bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Operating Conditions on Deposition Rate and Smoothness of Electrolytic Aluminum Foil Using Chloroaluminate Ionic Liquids
Authors: Ui Koichi , Kobayashi Satoshi , Sasaki Kuniaki , Takeguchi Tatsuya , Tsuda Tetsuya , Ueda Mikito , Nunomura Jyunji , Honkawa Yukio , Kojima Yoichi
Published: April 2021

The ionic liquid comprised of anhydrous aluminum chloride (AlCl3) and 1-ethyl-3-methylimidazolium chloride (EMIC) has attracted attention as an electrolyte for Al electrolysis. We have investigated the influence of the operating conditions on the deposition rate and the surface roughness of electrolytic Al foil by using the AlCl3-EMIC melt with/without 20 mmol dm−3 of an 1,10-phenanthroline anhydrate (OP) additive as the electrolyte. The cross-sectional SIM images revealed that the increase in the operating temperature affected the foil thickness and the OP addition affected the smoothness. At the operating temperature of 50 °C and the current density of 52.6 mA cm−2, the current efficiency was 90% or more and the deposition rate was about 0.9 μm min−1 regardless of the OP addition. An AFM image revealed that the surface roughness value of the Al foil obtained on the Ti plate substrate from the melt with the OP additive at 50 °C was 45.8 nm at the current density of 52.6 mA cm−2. The XRD patterns showed that the orientations of the (200) reflections became strong by the OP addition. A smooth Al foil was obtained even at a high current density by increasing the operating temperature and adding OP to the melt.
3D-Printed Testing Plate for the Optimization of High C-Rates Cycling Performance of Lithium-Ion Cells
Authors: Carbonari Gilberto , Scurtu Rares-George , Waldmann Thomas , Radloff Sonja , Flügel Marius , Hoffmann Alice , Wohlfahrt-Mehrens Margret
Published: April 2021

Nowadays, long charging times have become one of the main limitations to a greater worldwide spread of electric vehicles (EV). Enabling high C-rates charging is a promising approach to eliminate this problem and alleviate range anxiety. When a battery is charged at high currents, several factors have to be taken into account. Temperature is certainly a key parameter because when it is too high this can lead to degradation of components (binder, electrolyte, active material, etc), however, when it is too low intercalation kinetics becomes sluggish. Using 3D-printed testing plates (PP3D plates) with Li-reference electrode, we developed a tool for electrochemical investigations of pouch cells. These plates enabled to build a new well-designed 3-electrode pouch cell. This setup allows the identification of the best high C-rate cycling procedure to improve the performance and cycling life of the lithium ion cells. We explored the electrochemical behavior of NMC811 cathodes and graphite anodes, during high discharge C-rates test up to 7 C and charge C-rates up to 2 C. Moreover, the temperature influence on charging performance and longtime cycling stability is investigated. The cells cycled at 25 °C using optimized procedures reached an 80% state of health after more than 1000 cycles.
Interactive Metabolism, a simple and robust active learning tool that improves the biochemistry knowledge of undergraduate students
Authors: França Vitória Costa Pereira Lopes Alves de , Campos Wellington Ferreira
Published: April 2021

Advances in physiology and other fields are strongly associated with a solid base knowledge of biochemistry and cell metabolism. On the other hand, the complex and abstract nature of metabolic pathways, the traditional lecture method, and other factors made the teaching-learning process of biochemistry a challenging endeavor. To overcome this, we developed and tested a novel active learning tool called Interactive Metabolism ( iM-tool). The iM-tool was developed with simple and low-cost materials. We used it for interactive teaching of several metabolic pathways and physiological mechanisms for students enrolled in the Biochemistry subject belonging to different undergraduate courses. The results of evaluation tests showed that the iM-tool significantly (ANOVA, P < 0.01) and consistently improved the biochemistry knowledge of students in classrooms with up to 50 students for 7 different and consecutive academic semesters. A survey intended to mine students’ opinions on the tools showed significant satisfaction with the teaching using the iM-tool over traditional lecture-based teaching, and the iM-tool contributed to collaborative learning among students. Therefore, our results showed that the iM-tool improves the biochemistry and cell metabolism teaching-learning process in a more attractive and interactive manner.
New Solutions for the Generalized BBM Equation in terms of Jacobi and Weierstrass Elliptic Functions
Authors: Salas Alvaro H. , Martinez H Lorenzo J. , Ocampo R David L.
Published: April 2021

The Jacobi elliptic function method is applied to solve the generalized Benjamin-Bona-Mahony equation (BBM). Periodic and soliton solutions are formally derived in a general form. Some particular cases are considered. A power series method is also applied in some particular cases. Some solutions are expressed in terms of the Weierstrass elliptic function.
Decision Optimization of Four-Level Supply Chain with the Participation of Two-Echelon Logistics Service Providers under Different Power Structures
Authors: Zhang Jianjun , Song Zhigang
Published: April 2021

