bluuebunny/crossref_metadata_2025 huggingface dataset:
Baseline prognostic nutritional index and changes in pretreatment body mass index associate with immunotherapy response in patients with advanced cancer
Authors: Johannet Paul , Sawyers Amelia , Qian Yingzhi , Kozloff Samuel , Gulati Nicholas , Donnelly Douglas , Zhong Judy , Osman Iman
Published: November 2020

Background

Recent research suggests that baseline body mass index (BMI) is associated with response to immunotherapy. In this study, we test the hypothesis that worsening nutritional status prior to the start of immunotherapy, rather than baseline BMI, negatively impacts immunotherapy response.

Methods

We studied 629 patients with advanced cancer who received immune checkpoint blockade at New York University. Patients had melanoma (n=268), lung cancer (n=128) or other primary malignancies (n=233). We tested the association between BMI changes prior to the start of treatment, baseline prognostic nutritional index (PNI), baseline BMI category and multiple clinical end points including best overall response (BOR), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS).

Results

Decreasing pretreatment BMI and low PNI were associated with worse BOR (p=0.04 and p=0.0004), ORR (p=0.01 and p=0.0005), DCR (p=0.01 and p<0.0001), PFS (p=0.02 and p=0.01) and OS (p<0.001 and p<0.001). Baseline BMI category was not significantly associated with any treatment outcomes.

Conclusion

Standard of care measures of worsening nutritional status more accurately associate with immunotherapy outcomes than static measurements of BMI. Future studies should focus on determining whether optimizing pretreatment nutritional status, a modifiable variable, leads to improvement in immunotherapy response.
Benefit of endovascular thrombectomy for M2 middle cerebral artery occlusion in the ARISE II study
Authors: de Havenon Adam , Narata Ana Paula , Amelot Aymeric , Saver Jeffrey L , Bozorgchami Hormozd , Mattle Heinrich Paul , Ribo Marc , Andersson Tommy , Zaidat Osama O
Published: November 2020

Background

The benefit of endovascular thrombectomy for acute ischemic stroke with M2 segment middle cerebral artery occlusion remains controversial, with uncertainty and paucity of data specific to this population.

Objective

To compare outcomes between M1 and M2 occlusions in the Analysis of Revascularization in Ischemic Stroke with EmboTrap (ARISE II) trial.

Methods

We performed a prespecified analysis of the ARISE II trial with the primary outcome of 90-day modified Rankin Scale score of 0–2, which we termed good outcome. Secondary outcomes included reperfusion rates and major adverse events. The primary predictor was M2 occlusion, which we compared with M1 occlusion.

Results

We included 183 patients, of whom 126 (69%) had M1 occlusion and 57 (31%) had M2 occlusion. There was no difference in the reperfusion rates or adverse events between M2 and M1 occlusions. The rate of good outcome was not different in M2 versus M1 occlusions (70.2% vs 69.7%, p=0.946). In a logistic regression model adjusted for age, sex, and baseline National Institutes of Health Stroke Scale score, M2 occlusions did not have a significantly different odds of good outcome compared with M1 occlusions (OR 0.94, 95% CI 0.47 to 1.88, p=0.87).

Conclusion

In ARISE II, M2 occlusions achieved a 70.2% rate of good outcome at 90 days, which is above published rates for untreated M2 occlusions and superior to prior reports of M2 occlusions treated with endovascular thrombectomy. We also report similar rates of good outcome, successful reperfusion, death, and other adverse events when comparing the M1 and M2 occlusions.
Torrents of torment: turbulence as a mechanism of pulsatile tinnitus secondary to venous stenosis revealed by high-fidelity computational fluid dynamics
Authors: Pereira Vitor M , Cancelliere Nicole Mariantonia , Najafi Mehdi , MacDonald Dan , Natarajan Thangam , Radovanovic Ivan , Krings Timo , Rutka John , Nicholson Patrick , Steinman David A
Published: November 2020

Background

Pulsatile tinnitus (PT) is a debilitating condition that can be caused by a vascular abnormality, such as an arterial or venous lesion. Although treatment of PT-related venous lesions has been shown to successfully cure patients of the associated ‘tormenting’ rhythmical sound, much controversy still exists regarding their role in the etiology of PT.

Methods

A patient presented with a history of worsening, unilateral PT. A partial venous sinus obstruction related to the large arachnoid granulation was detected on the right side, and subsequently stented at the right transverse sinus. High-fidelity computational fluid dynamics (CFD) was performed on a 3D model digitally segmented from the pre-stent venogram, with assumed pulsatile flow rates. A post-stent CFD model was also constructed from this. Data-driven sonification was performed on the CFD velocity data, blinded to the patient’s self-reported sounds.

Results

The patient reported that the PT was completely resolved after stenting, and has had no recurrence of the symptoms after more than 2 years. CFD simulation revealed highly disturbed, turbulent-like flow at the sigmoid sinus close to auditory structures, producing a sonified audio signal that reproduced the subjective sonance of the patient’s PT. No turbulence or sounds were evident at the stenosis, or anywhere in the post-stent model.

