bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydroxychloroquine Enhances Efferocytosis and Modulates the Gut Microbiome in Mice With Pristane-induced Lupus
Authors: Xue Ting-Yin , Hsieh Fei-Hung , Tsay Jun-Chieh J. , Peng Hsin-Yi , Tsao Yen-Chi , Yin Mei-Chin , Chao Che-Yi , Tsai Shu-Yao , Lin Chung-Ping , Chen Jiunn-Horng , Huang Chung-Ming , Chang Hen-Hong , Szondy Zsuzsa , Tsay Gregory J 
Published: November 2021

Abstract
Background An important contributor to the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE) is the impaired clearance of apoptotic cells (efferocytosis) and increasing evidence implicates microbiota dysbiosis as another important player. The disease-modifying antirheumatic drug hydroxychloroquine (HCQ) is frequently prescribed for the treatment of SLE. Here, we evaluate changes in efferocytosis and the gut microbiome in mice with pristane-induced lupus (PIL) before and after HCQ administration.Methods PIL mice were studied with or without HCQ and/or resveratrol (RESV). Efferocytosis was determined in RAW 264.7 cells and peritoneal macrophages from mouse ascites fluid. The gut microbiome was analyzed using Illumina sequencing targeting the 16S ribosomal DNA gene (rDNA) amplicon sequencing.Results Both HCQ and RESV enhanced efferocytosis. HCQ also significantly suppressed ascites production of proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α). The Firmicutes/Bacteriodetes (F/B) ratio was significantly decreased in PIL mice compared with untreated controls (p<0.05). The F/B ratio in PIL mice was increased by HCQ alone and significantly increased by HCQ combined with RESV. Alpha- and beta-diversity differed between mice administered RESV and those that were not. Viable counts of lactic acid bacteria Lactobacillaceae, Lactobacillus and Lactobacillales were increased by RESV plus HCQ treatment.Conclusions In this study, HCQ and RESV enhanced efferocytosis in both RAW 264.7 cells and peritoneal macrophages of PIL mice and suppressed IL-6 and TNF-α production in ascites fluid. The pristane-induced reduction in the F/B ratio was restored by HCQ treatment. SLE treatment should consider the role of the gut microbiome.
Pembrolizumab in Combination with Bevacizumab and Oral Cyclophosphamide in Heavily Pretreated Platinum-Resistant Ovarian Cancer
Authors: Andrikopoulou Angeliki , Liontos Michalis , Skafida Efthymia , Koutsoukos Konstantinos , Apostolidou Kleoniki , Kaparelou Maria , Rouvalis Angeliki , Bletsa Garyfallia , Dimopoulos Meletios-Athanasios , Zagouri Flora 
Published: November 2021

Abstract
Background: Immune checkpoint inhibitors (ICIs) have been widely implemented in the treatment of solid tumors. Although epithelial ovarian carcinoma is considered as scarcely immunogenic, the presence of tumor-infiltrating T lymphocytes (TILs) in the ovarian tumor microenvironment (TME) could increase sensitivity to immune checkpoint inhibitors (ICIs). Combinations of ICIs with chemotherapy, anti-VEGF compounds and PARP inhibitors are under evaluation in ovarian cancer. Recently, a Phase II study evaluated the efficacy of Pembrolizumab in Combination with bevacizumab and oral cyclophosphamide in patients with recurrent platinum-sensitive, platinum-resistant, or refractory epithelial ovarian cancer.Methods: Herein, we present a retrospective study of all patients who received pembrolizumab in combination with bevacizumab and oral cyclophosphamide for recurrent platinum-resistant heavily pretreated ovarian cancer in the Oncology Unit of Alexandra University Hospital.Results: Median age at diagnosis was 54.5 years (SD; 8.9; range: 44–72). All patients were diagnosed with high-grade serous ovarian carcinoma (HGSC). Initial disease stage was FIGO IIIC (8/10; 80%), IIIB (1/10; 10%) and IIC (1/10; 10%)). Patients were heavily pretreated with a median of 6 (range: 4–9) prior lines of systemic therapy. All patients have experienced disease progression on first-line platinum-based chemotherapy and median PFS to first-line treatment was 20.1 months (95%CI; 11.4 – 28.7). Patients received a median of 4 cycles of pembrolizumab in combination with cyclophosphamide and bevacizumab (range 2-11). ORR was 20% (2/10) with two patients achieving partial response (PR) and two patients achieving stable disease (SD) while disease control rate (DCR) was 40% (4/10). Median PFS was 2.7 months (95%; 0.6 – 4.8) and 6-month PFS rate 20%. Conclusions: Though our data reflect a small population, we here demonstrate that the combination of pembrolizumab with bevacizumab and oral cyclophosphamide is an effective alternative in platinum-resistant recurrent ovarian carcinoma. This novel combination provides a promising alternative in heavily pretreated patients that have otherwise limited treatment options.
The effect of sub-climatic characteristics on urban behavior patterns based on two case studies: Yazd (hot and arid climate) and Fooman (moderate and humid climate) urban spaces
Authors: Ahmadi Sara , Bahrainy Hossein 
Published: November 2021

