bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolome Analysis Reveals a Diversity of Cancer Tissues in Advanced Epithelial Ovarian Cancer
Authors: Yoshida Kosuke , Yoshikawa Nobuhisa , Kitami Kazuhisa , Tamauchi Satoshi , Ikeda Yoshiki , Yokoi Akira , Nishino Kimihiro , Niimi Kaoru , Kajiyama Hiroaki
Published: April 2021

Background: Epithelial ovarian cancer remains one of the leading causes of cancer deaths among women worldwide, and advanced epithelial ovarian cancer frequently metastasizes to the omentum. Characteristics of the metastatic cancer may be different from that of primary ovarian cancer reflecting the unique omental microenvironment. This study investigated metabolomic differences in epithelial ovarian cancers.Methods: Patients with advanced epithelial ovarian cancer are eligible for this study. There were five patients who underwent surgery and resected primary ovarian and omental metastatic cancers at Nagoya University. Metabolome analysis was performed using these paired cancer and metastatic cancer tissues through a facility service (C-SCOPE) at Human Metabolome Technologies, Inc. The concentrations of 116 compounds were measured by CE-TOFMS and CE-QqQMS, and 30 metabolic parameters were calculated. For statistical analyses, Welch’s t-test was used for comparisons between two independent groups.Results: Metabolite profiles were different from each other reflecting a diversity in the cancer tissues. Of the measured compounds, urea was the only metabolite that was significantly decreased in the omental metastatic cancers compared with the primary cancers (p = 0.031). Moreover, in omental metastatic cancers, the pentose phosphate pathway was more dominant than glycolysis. Furthermore, lactic acids in omental metastatic cancers were markedly decreased compared with primary cancers in some cases. With regard to histological characteristics, the total amount of amino acids, especially the percentage of glutamine, were significantly rich in serous carcinomas than in non-serous carcinomas (p = 0.004 and p = 0.001, respectively). Moreover, the reduced form of glutathione and polyamines were also abundant in serous carcinomas than in non-serous carcinomas (p = 0.025 and 0.048, respectively).Conclusions: The metabolite profiles were different depending on the location of the tumor and the histological subtype. Metabolome analysis may be a useful tool for identifying cancer diagnostic and prognostic markers.
Triptolide Alleviates Murine Arthritis by Inhibiting Osteoclast Differentiation via TRAF6/MAPKs/NFATc1 Signaling Pathway
Authors: Jiang Baoping , Liu Tianyang , Han Jing , Shen Meiyu , Zhou Xueping , Zhou Lingling
Published: April 2021

Background: Bone erosion is an important problem in rheumatoid arthritis (RA). The role of osteoclast in bone resorption is critical in RA, and intervention of osteoclast differentiation can improve bone destruction. Tripterygium wilfordii Hook F (TW) can improve the symptoms of RA. The effect of triptolide (TP), which is a purified component of TW, on bone destruction in RA and its mechanism remain unclear. Methods: We investigated the effect of TP on osteoclast differentiation using a co-culture system of synovial fibroblasts and monocytes from adjuvant-induced arthritic rats. We also investigated the effect of TP on murine collagen-induced arthritis (CIA).Results: The results showed that a certain dose of TP inhibited the differentiation of osteoclast, and reduced the levels of interleukin (IL)-1, IL-34, macrophage colony stimulating factor (M-CSF), receptor activator for nuclear factor-κ B Ligand (RANKL), and osteopontin (OPN) in the co-culture supernatant of synovial fibroblasts and monocytes. Furthermore, a certain dose of TP reduced the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), mitogen-activated protein kinases (MAPKs) and nuclear factor of activated T cells 1 (NFATc1) in osteoclast. Meanwhile, TP reduced the symptoms of arthritis and bone destruction in CIA. Conclusion: Our results suggest that TP can improve the bone destruction of murine arthritis, and the mechanism is related to the inhibition of osteoclast differentiation via TRAF6/MAPKs/NFATc1 signaling pathway.
Oxidative Stress Reducing Osteogenesis Reversed by Curcumin via NF-κB Signaling and Had a Role in Anti-Osteoporosis
Authors: JiaQiang Xu , Gao Ran , Liang Wen , Wu ChangJian , Li FangLing , Huang Sheng , Zhang Bing , Qi QiHua
Published: April 2021

Objective: Curcumin has good anti-inflammatory and antioxidant properties, and whether it can resist osteoporosis through oxidative stress pathway in a dose-dependent manner.Method: we used an oxidative stress cell model by culture cells with hydrogen peroxide (H2O2), cells were osteogenic differentiation after treated with H2O2，different concentration curcumin were added during differentiation, then measured the early and late osteogenic index, and detected the potential signaling pathway involved. In addition, we employed rat OVX model treated with curcumin to confirm the protection of the anti-oxidant.Result: Low concentrations of curcumin (1-10μM) promoted the proliferation of MC3T3-E1 cells, improved alkaline phosphatase (ALP) activity, elevated calcium content against oxidative stress induced by H2O2, but high concentration (20 μM) failed, moreover, curcumin diminished supernatant receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 expression, inhibited the intracellular ROS triggered by H2O2, Notably, curcumin exerted protection by blocking the NF-κB signaling pathway. The curcumin administered for 12 weeks partially reversed the raito of blood malondialdehyde (MDA) and glutathione (GSH) activity in ovariectomized (OVX) rat in vivo. It also increased the bone mineral density (BMD) and improved the micro-architecture of trabecular bones. Conclusion: curcumin exerted protection on osteoporosis, the effect linked to a reduction of oxidative stress and bone resorbing cytokine, This study suggests that curcumin might be a candidate for osteoporosis prevention and the low concentration exerted obviously protection.
A Prothrombotic Thrombocytopenic Disorder Resembling Heparin-Induced Thrombocytopenia Following Coronavirus-19 Vaccination
Authors: Greinacher Andreas , Thiele Thomas , Warkentin Theodore E. , Weisser Karin , Kyrle Paul , Eichinger Sabine
Published: April 2021

