bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Area Recognition and Use-Intensity Analysis Based on Multi-Source Data: A Case Study of Jinan, China
Authors: Yu Mingyang , Li Jingqi , Lv Yongqiang , Xing Huaqiao , Wang Huimeng
Published: September 2021

This paper proposes a GIS-based field model for hot-spot extraction based on POI data and analyzes the use intensity of functional areas by using Tencent location data to identify and describe the morphological characteristics and dynamic use intensity of facilities in urban functional areas. Taking the four districts of Jinan City Center as an example, we used the generalized symmetric structure spectrum and digital field-based hierarchical geo-information Tupu to extract facility hot spots. Tencent location data were then applied to quantify differences in the use intensity of functional areas between workday and weekend, as well as between daytime and nighttime. Finally, refined research on functional areas was realized from a dynamic point of view. Results showed that (1) the generalized symmetric structure spectrum and digital field-based hierarchical geo-information Tupu can identify and express the characteristics of the spatial distribution and hierarchical structures of urban facility hot spots at the horizontal and vertical levels, respectively; (2) overall, the distribution of all types of functional areas presents the characteristics of “circular structures,” which form a spatial pattern of “multi-center” groups and “single/mixed” functional areas; (3) aside from residential facilities, green space and square land facilities have the highest use intensity; this finding highlights the tourism characteristics of Jinan. Low-use intensity areas are distributed at the periphery of the four districts, while high-use intensity areas, the functional type of which is mainly business facilities, are mainly distributed around the urban area. These results are helpful to the development strategy of the city’s efforts to adapt to economic change and provide a scientific basis for the functional orientation of Jinan City.
Accuracy of Regional Centrality Using Social Network Analysis: Evidence from Commuter Flow in South Korea
Authors: Lee Jongsang , Seo Ducksu
Published: September 2021

With the recent exponential growth in inter-regional movements of population and information, there is an urgent need for accurately measuring the connectivity and centrality of cities. This study aims to investigate the differences in centrality between different scales of a dataset and to propose a calibration method to minimize the gap between the measures from the two scales. Although urban and regional centrality is examined by analyzing regional commuting datasets, this study proposes that it should be measured using nationwide data to validate the centrality results. To demonstrate this, the differences in regional centrality between different spatial scales of commuting trips for two data groups are shown: Seoul regional data and nationwide data. In this structure, the centrality levels of the 25 districts of Seoul were calculated for both groups. The results clearly show the differences in the centrality levels of districts in both groups: Seongbuk district ranked 10th in the local dataset but fell to 18th in the nationwide dataset; Geumcheon district ranked 22nd in the former but rose to 9th in the latter. The ratio of inner commuting in Seoul is thus relatively low, and each district has dynamic connections with other provinces. Furthermore, the results of a linear regression analysis, which was conducted on a local dataset to obtain similar results as those obtained using a national dataset, demonstrate the significance of a wide-ranging commuting dataset for regional centrality analysis of a specific region.
Estimating the Soil Erosion Cover-Management Factor at the European Part of Russia
Authors: Mukharamova Svetlana , Saveliev Anatoly , Ivanov Maxim , Gafurov Artur , Yermolaev Oleg
Published: September 2021

Evaluation of the vegetation and agricultural-management factor (C-factor) is an important task, the solution of which affects the correct assessment of the intensity of soil erosion. For the vast area of the European part of Russia (EPR), this task is particularly relevant since no products allow taking into account the C-factor. An approach based on automated interpretation of the main crop groups based on MODIS satellite imaging data from Terra and Aqua satellites with the LSTM machine-learning method was used to achieve this goal. The accuracy of crop group recognition compared to the open data of the Federal State Statistics Service of Russia was 94%. The resulting crop maps were used to calculate the C-factor for each month of a particular year from 2014 to 2019. After that, summaries were made at the regional and landscape levels. The average C-factor value for the EPR was 0.401, for the forest landscape zone 0.262, for the forest-steppe zone 0.362, and for the steppe zone 0.454. The obtained results are in good correlation with the results of previous field studies and provide up-to-date (based on 2014–2019 data) estimates of C-factor for rainfall erosion (monthly, annual) with high spatial detail (250 m).
Ming and Qing Dynasty Official-Style Architecture Roof Types Classification Based on the 3D Point Cloud
Authors: Dong Youqiang , Hou Miaole , Xu Biao , Li Yihao , Ji Yuhang
Published: September 2021

The Ming and Qing Dynasty type of official-style architecture roof can provide plenty of prior knowledge relating to the structure and size of these works of architecture, and plays an important role in the fields of 3D modeling, semantic recognition and culture inheriting. In this paper, we take the 3D point cloud as the data source, and an automatic classification method for the roof type of Ming and Qing Dynasty official-style architecture based on the hierarchical semantic network is illustrated. To classify the roofs into the correct categories, the characteristics of different roof types are analyzed and features including SoRs, DfFtR, DoPP and NoREs are first selected; subsequently, the corresponding feature extraction methods are proposed; thirdly, aiming at the structure of the ridges, a matching graph relying on the attributed relational graph of the ridges is given; based on the former work, a hierarchical semantic network is proposed and the thresholds are determined with the help of the construction rules of the Ming and Qing Dynasty official-style architecture. In order to fully verify the efficiency of our proposed method, various types of Ming and Qing Dynasty official-style architecture roof are identified, and the experimental results show that all structures are classified correctly.
Nanoparticle-Aided Detection of Colorectal Cancer-Associated Glycoconjugates of Extracellular Vesicles in Human Serum
Authors: Vinod Rufus , Mahran Randa , Routila Erica , Leivo Janne , Pettersson Kim , Gidwani Kamlesh
Published: September 2021

