bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluorescent pyrene moiety in fluorinated C6F5-corroles increases the interaction with HSA and CT-DNA
Authors: Acunha Thiago V. , Chaves Otávio A. , Iglesias Bernardo A.
Published: October 2020

Two fluorinated meso-C6F5-corroles (5,15-bis(pentafluorophenyl)-10-(phenyl)corrole and 5,15-bis(pentafluorophenyl)-10-(1-pyrenyl)corrole) were biologically evaluated in terms of binding affinity to human serum albumin (HSA) and calf-thymus DNA (CT-DNA) via multiple spectroscopic techniques under physiological conditions combined with molecular docking calculations. The HSA:corrole interaction is spontaneous and moderate via static binding, disturbing both secondary and tertiary albumin structures at high fluorinated corrole concentrations. The competitive binding studies indicated positive cooperativity or allosteric activation, while molecular docking calculations suggested that both fluorinated corroles bind preferentially inside subdomains IIA and IB (sites I and III, respectively). The experimental CT-DNA binding assays indicated that fluorinated corroles interact spontaneously by non-classical modes in the minor groove of the CT-DNA strands via static fluorescence quenching mechanism. Molecular docking results also showed the minor groove as the main binding site for CT-DNA. Overall, the pyrene moiety increased the interaction with HSA and CT-DNA, which is probably due to the planarity and volume that favors the pyrene unit to be buried inside the biomacromolecule pockets.
Synthesis and characterization of a porphyrin-crown ether conjugate as a potential intermediate for drug delivery application
Authors: Fathalla Maher
Published: October 2020

The development of synthetic strategies for functional building units plays a central role in supramolecular chemistry. Both porphyrin and crown ethers have attracted the attention of researchers worldwide owing to their unique properties. It is envisioned that the integration of the two molecules will result in hybrid materials with potential applications in many fields. In the present study, a new porphyrin derivative 3 appended with four 18-crown-6 (18C6) ether moieties was synthesized through the Suzuki-Miyaura coupling of boronic ester porphyrin 1 and 4-bromobenzo-18-crown-6 2 in 80% yield. Porphyrin 3 was fully characterized by 1H/[Formula: see text]C NMR spectroscopy and high resolution mass spectrometry. The tendency of the 18C6 to form host-guest complexes with ammonium cations was exploited to assemble cation responsive hybrid material of porphyrin 3 and ammonium immobilized mesoporous silica nanoparticles (MSNs). Furthermore, the potential application of the 3/MSNs conjugate as a cation-responsive drug delivery vehicle was investigated in solution by UV-vis and fluorescence spectroscopies.
Aspirin in the Prevention of Colorectal Neoplasia
Authors: Drew David A. , Chan Andrew T.
Published: October 2020

High-quality evidence indicates that regular use of aspirin is effective in reducing the risk for precancerous colorectal neoplasia and colorectal cancer (CRC). This has led to US and international guidelines recommending aspirin for the primary prevention of CRC in specific populations. In this review, we summarize key questions that require addressing prior to broader adoption of aspirin-based chemoprevention, review recent evidence related to the benefits and harms of aspirin use among specific populations, and offer a rationale for precision prevention approaches. We specifically consider the mechanistic implications of evidence showing differences in aspirin's effects according to age, the potential role of modifiable mechanistic biomarkers for personalizing prevention, and emerging evidence that the gut microbiota may offer novel aspirin-associated preventive targets to reduce high-risk neoplasia.
Model-Informed Precision Dosing: Background, Requirements, Validation, Implementation, and Forward Trajectory of Individualizing Drug Therapy
Authors: Darwich Adam S. , Polasek Thomas M. , Aronson Jeffrey K. , Ogungbenro Kayode , Wright Daniel F.B. , Achour Brahim , Reny Jean-Luc , Daali Youssef , Eiermann Birgit , Cook Jack , Lesko Lawrence , McLachlan Andrew J. , Rostami-Hodjegan Amin
Published: October 2020

Model-informed precision dosing (MIPD) has become synonymous with modern approaches for individualizing drug therapy, in which the characteristics of each patient are considered as opposed to applying a one-size-fits-all alternative. This review provides a brief account of the current knowledge, practices, and opinions on MIPD while defining an achievable vision for MIPD in clinical care based on available evidence. We begin with a historical perspective on variability in dose requirements and then discuss technical aspects of MIPD, including the need for clinical decision support tools, practical validation, and implementation of MIPD in health care. We also discuss novel ways to characterize patient variability beyond the common perceptions of genetic control. Finally, we address current debates on MIPD from the perspectives of the new drug development, health economics, and drug regulations.
Novel approaches to restore parasympathetic activity to the heart in cardiorespiratory diseases
Authors: Dyavanapalli Jhansi
Published: October 2020

Neural control of the heart is regulated by sympathetic and parasympathetic divisions of the autonomic nervous system, both opposing each other to maintain cardiac homeostasis via regulating heart rate, conduction velocity, force of contraction, and coronary blood flow. Sympathetic hyperactivity and diminished parasympathetic activity are the characteristic features of many cardiovascular disease states including hypertension, myocardial ischemia, and arrhythmias that result in heart failure. Restoring parasympathetic activity to the heart has recently been identified as the promising approach to treat such conditions. However, approaches that used vagal nerve stimulation have been shown to be unsuccessful in heart failure. This review focuses on novel chemogenetic approaches used to identify the cardioprotective nature of activating neural points along the vagal pathway (both central and peripheral) while being selectively therapeutic in heart failure and obstructive sleep apnea.
Heterogeneity of Tumors in Breast Cancer: Implications and Prospects for Prognosis and Therapeutics
Authors: Tuasha Nigatu , Petros Beyene
Published: October 2020

