bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycemic Control by Combination Therapy of Sitagliptin-Metformin Versus Metformin Alone
Authors: Saha Misu Rani , Ara Shahin , Rahman AKM Shahidur , Rahman Shakilur , Hossain M Iqbal , Badhon Nazia Mahmud
Published: October 2020

Background: Type 2 diabetes is a chronic disease characterized by various metabolic defects. Uncontrolled diabetes mellitus gives rise to a number of life-threatening complications that can increase mortality and morbidity.

Objectives: This study was carried out to compare the effectiveness of glycemic control between combined therapy of sitagliptin-metformin and metformin monotherapy.

Materials and Methods: Total data of 40 newly diagnosed type-2 diabetic patients were compiled in the study. Those patients having HbA1c more than 6% were considered as uncontrolled diabetes. The total subjects were randomly divided into two experimental groups, treated by metformin alone and treated by sitagliptin-metformin combination. Both groups were treated for three consecutive months and they were followed up after 12 weeks of treatment. Fasting blood sugar (FBS), blood sugar 2 hours after breakfast (2-ABF) and glycated hemoglobin A1c(HbA1c) were estimated in both experimental groups before starting of treatment and after 12 weeks of treatment.

Results: HbA1c change from baseline was 0.82% with metformin and 1.83% with sitagliptin-metformin combination. Fasting blood glucose changed from 9.41±1.34mmol/l to 8.04±1.10mmol/l with metformin and from 9.75±1.40mmol to 7.25±0.80 with sitagliptin-metformin therapy. Blood sugar 2hours after breakfast changed from 12.68±1.07mmol/l to 10.34±1.68mmol/l with metformin and from 12.65±1.90mmol to 8.74±0.68 with sitagliptin-metformin therapy. The results showed that though both experimental groups reduced FBS, blood sugar 2-ABF, HbA1c at an acceptable level the combined therapy was found to be superior in terms of effectiveness.

Conclusion: The administration of sitagliptin-metformin combined therapy to control hyperglycemia uniquely is preferable.

KYAMC Journal Vol. 11, No.-3, October 2020, Page 150-153
Chemotherapy Induced Radiation Recall Injury
Authors: Chowdhury Aditi Paul , Haque Md Ershadul , Alam Md Nazmul , Ahmed Tanvir , Das Barun Kumar , Bari MA , Islam Md Shahidul
Published: October 2020

Radiation recall is characterized by an acute inflammatory reaction confined to previously irradiated areas that is triggered by the administration of precipitating systemic agents after radiation treatment. The most common responsible drugs are anticancer agents, but other drugs can also cause radiation recall including some antibiotics, antitubercular drugs, simvastatin can also cause radiation recall phenomenon. We report a case of paclitaxel induced radiation recall injury in a 57 year old male with carcinoma left lung with brain metastases.

KYAMC Journal Vol. 11, No.-3, October 2020, Page 158-160
Pengembangan Lembar Kerja Peserta Didik (LKPD) PJOK Senam Lantai Meroda Berbasis Penguatan Pendidikan Karakter Untuk Peserta Didik Kelas VII SMP Negeri 18 Kota Bengkulu
Authors: Nuryogatama Muhammad , Sugihartono Tono , Sutisyana Ari
Published: October 2020

Lembar Kerja Peserta Didik (LKPD), is research and development that is commonly called (R&D). The subjects of this study were Students of grade VII of SMP Negeri 18 Bengkulu City with 27 students and 2 teachers. Data analysis techniques using quantitative descriptive analysis as outlined in the form of percentages. Data collection instruments and techniques with a questionnaire. The results of the study stated that the products developed were feasible with expert validation scores, , in expert I, Content eligibility aspects "very good" 100%, aspects of conformity with character education "very good" 97%, didactic aspects "very good" 93%, construction aspects "very good" 100% and technical aspects "very good" 93%. whereas the final result of the assessment was conducted by expert II, the aspect of Feasibility of "very good" content was 100%, the suitability aspect of Character Education was "very good" 97%, the Didactic aspect was "very good" 100%, the construction aspect was "very good" 100% and the technical aspect was "very good” 96%. While overall the quality of LKPD percentage of students' responses to LKPD based on Character Education is "very good" with a percentage of 86% and the results of teacher responses are "very good" with a percentage of 93%.
Chillers of air-conditioning systems: An overview
Authors: Leung Michael Kwok Hi , Tso Chi Yan , Wu Wei , Zheng Zhanying , Cao Jingyu
Published: October 2020

In tropical and subtropical regions, air-conditioning commonly consumes the most energy in buildings. The chillers used in existing air-conditioning systems are largely based on thermodynamic vapour compression cycle because the cycle is highly effective, efficient and practical. Moreover, the system installation and operation are convenient when grid electricity is available. Popular vapour compression chiller types include air-cooled, water-cooled, seawater-cooled and oil-free chillers. In addition, thermal-driven absorption and adsorption chillers have become available in the market. Viable sources of thermal energy input include fuel combustion, renewable solar energy, waste heat, and so on. This paper
provides an overview of different types of chillers and system configurations in terms of mechanisms, characteristics, energy efficiency, environmental performance and costs. The technical information and comparisons should help engineers select the chiller type in air-conditioning system design for achieving high sustainability.
Measuring of Regional Growth Performance using Shift Share Analysis with Special Reference to Sabaragamuwa Province, Sri Lanka
Authors: Uduporuwa R.J.M.
Published: October 2020

