bluuebunny/crossref_metadata_2025 huggingface dataset:
ADAM15 Participates in Tick-Borne Encephalitis Virus Replication
Authors: Yang Qi , Pei Rongjuan , Wang Yun , Zhou Yuan , Yang Min , Chen Xinwen , Chen Jizheng
Published: November 2020

Tick populations are increasing, and their geographic ranges are expanding. Increases in tick-borne disease prevalence and transmission are important public health issues.
Insulin sensitivity predicts cognitive decline in individuals with prediabetes
Authors: Willmann Caroline , Brockmann Kathrin , Wagner Robert , Kullmann Stephanie , Preissl Hubert , Schnauder Günter , Maetzler Walter , Gasser Thomas , Berg Daniela , Eschweiler Gerhard W , Metzger Florian , Fallgatter Andreas J , Häring Hans-Ulrich , Fritsche Andreas , Heni Martin
Published: November 2020

Introduction

Epidemiological studies indicate an association between type 2 diabetes and cognitive dysfunction that appear to start already in the prediabetic state. Although cross-sectional studies have linked insulin resistance to impaired cognition, the potential predictive value of insulin resistance has not yet been sufficiently studied longitudinally without confounding by overt diabetes (and its pharmacological treatment).

Research design and methods

We investigated longitudinal data from participants of the ‘Tübinger Evaluation of Risk Factors for Early Detection of Neurodegeneration’ Study. Subjects underwent a neurocognitive assessment battery (CERAD Plus battery; Consortium to Establish a Registry for Alzheimer’s Disease) at baseline and followed every 2 years (median follow-up 4.0 Q1–3: 2.2–4.3 years). Subjects within a pre-diabetic glycated hemoglobin range of 5.6%–6.5% underwent 5-point 75 g oral glucose tolerance tests (OGTTs) with assessment of insulin sensitivity and insulin secretion (n=175). Subjects with newly diagnosed diabetes mellitus or with major depressivity (Beck Depression Inventory >20) were excluded (n=15). Data were analyzed by mixed models using sex, age and glycemic trait as fixed effects. Subject and time since first measurement were used as random effects.

Results

Insulin sensitivity was positively associated with the CERAD sum score (higher is better) in a time-dependent manner (p=0.0057). This result is mainly driven by a steeper decrease in the memory domain associated with lower insulin sensitivity (p=0.029). The interaction between age and insulin sensitivity was independent of glycemia (p=0.02). There was also no association between insulin secretion and cognition.

Conclusions

Insulin resistance rather than sole elevation of blood glucose predicts cognitive decline, specifically in the memory domain, in persons with prediabetes. Treatments of diabetes that improve insulin sensitivity might therefore have the potential to postpone or even prevent cognitive decline in patients with diabetes.
Methotrexate and prednisolone study in erythema nodosum leprosum (MaPs in ENL) protocol: a double-blind randomised clinical trial
Authors: de Barros Barbara , Lambert Saba M , Shah Mahesh , Pai Vivek V , Darlong Joydeepa , Rozario Benjamin Jewel , Alinda Medhi Denisa , Sales Anna M , Doni Shimelis , Hagge Deanna A , Shrestha Dilip , Listiawan M. Yulianto , Yitaye Abeba M , Nery Jose A C , Neupane Kapil D , Dias Vivianne L A , Butlin C. Ruth , Nicholls Peter G , Lockwood Diana , Walker Stephen L
Published: November 2020

Introduction

Erythema nodosum leprosum (ENL) is an immunological complication of leprosy. ENL results in morbidity and disability and if it is not treated can lead to death. The current treatment consists of thalidomide or high doses of oral corticosteroids for prolonged periods. Thalidomide is not available in many leprosy endemic countries. The use of corticosteroids is associated with morbidity and mortality. Identifying treatment regimens that reduce the use of corticosteroids in ENL is essential. Methotrexate (MTX) is used to treat many inflammatory diseases and has been used successfully to treat patients with ENL not controlled by other drugs, including prednisolone and thalidomide. We present the protocol of the ‘MTX and prednisolone study in ENL’ (MaPs in ENL) a randomised controlled trial (RCT) designed to test the efficacy of MTX in the management of ENL.

Methods and analysis

MaPs in ENL is an international multicentre RCT, which will be conducted in leprosy referral centres in Bangladesh, Brazil, Ethiopia, India, Indonesia and Nepal. Patients diagnosed with ENL who consent to participate will be randomly allocated to receive 48 weeks of weekly oral MTX plus 20 weeks of prednisolone or 48 weeks of placebo plus 20 weeks of prednisolone. Participants will be stratified by type of ENL into those with acute ENL and those with chronic and recurrent ENL. The primary objective is to determine whether MTX reduces the requirement for additional prednisolone. Patients’ reported outcome measures will be used to assess the efficacy of MTX. Participants will be closely monitored for adverse events.

Ethics and dissemination

Results will be submitted for publication in peer-reviewed journals. Ethical approval was obtained from the Observational/Interventions Research Ethics Committee of the London School of Hygiene & Tropical Medicine (15762); The Leprosy Mission International Bangladesh Institutional Research Board (in process); AHRI-ALERT Ethical Review Committee, Ethiopia; Ethics Committee of the Managing Committee of the Bombay Leprosy Project; and The Leprosy Mission Trust India Ethics Committee; the Nepal Health and Research Council and Health Research Ethics Committee Dr. Soetomo, Indonesia. This study is registered at www.clinicaltrials.gov. This is the first RCT of MTX for ENL and will contribute to the evidence for the management of ENL.