Background. Vaccines are important for managing the COVID-19 pandemic caused by SARS-CoV-2. However, following widespread vaccination using a recombinant adenoviral vector encoding the spike protein antigen of SARS-CoV-2 (AZD1222, AstraZeneca), reports have emerged of some vaccine recipients developing unusual thrombotic events and thrombocytopenia. We investigated whether such patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against platelet factor 4 (PF4), as is known to be caused by heparin and sometimes other environmental triggers.Methods. We summarized the clinical and laboratory features of 9 patients in Germany and Austria who developed thrombosis and thrombocytopenia events following AZD1222 vaccination. Serum from four patients was used to test for anti-PF4/heparin antibodies, both by immunoassay and by platelet activation assays performed in the presence of heparin, PF4, or both.Results. The 9 patients (8 female; median age, 36 [range, 22—49) presented with thrombosis beginning 4 to 16 days post-vaccination: 7 patients had cerebral venous thrombosis (CVT), 1 had pulmonary embolism, and 1 had splanchnic vein thrombosis and CVT; 4 patients died. None had received heparin prior to symptom onset. All four patients tested strongly positive for anti-PF4/heparin antibodies by immunoassay; all 4 patients tested strongly positive in the platelet activation assay in the presence of PF4 independently of heparin. Platelet activation was inhibited by high concentrations of heparin, Fc receptor-blocking monoclonal antibody, and intravenous immunoglobulin.Conclusions. The AZD1222 vaccine is associated with development of a prothrombotic disorder that clinically resembles heparin-induced thrombocytopenia but which shows a different serological profile.
Lessons from the Covid-19 pandemic. A collective autoethnography of bioethics education
Authors: Dercon Katrien , Domaradzki1 Mateusz , Elisenberg Herman Trondal , Głos Aleksandra , Handeland Ragnhild , Popowicz Agnieszka , Piasecki Jan
Published: April 2021

The Covid-19 pandemic disrupted academic life worldwide, for both students and teachers." Then the next sentence stating the purpose of study is highlighting that its specifically internal medical students and bioethics teachers. The purpose of this study is to shed light on the collective adversity experienced by international medical students and bioethics teachers amidst the Covid-19 pandemic in relation to both personal and academic life. The authors wrote subjective memoirs that were analyzed using a collective autoethnography method to find similarities and inconsistencies between their experiences. The results consist of three different sections; falling apart, bouncing back and bioethics. ‘Falling apart’ explores the breakdown of daily lives during the initial stages of the pandemic, shown through subjective quotes contextualized through the authors commentary. The consensus is that the journey home and the move to remote education, were the two main perpetrators for the breakdown ‘Bounce back’ focuses on the authors’ rebirth after the initial breakdown, by acquiring new information about the virus, discovering substitute hobbies, like home workout or dancing, and the students learning to adjust their exam expectations. 'Bioethics’ is about how it was to learn and teach this subject during the pandemic, and how you can apply bioethical knowledge to better understand and cope with some of the pandemic’s moral dilemmas. The study presents how important bioethics is during a global pandemic, as well as the struggles of remote learning, from both the students’ and the professors’ point of view.
Efficacy and safety of ICIs/ICIs combined with chemotherapy vs chemotherapy in advanced gastrointestinal tract cancer: a systematic review and meta-analysis
Authors: Fan Xiuqi , Gao Qilong , Guo Lanwei , Chen Yulong , Han Yicun , Meng Wei
Published: April 2021

Objective: To systematically access the efficacy and safety of ICIs monotherapy or ICIs combined with chemotherapy versus chemotherapy in advanced gastrointestinal cancers. Methods: Retrieved the randomized controlled trials (RCTs) of ICIs or ICIs combined with chemotherapy and chemotherapy in advanced gastrointestinal tumors included in PubMed, Cochrane Library, Embase, and Web of sciences. Meta-analysis was performed using Review Manager 5.3 software. The primary outcomes are overall survival (OS) and progression-free survival (PFS), and secondary outcomes include objective response rate (ORR) and adverse events (AEs).Results: A total of 13 RCTs including 5166 patients with advanced gastrointestinal tumors were included in this meta-analyses. ICIs or ICIs combined with chemotherapy exhibited superior OS (HR: 0.84, 95% CI: 0.76-0.94, P=0.001) compared with chemotherapy. Subgroup analysis shows that the use of anti-PD-1 antibodies significantly benefits OS (HR:0.80, 95%CI:0.70-0.91, P=0.0009). The second-line application of ICIs or ICIs combined with chemotherapy will have more significant OS benefits than chemotherapy ( HR: 0.85, 95%CI: 0.79-0.97, P=0.01). No significant difference was observed in PFS and ORR. The PFS of squamous cell carcinoma seemed to be better (HR:0.72, 95%CI:0.60-0.87, P=0.0005). No significant difference in AEs and grade≥3 AEs. But the incidence of AEs decreased when ICIs monotherapy (RR:0.81, 95%CI:0.66-0.99, P=0.04).Conclusion: For gastrointestinal malignant tumors, patients who received ICIs or ICIs combined with chemotherapy had a superior OS compared with chemotherapy, not at the cost of increased AEs, the proportion of AEs is reduced than chemotherapy while ICIs monotherapy. PFS and ORR are not significantly improved.
Estimating the ashfall distribution for a small eruption using ellipse-approximated isopach analysis: How many seeking points are required to determine a suitable axis?
Authors: Tajima Yasuhisa
Published: April 2021