Taking the four-level supply chain participated by two-echelon logistics service providers as the research object, this paper deeply studies the influence of different power structures on the optimal price and logistics service level decisions of the whole supply chain system. On this basis, this paper points out the optimal power structure of the whole supply chain system and then discusses the optimal cooperative decision-making mode to improve the operation efficiency of the supply chain system under optimal power structure. The results show that compared with the two power structures of manufacturer-led and logistics service integrator-led, the retailer-led structure is the optimal power structure, whether from the perspective of maximizing the total profit of the supply chain or the surplus of consumers. When the supply chain is facing consumers who are less sensitive to the retail price of products and more sensitive to the logistics service level, the advantages of retail-led decentralized supply chain are more significant. The centralized decision of product supply chain (PSC) and logistics service supply chain (LSSC) under different power structures is the dominant strategy, and the equilibrium strategy is Nash game adopted by both parties. At this time, the total profit of the supply chain system is the largest and the total social welfare is the largest, while the total profit and consumer surplus of the supply chain under LSSC-led structure are the smallest. When the supply chain is facing consumers with low sensitivity of logistics service level and product retail price, PSC and LSSC have more significant advantages in Nash game rather than Stackelberg game.
Hypnotic Effect of A. absinthium Hydroalcoholic Extract in Pentobarbital-Treated Mice
Authors: Rakhshandeh Hassan , Heidari Amirhossein , Pourbagher-Shahri Ali Mohammad , Rashidi Roghayeh , Forouzanfar Fatemeh
Published: April 2021

Background. Current drugs used in the management of insomnia are associated with side effects. The use of medicinal herbs for insomnia treatment has recently been suggested. Objective. The present study aimed to determine the hypnotic activity of the hydroalcoholic extract of Artemisia absinthium (A. absinthium) in mice. Method. The toxicity of A. absinthium extract is assessed by their lethal dose 50% (LD50), and cytotoxicity evaluation was also done with PC12 cell lines by MTT assay. A. absinthium extract (25, 50, 100, and 200 mg/kg) and 3 fractions (n-butanol fraction (NBF), ethyl acetate fraction (EAF), and aqueous fraction (AQF)) were administered intraperitoneally30 minutes before 30 mg/kg pentobarbital intraperitoneal injection; after that, the sleeping time and sleep latency were recorded. Results. The LD50 value was 2.4 g/kg. The extracts tested showed no negative effect on the proliferation of PC12 cells. A. absinthium extract increased the duration of pentobarbital-induced sleep at doses of 100 and 200 mg/kg (

P
<
0.01

-

P
<
0.001

). Similarly, AQF, EAF, and NBF at 200 mg/kg could increase sleep duration (

P
<
0.05

). The sleep latency was decreased by A. absinthium extract at doses of 100 and 200 mg/kg (

P
<
0.05

-

P
<
0.01

), AQF (

P
<
0.05

), and EAF (P < 0.05). Besides, flumazenil reversed the hypnotic effect of A. absinthium extract (

P
<
0.05

). Conclusion. A. absinthium extract probably demonstrated sleep-enhancing effects by regulating GABAergic system.
TBSMR: A Trust-Based Secure Multipath Routing Protocol for Enhancing the QoS of the Mobile Ad Hoc Network
Authors: Sirajuddin Mohammad , Rupa Ch. , Iwendi Celestine , Biamba Cresantus
Published: April 2021

Mobile ad hoc network (MANET) is a miscellany of versatile nodes that communicate without any fixed physical framework. MANETs gained popularity due to various notable features like dynamic topology, rapid setup, multihop data transmission, and so on. These prominent features make MANETs suitable for many real-time applications like environmental monitoring, disaster management, and covert and combat operations. Moreover, MANETs can also be integrated with emerging technologies like cloud computing, IoT, and machine learning algorithms to achieve the vision of Industry 4.0. All MANET-based sensitive real-time applications require secure and reliable data transmission that must meet the required QoS. In MANET, achieving secure and energy-efficient data transmission is a challenging task. To accomplish such challenging objectives, it is necessary to design a secure routing protocol that enhances the MANET’s QoS. In this paper, we proposed a trust-based multipath routing protocol called TBSMR to enhance the MANET’s overall performance. The main strength of the proposed protocol is that it considers multiple factors like congestion control, packet loss reduction, malicious node detection, and secure data transmission to intensify the MANET’s QoS. The performance of the proposed protocol is analyzed through the simulation in NS2. Our simulation results justify that the proposed routing protocol exhibits superior performance than the existing approaches.
Low-Grade Appendiceal Mucinous Neoplasm (LAMN) Primarily Diagnosed as an Ovarian Mucinous Tumor
Authors: Perivoliotis Konstantinos , Christodoulidis Gregory , Samara Athina A. , Sgantzou Ioanna-Konstantina , Floros Theodoros , Volakakis Georgios , Karasavvidou Foteini , Tepetes Konstantinos
Published: April 2021

Background. Low-grade appendiceal mucinous neoplasms (LAMN) are detected in 0.7 to 1.7% of all appendicectomies. The diagnosis can be challenging, particularly in female patients where the differential diagnosis of primary appendiceal and ovarian mucinous neoplasms is unclear. Case Presentation. A 71-year-old female was referred to our tertiary hospital with the working diagnosis of a right ovarian cystic tumor. The lesion was identified through a transvaginal ultrasound performed for vague lower abdominal pain symptoms. CT scan confirmed these findings. Intraoperatively, an appendiceal mucocele was identified and a right hemicolectomy was performed. The histopathology examination revealed a LAMN. Six months later, the patient remains disease-free. A close biannual oncological follow-up has been suggested. Conclusion. This case underlines the difficulty in determining the origin of mucinous neoplasms of the right pelvic area. Mucocele of the appendix should be considered in the differential diagnosis of a mass in the right iliac fossa.
Matrix Formulation of EISs of Graphs and Its Application to WSN Covering Problems
Authors: Yan Yongyi , Yue Jumei , Deng He
Published: April 2021