Extracellular vesicles (EVs) are found in all biological fluids, providing potential for the identification of disease biomarkers such as colorectal cancer (CRC). EVs are heavily glycosylated with specific glycoconjugates such as tetraspanins, integrins, and mucins, reflecting the characteristics of the original cell offering valuable targets for detection of CRC. We report here on europium-nanoparticle (EuNP)-based assay to detect and characterize different surface glycoconjugates of EVs without extensive purification steps from five different CRC and the HEK 293 cell lines. The promising EVs candidates from cell culture were clinically evaluated on small panel of serum samples including early-stage (n = 11) and late-stage (n = 11) CRC patients, benign condition (n = 11), and healthy control (n = 10). The majority of CRC cell lines expressed tetraspanin sub-population and glycovariants of integrins and conventional tumor markers. The subpopulation of CD151 having CD63 expression (CD151CD63) was significantly (p = 0.001) elevated in early-stage CRC (8 out of 11) without detecting any benign and late-stage samples, while conventional CEA detected mostly late-stage CRC (p = 0.045) and with only four early-stage cases. The other glycovariant assays such as CEACon-A, CA125WGA, CA 19.9Ma696, and CA 19.9Con-A further provided some complementation to the CD151CD63 assay. These results indicate the potential application of CD151CD63 assay for early detection of CRC patients in human serum.
ERβ Regulation of Gonadotropin Responses during Folliculogenesis
Authors: Lee Eun B. , Chakravarthi V. Praveen , Wolfe Michael W. , Rumi M. A. Karim
Published: September 2021

Gonadotropins are essential for regulating ovarian development, steroidogenesis, and gametogenesis. While follicle stimulating hormone (FSH) promotes the development of ovarian follicles, luteinizing hormone (LH) regulates preovulatory maturation of oocytes, ovulation, and formation of corpus luteum. Cognate receptors of FSH and LH are G-protein coupled receptors that predominantly signal through cAMP-dependent and cAMP-independent mechanisms that activate protein kinases. Subsequent vital steps in response to gonadotropins are mediated through activation or inhibition of transcription factors required for follicular gene expression. Estrogen receptors, classical ligand-activated transcriptional regulators, play crucial roles in regulating gonadotropin secretion from the hypothalamic–pituitary axis as well as gonadotropin function in the target organs. In this review, we discuss the role of estrogen receptor β (ERβ) regulating gonadotropin response during folliculogenesis. Ovarian follicles in Erβ knockout (ErβKO) mutant female mice and rats cannot develop beyond the antral state, lack oocyte maturation, and fail to ovulate. Theca cells (TCs) in ovarian follicles express LH receptor, whereas granulosa cells (GCs) express both FSH receptor (FSHR) and LH receptor (LHCGR). As oocytes do not express the gonadotropin receptors, the somatic cells play a crucial role during gonadotropin induced oocyte maturation. Somatic cells also express high levels of estrogen receptors; while TCs express ERα and are involved in steroidogenesis, GCs express ERβ and are involved in both steroidogenesis and folliculogenesis. GCs are the primary site of ERβ-regulated gene expression. We observed that a subset of gonadotropin-induced genes in GCs, which are essential for ovarian follicle development, oocyte maturation and ovulation, are dependent on ERβ. Thus, ERβ plays a vital role in regulating the gonadotropin responses in ovary.
The Effect of Mirid Density on Volatile-Mediated Foraging Behaviour of Apolygus lucorum and Peristenus spretus
Authors: Chen Han , Su Honghua , Zhang Shuai , Jing Tianxing , Liu Zhe , Yang Yizhong
Published: September 2021

Plants would release herbivore-induced plant volatiles (HIPVs) to repel herbivores and attract natural enemies after being damaged by herbivores. In this study, after cotton plants were damaged by different densities of Apolygus lucorum, the behavioral responses of A. lucorum and Peristenus spretus to cotton plants volatiles were evaluated, and the quality and quantity of volatiles from cotton plants were analyzed. Only when cotton plants were damaged by four bugs did both A. lucorum and P. spretus show an obvious response to damaged cotton plants, which indicates that cotton defense is correlated with pest density. The collection and analysis of volatiles reveals that the increase in pest density results in the emission of new compounds and an increase in the total number of volatiles with an alteration in proportions among the compounds in the blend. These changes in volatile profiles might provide wasps and mirids with specific information on host habitat quality and thus could explain the behavioral responses of parasitoids and pests.
Prediction of Spatiotemporal Invasive Risk of the Red Import Fire Ant, Solenopsis invicta (Hymenoptera: Formicidae), in China
Authors: Song Jinyue , Zhang Hua , Li Ming , Han Wuhong , Yin Yuxin , Lei Jinping
Published: September 2021

