and belief on coronavirus, 45.9% believed that Covid-19 is a hoax which was invented by interest groups for financial gains; 46.1% opined that the number of people reported by the NCDC as infected by the coronavirus in Nigeria is exaggerated. Again, 33.7% of the respondents believed that the second wave of the Covid-19 in Nigeria was a scam. The main source of Covid-19 information utilized by majority of the respondents was from Television programmes (34.2%) and Whatsapp (31.9%) platforms. The study concluded that while there was a high level of awareness of Covid-19 among residents of Kogi State and a remarkable level of precautionary practices against the spread of the Covid-19 virus, there are however, indications of misconceptions and misinformation that breeds skepticism and belief that may be detrimental to curbing effectively, the spread of the Covid-19 virus within the state.
BCAT1 Promotes Lung Adenocarcinoma Progression Through Enhanced Mitochondrial Respiration and NF-κB Pathway Activation
Authors: Yu Mengdan , Zhao Qianwei , Li Jinxia , Xu Fang , Zhang Zhibiao , Liu Yixian , Dai Liping , Zhang Bingxia , Zhang Jianying , Zhang Jintao
Published: June 2021

BCAT1 is up-regulated and acts as an oncogenic factor in many types of cancers, but its role in lung adenocarcinoma (LUAD) development is not clearly understood. Here we found BCAT1 protein level was up-regulated in tumor tissues, which was positively associated with TNM stage and local lymph node metastasis of LUAD patients. BCAT1 knockdown inhibited cell growth and mobility while BCAT1 overexpression promoted LUAD development both in vitro and in vivo. BCAAs metabolism and mitochondrial respiration were enhanced in BCAT1 overexpression cells, which were more sensitive to Leucine and Isoleucine supplements, compared to control cells. Moreover, RNA sequencing analysis suggested that differentially expressed genes (DEGs) in BCAT1 overexpression LUAD cells were enriched in metabolism, signal transduction, and immune response processes, and BCAT1 overexpression decreased NFKBIB mRNA level that induced NF-κB pathway activation in LUAD cells. As an inhibitor of NF-κB pathway, ammonium pyrrolidinedithiocarbamate (PDTC) treatment predominately counteracted the effect of NF-κB pathway activation and inhibited LUAD cells proliferation and migration, especially cells with BCAT1 overexpression. Taken together, our findings point a key role for BCAT1 in promoting LUAD development through metabolic reprogramming and NF-κB pathway activation, which provides promising molecular biomarker and therapeutic targets for LUAD diagnosis and treatment.
Clinical Effect of Plastic Splint for Treatment of New type of Midshaft Clavicle Fracture: A Retrospective Study
Authors: Zhu Xing-tao , Sun Yi-tao , Dai Yu-xiang , Lin Shun , Sun Yi-fu , Ma Zhi-jia , Jiang Hong , Liu Jin-tao
Published: June 2021

Background: On the basis of conservative treatment of 81 midshaft clavicle fractures, a new type of midshaft clavicle fracture was proposed and the clinical effect of plastic splinting in the treatment of these fractures was observed. Methods: Eighty-one patients with midshaft clavicle fractures treated with plastic splints from January 2018 to July 2020 were retrospectively analyzed. The fractures were divided into four types according to their displacement. All patients underwent plastic splint fixation for 4 weeks. The visual analog scale score, Constant–Murley shoulder joint score, patient satisfaction with the post-treatment appearance, nonunion rate, and malunion rate were examined at 1, 3, and 9 months after treatment. Results: Seventeen patients had type I fractures, 18 had type II, 9 had type III, and 37 had type IV. For all four fracture types, the mean visual analog scale score and Constant–Murley score considerably improved from pretreatment to 9 months post-treatment. Seven patients were not satisfied with the post-treatment appearance. Five patients still had no obvious callus at 9 months after treatment, indicating non-healing; most of these patients had type Ⅲ and Ⅳ fractures. Conclusions: Use of the new type of midshaft clavicle fracture is more appropriate for evaluation of the clinical treatment effect because it has more guiding significance for the treatment and prognosis of midshaft clavicle fractures. A plastic splint can be used to treat midshaft clavicle fractures. The short-term clinical effect is safe, and fracture reduction is accurate. Although the incidence of malunion after plastic splint treatment is high, most patients are still satisfied with the appearance after treatment. This technique can be popularized in clinical practice. The functional score and satisfaction with the post-treatment appearance were lower in patients with type Ⅲ and Ⅳ fractures than in those with type Ⅰ and Ⅱ fractures, and the rate of nonunion and abnormal healing were relatively high. Other treatment methods should be considered as early as possible for such patients to achieve the best treatment effect.
A Simplified Procedures for Cellulase Filter Paper Assay
Authors: Abulela Mohamed Abdelazim
Published: June 2021