Breast cancer is the most commonly diagnosed form of cancer in women comprising 16% of all female cancers. The disease shows high intertumoral and intratumoral heterogeneity posing diagnostic and therapeutic challenges with unpredictable clinical outcome and response to existing therapy. Mounting evidence is ascertaining that breast cancer stem cells (CSCs) are responsible for tumor initiation, progression, recurrence, evolution, metastasis, and drug resistance. Therapeutics selectively targeting the CSCs based on distinct surface molecular markers and enhanced intracellular activities of these cells continue to evolve and hold significant promise. Having plethora of heterogeneity accompanied with failure of existing conventional therapeutics and poor prognosis, the present review focuses on elucidating the main signaling pathways in breast CSCs as major therapeutic targets. The role of developments in nanomedicine and miRNA as targeted delivery of therapeutic anticancer agents is also highlighted.
Exosomes from Placenta-Derived Mesenchymal Stem Cells Are Involved in Liver Regeneration in Hepatic Failure Induced by Bile Duct Ligation
Authors: Jun Ji Hye , Kim Jae Yeon , Choi Jong Ho , Lim Ja-Yun , Kim Kyunggon , Kim Gi Jin
Published: October 2020

Although the liver has a regenerative capacity, hepatic failure is a severe and irreversible chronic disease. Placenta-derived mesenchymal stem cells (PD-MSCs) have distinctive features, such as recycling of the placenta waste after birth, ease of accessibility, abundant cell numbers, and strong immunosuppressive properties. Previously, we reported that PD-MSCs can regenerate the liver in hepatic failure through antifibrotic and autophagic mechanisms. Many reports have investigated whether exosomes, which are formed by the budding of vesicular bodies and are emitted into the blood, from stem cells have therapeutic potential in various diseases. C-reactive protein (CRP) is produced in hepatocytes and secreted via vessels. Therefore, the objectives of this study were to compare the expression of CRP in exosomes of a hepatic failure rat model (bile duct ligation, BDL) and to evaluate the therapeutic effect by their correlation between CRP and angiogenesis depending on PD-MSC transplantation. The exosomes were analyzed in a BDL rat model with transplantation of PD-MSCs through LC-MS analysis and precipitation solution. The exosomes, CRP, and factors related to these molecules were evaluated and quantified in exosomes as well as investigated by real-time PCR, Western blot, and immunofluorescence (IF) in vivo and in vitro. CRP was present in exosomes from serum of a rat model and increased by PD-MSC transplantation. In the exosomes, CRP upregulated the factors related to the Wnt signaling pathway and angiogenesis in the BDL rat liver-transplanted PD-MSCs. Also, CRP regulated the Wnt pathway and vascularization in rat hepatocytes by interacting with endothelial cells. Therefore, our findings indicate that CRP in exosomes excreted by PD-MSCs functions in angiogenesis via the Wnt signaling pathway.
Multiobjective Lightning Flash Algorithm Design and Its Convergence Analysis via Martingale Theory
Authors: Duan Jiandong , Wang Jing , Liu Xinghua , Xiao Gaoxi
Published: October 2020

In this paper, a novel multiobjective lightning flash algorithm (MOLFA) is proposed to solve the multiobjective optimization problem. The charge population state of the lightning flash algorithm is defined, and we prove that the charge population state sequence is a Markov chain. Since the convergence analysis of MOLFA is to investigate whether a Pareto optimal solution can be reached when the optimal charge population state is obtained, the development of a charge population state is analyzed to achieve the goal of this paper. Based on the martingale theory, the MOLFA convergence analysis is carried out in terms of the supermartingale convergence theorem, which shows that the MOLFA can reach the global optimum with probability one. Finally, the effectiveness of the proposed MOLFA is verified by a numerical simulation example.
A Second-Iteration Square Koch Fractal Slot Antenna for UHF Downlink Telemetry Applications in CubeSat Small Satellites
Authors: Simon Jorge , Flores-Troncoso Jorge , Alvarez-Flores Jose Luis , Soriano-Equigua Leonel , Cardenas-Juarez Marco , Arce Armando , Briones Edgar , Sosa-Pedroza Jorge
Published: October 2020

This article presents the design, fabrication, and measurement of a square Koch fractal slot antenna for UHF band using both the FR4-G10 and Cuclad 250 substrates. Conveniently, this 56.56 cm full-length antenna possesses a geometry that allows it to be incorporated into the standardized 10 cm × 10 cm faces of the CubeSats. Furthermore, it is shown that both selected substrates exhibit an acceptable performance at the frequency of interest despite the economic cost difference and relative permittivity. Hence, the commercial FR4-G10 antenna substrate can be preferred because of its low-cost and admissible performance at 458 MHz, which is a frequency in the UHF band that is commonly used for telemetry, tracking, and command downlinks of CubeSats. Measurements show that the proposed antenna exhibits a reflection coefficient of −16.53 dB, a bandwidth of 22.62 MHz at −10 dB, a VSWR of 1.3508, a normalized impedance of 0.794 − j0.173 at 50 Ω, and a directivity of 2.24 dBi. The contribution of this work consists in the use of a fractal geometry to construct a low-cost slot antenna working at UHF frequencies over the limited area of the CubeSat faces and in order to optimize the area for an eventual coexistence with solar cells.
Mathematical Model to Estimate and Predict the COVID-19 Infections in Morocco: Optimal Control Strategy
Authors: Zakary Omar , Bidah Sara , Rachik Mostafa , Ferjouchia Hanane
Published: October 2020