Trial registration number

NCT 03775460.
Role of echocardiography in screening and evaluation of athletes
Authors: Niederseer David , Rossi Valentina Alice , Kissel Christine , Scherr Johannes , Caselli Stefano , Tanner Felix C , Bohm Philipp , Schmied Christian
Published: November 2020

The term athlete’s heart describes structural, functional and electrical adaptations of the cardiovascular system due to repetitive intense exercise. Physiological cardiac adaptations in athletes, however, may mimic features of cardiac diseases and therefore make it difficult to distinguish physiological adaptions from disease. Furthermore, regular exercise may also lead to pathological adaptions that can promote or worsen cardiac disease (eg, atrial dilation/atrial fibrillation, aortic dilation/aortic dissection and rhythm disorders). Sudden cardiac death (SCD) is a major concern in sports cardiology, and preparticipation screening (PPS) has demonstrated to be effective in identifying athletes at risk for SCD. In Europe, PPS is advocated to include personal and family history, physical examination and ECG, with further workup including echocardiography only if the initial screening investigations show abnormal findings. We review the current available evidence for echocardiography as a screening tool for conditions associated with SCD in recreational and professional athletes and advocate to include screening echocardiography to be performed at least twice in an athlete’s career. We recommend that the first echocardiography is performed during adolescence to rule out structural heart conditions associated with SCD that cannot be detected by ECG, especially mitral valve prolapse, coronary artery anomalies, bicuspid aortic valve and dilatation of the aorta. A second echocardiography could be performed from the age of 30–35 years, when athletes age and become master athletes, to especially evaluate pathological cardiac remodelling to exercise (eg, atrial and/or right ventricular dilation), late onset cardiomyopathies and wall motion abnormalities due to myocarditis or coronary artery disease.
Interleukin-15 and cancer: some solved and many unsolved questions
Authors: Fiore Piera Filomena , Di Matteo Sabina , Tumino Nicola , Mariotti Francesca Romana , Pietra Gabriella , Ottonello Selene , Negrini Simone , Bottazzi Barbara , Moretta Lorenzo , Mortier Erwan , Azzarone Bruno
Published: November 2020

Soluble interleukin (IL)-15 exists under two forms: as monomer (sIL-15) or as heterodimeric complex in association with sIL-15Rα (sIL-15/IL-15Rα). Both forms have been successfully tested in experimental tumor murine models and are currently undergoing investigation in phase I/II clinical trials. Despite more than 20 years research on IL-15, some controversial issues remain to be addressed. A first point concerns the detection of the sIL-15/IL-15Rα in plasma of healthy donors or patients with cancer and its biological significance. The second and third unsolved question regards the protumorigenic role of the IL-15/IL-15Rα complex in human cancer and the detrimental immunological consequences associated to prolonged exposure of natural killer (NK) cells to both forms of soluble IL-15, respectively. Data suggest that in vivo prolonged or repeated exposure to monomeric sIL-15 or the soluble complex may lead to NK hypo-responsiveness through the expansion of the CD8+/CD44+T cell subset that would suppress NK cell functions. In vitro experiments indicate that soluble complex and monomeric IL-15 may cause NK hyporesponsiveness through a direct effect caused by their prolonged stimulation, suggesting that this mechanism could also be effective in vivo. Therefore, a better knowledge of IL-15 and a more appropriate use of both its soluble forms, in terms of concentrations and time of exposure, are essential in order to improve their therapeutic use. In cancer, the overproduction of sIL-15/IL-15Rα could represent a novel mechanism of immune escape. The soluble complex may act as a decoy cytokine unable to efficiently foster NK cells, or could induce NK hyporesponsiveness through an excessive and prolonged stimulation depending on the type of IL-15Rα isoforms associated. All these unsolved questions are not merely limited to the knowledge of IL-15 pathophysiology, but are crucial also for the therapeutic use of this cytokine. Therefore, in this review, we will discuss key unanswered issues on the heterogeneity and biological significance of IL-15 isoforms, analyzing both their cancer-related biological functions and their therapeutic implications.
SMART U(1)$$_X$$: standard model with axion, right handed neutrinos, two Higgs doublets and U(1)$$_X$$ gauge symmetry
Authors: Okada Nobuchika , Raut Digesh , Shafi Qaisar
Published: November 2020

To address five fundamental shortcomings of the Standard Model (SM) of particle physics and cosmology, we propose a phenomenologically viable framework based on a $$U(1)_X \times U(1)_{PQ}$$

U

(
1
)

X

×
U

(
1
)

PQ

extension of the SM, that we call “SMART U(1)$$_X$$

X

”. The $$U(1)_X$$

U

(
1
)

X

gauge symmetry is a well-known generalization of the $$U(1)_{B-L}$$

U

(
1
)

B
-
L

symmetry and $$U(1)_{PQ}$$

U

(
1
)

PQ

is the global Peccei–Quinn (PQ) symmetry. Three right handed neutrinos are added to cancel $$U(1)_X$$

U

(
1
)

X

related anomalies, and they play a crucial role in understanding the observed neutrino oscillations and explaining the observed baryon asymmetry in the universe via leptogenesis. Implementation of PQ symmetry helps resolve the strong CP problem and also provides axion as a compelling dark matter (DM) candidate. The $$U(1)_X$$

U

(
1
)

X

gauge symmetry enables us to implement the inflection-point inflation scenario with $$H_{inf} \lesssim 2 \times 10^{7}$$