Conclusions

For the first time, turbulence generated distal to a venous stenosis is shown to be a cause of PT. High-fidelity CFD may be useful for identifying patients with such ‘torrents’ of flow, to help guide treatment decision-making.
Neuralgic amyotrophy and hepatitis E infection: 6 prospective case reports
Authors: Garofoli Romain , Seror Paul , Zauderer Jennifer , Roren Alexandra , Guerini Henri , Rannou François , Drapé Jean-Luc , Nguyen Christelle , Lefèvre-Colau Marie-Martine
Published: November 2020

Introduction

Hepatitis E virus (HEV) represents the main cause of enterically transmitted hepatitis worldwide. It is known that neuralgic amyotrophy (NA) is one of the most frequent neurological manifestations of HEV. However, clinical, electrodiagnostic (EDX) and MRI characteristics, as well as long-term follow-up of HEV-related NA have not been fully described yet.

Case reports

We describe longitudinally clinical, EDX, biological and MRI results of six cases of HEV-associated NA, diagnosed from 2012 to 2017. Patients were between the ages of 33 and 57 years old and had a positive HEV serology. Clinical patterns showed the whole spectrum of NA, varying from extensive multiple mononeuropathy damage to single mononeuropathy. EDX results showed that the patients totalised 26 inflammatory mononeuropathies (1 to 8 per patient). These involved classical nerves such as suprascapular (6/6 cases), long thoracic (5/6 cases) and accessory spinal nerves (2/6 cases) and, some less frequent more distal nerves like anterior interosseous nerve (3/6 cases), as well as some unusual ones such as the lateral antebrachial cutaneous nerve (1/6 case), sensory fibres of median nerve (1/6 case) and phrenic nerves (1/6 case). After 2 to 8 years, all nerves had clinically recovered (muscle examination above 3/5 on MRC scale for all muscles except in one patient).

Discussion

HEV should be systematically screened when NA is suspected, whatever the severity, if the onset is less than 4 months (before IgM HEV-antibodies disappear) and appears to be frequently associated with severe clinical and EDX pattern, without increasing the usual recovery time.
Robust Distributed Filters Design for Discrete-Time Spatially Interconnected Systems with LFT Uncertainties
Authors: Feng Hongyan , Liu Wenhui , Chen Hui
Published: November 2020

In this paper, we investigate discrete-time uncertain spatially interconnected systems (USISs), where uncertainties are modeled by linear fractional transformation (LFT). First, the well-posedness, quadratic stability and contractiveness of discrete-time USISs are introduced. Second, a sufficient condition is proposed to guarantee that discrete-time USISs are well-posed, quadratically stable and contractive. Then, a more tractable condition is derived to check the well-posedness, quadratic stability and contractiveness of discrete-time USISs via a modified bilinear transformation. Besides, the robust distributed filters which inherit the structure of the plants are designed. A sufficient and necessary condition is presented to guarantee the existence of the robust distributed filters. Finally, a vehicle platoon model demonstrates the effectiveness of the proposed scheme.
SUPER COALESCENCE HIDDEN-VARIABLE FRACTAL INTERPOLATION FUNCTIONS
Authors: PRASAD SRIJANANI ANURAG
Published: November 2020

In this paper, a new notion of super coalescence hidden-variable fractal interpolation function (SCHFIF) is introduced. The construction of SCHFIF involves choosing an IFS from a pool of several non-diagonal IFS at each level of iteration. Further, the integral of a SCHFIF is studied and shown to be a SCHFIF passing through a different set of interpolation data.
Codimension bounds and rigidity of ancient mean curvature flows by the tangent flow at −∞
Authors: Stryker Douglas , Sun Ao
Published: November 2020

Motivated by the limiting behavior of an explicit class of compact ancient curve shortening flows, by adapting the work of Colding–Minicozzi[11], we prove codimension bounds for ancient mean curvature flows by their tangent flow at [Formula: see text]. In the case of the [Formula: see text]-covered circle, we apply this bound to prove a strong rigidity theorem. Furthermore, we extend this paradigm by showing that under the assumption of sufficiently rapid convergence, a compact ancient mean curvature flow is identical to its tangent flow at [Formula: see text].
On product-one sequences over dihedral groups
Authors: Geroldinger Alfred , Grynkiewicz David J. , Oh Jun Seok , Zhong Qinghai
Published: November 2020

Let [Formula: see text] be a finite group. A sequence over [Formula: see text] means a finite sequence of terms from [Formula: see text], where repetition is allowed and the order is disregarded. A product-one sequence is a sequence whose elements can be ordered such that their product equals the identity element of the group. The set of all product-one sequences over [Formula: see text] (with the concatenation of sequences as the operation) is a finitely generated C-monoid. Product-one sequences over dihedral groups have a variety of extremal properties. This paper provides a detailed investigation, with methods from arithmetic combinatorics, of the arithmetic of the monoid of product-one sequences over dihedral groups.
Bibliographic Study on the Difficulties Encountered by SMEs During the Implementation of Lean Manufacturing
Authors: Salma Arabi , Anas Chafi , Mohammed El Hammoumi
Published: November 2020