The Shift-Share analysis is an effective tool that is widely applied in regional economic research to understand regional growth change during a certain period. The objective of this paper is to review the recent growth performance of the Sabaragamuwa Province which is nine provinces in Sri Lanka, applying the Shift Share tool to give an insight into its growth performance for effective policy formulation. Employment data were taken for this analysis from the Annual Report of Sri Lanka Labour Force Survey conducted by the Department of Census and Statistics in the year 2013 and 2018 and Excel spreadsheets were used to perform the analysis. According to the statistics, the province has reported a negative change in employment during the period of 2013-2018 indicating a huge job loss. According to the Shift Share analysis, it is found that this job loss was primarily due to the unfavorable National Share (NS) since the overall national growth rate of the country was minus during this analysis period. The Industry Mix (IM) effect was considerably favorable since 70 percent of industries were able to increase their jobs. Agriculture is the main industry which lost a large number of jobs due to the declining trend of the agricultural sector at the national level. Results also show that the region is fairly competitive since its overall Regional Share (RS) value was positive representing a job-saving at the regional level. This job saving is due to the 40 percent of leading industries in the regions. Agriculture is the main industry sector which has performed well in the region. Results of the analysis suggest that a strong policy intervention both at the regional and the national level is essential to boost up the growth performance of the region.
Performance Evaluation of Data Compression Algorithms for IoT-Based Smart Water Network Management Applications
Authors: Adedeji Kazeem B.
Published: October 2020

IoT-based smart water supply network management applications generate a huge volume of data from the installed sensing devices which are required to be processed (sometimes in-network), stored and transmitted to a remote centre for decision making. When the volume of data produced by diverse IoT smart sensing devices intensify, processing and storage of these data begin to be a serious issue. The large data size acquired from these applications increases the computational complexities, occupies the scarce bandwidth of data transmission and increases the storage space. Thus, data size reduction through the use of data compression algorithms is essential in IoT-based smart water network management applications. In this paper, the performance evaluation of four different data compression algorithms used for this purpose is presented. These algorithms, which include RLE, Huffman, LZW and Shanon-Fano encoding were realised using MATLAB software and tested on six water supply system data. The performance of each of these algorithms was evaluated based on their compression ratio, compression factor, percentage space savings, as well as the compression gain. The results obtained showed that the LZW algorithm shows better performance base on the compression ratio, compression factor, space savings and the compression gain. However, its execution time is relatively slow compared to the RLE and the two other algorithms investigated. Most importantly, the LZW algorithm has a significant reduction in the data sizes of the tested files than all other algorithms
Efficient Data Structures for Range Shortest Unique Substring Queries
Authors: Abedin Paniz , Ganguly Arnab , Pissis Solon P. , Thankachan Sharma V.
Published: October 2020

Let T[1,n] be a string of length n and T[i,j] be the substring of T starting at position i and ending at position j. A substring T[i,j] of T is a repeat if it occurs more than once in T; otherwise, it is a unique substring of T. Repeats and unique substrings are of great interest in computational biology and information retrieval. Given string T as input, the Shortest Unique Substring problem is to find a shortest substring of T that does not occur elsewhere in T. In this paper, we introduce the range variant of this problem, which we call the Range Shortest Unique Substring problem. The task is to construct a data structure over T answering the following type of online queries efficiently. Given a range [α,β], return a shortest substring T[i,j] of T with exactly one occurrence in [α,β]. We present an O(nlogn)-word data structure with O(logwn) query time, where w=Ω(logn) is the word size. Our construction is based on a non-trivial reduction allowing for us to apply a recently introduced optimal geometric data structure [Chan et al., ICALP 2018]. Additionally, we present an O(n)-word data structure with O(nlogϵn) query time, where ϵ>0 is an arbitrarily small constant. The latter data structure relies heavily on another geometric data structure [Nekrich and Navarro, SWAT 2012].
Breeding Alfalfa for Semiarid Regions in the Northern Great Plains: History and Additional Genetic Evaluations of Novel Germplasm
Authors: Boe Arvid , Kephart Kevin D. , Berdahl John D. , Peel Michael D. , Brummer E. Charles , Xu Lan , Wu Yajun
Published: October 2020

Yellow-flowered alfalfa (Medicago sativa subsp. falcata) (also known as sickle medic) has been the cornerstone for breeding alfalfa for dual grazing and hay production in the semiarid regions of the northern Great Plains in the US and Canada. Most, if not all, of the cultivars developed for the northern Great Plains during the 20th century, had parentage tracing back to introductions by Niels Ebbesen Hansen that were obtained from expeditions to Russia, primarily the province of Siberia, on behalf of the United States Department of Agriculture during the early 1900s. The M. falcata genome contains alleles for high levels of drought-tolerance, winter hardiness, and tolerance to grazing, but is generally deficient for commercial seed production traits, such as non-shatter, compared with common alfalfa (M. sativa). A naturalized population, tracing to USDA plant introductions to Perkins County South Dakota by N.E. Hansen in early 1900, and subsequently, facilitated by the determined seed increase and interseeding of a population by a local rancher, Norman ‘Bud’ Smith, has shown highly desirable in situ characteristics for improving rangelands in the northern Great Plains. This includes adequate seed production to build a seed bank in the soil for natural seedling recruitment and population maintenance/expansion and support the production of a commercial seed source. This review documents the seminal events in the development of cultivars to date and describes novel germplasm with potential for new cultivars in the future.
Antimicrobial Resistance Profiles of Escherichia coli from Diarrheic Weaned Piglets after the Ban on Antibiotic Growth Promoters in Feed
Authors: Kyung-Hyo Do , Jae-Won Byun , Wan-Kyu Lee
Published: October 2020