A volcanic ash eruption began on March 3, 2018, and a lava flow was observed on March 6 at Shinmoedake volcano in the Kirishima Volcano Group. The small ash eruptions continued until June 27, 2018. The amounts of volcanic ashfall around Shinmoedake volcano from these eruptions were observed, and the volcanic ashfall volumes for each eruption were analyzed. However, many cases of small eruptions were insufficient observation points to determine the ashfall volumes. Therefore, the ellipse-approximated isopach (EAI) method was used. However, the EAI method requires verification seeking points to determine the angle of the calculation axis including two calculation points to perform the analysis. In this study, the ashfall amount values at some locations from one eruption on June 27, 2018 were observed, and the EAI analysis was conducted to determine the ashfall distribution using one to four seeking points. It is considered that a suitable axis requires three seeking points to determine the EAI distribution.
Effect of Pulsed Ultrasound on Plasma Morphology and Its Changing Mechanism
Authors: Zhang Huijing , Qing-Kai Fan , Fan Chenglei , Chao Chen
Published: April 2021

Arc plasma shape under pulsed and continuous ultrasound field were studied in this research using self-developed welding device which combines arc and ultrasound field coaxially. The results show that, compared with the arc of conventional tungsten inert gas welding, the shape of arc under pulsed ultrasound field relate to the pulse frequency. From 1 Hz to 20 Hz, the arc plasma expands and contracts periodically in one pulse. When more than 20 Hz, the arc plasma contracts as the pulse frequency increases. During high pulse frequency, the arc shape become steady and similar to those in continuous ultrasound field. When in 500 Hz, the contraction ratio of arc projected area under pulsed ultrasound field reaches 38 %, comparing with 30 % of the same power continuous ultrasound field, i.e., in high frequency, low power pulsed ultrasound can obtain arc control effect similar to high power continuous ultrasound, raising ultrasound energy efficiency. The mechanism of ultrasonic influence on arc is analyzed based on sound pressure and acoustic streaming.
A nomogram for clinical estimation of acute biliary pancreatitis risk among patients with gallstones
Authors: Guo Xiaoyu , Li Yilong , Lin Hui , Li Jie , Cheng Long , Huang Zijian , Lin Zhitao , Mao Ning , Wu Linfeng , Sun Bei , Wu Weidong , Wang Gang
Published: April 2021

Background Currently, there are no effective tools to accurately assess acute biliary pancreatitis (ABP) risk in patients with gallstones. This study aimed to develop an ABP risk nomogram in patients with gallstones.Methods Data on 2102 patients with gallstones admitted to the Department of General Surgery of The First Affiliated Hospital of Harbin Medical University between January 6, 2009 and January 22, 2018 were retrospectively collected. Some patients were randomly divided into the training cohort (n=1470) for nomogram development; the others formed the validation cohort (n=632) to confirm the model’s performance. The chi-square test was used to optimize feature selection, and logistic regression analysis was applied to build a prediction model incorporating the selected features. The area under the curve (AUC), Hosmer-Lemeshow test, calibration curve, decision curve analysis (DCA) and internal validation were used to validate the model’s accuracy, calibration and clinical effectiveness.Results Predictors included sex (male), diabetes, gallbladder wall thickness ≤3 mm, gallbladder stone diameter <3 mm, coexisting CBD stone, CBD diameter ≤10 mm, AST≥53.6 U/L, GGT≥150 U/L, DBIL≥1.0 mg/dL, WBC≥10Í109, and GRAN%≥80%. The model displayed good predictive power with AUCs of 0.850 (95% CI: 0.825~0.875) and 0.844 (95% CI: 0.825~0.875) in the training and validation cohorts, respectively. The DCA showed a 10-100% risk threshold. The Hosmer-Lemeshow test and calibration curve demonstrated the accuracy and effectiveness of this model, which could be applied in clinical practice.Conclusions The ABP risk nomogram incorporating 11 features is useful to predict ABP risk in gallstone patients.
Plasmodium Falciparum Phenotypic and Genotypic Resistance Profile During the Emergence of Piperaquine Resistance From Royal Thai Army and Civilian patients in Northeastern Thailand
Authors: Boonyalai Nonlawat , Thamnurak Chatchadaporn , Sai-ngam Piyaporn , Ta-aksorn Winita , Arsanok Montri , Uthaimongkol Nichapat , Sundrakes Siratchana , Chattrakarn Sorayut , Chaisatit Chaiyaporn , Praditpol Chantida , Fagnark Watcharintorn , Kirativanich Kirakarn , Chaorattanakawee Suwanna , Vanachayangkul Pattaraporn , Lertsethtakarn Paphavee , Gosi Panita , Utainnam Darunee , Rodkvamtook Wuttikon , Kuntawunginn Worachet , Vesely Brian A. , Spring Michele D. , Fukuda Mark M. , Lanteri Charlotte , Walsh Douglas , Saunders David L. , Smith Philip L. , Wojnarski Mariusz , Sirisopana Narongrid , Waters Norman C. , Jongsakul Krisada , Gaywee Jariyanart
Published: April 2021