The reduction of wastes, improved industrial performance, and the SME environment are very important topics for the image of the organization. Recently, several business managers have implemented lean manufacturing in order to improve and optimize productivity and quality of production, some of them have achieved significant results while others have not yet succeeded in setting up lean manufacturing. The purpose of this paper is to provide an in-depth analysis of the implementation of lean manufacturing in SMEs worldwide, to identify and present the critical difficulties and obstacles that impact the implementation, and to highlight the success factors of manufacturing firms. The bibliographic study findings allowed us to collect a list of the difficulties that we classified according to the amount of occurrences which showed that five difficulties represent 77, 78% of the discontent causes, from what we note: the lack of leadership and the lack of commitment of top management; lack of financial resources; resistance to change; lack of training and knowledge about lean tools; and lack of know-how, skills and expertise. We noticed that these difficulties are extremely identical whether in Morocco or elsewhere in the world. In the same way, we have pointed out that the commitment of top management is a key factor that determines the success of the implementation and the success of the company. Finally, the novelty of our paper lies in the preliminary proposal of a model that explains the impact of the management commitment on the performance of the company, and on its customers and employees.
Color Tuning of Biomass-Derived Carbon Nanodots by Reaction Temperature Toward White Light-Emitting Diodes
Authors: Gong Yi , Han Yanbing , Zhang Fang , Zhai Mingyue , Chen Xing , Long Qiaoyin , Wang Ziyuan , Chen Fuchun , Yang Jianwen
Published: November 2020

In this work, carbon nanodots (CNDs) were synthesized from extract of mango leaves. Sphere nanodots were formed rapidly by one-step microwave heating. The photoluminescence (PL) of the CNDs was found greatly dependent on the reaction temperature. The emission peak position of the CNDs changed from 550[Formula: see text]nm to 430[Formula: see text]nm when the heating temperature increased from 120[Formula: see text]C to 150[Formula: see text]C. Particularly, the CNDs synthesized at 130[Formula: see text]C showed multi-band emission at 411[Formula: see text]nm, 480[Formula: see text]nm and 530[Formula: see text]nm, providing emitting color from blue to yellow. Moreover, the free chlorophyll molecules in the solution added red fluorescence at 670[Formula: see text]nm, and the integrated emitting color of the CNDs solution was close to white. Coated on a commercial 365[Formula: see text]nm light-emitting diode (LED) chip, the CNDs showed greenish white light with CIE coordinates of (0.37, 0.44). This work provided a one-pot, rapid and green method to obtain multi-emissive CNDs toward white LEDs.
Co3O4 Nanoparticles as a Noninvasive Electrochemical Sensor for Glucose Detection in Saliva
Authors: Wang Mei , Liu Fang , Zhang Zhifeng , Meng Erchao , Gong Feilong , Li Feng
Published: November 2020

A new noninvasive glucose sensor is developed based on Co3O4 particles (Co3O4 NPs), which are synthesized by a single-step hydrothermal method with uniform structure and size. The electrochemical measurements reveal that the device exhibits outstanding performance for glucose detection, achieving a maximal sensitivity of 2495.79[Formula: see text][Formula: see text]A mM[Formula: see text] cm[Formula: see text] with a high [Formula: see text] of 0.99575, a ultra-low detection limit of 9.3[Formula: see text]nM with a signal-to-noise of 3 and linear range up to 3[Formula: see text]mM. The noninvasive glucose sensor can respond swiftly and selectively due to the high electrocatalytic activity of Co3O4 NPs. The sensor also shows its high sensitivity and selectivity in detecting glucose levels in human blood serum and saliva sample, confirming the application potential of Co3O4 NPs in noninvasive detection of glucose.
Facile Fabrication of Free-Standing and Flexible Anodes Composed of Entangled N-Doped Carbon Nanotubes for Application in Lithium Ion Batteries
Authors: Tang Yihua , Wang Xinxin , Chen Jingjing , Liu Zehua , Mao Zhiyong , Wang Dajian
Published: November 2020

In this work, innate free-standing and flexible anode composed of entangled N-doped carbon nanotubes (CNTs) is fabricated by a facile annealing method following a simple compression without needing any tedious processing operations. The well cross-linked CNTs of the resultant free-standing anode enable robust diffusion channels for lithium ions and high flexibility. Served as the anode in lithium-ion batteries (LIBs) without the utilization of binder and current collector, the fabricated free-standing electrode can deliver a reversible area capacity of 2.14[Formula: see text]mAh[Formula: see text]cm[Formula: see text] at 1[Formula: see text]mA[Formula: see text]cm[Formula: see text] with superior cycling stability and excellent rate capability. The obtained reversible area capacity for the fabricated free-standing electrode material is much higher than that of the commercial graphite anode ([Formula: see text][Formula: see text]mAh[Formula: see text]cm[Formula: see text] at 1[Formula: see text]mA[Formula: see text]cm[Formula: see text]). Furthermore, the assembled full flexible battery utilizing the fabricated free-standing electrode also exhibits attractive performance and can substantially supply power for an electronic watch at flat and 180∘ bending positions, indicating the promising application in flexible electronic devices.
Improving the Performance of Near-infrared CuInSe2 Quantum Dots by Two Strategies: Doping and Ligand Exchange
Authors: Li Weili , Geng Hongchao , Yao Lu , Xu Haiyan , Han Yongjun , Sheng Pengtao
Published: November 2020

