bluuebunny/crossref_metadata_2025 huggingface dataset:
Polypyrrole Coated Al-TDC Composite Structure as Lithium-Sulfur Batteries Cathode
Authors: Wang Xin , Han Guo-Dong , Wang Juan
Published: April 2021

Due to the high theoretical capacity of sulfur (1675[Formula: see text]mAh[Formula: see text][Formula: see text], low cost and environmental friendliness, lithium-sulfur batteries have shown broad prospects in future energy conversion and storage systems. However, the shuttle effect and insulating properties of sulfur restrict its practical application. Herein, we report a facile approach to fabricate Al-TDC@S-PPy composite material as lithium-sulfur battery electrode. In this strategy, a topological porous Al-TDC ([Formula: see text],5-thiophenedicarboxylate) with 8-connected clusters is reported, which can provide strong adsorption for dissolved intermediate polysulfides and alleviate volume expansion. Meanwhile, Polypyrrole, (PPy) as a conductive and flexible additive to expedite electron transport, improves electrical conductivity. Consequently, the Al-TDC@S-PPy composite cathode exhibits a higher initial specific capacity (1310.4[Formula: see text]mAh[Formula: see text][Formula: see text] at 0.2[Formula: see text]C). The final reversible capacity is 411.0[Formula: see text]mAh[Formula: see text][Formula: see text] after 200 cycles at 1 C. We can extend this strategy to other metal-organic frameworks (MOFs) and manufacture MOF/conductive polymer composite electrodes for high-performance lithium-sulfur batteries.
Hermitian–Toeplitz and Hankel determinants for certain starlike functions
Authors: Cho Nak Eun , Kumar Sushil , Kumar Virendra
Published: April 2021

The sharp lower and upper estimates on the second- and third-order Hermitian–Toeplitz determinants for the classes of starlike functions associated with the modified sigmoid function and a related function, whose Taylor coefficients are the Bell numbers, are investigated. Further, the third and fourth Hankel determinants for these classes are also estimated.
ESTIMATING THE POTENTIAL CO2EMISSION REDUCTION IN 97 CONTRACTING COUNTRIES OF THE PARIS AGREEMENT
Authors: LI YAN , WEI YIGANG
Published: April 2021

“The common but differentiated responsibilities” requires that participating countries in the Paris Agreement need to clarify their national emission reduction priorities and develop practical and feasible plans based on their local conditions. This paper aims to estimate the CO2emission efficiency and the potential emission reduction of the Paris Agreement contracting countries and identify the key influencing factors of CO2emission efficiency for the period of 1991–2014. A nonradial directional distance function, the metafrontier approach, and the bootstrapped truncated regression model are used. The following are the main conclusions: (1) China makes the highest annual potential CO2emission reduction of 2133.13 billion tons. (2) The technology gap appears to be a major contributor to the potential CO2emission reductions in the low income group (82.87%) and the lower–middle income group (66.01%), and thus these economies should pursue technological innovation to improve carbon emission efficiency; the potential CO2emission reductions in other groups are mainly the result of management inefficiency (with 57.52% and 78.38% of potential emission reductions by the upper–middle income and high income countries coming from management inefficiency). Therefore, some countries in the specific income group exhibit different emission reduction focus. (3) According to a regression analysis on the CO2emission efficiency contributing factors, the progress of total factor productivity and improvement of management level can improve the CO2emission efficiency. This study might be the first attempt to decompose the potential CO2emission reduction of these countries and provides each country with targeted, effective emission reduction priorities.
Synthesis and evaluation of nickel cobalt ferrite magnetic ceramics employing two alternative routes
Authors: Camargo Javier E. , Ramajo Leandro A. , Castro Miriam S.
Published: April 2021

[Formula: see text][Formula: see text]Fe2O4 (NCF) powders were obtained employing two alternative synthesis routes: solid-state reaction and Pechini’s methods. The ceramic powders were pressed and sintered in the temperature range of 1100[Formula: see text]C to 1250[Formula: see text]C. Microstructural and structural properties were evaluated by SEM, XRD, and Raman spectroscopy. Magnetic hysteresis loops of sintered samples were also recorded. A secondary phase was observed in samples synthesized by Pechini’s method, whereas samples obtained by the solid-state reaction method, with the mechanochemical activation of the reagents, only produced the spinel structure. Magnetic properties of samples obtained by the solid-state method displayed higher magnetic saturations and lower coercive fields than those obtained from the Pechini’s method.
Influence of the sintering temperature on ferroelectric properties of potassium-sodium niobate piezoelectric ceramics
Authors: Cortés J. A. , Camargo J. , Rachia M. F. , Rubio-Marcos F. , Ramajo L. , Castro M. , Ramírez M. A.
Published: April 2021

The effect of sintering condition on structure, microstructure, and ferroelectric properties of ([Formula: see text][Formula: see text][Formula: see text] ([Formula: see text][Formula: see text][Formula: see text]- O3(KNL–NTS) has been investigated. Ceramic powders have been synthesized by the solid-state reaction method and sintered at different temperatures (1115[Formula: see text]C, 1125[Formula: see text]C, and 1140[Formula: see text]C). Then, samples were characterized by thermogravimetric analysis, X-ray diffraction, scanning electron microscopy, and impedance spectroscopy. Through XRD results, the perovskite structure and small peaks corresponding to a secondary phase were detected. Ceramics processed at the highest temperatures showed higher densities and good piezoelectric properties ([Formula: see text], [Formula: see text], and [Formula: see text], particularly specimens sintered at 1125[Formula: see text]C presented the highest piezoelectric performance.
Synthesis, Spectroscopic Characterization (FT-IR, NMR, UV), NPA, NBO, NLO, Thermochemical Analysis and Molecular Docking Studies of 2-((4-hydroxyphenyl)(piperidin-1-yl)methyl)phenol
Authors: Ulaş Yeliz
Published: April 2021

