bluuebunny/crossref_metadata_2025 huggingface dataset:
MHCII-restricted T helper cells: an emerging trigger for chronic tactile allodynia after nerve injuries
Authors: Ding You-Quan , Luo Han , Qi Jian-Guo
Published: January 2020

Nerve injury-induced chronic pain has been an urgent problem for both public health and clinical practice. While transition to chronic pain is not an inevitable consequence of nerve injuries, the susceptibility/resilience factors and mechanisms for chronic neuropathic pain after nerve injuries still remain unknown. Current preclinical and clinical studies, with certain notable limitations, have shown that major histocompatibility complex class II–restricted T helper (Th) cells is an important trigger for nerve injury-induced chronic tactile allodynia, one of the most prevalent and intractable clinical symptoms of neuropathic pain. Moreover, the precise pathogenic neuroimmune interfaces for Th cells remain controversial, not to mention the detailed pathogenic mechanisms. In this review, depending on the biology of Th cells in a neuroimmunological perspective, we summarize what is currently known about Th cells as a trigger for chronic tactile allodynia after nerve injuries, with a focus on identifying what inconsistencies are evident. Then, we discuss how an interdisciplinary perspective would improve the understanding of Th cells as a trigger for chronic tactile allodynia after nerve injuries. Finally, we hope that the expected new findings in the near future would translate into new therapeutic strategies via targeting Th cells in the context of precision medicine to either prevent or reverse chronic neuropathic tactile allodynia.
TREM-2-p38 MAPK signaling regulates neuroinflammation during chronic cerebral hypoperfusion combined with diabetes mellitus
Authors: Zhang Jiawei , Liu Yu , Zheng Yaling , Luo Yan , Du Yu , Zhao Yao , Guan Jian , Zhang Xiaojie , Fu Jianliang
Published: January 2020

Background

Diabetes mellitus (DM) and chronic cerebral hypoperfusion(CCH)are both risk factors for cognitive impairment. However, whether DM and CCH can synergistically promote cognitive impairment and the related pathological mechanisms remain unknown.

Methods

To investigate the effect of DM and CCH on cognitive function, rats fed with high-fat diet (HFD) and injected with low-dose streptozotocin (STZ) followed by bilateral common carotid artery occlusion (BCCAO) were induced to mimic DM and CCH in vivo and mouse BV2 microglial cells were exposed to hypoxia and/or high glucose to mimic CCH complicated with DM pathologies in vitro. To further explore the underlying mechanism, TREM-2-specific small interfering RNA and TREM-2 overexpression lentivirus were used to knock out and overexpress TREM-2, respectively.

Results

Cognitive deficits, neuronal cell death, neuroinflammation with microglial activation, and TREM-2-MAPK signaling were enhanced when DM was superimposed on CCH both in vivo and in vitro. Manipulating TREM-2 expression levels markedly regulated the p38 MAPK signaling and the inflammatory response in vitro. TREM-2 knockout intensified while TREM-2 overexpression suppressed the p38 MAPK signaling and subsequent pro-inflammatory mediator production under high glucose and hypoxia condition.

Conclusions

These results suggest that TREM-2 negatively regulates p38 MAPK-mediated inflammatory response when DM was synergistically superimposed on CCH and highlight the importance of TREM-2 as a potential target of immune regulation in DM and CCH.
Fractionated carbon ion irradiations of the rat spinal cord: comparison of the relative biological effectiveness with predictions of the local effect model
Authors: Saager Maria , Glowa Christin , Peschke Peter , Brons Stephan , Grün Rebecca , Scholz Michael , Debus Jürgen , Karger Christian P.
Published: January 2020

Background

To determine the relative biological effectiveness (RBE) and α/β-values after fractionated carbon ion irradiations of the rat spinal cord with varying linear energy transfer (LET) to benchmark RBE-model calculations.

Material and methods

The rat spinal cord was irradiated with 6 fractions of carbon ions at 6 positions within a 6 cm spread-out Bragg-peak (SOBP, LET: 16–99 keV/μm). TD50-values (dose at 50% complication probability) were determined from dose-response curves for the endpoint radiation induced myelopathy (paresis grade II) within 300 days after irradiation. Based on TD50-values of 15 MV photons, RBE-values were calculated and adding previously published data, the LET and fractional dose-dependence of the RBE was used to benchmark the local effect model (LEM I and IV).

Results

At six fractions, TD50-values decreased from 39.1 ± 0.4 Gy at 16 keV/μm to 17.5 ± 0.3 Gy at 99 keV/μm and the RBE increased accordingly from 1.46 ± 0.05 to 3.26 ± 0.13. Experimental α/β-ratios ranged from 6.9 ± 1.1 Gy to 44.3 ± 7.2 Gy and increased strongly with LET. Including all available data, comparison with model-predictions revealed that (i) LEM IV agrees better in the SOBP, while LEM I fits better in the entrance region, (ii) LEM IV describes the slope of the RBE within the SOBP better than LEM I, and (iii) in contrast to the strong LET-dependence, the RBE-deviations depend only weakly on fractionation within the measured range.