In this paper, the problem of formulating and finding externally independent sets of graphs is considered by using a newly developed STP method, called semitensor product of matrices. By introducing a characteristic value of a vertex subset of a graph and using the algebraic representation of pseudological functions, several necessary and sufficient conditions of matrix form are proposed to express the externally independent sets (EISs), minimum externally independent sets (MEISs), and kernels of graphs. Based on this, the concepts of EIS matrix, MEIS matrix, and kernel matrix are introduced. By these matrices’ complete characterization of these three structures of graphs, three algorithms are further designed which can find all these kinds of subsets of graphs mathematically. The results are finally applied to a WSN covering problem to demonstrate the correctness and effectiveness of the proposed results.
A Criterion for the Existence of the Unique Periodic Solution of One-Dimensional Periodic Differential Equation
Authors: Hua Ni
Published: April 2021

In this paper, we discuss one-dimensional differential equation with

ω

-period. By using the fixed point theory, the existence of a periodic solution is obtained; by using the second Lyapunov method, the uniqueness and stability of the periodic solution are obtained.
Implant Prosthodontic Rehabilitation after Surgical Treatment for an Oropharyngeal Malignant Tumour Using Tantalum Dental Implants
Authors: Vuletić Marko , Pelivan Ivica , Gabrić Dragana
Published: April 2021

Oropharyngeal cancer (OPC) represents a significant portion of head and neck cancers. In most cases, it is localised in the soft palate, lingual and palatine tonsils, base of the tongue, and the surrounding tissues. Alcohol and tobacco exposure are well-known evidence-based risk factors for developing OPC; however, over the last decade, there has been a rapid increase in OPC linked to human papillomavirus (HPV). Dental implant therapy faces many challenges related to immediate and long-term success, and patients who are rehabilitated with implant prosthodontic therapy often have numerous comorbidities. Tantalum is a rare transitional metal element which has high corrosion resistance and is extremely inert. Porous tantalum trabecular metal (PTTM) has high volumetric porosity, a low modulus of elasticity, and very high friction. PTTM implant surface enhancement allows “osseoincorporation,” which means the neovascularisation and formation of new bone directly onto the implant. A 65-year-old patient presented to the Department of Oral Surgery of Clinical Hospital Centre Zagreb after resection of the mandible due to OPC had oral rehabilitation. Three Zimmer Biomet Trabecular Metal™ implants (

4.1
×
10
 
mm

) were inserted in the area of lower left first incisor, lower left second premolar, and lower right second premolar, and after four months, a new upper partial denture and the bar-retained mandibular overdenture were made. Implant prosthodontic rehabilitation of head and neck cancer patients is usually challenging in terms of achieving an improvement in its main aim, quality of life; however, today it is a safe and reliable therapy. Although radiation therapy may negatively affect the patient’s oral condition and influence the short- and long-term success of the implant, the presented case report showed that the excellent properties of PTTM-enhanced dental implants may give great basis for future comparative researches of using these implants in the treatment of oncologic patients.
Adenylyl Cyclase (AC) Mediates the Antidepressant-Like Effects of Tropisetron on a Mouse Model of Maternal Separation Stress
Authors: Hosseinzadeh Ali , Boroujeni Shakiba Nasiri , Saghaei Elham , Loriooini Zahra , Dehkordi Saeid Habibian , Balali-Dehkordi Shima , Rahimi-Madiseh Mohammad , Amini-Khoei Hossein
Published: April 2021

The adenylyl cyclase (AC) pathway is involved in the pathophysiology of depression. Finding new antidepressants with high medicinal properties and low side effects is warranted. Therefore, this study was designed to determine the antidepressant-like effect of tropisetron on a maternal separation (MS) model in mice, considering the possible role of AC. NMRI male mice were divided into eleven groups. The control group was treated with saline and MS groups were treated with saline, tropisetron (a 5-HT3 receptor antagonist) at doses of 1, 3, and 5 mg/kg; forskolin (an activator of AC) at doses of 5, 10, and 25 mg/kg; a subeffective dose of forskolin with a subeffective dose of tropisetron; and an effective dose of tropisetron plus an effective dose of NB001 (3 mg/kg) (an AC inhibitor). After treatment, animals were subjected to behavioral tests including the forced swimming test (FST), splash test, and open field test (OFT). We showed that MS caused depressive-like behaviors determined as an increase in the immobility time in the forced swimming test (FST) and decreased grooming time in the splash test. Our results showed that administration of tropisetron, as well as forskolin, mitigated the depressive-like behaviors in MS mice. We found that coadministration of a subeffective dose of tropisetron plus a subeffective dose of forskolin potentiated the antidepressant-like effect of tropisetron. However, coadministration of an effective dose of NB001 with an effective dose of tropisetron did not significantly affect the antidepressant-like effect of tropisetron. We concluded that the antidepressant-like effects of tropisetron on MS mice are partially mediated through the adenylyl cyclase pathway.
Preeclampsia and Its Complications Exacerbate Development of Postpartum Depression: A Retrospective Cohort Study
Authors: Ye Ying , Chen Li , Xu Jiani , Dai Qinjin , Luo Xin , Shan Nan , Qi Hongbo
Published: April 2021