In this study, a new alkylaminophenol compound was synthesized and characterized by spectroscopic techniques (FT-IR, NMR, UV). The optimized molecular geometry and the vibrational wavenumbers were calculated using density functional theory (DFT) B3LYP/WB97XD and HF methods with 6-311++ G([Formula: see text], [Formula: see text]) basis set. Thus, theoretical data were compared within themselves before comparing with experimental data. The detailed interpretation of the vibrational spectra has been carried out by VEDA program.1H-NMR and [Formula: see text]C-NMR chemical shifts of the compound were calculated using GIAO/IEFPCM method in CDCl3. Using time-dependent (TD-DFT) approach electronic properties such as HOMO and LUMO energies, the electronic spectrum of the title compound has been studied and reported. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. Linear polarizability, anisotropic linear polarizability and hyperpolarizability values of the title compound were found to be higher than the values of the pNA compound that are used as a standard substance in the NLO analysis. Molecular electrostatic potential (MEP), the thermodynamic properties (heat capacity, entropy and enthalpy) were calculated. Also, to investigate the biological properties of the title compound, molecular docking was done with DNA(PDB ID: 414D). It has been observed that the effective interaction is hydrogen bonds.
Achieving 5,000-h and 8,000-h Low-PGM Electrode Durability on Automotive Drive Cycles
Authors: Ahluwalia R. K. , Wang X. , Peng J-K , Konduru V. , Arisetty S. , Ramaswamy N. , Kumaraguru S.
Published: April 2021

Whereas total Pt loading in anode and cathode catalysts below 0.125 mg cm−2 is required to meet the stringent cost target for automotive fuel cell systems (FCS) for light duty vehicles, low-loaded cathode catalysts are susceptible to unacceptable aging-related performance losses at high current densities. A framework model, validated by accelerated stress test data, has identified cell voltage, relative humidity (RH) and temperature as the key operating variables that affect degradation of a high-activity d-PtCo/C cathode catalyst with 0.1 mg cm−2 Pt loading. Drive cycle simulations indicate that these can be controlled by properly selecting the minimum FCS power, compressor-expander module (CEM) turndown, and stack coolant temperature. The optimum system parameters are 4-kWe minimum power for an 80-kWe FCS, CEM turndown of 12.5, and 66 °C average coolant exit temperature that combine to limit the maximum cell voltage to 850 mV and outlet RH to 90%–100%. Depending on Pt loading, the mismatch between actual and allowable degradation for 10% power loss over 5,000-h lifetime requires the stack to be oversized by 2.4%–5%, resulting in 8.4%–41% lower Pt utilization and 7.1%–20.5% penalty in stack cost. The corresponding results for 8,000-h lifetime are 10.3%-14% stack oversizing, 23%–51.8% lower Pt utilization, and 24.1%–35.4% stack cost penalty.
Study of a GaN-Based Light-Emitting Diode with a Specific Hybrid Structure
Authors: Chen Wei-Cheng , Niu Jing-Shiuan , Liu I-Ping , Wang Zih-Fong , Cheng Shiou-Ying , Liu Wen-Chau
Published: April 2021

A specific hybrid structure, including 45° sidewalls, a shallower (0.25 μm in depth) microhole array, and a 3-D like backside reflector, is used to fabricate GaN-based light-emitting diodes (LEDs). The 3-D like backside reflector is formed by the deposition of 100 nm-diameter SiO2 nanospheres (NSs) and an Al layer on the sapphire substrate. Based on the use of 45° sidewall and microhole array, the reduced total internal reflection (TIR) and Fresnel reflection and the increased scattering probability and the opportunity of photons to find escape cones can be expected. In addition, the use of 3-D like backside reflector can effectively reflect scatter, and redirect the downward photons emitted from multiple quantum well (MQW) region into arbitrary directions. Thus, the light extraction performance can be substantially improved. In experiment, under an injection current of 400 mA, the studied Device D with this hybrid structure shows enhancements of 47.4%, 47.7%, 33.1%, and 47.8% in light output power (LOP), external quantum efficiency (EQE), luminous flux, and wall-plug efficiency (WPE), respectively, as compared to a conventional LED. Moreover, the related electrical properties are not degraded for the studied Device D. Therefore, this hybrid structure shows a promise for high-performance GaN-based LED applications.
Effect of Solder Particle Size on the Mechanical and Thermal Reliability of Au/Sn Ag Cu/Cu Solder Joints
Authors: Xinmeng Zhai , Yue Chen , Li Yuefeng , Jun Zou , Mingming Shi , Bobo Yang , Yang Li , Chunfeng Guo , Rongrong Hu , Qinglou Cao
Published: April 2021

This paper investigates the effect of solders with different grain sizes (5–15 μm, 2–15 μm, 2–11 μm) on the mechanical and thermal reliability of flip-chip LED chip Au/Sn Ag Cu/Cu solder joints during reflow soldering. The lead-free solder SAC305 was selected as the solder. The microstructure of the IMC interface and the inferred surface of the solder joint is observed, and the microstructure evolution of the solder joint is analyzed. The void ratio of the solder joints under different grain sizes is tested to characterize the influence of the contact area between the chip and the solder joints on the shear stress. In addition, the solder joints were aged for 1000 h under a relative humidity of 85 °C/85%. The photoelectric thermal performance of the FC-LED filament and the influence of high temperature and high humidity aging on the reliability of the filament were tested and analyzed. The results show that when the size of the solder paste is small and the uniformity is poor within a certain range of solder size, the voids in the flux layer are large and concentrated, and the void ratio is significantly higher, which leads to a decrease in the mechanical reliability of the solder joints. The thermal resistance test results show that the cavity will cause excessive thermal resistance, poor heat dissipation, a significant increase in junction temperature, and a decrease in thermal reliability, which in turn leads to severe light aging and ultimately changes in photoelectric performance. When the grain size is 5–15 μm, the uniformity of the particle size is good. After the filament is aged for 1000 h at high temperature and humidity, the light maintenance rate remains at 65.6%, and the filament performance is stable and reliable. It has certain reference value in the actual production process.
Junctionless Electric-Double-Layer TFTs on Paper Substrate
Authors: Yuan Xing , Tan Yuanyuan , Lei Liuhui , Dou Wei , Zhang Jiale , Wang Yongkang , Zeng Sizhe , Deng Shenyi , Guo Haoting , Zhou Weichang , Tang Dongsheng
Published: April 2021