In this paper, we aim to estimate and predict the situation of the new coronavirus pandemic (COVID-19) in countries under quarantine measures. First, we present a new discrete-time mathematical model describing the evolution of the COVID-19 in a population under quarantine. We are motivated by the growing numbers of infections and deaths in countries under quarantine to investigate potential causes. We consider two new classes of people, those who respect the quarantine and stay at home, and those who do not respect the quarantine and leave their homes for one or another reason. Second, we use real published data to estimate the parameters of the model, and then, we estimate these populations in Morocco. We investigate the impact of people who underestimate the quarantine by considering an optimal control strategy to reduce this category and then reducing the number of the population at risk in Morocco. We provide several simulations to support our findings.
The Amino-Terminal Oligomerization Domain of Angiopoietin-2 Affects Vascular Remodeling, Mammary Gland Tumor Growth, and Lung Metastasis in Mice
Authors: Kapiainen Emmi , Kihlström Minna K. , Pietilä Riikka , Kaakinen Mika , Ronkainen Veli-Pekka , Tu Hongmin , Heikkinen Anne , Devarajan Raman , Miinalainen Ilkka , Laitakari Anna , Ansarizadeh Mohammadhassan , Zhang Qin , Wei Gong-Hong , Ruddock Lloyd , Pihlajaniemi Taina , Elamaa Harri , Eklund Lauri
Published: October 2020

Angiopoietin-2 (ANGPT2) is a context-dependent TIE2 agonistic or antagonistic ligand that induces diverse responses in cancer. Blocking ANGPT2 provides a promising strategy for inhibiting tumor growth and metastasis, yet variable effects of targeting ANGPT2 have complicated drug development. ANGPT2443 is a naturally occurring, lower oligomeric protein isoform whose expression is increased in cancer. Here, we use a knock-in mouse line (mice expressing Angpt2443), a genetic model for breast cancer and metastasis (MMTV-PyMT), a syngeneic melanoma lung colonization model (B16F10), and orthotopic injection of E0771 breast cancer cells to show that alternative forms increase the diversity of Angpt2 function. In a mouse retina model of angiogenesis, expression of Angpt2443 caused impaired venous development, suggesting enhanced function as a competitive antagonist for Tie2. In mammary gland tumor models, Angpt2443 differentially affected primary tumor growth and vascularization; these varying effects were associated with Angpt2 protein localization in the endothelium or in the stromal extracellular matrix as well as the frequency of Tie2-positive tumor blood vessels. In the presence of metastatic cells, Angpt2443 promoted destabilization of pulmonary vasculature and lung metastasis. In vitro, ANGPT2443 was susceptible to proteolytical cleavage, resulting in a monomeric ligand (ANGPT2DAP) that inhibited ANGPT1- or ANGPT4-induced TIE2 activation but did not bind to alternative ANGPT2 receptor α5β1 integrin. Collectively, these data reveal novel roles for the ANGPT2 N-terminal domain in blood vessel remodeling, tumor growth, metastasis, integrin binding, and proteolytic regulation.

Significance:

This study identifies the role of the N-terminal oligomerization domain of angiopoietin-2 in vascular remodeling and lung metastasis and provides new insights into mechanisms underlying the versatile functions of angiopoietin-2 in cancer.

See related commentary by Kamiyama and Augustin, p. 35
Comparative Genomics Reveals Distinct Immune-oncologic Pathways in African American Men with Prostate Cancer
Authors: Awasthi Shivanshu , Berglund Anders , Abraham-Miranda Julieta , Rounbehler Robert J. , Kensler Kevin , Serna Amparo , Vidal Adriana , You Sungyong , Freeman Michael R. , Davicioni Elai , Liu Yang , Karnes R. Jeffrey , Klein Eric A. , Den Robert B. , Trock Bruce J. , Campbell Joshua D. , Einstein David J. , Gupta Raavi , Balk Steven , Lal Priti , Park Jong Y. , Cleveland John L. , Rebbeck Timothy R. , Freedland Stephen J. , Yamoah Kosj
Published: October 2020

Purpose:

The role of immune-oncologic mechanisms of racial disparities in prostate cancer remains understudied. Limited research exists to evaluate the molecular underpinnings of immune differences in African American men (AAM) and European American men (EAM) prostate tumor microenvironment (TME).

Experimental Design:

A total of 1,173 radiation-naïve radical prostatectomy samples with whole transcriptome data from the Decipher GRID registry were used. Transcriptomic expressions of 1,260 immune-specific genes were selected to assess immune-oncologic differences between AAM and EAM prostate tumors. Race-specific differential expression of genes was assessed using a rank test, and intergene correlational matrix and gene set enrichment was used for pathway analysis.

Results:

AAM prostate tumors have significant enrichment of major immune-oncologic pathways, including proinflammatory cytokines, IFNα, IFNγ, TNFα signaling, ILs, and epithelial–mesenchymal transition. AAM TME has higher total immune content score (ICSHIGH) compared with 0 (37.8% vs. 21.9%, P = 0.003). AAM tumors also have lower DNA damage repair and are genomically radiosensitive as compared with EAM. IFITM3 (IFN-inducible transmembrane protein 3) was one of the major proinflammatory genes overexpressed in AAM that predicted increased risk of biochemical recurrence selectively for AAM in both discovery [HRAAM = 2.30; 95% confidence interval (CI), 1.21–4.34; P = 0.01] and validation (HRAAM = 2.42; 95% CI, 1.52–3.86; P = 0.0001) but not in EAM.