A new procedures to minimize labor intensiveness and complexity that has long been recognized in cellulase filter paper activity measurement (FPAase) described by the international union of pure and applied chemistry (IUPAC) was developed. It follows the main idea of IUPAC with only exception finding at least two cellulase dilutions have optical densities slightly more and less than a reference optical density of an arbitrary fixed 2 mg absolute glucose amount after a red-ox color reaction and due to cellulase-filter paper hydrolysis. The yielding glucose amount difference as compared to this reference is expressed in terms of absorbance difference percent determined by 3,5-dinitrosalicylic acid (DNS), in case of cellulase is cellubiase rich. If not, an external supplemental portion should be added. The intersection of the line of these two cellulase dilutions with abscissa intersect a vertical at a hypothetical 0% absorbance difference percent corresponding to a critical cellulase dilution exactly release this fixed arbitrary 2 mg glucose amount value. The factor 0.37 of this critical cellulase dilution equals to its filter paper units expressed in FPU per ml.
Effects of Dexmedetomidine Administration on Outcomes in Critically Ill Patients with Acute Kidney Injury: A Propensity Score-Matching Analysis
Authors: Yang Aixiang , Yang Jing , Zhou Biying , Qian Jinxian , Jiang Liyang , Jiang Zhuo , Lu Guoyuan
Published: June 2021

Background

Dexmedetomidine (DEX) had organ protection effects and could decrease mortality in animal models, but its association with mortality and length of stay (LOS) in ICU and hospital in critically ill patients was conflicting. Whether acute kidney injury (AKI) subgroup of critically ill patients could benefit from DEX was unknown. The present study aimed to evaluate the effects of DEX on clinical outcomes of critically ill patients with AKI.
Methods

Data were extracted from the Medical Information Mart for Intensive Care Ⅲ database (MIMIC Ⅲ). Propensity score matching (PSM) analysis (1:3), cox proportional hazards model, linear regression and logistic regression model were used to assess the effect of DEX on clinical outcomes.
Results

After PSM, 324 pairs of patients were matched between the patients with DEX administration and those without. DEX administration was associated with decreased in-hospital mortality [hazard ratio (HR) 0.287; 95% CI 0.151–0.542; P < 0.001] and 90-day mortality [HR 0.344; 95% CI 0.221–0.534; P < 0.001], and it was also associated with reduced length of stay (LOS) in ICU [4.54(3.13,7.72) versus 5.24(3.15,10.91), P < 0.001] and LOS in hospital [11.63(8.02,16.79) versus 12.09(7.83,20.44), P = 0.002]. Subgroup analysis showed the above associations existed only in mild and moderate AKI subgroups, but not in severe AKI subgroup. Nevertheless, DEX administration was not associated with the recovery of renal function [HR 1.199; 95% CI 0.851–1.688; P = 0.300].
Conclusions

DEX administration improved outcomes in critically ill patients with mild and moderate AKI and could be a good choice of sedation.
RaDiCo, the French National Program on Rare Disease Cohorts
Authors: Amselem Serge , Gueguen Sonia , Weinbach Jérôme , Clement Annick , Landais Paul
Published: June 2021