Junctionless Low-voltage electric-double-layer (EDL) thin-film transistors (TFTs) gated by solution-processed chitosan dielectric have been fabricated on paper substrate. The operating voltage is found to be as low as 1.0 V due to the large gate specific capacitance (5.4 μF cm−2 at 20 Hz) related to EDL effect induced by mobile ion. The field-effect mobility, subthreshold gate voltage swing and current on/off ratio is estimated to be 2.3 cm2 Vs−1, 110 mV decade−1 and 2 × 105, respectively. The reproducibility of pulse respond and stability of such device are also demonstrated, which indicates that the Junctionless Low-voltage EDL TFT has a potential for flexible electronics.
Inhibition of the lipoxin A4 and resolvin D1 receptor impairs host response to acute lung injury caused by pneumococcal pneumonia in mice
Authors: Siegel Emily R. , Croze Roxanne H. , Fang Xiaohui , Matthay Michael A. , Gotts Jeffrey E.
Published: April 2021

Resolution of the acute respiratory distress syndrome (ARDS) from pneumonia requires repair of the injured lung endothelium and alveolar epithelium, removal of neutrophils from the distal airspaces of the lung, and clearance of the pathogen. Previous studies have demonstrated the importance of specialized proresolving mediators (SPMs) in the regulation of host responses during inflammation. Although ARDS is commonly caused by Streptococcus pneumoniae, the role of lipoxin A4 (LXA4) and resolvin D1 (RvD1) in pneumococcal pneumonia is not well understood. In the present experimental study, we tested the hypothesis that endogenous SPMs play a role in the resolution of lung injury in a clinically relevant model of bacterial pneumonia. Blockade of formyl peptide receptor 2 (ALX/FPR2), the receptor for LXA4 and RvD1, with the peptide WRW4 resulted in more pulmonary edema, greater protein accumulation in the air spaces, and increased bacteria accumulation in the air spaces and the blood. Inhibition of this receptor was also associated with decreased levels of proinflammatory cytokines. Even in the presence of antibiotic treatment, WRW4 inhibited the resolution of lung injury. In summary, these experiments demonstrated two novel findings: LXA4 and RvD1 contribute to the resolution of lung injury due to pneumococcal pneumonia, and the mechanism of their benefit likely includes augmenting bacterial clearance and reducing pulmonary edema via the restoration of lung alveolar-capillary barrier permeability.
Potency of Bone Marrow-Derived Mesenchymal Stem Cells and Indomethacin in Complete Freund’s Adjuvant-Induced Arthritic Rats: Roles of TNF-α, IL-10, iNOS, MMP-9, and TGF-β1
Authors: Ahmed Eman A. , Ahmed Osama M. , Fahim Hanaa I. , Ali Tarek M. , Elesawy Basem H. , Ashour Mohamed B.
Published: April 2021

Rheumatoid arthritis (RA) is an autoimmune syndrome affecting joint spaces, leading to the disabled state. Currently, there is no optimal therapy for RA except for systemic immunosuppressants that have variable undesirable effects after long-term use. Hence, the need for other treatment modalities has emerged in an attempt to develop a treating agent that is effective but without bad effects. Bone marrow-derived mesenchymal stem cells (BM-MSCs) may be an alternative medicine since they may differentiate into a variety of mesenchymal tissues including bone and cartilage. Indomethacin (IMC) could be suggested as an analgesic, anti-inflammatory, and antirheumatic potential agent against the course of RA since it possesses significant palliative effects and antipyretic properties. Therefore, our target of this study was to explore and compare the effect of BM-MSCs (1×106cells/rat at the 1st, 6th, 12th, and 18th days) and IMC (2 mg/kg b.w./day for 3 weeks) either alone or in combination on arthritic rats. The model of rheumatoid arthritis in rats was induced by subcutaneous injection of 0.1 mL/rat CFA into the footpad of the right hind paw. The BM-MSC intravenous injection and IMC oral administration significantly reduced the elevated right hind leg paw diameter and circumference, serum anti-CCP, and ankle joint articular tissue expressions of TNF-α, iNOS, MMP-9, and TGF-β1 while they significantly increased the lowered articular IL-10 expression in CFA-induced arthritic rats. The combinatory effect of the two treatments was the most potent. In conclusion, the treatment of RA with BM-MSCs and IMC together is more effective than the treatment with either BM-MSCs or IMC. The Th1 cytokine (TNF-α), Th2 cytokine (IL-10), iNOS, MMP-9, and TGF-β1 are important targets for mediating the antiarthritic effects of BM-MSCs and IMC in CFA-induced arthritis in rats.
The Anti-HER3 mAb Seribantumab Effectively Inhibits Growth of Patient-Derived and Isogenic Cell Line and Xenograft Models with Oncogenic NRG1 Fusions
Authors: Odintsov Igor , Lui Allan J.W. , Sisso Whitney J. , Gladstone Eric , Liu Zebing , Delasos Lukas , Kurth Renate I. , Sisso Exequiel M. , Vojnic Morana , Khodos Inna , Mattar Marissa S. , de Stanchina Elisa , Leland Shawn M. , Ladanyi Marc , Somwar Romel
Published: April 2021

Purpose:

Oncogenic fusions involving the neuregulin 1 (NRG1) gene are found in approximately 0.2% of cancers of diverse histologies. The resulting chimeric NRG1 proteins bind predominantly to HER3, leading to HER3-HER2 dimerization and activation of downstream growth and survival pathways. HER3 is, therefore, a rational target for therapy in NRG1 fusion–driven cancers.