The red imported fire ant, Solenopsis invicta (Hymenoptera: Formicidae), is an invasive pest, and it has spread rapidly all over the world. Predicting the suitable area of S. invicta growth in China will provide a reference that will allow for its invasion to be curbed. In this study, based on the 354 geographical distribution records of S. invicta, combined with 24 environmental factors, the suitable areas of S. invicta growth in China under current (2000s) and future (2030s and 2050s) climate scenarios (SSPs1-2.5s, SSPs2-3.5s and SSPs5-8.5s) were predicted by using the optimized MaxEnt model and geo-detector model. An iterative algorithm and knife-cut test were used to evaluate the important environmental factors that restrict the suitable area under the current climatic conditions. This study also used the response curve to determine the appropriate value of environmental factors to further predict the change and the center of gravity transfer of the suitable area under climate change. The optimized MaxEnt model has high prediction accuracy, and the working curve area (AUC) of the subjects is 0.974. Under climatic conditions, the suitable area is 81.37 × 104 km2 in size and is mainly located in the south and southeast of China. The main environmental factors affecting the suitable area are temperature (Bio1, Bio6, and Bio9), precipitation (Bio12 and Bio14) and NDVI. In future climate change scenarios, the total suitable area will spread to higher latitudes. This distribution will provide an important theoretical basis for relevant departments to rapidly prevent and control the invasion of S. invicta.
Red Cell Distribution Width and Patient Outcome in Cardiovascular Disease: A ‘’Real-World’’ Analysis
Authors: Talarico Marisa , Manicardi Marcella , Vitolo Marco , Malavasi Vincenzo Livio , Valenti Anna Chiara , Sgreccia Daria , Rossi Rosario , Boriani Giuseppe
Published: September 2021

Red cell distribution width (RDW) has been shown to predict adverse outcomes in specific scenarios. We aimed to assess the association between RDW and all-cause death and a clinically relevant composite endpoint in a population with various clinical manifestations of cardiovascular diseases. We retrospectively analyzed 700 patients (median age 72.7 years [interquartile range, IQR, 62.6–80]) admitted to the Cardiology ward between January and November 2016. Patients were divided into tertiles according to baseline RDW values. After a median follow-up of 3.78 years (IQR 3.38–4.03), 153 (21.9%) patients died and 247 (35.3%) developed a composite endpoint (all-cause death, acute coronary syndromes, transient ischemic attack/stroke, and/or thromboembolic events). With multivariate Cox regression analysis, the highest RDW tertile was independently associated with an increased risk of all-cause death (adjusted hazard ratio [HR] 2.73, 95% confidence interval [CI] 1.63–4.56) and of the composite endpoint (adjusted HR 2.23, 95% CI 1.53–3.24). RDW showed a good predictive ability for all-cause death (C-statistics: 0.741, 95% CI 0.694–0.788). In a real-world cohort of patients, we found that higher RDW values were independently associated with an increased risk of all-cause death and clinical adverse cardiovascular events thus proposing RDW as a prognostic marker in cardiovascular patients.
The Effect of Selective Retina Therapy with Automatic Real-Time Feedback-Controlled Dosimetry for Chronic Central Serous Chorioretinopathy: A Randomized, Open-Label, Controlled Clinical Trial
Authors: Lee Ji-young , Kim Min-hee , Jeon Seung-hee , Lee Seung-hoon , Roh Young-jung
Published: September 2021

This prospective randomized controlled trial evaluated the safety and efficacy of real-time feedback-controlled dosimetry (RFD)-guided selective retina therapy (SRT) in chronic central serous chorioretinopathy (CSC). Forty-four participants with chronic CSC were included and randomly assigned to the control group or SRT group. The SRT laser system with RFD-guidance was applied to cover the entire leakage area. If SRF remained at the 6-week follow-up visit, re-treatment and rescue SRT was performed for the SRT group and crossover group, respectively. The rate of complete resolution of subretinal fluid (SRF), mean SRF height, and mean retinal sensitivity were compared between the two groups at 6-weeks post-treatment. The complete SRF resolution rate in all SRT-treated eyes was evaluated at 12-weeks post-treatment. The rate of complete SRF resolution was significantly higher in the SRT group (63.6%) than in the control group (23.8%) at 6-weeks post-treatment (p = 0.020). The mean SRF height at 6 weeks after SRT was significantly lower in the SRT group (p = 0.041). Overall, SRT-treated eyes showed complete SRF resolution in 70.3% of eyes at 12-weeks post-treatment. RFD-guided SRT was safe and effective to remove SRF in chronic CSC patients during the 3-month follow-up period.
Real-World Data on Bleeding Patterns of Hemophilia A Patients Treated with Emicizumab
Authors: Levy-Mendelovich Sarina , Brutman-Barazani Tami , Budnik Ivan , Avishai Einat , Barg Assaf A. , Levy Tamara , Misgav Mudi , Livnat Tami , Kenet Gili
Published: September 2021

Emicizumab (Hemlibra™) is approved for prophylaxis of hemophilia A (HA) patients. The HAVEN studies addressed bleeding reduction in emicizumab-treated patients, but real-world data on bleeding patterns during emicizumab therapy are lacking. We aimed to compare the occurrence of breakthrough bleeding at different time points, starting from emicizumab initiation. This longitudinal prospective observational cohort study included HA patients (n = 70, aged 1 month to 74.9 years) that completed at least 18 months of follow-up in our center. We analyzed the number of spontaneous and traumatic bleeds during selected time points of the study (“bleeding periods”). The percentage of traumatic and spontaneous bleeding episodes was not significantly different among “bleeding periods” (P = 0.053 and P = 0.092, respectively). Most trauma-related treated bleeds resulted from either hemarthrosis (53%) or head trauma (33%). Spontaneous bleeding episodes were mostly hemarthroses (80%). Potential associations of the patients’ age, annualized bleeding rate before emicizumab treatment, and the presence of inhibitors with spontaneous bleed occurrence were analyzed with binomial logistic regression. The odds of bleeding while on emicizumab increased by a factor of 1.029 (P = 0.034) for every one year of age. Conclusions: Our real-world data revealed that the risk of bleeding persists, especially in older patients, despite therapy with emicizumab. These data may help clinicians in counselling their patients and in planning their management.
Acceptance and Commitment Therapy versus Social Support for Smoking Cessation for People with Schizophrenia: A Randomised Controlled Trial
Authors: Mak Yim-Wah , Loke Alice-Yuen , Leung Doris Y. P.
Published: September 2021