Background: Rare diseases (RDs) affect nearly 3 million people in France and at least 26-30 million people in Europe. These diseases, which represent a major medical concern, are mainly of genetic origin, often chronic, progressive, degenerative, life threatening and disabling, accounting for more than one third of all deaths occurring during infancy. In this context, there are needs for coordinated information on RDs at national /international levels, based on high quality, interoperable and sharable data. The main objective of the RaDiCo (Rare Disease Cohorts) program, coordinated by Inserm, was the development of RD e-cohorts via a national platform. The cohort projects were selected through a national call in 2014. The e-cohorts are supported by an interoperable platform, equivalent to an infrastructure, constructed on the "cloud computing" principle and in compliance with the European General Data Protection Regulation. It is dedicated to allow a continuous monitoring of data quality and consistency, in line with the French Health Data Hub. Results: Depending on cohorts, the objectives are to describe the natural history of the studied RD(s), establish phenotype-genotype correlations, decipher their pathophysiology, assess their societal and medico-economic impact, and/or identify patients eligible for new therapeutic approaches. Inclusion of prevalent and incident cases started at the end of 2016. As of April 2021, 5558 patients have been included within 13 RD e-cohorts covering 67 diseases integrated in 10 European Reference Networks and contributing to the European Joint Program on RDs. Several original results have been obtained in relation with the secondary objectives of the RaDiCo cohorts. They deal with discovery of new disease genes, assessment of treatment management, deciphering the underlying pathophysiological mechanisms, diagnostic approaches, genotype-phenotype relationships, development and validation of questionnaires relative to disease burden, or methodological aspects.Conclusion: RaDiCo currently hosts 13 RD e-cohorts on a sharable and interoperable platform constructed on the “cloud computing” principle. New RD e-cohorts at the European and international levels are targeted.
Source-tracking of the Chinese Chikungunya Viruses Suggests That Indian Subcontinent and Southeast Asia Act as Major Hubs for the Recent Global Spread of Chikungunya Virus
Authors: Qiu Shaofu , Guo Jinpeng , Li Peihan , Li Peng , Du Xinying , Hao Rongzhang , Yang Chaojie , Wang Qi , Liu Hongbo , Zhang Haoran , Tian Sai , Shi Hua , Wen Liang , An Daizhi , Yang Xiaocui , An Xiaoyuan , Wang Ligui , Song Hongbin , Wang Changjun
Published: June 2021

BackgroundChikungunya fever caused by Chikungunya virus (CHIKV) has become a major global health concern, which has caused un­expected large outbreaks in Africa, Asia, Europe, and the Ameri­cas. China is a non-indigenous region of CHIKV, and the origin of the Chinese CHIKV strains is not well understood. Especially, there is limited understanding of the recent global spread of CHIKV in the context of recent worldwide epidemic of CHIKV.MethodsHere we investigated a novel Chikungunya patient imported from Myanmar into China in August, 2019. The genome was sequenced directly from the serum sample by combined MinION sequencing with BGISEQ-500 sequencing. We constructed a complete CHIKV genome dataset, including 727 CHIKV genomes retrieved from Genbank and the genome sequenced in this study, and conducted an updated and comprehensive phylogenetic analysis to understand the origin, evolution, transmission routes and genetic adaptation of the virus.ResultsAll of the globally distributed CHIKV genomes were divided into three genotypes, including West Africa (WA), East/Central/South African (ECSA) and Asian genotypes. The genome sequenced in this study was located in the Indian Ocean lineage (IOL), and closely related to a strain isolated from a patient in Australia who returned from Bangladesh in 2017. Comprehensive phylogenetic analysis showed that the Chinese strains were mainly sourced from Indian subcontinent and Southeast Asia. Further analyses indicated that Indian subcontinent and Southeast Asia may act as major hubs for the recent global spread of CHIKV, leading to widespread epidemics and even many large outbreaks. Moreover, we identified 179 distinct sites containing some undescribed sites in the sP and nsP proteins, showing obvious genetic varieties associated with different CHIKV lineages.ConclusionsHere we reported a novel CHIKV isolate from a Chikungunya patient imported from Myanmar into China in 2019, and summarized the source and evolution of Chinese CHIKV strains. The present findings provided better understanding of the recent global evolution of CHIKV, highlighting the urgent need for the strengthened surveillance including the viral diversity surveillance.
Melatonin Attenuates Ropivacaine-Induced Apoptosis by Inhibiting Excessive Mitophagy Through the Parkin / PINK1 Pathway in PC12 and HT22 Cells
Authors: Zeng Lian , He Jiafeng , Liu Chenguang , Zhang Fuyu , Zhang Zhen , Chen Huaxian , Wang Qingsong , Ding Xudong , Luo Huiyu
Published: June 2021