Oil phase CuInSe2 quantum dots (CISe QDs) were synthesized via a hot-injection method, exhibiting a near-infrared (NIR) emission wavelength of 710[Formula: see text]nm with poor fluorescence intensity. Therefore, we address this challenge by introducing two strategies: doping and ligand exchange. First, Zn was used as a dopant to improve the fluorescent properties of CISe QDs synthesized by the same method. The PL peak position of the resulting Zn–CuInSe (ZnCISe) QDs could be tuned from 600[Formula: see text]nm to 662[Formula: see text]nm, and the PL intensity of the QDs was greatly improved. Except that, this Zn doping strategy can help to improve the fluorescence lifetime and reduce defects, leading to increased quantum yield. Next, the aqueous phase transfer of ZnCISe QDs was achieved through an efficient ligand exchange strategy using glutathione (GSH) as the bifunctional ligand. Mercaptoacetic acid (MPA) was also used as an essential additive for GSH ligand exchange. With this method, we obtained high-quality hydrophilic ZnCISe QDs with particle sizes less than 3[Formula: see text]nm and good monodispersity. In addition, DLS measurements showed a unimodal peak shape of the hydrated ZnCISe QDs in ultrapure water with particle sizes ranging from 7[Formula: see text]nm to 40[Formula: see text]nm. Finally, the cytotoxicity studies revealed that the viabilities of the cells incubated with ZnCISe QDs from 1[Formula: see text][Formula: see text]g/mL to 18[Formula: see text][Formula: see text]g/mL remained at levels greater than 90%, which indicates that QDs with good biocompatibility are promising fluorescent probes.
Fee Complexity and Investor Mistakes in Retail Financial Markets
Authors: Kahraman Bige
Published: November 2020

Mutual funds sold via brokers offer fund portfolios that investors can purchase in one of three classes: A, B or C. These classes are distinguished only by their fee schedules and thus have different net performance results. An analysis of relative class performances for a set of U.S. mutual funds between 1992 and 2008 reveals a striking fact about class B: while classes A and C provide the best performance results at long and short holding periods, respectively, class B is dominated by either class A or C at any holding period. The inferiority yet popularity of class B at first suggests that naïve investors who do not understand the fee schedule of this class are being exploited. However, I propose two hypothetical clienteles which might rationally demand class B shares: one (a) with uncertain holding periods, or one (b) that desires to have long holding periods but is unable to commit to them. I identify whether investors rationally or naïvely purchase class B by examining the flow-fee sensitivity and estimating investor holding periods. My results support the naïve investor explanation.
A Bispectral Analysis of the Radio Emissions of Pulsar J0437-4715
Authors: Faustmann Alexander , Gilmore Jacki , van Tonder Vereese , Serylak Maciej
Published: November 2020

A combination of the very low signal-to-noise ratio and the very large parameter space spanned by pulsar emissions makes pulsar detection a challenging task. Currently, brute force parameter searches are often used for pulsar detection and a cyclostationary Gaussian model is assumed for pulsar emissions. Higher-Order spectra offer high signal-to-noise ratio domains in problems where the desired signal is polluted by Gaussian noise. The presence of nonzero higher-order spectral components in pulsar bursts may offer alternative detection methods. This work presents a review of higher-order statistics and offers a motivation for their use in the characterization of pulsar bursts. A dish from the MeerKAT telescope was used to acquire recorded radio bursts from pulsar J0437-4715. These bursts were found to contain nonzero bispectral components that were dispersed in the same way as the components of the power spectrum.
Survey on the Development of Aerial–Aquatic Hybrid Vehicles
Authors: Tan Yu Herng , Chen Ben M.
Published: November 2020

As the development of mobile robots matures, there is an increasing amount of interest in expanding the functionality of such robots through developing multimodal locomotion. As compared to land–water or land–air hybrids, the design of air–water vehicles is much less straightforward due to the fact that both mediums are three-dimensional fluid spaces and there is inherent disparity in fluid properties between them. As such, the development of these vehicles has received limited attention until very recently. Nevertheless, the potential applications of such vehicles range widely from military surveillance, oceanic data collection to heterogeneous robot team operation, which has led to an increasing number of projects working on aerial–aquatic hybrid mobility. In this paper, we discuss the fundamental challenges associated with aerial–aquatic hybrid locomotion as well as the necessary trade-offs in design decisions. We also summarize and review the existing work and prototypes of aerial–aquatic vehicles that have been designed thus far, analyzing the range of solutions that have been adopted to solve the aforementioned challenges. Lastly, the limitations of these solutions are analyzed to offer a perspective on how future developments in the area can enable greater functionality for the concept.
Treatment of Systemic Sclerosis Associated Interstitial Lung Disease
Authors: Tang Iris Yan Ki , Ho So
Published: November 2020

Systemic sclerosis (SSc) is a systemic connective tissue disorder characterized by progressive skin and visceral organ fibrosis, vasculopathy, and immune dysregulation. Interstitial lung disease (ILD) is a common manifestation and major contributor to morbidity and mortality. Immunosuppression is usually indicated for extensive or progressive SSc-ILD. Recently, antifibrotic and biological therapies have been shown to be efficacious in treating SSc-ILD in various studies. In this article, we will descriptively review the latest evidence on the treatment of SSc-ILD.
Decentralized Computing
Authors: Kelly Terence
Published: November 2020

Feeding all relevant inputs to a central solver is the obvious way to tackle a problem, but it's not always the only way.
Decentralized
methods that make do with only local communication and local computation are sometimes the best way. This episode of Drill Bits reviews an elegant protocol for self-organizing wireless networks that can also solve a seemingly impossible
social
networking problem. The protocol preserves privacy among participants and is so simple that it can be implemented with pencil, paper, and postcards. Example software implements both the decentralized protocol and a centralized solver.
In vitro and in vivo cardiac toxicity of flavored electronic nicotine delivery systems
Authors: Abouassali Obada , Chang Mengmeng , Chidipi Bojjibabu , Martinez Jose Luis , Reiser Michelle , Kanithi Manasa , Soni Ravi , McDonald Thomas V. , Herweg Bengt , Saiz Javier , Calcul Laurent , Noujaim Sami F.
Published: November 2020