Smoking is prevalent among people with schizophrenia. It has been found that Acceptance and commitment therapy (ACT) is effective for treating psychotic symptoms and addictive behaviours, but the therapy has not been modified to help individuals with schizophrenia to quit smoking. A randomised controlled trial was conducted with the objective of comparing a 10-week, individual, face-to-face ACT programme (n = 65) to a social support programme on smoking cessation, experiential avoidance, and emotion-regulation strategies among people with schizophrenia who smoke (n = 65). The primary outcome was self-reported smoking abstinence for 7 days at 6 months after the start of the intervention. Secondary outcomes were self-reported and biochemically validated quit rates post-intervention. The Avoidance and Inflexibility Scale (AIS), Acceptance and Action Questionnaire II (AAQII), and Emotion Regulation Questionnaire (ERQ) were employed. The self-reported quit rates in the ACT group were higher than in the social support group, although no significant differences were found (6 months: 12.3% vs. 7.7%, p = 0.56, 12 months: 10.8% vs. 7.7%, p = 0.76). We found significantly greater improvements in smoking-specific and ACT-specific experiential avoidance and less reliance on emotion regulation strategies in the ACT group at some time points. Overall, ACT is better than social support at enhancing experiential avoidance and reducing reliance on emotion regulation strategies in adults with schizophrenia who smoke. However, ACT did not produce a much better result than social support in helping them to completely quit smoking.
Endothelial Activation and Stress Index (EASIX) as an Early Predictor for Mortality and Overall Survival in Hematological and Non-Hematological Patients with COVID-19: Multicenter Cohort Study
Authors: Kalicińska Elżbieta , Biernat Monika , Rybka Justyna , Zińczuk Aleksander , Janocha-Litwin Justyna , Rosiek-Biegus Marta , Morawska Marta , Waszczuk-Gajda Anna , Drozd-Sokołowska Joanna , Szukalski Łukasz , Rymko Marcin , Jabłonowska Paula , Simon Krzysztof , Wróbel Tomasz
Published: September 2021

COVID-19, as a disease involving the endothelium of multiple organs, is characterized by high mortality rates among hospitalized patients. Patients with hematological malignancies are particularly at risk of an unfavorable course of COVID-19. The endothelial activation and stress index (EASIX) score has been used as a simple predictor of overall survival (OS) in specific groups of hematological cancer patients. EASIX, as a biomarker of endothelial dysfunction, might play a prognostic role in patients with COVID-19. Here, we performed a comprehensive retrospective analysis of the EASIX score in 523 hospitalized COVID-19 patients with or without coexisting hematological cancer. Hematological cancer COVID-19 patients had higher EASIX scores compared to the overall population with COVID-19. In hematological patients, EASIX was a strong predictor of the occurrence of sepsis during COVID-19. Our findings demonstrated EASIX as a strong predictor of intensive care unit admission, in-hospital mortality, the occurrence of acute renal failure and the need for hemodialysis, both in hematological and non-hematological COVID-19 patients. Patients with a high EASIX score on COVID-19 diagnosis had significantly inferior OS compared to patients with low EASIX. We showed for the first time that EASIX might serve as a simple, universal prognostic tool of OS in both hematological and non-hematological COVID-19 patients.
Association of Acute Kidney Injury with the Risk of Dementia: A Meta-Analysis
Authors: Hussain Salman , Singh Ambrish , Antony Benny , Claure-Del Granado Rolando , Klugarová Jitka , Líčeník Radim , Klugar Miloslav
Published: September 2021

Acute kidney injury (AKI) is associated with several adverse outcomes, including new or progressive chronic kidney disease, end-stage kidney disease, and mortality. Epidemiological studies have reported an association between AKI and dementia as a long-term adverse outcome. This meta-analysis was aimed to understand the association between AKI and dementia risk. A literature search was performed in MEDLINE and Embase databases, from inception to July 2021, to identify epidemiological studies reporting the association between AKI and dementia risk. Title and abstract followed by the full-text of retrieved articles were screened, data were extracted, and quality was assessed, using the Newcastle–Ottawa scale by two investigators independently. The primary outcome was to compute the pooled risk of dementia in AKI patients. Subgroup analysis was also performed based on age and co-morbidities. Certainty of evidence was assessed using the GRADE approach. Statistical analysis was performed using Review Manager 5.4 software. Four studies (cohort (n = 3) and case–control (n = 1)) with a total of 429,211 patients, of which 211,749 had AKI, were identified. The mean age of the patients and the follow-up period were 64.15 ± 16.09 years and 8.9 years, respectively. Included studies were of moderate to high quality. The pooled estimate revealed a significantly higher risk of dementia in AKI patients with an overall relative risk/risk ratio (RR) of 1.92 (95% CI: 1.52–2.43), p ≤ 0.00001. Dementia risk increases by 10% with one year increase in age with an RR of 1.10 (95% CI: 1.09–1.11), p < 0.00001. Subgroup analysis based on stroke as a co-morbid condition also revealed significantly higher dementia risk in AKI patients (RR 2.30 (95% CI: 1.62–3.28), p = 0.009). All-cause mortality risk was also significantly higher in AKI patients with dementia with a pooled RR of 2.11 (95% CI: 1.20–3.70), p = 0.009. The strength of the evidence was of very low certainty as per the GRADE assessment. Patients with AKI have a higher risk of dementia. Further large epidemiological studies are needed to confirm the mechanistic association.
Clinical Predictors of Prolonged Hospital Stay in Patients with Myasthenia Gravis: A Study Using Machine Learning Algorithms
Authors: Chang Che-Cheng , Yeh Jiann-Horng , Chen Yen-Ming , Jhou Mao-Jhen , Lu Chi-Jie
Published: September 2021