Abstract
Severe climatic conditions are considered as one of the main factors shaping and in some cases limiting urban behaviors. Accordingly, environmental designers seek to make urban spaces usable for a wide range of behaviors during different times by bringing sub-climates closer to the comfort zone. The present study aims to evaluate the effects of sub-climate on behavioral patterns and explore solutions to moderate harsh climatic conditions in architecture and urban planning. This study compared the behavioral patterns of space users in hot and arid (Yazd) and moderate and humid (Fooman) climates. The recording of behavioral patterns was achieved by using the observation method (time-lapse photography) and analysis through the spatial analysis method. Based on the results, climatic characteristics affect both types of urban activities and the time cycles of their occurrence. Severe climatic conditions limit urban behaviors to essential activities and merely transcend space. Such states do not allow for a wide range of optional and social activities. Spatial physical tools such as building density, enclosure, occupancy level, amount of retreat on the ground floor and upper floors, type of building material, and the amount of green space have been used in historical formal-spatial patterns of Iran to moderate the harsh climatic conditions.
Growth and nitrogen accumulation assessment of banana (Musa acuminata) after exposure to hydroquinone in a charcoal-ultisol mix
Authors: Ikhajiagbe Beckley , Ebinum Marychoice N. 
Published: November 2021

Abstract
The present study investigates plant growth and nitrogen accumulation assessment of young banana plant (Musa acuminata) after exposure to hydroquinone (a mutagen) in a charcoal-ultisol mix. Charcoal was obtained from the wood of Pentaclethra macrophylla aerobically, and was crushed into a smooth powdered form. This was mixed with an ultisol obtained from the University of Benin Botanic garden. Different levels of the soil-charcoal mix were prepared as follows; 100% charcoal, 75% charcoal-25% soil, 50% charcoal-50% soil, 25% charcoal- 75% soil, and 100% sand. The charcoal-ultisol mix was then amended with 5ppm hydroquinone one week before propagating young banana suckers. Results showed that sprouting began fifteen days after propagation. There were also different changes in plant height in the various soil treatments; the lowest was reported in the 75-25 charcoal ultisol mix (10.50cm), compared to 45.83cm in plants sown in 100% charcoals. Foliar yield was lowest in the 75-25 charcoal-ultisol mix (8.55 grams per plant), compared to 29.15 grams per plant in the 100% charcoal. The below ground morphological characteristics test plant revealed that there were significant differences between the growth parameters. Nitrate nitrogen, Ammonia Nitrogen and total nitrogen were significantly accumulated on the leaves of plant. However, higher nitrogen accumulation in the leaves was found in treatment with high charcoal percentage.
Verification of Stress Transformation in Anisotropic Material Additively Manufactured by Fused Deposition Modeling (FDM)
Authors: Sehhat M. Hossein , Mahdianikhotbesara Ali , Yadegari Farzad 
Published: November 2021