Conclusions

This study extends the available RBE data base to significantly lower fractional doses and performes detailed tests of the RBE-models LEM I and IV. In this comparison, LEM IV agrees better with the experimental data in the SOBP than LEM I. While this could support a model replacement in treatment planning, careful dosimetric analysis is required for the individual patient to evaluate potential clinical consequences.
Behavioral Economics Incentives to Support HIV Treatment Adherence (BEST): Protocol for a randomized controlled trial in Uganda
Authors: Linnemayr Sebastian , Stecher Chad , Saya Uzaib , MacCarthy Sarah , Wagner Zachary , Jennings Larissa , Mukasa Barbara
Published: January 2020

Background

Many HIV-positive patients do not appropriately adhere to their antiretroviral medication (ART). This leads to higher viral loads and greater probability of HIV transmission. Present bias—a tendency to give in to short-term temptations at the expense of long-term outcomes—is a potential driver of low adherence. In this study we test a novel intervention rooted in behavioral economics that is designed to overcome present bias and increase ART adherence.

Methods/design

We will enroll 330 HIV-positive patients at Mildmay Hospital in Kampala, Uganda, into a 2-year randomized controlled trial. Participants will be randomized to one of three groups. The first intervention group (T1, n = 110) will be eligible for small lottery prizes based on timely clinic visits and demonstration of viral suppression. Group 2 (T2, n = 110) will be eligible for the same lottery prizes conditional on high adherence measured by a medication event management system (MEMS) cap. The control group (n = 110) will receive the usual standard of care. Adherence will be measured continuously throughout the intervention period and for 12 months post-intervention to evaluate effect persistence. Surveys will be conducted at baseline and then every 6 months. Viral loads will be measured annually. Primary outcomes are whether the viral load is detectable and MEMS-measured adherence. Secondary outcomes are the log-transformed viral load as a continuous measure and a binary measure for whether the person took at least 90% of their ART pills.

Discussion

Our study is one of the first to investigate the effectiveness of lottery incentives for improving ART adherence, and in addition, it compares the relative efficacy of using electronically measured adherence versus viral load to determine lottery eligibility. MEMS caps are relatively costly, whereas viral load testing is now part of routine clinical care in Uganda. BEST will test whether directly incentivizing viral suppression (which can be implemented using readily available clinic data) is as effective as incentivizing electronically measured adherence. Cost-effectiveness analyses of the two implementation modes will also be performed.

Trial registration

ClinicalTrials.gov, NCT03494777. Registered on 11 April 2018.
Enhanced quantitative urine culture technique, a slight modification, in detecting under-diagnosed pediatric urinary tract infection
Authors: Thapaliya Januka , Khadka Priyatam , Thapa Shovana , Gongal Chenu
Published: January 2020

Objectives

The pediatric urinary tract infection (UTI) often remains under-diagnosed or neglected owing to non-specific clinical presentations, patients failing to describe the actual situation and of clinical practice in diagnosis. The study was aimed to determine the etiologies of UTI in children with enhanced quantitative urine culture (EQUC) technique.

Results

Of enrolled 570 pediatric urine samples, the significant growth positivity was higher in EQUC 92 (16.15%) compared to standard urine culture (SUC) 73 (12.80%) technique. 20.6% of the significant isolates as detected with EQUC were missed on the SUC technique. The age group, in range 1–4 years, was more prone to the infection, where E. coli was the commonest pathogen. EQUC detected, probably all isolates, contributing UTI i.e. multidrug-resistant (MDR), extensive drug-resistant (XDR), and extended-spectrum β-lactamase (ESBL) producers, as some of them skipped on the SUC technique. Of total organisms isolated from EQUC, 46% were ESBL producer, 56.5% were MDR, and 1.4% were XDR. However, 40.5% ESBL, 44% MDR but no XDR detected on SUC. Hence a simple modification on conventional culture protocol could be a crucial modification for the detection of etiologies, contributing UTI, and hence to reduce inapt antimicrobial burden.
Dysfunctional epigenetic aging of the normal colon and colorectal cancer risk
Authors: Wang Ting , Maden Sean K. , Luebeck Georg E. , Li Christopher I. , Newcomb Polly A. , Ulrich Cornelia M. , Joo Ji-Hoon E. , Buchanan Daniel D. , Milne Roger L. , Southey Melissa C. , Carter Kelly T. , Willbanks Amber R. , Luo Yanxin , Yu Ming , Grady William M.
Published: January 2020

Background

Chronological age is a prominent risk factor for many types of cancers including colorectal cancer (CRC). Yet, the risk of CRC varies substantially between individuals, even within the same age group, which may reflect heterogeneity in biological tissue aging between people. Epigenetic clocks based on DNA methylation are a useful measure of the biological aging process with the potential to serve as a biomarker of an individual’s susceptibility to age-related diseases such as CRC.

Methods

We conducted a genome-wide DNA methylation study on samples of normal colon mucosa (N = 334). Subjects were assigned to three cancer risk groups (low, medium, and high) based on their personal adenoma or cancer history. Using previously established epigenetic clocks (Hannum, Horvath, PhenoAge, and EpiTOC), we estimated the biological age of each sample and assessed for epigenetic age acceleration in the samples by regressing the estimated biological age on the individual’s chronological age. We compared the epigenetic age acceleration between different risk groups using a multivariate linear regression model with the adjustment for gender and cell-type fractions for each epigenetic clock. An epigenome-wide association study (EWAS) was performed to identify differential methylation changes associated with CRC risk.