Background. Hypertensive disorders were proved to be associated with the development of depression. But it is unclear if pregnancy‐induced hypertensive diseases, especially preeclampsia (PE), will affect postpartum moods. We aimed to determine the incidence rate of postpartum depression (PPD) in PE patients and comprehensively evaluate the association between PPD and PE, including its severity and complications. Methods. 425 participants including 130 PE mothers were enrolled in this retrospective cohort study. Each woman was asked to complete a questionnaire integrating the Edinburgh Postnatal Depression Scale (EPDS), the Leakage Index Questionnaire, and a pain scale questionnaire within 6 weeks after delivery. The EPDS cut‐off score above 13 was recognized as screening positive for PPD. Data between groups were compared by bivariate analysis. Results. PE mothers showed a direct tendency to PPD development. The positive screening for PPD in the PE group was significantly higher than that of the control group (30.77% vs. 14.58%). Based on the results of the regression model, women diagnosed with severe PE and fetal growth restriction were more inclined to develop PPD than normal ones (AOR: 2.759, 95% CI: 1.206‐6.315 and AOR: 3.450, 95% CI: 1.596‐7.458). It is also indicated that postpartum pain exacerbated the odds of PPD in PE patients (AOR: 1.509, 95% CI: 1.078‐2.114). Conclusions. PE was an independent risk factor for PPD. Its severity and complications exacerbate the development of PPD. Doctors and society should pay more attention to PE patients after delivery against the development of PPD.
Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration Capacity
Authors: Ocaña-Guzmán Ranferi , Téllez-Navarrete Norma A. , Ramón-Luing Lucero A. , Herrera Iliana , De Ita Marlon , Carrillo-Alduenda José-Luis , Choreño-Parra José Alberto , Medina-Quero Karen , Zúñiga Joaquín , Chávez-Galán Leslie
Published: April 2021

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains as a leading infectious cause of death worldwide. The increasing number of multidrug-resistant TB (MDR-TB) cases contributes to the poor control of the TB epidemic. Currently, little is known about the immunological requirements of protective responses against MDR-TB. This is of major relevance to identify immune markers for treatment monitoring and targets for adjuvant immunotherapies. Here, we hypothesized that MDR-TB patients display unique immunophenotypical features and immune cell migration dynamics compared to drug-sensitive TB (DS-TB). Hence, we prospectively conducted an extensive characterization of the immune profile of MDR-TB patients at different time points before and after pharmacological therapy. For this purpose, we focused on the leukocyte expression of chemokine receptors, distribution of different monocyte and lymphocyte subsets, plasma levels of chemotactic factors, and in vitro migration capacity of immune cells. Our comparative cohort consisted of DS-TB patients and healthy volunteer donors (HD). Our results demonstrate some unique features of leukocyte migration dynamics during MDR-TB. These include increased and prolonged circulation of CD3+ monocytes, CCR4+ monocytes, EM CD4+ T cells, EM/CM CD8+ T cells, and CXCR1+CXCR3+ T cells that is sustained even after the administration of anti-TB drugs. We also observed shared characteristics of both MDR-TB and DS-TB that include CCR2+ monocyte depletion in the blood; high plasma levels of MPC-1, CCL-7, and IP-10; and increased responsiveness of leukocytes to chemotactic signals in vitro. Our study contributes to a better understanding of the MDR-TB pathobiology and uncovers immunological readouts of treatment efficacy.
Understanding the Impact of Startups’ Features on Investor Recommendation Task via Weighted Heterogeneous Information Network
Authors: Wu Sen , Chen Ruojia , Wei Guiying , Gao Xiaonan , Huo Lifang
Published: April 2021

Investor recommendation is a critical and challenging task for startups, which can assist startups in locating suitable investors and enhancing the possibility of obtaining investment. While some efforts have been made for investor recommendation, few of them explore the impact of startups’ features, including partners, rounds, and fields, to investor recommendation performance. Along this line, in this paper, with the help of the heterogeneous information network, we propose a FEatures’ COntribution Measurement approach of startups on investor recommendation, named FECOM. Specifically, we construct the venture capital heterogeneous information network at first. Then, we define six venture capital metapaths to represent the features of startups that we focus on. In this way, we can measure the contribution of startups’ features on the investor recommendation task by validating the recommendation performance based on different metapaths. Finally, we extract four practical rules to assist in further investment tasks by using our proposed FECOM approach.
Evaluation of Sonocatalytic and Photocatalytic Processes Efficiency for Degradation of Humic Compounds Using Synthesized Transition-Metal-Doped ZnO Nanoparticles in Aqueous Solution
Authors: Maleki Afshin , Seifi Mehran , Marzban Nader
Published: April 2021

The existence of a humic substance in water causes the growth of microorganisms and reduces the quality of water; therefore, the removal of these materials is crucial. Here, the ZnO nanoparticles doped using transition metals, copper (Cu) and manganese (Mn), were used as an effective catalyst for photocatalytic removal of humic substances in an aqueous environment under ultraviolet, visible light, and light-emitting diode irradiations. Also, we study the effect of the sonocatalytic method. A solvothermal procedure is used for doping, and the Cu- and Mn-doped ZnO nanocatalyst were characterized by means of FTIR, XRD, AFM, SEM, and EDAX analyses. We investigate the effect of operational variables, including doping ratio, initial pH, catalyst dose, initial HS content, and illuminance on the removal efficiency of the processes. The findings of the analyses used for the characterization of the nanoparticles illustrate the appropriate synthesis of the Cu- and Mn-doped ZnO nanocatalysts. We observe the highest removal efficiency rate under acidic conditions and the process efficiency decreased with increasing solution pH, when we tested it in the range of 3–7. Photocatalytic decomposition of HS increases with a rise in catalyst dose, but an increase in initial HS content results in decreasing the removal efficiency. We observe the highest photocatalytic degradation of humic acid while using the visible light, and the highest removal efficiency is obtained using Cu.ZnO. The Cu.ZnO also shows better performance under ultraviolet irradiation compared to other agents.
Atezolizumab plus Bevacizumab versus Sorafenib in the Chinese Subpopulation with Unresectable Hepatocellular Carcinoma: Phase 3 Randomized, Open-Label IMbrave150 Study
Authors: Qin Shukui , Ren Zhenggang , Feng Yin-Hsun , Yau Thomas , Wang Baocheng , Zhao Haitao , Bai Yuxian , Gu Shanzhi , Li Lindong , Hernandez Sairy , Xu Derek-Zhen , Mulla Sohail , Wang Yifan , Shao Hui , Cheng Ann Lii
Published: April 2021