Abstract
The widespread use of Additive Manufacturing (AM) has been extensively progressed in the past decade due to the convenience provided by AM in rapid and reliable part production. Fused Deposition Modeling (FDM) has witnessed even faster growth of application as its equipment is environmentally-friendly and easily adaptable. This increased use of FDM to manufacture prototypes and finished parts is accompanied by concerns that 3D printed parts do not perform the same as relatively homogeneous parts produced by molding or machining. As the interface between two faces of bonded material may be modeled by stress elements, in theory by modeling 3D printed layers subjected to tension at varying angles as transformed stress elements, the stress required to break the layer bonds can be determined. To evaluate such a relationship, in this study, the stresses calculated from stress transformation were compared with the behavior of 3D printed specimens subjected to tensile loads.
Sexual Knowledge and Teenage Pregnancy Among Female Hawkers in Ekiti State, Nigeria
Authors: Owoseni Joseph Sina , Agbana Richard Dele 
Published: November 2021

Abstract
Background: This study investigated patterns of Sexual Knowledge and teenage pregnancy among female hawkers in Ekiti State, Nigeria. Method: The study population consisted of female adolescents aged 8-19 years. The samples 113 girls were drawn for the study. Two pregnant girls were interviewed. The sampling technique used was the purposive sampling. The hypotheses were tested at calculated value of 0.000 level of significance for validity. The hypotheses were analysed based on the Pearson chi-square test version of the SPSS. The data generated were analysed using frequency count and percentage for describing the data. The chi-square statistics as well as the in-depth interview were used to make inferences about the data. Findings: It was found that teenage hawkers have experienced one form of sexual activity while hawking including unwanted touching (sexual harassment), sexual intercourse, rape, sexual abuse and unwanted pregnancy. Conclusion: Based on these findings, it was recommended that skills and training need to be provided in and outside the school system. Parent, teachers and counsellors should convey abstinence and prevention messages so as to sensitize or discourage early sexual activity and teenage pregnancy of female hawkers. A poverty alleviation programme should also be put in place at the local level to reduce this form of child labour. Protective child right policy should be intensified to reduce child labour in the society.
Algorithm for Configuring Fuzzy Inference Systems by Reference Points Based on the Average Value
Authors: Golosovskiy Mikhail , Bogomolov Aleksey , Tobin Dmitriy 
Published: November 2021

Abstract
In the article an algorithm for configuring Sugeno type fuzzy inference systems based on statistical data is proposed. The algorithm uses the principle of operation based on selecting the area around the reference points, finding the average value in the selected areas, and using it to configure the fuzzy logic output system. The work of the algorithm takes place under the conditions of changing the number of functions belonging to input variables and the number of points of statistical data, on the basis of which the models were configured.
Patient Age Associates with Tumor-Infiltrating Lymphocytes Density in Breast Cancer
Authors: Takada Koji , Kashiwagi Shinichiro , Asano Yuka , Goto Wataru , Morisaki Tamami , Shibutani Masatsune , Tanaka Hiroaki , Hirakawa Kosei , Ohira Masaichi 
Published: November 2021

Abstract
Background: Lymphocytes surrounding the cancer participate in tumor-related immune responses, and are called tumor-infiltrating lymphocytes (TILs). Several recent reports suggest TILs to index the tumor-microenvironment (TME), and predict the therapeutic effect of chemotherapy. However, only few studies have studied the relationship between age and TILs. Aging reduces host immunity, and we predict that it may also affect TILs. Thus, we hypothesized that older breast cancer (BC) patients may have low TILs density than younger BC patients. Here, we retrospectively analyzed the differences in TILs by age and the therapeutic effects of pre-operative chemotherapy (POC) in BC patients aged less than 45 years and more than 60 years.Methods: POC was administered to 356 patients. We confirmed and compared TILs density and therapeutic effects in patients aged < 45 years (n=75) and those aged >61 years (n=116). TIL density was evaluated using pre-treatment needle biopsy specimens. Definition and evaluation of TILs was based on the International TILs Working Group 2014.Results: Based on subtype, younger patients showed significantly higher pathological complete response rates than older patients with hormone receptor (HR)+ human epidermal growth factor receptor 2 (HER2)+ and HER2-enriched BC. In HR+HER2+BC, the objective response rate was significantly high in younger than in older patients. Further, a significant difference was observed for overall survival between these patients with triple-negative BC.Conclusions: Our study suggests that younger BC patients possess significantly high TILs density than older patients. These differences may influence the therapeutic efficacy in highly immunogenic subtypes.
A Comprehensive Analysis of Renal Cell Carcinoma as First and Second Primary Cancers
Authors: Chen Jinchao , Lou Jianmin , He Yedie , Zhu Zhenjie , Zhu Shaoxing 
Published: November 2021