This study aimed to survey the antimicrobial resistance profiles of 690 pathogenic Escherichia coli isolates obtained from Korean pigs with symptoms of enteric colibacillosis between 2007 and 2017, while assessing the change in antimicrobial resistance profiles before and after the ban on antibiotic growth promoters (AGPs). Following the Clinical and Laboratory Standards Institute guidelines, the antimicrobial resistance phenotype was analyzed through the disk diffusion method, and the genotype was analyzed by the polymerase chain reaction. After the ban on AGPs, resistance to gentamicin (from 68.8% to 39.0%), neomycin (from 84.9% to 57.8%), ciprofloxacin (from 49.5% to 39.6%), norfloxacin (from 46.8% to 37.3%), and amoxicillin/clavulanic acid (from 40.8% to 23.5%) decreased compared to before the ban. However, resistance to cephalothin (from 51.4% to 66.5%), cefepime (from 0.0% to 2.4%), and colistin (from 7.3% to 11.0%) had increased. We confirmed a high percentage of multidrug resistance before (95.0%) and after (96.6%) the ban on AGPs. The AmpC gene was the most prevalent from 2007 to 2017 (60.0%), followed by the blaTEM gene (55.5%). The blaTEM was prevalent before (2007–2011, 69.3%) and after (2012–2017, 49.2%) the ban on AGPs. These results provide data that can be used for the prevention and treatment of enteric colibacillosis.
Inflammation, Peripheral Signals and Redox Homeostasis in Athletes Who Practice Different Sports
Authors: Luti Simone , Modesti Alessandra , Modesti Pietro A.
Published: October 2020

The importance of training in regulating body mass and performance is well known. Physical training induces metabolic changes in the organism, leading to the activation of adaptive mechanisms aimed at establishing a new dynamic equilibrium. However, exercise can have both positive and negative effects on inflammatory and redox statuses. In recent years, attention has focused on the regulation of energy homeostasis and most studies have reported the involvement of peripheral signals in influencing energy and even inflammatory homeostasis due to overtraining syndrome. Among these, leptin, adiponectin, ghrelin, interleukin-6 (IL6), interleukin-1β (IL1β) and tumour necrosis factor a (TNFa) were reported to influence energy and even inflammatory homeostasis. However, most studies were performed on sedentary individuals undergoing an aerobic training program. Therefore, the purpose of this review was to focus on high-performance exercise studies performed in athletes to correlate peripheral mediators and key inflammation markers with physiological and pathological conditions in different sports such as basketball, soccer, swimming and cycling.
Bit Independence Criterion Extended to Stream Ciphers
Authors: Madarro-Capó Evaristo José , Legón-Pérez Carlos Miguel , Rojas Omar , Sosa-Gómez Guillermo , Socorro-Llanes Raisa
Published: October 2020

The bit independence criterion was proposed to evaluate the security of the S-boxes used in block ciphers. This paper proposes an algorithm that extends this criterion to evaluate the degree of independence between the bits of inputs and outputs of the stream ciphers. The effectiveness of the algorithm is experimentally confirmed in two scenarios: random outputs independent of the input, in which it does not detect dependence, and in the RC4 ciphers, where it detects significant dependencies related to some known weaknesses. The complexity of the algorithm is estimated based on the number of inputs l, and the dimensions, n and m, of the inputs and outputs, respectively.
Experimental Study of EICP Combined with Organic Materials for Silt Improvement in the Yellow River Flood Area
Authors: Yuan Hua , Ren Guanzhou , Liu Kang , Zheng Wei , Zhao Zhiliang
Published: October 2020

Enzyme-induced carbonate precipitation (EICP) is an emerging biogeotechnical technique that uses free urease to improve soil. Despite its advantages of eliminating complex microbial cultures and reducing reaction byproducts, its efficiency is considered lower than that of microbial induced calcite precipitation (MICP) due to the lack of nucleation sites that induce calcium carbonate deposition. To enhance the strengthening efficiency of EICP for fine-grained soils, an improved EICP method that involves adding an appropriate mass concentration of organic materials (skim milk powder, glutinous rice powder, and brown sugar) into urease solution was proposed and applied to reinforce silt in the Yellow River flood area of China. The preferred concentration and ratio of cementation solution and the optimum concentration of each of the organic materials were determined. Then, the reinforcement effect of the improved EICP at the optimum concentration was compared with the control group, and the reinforcement mechanism for this method was discussed. The results show that after the organic material inclusions, soil strength can be enhanced by 33% compared with EICP-treated soil and is nearly four times higher than that of untreated soil. The superiority of this method over traditional EICP and MICP mainly stems from its ability to provide templates and nucleation sites for calcium carbonate deposition and to improve the size, morphology, and structure of calcium carbonate crystals.
Quasi-Yagi Slotted Array Antenna with Fan-Beam Characteristics for 28 GHz 5G Mobile Terminals
Authors: Kim Sungpeel , Choi Jaehoon
Published: October 2020