Experimental Design:

We developed novel patient-derived and isogenic models of NRG1-rearranged cancers and examined the effect of the anti-HER3 antibody, seribantumab, on growth and activation of signaling networks in vitro and in vivo.

Results:

Seribantumab inhibited NRG1-stimulated growth of MCF-7 cells and growth of patient-derived breast (MDA-MB-175-VII, DOC4-NRG1 fusion) and lung (LUAD-0061AS3, SLC3A2-NRG1 fusion) cancer cells harboring NRG1 fusions or NRG1 amplification (HCC-95). In addition, seribantumab inhibited growth of isogenic HBEC cells expressing a CD74-NRG1 fusion (HBECp53-CD74-NRG1) and induced apoptosis in MDA-MB-175-VII and LUAD-0061AS3 cells. Induction of proapoptotic proteins and reduced expression of the cell-cycle regulator, cyclin D1, were observed in seribantumab-treated cells. Treatment of MDA-MB-175-VII, LUAD-0061AS3, and HBECp53-CD74-NRG1 cells with seribantumab reduced phosphorylation of EGFR, HER2, HER3, HER4, and known downstream signaling molecules, such as AKT and ERK1/2. Significantly, administration of seribantumab to mice bearing LUAD-0061AS3 patient-derived xenograft (PDX) and OV-10-0050 (ovarian cancer with CLU-NRG1 fusion) PDX tumors induced regression of tumors by 50%–100%. Afatinib was much less effective at blocking tumor growth.

Conclusions:

Seribantumab treatment blocked activation of the four ERBB family members and of downstream signaling, leading to inhibition of NRG1 fusion–dependent tumorigenesis in vitro and in vivo in breast, lung, and ovarian patient-derived cancer models.
Multimodal Imaging Findings and Treatment with Dexamethasone Implant in Three Cases of Idiopathic Macular Telangiectasia Type 1
Authors: Cirafici Paola , Musolino Maria , Saccheggiani Michela , Traverso Carlo Enrico , Nicolò Massimo
Published: April 2021

This is a report of 3 patients diagnosed with idiopathic macular telangiectasia type 1 (MacTel 1) at Medical Retina Center of the University of Eye Clinic of Genova and then prospectically followed for a mean time of 26 months between 2016 and 2019. It is the first report of patients affected by MacTel 1 treated with dexamethasone (DEX) implant as a first choice of treatment. Aim of our study is to better characterize the disease using a multimodal wide-field imaging and to determine efficacy of DEX implant on MacTel 1 in terms of central macular thickness (CMT) and best-corrected visual acuity (BCVA). MacTel 1 is a rare unilateral disease, characterized by telangiectatic retinal capillaries, cystoid macular edema, and lipid deposition occurring temporal to the fovea. Patients underwent a comprehensive ophthalmic examination, BCVA, swept-source optical coherence tomography (SS-OCT), SS-OCT angiography (SS-OCTA), ultra-widefield (UWF) color, and fluorescein angiography (FA) fundus photograph. All the patients presented monolateral reduced BCVA and macular edema with increased CMT evaluated by SS-OCT. With SS-OCTA, we showed that the telangiectasia-associated vascular changes originate in the deep retinal vascular plexus and as a consequence macular edema and exudation develop causing vision loss. Furthermore, UWF imaging helped us to highlight vascular changes typical of Coats Disease at the far retinal periphery. All the patients were treated with DEX intravitreal implant, showing a decrease in CMT and a stabilization of visual acuity. Due to the recurrent nature of macular edema, patients underwent a mean of 4 DEX implants during the follow-up period. In order to address the clinical features of this uncommon disease avoiding diagnostic errors, it might be important to use a multimodal imaging approach. The anatomical and functional beneficial effects of DEX implant were well evident although transient.
Granulomatosis with Polyangiitis with Ocular Manifestations
Authors: Orazbekov Lukpan , Issergepova Botagoz , Assainova Makpal , Ruslanuly Kairat
Published: April 2021

Granulomatosis with polyangiitis (GPA) is a granulomatous-necrotic systemic vasculitis with a lesion of predominantly the upper and lower respiratory tracts at the onset of the disease (vasculitis, accompanied by granulomatous inflammation), and subsequently renal (glomerulonephritis). In addition, GPA may manifest as inflammation of small arteries and veins. Despite many years of study of this disease, the etiology of GPA remains unknown. The present case is about a 47-year-old female, who had been suffering from necrotizing scleritis, corneal ulcer, and secondary glaucoma in both eyes for 3 months, and she was treated with anti-inflammatory and antimicrobial therapy that showed no effect; the patient’s general condition became worse. In the second week of treatment, multiple abscess ruptures exposed the sclera. Sampling of the affected conjunctival tissue and positive HLA B8 haplotype and ANCA (PR3-ANCA) testings make it clear that GPA was the main reason of necrotizing scleritis with inflammation. The targeted treatment of the underlying disease allows to stabilize an inflammation of corneal and scleral lesions.
Drug Development for Target Ribosomal Protein rpL35/uL29 for Repair of LAMB3R635X in Rare Skin Disease Epidermolysis Bullosa
Authors: Rathner Adriana , Rathner Petr , Friedrich Andreas , Wießner Michael , Kitzler Christian Manuel , Schernthaner Jan , Karl Thomas , Krauß Jan , Lottspeich Friedrich , Mewes Werner , Hintner Helmut , Bauer Johann W. , Breitenbach Michael , Müller Norbert , Breitenbach-Koller Hannelore , von Hagen Jörg
Published: April 2021