Introduction: Atezolizumab plus bevacizumab significantly improved overall survival (OS) and progression-free survival (PFS) versus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in IMbrave150. Efficacy and safety data from the Chinese subpopulation are reported. Methods: IMbrave150, a global, randomized, open-label, phase 3 study in patients with systemic treatment-naive unresectable HCC, included an extension phase that enrolled additional patients from mainland China. Patients were randomized (2:1) to receive intravenous atezolizumab 1,200 mg plus bevacizumab 15 mg/kg once every 3 weeks or sorafenib 400 mg twice a day until unacceptable toxicity or loss of clinical benefit. Co-primary endpoints were OS and independent review facility-assessed PFS per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population. Results: Of 194 Chinese patients enrolled from April 16, 2018, to April 8, 2019 (137 in the global study and 57 in the China extension phase), 133 received atezolizumab plus bevacizumab and 61 received sorafenib. At the data cutoff (August 29, 2019), the stratified hazard ratio for OS was 0.44 (95% CI, 0.25–0.76) and for PFS was 0.60 (95% CI, 0.40–0.90). The respective median OS and PFS with atezolizumab plus bevacizumab were not reached (NR; 95% CI, 13.5 months to NR) and 5.7 months (95% CI, 4.2–8.3) versus 11.4 months (95% CI, 6.7 to NR) and 3.2 months (95% CI, 2.6–4.8) with sorafenib. Grade 3–4 adverse events (AEs) occurred in 78 of 132 (59.1%) atezolizumab plus bevacizumab-treated and 27 of 58 (46.6%) sorafenib-treated patients. The most common grade 3–4 AE with atezolizumab plus bevacizumab was hypertension, occurring in 15.2% of patients; however, other high-grade AEs were infrequent. Conclusion: Clinically meaningful improvements in OS and PFS observed with atezolizumab plus bevacizumab versus sorafenib suggest that atezolizumab plus bevacizumab may become a practice-changing treatment for Chinese patients with unresectable HCC.
Identification of Lumican and Fibromodulin as Hub Genes Associated with Accumulation of Extracellular Matrix in Diabetic Nephropathy
Authors: Feng Songtao , Gao Yueming , Yin Di , Lv Linli , Wen Yi , Li Zuolin , Wang Bin , Wu Min , Liu Bicheng
Published: April 2021

Introduction: Diabetic nephropathy (DN) remains a major cause of end-stage renal disease. The development of novel biomarkers and early diagnosis of DN are of great clinical importance. The goal of this study was to identify hub genes with diagnostic potential for DN by weighted gene co-expression network analysis (WGCNA). Methods: Gene Expression Omnibus database was searched for microarray data including distinct types of CKD. Gene co-expression network was constructed, and modules specific for DN were identified by WGCNA. Gene ontology (GO) analysis was performed, and the hub genes were screened out within the selected gene modules. In addition, cross-validation was performed in an independent dataset and in samples of renal biopsies with DN and other types of glomerular diseases. Results: Dataset GSE99339 was selected, and a total of 179 microdissected glomeruli samples were analyzed, including DN, normal control, and 7 groups of other glomerular diseases. Twenty-three modules of the total 10,947 genes were grouped by WGCNA, and a module was specifically correlated with DN (r = 0.54, p = 9e−15). GO analysis showed that module genes were mainly enriched in the accumulation of extracellular matrix (ECM). LUM, ELN, FBLN1, MMP2, FBLN5, and FMOD were identified as hub genes. Cross verification showed LUM and FMOD were higher in the DN group and were negatively correlated with estimated glomerular filtration rate (eGFR). In renal biopsies, expression levels of LUM and FMOD were higher in DN than IgA nephropathy, membranous nephropathy, and normal controls. Conclusion: By using WGCNA approach, we identified LUM and FMOD related to ECM accumulation and were specific for DN. These 2 genes may represent potential candidate diagnostic biomarkers of DN.
Outcomes of Interleukin-2 Receptor Antagonist Induction Therapy in Standard-Risk Renal Transplant Recipients Maintained on Tacrolimus: A Systematic Review and Meta-Analysis
Authors: Ali Hatem , Mohamed Mahmoud M. , Sharma Ajay , Fulop Tibor , Halawa Ahmed
Published: April 2021

Introduction: The additive benefit of interleukin-2 receptor antagonist (IL2-RA) induction in standard-risk kidney transplant recipients, while maintained on tacrolimus-based immunosuppressive therapy, is uncertain. Methods: We divided the studies included in this meta-analysis into 2 groups: group A (included studies that used same dose of tacrolimus in both arms of each study) and group B (included studies that compared patients who received induction therapy and low-dose tacrolimus vs. those who received no-induction therapy and high dose of tacrolimus). Results: In group A, 11 studies were included (n = 2,886). IL2-RA induction therapy was not associated with significant differences in comparison to no-induction therapy in terms of acute rejection rates at 6 months post-transplant (risk ratio = 1.12 and 95% confidence interval [CI] range: 0.94–1.35) or graft survival at 1 year post-transplant (risk ratio = 0.78 and 95% CI range: 0.45–1.36). In group B, 2 studies were included (n = 669). There was no difference between both arms in terms of acute rejection rates (risk ratio = 0.62, with 95% CI range: 0.33–1.14) or graft survival (risk ratio = 1 and 95% CI range: 0.57–1.74). Conclusion: IL2-RA induction therapy does not improve outcomes in patients maintained on tacrolimus-based immunotherapy in standard-risk population.
Management of Home Parenteral Nutrition: Complications and Survival
Authors: Reber Emilie , Staub Kaspar , Schönenberger Katja A. , Stanga Anastasia , Leuenberger Michèle , Pichard Claude , Schuetz Philipp , Mühlebach Stefan , Stanga Zeno
Published: April 2021