Results

Each epigenetic clock was significantly correlated with the chronological age of the subjects, and the Horvath clock exhibited the strongest correlation in all risk groups (r > 0.8, p < 1 × 10−30). The PhenoAge clock (p = 0.0012) revealed epigenetic age deceleration in the high-risk group compared to the low-risk group.

Conclusions

Among the four DNA methylation-based measures of biological age, the Horvath clock is the most accurate for estimating the chronological age of individuals. Individuals with a high risk for CRC have epigenetic age deceleration in their normal colons measured by the PhenoAge clock, which may reflect a dysfunctional epigenetic aging process.
Combining molecular and imaging metrics in cancer: radiogenomics
Authors: Lo Gullo Roberto , Daimiel Isaac , Morris Elizabeth A. , Pinker Katja
Published: January 2020

Background

Radiogenomics is the extension of radiomics through the combination of genetic and radiomic data. Because genetic testing remains expensive, invasive, and time-consuming, and thus unavailable for all patients, radiogenomics may play an important role in providing accurate imaging surrogates which are correlated with genetic expression, thereby serving as a substitute for genetic testing.

Main body

In this article, we define the meaning of radiogenomics and the difference between radiomics and radiogenomics. We provide an up-to-date review of the radiomics and radiogenomics literature in oncology, focusing on breast, brain, gynecological, liver, kidney, prostate and lung malignancies. We also discuss the current challenges to radiogenomics analysis.

Conclusion

Radiomics and radiogenomics are promising to increase precision in diagnosis, assessment of prognosis, and prediction of treatment response, providing valuable information for patient care throughout the course of the disease, given that this information is easily obtainable with imaging. Larger prospective studies and standardization will be needed to define relevant imaging biomarkers before they can be implemented into the clinical workflow.
Study of breast implants mammography examinations for identification of suitable image quality criteria
Authors: Sá dos Reis Cláudia , Gremion Isabelle , Richli Meystre Nicole
Published: January 2020

Purpose

To characterise the mammography technique used in breast cancer screening programmes for breast implants (BI) and to identify if the image quality (IQ) criteria available in literature are applicable to BI imaging.

Methods

The study was conducted in two phases: literature review to find IQ criteria used in mammography combining keywords in several sources; and assessment of 1207 BI mammograms using the criteria that was identified previously to see if they were achieved or not. An observation grid was used to collect information about positioning, beam energy, compression force, and exposure mode. Descriptive statistics and Student’s t test and χ2 test were performed according to the nature of the variables.

Results

Forty-seven out of 2188 documents were included in the analysis, with 13 items identified to assess the quality of positioning, 4 for sharpness, 3 for artefacts, and 2 for exposure parameters. After applying the criteria to BI mammograms, retroglandular fat was not included in 37.3% of the images. The “Pectoral-Nipple-Line” criterion was achieved in 35% of MLO/ML images. The placement of the implant (subpectoral/subglandular) or performing the Eklund had significant influence on the visible anatomy (p = < 0.005), alongside whether the breast was aligned to the detector’s centre.

Conclusions

Some of the criteria used to assess standard mammograms were not applicable to BI due to implant overlap. The alignment of the image with the detector’s centre seems to have an impact on the amount of visible tissue. Further studies are necessary to define the appropriate protocol, technique, and suitable quality criteria to assess BI mammograms.
Imaging indications and findings in evaluation of lung transplant graft dysfunction and rejection
Authors: Bin Saeedan Mnahi , Mukhopadhyay Sanjay , Lane C. Randall , Renapurkar Rahul D.
Published: January 2020

Lung transplantation is a treatment option in end-stage lung disease. Complications can develop along a continuum in the immediate or longer post-transplant period, including surgical and technical complications, primary graft dysfunction, rejection, infections, post-transplant lymphoproliferative disorder, and recurrence of the primary disease. These complications have overlapping clinical and imaging features and often co-exist. Time of onset after transplant is helpful in narrowing the differential diagnosis. In the early post transplantation period, imaging findings are non-specific and need to be interpreted in the context of the clinical picture and other investigations. In contrast, imaging plays a key role in diagnosing and monitoring patients with chronic lung allograft dysfunction. The goal of this article is to review primary graft dysfunction, acute rejection, and chronic rejection with emphasis on the role of imaging, pathology findings, and differential diagnosis.
Alteration of fatty acid oxidation by increased CPT1A on replicative senescence of placenta-derived mesenchymal stem cells
Authors: Seok Jin , Jung Hyun Sook , Park Sohae , Lee Jung Ok , Kim Chong Jai , Kim Gi Jin
Published: January 2020

Background

Human placenta-derived mesenchymal stem cells (PD-MSCs) are powerful sources for cell therapy in regenerative medicine. However, a limited lifespan by senescence through mechanisms that are well unknown is the greatest obstacle. In the present study, we first demonstrated the characterization of replicative senescent PD-MSCs and their possible mitochondrial functional alterations.

Methods

Human PD-MSCs were cultured to senescent cells for a long period of time. The cells of before passage number 8 were early cells and after passage number 14 were late cells. Also, immortalized cells of PD-MSCs (overexpressed hTERT gene into PD-MSCs) after passage number 14 were positive control of non-senescent cells. The characterization and mitochondria analysis of PD-MSCs were explored with long-term cultivation.