Melatonin, as an endogenous circadian indoleamine, is secreted from the pineal gland and has extensive biological functions, including antioxidant, anti-inflammatory, anti-tumor and neuroprotective effects. Its neuroprotective effects make it to be a potential therapeutic for many nerve damages, but its effect on ropivacaine-induced neurotoxicity remains unclear. The aims of our research were to explore the impact and mechanism of melatonin on ropivacaine-induced neurotoxicity. Our results shown that melatonin pretreatment protected the cell viability, morphology, and apoptosis of PC12 and HT22 cells from ropivacaine, it also improved ropivacaine-induced mitochondrial dysfunction and it inhibited an increase of mitophagy levels by ropivacaine. In addition, our study also revealed that the increase of mitophagy levels could reduce the protective effect of melatonin on ropivacaine-induced apoptosis in PC12 and HT22 cells, but the inhibition of mitophagy could enhance this effect of melatonin. To further illustrate the mechanism of melatonin inhibited mitophagy, the expressions of Parkin and PINK1 were detected, and results shown that melatonin inhibited the activation of Parkin / PINK1 pathway. In conclusion, our results indicated that melatonin protected ropivacaine-induced apoptosis through suppressing excessive mitophagy by inhibiting the Parkin / PINK1 pathway. Melatonin may be a useful potential therapeutic agent against ropivacaine-induced neurotoxicity.
High Prevalence of Antinuclear Antibodies in Patients With Chronic Hepatitis C Virus Infection
Authors: de Castro Geison Luiz Costa , Amoras Ednelza Silva Graça , Araujo Mauro Sérgio , Conde Simone Regina da Silva Souza , Bichara Carlos David Araújo , Queiroz Maria Alice Freitas , Vallinoto Antonio Carlos Rosário
Published: June 2021

Hepatitis C virus (HCV) infection is a serious public health concern due to its high prevalence and mortality rate. In chronic infection, HCV may induce autoimmune responses through the production of autoantibodies, including anti-nuclear antibodies (ANA). We assessed the presence of ANA by indirect immunofluorescence using HEp-2 cells in 89 patients with chronic hepatitis C. We also collected data on epidemiological variables; clinical characteristics; and biochemical, hematological, molecular and histopathological information from the patients to assess the impact of the presence of ANA in those patients. The prevalence of ANA in the patients was 20.2%, which was significantly higher than that found in healthy controls (2%). However, there was no association of this marker with epidemiological, clinical-laboratory, molecular or histopathological characteristics of hepatitis C, although a slightly higher prevalence of ANA was detected in women and in patients infected with subgenotype 1a. In a specific analysis, chronic HCV patients with the “rods and rings” cytoplasmic pattern had higher degrees of hepatic fibrosis than did ANA-negative patients. The results suggest a greater predisposition to the presence of ANA in patients with HCV, which may be associated with a worse prognosis, especially in the presence of the “rods and rings” cytoplasmic pattern.
CO2 Dynamics and Heterogeneity in a Cave Atmosphere: Role of Ventilation Patterns and Airflow Pathways
Authors: Kukuljan Lovel , Gabrovsek Franci , Covington Matthew D. , Johnston Vanessa E.
Published: June 2021

Understanding the dynamics and distribution of CO2 in the subsurface atmosphere of carbonate karst massifs provides important insights into dissolution and precipitation processes, the role of karst systems in the global carbon cycle, and the use of speleothems for paleoclimate reconstructions. We discuss long-term microclimatic observations in a passage of Postojna Cave, Slovenia, focusing on high spatial and temporal variations of pCO2. We show 1) that the airflow through the massif is determined by the combined action of the chimney effect and external winds and 2) that the relationship between the direction of the airflow, the geometry of the airflow pathways, and the position of the observation point explains the observed variations of pCO2. Namely, in the terminal chamber of the passage, the pCO2 is low and uniform during updraft, when outside air flows to the site through a system of large open galleries. When the airflow reverses direction to downdraft, the chamber is fed by inlets with diverse flow rate and pCO2, which enter via small conduits and fractures embedded in a CO2-rich vadose zone. If the spatial distribution of inlets and outlets produces minimal mixing between low and high pCO2 inflows, high and persistent gradients in pCO2 are formed. Such is the case in the chamber, where vertical gradients of up to 1000 ppm/m is observed during downdraft. The results presented in this work provide new insights into the dynamics and composition of the subsurface atmosphere and demonstrate the importance of long-term and spatially distributed observations.
Tibial Cortex Transverse Distraction Combined With Debridement and Vacuum Sealing Drainage for Diabetic Foot Ulcers: Validation of Previous Published Study
Authors: Fan Zhi-Qiang , Liu De-Wu
Published: June 2021