Myasthenia gravis (MG) is an autoimmune disorder that causes muscle weakness. Although the management is well established, some patients are refractory and require prolonged hospitalization. Our study is aimed to identify the important factors that predict the duration of hospitalization in patients with MG by using machine learning methods. A total of 21 factors were chosen for machine learning analyses. We retrospectively reviewed the data of patients with MG who were admitted to hospital. Five machine learning methods, including stochastic gradient boosting (SGB), least absolute shrinkage and selection operator (Lasso), ridge regression (Ridge), eXtreme gradient boosting (XGboost), and gradient boosting with categorical features support (Catboost), were used to construct models for identify the important factors affecting the duration of hospital stay. A total of 232 data points of 204 hospitalized MG patients admitted were enrolled into the study. The MGFA classification, treatment of high-dose intravenous corticosteroid, age at admission, treatment with intravenous immunoglobulins, and thymoma were the top five significant variables affecting prolonged hospitalization. Our findings from machine learning will provide physicians with information to evaluate the potential risk of MG patients having prolonged hospital stay. The use of high-dose corticosteroids is associated with prolonged hospital stay and to be used cautiously in MG patients.
Influence of Multiple Donor Renal Arteries on the Outcome and Graft Survival in Deceased Donor Kidney Transplantation
Authors: Scheuermann Uwe , Rademacher Sebastian , Wagner Tristan , Lederer Andri , Hau Hans-Michael , Seehofer Daniel , Sucher Robert
Published: September 2021

Aim: Complex arterial reconstruction in kidney transplantation (KT) using kidneys from deceased donors (DD) warrants additional study since little is known about the effects on the mid- and long-term outcome and graft survival. Methods: A total of 451 patients receiving deceased donor KT in our department between 1993 and 2017 were included in our study. Patients were divided into three groups according to the number of arteries and anastomosis: (A) 1 renal artery, 1 arterial anastomosis (N = 369); (B) >1 renal artery, 1 arterial anastomosis (N = 47); and (C) >1 renal artery, >1 arterial anastomosis (N = 35). Furthermore, the influence of localization of the arterial anastomosis (common iliac artery (CIA), versus non-CIA) was analyzed. Clinicopathological characteristics, outcome, and graft and patient survival of all groups were compared retrospectively. Results: With growing vascular complexity, the time of warm ischemia increased significantly (groups A, B, and C: 40 ± 19 min, 45 ± 19 min, and 50 ± 17 min, respectively; p = 0.006). Furthermore, the duration of operation was prolonged, although this did not reach significance (groups A, B, and C: 175 ± 98 min, 180 ± 35 min, and 210 ± 43 min, respectively; p = 0.352). There were no significant differences regarding surgical complications, post-transplant kidney function (delayed graft function, initial non-function, episodes of acute rejection), or long-term graft survival. Regarding the localization of the arterial anastomosis, non-CIA was an independent prognostic factor for deep vein thrombosis in multivariate analysis (CIA versus non-CIA: OR 11.551; 95% CI, 1.218–109.554; p = 0.033). Conclusion: Multiple-donor renal arteries should not be considered a contraindication to deceased KT, as morbidity rates and long-term outcomes seem to be comparable with grafts with single arteries and less complex anastomoses.
Delirium in Critically Ill Patients with and without COVID-19—A Retrospective Analysis
Authors: Jäckel Markus , Aicher Nico , Biever Paul Marc , Heine Laura , Bemtgen Xavier , Rilinger Jonathan , Zotzmann Viviane , Supady Alexander , Stachon Peter , Wengenmayer Tobias , Bode Christoph , Staudacher Dawid Leander
Published: September 2021

Background: Delirium complicating the course of Intensive care unit (ICU) therapy is a known driver of morbidity and mortality. It has been speculated that infection with the neurotrophic SARS-CoV-2 might promote delirium. Methods: Retrospective registry analysis including all patients treated at least 48 h on a medical intensive care unit. The primary endpoint was development of delirium as diagnosed by Nursing Delirium screening scale ≥2. Results were confirmed by propensity score matching. Results: 542 patients were included. The primary endpoint was reached in 352/542 (64.9%) patients, without significant differences between COVID-19 patients and non-COVID-19 patients (51.4% and 65.9%, respectively, p = 0.07) and correlated with prolonged ICU stay in both groups. In a subgroup of patients with ICU stay >10 days delirium was significantly lower in COVID-19 patients (p ≤ 0.01). After adjustment for confounders, COVID-19 correlated independently with less ICU delirium (p ≤ 0.01). In the propensity score matched cohort, patients with COVID-19 had significantly lower delirium incidence compared to the matched control patients (p ≤ 0.01). Conclusion: Delirium is frequent in critically ill patients with and without COVID-19 treated at an intensive care unit. Data suggests that COVID-19 itself is not a driver of delirium per se.
L-Asparaginase Toxicity in the Treatment of Children and Adolescents with Acute Lymphoblastic Leukemia
Authors: Schmidt Madalina-Petronela , Ivanov Anca-Viorica , Coriu Daniel , Miron Ingrith-Crenguta
Published: September 2021