Malaria remains a public health problem in Thailand, especially along its borders where highly mobile populations can contribute to persistent transmission. This study aimed to determine resistant genotypes and phenotypes of 112 Plasmodium falciparum isolates from patients along the Thai-Cambodia border during 2013-2015. The majority of parasites harbored pfmdr1-Y184F mutation. A single pfmdr1 copy number, had CVIET haplotype of amino acids 72-76 of pfcrt and no pfcytb mutations. All isolates had a pfk13 point mutation (R539T, R539I, and C580Y), and increased ring-stage survival assay (except R539I). Multiple copies of pfpm2 and pfcrt-F145I were first detected in 2014 (12.8%) and increased to 30.4% in 2015. Parasites containing either multiple pfpm2 copies with and without pfcrt-F145I or a single pfpm2 copy with pfcrt-F145I exhibited the elevated IC90 values of piperaquine. Antimalarials were detected in 21 samples (18.8%) by mass spectrometer, and 12 samples (10.7%) by bioassay. Collectively, the emergence of these resistance patterns mirrored the reports of dihydroartemisinin-piperaquine treatment failures in the adjacent province of Cambodia, Oddar Meanchey, suggesting a migration of parasites across the border. As malaria elimination efforts ramp up in Southeast Asia, host nations militaries and other groups in border regions must be a focus for interventions
Dynamic spine hyperflexion is related to vertebral compression fractures in postmenopausal women
Authors: Zheng ZhiRong , Tian Tian , Liu WeiBo , Wang XiangYu , Gao Meng , You YongGang , Hu WenHao , Zhang XueSong
Published: April 2021

Background: Previous studies on osteoporotic vertebral fractures are usually based on the neutral posture of the spine; however, the fractures are usually associated with the curvature of the spine. Therefore, we aimed to ascertain the relationship between vertebral compression fractures and thoracolumbar hyperflexion Cobb angles (TLHCobb) and determine the clinical cut-off of the TLHCobb angle.Methods: In this retrospective case-control study, TLHCobbs were collected from 154 postmenopausal women with thoracolumbar fractures (study group) and 310 postmenopausal women with lumbar instability or spondylolisthesis (control group). Demographic data, clinical data, and quantitative computed tomography (QCT) findings were compared between the groups. Chi-squared tests and unpaired t-tests were used to assess the group characteristics and proportions. Logistic regression was used to examine the association between vertebral compression fractures and TLHCobb.Results: Fracture prevalence was higher in the higher TLHCobb study group than that in the control group [OR = 2.81 (2.15–3.67)] after adjusting for age, BMI, and QCT findings. TLHCobbs at and > 20.05° were associated with an increased fracture prevalence and ORs of 2.79 (1.82–4.27) and 4.83 (3.24–7.20), respectively. TLHCobb and QCT values differed between the study and control groups (p < 0.001 for both). There were no significant differences in body mass index (BMI), disk height, or coronal TLCobb between the two groups.Conclusion: There was an association between the prevalence of vertebral compression fractures and TLHCobbs in postmenopausal women, and a TLHCobb > 20.05° can be an indicator of vertebral fracture.
Neuroprotective poly(propylene imine) dendrimers with histidine- maltose shell reduce early amyloid aggregates and fibrils in Alzheimer’s disease transgenic mice
Authors: Benseny-Cases Núria , Álvarez-Marimon Elena , Aso Ester , Carmona Margarita , Klementieva Oxana , Appelhans Dietmar , Ferrer Isidre , Cladera Josep
Published: April 2021

Amyloid plaques composed of Aβ amyloid peptides and neurofibrillary tangles are a pathological hallmark of Alzheimer Disease. In situ identification of early-stage amyloid aggregates in Alzheimer’s disease is relevant for their importance as potential targets for effective drugs. Synchrotron-based infrared imaging is here used to identify early-stage oligomeric/granular aggregated amyloid species in situ in the brain of APP/PS1 transgenic mice for the first time. Also, APP/PS1 mice show fibrillary aggregates at 6 and 12 months. A significant decreased burden of early-stage aggregates and fibrillary aggregates is obtained following treatment with poly(propylene imine) dendrimers with histidine-maltose shell (a neurodegenerative protector) in 6-month-old APP/PS1 mice, thus demonstrating their putative therapeutic properties of in AD models. Identification, localization, and characterization using infrared imaging of these non-fibrillary species in the cerebral cortex at early stages of AD progression in transgenic mice point to their relevance as putative pharmacological targets. No less important, early detection of these structures may be useful in the search for markers for non-invasive diagnostic techniques.
Experimental Study of the Effects of Hypoxia Simulator on Osteointegration of Titanium Prosthesis in Osteoporotic Rats
Authors: Liu Jiangfeng , Kang Huijun , Lu Jiangfeng , Dai Yike , Wang Fei
Published: April 2021

Purpose: Poor osseointegration is the key reason for implant failure after arthroplasty, whether in osteoporotic or normal bone conditions. To date, osseointegration remains a major challenge. Recent studies have shown that deferoxamine(DFO) can accelerate osteogenesis by activation of the hypoxia signal pathway. The purpose of this study is to test the following hypothesis: after knee replacement, intra-articular injection of DFO will promote osteogenesis and osseointegration with titanium prosthesis in the bones of osteoporotic rats.Materials and Methods: 90 female sprague-dawley rats were used for the experiment. Ovariectomy and knee arthroplasty were performed. Then, the rats were randomly divided into DFO and control group(n=40 per group). The two groups were treated by intraarticular injection of DFO and saline respectively. After 2 weeks, polymerase chain reaction(PCR) and immunohistochemistry were used to evaluate the levels of HIF-1a, VEGF and CD31. After 12 weeks, the specimens were examined by micro CT, biomechanics and histopathology to evaluate osteogenesis and osseointegration.Results: The results of PCR showed mRNA levels of VEGF and CD31 in DFO group were significantly higher than those in control group. The immunohistochemistry results indicated positive cell expressions of HIF-1a, VEGF and CD31 in DFO group were also higher. Compared to control group, the microCT parameters of BMD, BV/TV, TB.N, TB.Th were significantly higher. The maximal pull-out force and the bone-to-implant contact (BIC) value were also higher . Conclusions: The local administration of DFO which is used to activate HIF-1a signaling pathway can promote osteogenesis and osseointegration with the prosthesis in osteoporotic bone.
Estimation of the Absolute Defects in the Visual Field using OCT in Glaucoma Patients who Cannot Perform a Reliable Test.
Authors: Baybora Hakan
Published: April 2021