A quasi-Yagi slotted array antenna with fan-beam characteristics is proposed for 28 GHz 5G mobile terminals. The antenna is composed of a 1 × 8 slot antenna array with directors to enhance the half-power beamwidth (HPBW). The proposed antenna has a fan-beam radiation pattern with a simulated HPBW of 256.72° and a peak gain of 11.16 dBi. In addition, the proposed antenna covers ±48° using a beam steering mechanism. Mutual coupling reduction is achieved by inserting slits between the adjacent slot radiators on the ground plane. The simulated −10 dB reflection coefficient bandwidth of the proposed antenna is 1.79 GHz (27.03–28.82 GHz), and the mutual coupling between each of the slot radiators is lower than −25.02 dB over the 28 GHz target band (27.5–28.35 GHz). To investigate the effect of a human body in a practical environment, the power density was considered to estimate the electromagnetic exposure with a simplified skin model. The measured results were in good agreement with the simulated ones and demonstrated that the proposed antenna could be used for 5G mobile terminals.
Workers’ Aging Management—Human Fatigue at Work: An Experimental Offices Study
Authors: Fera Marcello , De Padova Vittoria , Di Pasquale Valentina , Caputo Francesco , Caterino Mario , Macchiaroli Roberto
Published: October 2020

The aging issue in the work context is becoming a significant element of the future sustainability of service and industrial companies. It is well known that with increasing worker age the problem of maintaining the performance and the safety level when fatigue increases is a crucial point, and fatigue increases with the age. Due to social and political developments, especially in Western countries, the retirement age is increasing and companies operate with a higher workforce mean age. Therefore, the problem of recognizing and measuring fatigue has become a key aspect in the management of aging. Note that in the scientific engineering field, the problem of fatigue evaluation when a worker is performing his/her work activities is an important issue in the industrial and service world and especially in the context of the researchers that are investigating the human reliability assessment. As it is clear from the literature, the industrial operations management are suffering from some misleading concepts that only the medicine scientific context can clarify. Therefore, the aim of this paper is to define what are the open issues and the misleading concepts present in the classical fatigue evaluation methods, and second to define two experimental curves of fatigue that will help the decision makers to minimize the impact of fatigue on the workers, thus maximizing the sustainability of the working tasks assigned. This aim is achieved by examining the medical literature about the measurement of a particular kind of fatigue related to the circadian cycle, i.e., the cognitive one; after that, a survey about the possible technologies for measurements is performed. On the basis of technology selection, an experiment on real work activities is performed and some remarkable results about the fatigue in the workers observed and the technology use and its limitations are defined.
Development of Mathematical Models in Explicit Form for Design and Analysis of Axial Flux Permanent Magnet Synchronous Machines
Authors: Pranjić Franjo , Virtič Peter
Published: October 2020

This article proposes a methodology for the design of double-sided coreless axial flux permanent magnet synchronous machines, which is based on a developed model for calculating the axial component of the magnetic flux density in the middle of the distance between opposite permanent magnets, which also represents the middle of the stator. Values for different geometric parameters represent the input data for the mathematical model in explicit form. The input data are calculated by using a simplified finite element method (FEM), which means that calculations of simplified 3D models are performed. The simplified model consists of two rotor disks with surface-mounted permanent magnets and air between them, instead of stator windings. Such a simplification is possible due to similar values of permeability of the air and copper. For each simplified model of the machine the axial component of the magnetic flux density is analyzed along a line passing through the center of opposite permanent magnets and both rotor disks. Values at the middle of the distance between the opposite permanent magnets are the lowest and are therefore selected for the input data at different stator, rotor disks and permanent magnets (PM) thicknesses. Such input data enable the model to consider the nonlinearity of materials.
TLR9 Binding to Beclin 1 and Mitochondrial SIRT3 by a Sodium-Glucose Co-Transporter 2 Inhibitor Protects the Heart from Doxorubicin Toxicity
Authors: Wang Chao-Yung , Chen Chun-Chi , Lin Mei-Hsiu , Su Hui-Ting , Ho Ming-Yun , Yeh Jih-Kai , Tsai Ming-Lung , Hsieh I-Chang , Wen Ming-Shien
Published: October 2020

Large cardiovascular outcome trials have reported favorable effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on heart failure. To study the potential mechanism of the SGLT2 inhibition in heart failure, we used the murine doxorubicin-induced cardiomyopathy model and identified the toll-like receptor 9 (TLR9), NAD-dependent deacetylase sirtuin-3 (SIRT3), and Beclin 1, acting in a complex together in response to empagliflozin treatment. The interactions and implications in mitochondrial function were evaluated with TLR9 deficient, SIRT3 deficient, Beclin 1 haplodeficient, and autophagy reporter mice and confirmed in a patient with SIRT3 point mutation and reduced enzymatic activity. The SGLT2 inhibitor, empagliflozin, protects the heart from doxorubicin cardiomyopathy in mice, by acting through a novel Beclin 1-toll-like receptor (TLR) 9-sirtuin-(SIRT) 3 axis. TLR9 and SIRT3 were both essential for the protective effects of empagliflozin. The dilated cardiomyopathy patient with SIRT3 point mutation and reduced enzymatic activity is associated with reduced TLR9 activation and the absence of mitochondrial responses in the heart after the SGLT2 inhibitor treatment. Our data indicate a dynamic communication between autophagy and Beclin 1-TLR9-SIRT3 complexes in the mitochondria in response to empagliflozin that may serve as a potential treatment strategy for heart failure.
Intrinsically Disordered Proteins: Insights from Poincaré, Waddington, and Lamarck
Authors: Kulkarni Prakash
Published: October 2020