H

inf

≲
2
×

10
7

 GeV, where $$H_{inf}$$

H

inf

is the value of Hubble parameter during inflation. This is crucial to overcome a potential axion domain wall problem as well as the axion isocurvature problem. The SMART U(1)$$_X$$

X

framework can be successfully implemented in the presence of SU(5) grand unification, as we briefly show.
Titration of Adenine in a GA Mismatch with Grand Canonical Simulations
Authors: Huai Zhe , Sun Zhaoxi
Published: November 2020

Computational prediction of the pKa of ionizable groups remains a central challenge in biomolecular modeling. Although all-atom fixed-charge force fields could be accurate to describe the interaction network within the biomolecules, proper sampling techniques are required to obtain the thermodynamic information in the (de)protonation event. Sufficient sampling requires an ensemble of structures from simulations with proper treatments of the acid-base equilibria, and the grand canonical simulation technique could be used to model the growth/annihilation of hydrogen atoms by merging Hamiltonians of different protonation states into one simulation ensemble. The electrostatic feature of nucleotide systems is especially difficult to model, and the situation becomes more challenging when the ionizable site is highly perturbed. Although there are many successful predictions obtained from the grand canonical constant pH simulations, few reports focus on highly perturbed nucleotide systems with unconventional base-pair features. In this work, with the discrete constant pH method, we investigate the titration thermodynamics of an adenine in the catalytic triad in a 35-nucleotide single-stranded RNA hairpin, featuring an unconventional GA mismatch and a substantially shifted pKa value. Validation tests are performed with two system setups, both of which provide pKa predictions in good agreement with the experimental value. A single-configuration-based technique is used to calculate the pKa for comparison. The current success indicates the predictive power of the current nucleotide modeling framework.
Compatibility of Carbon Composite Biomaterials for Repairing Bone Tissue Injury in Wushu Training
Authors: Ren Jingfeng
Published: November 2020

With the improvement of economic level, more and more people begin to pursue a healthy lifestyle, among which sports have become an important way of modern people’s sports, but in the process of sports, there will inevitably be some injuries, especially in martial arts training, and bone is the most vulnerable part. Because of the special physiological characteristics of cartilage tissue, it is difficult to recover after injury. This problem has become the main health problem in real life, which greatly affects people’s health and quality of life. At present, the technology of carbon composite biological nanomaterials is more and more mature, and the bioactive composite materials are composed of polymers and bioactive components, which have very good biocompatibility. In recent years, the bioactive composite materials have been applied to clinical practice and achieved very good results. Based on this, this paper considers linking the bioactive carbon composite biomaterials with the recovery of bone tissue damage, and according to the biocompatibility of bioactive composite materials, it is applied to the repair of bone tissue injury in clinical practice. In this paper, two kinds of carbon composite biomaterials, calcium carbonate composite and graphene composite, were synthesized by electrochemical method and photocatalytic reduction method. The crystal of calcium carbonate complex and graphene composite was extracted by changing the experimental time and the parameters of the solution in the experiment, and then the two carbon composite materials were analyzed as biomineralization complex biocompatibility, cell growth, and cell activity of the complex as a drug carrier for bone tissue injury. The experimental results show that the two kinds of carbon composite biomaterials can provide a very good interface for cell adhesion and spreading. This experiment proves that the artificial bone made of carbon composite biological nanomaterials has good biocompatibility, and the biocompatibility of carbon composite biological nanomaterials can be directly applied to clinical bone tissue repair surgery.
Management of Total Transection of Nasoendotracheal Tube during LeFort I Osteotomy
Authors: Somers Miles , Tsakiris Peter , Isert Peter , Kim Samuel
Published: November 2020

Transection of the nasoendotracheal tube during orthognathic surgery is a rare, but life-threatening complication. We present a case of complete nasoendotracheal tube transection during a LeFort 1 osteotomy and discuss appropriate preventative and management techniques.
Multivalued Fixed Point Results for Two Families of Mappings in Modular-Like Metric Spaces with Applications
Authors: Rasham Tahair , Shoaib Abdullah , Park Choonkil , de la Sen Manuel , Aydi Hassen , Lee Jung Rye
Published: November 2020

The aim of this research work is to find out some results in fixed point theory for a pair of families of multivalued mappings fulfilling a new type of

U

-contractions in modular-like metric spaces. Some new results in graph theory for multigraph-dominated contractions in modular-like metric spaces are developed. An application has been presented to ensure the uniqueness and existence of a solution of families of nonlinear integral equations.
Oxymatrine Ameliorates Memory Impairment in Diabetic Rats by Regulating Oxidative Stress and Apoptosis: Involvement of NOX2/NOX4
Authors: Huang Yongpan , Li Xinliang , Zhang Xi , Tang Jiayu
Published: November 2020