Background: To find a method to predict the visual field (VF) of glaucoma patients who cannot perform a reliable test by using RNFL thickness and VF of other glaucoma patients. Methods: Seventy eight primary open angle and pseudoexfoliation glaucoma follow-up patients were included in the study. Optic disc OCT measurements and VF analysis were obtained in the same day. Garway-Heats maps made, RNFL sectors matched with pattern deviation 24-2 VF sectors and absolute defects were counted. Regression analysis were made. Equations generated between RNFL thickness and absolute defect number. Correlation analysis were performed for the numbers of absolute defects and the findings.Results: The regression analysis was significantly linear for defect number and RNFL thickness in sectors 3, 4, and 6 (t values were 0.047, 0.04, and 0.001, respectively, p < 0.05). The analysis was nonlinear in other sectors (t values were 1.66, 0.37, 0.14, 0.88, and 0.36, respectively, for sectors 1, 2, 5, 7, and 8, p > 0.05). The linear and nonlinear equations were generated for these sectors. The correlation between the number of absolute defects of the patient and the number we found by using our formulas in VF Sectors of 1,3,4 and 8 there was a strong correlation (r=0.68, r=0.57, r=0.82 and r=0.58 respectively). In VF sectors 3,5,6 and 7 there was a weak correlation (r= 0.22, r= 0.47, r=0.32 and r=0.48 respectively).Conclusion: We think the method that we found is practical to predict the VF of a patient who can not perform it.
Manganese Sulphide Nano Rods grown inside Acacia Senegal Gum Hydrogels; A Biocompatible Nanofabrication for Enhanced Biological activities
Authors: Ullah Hidayat , Farooq Muhammad , Ihsan Junaid , Khan Muhammad Aslam , Ghani Marvi , Siddiq Mohammad , Khan Gul Shahzada
Published: April 2021

The authors have requested that this preprint be removed from Research Square.
Patients With Hereditary Angioedema Do Not Develop More Severe COVID-19 but SARS-CoV-2 Infection May Trigger Attacks: 66 Cases
Authors: Olivares Maria Margarita , Zwiener Ricardo Dario , Panqueva Lina Maria Leiva , Verduzco Francisco Alberto Contreras , Mansour Eli , Rodriguez Jairo Antonio , Valle Solange Oliveira Rodrigues , Nieto Sandra , Silva Jane Da , Vazquez Daniel O , Llosa Oscar Calderon , Marcelino Fernanda Casares , Ratti-Sisa Manuel , Beas Ileana María Madrigal , Zaragoza-Urdaz Rafael , Toledo Eliana Cristina , Fili Natalia Lorena , Barrero Olga M , Aguirre Juan Carlos Fernandez de Cordova , Mora Sergio Castro , Sarrazola Mauricio , Raad Rodolfo Jaller , Cardenas Edison Morales , Josviak Dario Oscar , Fantini Claudio , Marocco Monica , Nievas Elma I , Serpa Faradiba Sarquis , Neto Herberto Jose Chong , Alonso Maria Luiza Oliva , Junior Sergio Dortas , Ulaf Raisa Gusso , Rosario Nelson , Barrero Rodolfo Ramón Leyva , Grumach Anete Sevciovic
Published: April 2021

PurposeHereditary angioedema (HAE) is a rare genetic disease with hyperactivated contact and kallikrein-kinin systems leading to bradykinin (BK) release and edema. SARS-CoV-2 infection results in inflammatory exacerbation. C1 inhibitor (C1-INH) deficiency could aggravate clinical outcomes, with HAE patients at a greater risk of adverse outcomes of COVID-19, however, data are still limited. Our aim was to characterize the course and severity of COVID-19 in patients with HAE.MethodsLatin American HAE reference centers evaluated SARS-CoV-2 infection in this population. Patients with confirmed diagnosis of HAE with (HAE-C1-INH) or without C1-INH deficiency (HAE-nC1-INH) were included. HAE symptomatology and the course of COVID-19 were characterized with the application of a questionnaire. Results66 patients from 10 countries (HAE-C1-INH 80,3%; HAE-nC1-INH 19.6%) were reported with SARS-CoV-2 infection. Comorbidities were absent in 69.7% of the patients and obesity present in 12.1%. Attacks occurred in 45.5% of patients with HAE during SARS-CoV-2 infection. Long term prophylaxis was reported in 52% (34/66) of HAE patients. Complete cure was observed in 61 patients (92.4%), pulmonary sequelae in 4 and death in one HAE-C1-INH patient. The cause of death was septic shock secondary to bacterial pulmonary coinfection. Disease progression was not impacted by sex, therapy or type of HAE (p = 0.803). Conclusion﻿Attacks occurred in almost half of HAE patients suggesting that SARS-CoV-2 infection is a trigger. HAE did not represent a risk factor for a worse outcome of COVID-19, even in use of androgens.
Effect of Diets With Different Lysine Levels on the Hemograms of Juvenile Tambaqui Colosssoma Macropomum (CUVIER, 1818)
Authors: Liebl Ariany Rabello da Silva , Nascimento Marcelo dos Santos , Castro Philp Dalbert da Silva , Aride Paulo Henrique Rocha , Bussons Márcia Regina Fragoso Machado , Faggio Caterina , Oliveira Adriano Teixeira de
Published: April 2021