Conclusions:

Prostate tumors of AAM manifest a unique immune repertoire and have significant enrichment of proinflammatory immune pathways that are associated with poorer outcomes. Observed immune-oncologic differences can aid in a genomically adaptive approach to treating prostate cancer in AAM.
Heat Shock Protein-90 Inhibition Alters Activation of Pancreatic Stellate Cells and Enhances the Efficacy of PD-1 Blockade in Pancreatic Cancer
Authors: Zhang Yuchen , Ware Michael B. , Zaidi Mohammad Y. , Ruggieri Amanda N. , Olson Brian M. , Komar Hannah , Farren Matthew R. , Nagaraju Ganji Purnachandra , Zhang Chao , Chen Zhengjia , Sarmiento Juan M. , Ahmed Rafi , Maithel Shishir K. , El-Rayes Bassel F. , Lesinski Gregory B.
Published: October 2020

Pancreatic ductal adenocarcinoma (PDAC) has a prominent fibrotic stroma, which is a result of interactions between tumor, immune and pancreatic stellate cells (PSC), or cancer-associated fibroblasts (CAF). Targeting inflammatory pathways present within the stroma may improve access of effector immune cells to PDAC and response to immunotherapy. Heat shock protein-90 (Hsp90) is a chaperone protein and a versatile target in pancreatic cancer. Hsp90 regulates a diverse array of cellular processes of relevance to both the tumor and the immune system. However, to date the role of Hsp90 in PSC/CAF has not been explored in detail. We hypothesized that Hsp90 inhibition would limit inflammatory signals, thereby reprogramming the PDAC tumor microenvironment to enhance sensitivity to PD-1 blockade. Treatment of immortalized and primary patient PSC/CAF with the Hsp90 inhibitor XL888 decreased IL6, a key cytokine that orchestrates immune changes in PDAC at the transcript and protein level in vitro. XL888 directly limited PSC/CAF growth and reduced Jak/STAT and MAPK signaling intermediates and alpha-SMA expression as determined via immunoblot. Combined therapy with XL888 and anti–PD-1 was efficacious in C57BL/6 mice bearing syngeneic subcutaneous (Panc02) or orthotopic (KPC-Luc) tumors. Tumors from mice treated with both XL888 and anti–PD-1 had a significantly increased CD8+ and CD4+ T-cell infiltrate and a unique transcriptional profile characterized by upregulation of genes associated with immune response and chemotaxis. These data demonstrate that Hsp90 inhibition directly affects PSC/CAF in vitro and enhances the efficacy of anti–PD-1 blockade in vivo.
Targeting Dormant Ovarian Cancer CellsIn Vitroand in anIn VivoMouse Model of Platinum Resistance
Authors: Huang Zhiqing , Kondoh Eiji , Visco Zachary R. , Baba Tsukasa , Matsumura Noriomi , Dolan Emma , Whitaker Regina S. , Konishi Ikuo , Fujii Shingo , Berchuck Andrew , Murphy Susan K.
Published: October 2020

Spheroids exhibit drug resistance and slow proliferation, suggesting involvement in cancer recurrence. The protein kinase C inhibitor UCN-01 (7-hydroxystaurosporine) has shown higher efficacy against slow proliferating and/or quiescent ovarian cancer cells. In this study, tumorigenic potential was assessed using anchorage-independent growth assays and spheroid-forming capacity, which was determined with ovarian cancer cell lines as well as primary ovarian cancers. Of 12 cell lines with increased anchorage-independent growth, 8 formed spheroids under serum-free culture conditions. Spheroids showed reduced proliferation (P < 0.0001) and Ki-67 immunostaining (8% vs. 87%) relative to monolayer cells. Spheroid formation was associated with increased expression of mitochondrial pathway genes (P ≤ 0.001) from Affymetrix HT U133A gene expression data. UCN-01, a kinase inhibitor/mitochondrial uncoupler that has been shown to lead to Puma-induced mitochondrial apoptosis as well as ATP synthase inhibitor oligomycin, demonstrated effectiveness against spheroids, whereas spheroids were refractory to cisplatin and paclitaxel. By live in vivo imaging, ovarian cancer xenograft tumors were reduced after primary treatment with carboplatin. Continued treatment with carboplatin was accompanied by an increase in tumor signal, whereas there was little or no increase in tumor signal observed with subsequent treatment with UCN-01 or oltipraz. Taken together, our findings suggest that genes involved in mitochondrial function in spheroids may be an important therapeutic target in preventing disease recurrence.
A Prospective Registry of Atrial Fibrillation Ablation with the Ablation Index Technology: Rationale and Study Design
Authors: Gasimova Nigar Z. , Kolunin Grigory V. , Artyukhina Elena A. , Ivanitsky Eduard A. , Lebedev Dmitry S. , Mikhaylov Evgeny N.
Published: October 2020

This is a prospective multicenter registry of atrial fibrillation (AF) ablation with the Ablation Index (AI) technology, which has been introduced as a marker predicting ablation lesion depth. The index incorporates the main parameters of radiofrequency point-by-point ablation: power, contact force, and time of ablation. The AI is calculated for every operator depending on personal skills, and there are no strict indications on the range of the parameter considering its safety and efficacy during pulmonary vein isolation. The registry aims to evaluate AI values used in different centers by different operators and to evaluate the optimal limits associated with better acute and long-term AF ablation results.
Clobetasol Attenuates White Matter Injury by Promoting Oligodendrocyte Precursor Cell Differentiation
Authors: Su Xuewen , Yuan Haifeng , Bai Yuxin , Chen Junlong , Sui Mingze , Zhang Xiaomei , Liang Yanyan , Feng Wanyu , Dou Zhongxia , Zhu Hua
Published: October 2020