Oxymatrine (OMT) is the major quinolizidine alkaloid extracted from the root of Sophora flavescens Ait and has been shown to exhibit a diverse range of pharmacological properties. The aim of the present study was to investigate the role of OMT in diabetic brain injury in vivo and in vitro. Diabetic rats were induced by intraperitoneal injection of a single dose of 65 mg/kg streptozotocin (STZ) and fed a high-fat and high-cholesterol diet. Memory function was assessed using a Morris water maze test. A SH-SY5Y cell injury model was induced by incubation with glucose (30 mM/l) to simulate damage in vitro. The serum fasting blood glucose, insulin, serum S100B, malondialdehyde (MDA), and superoxide dismutase (SOD) levels were analyzed using commercial kits. Morphological changes were observed using Nissl staining and electron microscopy. Cell apoptosis was assessed using Hoechst staining and TUNEL staining. NADPH oxidase (NOX) and caspase-3 activities were determined. The effects of NOX2 and NOX4 knockdown were assessed using small interfering RNA. The expression levels of NOX1, NOX2, and NOX4 were detected using reverse transcription-quantitative PCR and western blotting, and the levels of caspase-3 were detected using western blotting. The diabetic rats exhibited significantly increased plasma glucose, insulin, reactive oxygen species (ROS), S-100B, and MDA levels and decreased SOD levels. Memory function was determined by assessing the percentage of time spent in the target quadrant, the number of times the platform was crossed, escape latency, and mean path length and was found to be significantly reduced in the diabetic rats. Hyperglycemia resulted in notable brain injury, including histological changes and apoptosis in the cortex and hippocampus. The expression levels of NOX2 and NOX4 were significantly upregulated at the protein and mRNA levels, and NOX1 expression was not altered in the diabetic rats. NOX and caspase-3 activities were increased, and caspase-3 expression was upregulated in the brain tissue of diabetic rats. OMT treatment dose-dependently reversed behavioral, biochemical, and molecular changes in the diabetic rats. In vitro, high glucose resulted in increases in reactive oxygen species (ROS), MDA levels, apoptosis, and the expressions of NOX2, NOX4, and caspase-3. siRNA-mediated knockdown of NOX2 and NOX4 decreased NOX2 and NOX4 expression levels, respectively, and reduced ROS levels and apoptosis. The results of the present study suggest that OMT alleviates diabetes-associated cognitive decline, oxidative stress, and apoptosis via NOX2 and NOX4 inhibition.
Synergism and Antagonism of Two Distinct, but Confused, Nrf1 Factors in Integral Regulation of the Nuclear-to-Mitochondrial Respiratory and Antioxidant Transcription Networks
Authors: Zhang Shuwei , Deng Yangxu , Xiang Yuancai , Hu Shaofan , Qiu Lu , Zhang Yiguo
Published: November 2020

There is hitherto no literature available for explaining two distinct, but confused, Nrf1 transcription factors, because they shared the same abbreviations from nuclear factor erythroid 2-related factor 1 (also called Nfe2l1) and nuclear respiratory factor (originally designated α-Pal). Thus, we have here identified that Nfe2l1Nrf1 and α-PalNRF1 exert synergistic and antagonistic roles in integrative regulation of the nuclear-to-mitochondrial respiratory and antioxidant transcription profiles. In mouse embryonic fibroblasts (MEFs), knockout of Nfe2l1-/- leads to substantial decreases in expression levels of α-PalNRF1 and Nfe2l2, together with TFAM (mitochondrial transcription factor A) and other target genes. Similar inhibitory results were determined in Nfe2l2-/- MEFs but with an exception that both GSTa1 and Aldh1a1 were distinguishably upregulated in Nfe2l1-/- MEFs. Such synergistic contributions of Nfe2l1 and Nfe2l2 to the positive regulation of α-PalNRF1 and TFAM were validated in Keap1-/- MEFs. However, human α-PalNRF1 expression was unaltered by hNfe2l1α-/-, hNfe2l2-/-ΔTA, or even hNfe2l1α-/-+siNrf2, albeit TFAM was activated by Nfe2l1 but inhibited by Nfe2l2; such an antagonism occurred in HepG2 cells. Conversely, almost all of mouse Nfe2l1, Nfe2l2, and cotarget genes were downexpressed in α-PalNRF1+/- MEFs. On the contrary, upregulation of human Nfe2l1, Nfe2l2, and relevant reporter genes took place after silencing of α-PalNRF1, but their downregulation occurred upon ectopic expression of α-PalNRF1. Furtherly, Pitx2 (pituitary homeobox 2) was also identified as a direct upstream regulator of Nfe2l1 and TFAM, besides α-PalNRF1. Overall, these across-talks amongst Nfe2l1, Nfe2l2, and α-PalNRF1, along with Pitx2, are integrated from the endoplasmic reticulum towards the nuclear-to-mitochondrial communication for targeting TFAM, in order to finely tune the robust balance of distinct cellular oxidative respiratory and antioxidant gene transcription networks, albeit they differ between the mouse and the human. In addition, it is of crucial importance to note that, in view of such mutual interregulation of these transcription factors, much cautions should be severely taken for us to interpret those relevant experimental results obtained from knockout of Nfe2l1, Nfe2l2, α-Pal or Pitx2, or their gain-of-functional mutants.
Towards a Framework for Acquisition and Analysis of Speeches to Identify Suspicious Contents through Machine Learning
Authors: Rahman Md. Rashadur , Arefin Mohammad Shamsul , Hossain Md. Billal , Habib Mohammad Ashfak , Kayes A. S. M.
Published: November 2020

The most prominent form of human communication and interaction is speech. It plays an indispensable role for expressing emotions, motivating, guiding, and cheering. An ill-intentioned speech can mislead people, societies, and even a nation. A misguided speech can trigger social controversy and can result in violent activities. Every day, there are a lot of speeches being delivered around the world, which are quite impractical to inspect manually. In order to prevent any vicious action resulting from any misguided speech, the development of an automatic system that can efficiently detect suspicious speech has become imperative. In this study, we have presented a framework for acquisition of speech along with the location of the speaker, converting the speeches into texts and, finally, we have proposed a system based on long short-term memory (LSTM) which is a variant of recurrent neural network (RNN) to classify speeches into suspicious and nonsuspicious. We have considered speeches of Bangla language and developed our own dataset that contains about 5000 suspicious and nonsuspicious samples for training and validating our model. A comparative analysis of accuracy among other machine learning algorithms such as logistic regression, SVM, KNN, Naive Bayes, and decision tree is performed in order to evaluate the effectiveness of the system. The experimental results show that our proposed deep learning-based model provides the highest accuracy compared to other algorithms.
Screening of T Cell‐Related Long Noncoding RNA‐MicroRNA‐mRNA Regulatory Networks in Non‐Small‐Cell Lung Cancer
Authors: Duan Jinlong , Pan Yuefen , Yang Xi , Zhong Liping , Jin Yin , Xu Jiamin , Zhuang Jing , Han Shuwen
Published: November 2020