The past quarter-century may justly be referred to as a period analogous to the “Cambrian explosion” in the history of proteins. This period is marked by the appearance of the intrinsically disordered proteins (IDPs) on the scene since their discovery in the mid-1990s. Here, I first reflect on how we accidentally stumbled on these fascinating molecules. Next, I describe our research on the IDPs over the past decade and identify six areas as important for future research in this field. In addition, I draw on discoveries others in the field have made to present a more comprehensive essay. More specifically, I discuss the role of IDPs in two fundamental aspects of life: in phenotypic switching, and in multicellularity that marks one of the major evolutionary transitions. I highlight how serendipity, imagination, and an interdisciplinary approach embodying empirical evidence and theoretical insights from the works of Poincaré, Waddington, and Lamarck, shaped our thinking, and how this led us to propose the MRK hypothesis, a conceptual framework addressing phenotypic switching, the emergence of new traits, and adaptive evolution via nongenetic and IDP conformation-based mechanisms. Finally, I present a perspective on the evolutionary link between phenotypic switching and the origin of multicellularity.
Structural Conservation and Adaptation of the Bacterial Flagella Motor
Authors: Carroll Brittany L. , Liu Jun
Published: October 2020

Many bacteria require flagella for the ability to move, survive, and cause infection. The flagellum is a complex nanomachine that has evolved to increase the fitness of each bacterium to diverse environments. Over several decades, molecular, biochemical, and structural insights into the flagella have led to a comprehensive understanding of the structure and function of this fascinating nanomachine. Notably, X-ray crystallography, cryo-electron microscopy (cryo-EM), and cryo-electron tomography (cryo-ET) have elucidated the flagella and their components to unprecedented resolution, gleaning insights into their structural conservation and adaptation. In this review, we focus on recent structural studies that have led to a mechanistic understanding of flagellar assembly, function, and evolution.
XIAP’s Profile in Human Cancer
Authors: Tu Huailu , Costa Max
Published: October 2020

XIAP, the X-linked inhibitor of apoptosis protein, regulates cell death signaling pathways through binding and inhibiting caspases. Mounting experimental research associated with XIAP has shown it to be a master regulator of cell death not only in apoptosis, but also in autophagy and necroptosis. As a vital decider on cell survival, XIAP is involved in the regulation of cancer initiation, promotion and progression. XIAP up-regulation occurs in many human diseases, resulting in a series of undesired effects such as raising the cellular tolerance to genetic lesions, inflammation and cytotoxicity. Hence, anti-tumor drugs targeting XIAP have become an important focus for cancer therapy research. RNA–XIAP interaction is a focus, which has enriched the general profile of XIAP regulation in human cancer. In this review, the basic functions of XIAP, its regulatory role in cancer, anti-XIAP drugs and recent findings about RNA–XIAP interactions are discussed.
Biomolecules from Plant Residues
Authors: Ancín-Azpilicueta Carmen , Esparza Irene , Jiménez-Moreno Nerea
Published: October 2020

The circular economy is a new model of production and consumption that involves reusing, renewing and recycling products to create added value [...]
Natural Killer Cells in Immunotherapy: Are We Nearly There?
Authors: Bachiller Mireia , Battram Anthony M. , Perez-Amill Lorena , Martín-Antonio Beatriz
Published: October 2020

Natural killer (NK) cells are potent anti-tumor and anti-microbial cells of our innate immune system. They are equipped with a vast array of receptors that recognize tumor cells and other pathogens. The innate immune activity of NK cells develops faster than the adaptive one performed by T cells, and studies suggest an important immunoregulatory role for each population against the other. The association, observed in acute myeloid leukemia patients receiving haploidentical killer-immunoglobulin-like-receptor-mismatched NK cells, with induction of complete remission was the determinant to begin an increasing number of clinical studies administering NK cells for the treatment of cancer patients. Unfortunately, even though transfused NK cells demonstrated safety, their observed efficacy was poor. In recent years, novel studies have emerged, combining NK cells with other immunotherapeutic agents, such as monoclonal antibodies, which might improve clinical efficacy. Moreover, genetically-modified NK cells aimed at arming NK cells with better efficacy and persistence have appeared as another option. Here, we review novel pre-clinical and clinical studies published in the last five years administering NK cells as a monotherapy and combined with other agents, and we also review chimeric antigen receptor-modified NK cells for the treatment of cancer patients. We then describe studies regarding the role of NK cells as anti-microbial effectors, as lessons that we could learn and apply in immunotherapy applications of NK cells; these studies highlight an important immunoregulatory role performed between T cells and NK cells that should be considered when designing immunotherapeutic strategies. Lastly, we highlight novel strategies that could be combined with NK cell immunotherapy to improve their targeting, activity, and persistence.
Whole-Body Functional MRI and PET/MRI in Multiple Myeloma
Authors: Mulé Sébastien , Reizine Edouard , Blanc-Durand Paul , Baranes Laurence , Zerbib Pierre , Burns Robert , Nouri Refaat , Itti Emmanuel , Luciani Alain
Published: October 2020