Introduction: White matter injury (WMI) is the most common brain injury in preterm infants and can result in life-long neurological deficits. The main cause of WMI is damage to the oligodendrocyte precursor cells (OPC) in the brain that results in delayed myelin sheath formation, or the destruction of existing myelin sheaths. OPC undergo highly regulated and strictly timed developmental changes that result in their transformation to mature oligodendrocytes capable of myelin production. Objective: Studies have shown that clobetasol strongly promotes differentiation of OPC into myelin sheaths. Therefore, we hypothesized that clobetasol may be a therapeutic option for the treatment of preterm WMI. Methods: We induced a WMI rat model and observed white matter damage under an optical microscope. Rats subjected to WMI were injected intraperitoneally with clobetasol (2 or 5 mg/kg daily) from day 1 to day 5 in the early treatment groups, or from day 6 to day 10 in the late treatment groups. After 17 days, the rats were sacrificed and the expression of myelin basic protein (MBP) was visualized using immunofluorescence. In addition, we evaluated myelin sheath formation using electron microscopy. The rats were also subjected to the suspension test, ramp test, and open field test to evaluate neurobehavioral functions. Results: A rat model of WMI was successfully induced. It was found that clobetasol significantly induced MBP expression and myelin sheath formation and improved neurobehavioral function in the rats subjected to WMI. Conclusions: Our results indicate that clobetasol attenuates WMI by promoting OPC differentiation, and it may be an effective therapeutic agent for the treatment of preterm WMI.
Gastrointestinal Luminal Stenting: The Early US Experience with the Duodenal HANAROSTENT
Authors: Fung Brian M. , Kadera Brian E. , Tabibian James H.
Published: October 2020

Self-expandable metal stents (SEMSs) are frequently utilized for palliation of malignant gastric and/or duodenal outlet obstruction (GDOO). Re-establishing luminal patency with accurate SEMS positioning while limiting migration and adjacent tissue injury is an important technical consideration and aim. The duodenal HANAROSTENT® was introduced in the USA in 2019 and developed with these challenges in mind. As the first center in the USA to deploy the duo­denal HANAROSTENT® in clinical practice, we herein examine our early experience with its use. Specifically, we describe 7 consecutive cases of malignant GDOO in which a duodenal HANAROSTENT® was placed for on-label use, defined as palliative treatment of malignant gastric and/or duodenal obstruction. All stents were 22 mm in diameter, with 5 being 90 mm and 2 being 120 mm in length. Technical and clinical success with duodenal HANAROSTENT® placement were achieved in all 7 cases (100%). In no case was stent adjustment required post-deployment. There were no stent-related adverse events, and no subsequent endoscopic procedures were necessary in any of the patients during a mean follow-up of 5 months (range 1–12 months). In summary, the duodenal HANAROSTENT® appears to perform well and be a promising alternative to other available duodenal SEMSs. As experience in the USA with this newly introduced duodenal SEMS grows, multicenter prospective data should be collected to better establish its relative safety and efficacy.
Lipid-Producing Ciliochoroidal Melanoma with Expression of HMG-CoA Reductase
Authors: Van Ly David , Wang Duo , Conway Robert Max , Giblin Michael , Liang Sharron , Lukeis Robyn , Lim Li-Anne , Hesson Luke , Cherepanoff Svetlana
Published: October 2020

Uveal melanoma (UM) is the commonest primary intraocular malignancy in adults. There is limited published data on lipid production in UM. Here, we describe the clinical, histological, immunohistochemical, and molecular findings in a ciliochoroidal melanoma with lipid production and expression of the enzyme HMG-CoA reductase. This case highlights an unusual UM tumour phenotype with a high-risk molecular metastatic profile and discusses tumour lipogenesis and activation of the mevalonate pathway as a potential therapeutic target in managing lipidised ciliochoroidal UM.
N-Acetylcystein steigert den zerebralen Glukosemetabolismus
Authors: Pul Refik , Kleinschnitz Christoph
Published: October 2020

Background: Multiple Sclerosis (MS) is an autoimmune disease marked by progressive neurocognitive injury. Treatment options affording neuroprotective effects remain largely experimental. The purpose of this proof of concept study was to explore the effects of N-acetyl-cysteine (NAC) on cerebral glucose metabolism (CMRGlu) and symptoms in patients with multiple sclerosis (MS). Methods: Twenty-four patients with MS were randomized to either NAC plus standard of care, or standard of care only (waitlist control). The experimental group received NAC intravenously once per week and orally the other 6 days. Patients in both groups were evaluated at baseline and after 2 months (of receiving the NAC or waitlist control period) with an integrated Position Emission Tomography (PET)/ Magnetic Resonance Imaging (MRI) scanner, using 18F Fluorodeoxyglucose (FDG) to measure cerebral glucose metabolism. Following imaging evaluation at 2 months, subjects initially attributed to the standard of care arm were eligible for treatment with NAC. Clinical and symptom questionnaires were also completed initially and after 2 months. Results: The FDG PET data showed significantly increased cerebral glucose metabolism in several brain regions including the caudate, inferior frontal gyrus, lateral temporal gyrus, and middle temporal gyrus (p < 0.05) in the MS group treated with NAC, as compared to the control group. Self-reported scores related to cognition and attention were also significantly improved in the NAC group as compared to the control group. Conclusions: The results of this study suggest that NAC positively affects cerebral glucose metabolism in MS patients, which is associated with qualitative, patient reported improvements in cognition and attention. Larger scale studies may help to determine the clinical impact of NAC on measures of functioning over the course of illness, as well as the most effective dosage and dosage regimen.
Belastungstest bei chronisch-obstruktiver Lungenerkrankung: Wege zur optimalen Trainingssteuerung finden
Authors: Leitl Daniela , Koczulla A. Rembert
Published: October 2020