Results

Long-term cultivation of PD-MSCs exhibited increases of senescent markers such as SA-β-gal and p21 including apoptotic factor, and decreases of proliferation, differentiation potential, and survival factor. Mitochondrial dysfunction was also observed in membrane potential and metabolic flexibility with enlarged mitochondrial mass. Interestingly, we founded that fatty acid oxidation (FAO) is an important metabolism in PD-MSCs, and carnitine palmitoyltransferase1A (CPT1A) overexpressed in senescent PD-MSCs. The inhibition of CPT1A induced a change of energy metabolism and reversed senescence of PD-MSCs.

Conclusions

These findings suggest that alteration of FAO by increased CPT1A plays an important role in mitochondrial dysfunction and senescence of PD-MSCs during long-term cultivation.
Age-dependent impairment of adipose-derived stem cells isolated from horses
Authors: Alicka Michalina , Kornicka-Garbowska Katarzyna , Kucharczyk Katarzyna , Kępska Martyna , Rӧcken Michael , Marycz Krzysztof
Published: January 2020

Background

Progressive loss of cell functionality caused by an age-related impairment in cell metabolism concerns not only mature specialized cells but also its progenitors, which significantly reduces their regenerative potential. Adipose-derived stem cells (ASCs) are most commonly used in veterinary medicine as an alternative treatment option in ligaments and cartilage injuries, especially in case of high-value sport horses. Therefore, the main aim of this study was to identify the molecular alternations in ASCs derived from three age-matched horse groups: young (< 5), middle-aged (5–15), and old (> 15 years old).

Methods

ASCs were isolated from three age-matched horse groups using an enzymatic method. Molecular changes were assessed using qRT-PCR, ELISA and western blot methods, flow cytometry-based system, and confocal and scanning electron microscopy.

Results

Our findings showed that ASCs derived from the middle-aged and old groups exhibited a typical senescence phenotype, such as increased percentage of G1/G0-arrested cells, binucleation, enhanced β-galactosidase activity, and accumulation of γH2AX foci, as well as a reduction in cell proliferation. Moreover, aged ASCs were characterized by increased gene expression of pro-inflammatory cytokines and miRNAs (interleukin 8 (IL-8), IL-1β, tumor necrosis factor α (TNF-α), miR-203b-5p, and miR-16-5p), as well as apoptosis markers (p21, p53, caspase-3, caspase-9). In addition, our study revealed that the protein level of mitofusin 1 (MFN1) markedly decreased with increasing age. Aged ASCs also displayed a reduction in mRNA levels of genes involved in stem cell homeostasis and homing, like TET-3, TET-3 (TET family), and C-X-C chemokine receptor type 4 (CXCR4), as well as protein expression of DNA methyltransferase (DNMT1) and octamer transcription factor 3/4 (Oct 3/4). Furthermore, we observed a higher splicing ratio of XBP1 (X-box binding protein 1) mRNA, indicating elevated inositol-requiring enzyme 1 (IRE-1) activity and, consequently, increased endoplasmic reticulum (ER) stress. We also observed reduced levels of glucose transporter 4 (GLUT-4) and insulin receptor (INSR) which indicated impaired insulin sensitivity.

Conclusions

Obtained data suggest that ASCs derived from horses older than 5 years old exhibited several molecular alternations which markedly limit their regenerative capacity. The results provide valuable information that allows for a better understanding of the molecular events occurring in ASCs in the course of aging and may help to identify new potential drug targets to restore their regenerative potential.

Graphical abstract
Reproducibility of GMP-compliant production of therapeutic stressed peripheral blood mononuclear cell-derived secretomes, a novel class of biological medicinal products
Authors: Laggner Maria , Gugerell Alfred , Bachmann Christiane , Hofbauer Helmut , Vorstandlechner Vera , Seibold Marcus , Gouya Lechner Ghazaleh , Peterbauer Anja , Madlener Sibylle , Demyanets Svitlana , Sorgenfrey Dirk , Ostler Tobias , Erb Michael , Mildner Michael , Ankersmit Hendrik Jan
Published: January 2020

Background

The recent concept of secretome-based tissue regeneration has profoundly altered the field of regenerative medicine and offers promising novel therapeutic options. In contrast to medicinal products with a single active substance, cell-derived secretomes comprise pleiotropic bioactive ingredients, representing a major obstacle for reproducible drug product efficacy and warranting patient safety. Good manufacturing practice (GMP)-compliant production guarantees high batch-to-batch consistency and reproducible efficacy of biological medicinal products, but different batches of cellular secretomes produced under GMP have not been compared yet, and suitable quality control parameters have not been established. To this end, we analyzed diverse biological and functional parameters of different batches produced under GMP of the secretome obtained from γ-irradiated peripheral blood mononuclear cells with proven tissue regenerative properties in infarcted myocardium, stroke, spinal cord injury, and skin wounds.

Methods

We quantified key secretome ingredients, including cytokines, lipids, and extracellular vesicles, and functionally assessed potency in tube formation assay, ex vivo aortic ring sprouting assay, and cell-based protein and reporter gene assays. Furthermore, we determined secretome stability in different batches after 6 months of storage at various ambient temperatures.