Objective: Tibial cortex transverse distraction (TCTD) has been recently reported in treating diabetic foot ulcers. However, there is no further studies verifying the effectiveness. We performed TCTD combined with debridement and vacuum sealing drainage (VSD) for diabetic foot ulcers to test the effectiveness.Methods: This study includes 25 patients with diabetic foot ulcers from 3 hospitals. The ulcers of all the cases didn't heal for over 3 months. Then we performed TCTD combined with debridement and VSD for them. After the surgery, the patients were regularly followed-up for more than one year.Results: Among all the patients, one case underwent amputation because of aggravated infections. There were no cases with complication like tibia fractures. Pin-site infections occurred in 2 patients. The infected pin-site healed after changing dressings for 2 weeks. For the rest 22 patients, their ulcers healed at postoperative 8.2 ± 4.5 weeks. The postoperative visual analogue score (VAS) which indicated pain degree, reduced significantly when compared with preoperative VAS.Conclusions: When combined with other measures like debridement and VSD, TCTD can bring advantages for patients diagnosed with diabetic foot ulcers, and the trauma of this operation remains a factor to be considered.Type of study/level of evidence: Therapeutic IV.
Cancer-Associated Adipocytes Release FUCA2 to Promote Aggressive Phenotype in Triple-Negative Breast Cancer
Authors: Liu Qun , Dong Hui-ting , Zhao Tingting , Yao Fan , Xu Yingying , Chen Bo , Wu Yunfei , Jin Feng , Xing Peng
Published: June 2021

Background: Cancer-associated adipocytes (CAAs) have been suggested to promote tumor progression. Yet, the role of CAAs in triple-negative breast cancer (TNBC) is poorly investigated. Methods: We compared the expression of secretory protein-encoding genes in CAAs and control adipocytes. The effect of key secretory protein(s) on TNBC cell behaviors was explored. Results: CAAs expressed and secreted FUCA2 at greater levels than control adipocytes. When FUCA2 activity was blocked with a neutralizing antibody, TNBC cell proliferation and migration induced by CAA conditioned medium was impaired. In contrast, supplement of exogenous FUCA2 protein reinforced the proliferation, colony formation, and migration of TNBC cells. In vivo studies confirmed that FUCA2 exposure enhanced tumorigenesis and metastasis of TNBC cells. Mechanistic investigation revealed that FUCA2 induced TNBC aggressiveness through TM9SF3-dependent signaling. Depletion of TM9SF3 blocked CAA- and FUCA2-induced TNBC cell proliferation and migration. Compared to adjacent breast tissues, TNBC tissues had increased expression of TM9SF3. Moreover, high TM9SF3 expression was associated with advanced TNM stage, lymph node metastasis, and shorter overall survival of TNBC patients. Conclusions: Altogether, CAAs secrete FUCA2 to promote TNBC growth and metastasis through interaction with TM9SF3. Inhibition of TM9SF3 may represent a potential therapeutic strategy in the treatment of TNBC.
Dopaminergic Receptors as Neuroimmune Mediators in Experimental Autoimmune Encephalomyelitis
Authors: Gonçalves Elaine Cristina Dalazen , Lieberknecht Vicente , Horewicz Verônica Vargas , Rabelo Bruna Daniel , Felipetti Francielly Andressa , Rodrigues Ana Lúcia Severo , Martins Daniel Fernandes , Dutra Rafael Cypriano
Published: June 2021

The dopaminergic system plays an essential role in maintaining homeostasis between the central nervous system (CNS) and the immune system. Previous studies have associated imbalances in the dopaminergic system with the pathogenesis of multiple sclerosis (MS). Herein, we investigate the protein levels of dopaminergic receptors (D1R and D2R) in different phases of the experimental autoimmune encephalomyelitis (EAE) model. We also examined if the treatment with pramipexole (PPX) – a dopamine D2/D3 receptor-preferring agonist – would be able to prevent the EAE-induced motor and mood dysfunction, as well as the underlying mechanisms of action. Our findings showed that D2R immunocontent upregulated in the spinal cord of EAE mice 14 days post-induction. Moreover, D1R and D2R immunocontent was significantly increased in the lymph nodes during the chronic phase of EAE. Also, during this phase, oxidative damage in the spinal cord and striatum of EAE animals was significantly higher. During the pre-symptomatic phase, axonal damage in the spinal cord of EAE mice could already be found. In addition, PPX treatment failed to inhibit EAE progression and anhedonic-like behavior. Otherwise, PPX inhibited the depressive-like behavior. Relevantly, PPX oral treatment downregulated IL-1β levels and increased BNDF content in the spinal cord after EAE induction. Altogether, it is possible to conclude that D2R participates in crosstalk between CNS and immune system during autoimmune and neuroinflammatory response induced by EAE, mainly in the acute and chronic phase of the disease. Relevantly, a dopamine D2/D3 receptor-preferring agonist mitigated depressive-like behavior induced by EAE, which offers a new possibility for treating depressive symptoms in MS patients.