Background: In moderate-to-severe chronic obstructive pulmonary disease (COPD) patients the 6-min walk test (6MWT) is often exhaustive and correlates with the incremental cycle cardiopulmonary exercise test (CPET). Objectives: The aim of this study was to assess the agreement between oxygen uptake (VO2) measured during the 6MWT by portable equipment and incremental cycle exercise in COPD patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) I–IV. Methods: A total of 30 patients with COPD GOLD I–IV (14 patients GOLD stage I and II and 16 patients GOLD stage III and IV) underwent a 6MWT and an incremental CPET. Breath-by-breath analysis for VO2, carbon dioxide output (VCO2), and minute ventilation (VE) were measured during each test. Blood gas analysis and lactate measurements were performed before, during, and after the test. Results: VO2 in COPD patients GOLD stage I and II was 16.2 ± 4.2 mL/kg/min measured by 6MWT and 20.5 ± 7.0 mL/kg/min measured by CPET as compared to GOLD stage III and IV (11.2 ± 3.7 mL/kg/min measured by 6MWT and 15.5 ± 4.3 mL/kg/min measured by CPET). No significant correlation in VO2 measurements could be found between both tests in COPD GOLD I and II (r = 0.17), whereas the VO2 significantly correlated in patients with COPD stage III and IV (r = 0.7). Conclusions: A significant relationship between VO2 measured by 6MWT and CPET could only be found in patients with more severe COPD but not in milder stages. 6MWT and CPET provide different VO2 measurements in COPD patients. The two methods cannot be used interchangeably.
Revisiting the taxonomy and nomenclature of Eriocaulon modestum (Eriocaulaceae)

Authors: CHAGAS EARL CELESTINO DE OLIVEIRA , COSTA-LIMA JAMES LUCAS DA
Published: October 2020

The taxonomy of Eriocaulon modestum and its infraspecific taxa is revised. Eriocaulon modestum var. brevifolium and E. modestum f. viviparum are accepted as distinct taxa and raised to the species level under the names E. candango E.C.O.Chagas and E. ibeji E.C.O.Chagas, respectively. We present a complete list of synonyms and examined specimens of E. modestum and a comparative morphological table for the three species. In addition, we designate lectotypes for the names E. modestum and its synonyms E. burchellii, E. glaziovii, E. melanolepis, and E. proximum.
A new species of Amorphophallus (Araceae—Thomsoniaea) from Sulawesi, Indonesia

Authors: YUZAMMI YUZAMMI , Hetterscheid Wilbert
Published: October 2020

Amorphophallus ardii is described and illustrated, and compared to other Indonesian Amorphophallus species. The species was collected in the Matarombeo limestone mountain range in Southeast Sulawesi, Indonesia. The species is restricted to karst areas and endemic to Southeast Sulawesi.
The place of social work in improving access to health services among refugees: A case study of Nakivale settlement, Uganda
Authors: Mwenyango Hadijah
Published: October 2020

About 70.8 million individuals are displaced worldwide, and of these, 25.9 million are refugees. Accessibility to health care is a central aspect of the well-being of refugees. This article examines the communication, institutional and socio-cultural challenges to access and use of health services among refugee women and children and conceptualises the social work position in tackling such issues. The study used mixed quantitative and qualitative methods. The findings indicate complex experiences of refuge and ongoing gendered oppression and vulnerability. This research proposes a rights-based social work approach to addressing impediments at micro, meso and macro levels.
An Alternative Structure of Delivering Management Education in India
Authors: Goyal J. K. , Daipuria Pratima , Jain Somya
Published: October 2020

The coronavirus pandemic has adversely affected all sectors globally including the education sector. Education institutes across all levels (preprimary, primary, secondary, and higher education) have closed in 188 countries across the globe. Prolonged closure of colleges and schools has forced the educational sector to adopt the online mode of teaching. But one question that is bothering most of the academicians is: Can this online mode of teaching standalone in the long run? To answer this question, our article has proposed an alternative model of delivering education in the time of crisis. This article also helps to explore and compare different modes of course delivery. It also tries to compare and contrast different modes of education through Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis. This article limits its analysis to management education only. An in-depth systematic review from various research papers, articles, cases was done for this article to suggest the model. We found that the management education in India needs a paradigm shift in design, delivery, and assessment and as has been the trend, the trend-setter has to be the faculty in association with the learner. The article recommends that the college administration and faculties should design curriculum in such a system which is more practice-oriented, has more interning hours and where theory gets tested and tried in the field.
Obstacles to Greener Beekeeping in France: Anthropological Approach
Authors: Faugère Elsa , Dussy Dorothée
Published: October 2020