Bone disease is one of the major features of multiple myeloma (MM), and imaging has a pivotal role in both diagnosis and follow-up. Whole-body magnetic resonance imaging (MRI) is recognized as the gold standard for the detection of bone marrow involvement, owing to its high sensitivity. The use of functional MRI sequences further improved the performances of whole-body MRI in the setting of MM. Whole-body diffusion-weighted (DW) MRI is the most attractive functional technique and its systematic implementation in general clinical practice is now recommended by the International Myeloma Working Group. Whole-body dynamic contrast-enhanced (DCE) MRI might provide further information on lesions vascularity and help evaluate response to treatment. Whole Body PET/MRI is an emerging hybrid imaging technique that offers the opportunity to combine information on morphology, fat content of bone marrow, bone marrow cellularity and vascularization, and metabolic activity. Whole-body PET/MRI allows a one-stop-shop examination, including the most sensitive technique for detecting bone marrow involvement, and the most recognized technique for treatment response evaluation. This review aims at providing an overview on the value of whole-body MRI, including DW and DCE MRI, and combined whole-body 18F-FDG PET/MRI in diagnosis, staging, and response evaluation in patients with MM.
Roles of Non-Coding RNAs on Anaplastic Thyroid Carcinomas
Authors: Das Plabon Kumar , Asha Saharia Yeasmin , Abe Ichiro , Islam Farhadul , Lam Alfred K.
Published: October 2020

Anaplastic thyroid cancer (ATC) remains as one of the most aggressive human carcinomas with poor survival rates in patients with the cancer despite therapeutic interventions. Novel targeted and personalized therapies could solve the puzzle of poor survival rates of patients with ATC. In this review, we discuss the role of non-coding RNAs in the regulation of gene expression in ATC as well as how the changes in their expression could potentially reshape the characteristics of ATCs. A broad range of miRNA, such as miR-205, miR-19a, miR-17-3p and miR-17-5p, miR-618, miR-20a, miR-155, etc., have abnormal expressions in ATC tissues and cells when compared to those of non-neoplastic thyroid tissues and cells. Moreover, lncRNAs, such as H19, Human leukocyte antigen (HLA) complex P5 (HCP5), Urothelial carcinoma-associated 1 (UCA1), Nuclear paraspeckle assembly transcript 1 (NEAT1), etc., participate in transcription and post-transcriptional regulation of gene expression in ATC cells. Dysregulations of these non-coding RNAs were associated with development and progression of ATC by modulating the functions of oncogenes during tumour progression. Thus, restoration of the abnormal expression of these miRNAs and lncRNAs may serve as promising ways to treat the patients with ATC. In addition, siRNA mediated inhibition of several oncogenes may act as a potential option against ATC. Thus, non-coding RNAs can be useful as prognostic biomarkers and potential therapeutic targets for the better management of patients with ATC.
Cancer Extracellular Vesicles: Next-Generation Diagnostic and Drug Delivery Nanotools
Authors: Palazzolo Stefano , Memeo Lorenzo , Hadla Mohamad , Duzagac Fahriye , Steffan Agostino , Perin Tiziana , Canzonieri Vincenzo , Tuccinardi Tiziano , Caligiuri Isabella , Rizzolio Flavio
Published: October 2020

Nanosized extracellular vesicles (EVs) with dimensions ranging from 100 to 1000 nm are continuously secreted from different cells in their extracellular environment. They are able to encapsulate and transfer various biomolecules, such as nucleic acids, proteins, and lipids, that play an essential role in cell‒cell communication, reflecting a novel method of extracellular cross-talk. Since EVs are present in large amounts in most bodily fluids, challengeable hypotheses are analyzed to unlock their potential roles. Here, we review EVs by discussing their specific characteristics (structure, formation, composition, and isolation methods), focusing on their key role in cell biology. Furthermore, this review will summarize the biomedical applications of EVs, in particular those between 30 and 150 nm (like exosomes), as next-generation diagnostic tools in liquid biopsy for cancer and as novel drug delivery vehicles.
Id1 and PD-1 Combined Blockade Impairs Tumor Growth and Survival of KRAS-mutant Lung Cancer by Stimulating PD-L1 Expression and Tumor Infiltrating CD8+ T Cells
Authors: Baraibar Iosune , Roman Marta , Rodríguez-Remírez María , López Inés , Vilalta Anna , Guruceaga Elisabeth , Ecay Margarita , Collantes María , Lozano Teresa , Alignani Diego , Puyalto Ander , Oliver Ana , Ortiz-Espinosa Sergio , Moreno Haritz , Torregrosa María , Rolfo Christian , Caglevic Christian , García-Ros David , Villalba-Esparza María , De Andrea Carlos , Vicent Silvestre , Pío Rubén , Lasarte Juan José , Calvo Alfonso , Ajona Daniel , Gil-Bazo Ignacio
Published: October 2020