Results

We observed that inter-batch differences in the bioactive components and secretome properties were small despite considerable differences in protein concentrations and potencies between individual donor secretomes. Stability tests showed that the analytical and functional properties of the secretomes remained stable when lyophilisates were stored at temperatures up to + 5 °C for 6 months.

Conclusions

We are the first to demonstrate the consistent production of cell-derived, yet cell-free secretome as a biological medicinal product. The results from this study provide the basis for selecting appropriate quality control parameters for GMP-compliant production of therapeutic cell secretomes and pave the way for future clinical trials employing secretomes in tissue regenerative medicine.
Extracellular vesicles for acute kidney injury in preclinical rodent models: a meta-analysis
Authors: Liu Chao , Wang Jin , Hu Jie , Fu Bo , Mao Zhi , Zhang Hengda , Cai Guangyan , Chen Xiangmei , Sun Xuefeng
Published: January 2020

Introduction

Extracellular vesicles (EVs), especially stem cell-derived EVs, have emerged as a potential novel therapy for acute kidney injury (AKI). However, their effects remain incompletely understood. Therefore, we performed this meta-analysis to systematically review the efficacy of EVs on AKI in preclinical rodent models.

Methods

We searched PubMed, EMBASE, and the Web of Science up to March 2019 to identify studies that reported the treatment effects of EVs in a rodent AKI model. The primary outcome was serum creatinine (Scr) levels. The secondary outcomes were the blood urea nitrogen (BUN) levels, renal injury score, percentage of apoptotic cells, and interleukin (IL)-10 and tumour necrosis factor (TNF)-α levels. Two authors independently screened articles based on the inclusion and exclusion criteria. The meta-analysis was conducted using RevMan 5.3 and R software.

Results

Thirty-one studies (n = 552) satisfied the inclusion criteria. Pooled analyses demonstrated that the levels of Scr (SMD = − 3.71; 95% CI = − 4.32, − 3.10; P < 0.01), BUN (SMD = − 3.68; 95% CI = − 4.42, − 2.94; P < 0.01), and TNF-α (SMD = − 2.65; 95% CI = − 4.98, − 0.32; P < 0.01); the percentage of apoptotic cells (SMD = − 6.25; 95% CI = − 8.10, − 4.39; P < 0.01); and the injury score (SMD = − 3.90; 95% CI = − 5.26, − 2.53; P < 0.01) were significantly decreased in the EV group, and the level of IL-10 (SMD = 2.10; 95% CI = 1.18, 3.02; P < 0.01) was significantly increased. Meanwhile, no significant difference was found between stem cell-derived EVs and stem cells.

Conclusion

The present meta-analysis confirmed that EV therapy could improve renal function and the inflammatory response status and reduce cell apoptosis in a preclinical rodent AKI model. This provides important clues for human clinical trials on EVs.
Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors
Authors: Bandeira Francisco , Goh Tze-Wei , Setiawan Melina , Yam Gary Hin-Fai , Mehta Jodhbir S.
Published: January 2020

Background

Persistent epithelial defects (PED), associated with limbal stem cell deficiency (LSCD), require ocular surface reconstruction with a stable corneal epithelium (CE). This study investigated CE reformation using human adipose mesenchymal stem cells (ADSC), which derived epithelial progenitors via mesenchymal-epithelial transition (MET).

Methods

STEMPRO human ADSC were cultured with specific inhibitors antagonizing glycogen synthase kinase-3 and transforming growth factor-β signaling, followed by culture under a defined progenitor cell targeted-epithelial differentiation condition to generate epithelial-like cells (MET-Epi), which were characterized for cell viability, mesenchymal, and epithelial phenotypes using immunofluorescence and flow cytometry. Tissue-engineered (TE) MET-Epi cells on fibrin gel were transplanted to corneal surface of the rat LSCD model caused by alkali injury. Epithelial healing, corneal edema, and haze grading, CE formation were assessed by fluorescein staining, slit lamp bio-microscopy, anterior segment optical coherence tomography, and immunohistochemistry.

Results

CD73high/CD90high/CD105high/CD166high/CD14negative/CD31negative human ADSC underwent MET, giving viable epithelial-like progenitors expressing δNp63, CDH1 (E-cadherin), epidermal growth factor receptor, integrin-β4, and cytokeratin (CK)-5, 9. Under defined epithelial differentiation culture, these progenitors generated MET-Epi cells expressing cell junction proteins ZO1 and occludin. When transplanted onto rat corneal surface with LSCD-induced PED, TE-MET-Epi achieved more efficient epithelial healing, suppressed corneal edema, and opacities, when compared to corneas without treatment or transplanted with TE-ADSC. CE markers (CK3, 12, and CDH1) were expressed on TE-MET-Epi-transplanted corneas but not in other control groups.