Abstract
Objective Second primary renal cell carcinoma (2nd RCC) refers to renal cell carcinoma (RCC) diagnosed after another unrelated malignancy. This study aims Tto compare the clinical manifestation, pathology, treatment, and prognostic features of patients with second primary renal cell carcinoma (2nd RCC) and first primary renal cell carcinoma (1st RCC). Materials and Methods Data of the Ppatients with localized RCC were retrospectively collected. They were classified as 2nd RCC or 1st RCC according to a previously diagnosed cancer, including 113 cases of 2nd RCC and 749 cases of 1st RCC. ResultsThe most common types of extrarenal malignancies in patients with 2nd RCC include lung, colorectal, breast, gynecological, and gastric cancers. The age and smoking rate of 2nd RCC patients were significantly higher than in those of 1st RCC patients. For 2nd RCC patients, fFewer 2nd RCC patients had clinical symptoms and a large renal masses tend to be smaller. One hundred and eight (95.6%) patients with 2nd RCC received surgical interventions. All patients with 1st RCC underwent renal surgery. More patients with 2nd RCC underwent a partial nephrectomy. Pathologically, there was no significant difference in postoperative pathological types between the 2nd and 1st RCCs. However, the 2nd RCCs commonly occurred inhad the early stages. The median overall survival (OS) of 2nd RCC patients was 117 months, which was shorter than that of 1st RCC patients. ConclusionsPatients with 2ndSecond RCC are not uncommon. More attention should be paid to screening for 2nd RCC in cancer survivors. There are some differences between patients with 2nd and 1st RCCs that should be viewed separately.
Application Research on the Medical imaging testing of Novel Coronavirus Pneumonia COVID-19 based on Transfer Learning
Authors: Liu shouqiang , Jiang Mingyue , Chen Liming , Wang Yang 
Published: November 2021

Abstract
Novel coronavirus pneumonia (COVID-19) is a highly infectious and fatal pneumonia-type disease that poses a great threat to the public safety of society. A fast and efficient method for screening COVID19-positive patients is essential. At present, the main detection methods are nucleic acid detection of manual diagnosis and medical imaging (CT image/X-ray image), both of which take a long time to obtain the diagnosis result. This paper discusses the common processing methods for the problem of insufficient medical image data. Then, transfer learning and convolutional neural network were used to construct the screening and diagnosis model of COVID-19, and different migration models were analyzed and compared to select a better pre-training model, which was trained and analyzed under small data sets. Finally, it analyzes and discusses how to train a highly reliable model to quickly help doctors provide advice in the critical moment of epidemic prevention and control when only a small sample data set is available.
A Functional Outcome Prediction Model of Acute Traumatic Spinal Cord Injury Based on Extreme Gradient Boost
Authors: Zhan Sizheng , Huang Boxuan , Xie Wenyong , Xue Feng , Zhang Dianying , Jiang Baoguo 
Published: November 2021

Abstract
Purpose: We aimed to construct a nonlinear regression model through Extreme Gradient Boost (XGBoost) to predict functional outcome 1 year after surgical decompression for patients with acute spinal cord injury (SCI).Methods: We prospectively enrolled 249 patients with acute SCI from 5 primary orthopedic centers from June 1, 2016, to June 1, 2020. We identified a total of 6 predictors with three aspects: 1) clinical characteristics, including age, American Spinal Injury Association (ASIA) Impairment Scale (AIS) at admission, level of injury and baseline ASIA motor score (AMS); 2) MR imaging, mainly including Brain and Spinal Injury Center (BASIC) score; 3) surgical timing, specifically comparing whether surgical decompression was received within 24 hours or not. We assessed the SCIM score at 1 year after the operation as the functional outcome index. XGBoost was used to build a nonlinear regression prediction model through the method of boosting integrated learning.Results: We successfully constructed a nonlinear regression prediction model through XGBoost and verified the credibility. The average absolute value of the difference between the predicted value and the actual value is 3.72 (t=1.29, P=0.203), ranging from 0 to 8.44. AMS and age ranked first and second in predicting the functional outcome.Conclusion: We verified the feasibility of using XGBoost to construct a nonlinear regression prediction model for the functional outcome of patients with acute SCI, and we found that age and AMS play the most important role in predicting the functional outcome.Trial registration: ClinicalTrials.gov identifier: NCT03103516.
Development of a dynamics-based model for analyzing strategic water–environmental conflicts: systems thinking instead of linear thinking
Authors: Shahbaznezhadfard Mohsen , Yousefi Saied 
Published: November 2021