Introduction: Epidermolysis bullosa (EB) describes a family of rare genetic blistering skin disorders. Various subtypes are clinically and genetically heterogeneous, and a lethal postpartum form of EB is the generalized severe junctional EB (gs-JEB). gs-JEB is mainly caused by premature termination codon (PTC) mutations in the skin anchor protein LAMB3 (laminin subunit beta-3) gene. The ribosome in majority of translational reads of LAMB3PTC mRNA aborts protein synthesis at the PTC signal, with production of a truncated, nonfunctional protein. This leaves an endogenous readthrough mechanism needed for production of functional full-length Lamb3 protein albeit at insufficient levels. Here, we report on the development of drugs targeting ribosomal protein L35 (rpL35), a ribosomal modifier for customized increase in production of full-length Lamb3 protein from a LAMB3PTC mRNA. Methods: Molecular docking studies were employed to identify small molecules binding to human rpL35. Molecular determinants of small molecule binding to rpL35 were further characterized by titration of the protein with these ligands as monitored by nuclear magnetic resonance (NMR) spectroscopy in solution. Changes in NMR chemical shifts were used to map the docking sites for small molecules onto the 3D structure of the rpL35. Results: Molecular docking studies identified 2 FDA-approved drugs, atazanavir and artesunate, as candidate small-molecule binders of rpL35. Molecular interaction studies predicted several binding clusters for both compounds scattered throughout the rpL35 structure. NMR titration studies identified the amino acids participating in the ligand interaction. Combining docking predictions for atazanavir and artesunate with rpL35 and NMR analysis of rpL35 ligand interaction, one binding cluster located near the N-terminus of rpL35 was identified. In this region, the nonidentical binding sites for atazanavir and artesunate overlap and are accessible when rpL35 is integrated in its natural ribosomal environment. Conclusion: Atazanavir and artesunate were identified as candidate compounds binding to ribosomal protein rpL35 and may now be tested for their potential to trigger a rpL35 ribosomal switch to increase production of full-length Lamb3 protein from a LAMB3PTC mRNA for targeted systemic therapy in treating gs-JEB.
A Case of Delayed Diagnostic Pulmonary Tuberculosis during Targeted Therapy in an EGFR Mutant Non-Small Cell Lung Cancer Patient
Authors: Jin Caibao , Yang Bin
Published: April 2021

The coexistence of lung cancer and pulmonary tuberculosis (TB) is rare, and the clinical and radiological features are always similar between lung cancer and pulmonary TB. In the present case, a non-small cell lung cancer patient with an epidermal growth factor receptor (EGFR)-sensitive mutation was diagnosed with pulmonary TB during the treatment of tyrosine kinase inhibitor (TKI) because of the discrepant and confusing responses among different lesions. Therefore, we should combine clinical and radiological characteristics with pathological and microbiological tests to confirm the diagnosis of TB or lung cancer. It is a safe and selectable therapeutic strategy to treat EGFR mutant lung cancer patients with active TB using anti-TB medications and TKIs simultaneously.
Pharmacological Treatment of Osteoporosis in Elderly People: A Systematic Review and Meta-Analysis
Authors: Wang Qin-Yi , Ding Na , Dong Yi-He , Wen Zhang-Xin , Chen Rong , Liu Shu-Ying , Liu Hong , Sheng Zhi-Feng , Ou Yang-Na
Published: April 2021

Background: The evidence supporting the use of antiresorptive and anabolic agents for fracture prevention in elderly patients is still inconclusive. Whether it is too late to alter the course of the disease in this age-group has remained uncertain. Objectives: The objective of this study was to determine the efficacy and safety of antiresorptive and anabolic agents in elderly patients. Methods: PubMed, Web of Science, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and post hoc analyses of RCTs reporting efficacy outcomes or adverse events of antiresorptive and anabolic agents in elderly patients. Statistical heterogeneity was assessed with the Cochran Q χ2 test and I2 statistic. All results were expressed as relative risk (RR) with 95% confidence intervals (CIs). Results: The meta-analysis included 1 RCT and 11 post hoc analyses of data from 10 double-blind placebo-controlled RCTs. Antiresorptive therapy significantly reduced the pooled incidence of vertebral fractures (RR = 0.43; 95% CI = 0.35–0.53; and p < 0.001). It was also associated with lower risk of nonvertebral and hip fractures (RR = 0.84; 95% CI = 0.74–0.96; and p = 0.009 and RR = 0.75; 95% CI = 0.58–0.97; and p = 0.028, respectively). For any adverse events, no difference was observed between antiresorptive agents and placebo groups (RR = 1.01; 95% CI = 1.00–1.02; and p = 0.23). Conclusions: Both antiresorptive and anabolic agents represented potentially important osteoporosis treatments, showing significant effects on reducing vertebral, nonvertebral, or hip fracture risk, and were well-tolerated by elderly patients. Even in the elderly, maybe it is not too late to alter the course of the disease.
Cochlear Implant Outcomes in Patients with Neurosarcoidosis
Authors: Ebode Dario , Cohen-Aubart Fleur , Trunet Stéphanie , Ferrary Evelyne , Lahlou Ghizlène , Mosnier Isabelle
Published: April 2021