Background. Lung cancer (LC) has the highest mortality rate among all the other types of cancer in the world. T cells are known to be the key factor in inducing the immune response during LC. Objective. In this study, we aimed to screen and analyze RNAs associated with CD8(+) T cells and activated memory CD4(+) T cells in lung adenocarcinomas, a subtype of non‐small‐cell lung cancer (NSCLC‐LUAD). Methods. Gene expression RNA‐seq data and clinical data of NSCLC‐LUAD were downloaded from the XENA database. The data were divided into low scores and high scores based on the Stromal and Immune scores. Then, all the genes were screened for identifying those specifically associated with CD8(+) T cells and activated memory CD4(+) T cells. The screened genes were used for the construction of the protein‐protein interaction (PPI) network and for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis along with prognosis analysis. Based on the results of the prognostic analysis, the prognostic‐related genes were used to analyze long noncoding (lnc)RNA‐micro(mi)RNA‐mRNA networks and to predict small chemical molecules. Results. According to the Immune and Stromal scores, a total of 885 upregulated and 29 downregulated RNAs were identified. A total of 90 differentially expressed genes (DEGs) were found to be related to CD8(+) T immune cells, and 48 DEGs were related to activated memory CD4(+) T cells. GPR174 and CD226 suggested a favorable prognosis. For CD8(+) and activated memory CD4(+) T cells, 112 and 113 PPI edges were obtained, respectively. GPR174 was found to be regulated by hsa‐miR‐19b‐5p and hsa‐miR‐19b‐2‐5p, and both of these two miRNAs were regulated by lncRNA PCED1B‐AS1. CD226 was regulated by hsa‐miR‐379‐5p, which was in turn regulated by lncRNA RP11‐81H14.2. Conclusion. Our findings provide a deeper understanding of the T cell‐related ceRNA regulatory mechanism in NSCLC‐LUAD pathogenesis.
Model Analysis and Simulation of Equipment-Manufacturing Value Chain Integration Process
Authors: Dong Sisi , Qi Liangqun
Published: November 2020

The servitization of construction enterprises based on value chain integration means that construction enterprises use prefabricated buildings and combine advantageous resources to integrate preconstruction feasibility analysis, investment and financing services, design, etc., and postconstruction decoration, operation and maintenance, and waste disposal. This article takes the equipment-manufacturing industry as the research object, and based on the analysis of the service-based value chain integration process, it puts forward research hypotheses, constructs research models, and conducts data simulation research to explore how the equipment-manufacturing industry can realize the logic of industrial value through service reintegration and optimization reveal the changing laws and key influencing factors of the equipment-manufacturing industry’s value-added capabilities during this process. The results show that the industrial connection density, service element embedding methods, and knowledge absorption capacity have a significant impact on the value-added ability of the equipment-manufacturing industry during the integration process. The increase in industrial connection density promotes the enhancement of value-added capabilities, and it is significant at the initial stage and then weakened. Both the input-side and output-side service element embedding can affect the value-added ability, but the effects of the two are different. The improvement of knowledge absorptive capacity can promote the occurrence of service innovation, thereby enhancing the value-added capacity of the equipment-manufacturing industry.
Prone Position after Liberation from Prolonged Mechanical Ventilation in COVID-19 Respiratory Failure
Authors: Karpov Andrei , Mitra Anish R. , Crowe Sarah , Haljan Gregory
Published: November 2020

Objective and Rationale. Prone positioning of nonintubated patients has prevented intubation and mechanical ventilation in patients with respiratory failure from coronavirus disease 2019 (COVID-19). A number of patients in a recently published cohort have undergone postextubation prone positioning (PEPP) following liberation from prolonged mechanical ventilation in attempt to prevent reintubation. The objective of this study is to systematically search the literature for reports of PEPP as well as describe the feasibility and outcomes of PEPP in patients with COVID-19 respiratory failure. Design. This is a retrospective case series describing the feasibility and tolerability of postextubation prone positioning (PEPP) and its impact on physiologic parameters in a tertiary intensive care unit during the COVID-19 pandemic. Setting and Patients. This study was conducted on patients with COVID-19 respiratory failure hospitalized in a tertiary Intensive Care Unit at Surrey Memorial Hospital during the COVID-19 pandemic. Measurements and Results. We did not find prior reports of PEPP following prolonged intubation in the literature. Four patients underwent a total of 13 PEPP sessions following liberation from prolonged mechanical ventilation. Each patient underwent a median of 3 prone sessions (IQR: 2, 4.25) lasting a median of 1.5 hours (IQR: 1.2, 2.1). PEPP sessions were associated with a reduction in median oxygen requirements, patient respiratory rate, and reintubation rate. The sessions were well tolerated by patients, nursing, and the allied health team. Conclusions. The novel practice of PEPP after liberation from prolonged mechanical ventilation in patients with COVID-19 respiratory failure is feasible and well tolerated, and may be associated with favourable clinical outcomes including improvement in oxygenation and respiratory rate and a low rate of reintubation. Larger prospective studies of PEPP are warranted.
Invalid Self-Assessment of Olfactory Functioning in Parkinson’s Disease Patients May Mislead the Neurologist
Authors: Schmidt Nele , Paschen Laura , Witt Karsten
Published: November 2020