Background and Aims: Parenteral nutrition (PN) has become an efficient, safe, and convenient treatment over years for patients suffering from intestinal failure. Home PN (HPN) enables the patients to have a high quality of life in their own environment. The therapy management however implies many restrictions and potentially severe lethal complications. Prevention and therapy of the latter are therefore of utmost importance. This study aims to assess and characterize the situation of patients with HPN focusing on prevalence of catheter-related complications and mortality. Methods: Swiss multicentre prospective observational study collecting demographic, anthropometric, and catheter-related data by means of questionnaires every sixth month from 2017 to 2019 (24 months), focusing on survival and complications. Data were analysed using descriptive statistics. Logistic regression models were fitted to investigate association between infection and potential co-factors. Results: Seventy adult patients (50% women) on HPN were included (≈5 patients/million adult inhabitants/year). The most common underlying diseases were cancer (23%), bariatric surgery (11%), and Crohn’s disease (10%). The most prevalent indication was short bowel syndrome (30%). During the study period, 47% of the patients were weaned off PN; mortality rate reached 7% for a median treatment duration of 1.31 years. The rate of catheter-related infection was 0.66/1,000 catheter-days (0.28/catheter-year) while the rate of central venous thrombosis was 0.13/1,000 catheter-days (0.05/catheter-year). Conclusion: This prospective study gives a comprehensive overview of the adult Swiss HPN patient population. The collected data are prerequisite for evaluation, comparison, and improvement of recommendations to ensure best treatment quality and safety.
Physical Frailty and Cognitive Impairment in Older Adults in United States Nursing Homes
Authors: Yuan Yiyang , Lapane Kate L. , Tjia Jennifer , Baek Jonggyu , Liu Shao-Hsien , Ulbricht Christine M.
Published: April 2021

Introduction: In older US nursing home (NH) residents, there is limited research on the prevalence of physical frailty, its potential dynamic changes, and its association with cognitive impairment in older adults’ first 6 months of NH stay. Methods: Minimum Data Set (MDS) 3.0 is the national database on residents in US Medicare-/Medicaid-certified NHs. MDS 3.0 was used to identify older adults aged ≥65 years, newly admitted to NHs during January 1, 2014, and June 30, 2016, with life expectancy ≥6 months at admission and NH length of stay ≥6 months (N = 571,139). MDS 3.0 assessments at admission, 3 months, and 6 months were used. In each assessment, physical frailty was measured by FRAIL-NH (robust, prefrail, and frail) and cognitive impairment by Brief Interview for Mental Status and Cognitive Performance Scale (none/mild, moderate, and severe). Demographic characteristics and diagnosed conditions were measured at admission, while presence of pain and receipt of psychotropic medications were at each assessment. Distribution of physical frailty and its change over time by cognitive impairment were described. A nonproportional odds model was fitted with a generalized estimation equation to longitudinally examine the association between physical frailty and cognitive impairment, adjusting for demographic and clinical characteristics. Results: Around 60% of older residents were physically frail in the first 6 months. Improvement and worsening across physical frailty levels were observed. Particularly, in those who were prefrail at admission, 23% improved to robust by 3 months. At admission, 3 months, and 6 months, over 37% of older residents had severe cognitive impairment and about 70% of those with cognitive impairment were physically frail. At admission, older residents with moderate cognitive impairment were 35% more likely (adjusted odds ratio [aOR]: 1.35, 95% confidence interval [CI]: 1.33–1.37) and those with severe impairment were 74% more likely (aOR: 1.74, 95% CI: 1.72–1.77) to be frail than prefrail/robust, compared to those with none/mild impairment. The association between the 2 conditions remained positive and consistently increased over time. Discussion/Conclusion: Physical frailty was prevalent in NHs with potential to improve and was strongly associated with cognitive impairment. Physical frailty could be a modifiable target, and interventions may include efforts to address cognitive impairment.
Pure Red Cell Aplasia following ABO-Mismatched Allogeneic Hematopoietic Stem Cell Transplantation: Resolution with Daratumumab Treatment
Authors: Henig Israel , Yehudai-Ofir Dana , Zohar Yaniv , Zuckerman Tsila
Published: April 2021

Pure red cell aplasia (PRCA) can potentially occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT) if recipient and donor ABO blood groups are mismatched, with the recipient having isoagglutinins against the donor blood group. Patient plasma cells that survive transplant conditioning produce anti-ABO isoagglutinins targeting donor erythroid precursors in the bone marrow and thus causing red cell aplasia. Therapeutic options include steroids, discontinuation of immunosuppression, plasmapheresis, donor lymphocyte infusion, rituximab, and bortezomib, all with limited benefit. Daratumumab utilized in the treatment of multiple myeloma is an anti-CD38 monoclonal antibody targeting plasma cells, which makes it a potentially efficient therapy for PRCA. The current case report presents a patient with post-allo-HSCT PRCA cured with daratumumab applied after failure of other therapies. Our findings demonstrate safety and high efficiency of daratumumab, suggesting its applicability as early treatment of post-allo-HSCT PRCA.
Rapid Serological Tests for SARS-CoV-2: Diagnostic Performance of 4 Commercial Assays
Authors: de Almeida Sérgio M. , Spalanzani Regiane N. , Nogueira Meri B. , Sanada Beatriz , Cavalli Barbara M. , Rotta Indianara , Takahashi Gislene R.A. , Pereira Luciane A. , Moreira Francielli B. , Dino Carolina L.T. , Graf Maria E. , de Almeida Bernardo M.M. , Domino Natalia R. , Genelhoud Gustavo , Bochnia-Bueno Lucas , Raboni Sonia M.
Published: April 2021