The use of PD-1/PD-L1 checkpoint inhibitors in advanced NSCLC is associated with longer survival. However, many patients do not benefit from PD-1/PD-L1 blockade, largely because of immunosuppression. New immunotherapy-based combinations are under investigation in an attempt to improve outcomes. Id1 (inhibitor of differentiation 1) is involved in immunosuppression. In this study, we explored the potential synergistic effect of the combination of Id1 inhibition and pharmacological PD-L1 blockade in three different syngeneic murine KRAS-mutant lung adenocarcinoma models. TCGA analysis demonstrated a negative and statistically significant correlation between PD-L1 and Id1 expression levels. This observation was confirmed in vitro in human and murine KRAS-driven lung cancer cell lines. In vivo experiments in KRAS-mutant syngeneic and metastatic murine lung adenocarcinoma models showed that the combined blockade targeting Id1 and PD-1 was more effective than each treatment alone in terms of tumor growth impairment and overall survival improvement. Mechanistically, multiplex quantification of CD3+/CD4+/CD8+ T cells and flow cytometry analysis showed that combined therapy favors tumor infiltration by CD8+ T cells, whilst in vivo CD8+ T cell depletion led to tumor growth restoration. Co-culture assays using CD8+ cells and tumor cells showed that T cells present a higher antitumor effect when tumor cells lack Id1 expression. These findings highlight that Id1 blockade may contribute to a significant immune enhancement of antitumor efficacy of PD-1 inhibitors by increasing PD-L1 expression and harnessing tumor infiltration of CD8+ T lymphocytes.
Prognostic and Monitoring Value of Circulating Tumor Cells in Adrenocortical Carcinoma: A Preliminary Monocentric Study
Authors: Cantini Giulia , Canu Letizia , Armignacco Roberta , Salvianti Francesca , De Filpo Giuseppina , Ercolino Tonino , Nesi Gabriella , Maggi Mario , Mannelli Massimo , Pinzani Pamela , Luconi Michaela
Published: October 2020

Adrenocortical carcinoma (ACC), a rare and aggressive neoplasia, presents poor prognosis when metastatic at diagnosis and limited therapies are available. Specific and sensitive markers for early diagnosis and a monitoring system of therapy and tumor evolution are urgently needed. The liquid biopsy represents a source of tumor material within a minimally invasive blood draw that allows the recovery of circulating tumor cells (CTCs). CTCs have been recently shown to be detectable in ACC. In the present paper, we evaluated the prognostic value of CTCs obtained by size-filtration in a small pilot cohort of 19 ACC patients. We found CTCs in 68% of pre-surgery and in 38% of post-surgery blood samples. In addition, CTC clusters (CTMs) and cancer associated macrophages (CAMLs) were detectable in some ACC patients. The median number of CTCs significantly decreased after the mass removal. Finally, stratifying patients in high and low pre-surgery CTC number groups, assuming the 75th percentile CTC value as cut-off, CTCs significantly predicted patients’ overall survival (log rank = 0.005), also in a multivariate analysis adjusted for age and tumor stage. In conclusion, though preliminary and performed in a small cohort of patients, our study suggests that CTC number may represent a promising marker for prognosis and disease monitoring in ACC.
Acid-Producing Diet and Depressive Symptoms among Breast Cancer Survivors: A Longitudinal Study
Authors: Wu Tianying , Hsu Fang-Chi , Pierce John P.
Published: October 2020

The incidence of depression is two-to-three times higher in cancer survivors than the general population. Acid-producing diets may play important roles in the development of depression. Cancer survivors are more susceptible to acid-producing diets, yet few prospective studies have investigated the association of acid-producing diets with depression among breast cancer survivors. We leveraged a large cohort of 2975 early stage breast cancer survivors, which collected detailed dietary data via 24-h recalls. Potential renal acid load (PRAL) and net endogenous acid production (NEAP), two commonly used dietary acid load scores, were used to estimate acid-producing diets. Intakes of PRAL and NEAP were assessed at baseline and years one and four. Increased PRAL and NEAP were each independently associated with increased depression in the longitudinal analyses, after adjusting for covariates. The magnitude of the associations was stronger for PRAL than NEAP. Women with the highest quartile intakes of PRAL had 1.34 (95% CI 1.11–1.62) times the risk of depression compared to women with the lowest quartile. Furthermore, we also observed a joint impact of PRAL and younger age on depression, as well as a joint impact of PRAL and physical activity on depression. Decreasing the consumption of acid-producing diets may be a novel and practical strategy for reducing depressive symptoms among breast cancer survivors, especially those who are younger and have a sedentary lifestyle.
Epidemiology of Mucinous Adenocarcinomas
Authors: Benesch Matthew G. K. , Mathieson Alexander
Published: October 2020

Mucinous (colloid) adenocarcinomas (MAs) are a rare histological subtype of adenocarcinomas where extracellular mucin comprises more than 50% of the tumor. Most literature on MAs relate to cancers from colorectal and breast sites; however, the literature lacks a standardized overview of the MA disease entity. Particularly in colorectal cancer, some MAs may have signet ring cells floating within the mucin, which may represent a highly metastatic phenotype. MAs and signet ring cell adenocarcinomas represent a spectrum of mucin-producing neoplastic conditions where in the latter most mucin is intracellular rather than extracellular. We recently published a standardized overview of signet ring cells, and in this companion work, using a retrospective cohort approach, we summarize the clinicodemographic and mortality outcomes of MAs in sixteen primary sites, comprising 95.6% of all MAs in the Surveillance, Epidemiology, and End Results Program (SEER), a population-level cancer database covering nearly one-third of the United States population. Compared to matching nonvariant adenocarcinomas, MAs have a slightly earlier age of onset with increased rates of regional and distant disease at presentation. Survival outcomes are highly dependent on tumor location, illustrating our poor understanding of MA tumor biology. The clinical significance of MA histology depends largely on tumor site.
Soil Carbon Sequestration Potential of Climate-Smart Villages in East African Countries
Authors: Ambaw Gebermedihin , Recha John W. , Nigussie Abebe , Solomon Dawit , Radeny Maren
Published: October 2020