Asparaginase is a basic component of chemotherapy in pediatric acute lymphoblastic leukemia (ALL) and has played a crucial role in improving the long-term survival of this disease. The objectives of this retrospective study were to elucidate the toxicity profile associated with asparaginase in children and adolescents with ALL, to analyze the impact of each type of toxicity on long-term outcomes, and to identify risk factors. We analyzed the medical charts of 165 patients diagnosed with ALL at Sf. Maria Iasi Children’s Hospital from 2010 to 2019 and treated according to a chemotherapeutic protocol containing asparaginase. The median duration of follow-up was 5 years (0.1–11.5 years). Groups of patients with specific types of toxicity were compared to groups of patients without toxicity. We found the following incidence of asparaginase-associated toxicity: 24.1% clinical hypersensitivity, 19.4% hepatotoxicity, 6.7% hypertriglyceridemia, 4.2% hyperglycemia, 3.7% osteonecrosis, 3% pancreatitis, 2.4% thrombosis, and 1.2% cerebral thrombosis. Overall, 82 patients (49.7%) had at least one type of toxicity related to asparaginase. No type of toxicity had a significant impact on overall survival or event-free survival. Being older than 14 years was associated with a higher risk of osteonecrosis (p = 0.015) and hypertriglyceridemia (p = 0.043) and a lower risk of clinical hypersensitivity (p = 0.04). Asparaginase-related toxicity is common and has a varied profile, and its early detection is important for realizing efficient and appropriate management.
Endoscopic Resection for Gastric Subepithelial Tumor with Backup Laparoscopic Surgery: Description of a Single-Center Experience
Authors: Chang Wei-Jung , Tsao Lien-Cheng , Yen Hsu-Heng , Yang Chia-Wei , Lin Joseph , Lin Kuo-Hua
Published: September 2021

The aim of this study was to analyze patients who underwent endoscopic resection (ER) for gastric subepithelial tumors (SETs) with a high probability of surgical intervention. Between January 2013 and January 2021, 83 patients underwent ER at the operation theater and 27 patients (32.5%) required backup surgery mainly due to incidental perforation or uncontrolled bleeding despite endoscopic repairing. The tumor was predominantly located in the upper-third stomach (81%) with a size ≤ 2 cm (69.9%) and deep to the muscularis propria (MP) layer (92.8%) but there were no significant differences between two groups except tumor exophytic growth as a risk factor in the surgery group (37% vs. 0%, p < 0.0001). Patients in the ER-only group had shorter durations of procedure times (60 min vs. 185 min, p < 0.0001) and lengths of stay (5 days vs. 7 days, p < 0.0001) but with a higher percentage of overall morbidity graded III (0% vs. 7.1%, p = 0.1571). After ER, five patients (6%) had delayed perforation and two (2.4%) required emergent laparoscopic surgery. Neither recurrence nor gastric stenosis was reported during long-term surveillance. Here, we provide a minimally invasive strategy of endoscopic resection with backup laparoscopic surgery for gastric SETs.
The Influence of Psychotherapy on Peripheral Brain-Derived Neurotrophic Factor Concentration Levels and Gene Methylation Status: A Systematic Review
Authors: Piotrkowicz Michal , Janoska-Jazdzik Marlena , Koweszko Tytus , Szulc Agata
Published: September 2021

Psychotherapy is a well-established method of treating many mental disorders. It has been proven that psychotherapy leads to structural and functional changes in the brain; however, knowledge about the molecular and cellular mechanisms of these changes is limited. Neuroplasticity and one of its mediators, brain-derived neurotrophic factor (BDNF), are potential research targets in this field. To define the role of BDNF concentration in serum, or in plasma, and BDNF promoter gene methylation in saliva or leucocytes, in psychotherapy, an extensive literature search was conducted in the PubMed and Web of Science databases. The literature review was conducted based on papers published up until May 2021 that included pre and post psychotherapy measurements of either BDNF concentration levels or promoter gene methylation status. Ten studies were indicated as eligible for analysis: eight studies that investigated peripheral BDNF concentration levels, one study that investigated methylation status, and one study that included an evaluation of both subject matters. Patients underwent cognitive behavioral therapy or interpersonal psychotherapy. Patients were diagnosed with borderline personality disorder, major depressive disorder, anorexia nervosa, bulimia nervosa, or post-traumatic stress disorder. There were only three of the nine studies that showed statistically significant increases in BDNF concentration levels after psychotherapy. The two studies that involved BDNF gene methylation status showed a decrease in methylation after dialectical behavioral therapy of borderline patients.
Real-Life Analysis with Erenumab: First Target Therapy in the Episodic and Chronic Migraine’s Prophylaxis
Authors: Maraia Zaira , Ricci Diletta , Rocchi Marco Bruno Luigi , Moretti Alessandro , Bufarini Celestino , Cavaliere Arturo , Peverini Manola
Published: September 2021