Olfactory dysfunction (OD) is a prominent nonmotor symptom in Parkinson’s disease (PD), and OD is a supportive diagnostic criterion for PD. Physicians often ask their patients if they have noticed a smell disorder. This study evaluates the diagnostic validity of OD self-assessment in PD. To this end, 64 PD patients and 33 age-matched healthy controls were enrolled in a study assessing subjective and objective olfactory functioning. To examine subjective olfactory abilities, first, patients and controls had to classify their olfactory sense as “impaired” or “unimpaired,” comparable to a realistic situation in an outpatient setting. Second, to evaluate subjective olfactory acuity, a visual analogue scale (VAS) was used. Third, the Sniffin’ Sticks test battery was used as an objective instrument to diagnose OD. Categorical olfactory self-assessment predicts the classification normosmic versus hyposmic based on the global Sniffin’ Sticks score (TDI) with a sensitivity of 0.79 and a specificity of 0.45. TDI correlated significantly with the VAS (r = 0.297,

p
=
0.017

). The ROC curve analysis, using the VAS rating as a predictor for objective olfaction, revealed 42 as the best possible cutoff score with an area under the curve of 0.63. These results demonstrate that olfactory self-assessments show a low accuracy and are not suitable for the diagnosis of a smell disorder in PD. Objective measures are necessary to evaluate olfactory sense in clinical and research settings.
Adaptive Boundary Control of Flexible Manipulators with Parameter Uncertainty Based on RBF Neural Network
Authors: He Cang , Zhang Fang , Jiang Jinhui
Published: November 2020

In this paper, nonlinear dynamical equations of the flexible manipulator with a lumped payload at the free end are derived from Hamilton's principle. The obtained model consists of both distributed parameters and lumped parameters, namely, partial differential equations (PDEs) governing the flexible motion of links and boundary conditions in the form of ordinary differential equations (ODEs). Considering the great nonlinear approximation ability of the radial basis function (RBF) neural network, we propose a combined control algorithm that includes two parts: one is a boundary controller to track the desired joint positions and suppress the vibration of flexible links; another is a RBF neural network designed to compensate for the parametric uncertainties. The iteration criterion of the RBF neural network weight matrix is derived from the extended Lyapunov function. Stabilization analysis is further carried out theoretically via LaSalle’s invariance principle. Finally, the results of the numerical simulation verify that the proposed control law can realize the asymptotic convergence of tracking error and suppression of the elastic vibration as well.
The First Case of L. pseudomesenteroides Pulmonary Infection and Literature Review
Authors: Dai Liwan , Li Yishi , Zhang Xiaobing , Ding Ming , Guo Shuliang
Published: November 2020

L. pseudomesenteroides is a very rare bacterium that infects human beings, and it has been used as an industrial fermentation bacterium. At present, only a few cases have been reported about this bacterium infecting the human body, but most reports are mainly about sepsis. We will report on a woman with lymphoma who was successfully diagnosed by the use of transbronchial cryobiopsy (TBCB) with L. pseudomesenteroides pulmonary infection.
Online Supervised Learning with Distributed Features over Multiagent System
Authors: An Xibin , He Bing , Hu Chen , Liu Bingqi
Published: November 2020

Most current online distributed machine learning algorithms have been studied in a data-parallel architecture among agents in networks. We study online distributed machine learning from a different perspective, where the features about the same samples are observed by multiple agents that wish to collaborate but do not exchange the raw data with each other. We propose a distributed feature online gradient descent algorithm and prove that local solution converges to the global minimizer with a sublinear rate

O

2
T

. Our algorithm does not require exchange of the primal data or even the model parameters between agents. Firstly, we design an auxiliary variable, which implies the information of the global features, and estimate at each agent by dynamic consensus method. Then, local parameters are updated by online gradient descent method based on local data stream. Simulations illustrate the performance of the proposed algorithm.
Cryptococcus: A Rare Cause of Parotid Abscess in Liver Cirrhosis
Authors: Okamoto Takeshi , Fukuda Katsuyuki
Published: November 2020

A 61-year-old man with decompensated liver cirrhosis presented with a parotid mass. Fine-needle aspiration of the parotid gland revealed Cryptococcus neoformans. Lumbar puncture confirmed cryptococcal meningitis. Multiple splenic lesions with radiographic features consistent with cryptococcal splenic abscesses were also seen. Despite antifungal therapy, the patient died 17 days after infection was confirmed. This is the first report of a cryptococcal parotid abscess in a patient with liver cirrhosis.
Awareness and Treatment Decisions on Tooth Wear among Jordanian Dentists and Prosthodontists: A Cross-Sectional Survey Study
Authors: Sartawi Samiha , Salim Nesreen A. , Taim Duaa
Published: November 2020