Blood transports lysine and other nutrients derived from the diet and ensures good health and greater productivity for the fish. Therefore, this study aimed to verify the hematological behavior of juvenile tambaqui Colossoma macropomum nourished with levels of 9.72, 12.84, 15.96, 19.08 and 22.20 g.Kg-1 of total lysine, corresponding, respectively, to the supplementation levels with L-lysine: 0.00, 4.00, 8.00, 12.00, 16.00 and 20.00 g.Kg-1 of L-lysine. The blood of the fish was collected in the initial and final periods by puncture of the caudal vein. The variables were validated by ANOVA and Tukey's test (p< 0.05). No differences were found for hemoglobin, hematocrit, CHCM, leukocytes of the eosinophil and monocyte types, and thrombocytes (p> 0.05). The changes observed in total leukocytes were not attributed to diets (p= 0.00). Means of CMV, HCM, lymphocytes and neutrophils, varied over the initial period, but not in regard to different lysine levels (p< 0.05). Thus, it is concluded that the varying lysine levels of the diets did not compromise the hematological parameters analyzed.
A Novel Weighting Method to Remove Bias from Within-subject Exposure Dependency in Case-crossover Studies
Authors: Kubota Kiyoshi , Kelly Lan , Sato Tsugumichi , Pratt Nicole , Roughead Elizabeth , Yamaguchi Takuhiro
Published: April 2021

Background:Case-crossover studies have been widely used in various fields including pharmacoepidemiology. Vines and Farrington indicated in 2001 that when within-subject exposure dependency exists, conditional logistic regression can be biased. However, this bias has not been well studied.Methods:We have extended findings by Vines and Farrington to develop a weighting method for the case-crossover study which removes bias from within-subject exposure dependency. Our method calculates the exposure probability at the case period in the case-crossover study which is used to weight the likelihood formulae presented by Greenland in 1999. We simulated data for the population with a disease where most patients receive a cyclic treatment pattern with within-subject exposure dependency but no time trends while some patients stop and start treatment. Finally, the method was applied to real-world data from Japan to study the association between celecoxib and peripheral edema and to study the association between selective serotonin reuptake inhibitor (SSRI) and hip fracture in Australia.Results:When the simulated rate ratio of the outcome was 4.0 in a case-crossover study with no time-varying confounder, the proposed weighting method and the Mantel-Haenszel odds ratio reproduced the true rate ratio. When a time-varying confounder existed, the Mantel-Haenszel method was biased but the weighting method was not. When more than one control period was used, standard conditional logistic regression was biased either with or without time-varying confounding and the bias increased (up to 9.4) when the study period was extended. In real-world analysis with a binary exposure variable in Japan and Australia, the point estimate of the odds ratio (around 2.5 for the association between celecoxib and peripheral edema and around 1.6 between SSRI and hip fracture) by our weighting method was equal to the Mantel-Haenszel odds ratio and stable compared with standard conditional logistic regression. Conclusion:Case-crossover studies may be biased from within-subject exposure, even without exposure time trends. This bias can be identified by comparing the odds ratio calculated by the Mantel-Haenszel method and that by standard conditional logistic regression. Our proposed method will remove bias from within-subject exposure dependency and can account for time-varying confounders.
Covid-19 Related Poor Mental Health and Sleep Disorders in Rheumatic Patients: a Citizen Science Project.
Authors: Ingegnoli Francesca , Buoli Massimiliano , Posio Cristina , Taranto Raffaele Di , Muscio Alessandro Lo , Cumbo Enrico , Ostuzzi Silvia , Caporali Roberto
Published: April 2021

BACKGROUND Patients with chronic rheumatic diseases (RDs) are more vulnerable and the containment measures related to COVID-19 pandemic might have severe psychological consequences. We investigated the presence of and risk factors associated with poor mental health, sleep disorders among RDs during the pandemic.METHODS This cross-sectional Italian citizen science project evaluated the psychological impact of the COVID-19 pandemic in patients with RDs. Between May and September 2020, eleven RD patients’ associations sent the survey by using their mailing list and the related webpage and social network. 507 RD patients completed an ad-hoc anonymous online survey including the Perceived Stress Scale (PSS) and Impact Event Scale-Revised (IES-R). RESULTS The mean scores on the PSS-10 and the IES-R were 18.1 and 29.7, respectively. Higher PSS scores were associated with younger age (p<0.01), female gender (p<0.01), overweight/obesity (p=0.01), psychiatric pharmacotherapy (p<0.01), and anxiety for loss of income (p<0.01). Higher IES-R scores were associated with female gender (p<0.01), intestinal diseases (p=0.03), anxiety (p<0.01), and health concern (p<0.01). Among 375 of patients with inflammatory arthritis, 246 (65.6%) had trouble staying asleep, 238 (63.5%) in falling asleep, and 112 (29.9%) had dreams about the pandemic. Older age (OR= 1.038, CI 1.002-1.076), psychiatric pharmacotherapy (OR = 25.819, CI 11.465-58.143), and COVID infection (OR = 2.783, CI 1.215-6.372) were predictive of insomnia during the pandemic.CONCLUSIONS A considerable COVID-19 related psychosocial burden has been detected in RDs. Different factors were predictive of poor mental health and sleep disorders in these patients. Focused supportive strategies should be implemented to improve the psychological well-being of fragile patients during pandemics.
A New Strategy for Canine Visceral Leishmaniasis Diagnosis Based on Molecular Spectroscopy and Machine Learning
Authors: Larios Gustavo , Ribeiro Matheus , Arruda Carla , Oliveira Samuel L. , Canassa Thalita , Baker Matthew J. , Marangoni Bruno , Ramos Carlos , Cena Cícero
Published: April 2021