Background: to research retrospectively the efficacy of Erenumab’s treatment, thus allowing to describe a summary more in line with the reality observed every day in clinical practice, relative to a sample of patients widely heterogeneous. The study aims to confirm the efficacy of Erenumab, in terms of reduction of migraine days per month, from baseline to month 12 of treatment. Additional objectives included a reduction in the number of days of symptomatic drug use and change from baseline in the Migraine Disability Assessment Score Questionnaire (MIDAS); Methods: the analysis included all patients treated for 12 months with Erenumab during the year 2019–2020. The population analyzed consists of twenty-six patients from the Neurology outpatient clinic in Fossombrone. Several quantitative and qualitative variables were recorded by reading the medical records of the patients. The MIDAS was administered to patients to assess the disability related to migraine; Results: at the end of treatment, a statistically significant reduction in the mean number of monthly migraine days, acute medication use per month, and MIDAS questionnaire score was observed; Conclusions: as a preventive treatment of episodic and chronic migraine, our analysis data confirm the efficacy of Erenumab for the prevention of the migraine. The success is achieved in 96% of cases.
Autoimmune Rheumatic Diseases and Vascular Function: The Concept of Autoimmune Atherosclerosis
Authors: Hedar Ahmed M. , Stradner Martin H. , Roessler Andreas , Goswami Nandu
Published: September 2021

Autoimmune rheumatic diseases (AIRDs) with unknown etiology are increasing in incidence and prevalence. Up to 5% of the population is affected. AIRDs include rheumatoid arthritis, system lupus erythematosus, systemic sclerosis, and Sjögren’s syndrome. In patients with autoimmune diseases, the immune system attacks structures of its own body, leading to widespread tissue and organ damage, which, in turn, is associated with increased morbidity and mortality. One third of the mortality associated with autoimmune diseases is due to cardiovascular diseases. Atherosclerosis is considered the main underlying cause of cardiovascular diseases. Currently, because of finding macrophages and lymphocytes at the atheroma, atherosclerosis is considered a chronic immune-inflammatory disease. In active inflammation, the liberation of inflammatory mediators such as tumor necrotic factor alpha (TNFa), interleukine-6 (IL-6), IL-1 and other factors like T and B cells, play a major role in the atheroma formation. In addition, antioxidized, low-density lipoprotein (LDL) antibodies, antinuclear antibodies (ANA), and rheumatoid factor (RF) are higher in the atherosclerotic patients. Traditional risk factors like gender, age, hypercholesterolemia, smoking, diabetes mellitus, and hypertension, however, do not alone explain the risk of atherosclerosis present in autoimmune diseases. This review examines the role of chronic inflammation in the etiology—and progression—of atherosclerosis in autoimmune rheumatic diseases. In addition, discussed here in detail are the possible effects of autoimmune rheumatic diseases that can affect vascular function. We present here the current findings from studies that assessed vascular function changes using state-of-the-art techniques and innovative endothelial function biomarkers.
Characterisation of Drug-Induced Liver Injury in Patients with COVID-19 Detected by a Proactive Pharmacovigilance Program from Laboratory Signals
Authors: Delgado Ana , Stewart Stefan , Urroz Mikel , Rodríguez Amelia , Borobia Alberto M. , Akatbach-Bousaid Ibtissam , González-Muñoz Miguel , Ramírez Elena
Published: September 2021

Coronavirus disease 2019 (COVID-19) has a wide spectrum of clinical manifestations. An elevation of liver damage markers has been observed in numerous cases, which could be related to the empirical use of potentially hepatotoxic drugs. The aim of this study was to describe the clinical and analytical characteristics and perform a causality analysis from laboratory signals available of drug-induced liver injury (DILI) detected by a proactive pharmacovigilance program in patients hospitalised for COVID-19 at La Paz University Hospital in Madrid (Spain) from 1 March 2020 to 31 December 2020. The updated Roussel Uclaf Causality Assessment Method (RUCAM) was employed to assess DILI causality. A lymphocyte transformation test (LTT) was performed on 10 patients. Ultimately, 160 patients were included. The incidence of DILI (alanine aminotransferase >5, upper limit of normal) was 4.9%; of these, 60% had previous COVID-19 hepatitis, the stay was 8.1 days longer and 98.1% were being treated with more than 5 drugs. The most frequent mechanism was hepatocellular (57.5%), with mild severity (87.5%) and subsequent recovery (88.1%). The most commonly associated drugs were hydroxychloroquine, azithromycin, tocilizumab and ceftriaxone. The highest incidence rate of DILI per 10,000 defined daily doses (DDD) was with remdesivir (992.7/10,000 DDD). Some 80% of the LTTs performed were positive, with a RUCAM score of ≥4. The presence of DILI after COVID-19 was associated with longer hospital stays. An immune mechanism has been demonstrated in a small subset of DILI cases.
Vimentin-Positive Circulating Tumor Cells as Diagnostic and Prognostic Biomarkers in Patients with Biliary Tract Cancer
Authors: Han Sung Yong , Park Sung Hee , Ko Hyun Suk , Jang Aelee , Seo Hyung Il , Lee So Jeong , Kim Gwang Ha , Kim Dong Uk
Published: September 2021