The use of electronic nicotine delivery systems (ENDS) is not harm free. It is not known whether ENDS negatively affect cardiac electrophysiological function. Our study in cell lines and in mice shows that ENDS can compromise cardiac electrophysiology, leading to action potential instability and inducible ventricular arrhythmias. Further investigations are necessary to assess the long-term cardiac safety profile of ENDS products in humans and to better understand how individual components of ENDS affect cardiac toxicity.
Acute e-cig inhalation impacts vascular health: a study in smoking naïve subjects
Authors: Chatterjee Shampa , Caporale Alessandra , Tao Jian Qin , Guo Wensheng , Johncola Alyssa , Strasser Andrew A. , Leone Frank T. , Langham Michael C. , Wehrli Felix W.
Published: November 2020

Endothelial cell signaling and blood biomarkers were found to correlate with functional vascular changes in a single episode e-cigarettes inhalation in healthy adults. This is indicative of the potential of e-cigarettes (even when inhaled acutely) to lead of vascular dysfunction.
Impact of anesthesia, sex, and circadian cycle on renal afferent nerve sensitivity
Authors: DeLalio Leon J. , Stocker Sean D.
Published: November 2020

We determined the impact of anesthesia, sex, and circadian cycle on renal afferent nerve (ARNA) sensitivity to chemical and mechanical stimuli. ARNA sensitivity to renal capsaicin infusion was greatest in decerebrate > Inactin > urethane or isoflurane groups. Elevated renal pelvic pressure significantly increased ARNA; decerebrate and Inactin groups exhibited the greatest ARNA sensitivity. Sex differences in renal afferent responses were not consistently observed. Circadian cycle altered chemosensory but not mechanosensory responses.
Research on Ambiguity Resolution Algorithm by Quaternion Based on Acoustic Vector Sensor
Authors: Wang Guibao , Wang Xinkuan , Wang Lanmei , Wang Xiangyu
Published: November 2020

The increase in element spacing can increase the aperture of the array and improve its resolution performance. However, phase ambiguity will occur when the array element interval is larger than the minimum half wavelength of the incident signal. The three acoustic velocity components of the acoustic vector are ingeniously constructed into a new kind of quaternions because of the special structure of the acoustic vector sensor array, and the rough estimation of the direction of arrival (DOA) is obtained using the rotation relationship between the subarray steering vectors corresponding to quaternion data. The rough estimate is used to resolve the phase ambiguity of the spatial phase difference between the array elements, and the high-precision DOA estimation of the signal can be obtained. Simulation results show that the method is effective.
Regulatory Effects of Nur77 on Airway Remodeling and ASMC Proliferation in House Dust Mite-Induced Asthma
Authors: Wang Kun , Wang Muyun , Shang Yan , He Yanan , Li Qiang , Gao Wei , Yin Huiming
Published: November 2020

Airway remodeling played a vital role in the development of asthma, and airway smooth muscle (ASM) mass was its hallmark. However, few strategies targeting ASM remodeling were developed in treating asthma. Nur77 was the transcription factor nuclear receptor involved in the pathogenesis of several lung diseases. Nur77 distribution and expression were determined in an HDM-mediated allergic asthma model. Its effect on airway hyperresponsiveness (AHR), chronic inflammation, and ASM remodeling in asthmatic mice was evaluated using a lentivirus-mediated shRNA. Possible mechanisms were explored by examining Nur77 actions and its underlying pathways in primary human AMC cells (ASMCs). In this study, we reported that Nur77 expression was mainly distributed along ASM and increased in lungs of HDM-challenged mice. Nur77 depletion by lentivirus-mediated shRNA ameliorated AHR, chronic inflammation, goblet cell hyperplasia, and airway remodeling in the asthmatic mouse model. By means of primary human ASMC, we discovered that Nur77 upregulation by HDM stimulation promoted cell proliferation and ROS production, as well as reduced antioxidant gene expression. These alterations might associate with MFN2/MAPK/AKT pathways. These findings broadened our understanding of airway remodeling and ASMC proliferation, which might provide a novel therapeutic target for asthma patients.
Some Existence Results for a System of Nonlinear Fractional Differential Equations
Authors: Ameer Eskandar , Aydi Hassen , Işık Hüseyin , Nazam Muhammad , Parvaneh Vahid , Arshad Muhammad
Published: November 2020

In this paper, we show that a sequence satisfying a Suzuki-type JS-rational contraction or a generalized Suzuki-type Ćirić JS-contraction, under some conditions, is a Cauchy sequence. This paper presents some common fixed point theorems and an application to resolve a system of nonlinear fractional differential equations. Some examples and consequences are also given.
The Impact of Diabetes Mellitus in COVID-19: A Mechanistic Review of Molecular Interactions
Authors: Yaribeygi Habib , Sathyapalan Thozhukat , Jamialahmadi Tannaz , Sahebkar Amirhossein
Published: November 2020