Visceral leishmaniasis is a neglected disease caused by protozoan parasites of the genus Leishmania. The successful control of the disease depends on its accurate and early diagnosis, which is usually made by combining clinical symptoms with laboratory tests such as serological, parasitological, and molecular tests. However, early diagnosis based on serological tests may exhibit low accuracy due to lack of specificity caused by cross-reactivities with other pathogens, and sensitivity issues related, among other reasons, to disease stage, leading to misdiagnosis. In this work was investigated the use of mid-infrared spectroscopy and multivariate analysis to perform a fast, accurate and easy canine visceral leishmaniasis diagnosis. Canine blood sera of non-infected, Leishmania infantum, and Trypanosoma evansi infected groups were studied. The data demonstrate that principal component analysis with machine learning algorithms achieved an overall accuracy above 85% in the diagnosis.
Local characterization of the Covid19 Response in low-income country: The case of a Lockdown in Zambia
Authors: Muzyamba Choolwe
Published: April 2021

Background The onset of the covid19 pandemic has sparked heated debate among scholars on the relevance of lockdowns. There are those in favor of the lockdown and others who are critical of it. However, despite the increased interest in understanding the relevance of lockdowns, there still has not been much focus on its relevance in low income countries like Zambia. Thus with the help of the SRT, we set out to explore and document the local characterization of the lockdown by residents of Lusaka, Zambia.Methods A qualitative study in the form of interviews was conducted in Lusaka, Zambia involving a sample of 68 participants. Due to the lockdown measures that were in place during the study, the interviews were conducted via phone calls and the data collected were later analyzed by use of thematic analysis technique.Results The lockdown was on one hand lauded for slowing down the incidence rates, preventing fatalities, and for protecting the healthcare system from collapse. On the other hand, it was criticized for exacerbating poverty levels, unemployment rates, increasing the rate of mental health problems, aiding gender based violence, and intensifying political repression and corruption. The results speak to the complexity in the characterization of the lockdown as a response to covid19 in Zambia. This observation demonstrates the folly of viewing, applying and characterizing the covid19 lockdown as a ‘one-size-fits-all’ approach in Zambia.Conclusion Thus rather than definitely establishing the lockdown as an incontestable good, as it is depicted by some scholars or as useless by its critics, our findings instead demonstrate the diversity and complexity in how it is locally viewed by Zambians. The study provides grounds for caution on simplistic and binary characterization of lockdowns. It indicates the need for careful dialog between the designers of lockdowns and citizens in order to tailor such interventions to local realities in context-specific ways. It also shows that though the development of such interventions, all the various and complex elements it embodies must be taken into account in order to realize optimum outcomes.
Graphene Oxide–Polymer Hydrogel: Wettability and Sound Absorption
Authors: Khosrozadeh A. , Rasuli R. , Hamzeloopak H. , Abedini Y.
Published: April 2021

In this paper, we introduce a nanocomposite as a humidity-sensitive sound absorber. The nanocomposites were prepared using hydrogel polymer (HP) as a matrix and graphene oxide (GO) as a filler. Results show that the surface energy of the nanocomposite is 58.4 mJm-2, and GO sheets increase the nanocomposite porosity from 2.6716 cm2 g-1 (for HP) up to 3.246 cm2 g-1. In addition, the diameter of nanocomposite pores is 8.5202 nm lower than that of HP (10.274 nm). To study the effect of humidity on the sound absorption, we exposed them to moisture for 30 and 60 min and then measured sound absorption. Results show an absorption peak for the HP at 1022 Hz with an attenuation value of 30%, while nanocomposite shows two main peaks around 1898 and 3300 Hz. In addition, results show that sound absorption peaks shift to higher frequency according to humidification time.
Improvement of Ligand-Free Modification Strategy: How to Obtain Water-Stable Up-Converting Nanoparticles With Bright Emission and High Reaction Yield?
Authors: Jurga Natalia , Przybylska Dominika , Kamiński Piotr , Grzyb Tomasz
Published: April 2021

Water-dispersible up-converting nanoparticles (UCNPs) are known to be very effective in biomedical applications. Research groups have paid special attention to the synthesis of hydrophilic UCNPs with good physicochemical properties. Being aware of this, we decided to improve the ligand-free modification method of OA-capped NaYF4:Yb3+,Er3+/NaYF4 UCNPs prepared by precipitation in high-boiling-point solvents as the thus-far reported methods do not provide satisfactory results. Different molarities of hydrochloric acid and various mixing times were selected to remove the organic ligand from the NPs’ surface and to discover the most promising modification approach. Highly water-stable colloids were obtained with a very high reaction yield of up to 96%. Moreover, the acid treatment did not affect the morphology and the size of the product. All of the crystals exhibited a bright up-conversion emission under 975-nm excitation, which confirmed the two-photon excitation and effective energy transfer between the used dopant ions. Thus, we could establish the most successful ligand-free modification procedure.
A novel 2 bp deletion variant in Ovine-DRB1 gene is associated with increased Visna/maedi susceptibility in Turkish sheep
Authors: Yaman Yalçın , Bay Veysel , Aymaz Ramazan , Keleş Murat , Öner Yasemin , Teferedegn Eden Yitna , Ün Cemal
Published: April 2021