Biliary tract cancer (BTC) has poor prognosis; thus, early diagnosis is important to decrease mortality. Although vimentin-positive circulating tumor cells (V-CTCs) are a good candidate for diagnostic and prognostic biomarkers, studies on the topic are limited. We aimed to evaluate the diagnostic efficacy of V-CTCs between BTC and benign biliary disease (BBD) and determine the prognostic value of V-CTCs in BTC patients. We recruited 69 participants who had BTCs and BBDs from a single tertiary referral center. We analyzed CTCs and V-CTCs in peripheral blood using the CD-PRIMETM system. Seven patients were excluded due to a technical failure of CTC detection. CTCs were detected in all 62 patients. CTC count > 40/mL blood (55.8% vs. 20%, p = 0.039), V-CTC count > 15/mL blood (57.7% vs. 10%, p = 0.005), and V-CTC/CTC ratio > 40% (48.1% vs. 10%, p = 0.025) were significantly different between BTCs and BBDs. Two or more of these three parameters (61.5% vs. 10%, p = 0.002) increased the accuracy. A combination of CTC markers with CA19-9 and biopsy increased the accuracy (90.4% vs. 10%, p = 0.000). V-CTC > 50/mL blood was a significant factor affecting survival (140 (66.6–213.3) vs. 253 (163.9–342.1) days, p = 0.008). V-CTC could be a potential biomarker for early diagnosis and predicting prognosis in patients with BTC.
Fungal Endophytes: A Promising Frontier for Discovery of Novel Bioactive Compounds
Authors: Gakuubi Martin Muthee , Munusamy Madhaiyan , Liang Zhao-Xun , Ng Siew Bee
Published: September 2021

For years, fungi have served as repositories of bioactive secondary metabolites that form the backbone of many existing drugs. With the global rise in infections associated with antimicrobial resistance, in addition to the growing burden of non-communicable disease, such as cancer, diabetes and cardiovascular ailments, the demand for new drugs that can provide an improved therapeutic outcome has become the utmost priority. The exploration of microbes from understudied and specialized niches is one of the promising ways of discovering promising lead molecules for drug discovery. In recent years, a special class of plant-associated fungi, namely, fungal endophytes, have emerged as an important source of bioactive compounds with unique chemistry and interesting biological activities. The present review focuses on endophytic fungi and their classification, rationale for selection and prioritization of host plants for fungal isolation and examples of strategies that have been adopted to induce the activation of cryptic biosynthetic gene clusters to enhance the biosynthetic potential of fungal endophytes.
The Survival and Treatment of Fusarium oxysporum f. sp. cubense in Water
Authors: Ullah Sahabne , Mostert Diane , Serfontein Kobus , Viljoen Altus
Published: September 2021

Fusarium oxysporum f. sp cubense (Foc), the causal agent of Fusarium wilt, is one of the most devastating constraints to banana production worldwide. The spread of Foc in water is particularly concerning, as infested water can rapidly contaminate disease-free areas. The objectives of this study were to investigate the survival of Foc in water and to test the effectiveness of water treatment with chlorine, ozone, UV, and peracetic acid. The study indicated that Foc spores can survive in water for more than 120 days, but that viability was reduced in stagnant water, probably due to anaerobic conditions when spores settled at the bottom. It is therefore recommended that surface water be extracted and treated before it is used for irrigation. The efficacy of all water treatments was reduced in the presence of soil, implying that water needs to be soil-free before treatment. The use of peracetic acid is recommended to treat Foc-contaminated water, as it is safe for use and does not require installation costs although it is effective at treating Foc-contaminated water, ozone would require significant input costs and chlorine can produce harmful disinfection by-products. UV would be impractical for field application because of the high doses required to eliminate Foc.
Micafungin Is an Efficient Treatment of Multi Drug-Resistant Candida glabrata Urosepsis: A Case Report
Authors: Javorova Rihova Zuzana , Slobodova Lubica , Hrabovska Anna
Published: September 2021

Candiduria is a common nosocomial infection in hospitalized patients, which may progress into life-threatening candidemia. Successful treatment of urosepsis requires early and effective antifungal therapy, while the available agents within three pharmacological classes each have characteristic pharmacokinetics and side effect profiles. Moreover, treatment of Candida spp. infections is becoming challenging due to increasing multi drug-resistance. Here, we present a case of candidemia resulting from a multi drug-resistant C. glabrata infection of the urinary tract. Due to resistance to fluconazole and a contraindication for amphotericin B, micafungin was used in the treatment, regardless of its unfavorable pharmacokinetic properties. Our study showed that despite the expected low levels in the urinary tract, micafungin was successful in the eradication of C. glabrata allowing full recovery of the patient. Thus, micafungin should be considered in the management of urosepsis caused by sensitive Candida spp.
Berberine Photo-Activation Potentiates Cytotoxicity in Human Astrocytoma Cells through Apoptosis Induction
Authors: Carriero Francesca , Martinelli Carolina , Gabriele Fabio , Barbieri Giulia , Zanoletti Lisa , Milanesi Gloria , Casali Claudio , Azzalin Alberto , Manai Federico , Paolillo Mayra , Comincini Sergio
Published: September 2021

Photodynamic therapy (PDT) has recently attracted interest as an innovative and adjuvant treatment for different cancers including malignant gliomas. Among these, Glioblastoma (GBM) is the most prevalent neoplasm in the central nervous system. Despite conventional therapeutic approaches that include surgical removal, radiation, and chemotherapy, GBM is characterized by an extremely poor prognosis and a high rate of recurrence. PDT is a physical process that induces tumor cell death through the genesis and accumulation of reactive oxygen species (ROS) produced by light energy interaction with a photosensitizing agent. In this contribution, we explored the potentiality of the plant alkaloid berberine (BBR) as a photosensitizing and cytotoxic agent coupled with a PDT scheme using a blue light source in human established astrocytoma cell lines. Our data mainly indicated for the combined BBR-PDT scheme a potent activation of the apoptosis pathway, through a massive ROS production, a great extent of mitochondria depolarization, and the sub-sequent activation of caspases. Altogether, these results demonstrated that BBR is an efficient photosensitizer agent and that its association with PDT may be a potential anticancer strategy for high malignant gliomas.