Over the last few years, the amount of space occupied by bees in the French public debate together with the well-known benefits of the products of their hive has attracted the interest of social scientists. Indeed, bees have become a symbol of the biodiversity crisis. Social scientists, like us, are sometimes invited to join multidisciplinary projects run by biologists specializing in bees. The aim of such involvement is to help the biologists to convince professional beekeepers to make their practices greener, notably with respect to their handling of the Varroa mite. However, the beekeepers we studied in the south of France are not keen to give up their conventional practices. Based on chemical products, these are efficient, simple, and cheap as opposed to environmentally friendly, chemical-free techniques (scraping or removal of the brood), which are seen to be riskier and more complicated to implement. This article describes and analyzes these obstacles and the relationship to scientific and nonscientific knowledge they reveal.
Effects of fabrication method of composite yarn intermediate material and resin melt viscosity on the impregnation properties and mechanical properties of PA66 fiber and glass fiber composites
Authors: Saito Taiga , Nakai Asami , Ohtani Akio
Published: October 2020

Continuous fiber-reinforced thermoplastic (c-FRTP) has received attention for reducing automobile weight. Hollow molded parts made by pultrusion molding of braided composites may improve the performance and reduce the weight of automotive parts. However, pultrusion molding of braided composites suffers from productivity problems. This research aimed to increase the productivity of pultrusion molding of braided fabrics to facilitate its practical application. The effects of the fiber intermediate fabrication method and the resin melt viscosity on the impregnation and mechanical properties of the composite were investigated. Glass fiber and polyamide 66 (PA66) were used as the fiber intermediates. Two types of fiber intermediates were used, one with interlace processing and one with the fibers lined up. PA66 fibers with high and low viscosity were used. A correlation was found between impregnation properties and mechanical properties of the molded products, which improved as the unimpregnated ratio decreased. Detailed observations revealed that impregnation of PA66 resin into glass fiber bundles started from interlaced points in the fiber intermediates introduced by interlace processing. Furthermore, low-viscosity PA66 resin had higher fluidity, which better promoted impregnation into glass fiber bundles. These results clarify design guidelines for fiber intermediates to realize better mechanical properties and shorter molding cycles.
Highly Thermally Conductive UHMWPE/NG Composites with the Segregated Structure and their Application for Heat Spreader
Authors: Wang Xiao , Lu Hui , Chen Jun
Published: October 2020

In this work, ultra-high molecular weight polyethylene (UHMWPE)/natural flake graphite (NG) polymer composites with the extraordinary high thermal conductivity were prepared by a facile mixed-heating powder method. Morphology observation and X-ray diffraction (XRD) tests revealed that the graphite NG flakes could be more tightly coated on the surface of UHMWPE granules by mixed-heating process and align horizontally (perpendicular to the hot compression direction of composites). Laser flash thermal analyzer (LFA) demonstrated that the thermal conductivity (TC) of composites with 21.6 vol% of NG reached 19.87 W/(m∙K) and 10.67 W/(m∙K) in the in-plane and through-plane direction, respectively. Application experiment further demonstrated that UHMWPE/NG composites had strong capability to dissipate the heat as heat spreader. The obtained results provided a valuable basis for fabricating high thermal conductive composites which can act as advanced thermal management materials.
Regulatory Arbitrage and Presence of Foreign Banks: Evidence from the Indian Banking Sector
Authors: Prashad Anjali
Published: October 2020

Presence of a heterogeneous banking system across countries provides opportunities for cross-border banks to indulge in activities of regulatory arbitrage. This article attempts to investigate whether regulatory arbitrage induces the presence of foreign banks in India. Using relevant country-level data on various aspects of banking regulations, we conduct a series of panel regressions to examine the effect of cross-country gap in banking regulations on foreign banks’ presence in India. We find regulatory arbitrage as significantly determining foreign banks’ presence in India, after controlling for other factors (income level of home country, bilateral economic relationship, colonial and linguistic commonality, and geographic proximity).
Informal Caregivers’ Administration of Hospice Prescribed Lorazepam to Homecare Patients With Anxiety
Authors: Ropri Fatima , Weisse Carol S.
Published: October 2020

Background:

A growing number of informal caregivers (IFCs) manage hospice patients’ anxiety by administering lorazepam (Ativan), yet little is known about prescribing practices in home care or the extent to which IFCs carry out regimens.

Design and Methods:

Data on hospice prescribed lorazepam was determined through a retrospective review of medication records from 216 deceased patients. The dose of lorazepam and type of regimen (i.e., scheduled, PRN, combination) as well as frequency with which it was administered by IFCs was calculated upon admission to a residential care home and on patients’ day of death.

Results:

The majority (63.1%) of patients were prescribed lorazepam on admission to the home, and more (79.5%) were prescribed lorazepam on the day of death. While higher doses of lorazepam were prescribed and administered on the day of death, the percentage of medication consumed was low on admission (17%) and day of death (27%). Nearly all (92.8%) prescribed lorazepam on the day of death were allowed PRN medication. For PRN only regimens, less than a quarter (24.4%) of patients were given lorazepam on admission with less than half (40.4%) given it while dying. Highest lorazepam administration rates (91.2%) occurred on the day of death when lorazepam was prescribed under a combined regimen.

Conclusion:

The high frequency of PRN regimens reveal that IFCs are frequently tasked with making decisions about if and when to administer lorazepam. Low overall lorazepam administration suggests a closer monitoring of lorazepam use and enhanced support of IFCs may be needed.
Satisfaction, functional outcomes and predictors in hip arthroscopy: a cohort study
Authors: van der Valk Mara R , Wolterbeek Nienke , van Assen Tijmen , Veen M Remmelt
Published: October 2020

Introduction:

Hip arthroscopy is not always successful, leading to high rates of total hip arthroplasty (THA) after arthroscopy. The aim of this study was to identify risk factors for THA, revision arthroscopy and low patient satisfaction and to compare outcomes of the different procedures of primary hip arthroscopy.