The ongoing pandemic of COVID-19 is now the major issue in global health. Evidence implies that patients with diabetes are at a higher risk of severe disease or death due to COVID-19 than individuals without diabetes. However, the underlying mechanism for this differential effect in individuals with and without diabetes is not clearly understood. We have reviewed the pathophysiological pathways which may facilitate the entry of virus or an increase in its infectivity in host cells in the diabetic milieu. We suggest that the preexisting pathological pathways in patients with poorly controlled diabetes increase the risk of infectivity and are responsible for the higher levels of tissue injury and death in patients with diabetes.
A Data Mining Method Using Deep Learning for Anomaly Detection in Cloud Computing Environment
Authors: Gao Jin , Liu Jiaquan , Guo Sihua , Zhang Qi , Wang Xinyang
Published: November 2020

Aiming at problems such as slow training speed, poor prediction effect, and unstable detection results of traditional anomaly detection algorithms, a data mining method for anomaly detection based on the deep variational dimensionality reduction model and MapReduce (DMAD-DVDMR) in cloud computing environment is proposed. First of all, the data are preprocessed by a dimensionality reduction model based on deep variational learning and based on ensuring complete data information as much as possible, the dimensionality of the data is reduced, and the computational pressure is reduced. Secondly, the data set stored on the Hadoop Distributed File System (HDFS) is logically divided into several data blocks, and the data blocks are processed in parallel through the principle of MapReduce, so the k-distance and LOF value of each data point can only be calculated in each block. Thirdly, based on stochastic gradient descent, the concept of k-neighboring distance is redefined, thus avoiding the situation where there are greater than or equal to k-repeated points and infinite local density in the data set. Finally, compared with CNN, DeepAnt, and SVM-IDS algorithms, the accuracy of the scheme is increased by 10.3%, 18.0%, and 17.2%, respectively. The experimental data set verifies the effectiveness and scalability of the proposed DMAD-DVDMR algorithm.
Radon-222 Exposure and Dose Concentration Levels in Jordanian Dwellings
Authors: Al-Kazwini Akeel T. , Al-Arnaout Mohannad M. , Abdulkareem Tiba R.
Published: November 2020

Exposure to high concentrations of radon gas is the leading cause of lung cancer for nonsmokers according to the World Health Organization (WHO) figures. With poor ventilation standards and lack of awareness among Jordanians, constant monitoring of radon concentrations is vital. Multiple efforts have been made since the 1990s in order to create a national radon map of Jordan, by acquiring average values of radon concentrations in major Jordanian cities. This study aims to replicate those efforts using a more accurate and modern way of detection for the purpose of comparing the current values with literature values and to update the previous radon concentration map of Jordan. The study concludes that radon concentrations in Jordan have mostly increased in the past 30 years from an overall average of 52 Bq/m3 to an average of 60.4 Bq/m3. Despite the increase, these results are considered under the threat line that is estimated conventionally by most of the international environmental and radiation-related organizations, which is 100–300 Bq/m3. It should be noted that only the Russeifa city has scored a value higher than the estimated threat line. This is due to the existence of abundant phosphate mines filled with condensed radon levels leaking from these ores. It is expected that radon concentrations in Jordan will increase in the coming years with the continuous urban sprawl and lack of public awareness about the radon gas health issue. A number of suggestions have been proposed in this study that could help the Jordanian society avoid a future possible health threat.
Detection of Genetic Mutations by Next-Generation Sequencing for Predicting Prognosis of Extensive-Stage Small-Cell Lung Cancer
Authors: Chen Dongfang , Xu Jianlin , Qiao Rong , Zhao Yizhuo , Chu Tianqing , Han Baohui , Zhong Runbo
Published: November 2020

Some studies have revealed that specific genetic mutations could be associated with chemotherapy response or even survival in small-cell lung cancer (SCLC). Our retrospective study aimed to identify the correlation between genetic mutations and progression-free survival (PFS) in extensive-stage SCLC after first-line chemotherapy. A total of 75 patients with extensive-stage SCLC confirmed by histopathology from February 2018 to February 2019 were retrospectively analyzed. The biopsy specimens of all patients were analyzed by Next-Generation Sequencing (NGS). All patients received first-line chemotherapy and follow-up at Shanghai Chest Hospital. Eleven genes were mutated in, at least, 10% of the 75 patients, including TP53 (96%), RB1 (77%), SMAD4 (32%), NOTCH1 (21%), PTEN (16%), FGFR1 (16%), KDR (15%), PIK3CA (15%), ROS1 (15%), BRCA2 (13%), and ERBB4 (10%). The median number of mutated genes among all patients was 5. Patients with more than 5 mutated genes (PFS = 6.7 months,

P
=
0.004

), mutant TP53 (PFS = 5.0 months,

P
=
0.011

), and mutant BRCA2 (PFS = 6.7 months,

P
=
0.046

) had better PFS after first-line chemotherapy than other patients. Multivariate Cox regression analysis showed that patients who achieved a PR (HR 3.729, 95% CI 2.038–6.822), had more than 5 mutated genes (HR 1.929, 95% CI 1.096–3.396), had BRCA2 mutations (HR 4.581, 95% CI 1.721–12.195), and had no liver metastasis (HR 0.415, 95% CI 0.181–0.951) showed improvements in PFS after first-line chemotherapy. In conclusion, the number of mutated genes and BRCA2 mutation status in extensive-stage SCLC were significantly related to PFS after first-line chemotherapy.
Human Periodontal Ligament Stem Cell-Derived Exosomes Promote Bone Regeneration by Altering MicroRNA Profiles
Authors: Liu Ting , Hu Wenyun , Zou Xue , Xu Jingchen , He Shushu , Chang Le , Li Xinyi , Yin Yuanyuan , Tian Mi , Li Ziyu , Zhou Jialiang , Jiang Xiaoge , Chen Song
Published: November 2020