Abstract
A new evolution in graph modeling for conflict resolution (GMCR), a robust methodology for conflict resolution, is presented in this research to incorporate the systems thinking concept into the conventional paradigm of GMCR so that the dynamic nature of water–environmental conflicts can be modeled, and better outcomes obtained. To achieve this objective, a methodology is developed in three phases: static, dynamic, and outcome-based analyses. To develop the methodology, the Tigris–Euphrates basin conflict in the Middle East over the past 30 years, as a real-life case study, is used to show the robustness and capabilities of the proposed approach. Finally, a sustainable resolution to the current conflict is proposed, and the results are discussed. The proposed methodology benefits from improving the existing and often static-based conflict resolution developments by considering the dynamic nature so that the true root causes of complex conflicts are addressed, better strategic insights achieved, and comprehensive resolution provided.
Impact on Pharmaceutical Industry due to Sudden Pandemic Attack
(COVID-19)
Authors: Malviya Rishabha , Mishra Sudhanshu , Sharma Disha , Srivastava Shobhit Prakash , Verma Swati 
Published: November 2021

:
The coronavirus disease (COVID-19) was first detected in Wuhan, China, in the month
of December 2019. Further, in March 2020, the COVID-19 epidemic was described by the World
Health Organisation (WHO) as a global pandemic. COVID-19 quickly spread around the world in
the following months, affecting about 2.5 million individuals by April 2020. World markets, including
the pharmaceutical industry, were devastated by this pandemic. Although no specific solution
for this emerging infectious disease is currently available, the pharmaceutical industry is helping
policymakers meet unmet COVID-19 desires, ranging from research and advancement initiatives
on possible prevention methods to the management of the supply chain of drugs in times of crisis.
Changes in demand, commodity shortages, contact adjustments, etc., are hindering developments
in the mechanism of technology, research and development and are putting an impact on the health
market of COVID-19. Other implications of COVID-19 on the physical condition and pharmaceutical
market may include acceptance delays, heading to self-sufficiency in the delivery chain, etc. In
addition, the pharmaceutical markets are battling to sustain natural consumer flows, as the latest
pandemic has had an effect on access to essential drugs at reasonable rates, which is the key priority
of all pharmaceutical systems.
The Potential Use of Cyclosporine Ultrafine Solution Pressurised Metered-
Dose Inhaler in the Treatment of COVID-19 Patients
Authors: Ehtezazi Touraj 
Published: November 2021

Introduction:
Serious COVID-19 respiratory problems start when the virus reaches the
alveolar level, where type II cells get infected and die. Therefore, virus inhibition at the alveolar
level would help preventing these respiratory complications.

Method:
A literature search was conducted to collect physicochemical properties of small
molecule compounds that could be used for the COVID-19 treatment. Compounds with low melting
points were selected along with those soluble in ethanol, hydrogen-bond donors, and acceptors.

Results :
There are severe acute respiratory syndrome coronavirus inhibitors with physicochemical
properties suitable for the formulation as an ultrafine pressurised metered-dose inhaler (pMDI). Mycophenolic
acid, Debio 025, and cyclosporine A are prime candidates among these compounds. Cyclosporine
A (hereafter cyclosporine) is a potent SARS-CoV-2 inhibitor, and it has been used for
the treatment of COVID-19 patients, demonstrating an improved survival rate. Also, inhalation
therapy of nebulised cyclosporine was tolerated, which was used for patients with lung transplants.
Finally, cyclosporine has been formulated as a solution ultrafine pMDI. Although vaccine therapy
has started in most countries, inhalation therapies with non-immunological activities could minimise
the spread of the disease and be used in vaccine-hesitant individuals.

Conclusion:
Ultrafine pMDI formulation of cyclosporine or Debio 025 should be investigated for
the inhalation therapy of COVID-19.