Conclusion

Human ADSC-derived epithelial-like cells, via MET, recovered the CE from PED associated with LSCD. ADSC can be a viable adult stem cell source for potential autologous epithelial cell-based therapy for corneal surface disorders.
Entropy clustering-based granular classifiers for network intrusion detection
Authors: Liu Hui , Hao Gang , Xing Bin
Published: January 2020

Support vector machine (SVM) is one of the effective classifiers in the field of network intrusion detection; however, some important information related to classification might be lost in the reprocessing. In this paper, we propose a granular classifier based on entropy clustering method and support vector machine to overcome this limitation. The overall design of classifier is realized with the aid of if-then rules that consists of a premise part and conclusion part. The premise part realized by the entropy clustering method is used here to address the problem of a possible curse of dimensionality, while the conclusion part realized by support vector machines is utilized to build local models. In contrast to the conventional SVM, the proposed entropy clustering-based granular classifiers (ECGC) can be regarded as an entropy-based support function machine. Moreover, an opposition-based genetic algorithm is proposed to optimize the design parameters of the granular classifiers. Experimental results show the effectiveness of the ECGC when compared with some classical models reported in the literatures.
Fourth-order finite difference scheme and efficient algorithm for nonlinear fractional Schrödinger equations
Authors: Chang Yan , Chen Huanzhen
Published: January 2020

To improve the computing efficiency, a fourth-order difference scheme is proposed and a fast algorithm is designed to simulate the nonlinear fractional Schrödinger (FNLS) equation oriented from the fractional quantum mechanics. The numerical analysis and experiments conducted in this article show that the proposed difference scheme has the optimal second-order and fourth-order convergence rates in time and space respectively, reduces its computation cost to$\mathcal{O}(M\log M)$O(MlogM), and recognizes accurately its physical feature of FNLS such as the mass balance.
A hybrid predator–prey model with general functional responses under seasonal succession alternating between Gompertz and logistic growth
Authors: Hang Lei , Zhang Long , Wang Xiaowen , Li Hongli , Teng Zhidong
Published: January 2020

In this paper, a hybrid predator–prey model with two general functional responses under seasonal succession is proposed. The model is composed of two subsystems: in the first one, the prey follows the Gompertz growth, and it turns to the logistic growth in the second subsystem since seasonal succession. The two processes are connected by impulsive perturbations. Some very general, weak criteria on the ultimate boundedness, permanence, existence, uniqueness and global attractivity of predator-free periodic solution are established. We find that the hybrid population model with seasonal succession has more survival possibilities of natural species than the usual population models. The theoretical results are illustrated by special examples and numerical simulations.
Magnetic micropump embedded in contact lens for on-demand drug delivery
Authors: Wang Cong , Park Jungyul
Published: January 2020

In this paper, we report a thin magnetic micropump embedded in contact lens, which is capable of on-demand one-directional drug delivery. The proposed micropump can be actuated by the external magnetic field whenever needed without the need of battery. A micro check valve was integrated with the micropump for one-directional drug delivery from the micropump to the post-lens tear film. With actuation of the external magnetic field, the micro check valve is opened, and on-demand drug release can be realized. On the contrary, without an external magnetic field, the micro check valve is closed, and the undesired drug diffusion can be prevented. Through the control of the strength and the frequency of the magnetic field pulse, on-demand drug release and controlled dose can be realized.
High validity of measuring the width and volume of medial meniscal extrusion three-dimensionally using an MRI-derived tibial model
Authors: Watanabe Goro , Hoshi Kenji , Kurose Yasuo , Gamada Kazuyoshi
Published: January 2020

Background

Medial meniscal extrusion (MME) is an important marker of knee osteoarthritis (KOA) progression. The purposes of this study were: 1) to determine whether there are morphological differences between CT- and MRI-derived tibial plateau models; and 2) to determine whether measurement of MME volume and width using an MRI-derived tibial model is as accurate as measurements on a CT-derived tibial model.

Methods

This was a cross-sectional study that enrolled ten participants with medial KOA (Kellgren-Lawrence grade 1 to 3). Primary outcome was surface difference of the medial tibial plateau between CT- and MRI-derived models. Furthermore, volume and cross-sectional area of the medial tibial plateau were compared between CT- and MRI-derived models. Measurements of MME volume and width were compared between CT- and MRI-derived tibial models.

Results

Minimal and maximal surface differences of the medial tibial plateau between the CT- and MRI-derived models were − 0.15 [− 0.44, 0.14] mm (mean [95% confidence interval]) and 0.24 [− 0.09, 0.57] mm, respectively. There were no significant differences in volume and cross-sectional area of the medial tibial plateau between CT- and MRI-derived tibial models. The MME volumes measured on CT- and MRI-derived models were 942.6 [597.7, 1287.6] mm3 and 916.2 [557.9, 1274.6] mm3, respectively (p = 0.938). The MME widths measured on CT- and MRI-derived models were 4.2 [1.9, 6.5] mm and 4.5 [2.2, 6.9] mm, respectively (p = 0.967).

Conclusions

CT- and MRI-derived models of the medial tibial plateau did not show significant morphological differences. Both CT- and MRI-derived tibia can be used as a reference to measure MME in early-to-moderate medial KOA.
Suction pad unit using a bellows pneumatic actuator as a support mechanism for an end effector of depalletizing robots
Authors: Tanaka Junya , Ogawa Akihito , Nakamoto Hideichi , Sonoura Takafumi , Eto Haruna
Published: January 2020