Introduction: Audiovestibular symptoms are rare in sarcoidosis, but they may also be the first manifestation of the disease. Sudden or progressive bilateral hearing loss is usually associated with vestibular impairment. The mechanism of hearing loss remains unclear, but clinical presentation and magnetic resonance imaging suggest a retrocochlear site for the lesion in most patients. Several cases of hearing recovery after corticosteroid treatment have been reported. In patients with severe or profound hearing loss, the benefit of cochlear implantation is challenging to predict in the case of auditory neuropathy and is rarely described. We present a case series of cochlear implantation in patients with documented neurosarcoidosis. Results: Seven cases of cochlear implantation in 4 patients with neurosarcoidosis are reported. All of the patients showed a great improvement very quickly in both quiet and noise. Speech performance remained stable over time with a follow-up ranging from 4 to 11 years, even in patients who had disease exacerbation. Conclusion: Cochlear implantation is possible in deaf patients with neurosarcoidosis. The excellent benefit obtained in our patients suggests a particular type of neuropathy, but endocochlear involvement cannot be entirely ruled out.
Clinicogenetic Profile, Treatment Modalities, and Mortality Predictors of Gaucher Disease: A 15-Year Retrospective Study
Authors: Barney Anitha M. , Danda Sumita , Abraham Aby , Fouzia N.A. , Gowdra Aruna , Abraham Suneetha Susan Cleave , Sony Mohan , Das Sweta , Korula Sophy , Mathai Sarah , Simon Anna , Kumar Sathish
Published: April 2021

Introduction: Gaucher disease (GD) is a rare autosomal recessive lysosomal storage disorder, in which biallelic pathogenic variants in the Glucosidase beta acid (GBA) gene result in defective functioning of glucosylceramidase that causes deposition of glucocerebroside in cells. GD has 3 major types namely, non-neuronopathic (type I), acute neuronopathic (type II), and chronic neuronopathic (type III). Definite treatment options are limited and expensive. They succumb early to the disease, if untreated. There is paucity of studies from the Indian subcontinent, which elicit the factors resulting in their premature mortality. Materials and Methods: A retrospective study was carried out in a tertiary care setting of South India to assess the clinical profile, mutation spectrum, and various management strategies (only supportive therapy, enzyme replacement therapy [ERT], substrate reduction therapy [SRT] haematopoietic stem cell transplant [HSCT]), and mortality predictors of patients with GD from 2004 to 2019. A Kaplan-Meier survival curve was plotted. In silico predictions were performed for novel variants. Results: There were 60 patients with all types of GD seen over the study period of 15 years. Their median age at diagnosis was 2 years. The median follow-up was for 5 years (interquartile range [IQR] = 2–8). The overall mortality rate was 35%; however, it was only 10% in those receiving definite treatment. Mortality was higher (47.5%) by more than 4 folds in those only on supportive therapy. The median survival from the time of diagnosis was 6.3 years (IQR = 3.5–10.8) in the definite treatment group and 3.5 years (IQR = 1–5) in those on supportive therapy. The Kaplan-Meier survival analysis showed significant (p value 0.001) mortality difference between these groups. The multiple logistic regression analysis found the neuronopathic type (OR = 5) and only supportive therapy (OR = 6.3) to be the independent risk factors for premature mortality. Conclusion: GD is a rare disease with a high mortality rate, if left untreated. ERT and SRT are the definitive treatments which increase the survival. In resource-limited settings like India, with higher prevalence of the neuronopathic type, HSCT may be a more suitable definitive treatment option, due to its one-time intervention and cost, assuming similar efficacy to ERT. However, the efficacy and safety of HSCT in GD needs to be established further by substantial patient numbers undergoing it.
The Detection, Outcome, and Presentation of Twin-Twin Transfusion Syndrome in Monochorionic Diamniotic Twin Pregnancies Followed with a Protocol of Fortnightly Ultrasound Examination
Authors: Couck Isabel , Ponnet Sophie , Thewissen Liesbeth , Russo Francesca , Deprest Jan , De Catte Luc , Devlieger Roland , Lewi Liesbeth
Published: April 2021

Background: Evidence to support a fortnightly scan protocol for monochorionic diamniotic (MCDA) pregnancies to detect twin-twin transfusion syndrome (TTTS) is scarce. Also, TTTS-related mortality in an unselected cohort is not well documented. Finally, common knowledge suggests that a more frequent follow-up may pick up the disease at a milder stage, but little is known on the ultrasound findings before the diagnosis. Objectives: We examine if a fortnightly ultrasound scan from 16 weeks onward detects TTTS in time. Also, we document the outcomes in a large unselected cohort of MCDA twins and examine the ultrasound findings within 14 days before diagnosis. Methods: Retrospective cohort of 675 MCDA twin pregnancies followed with a fortnightly scan protocol from 16 weeks onward. Timely detection of TTTS was defined as before fetal demise (stage V), ruptured membranes, or a dilated cervix. We compared the ultrasound findings before the diagnosis between stage I–II and stage III–IV. Results: A total of 82/675 (12%) pregnancies developed TTTS, of which 74/82 (90%) were detected in time. In 8/82 (10%), TTTS was diagnosed in stage V: 5 before 16 weeks and 2 after 26 weeks. Fetoscopic laser photocoagulation (FLP) of the placental anastomoses was performed in 48/82 (59%). The survival of TTTS in the entire cohort was 105/164 (64%). In contrast, survival after FLP was 77/96 (80%). In 16/19 (84%) of stage III–IV TTTS, abnormal Doppler findings preceded the diagnosis of TTTS. Conclusions: A scheme of fortnightly ultrasound scans from 16 weeks onward detects 9 out of ten TTTS pregnancies in time. Most stage V cases presented outside the typical time window of 16 and 26 weeks. Survival rates after FLP underestimate the mortality of TTTS. Most stage III–IV cases have abnormal Doppler findings before the diagnosis of TTTS.
Acute Hemodynamic Improvement by Thermal Vasodilation inside the Abdominal and Iliac Arterial Segments of Young Sedentary Individuals
Authors: Li Zhongyou , Jiang Wentao , Salerno Stephen , Li Yi , Chen Yu , Xu Zhi , Wang Guanshi
Published: April 2021