Climate-Smart Villages (CSVs) were established by the CGIAR Research Program on Climate Change, Agriculture and Food Security (CCAFS) in the East African countries of Kenya, Tanzania and Uganda to test and promote a portfolio of climate-smart agriculture (CSA) practices that have climate change mitigation potential. This study evaluated the soil carbon sequestration potential of these CSVs compared to the control land use that did not have CSA practices. At the one-meter depth, soil carbon stocks increased by 20–70%, 70–86%, and 51–110% in Kenya, Tanzania and Uganda CSVs, respectively, compared to control. Consequently, CSVs contributed to the reduction of emissions by 87–420 Mg CO2 eq ha−1. In the topsoil (0–15 cm), CSVs sequestered almost twice more soil carbon than the control and subsequently emissions were reduced by 42–158 Mg CO2 eq ha−1 under CSVs. The annual increase in carbon sequestration under CSVs ranged between 1.6 and 6.2 Mg C ha−1 yr−1 and substantially varied between the CSA land use types. The forests sequestered the highest soil carbon (5–6 Mg C ha−1 yr−1), followed by grasslands and croplands. The forest topsoil also had lower bulk density compared to the control. The findings suggest that CSA practices implemented through the CSVs approach contribute to climate change mitigation through soil carbon sequestration.
Sex-Gender Differences in Diabetic Retinopathy
Authors: Cherchi Sara , Gigante Alfonso , Spanu Maria , Contini Pierpaolo , Meloni Gisella , Fois Maria , Pistis Danila , Pilosu Rosangela , Lai Alessio , Ruiu Salvatore , Campesi Ilaria , Tonolo Giancarlo
Published: October 2020

Diabetic retinopathy (DR) is one of the main causes of visual loss in individuals aged 20–64 years old. The aim of this study was to investigate, in a multicenter retrospective cross-sectional study, sex-gender difference in DR in a large sample of type 2 diabetic patients (T2DM). 20,611 T2DM regularly attending the units for the last three years were classified as having: (a) No DR (NDR), (b) nonproliferative DR (NPDR), or (c) preproliferative/proliferative DR (PPDR). DR of all grades was present in 4294 T2DM (20.8%), with a significant higher prevalence in men as compared to women (22.0% vs. 19.3% p < 0.0001). Among DR patients, both NPDR and PPDR were significantly more prevalent in men vs. women (p = 0.001 and p = 0.0016, respectively). Women had similar age and BMI, but longer diabetes duration, worse glycemic metabolic control, and more prevalence of hypertension and chronic renal failure (CRF) of any grade vs. men. No significant differences between sexes were evident in term of drug therapy for diabetes and associate pathologies. Conclusions: In this large sample of T2DM, men show higher prevalence of DR vs. women, in spite of less represented risk factors, suggesting that male sex per se might be a risk factor for DR development.
Rapid Destructive Arthrosis Due to Subchondral Insufficiency Fracture of the Shoulder: Clinical Characteristics, Radiographic Appearances, and Outcomes of Treatment
Authors: Cho Chul-Hyun , Min Byung-Woo , Lee Kyung-Jae , Kim Jun-Young , Kim Du-Han
Published: October 2020

The purpose of our study was the clinical characteristics, radiographic appearance, and outcomes after treatment in patients with rapid destructive arthrosis (RDA) due to subchondral insufficiency fracture (SIF) of the shoulder. Twenty-two cases of RDA of the shoulder were retrospectively reviewed. Clinical outcomes for 15 cases who underwent shoulder arthroplasty were evaluated at an average of 41.4 months. The mean age of patients was 73.7 years (range 50–83 years), and there were 20 women and 2 men. The mean time from onset of symptoms to head collapse was 6.8 months (range 1–12 months). The mean t-score of bone mineral density was −3.1. Nine patients had pseudoparalysis. Based on radiographic appearance, a diversity of types of head destruction with subchondral fracture, bone marrow edema, joint effusion, and synovitis were observed in all cases. In conclusion, RDA due to SIF of the shoulder, presenting with severe short-term pain and functional disability, commonly occurred in elderly women with bone fragility. MRI revealed bone marrow edema, extensive joint effusion, and synovitis as well as a diversity of types of head destruction with subchondral fracture within several months from onset of symptoms.
Analysis of an Impact of Inertia Parameter in Active Disturbance Rejection Control Structures
Authors: Pazderski Dariusz , Patelski Radosław , Krysiak Bartłomiej , Kozłowski Krzysztof
Published: October 2020

This paper is focused on a distributed control of fully actuated manipulators under operating conditions when dynamic couplings between their joints are insignificant. The main research aspect was to examine the influence of the inertia parameter on the tracking quality for control systems based on the active rejection paradigm. The theoretical description and preliminary hypothesis were supported by extensive simulation and experimental results. In particular, it is demonstrated that choosing the inertia parameter according to the real dynamics properties does not guarantee the best performance of the considered control structures.
RETRACTED: Jin et al. Blockchain-Enabled Charging Right Trading Among EV Charging Stations. Energies 2019, 12, 3922
Authors:   Energies Editorial Office
Published: October 2020

It has come to our attention that the majority of the content in the title paper [...]