The role and underlying mechanism of exosomes derived from human periodontal ligament stem cells (PDLSC) in osteogenesis are unclear. In the present study, we identified the exosomes derived from PDLSCs and found that osteogenic induction can enhance the osteogenic ability of PDLSC-derived exosomes in promoting the osteogenic differentiation of rat bone marrow stem cells (BMSCs). To investigate the underlying mechanism, we analyzed the exosomal miRNA expression profiles of undifferentiated and osteogenic differentiated PDLSCs by RNA sequencing. The results showed that seventy-two miRNAs were upregulated and thirty-five miRNAs were downregulated after osteogenic induction. The results of Gene Ontology analysis and pathway analysis demonstrated that the target genes of differentially expressed exosomal miRNAs participate in the regulation of a variety of biological processes, such as catalytic activity, protein binding, metabolic processes, cell development, and differentiation, and are enriched in osteogenic differentiation-related pathways, such as MAPK signaling, AMPK signaling, and insulin signaling pathways. Our results reveal for the first time that the exosomal miRNAs derived from osteogenic differentiated PDLSCs may promote the osteogenic differentiation of BMSCs, which provides a basis for further research on the regulatory function of exosomal miRNA of PDLSCs during osteogenesis.
4-tert-Octylphenol Exposure Disrupts Brain Development and Subsequent Motor, Cognition, Social, and Behavioral Functions
Authors: Tran Dinh Nam , Jung Eui-Man , Yoo Yeong-Min , Jeung Eui-Bae
Published: November 2020

The endocrine-disrupting chemical 4-tert-octylphenol (OP) is a widespread estrogenic chemical used in consumer products such as epoxy resins and polycarbonate plastic. However, the effects of OP on brain development are unknown. The present study examined the effects of OP on neuron and neurobehavioral development in mice. By using primary cortical neuron cultures, we found that OP-treated showed a decreased length of axons and dendrites and an increased number of primary and secondary dendrites. OP reduced bromodeoxyuridine (BrdU), mitotic marker Ki67, and phospho-histone H3 (p-Histone-H3), resulting in a reduction of neuronal progenitor proliferation in offspring mouse brain. Moreover, OP induced apoptosis in neuronal progenitor cells in offspring mouse brain. Furthermore, offspring mice from OP-treated dams showed abnormal cognitive, social, and anxiety-like behaviors. Taken together, these results suggest that perinatal exposure to OP disrupts brain development and behavior in mice.
Analysis of Factors Affecting the Severity of Automated Vehicle Crashes Using XGBoost Model Combining POI Data
Authors: Chen Hengrui , Chen Hong , Liu Zhizhen , Sun Xiaoke , Zhou Ruiyu
Published: November 2020

The research and development of autonomous vehicle (AV) technology have been gaining ground globally. However, a few studies have performed an in-depth exploration of the contributing factors of crashes involving AVs. This study aims to predict the severity of crashes involving AVs and analyze the effects of the different factors on crash severity. Crash data were obtained from the AV-related crash reports presented to the California Department of Motor Vehicles in 2019 and included 75 uninjured and 18 injured accident cases. The points-of-interest (POI) data were collected from Google Map Application Programming Interface (API). Descriptive statistics analysis was applied to examine the features of crashes involving AVs in terms of collision type, crash severity, vehicle movement preceding the collision, and degree of vehicle damage. To compare the classification performance of different classifiers, we use two different classification models: eXtreme Gradient Boosting (XGBoost) and Classification and Regression Tree (CART). The result shows that the XGBoost model performs better in identifying the injured crashes involving AVs. Compared with the original XGBoost model, the recall and G-mean of the XGBoost model combining POI data improved by 100% and 11.1%, respectively. The main features that contribute to the severity of crashes include weather, degree of vehicle damage, accident location, and collision type. The results indicate that crash severity significantly increases if the AVs collided at an intersection under extreme weather conditions (e.g., fog and snow). Moreover, an accident resulting in injuries also had a higher probability of occurring in areas where land-use patterns are highly diverse. The knowledge gained from this research could ultimately contribute to assessing and improving the safety performance of the current AVs.
A High-Content Screen Identifies Drugs That Restrict Tumor Cell Extravasation across the Endothelial Barrier
Authors: Hilfenhaus Georg , Mompeón Ana , Freshman Jonathan , Prajapati Divya P. , Hernandez Gloria , Freitas Vanessa M. , Ma Feiyang , Langenbacher Adam D. , Mirkov Snezana , Song Dana , Cho Byoung-Kyu , Goo Young Ah , Pellegrini Matteo , Chen Jau-Nian , Damoiseaux Robert , Iruela-Arispe M. Luisa
Published: November 2020