Methods:

A total of 91 primary hip arthroscopy procedures in 90 patients (66% female) were analysed. Data were gathered from patient files and a questionnaire was sent to patients including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), modified Harris Hip Score (mHHS), the EuroQol 5-dimension and questions about return to sports, satisfaction and pain before and after surgery. Using regression analyses, predictive factors for the outcomes were identified.

Results:

After a mean of 1.6 years, 4 patients (4%) underwent revision arthroscopy and 10 (11%) a THA. Of the responders (62%), 66% of the patients was satisfied to very satisfied about the surgery. Mean mHHS score was 75.3 (SE 1.9) and the mean WOMAC score was 81.0 (SE 2.8). Return to sports rate was 58%. A higher age was a significant predictor for lower satisfaction ( p = 0.008) and a longer duration of symptoms was a significant predictor for worse mHHS outcome scores ( p = 0.005).

Conclusion:

A higher age is a predictor for a lower satisfaction and a longer duration of symptoms before surgery has a negative influence on functional outcome. No risk factors for THA or revision arthroscopy were found and there were no significant differences in outcome measurements between the performed surgeries.
Tyrosine Kinase Inhibitors in the Combination Therapy of HER2 Positive Breast Cancer
Authors: Yang Xue , Wu Dapeng , Yuan Shengli
Published: October 2020

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) accounts for about 20% to 30% of all BC subtypes and is characterized by invasive disease and poor prognosis. With the emergence of anti-HER2 target drugs, HER2-positive BC patient outcomes have changed dramatically. However, treatment failure is mostly due to drug resistance and the special treatment needs of different subgroups. Small molecule tyrosine kinase inhibitors can inhibit multiple targets of the human epidermal growth factor receptor family and activate PI3K/AKT, MAPK, PLC γ, ERK1/2, JAK/STAT, and other pathways affecting the expression of MDM2, mTOR, p27, and other transcription factors. This can help regulate the differentiation, apoptosis, migration, growth, and adhesion of normal cells and reverse drug resistance to a certain extent. These inhibitors can cross the blood-brain barrier and be administered orally. They have a good synergistic effect with effective drugs such as trastuzumab, pertuzumab, t-dm1, and cyclin-dependent kinase 4 and 6 inhibitors. These advantages have resulted in small-molecule tyrosine kinase inhibitors attracting attention. The new small-molecule tyrosine kinase inhibitor was investigated in multi-target anti-HER2 therapy, showed a good effect in preclinical and clinical trials, and to some extent, improved the prognosis of HER2-positive BC patients. Its use could lead to a de-escalation of treatment in some patients, possibly preventing unnecessary procedures along with the associated side effects and costs.
An architectural framework for information integration using machine learning approaches for smart city security profiling
Authors: Abid Adnan , Abbas Ansar , Khelifi Adel , Farooq Muhammad Shoaib , Iqbal Razi , Farooq Uzma
Published: October 2020

In the past few decades, the whole world has been badly affected by terrorism and other law-and-order situations. The newspapers have been covering terrorism and other law-and-order issues with relevant details. However, to the best of our knowledge, there is no existing information system that is capable of accumulating and analyzing these events to help in devising strategies to avoid and minimize such incidents in future. This research aims to provide a generic architectural framework to semi-automatically accumulate law-and-order-related news through different news portals and classify them using machine learning approaches. The proposed architectural framework discusses all the important components that include data ingestion, preprocessor, reporting and visualization, and pattern recognition. The information extractor and news classifier have been implemented, whereby the classification sub-component employs widely used text classifiers for a news data set comprising almost 5000 news manually compiled for this purpose. The results reveal that both support vector machine and multinomial Naïve Bayes classifiers exhibit almost 90% accuracy. Finally, a generic method for calculating security profile of a city or a region has been developed, which is augmented by visualization and reporting components that maps this information onto maps using geographical information system.
Abnormalities of prolactin
Authors: Dinarkhail Shugufa , Maarij Khyber
Published: October 2020

Abnormalities of prolactin can present with a myriad of signs and symptoms that are difficult to distinguish from other pathologies within the constraints of a GP consultation. It is important to know when it is appropriate to check the prolactin level, how to interpret the result and what to do about abnormal results. Management is dependent on the underlying cause and clinical context. This article will address abnormalities of prolactin in a practical, step-by-step manner with the aim of providing a tool for use by GPs.
WHO Year of the Nurse and Midwife: More clean and educated hands for all
Authors: Peters Alexandra , Palao Victor Cegarra , Lotfinejad Nasim , Pittet Didier
Published: October 2020

For the last 10 years, the World Health Organization has been celebrating World Hand Hygiene Day on the 5th of May, bringing together the global healthcare ecosystem to celebrate hand hygiene. This day was created to raise awareness about the importance of hand hygiene in healthcare settings, as well as to focus on a specific annual topic to be highlighted to a global audience. The World Health Assembly designated 2020 as the Year of the Nurse and Midwife, and the slogan of this year’s 5th of May was “Nurses and Midwifes: Clean Care is in Your Hands”. This 5th of May helped us to highlight the need for increased staffing and hand hygiene training. In this paper we aimed to raise awareness about the global impact linked to adherence to proper hand hygiene practices by nurses and midwives.