This paper describes a vacuum suction-type end effector for depalletizing robots in distribution centers. The developed end effector has multiple suction pad units to which a bellows pneumatic actuator is applied as the support mechanism. Load-bearing capacity is improved due to a high-strength wire provided inside the bellows, and the contraction force is improved due to ring members placed inside of the ridges of the rubber bellows. The developed end effector is attached to the arm of a linear motion-type depalletizing robot, and its real-world performance is verified. Verification results confirm that the suction pad units tolerate cardboard box inclination and differences in box height by a simple lowering motion of the arm, and multiple cardboard boxes can be simultaneously unloaded. Moreover, as compared with conventional end effectors, the developed end effector achieves large expansion and contraction in a thin structure. The developed end effector is expected to broaden applications for depalletizing robots.
Development of a vibratory cueing system using an implicit method to increase walking speed in patients with stroke: a proof-of-concept study
Authors: Yasuda Kazuhiro , Hayashi Yuki , Tawara Anna , Iwata Hiroyasu
Published: January 2020

One of the main sequelae of stroke is dificulty walking, which is characterized by a decreased gait velocity and asymmetrical walking patterns. The purpose of this research was initially focused on developing a vibro-tactile cueing device that recognizes an implicit increase in cadence frequency. Subsequently, a proof-of-concept study with patients who had experienced stroke was conducted to examine the applicability of the system that had been developed. We applied Weber’s law to provide an implicit method for increasing cueing frequency. This law involves the calculation of just-noticeable difference (JND) relative to a previous state. Throughout training with the proposed cueing device, patients marginally increased cadence, and their cadence and gait speeds were significantly increased post-test. Hip circumduction gait (i.e., abnormal gait patterns) did not change significantly throughout training. Notably, patients reported that they were unaware of any changes associated with the vibration stimulus. Our result demonstrates the immediate changes to cadence and gait speed that occurred through training with the proposed implicit cueing device. However, the result of this study is confined to immediate gait changes after training and utilized only a small sample of stroke patients. Thus, the limited volume of data obtained prevents rigorous analysis regarding the applicability of this training method. Nonetheless, these results are promising and provide a starting point from which to base larger studies.
Impact of US industry payment disclosure laws on payments to surgeons: a natural experiment
Authors: Rhee Taeho Greg , Stanic Tijana , Ross Joseph S.
Published: January 2020

Objectives

To compare changes in the number and amount of payments received by orthopedic and non-orthopedic surgeons from industry between 2014 and 2017.

Methods

Using the Centers for Medicare and Medicaid Services (CMS) Open Payment database from 2014 to 2017, we conducted a retrospective cohort study of industry payments to surgeons, including general payments and research payments.

Results

Among orthopedic surgeons, the total number of general payments decreased from 248,698 in 2014 to 241,966 in 2017, but their total value increased from $97.1 million in 2014 to $110.2 million in 2017. Among non-orthopedic surgeons, the total number decreased from 604,884 in 2014 to 582,490 in 2017, while the total value remained stable at approximately $159 million. Between 2014 and 2017, there was a differential increase in the median number of general payments received by non-orthopedic when compared to orthopedic surgeons (incidence rate ratio, 1.09; 95% CI, 1.08–1.09; p < 0.001), but a differential decline in the median value of general payments (− 8.9%; 95% CI, − 9.5%, − 8.4%; p < 0.001). Findings were consistent when stratified by nature of payment. In contrast, between 2014 and 2017, there was neither a differential change in the median number nor median value of research payments received by non-orthopedics.

Conclusion

Examination of a natural experiment of prior public disclosure of payments to orthopedic surgeons suggests that the Physician Payment Sunshine Act was associated with an increase in the number, but a decline in the value, of general payments received by non-orthopedic surgeons, but not on research payments received.
Assessing the effects of trade openness on sustainable development: evidence from India
Authors: Sheikh Mehraj Ahmad , Malik Mushtaq Ahmad , Masood Rana Zehra
Published: January 2020

Over the years, world market is integrating at much faster pace through increasing trade openness. Not being an unmixed blessing, consistent efforts have been made to examine impact of trade openness on economic, environmental and social welfare. This study is an attempt to empirically examine the implications of trade openness on sustainable development in India since liberalization policy 1991. We used the Autoregressive Distributed Lag (ARDL) model to test the relationship between sustainable development and trade openness along with other control variables that are supposed to affect sustainable development. The results established supports the opinion of environmentalists. The empirical results are contrary to the conventionally held belief, indicating that trade shares a negative correlation with green GDP growth and positive correlation with gap between conventional GDP and green GDP. These findings support the arguments that trade openness tend to be both distorting and detrimental to the future generations.
Offloading items from memory: individual differences in cognitive offloading in a short-term memory task
Authors: Morrison Alexandra B. , Richmond Lauren L.
Published: January 2020

Cognitive offloading refers to the act of reducing the mental processing requirements of a task through physical actions like writing down information or storing information on a cell phone or computer. Offloading can lead to improved performance on ongoing tasks with high cognitive demand, such as tasks where multiple pieces of information must be simultaneously maintained. However, less is known about why some individuals choose to engage in offloading and under what conditions they might choose to do so. In the present study, offloading behavior is investigated in a short-term memory task requiring memory for letters. The present study is a replication and extension of a previous study conducted by Risko and Dunn, and tests the new prediction that individuals with lower working memory capacity will be more likely to offload. Here, we find that offloading information confers a performance advantage over relying on internal memory stores, particularly at higher memory loads. However, we fail to observe that those with poorer memory abilities have a greater propensity for offloading or benefit more from it. Instead, our findings suggest that cognitive offloading may be a valid compensatory strategy to improve performance of memory-based tasks for individuals with a wide range of memory ability.
Imaging of tumour response to immunotherapy
Authors: Dromain Clarisse , Beigelman Catherine , Pozzessere Chiara , Duran Rafael , Digklia Antonia
Published: January 2020