Objectives. To assess the awareness, knowledge, and treatment decisions by dentists in Jordan regarding tooth wear. Materials and Methods. A questionnaire was disseminated to a random sample of 200 general dentists and 100 prosthodontists working in the Ministry of Health, academia, private practices, and military services. Chi square and independent t-tests were performed for statistical analysis. Results. Hundred and seventy-nine dentists and prosthodontists responded (59.7% response rate), of which 71.5% was females. 83.8% of the dentists reported they see patients with tooth wear. 61.5% registered wear lesions in the patient file, and 68.2% reported they find a probable cause of tooth wear. 87.2% of the dentists reported that bruxism is the most common cause in Jordan. 63.3% dentists treated their patients. 46.4% reported they “always” record a dietary history. 77.7% did not think that tooth wear is linked to caries. Low confidence levels were demonstrated among general practitioners in diagnosing and treating tooth wear. Regarding treatment decisions, most dentists decided to restore worn teeth with composite and to construct a night guard. Minimally affected anterior teeth were mostly treated with fluoride. Restoration of posterior worn teeth with overlay was suggested by one-third of the dentists. Conclusion. The dentists and prosthodontists in Jordan are aware of tooth wear. However, examination and documentation were given a little priority by general dentists. On the other hand, there was an agreement among the dentists and prosthodontists on applying the minimally invasive approach. Clinical Significance. It is challenging for dentists to make the best treatment decision for tooth wear especially as no standard treatment is available. Therefore, this study investigated the awareness and treatment decisions of a sample of dentists and prosthodontists in Jordan.
A Case of Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP) in Childhood
Authors: Abbasion Reza , Jafarpisheh Amir , Dehghanian Paria , Mottaghi Mahdi
Published: November 2020

Urothelial carcinoma (UC) of the bladder is exceedingly rare in the pediatric population. It commonly presents as isolated hematuria. Considering the age group, the physician’s low index of suspicion causes a delay in diagnosis. We present a seven-year-old girl complaining of dysuria and painless, intermittent hematuria. She was misdiagnosed with urinary tract infection several times. Although the initial ultrasound showed no abnormality, the second ultrasound after one year detected the tumor. The confirmation and resection are simultaneously achieved by cystoscopy. We concluded that chemotherapy is unnecessary due to the tumor’s low-grade nature and the absence of detrusor involvement. One-year follow-up showed no relapse.
Analysis of Long Noncoding RNA ZNF667-AS1 as a Potential Biomarker for Diagnosis and Prognosis of Glioma Patients
Authors: Yuan Qin , Gao Chao , Lai Xiao-dong , Chen Liang-yi , Lai Tian-bao
Published: November 2020

Objective. Long noncoding RNAs (lncRNAs) have been strongly associated with various types of cancer. The present study aimed at exploring the diagnostic and prognostic value of lncRNA Zinc finger protein 667-antisense RNA 1 (ZNF667-AS1) in glioma patients. Patients and Methods. The expressions of ZNF667-AS1 were detected in 155 glioma tissues and matched normal brain tissue samples by qRT-PCR. The receiver operating characteristic (ROC) curve was performed to estimate the diagnostic value of ZNF667-AS1. The association between the ZNF667-AS1 expression and clinicopathological characteristics was analyzed by the chi-square test. The Kaplan-Meier method was performed to determine the influence of the ZNF667-AS1 expression on the overall survival and disease-free survival of glioma patients. The Cox regression analysis was used to evaluate the effect of independent prognostic factors on survival outcome. Cell proliferation was measured by the respective cell counting Kit-8 (CCK-8) assays. Results. We observed that ZNF667-AS1 was significantly upregulated in glioma tissues compared to normal tissue samples (

p
<
0.01

). Higher levels of ZNF667-AS1 were positively associated with the WHO grade (

p
=
0.018

) and KPS score (

p
=
0.008

). ROC assays revealed that the high ZNF667-AS1 expression had an AUC value of 0.8541 (95% CI: 0.8148 to 0.8934) for glioma. Survival data revealed that glioma patients in the high ZNF667-AS1 expression group had significantly shorter 5-year overall survival (

p
=
0.0026

) and disease-free survival (

p
=
0.0005

) time than those in the low ZNF667-AS1 expression group. Moreover, multivariate analyses confirmed that the ZNF667-AS1 expression was an independent predictor of the overall survival and disease-free survival for glioma patients. Functionally, we found that knockdown of ZNF667-AS1 suppressed the proliferation of glioma cells. Conclusions. Our results suggest that ZNF667-AS1 could be used as a potential diagnostic and prognostic biomarker in glioma.
Rediseño e implementación de un curso de psicología médica desde metodología docente presencial, a una semipresencial. Curso de psicología médica en formato b-learning.
Authors: Vargas Gajardo Bryan , Gonzalez Isla Vicente , Orozco Soto Constanza , Reyes Guzman Ignacio , Santander Toro Jaime , Pinedo Jose
Published: November 2020

Resumen
Introducción: el curso mínimo de psicología médica tiene como propósito introducir y sensibilizar a los estudiantes en temas psicológicos básicos relevantes para la comprensión y desarrollo del ejercicio de la medicina. Entre las últimas evaluaciones de estudiantes de la Pontificia Universidad Católica, destacan comentarios negativos sobre las extensas jornadas de clases y la poca flexibilidad en la entrega de material de estudio. Métodos: se propuso implementar una metodología de clases b-learning, permitiendo al estudiante auto gestionar su tiempo y recibir los contenidos a distancia. Se evaluó posteriormente la aceptación de la nueva metodología a través de encuestas de satisfacción y se evaluó comparativamente el efecto de metodología en las calificaciones del alumnado. Resultados: se obtuvo resultados favorables con un promedio global al curso de 6,23 ± 0,67 para el año 2016 y 6,38 ± 0,49 para el 2017, y específicamente para la metodología b-learning de 6,03 ± 0,97 para el 2016, y para el 2017 6,41 ± 0,63. Conclusión:Se concluye que la modalidad de b-learning es una metodología de aprendizaje valorada positivamente por los alumnos con repercusión favorable en sus resultados académicos.
Metahemoglobinemia secundaria a inhalación de “poppers”: caso clínico y revisión de la literatura
Authors: Corsi Sotelo Oscar , Muñoz Mery Tamara , Peña Rivero Arturo
Published: November 2020