Objective: To assess the diagnostic performance of lateral flow immunochromatographic assays (LFAs) of 4 different manufacturers to identify SARS-CoV-2 antibodies (IgM, IgG, or total), comparing them with the nucleic acid amplification test (NAAT) or the clinical defined test (definite or probable SARS-CoV-2 infection, respectively). Methods: One hundred nineteen serum samples were randomly selected by convenience and distributed in the following groups: (1) group with SARS-CoV-2 infection (n = 82; RT-qPCR positive [definite, n = 70] and probable [n = 12]); (2) other diseases (n = 27; other viruses identified [n = 8] and SARS of other etiologies [n = 19]); and (3) healthy control group (n = 10). LFAs of 4 manufacturers were compared: MedTest Coronavirus (COVID-19) IgG/IgM (MedLevensohn, Brazil); COVID-19 IgG/IgM ECO Test (Ecodiagnóstica, Brazil); Camtech COVID-19 IgM/IgG Rapid Test Kit (Camtech Diagnostics Pte Ltd, Singapore); and 1-Step COVID-19 Test for total antibodies (Guangzhou Wondfo Biotech Co., China). Results: The 4 tests studied showed high diagnostic performance characteristics for the diagnoses of definite or probable SARS-CoV-2 infection. The best measures were for the Wondfo test: sensitivity (86.59%; 95% CI: 77.26–93.11%), specificity (100%; 90.51–100%), DOR (257; 60–1,008), LR+ (33.43; 4.82–231.85), LR− (0.13; 0.08–0.23), accuracy (90.76%; 84.06–95.29%), and Matthews correlation coefficient (MCC) 0.82. Although considering only the probable SARS-CoV-2 infection (PCR−) cases, all the kits studied showed limited values. Conclusion: Our data demonstrate the excellent performance of LFA for the diagnoses of definite or probable SARS-CoV-2 infection. There was substantial heterogeneity in sensitivities of IgM and IgG antibodies among the different kits. LFA tests cannot replace molecular diagnostics but should be used as an additional screening tool.
Targeting Trained Innate Immunity With Nanobiologics to Treat Cardiovascular Disease
Authors: Teunissen Abraham J.P. , van Leent Mandy M.T. , Prévot Geoffrey , Brechbühl Eliane E.S. , Pérez-Medina Carlos , Duivenvoorden Raphaël , Fayad Zahi A. , Mulder Willem J.M.
Published: April 2021

The innate immune system plays a key role in atherosclerosis progression and the pathogenesis of cardiovascular disease. Trained immunity, an epigenetically regulated hyperresponsive state of myeloid cells, is a driving force underlying chronic inflammation in atherosclerosis. Therapeutically targeting innate trained immunity therefore may mature into a compelling new paradigm for the effective treatment of cardiovascular patients, which would require effective engagement of myeloid cells. For over a decade, we have worked on apolipoprotein A1-based nanomaterials, referred to as nanobiologics, which we have utilized for myeloid cell-directed immunotherapy. Here, we review the application of our nanobiologic immunotherapies in treating vascular disease. The design of nanobiologic therapeutics, as well as their use in targeting myeloid cells and cellular pathways related to trained immunity, is discussed. Furthermore, we show that nanobiologic biocompatibility and in vivo behavior are conserved across species, from mice to larger animals, including rabbits, pigs, and nonhuman primates. Last, we deliberate on the hurdles that currently prevent widespread translation of trained immunity targeting cardiovascular nanotherapies.
Prediction of Genotype Positivity in Patients With Hypertrophic Cardiomyopathy Using Machine Learning
Authors: Liang Lusha W. , Fifer Michael A. , Hasegawa Kohei , Maurer Mathew S. , Reilly Muredach P. , Shimada Yuichi J.
Published: April 2021

Background:

Genetic testing can determine family screening strategies and has prognostic and diagnostic value in hypertrophic cardiomyopathy (HCM). However, it can also pose a significant psychosocial burden. Conventional scoring systems offer modest ability to predict genotype positivity. The aim of our study was to develop a novel prediction model for genotype positivity in patients with HCM by applying machine learning (ML) algorithms.

Methods:

We constructed 3 ML models using readily available clinical and cardiac imaging data of 102 patients from Columbia University with HCM who had undergone genetic testing (the training set). We validated model performance on 76 patients with HCM from Massachusetts General Hospital (the test set). Within the test set, we compared the area under the receiver operating characteristic curves (AUROCs) for the ML models against the AUROCs generated by the Toronto HCM Genotype Score (the Toronto score) and Mayo HCM Genotype Predictor (the Mayo score) using the Delong test and net reclassification improvement.