Objective: To study the hemodynamic response to lower leg heating intervention (LLHI) inside the abdominal and iliac arterial segments (AIAS) of young sedentary individuals. Methods: A Doppler measurement of blood flow was conducted for 5 young sedentary adults with LLHI. Heating durations of 0, 20, and 40 min were considered. A lumped parameter model (LPM) was used to ascertain the hemodynamic mechanism. The hemodynamics were determined via numerical approaches. Results: Ultrasonography revealed that the blood flow waveform shifted upwards under LLHI; in particular, the mean flow increased significantly (p < 0.05) with increasing heating duration. The LPM showed that its mechanism depends on the reduction in afterload resistance, not on the inertia of blood flow and arterial compliance. The time-averaged wall shear stress, time-averaged production rate of nitric oxide, and helicity in the external iliac arteries increased more significantly than in other segments as the heating duration increased, while the oscillation shear index (OSI) and relative residence time (RRT) in the AIAS declined with increasing heating duration. There was a more obvious helicity response in the bilateral external iliac arteries than the OSI and RRT responses. Conclusion: LLHI can effectively induce a positive hemodynamic environment in the AIAS of young sedentary individuals.
The Role of CXCL12 in Kidney Diseases: A Friend or Foe?
Authors: Song Anni , Jiang Anni , Xiong Wei , Zhang Chun
Published: April 2021

Background: Chemokines are a family of proteins mainly mediating the homing and migration of various cells. The CXC chemokine CXCL12 is a member of low-weight-molecular chemokines. In the kidney, CXCL12 is pivotal for renal development and exerts a modulatory effect in kidney diseases under different etiologic settings by binding with CXC chemokine receptor 4 (CXCR4) or CXC chemokine receptor 7 (CXCR7). Besides, CXCL12 also exerts homeostasis influence in diverse physical conditions and various pathological situations. Thus, we conclude the complicated relationship between CXCL12 and kidney diseases in this review. Summary: In renal development, CXCL12 contributes a lot to nephrogenesis and the formation of renal vasculature via correlating with CXCR4. CXCL12 also plays an essential role in renal recovery from acute kidney injury. However, the CXCL12/CXCR4 axis plays a dual regulatory role in the initiation and development of diabetic kidney disease as well as chronic allogeneic nephropathy after kidney transplantation through dialectical consideration. Additionally, the CXCL12/CXCR4 link is considered as a new risk factor for lupus nephritis and renal cell carcinoma. Key Messages: Plenty of studies have presented the influence of CXCL12 and the relation with corresponding receptors in diverse biological and pathological statuses. Simultaneously, some drugs and antagonists targeting CXCL12/CXCR4 axis effectively treat various kidney diseases. However, more researches are needed to explore thorough influence and mechanisms, providing more cues for clinical treatments.
The Increased Trend of Medical Treatment for Thyroid Diseases during Pregnancy: A 13-Year National Study
Authors: Turunen Suvi , Vääräsmäki Marja , Leinonen Maarit , Gissler Mika , Männistö Tuija , Suvanto Eila
Published: April 2021

Objective: Thyroid dysfunction affects up to 5–7% of all pregnancies. The rates of thyroid hormone use in nonpregnant population have substantially increased in recent years. The aim of this study was to assess possible changes in the use of levothyroxine substitution and antithyroid drugs over time in pregnant women. Methods: The study data consisted of all singleton pregnancies (N = 736,873) between 2004 and 2016 in Finland collected from the Finnish Medical Birth Register. The Prescription Register and Special Refund Entitlement Register provided information on levothyroxine and antithyroid drug purchases. The annual rates of levothyroxine and antithyroid drug prescription redemptions were explored to estimate changes in exposure rates to thyroid medication from 2004 to 2016. Joinpoint regression analyses were performed to explore interannual variability in levothyroxine and antithyroid drug treatment. Results: There was more than a five-fold increase in levothyroxine use during the study period; in 2004, 1.1% of pregnant women had levothyroxine treatment, and by 2016, the prevalence increased to 6.2%. In addition, we observed a slight increase in antithyroid medication during pregnancy, but antithyroid drug use during pregnancy overall was very rare. In 2004, 0.05% of pregnant women used antithyroid drugs, and by 2016, this percentage had increased to 0.14%. Conclusions: Our study shows that the rate of levothyroxine use in pregnancy has markedly increased. This suggests that tracing and screening relevant patients and awareness of thyroid disorders on pregnancy and their significance for the pregnancy outcome have increased and the threshold to treat thyroid disorders has declined.
Abnormal Cerebellar Development in Autism Spectrum Disorders
Authors: van der Heijden Meike E. , Gill Jason S. , Sillitoe Roy V.
Published: April 2021