Visna/Maedi (VM) is a multisystemic lentivirus infection of sheep that affecting sheep industry across the globe. TMEM154 gene has been identified to be a major VM associated host gene, nevertheless, a recent study showed that the frequency of the VM-resistant TMEM154 haplotypes was very low or absent in indigenous sheep. Thus, the present study was designed to determine other possible co-receptors associated with VM. For this purpose, DRB1 gene, which is renowned for its role in host immune response activity against various diseases was targeted. A total number of 151 case-control matched pairs were constructed from 2266 ELISA tested sheep. A broad range of DRB1 haplotype diversity was detected by sequence-based genotyping. Moreover, a novel 2 bp deletion (del) in the DRB1 intron 1 was identified. For final statistic, the sheep carrying VM-resistant TMEM154 diplotypes were removed and a McNemar’s test with a matched pairs experimental design was conducted. Consequently, it was identified for the first time that the 2 bp del variant is a genetic risk factor for VM (p-value, 0.002; chi-square, 9.3; odds ratio, 2.9; statistical power > 0.93) in dominant model. Thus, negative selection for 2 bp del variant could decrease VM infection risk in Turkish sheep.
Genetic Mapping of the Tomato Quality Traits Brix and Blossom-end Rot Under Supplemental LED and HPS Lighting Conditions
Authors: Prinzenberg Aina , Schoot Hanneke van der , Visser Richard GF , Marcelis Leo , Heuvelink Ep , Schouten Henk J
Published: April 2021

LED lighting has emerged as alternative to the current HPS standard in greenhouse production. However little is known about the impact on fruit quality under the different light spectra. We grew a biparental tomato RIL population between September 2019 and January 2020 under two commercial greenhouse supplemental lighting conditions, i.e. HPS, and 95% red/ 5% blue- LED, of about 220 µmol m− 2 s− 1 at maximum canopy height for 16h per day. Differences in Brix and blossom-end rot (BER) between the two light conditions were observed and we studied the genetic influences on those traits, separating genetics located on chromosomes from genetics located in plastids. The Brix value was on average 11% lower under LED than under HPS supplemental lighting. A LED-light specific QTL for Brix was identified on chromosome 6. This QTL can be of interest for breeding for tomato varieties cultivated under LED supplemental lighting. A Brix-QTL on chromosome 2 was found for both light conditions. In our study fewer plants developed BER under LED supplemental lighting than under HPS. We identified a novel genetic locus on chromosome 11 for the incidence of BER that lead to a difference in about 20% of fruits with BER. This genetic component was independent of the light.
Use of A Community of Practice For The Implementation of Evidence-Based Practices For Heart Failure Within The United States Department of Veterans Affairs
Authors: Sahay Anju , Heidenreich Paul A. , Mittman Brian S , Gholami Parisa , Lin Shoutzu
Published: April 2021

Communities of Practice (CoPs) are a promising approach to facilitate the implementation of evidence-based practices (EBPs) to improve care for chronic conditions like heart failure (HF). COPs involve a complex process of acquiring and converting both explicit and tacit knowledge into clinical activities. Formation: In July 2006, a CoP called the Heart Failure Provider Network (HF Network) was established in the United States (US) Department of Veterans Affairs (VA) with the overarching goal of improving the quality of care for HF patients. The CoP has involved a total of 1,341 multidisciplinary and multilevel members at all 144 VA Health Care Systems (sites). Examples of CoP activities include discussions of interventions to decrease hospitalization rates and to empower patients and caregivers for self-management. Goals of the CoP include networking facilitation, information dissemination and exchange, collaboration and implementation of EBPs. Assessment: We conceptualized the assessment (formative evaluation) of the HF Network in terms of its various activities (inputs) and proximal impacts (mediators) at the individual-level, and its distal and ultimate impacts (outcomes) at the site-level leading to an improved culture of implementation of new/improved EBPs at the system-wide level. The HF Network membership grew steadily over the nine years. Most members were practicing clinicians (n = 891, 66.4%), followed by administrators (n = 342, 25.5%), researchers (n = 70, 5.2%), and others (n = 38, 2.8%). Participation was “active” for 70.9% versus “passive” for 29.4% of members. The distribution of active members (clinicians 64.7%, administrators 21.6%) was similar to the distribution of overall membership. Survey respondents perceived the HF Network as useful in terms of its varied activities and resources relevant for patient care. Members, particularly those that consider themselves influential in improving quality of care, noted multiple benefits of membership. These included confirmation of one’s own clinical practices, evidence-based changes to their practice and help in understanding facilitators and barriers in setting up or running HF clinics and other programs.
Approximate Solutions of the Space-Fractional Diffusion Equations with Additive Noise
Authors: Mohammed Wael W. , Ahmad Hijaz
Published: April 2021

In this article we take into account a class of stochastic space diffusion equations with polynomials forced by additive noise. We derive rigorously limiting equations which de…ne the critical dynamics. Also, we approximate solutions of stochastic fractional space di¤usion equations with polynomial term by limiting equations, which are ordinary di¤er-ential equations. Moreover, we address the e¤ect of the noise on the solution’s stabilization. Finally, we apply our results to Fisher’s equation and Ginzburg–Landau models.