Metastases largely rely on hematogenous dissemination of tumor cells via the vascular system and significantly limit prognosis of patients with solid tumors. To colonize distant sites, circulating tumor cells must destabilize the endothelial barrier and transmigrate across the vessel wall. Here we performed a high-content screen to identify drugs that block tumor cell extravasation by testing 3,520 compounds on a transendothelial invasion coculture assay. Hits were further characterized and validated using a series of in vitro assays, a zebrafish model enabling three-dimensional (3D) visualization of tumor cell extravasation, and mouse models of lung metastasis. The initial screen advanced 38 compounds as potential hits, of which, four compounds enhanced endothelial barrier stability while concurrently suppressing tumor cell motility. Two compounds niclosamide and forskolin significantly reduced tumor cell extravasation in zebrafish, and niclosamide drastically impaired metastasis in mice. Because niclosamide had not previously been linked with effects on barrier function, single-cell RNA sequencing uncovered mechanistic effects of the drug on both tumor and endothelial cells. Importantly, niclosamide affected homotypic and heterotypic signaling critical to intercellular junctions, cell–matrix interactions, and cytoskeletal regulation. Proteomic analysis indicated that niclosamide-treated mice also showed reduced levels of kininogen, the precursor to the permeability mediator bradykinin. Our findings designate niclosamide as an effective drug that restricts tumor cell extravasation through modulation of signaling pathways, chemokines, and tumor–endothelial cell interactions.

Significance:

A high-content screen identified niclosamide as an effective drug that restricts tumor cell extravasation by enhancing endothelial barrier stability through modulation of molecular signaling, chemokines, and tumor–endothelial cell interactions.
Could HPV Testing on Self-collected Samples Be Routinely Used in an Organized Cervical Screening Program? A Modeled Analysis
Authors: Smith Megan A. , Hall Michaela T. , Saville Marion , Brotherton Julia M.L. , Simms Kate T. , Lew Jie-Bin , Bateson Deborah , Skinner S. Rachel , Kelaher Margaret , Canfell Karen
Published: November 2020

Background:

Cervical screening on self-collected samples has mainly been considered for targeted use in underscreened women. Updated evidence supports equivalent sensitivity of PCR-based human papillomavirus (HPV) testing on self-collected and clinician-collected samples.

Methods:

Using a well-established model, we compared the lifetime impact on cancer diagnoses and deaths resulting from cervical screening using self-collected samples only, with and without the existing restriction in Australia to women aged 30+ years and ≥2 years overdue, compared with the mainstream program of 5-yearly HPV screening on clinician-collected samples starting at 25 years of age. We conservatively assumed sensitivity of HPV testing on self-collected relative to clinician-collected samples was 0.98. Outcomes were estimated either in the context of HPV vaccination (“routinely vaccinated cohorts;” uptake as in Australia) or in the absence of HPV vaccination (“unvaccinated cohorts”).

Results:

In unvaccinated cohorts, the health benefits of increased participation from self-collection outweighed the worst case (2%) loss of relative test sensitivity even if only 15% of women, who would not otherwise attend, used it (“additional uptake”). In routinely vaccinated cohorts, population-wide self-collection could be marginally (0.2%–1.0%) less effective at 15% additional uptake but 6.2% to 12.4% more effective at 50% additional uptake. Most (56.6%–65.0%) of the loss in effectiveness in the restricted self-collection pathway in Australia results from the requirement to be 2 or more years overdue.

Conclusions:

Even under pessimistic assumptions, any potential loss in test sensitivity from self-collection is likely outweighed by improved program effectiveness resulting from feasible levels of increased uptake.

Impact:

Consideration could be given to offering self-collection more widely, potentially as an equal choice for women.

See related commentary by Lim, p. 245
Systemic Effects of Radiation Therapy-Induced Abscopal Responses in Patients with Advanced Lung Cancer
Authors: D’Andrea Mark A. , Reddy G. Kesava
Published: November 2020

Background: Out-of-field tumor regression effects of radiation therapy (abscopal response) have been sporadically observed in the past, but they have only recently gained significant importance due to the use of innovative high-precision radiation delivery devices for the treatment of various cancers including non-small cell lung cancer (NSCLC). In this study, we provide a detailed overview of the current state of knowledge and clinical experience of radiation therapy-induced abscopal effects in patients with advanced NSCLC. Summary: Peer-reviewed published clinical evidence on the abscopal effect of radiation therapy was collected using electronic databases such as MEDLINE via PubMed and Google Scholar. The clinical data on the abscopal effect of radiation therapy were reviewed and the outcomes have been summarized. Most studies describing the abscopal effects of radiation therapy in patients with advanced NSCLC have been in the form of either case reports or small cohort studies. Although the exact molecular mechanisms for the abscopal effect are yet to be established, current evidence indicates that tumor cell destruction induced by local radiation therapy releases tumor antigens, which stimulate the immune system of the host to activate the body’s immune effector cells systemically and trigger the regression of distant nonirradiated cancer cells. These off-target antitumor effects of radiation therapy provide an opportunity to explore the use of the radiation therapy in combination with novel immunotherapy agents to maximize treatment outcomes in patients with advanced NSCLC and other cancers. Key Message: The findings suggest that radiation therapy has the ability to induce abscopal effects with an increased potential to boost these effects when it is used in combination with immunotherapy for the treatment of patients with advanced NSCLC and other cancers. Clinical trials investigating radiation therapy-induced abscopal effects may lead to a dramatic change in its use especially when it is combined with immunotherapy for the treatment of patients with advanced NSCLC.