Autism spectrum disorders (ASD) comprise a group of heterogeneous neurodevelopmental conditions characterized by impaired social interactions and repetitive behaviors with symptom onset in early infancy. The genetic risks for ASD have long been appreciated: concordance of ASD diagnosis may be as high as 90% for monozygotic twins and 30% for dizygotic twins, and hundreds of mutations in single genes have been associated with ASD. Nevertheless, only 5–30% of ASD cases can be explained by a known genetic cause, suggesting that genetics is not the only factor at play. More recently, several studies reported that up to 40% of infants with cerebellar hemorrhages and lesions are diagnosed with ASD. These hemorrhages are overrepresented in severely premature infants, who are born during a period of highly dynamic cerebellar development that encompasses an approximately 5-fold size expansion, an increase in structural complexity, and remarkable rearrangements of local neural circuits. The incidence of ASD-causing cerebellar hemorrhages during this window supports the hypothesis that abnormal cerebellar development may be a primary risk factor for ASD. However, the links between developmental deficits in the cerebellum and the neurological dysfunctions underlying ASD are not completely understood. Here, we discuss key processes in cerebellar development, what happens to the cerebellar circuit when development is interrupted, and how impaired cerebellar function leads to social and cognitive impairments. We explore a central question: Is cerebellar development important for the generation of the social and cognitive brain or is the cerebellum part of the social and cognitive brain itself?
Long-Term Results of the TARGIT-A Trial: More Questions than Answers
Authors: Piroth Marc D. , Strnad Vratislav , Krug David , Fastner Gerd , Baumann René , Combs Stephanie E. , Duma Marciana Nona , Dunst Jürgen , Feyer Petra , Fietkau Rainer , Haase Wulf , Harms Wolfgang , Hehr Thomas , Sedlmayer Felix , Souchon Rainer , Budach Wilfried ,   Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO)
Published: April 2021

Background: During the last decade, partial breast irradiation (PBI) has gained traction as a relevant treatment option for patients with early-stage low-risk breast cancer after breast-conserving surgery. The TARGIT-A prospective randomized trial compared a “risk-adapted” intraoperative radiotherapy (IORT) approach with 50-kv X-rays (INTRABEAM®) as the PBI followed by optional whole-breast irradiation (WBI) and conventional adjuvant WBI in terms of observed 5-year in-breast recurrence rates. Recently, long-term data were published. Since the first publication of the TARGIT-A trial, a broad debate has been emerged regarding several uncertainties and limitations associated with data analysis and interpretation. Our main objective was to summarize the data, with an emphasis on the updated report and the resulting implications. Summary: From our point of view, the previously unresolved questions still remain and more have been added, especially with regard to the study design, a change in the primary outcome measure, the significant number of patients lost to follow-up, and the lack of a subgroup analysis according to risk factors and treatment specifications. Key Message: Taking into account the abovementioned limitations of the recently published long-term results of the TARGIT-A trial, the German Society of Radiation Oncology (DEGRO) Breast Cancer Expert Panel adheres to its recently published recommendations on PBI: “the 50-kV system (INTRABEAM) cannot be recommended for routine adjuvant PBI treatment after breast-conserving surgery.”
Porchat e o caminho aos princípios
Authors: Zingano Marco
Published: April 2021

O texto busca apresentar a discussão em torno de Ciência e Dialética em Aristóteles, de Porchat.
Niilismo e crença no diálogo David Hume de Jacobi
Authors: Martin Luiz Fernando  Barrére
Published: April 2021

Podemos afirmar de modo fundamental que a crítica de Jacobi à filosofia deriva de seu afastamento do sensível em direção à constituição de verdades cada vez mais abstratas e passíveis de demonstração. Com isso a filosofia apenas conseguiu gerar disputas a respeito do que ela seja, sem conseguir demonstrar qual posição filosófica deu conta da tarefa e que terminam por levar à perda de confiança no empreendimento, ou em outras palavras, levar ao ceticismo. Trata-se aqui de, sem desconsiderar a influência da filosofia do senso comum de Thomas Reid, além em certa medida também da influência de Hume, como Jacobi procura sair desse impasse a partir do modo como compreende a noção de crença.
A revalorização filosófica da visão comum de mundo segundo Porchat e o equilíbrio reflexivo e a solução de problemas em metafilosofia
Authors: Bezerra Valter Alnis
Published: April 2021

Neste texto investigamos a compatibilidade entre o ceticismo de Oswaldo Porchat (em suas duas fases: a filosofia da Visão Comum de Mundo e o neopirronismo) e outras duas ideias metafilosóficas gerais, a saber, o equilíbrio reflexivo e a visão de solução de problemas. Procuramos mostrar de que modo o ceticismo e as outras duas ideias são compatíveis e iluminam-se mutuamente, e sugerimos uma articulação entre elas. O equilíbrio reflexivo ajuda a compreender a relação de uma filosofia cética e pós-cética, primeiro, com a vida comum e, depois, com o domínio fenomênico. O enfoque de solução de problemas é a perspectiva metafilosófica resgatada por Porchat em sua fase neopirrônica. Mostramos que, se na primeira fase do ceticismo porchatiano, o que está em equilíbrio com a vida comum ainda são teses filosóficas (não dogmáticas, mas que tenham como condição de contorno o lastro na vida comum), na segunda fase o que se pretende que esteja em equilíbrio com o domínio fenomênico é outro tipo de unidade epistêmica — os problemas, nomeadamente, aqueles problemas filosóficos que sejam passíveis de retradução a esse domínio fenomênico e oriundos de uma dinâmica de certo tipo. Para levar a cabo a análise, é crucial investigar as noções de fenômeno e de objetividade em Porchat. O texto se encerra com considerações sobre o lugar do conhecimento científico na visão de Porchat.
Anatomia e terapia da mente humana: o De intellectus emendatione de Espinosa
Authors: Chaui Marilena
Published: April 2021

O artigo busca reavaliar a tradição interpretativa do Tratactus de Intellectus Emendatione, propondo uma outra maneira de ler a primeira obra de Espinosa.
Sobre a maneira neopirrônica de agir e pensar
Authors: Smith Plínio Junqueira
Published: April 2021

O texto busca apresentar a atualização das atitudes céticas, como a suspensão do juízo, e sua incidência no campo da atitude nas ciências e na vida. Com o intuito de descrever em linhas gerais como é, ou pode ser, uma vida neopirrônica, para que o leitor julgue isso por si mesmo.
Uma amizade impensável
Authors: Gianotti José Arthur
Published: April 2021

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