Results:

Overall, 63 of the 178 patients (35%) were genotype positive. The random forest ML model developed in the training set demonstrated an AUROC of 0.92 (95% CI, 0.85–0.99) in predicting genotype positivity in the test set, significantly outperforming the Toronto score (AUROC, 0.77 [95% CI, 0.65–0.90],
P
=0.004, net reclassification improvement:
P
<0.001) and the Mayo score (AUROC, 0.79 [95% CI, 0.67–0.92],
P
=0.01, net reclassification improvement:
P
=0.001). The gradient boosted decision tree ML model also achieved significant net reclassification improvement over the Toronto score (
P
<0.001) and the Mayo score (
P
=0.03), with an AUROC of 0.87 (95% CI, 0.75–0.99). Compared with the Toronto and Mayo scores, all 3 ML models had higher sensitivity, positive predictive value, and negative predictive value.

Conclusions:

Our ML models demonstrated a superior ability to predict genotype positivity in patients with HCM compared with conventional scoring systems in an external validation test set.
Clinical Implications of Monogenic Versus Polygenic Hypercholesterolemia: Long‐Term Response to Treatment, Coronary Atherosclerosis Burden, and Cardiovascular Events
Authors: D’Erasmo Laura , Minicocci Ilenia , Di Costanzo Alessia , Pigna Giovanni , Commodari Daniela , Ceci Fabrizio , Montali Anna , Brancato Francesca , Stanca Ilaria , Nicolucci Antonio , Ascione Andrea , Galea Nicola , Carbone Iacopo , Francone Marco , Maranghi Marianna , Arca Marcello
Published: April 2021

Background

Familial hypercholesterolemia (FH) may arise from deleterious monogenic variants in FH‐causing genes as well as from a polygenic cause. We evaluated the relationships between monogenic FH and polygenic hypercholesterolemia in influencing the long‐term response to therapy and the risk of atherosclerosis.

Methods and Results

A cohort of 370 patients with clinically diagnosed FH were screened for monogenic mutations and a low‐density lipoprotein‐rising genetic risk score >0.69 to identify polygenic cause. Medical records were reviewed to estimate the response to lipid‐lowering therapies and the occurrence of major atherosclerotic cardiovascular events during a median follow‐up of 31.0 months. A subgroup of patients (n=119) also underwent coronary computed tomographic angiography for the evaluation of coronary artery calcium score and severity of coronary stenosis as compared with 135 controls. Two hundred nine (56.5%) patients with hypercholesterolemia were classified as monogenic (FH/M+), 89 (24.1%) as polygenic, and 72 (19.5%) genetically undefined (FH/M−). The response to lipid‐lowering therapy was poorest in monogenic, whereas it was comparable in patients with polygenic hypercholesterolemia and genetically undetermined. Mean coronary artery calcium score and the prevalence of coronary artery calcium >100 units were significantly higher in FH/M+ as compared with both FH/M− and controls. Finally, after adjustments for confounders, we observed a 5‐fold higher risk of incident major atherosclerotic cardiovascular events in FH/M+ (hazard ratio, 4.8; 95% CI, 1.06–21.36;
P
adj
=0.041).

Conclusions

Monogenic cause of FH is associated with lower response to conventional cholesterol‐lowering therapies as well as with increased burden of coronary atherosclerosis and risk of atherosclerotic‐related events. Genetic testing for hypercholesterolemia is helpful in providing important prognostic information.
Might a Single Neuron Solve Interesting Machine Learning Problems Through Successive Computations on Its Dendritic Tree?
Authors: Jones Ilenna Simone , Kording Konrad Paul
Published: April 2021

Physiological experiments have highlighted how the dendrites of biological neurons can nonlinearly process distributed synaptic inputs. However, it is unclear how aspects of a dendritic tree, such as its branched morphology or its repetition of presynaptic inputs, determine neural computation beyond this apparent nonlinearity. Here we use a simple model where the dendrite is implemented as a sequence of thresholded linear units. We manipulate the architecture of this model to investigate the impacts of binary branching constraints and repetition of synaptic inputs on neural computation. We find that models with such manipulations can perform well on machine learning tasks, such as Fashion MNIST or Extended MNIST. We find that model performance on these tasks is limited by binary tree branching and dendritic asymmetry and is improved by the repetition of synaptic inputs to different dendritic branches. These computational experiments further neuroscience theory on how different dendritic properties might determine neural computation of clearly defined tasks.
X-DC: Explainable Deep Clustering Based on Learnable Spectrogram Templates
Authors: Watanabe Chihiro , Kameoka Hirokazu
Published: April 2021

Deep neural networks (DNNs) have achieved substantial predictive performance in various speech processing tasks. Particularly, it has been shown that a monaural speech separation task can be successfully solved with a DNN-based method called deep clustering (DC), which uses a DNN to describe the process of assigning a continuous vector to each time-frequency (TF) bin and measure how likely each pair of TF bins is to be dominated by the same speaker. In DC, the DNN is trained so that the embedding vectors for the TF bins dominated by the same speaker are forced to get close to each other. One concern regarding DC is that the embedding process described by a DNN has a black-box structure, which is usually very hard to interpret. The potential weakness owing to the noninterpretable black box structure is that it lacks the flexibility of addressing the mismatch between training and test conditions (caused by reverberation, for instance). To overcome this limitation, in this letter, we propose the concept of explainable deep clustering (X-DC), whose network architecture can be interpreted as a process of fitting learnable spectrogram templates to an input spectrogram followed by Wiener filtering. During training, the elements of the spectrogram templates and their activations are constrained to be nonnegative, which facilitates the sparsity of their values and thus improves interpretability. The main advantage of this framework is that it naturally allows us to incorporate a model adaptation mechanism into the network thanks to its physically interpretable structure. We experimentally show that the proposed X-DC enables us to visualize and understand the clues for the model to determine the embedding vectors while achieving speech separation performance comparable to that of the original DC models.