A wide range of cancer immunotherapy approaches has been developed including non-specific immune-stimulants such as cytokines, cancer vaccines, immune checkpoint inhibitors (ICIs), and adoptive T cell therapy. Among them, ICIs are the most commonly used and intensively studied. Since 2011, these drugs have received marketing authorisation for melanoma, lung, bladder, renal, and head and neck cancers, with remarkable and long-lasting treatment response in some patients. The novel mechanism of action of ICIs, with immune and T cell activation, leads to unusual patterns of response on imaging, with the advent of so-called pseudoprogression being more pronounced and frequently observed when compared to other anticancer therapies. Pseudoprogression, described in about 2–10% of patients treated with ICIs, corresponds to an increase of tumour burden and/or the appearance of new lesions due to infiltration by activated T cells before the disease responds to therapy. To overcome the limitation of response evaluation criteria in solid tumors (RECIST) to assess these specific changes, new imaging criteria—so-called immune-related response criteria and then immune-related RECIST (irRECIST)—were proposed. The major modification involved the inclusion of the measurements of new target lesions into disease assessments and the need for a 4-week re-assessment to confirm or not confirm progression. The RECIST working group introduced the new concept of “unconfirmed progression”, into the irRECIST. This paper reviews current immunotherapeutic approaches and summarises radiologic criteria to evaluate new patterns of response to immunotherapy. Furthermore, imaging features of immunotherapy-related adverse events and available predictive biomarkers of response are presented.
Real-financial connectedness in the Swiss economy
Authors: Uluceviz Erhan , Yilmaz Kamil
Published: January 2020

We study macro-financial linkages and their importance within the Swiss economy from a network perspective. First, we investigate the real-financial connectedness in the Swiss economy, using the KOF economic barometer, obtained from real and financial variables, and, the real activity index (RAI), we distilled from a small set of real variables, as two alternative proxies for the real side. Whereas the KOF-barometer-based analysis shows that both sides transmit sizeable shocks to each other without one dominating the other, the RAI-based analysis shows that in the aggregate, the financial side turns out to be the net shock transmitter to the real sector. In the second part, we focus on the relative importance of financial markets as shock propagators using a network centrality measure. We find that 2008–2009 recession in Switzerland and the Swiss National Bank’s (SNB) exchange rate policy changes in 2011 and 2015 have significantly altered the way the shocks are transmitted across the two sides of the economy. During 2009–2011, stock, bond, and foreign exchange (FX) markets, in descending order, played important roles as shock propagators. Following the SNB’s 2015 policy decision to discontinue the lower bound for the EUR/CHF exchange rate, FX market has become equally important as the stock market but more important than the bond market as a shock propagator.
Efficacy and Prognostic Factors of Sunitinib as First-Line Therapy for Patients With Metastatic Renal Cell Carcinoma in an Arab Population
Authors: Badran Ahmed , Elshenawy Mahmoud A. , Shahin Amgad , Aljubran Ali , Alzahrani Ahmed , Eldali Abdelmoneim , Bazarbashi Shouki
Published: January 2020

PURPOSE

Antiangiogenic tyrosine kinase inhibitors have been the mainstay first-line therapy for metastatic renal cell carcinoma (mRCC). We reviewed the efficacy of first-line therapy with sunitinib in patients with mRCC in an Arab population.

METHODS

Medical records of patients with mRCC treated at a tertiary care center in Saudi Arabia, during the period from 2007 to 2016, were reviewed. Demographic data, treatment received, response, and prognostic factors were analyzed.

RESULTS

Fifty-five patients who received sunitinib were identified. The median age was 60 years (range, 18 to 78 years), and 42 of the 55 patients were men (76.3%). International Metastatic RCC Diagnostic Consortium prognostic scores for favorable/intermediate/poor were 14.5%/43.6%/38.2%, respectively. The median performance status was 1, and the median Charlson comorbidity index score was 9. Thirty-seven patients (67.2%) had cytoreductive nephrectomy. Thirty-seven patients (67.2%) had clear cell histology. Twenty-two patients (40%) underwent dose reduction. Twenty-seven patients (49%) received second-line therapy, and seven patients (12.7%) received third-line therapy. Response rates were complete response in one patient (1.8%), partial response in 17 (30.9%), stable disease in 10 (18.1), and disease progression in 20 (36.3%). Progression-free survival (PFS) and overall survival (OS) were 6.0 and 24.7 months, respectively. Univariate analysis showed statistically improved PFS for dose reduction ( P = .015) and the development of hypothyroidism ( P = .03). It also showed statistically improved OS for dose reduction ( P = .035), hypothyroidism ( P = .0002), and cytoreductive nephrectomy ( P = .0052). Multivariate analysis showed statistically improved PFS for dose reduction ( P = .01) and OS for development of hypothyroidism ( P = .007).

CONCLUSION

Our data for sunitinib in mRCC show significantly lower PFS than expected. The absence of prognostic value of the International Metastatic RCC Diagnostic Consortium scoring system and pathologic subtype warrant further investigation and possible inclusion of genetic scoring in this ethnic group of patients.