El nitrito de amilo, conocida como “poppers”, se ha masificado como droga recreacional en parte por sus efectos con objetivos sexuales. Su consumo se asocia a complicaciones psiquiátricas y médicas. Reportamos el caso de un paciente que se presenta con metahemoglobinemia moderada secundaria a la inhalación de nitrito de amilo asociado a alcohol. Al ingreso presenta cianosis peribucal y en extremidades, disociación entre oximetría de pulso y presión parcial de oxígeno en gases arteriales, además de metahemoglobinemia 29,9%. Se descartan otras intoxicaciones y causas primarias de metahemoglobinemia. Se maneja con oxigenoterapia, hidratación y ácido ascórbico, presentando una evolución favorable. Presentamos el primer caso en Chile de metahemoglobinemia secundaria al consumo de nitrito de amilo con fines recreativos.
Modelos epidemiológicos y la pandemia COVID-19 en Chile
Authors: Canals L Dr. Mauricio
Published: November 2020

El aumento de la población, la globalización y el cambio climático han significado un cambio en la prevalencia y aparición de nuevas enfermedades infecciosas, muchas de ellas zoonóticas y transmitidas por insectos hematófagos, con cambios en los patrones espaciales y temporales de reservorios, vectores y hospederos. Esto ha significado la emergencia y re-emergencia de numerosas enfermedades. Más del 70% de estas son zoonóticas, donde el factor más importante es la transgresión de la barrera entre especies, concepto conocido como “spillover” (Jones, 2008). Últimamente, han llamado la atención las enfermedades cuyo reservorio son los murciélagos, principalmente los frugívoros. Los murciélagos tienen al menos 76 virus de peligro potencial para el humano, entre los que destacan los virus Rabia, Marburg, Hendra, Nipah, Menangle, Tioman, Ébola y los coronavirus SARS y MERS (Callisher, 2006). Los estudios actuales muestran casi con seguridad que el virus SARS CoV-2 tiene un origen en murciélagos frugívoros (Andersen, 2020; Lam, 2020). Este nuevo “spillover” está impactando la humanidad con una gran pandemia (COVID-19) y actualmente ya cuenta con cerca de 8,5 millones de casos reportados y cerca de 460 mil fallecidos afectando todos los aspectos de la vida de la humanidad (WHO, 2019).
Toma de decisiones en ética clínica y su aplicación a un caso de síndrome de enclaustramiento
Authors: López Paulo Ibrain
Published: November 2020

La ética clínica, como parte de la bioética, tiene como función ayudar al personal sanitario, al paciente o a la familia en la toma de decisiones cuando estas abordan cuestiones éticas de difícil solución. En algunos problemas, esta toma de decisiones se enfrenta no solo a posturas clínicas diversas, sino que también a apremios por parte de familiares -o del mismo equipo médico- que claman por una solución ante casos que entran en el área gris del debate ético. Nuestra respuesta frente a estos problemas ingentes es la aplicación de un método de análisis clínico, el cual, mediante una metodología propia y replicable, pueda orientar la discusión sobre principios comunes y, a la vez, poder evaluar las decisiones clínicas emanadas.
Más allá de las respuestas clínicas que se puedan dar frente a casos diversos, no debemos olvidar los fundamentos que la antropología cristiana nos presenta a la hora de ver al ser humano como totalidad unificada. Este criterio debe ser la base que guíe una reflexión que no solo busque criterios de calidad, sino que además valore la inviolabilidad de la vida y con ella la dignidad de cada persona, en especial, en aquellas condiciones de fragilidad como el síndrome de enclaustramiento.
Abstract IA-07: Mechanisms of cellular heterogeneity in pancreatic cancer
Authors: Behrens Axel
Published: November 2020

Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic cancer and is predicted to be the second leading cause of cancer-related mortality in the next decade in Western countries. Treatment options are very limited, with even resectable tumours conferring a five-year survival rate of only 30%. Thus, there is an urgent need to better understand the biology of PDAC. Cancer cell heterogeneity is believed to be one of the main causes of tumour aggressiveness and resistance to therapy. I will describe our work to understand the sources of intratumoural PDAC diversity and the characterisation of a PDAC cancer stem cell population.

Citation Format: Axel Behrens. Mechanisms of cellular heterogeneity in pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-07.
Abstract IA-10: Overcoming the seven deadly hallmarks of pancreatic cancer
Authors: Tuveson David
Published: November 2020

Pancreatic cancer remains highly lethal, however recent insights regarding disease pathogenesis coupled with the emergence of new diagnostic methods and therapeutic agents engender a more hopeful outlook. We delineate 7 common characteristics of pancreatic cancer including desmoplastic stroma, dysregulated metabolism, chronic inflammation, undruggable KRAS, early metastasis, diagnostic deficiencies, and rapid deconditioning and posit that these hallmarks are collectively responsible for disease aggressiveness and clinical failure. Finally, we propose a strategic framework to address these challenges and thereby improve patient outcomes.

Citation Format: David Tuveson. Overcoming the seven deadly hallmarks of pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-10.