bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on ARKFCM Algorithm Based on Membership Constraint and Bias Field Correction in Neonatal HIE Image Segmentation Method
Authors: Huang Chao , Wang Jihua
Published: May 2021

First, this paper presents the algorithm of adaptively regularized kernel-based fuzzy C-means based on membership constraint (G-ARKFCM). Under the idea of competitive learning based on penalizing opponents, a new membership constraint function penalty item is introduced for each sample point in the segmented image, so that the ARKFCM algorithm is no longer limited to the fuzzy index m = 2. Secondly, the multiplicative intrinsic component optimization (MICO) is introduced into G-ARKFCM to obtain the GM-ARKFCM algorithm, which can correct the bias field when segmenting neonatal HIE images. Compared with other algorithms, the GM-ARKFCM algorithm has better segmentation quality and robustness. The GM-ARKFCM algorithm can more completely segment the neonatal ventricles and surrounding white matter and can retain more information of the original image.
Systematic Pharmacology Reveals the Antioxidative Stress and Anti-Inflammatory Mechanisms of Resveratrol Intervention in Myocardial Ischemia-Reperfusion Injury
Authors: Xing Zuzhong , He Qi , Xiong Yinliang , Zeng Xiaomei
Published: May 2021

Objective. To explore the oxidative stress and inflammatory mechanisms of resveratrol intervention in myocardial ischemia-reperfusion injury (MIRI). Methods. The potential targets of resveratrol were predicted by PharmMapper. The MIRI genes were collected by Online Mendelian Inheritance in Man (OMIM), GeneCards is used to collect related disease genes, and String is used for enrichment analysis. Animal experiments were then performed to verify the systematic pharmacological results. Hematoxylin-eosin (HE) staining was used to observe myocardial damage. The levels of serum interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in each experimental group were detected. The protein and mRNA expressions of Toll-like receptor 4 (TLR4), nuclear factor-kappa (NF-κB) p65, IL-1β, IL-6, and TNF-α in rat myocardial tissue were measured. Results. The results of systematic pharmacology showed that insulin resistance, FoxO signaling pathway, adipocytokine signaling pathway, insulin signaling pathway, PI3K-Akt signaling pathway, ErbB signaling pathway, T-cell receptor signaling pathway, peroxisome proliferator-activated receptors (PPAR) signaling pathway, Ras signaling pathway, TNF signaling pathway, and so on were regulated to improve MIRI. The results of animal experiments showed that the myocardial cells of the sham operation group were arranged in fibrous form, and the myocardial ischemia-reperfusion injury group had obvious cell morphology disorder. Compared with the MIRI group, the resveratrol group had a certain degree of relief. Compared with the MIRI group, serum IL-1β, TNF-α, and IL-6 in the resveratrol group was significantly reduced (

P

 < 0.05), and myocardial tissue TLR4, NF-κB p65, IL-1β, IL-6, and TNF-α mRNA and protein expressions were significantly reduced (

P

 < 0.05). Conclusion. Resveratrol can effectively improve MIRI, and its mechanism may be related to antioxidative stress and anti-inflammatory.
Determining Optimum Tilt Angle for 1 MW Photovoltaic System at Sukkur, Pakistan
Authors: Memon Qasir Ali , Rahimoon Abdul Qadir , Ali Khurshed , Shaikh Muhammad Fawad , Shaikh Shoaib Ahmed
Published: May 2021

Solar energy is directly converted into electrical energy by using photovoltaic (PV) panels. The efficiency of PV panel varies with its orientation and tilt angle with the horizontal plane. In this paper, we investigate the optimum tilt angle of solar panels installed at Sukkur IBA University. The optimum angle for tilted surfaces varying from 0° to 90° in steps of 1° was calculated for the values of which the daily total solar radiation was maximum for a specific period. It was found that the optimum tilt angle changed between 0° and 61.1° throughout the year in Sukkur IBA University, Sindh Pakistan (

latitude
=

27.7268

°

N,

longitude
=

68.8191

°

E). For calculating irradiance, optimal fixed (15 and 29.5 degrees) and variable tilt angles are used for every month of year 2019. The irradiance calculated at 15 degrees tilt angle is compared with the fixed angle of 29.5 and variable angles. It was found that optimal tilt angle for the region of Sukkur located in northern Pakistan is to be 29.5 degrees.
Microglia: A Potential Drug Target for Traumatic Axonal Injury
Authors: Huang Xin , You Wendong , Zhu Yuanrun , Xu Kangli , Yang Xiaofeng , Wen Liang
Published: May 2021

Traumatic axonal injury (TAI) is a major cause of death and disability among patients with severe traumatic brain injury (TBI); however, no effective therapies have been developed to treat this disorder. Neuroinflammation accompanying microglial activation after TBI is likely to be an important factor in TAI. In this review, we summarize the current research in this field, and recent studies suggest that microglial activation plays an important role in TAI development. We discuss several drugs and therapies that may aid TAI recovery by modulating the microglial phenotype following TBI. Based on the findings of recent studies, we conclude that the promotion of active microglia to the M2 phenotype is a potential drug target for the treatment of TAI.
Coexistence of Virulence Factors and Efflux Pump Genes in Clinical Isolates of Pseudomonas aeruginosa: Analysis of Biofilm-Forming Strains from Iran
Authors: Zahedani Shahram Shahraki , Tahmasebi Hamed , Jahantigh Mojdeh
Published: May 2021

Background. Biofilm formation and efflux pumps (EPs) correlation play a critical role in the pathogenicity and antibiotic resistance of Pseudomonas aeruginosa. In this study, biofilm formation and EP’s collaborative role in clinical isolates of P. aeruginosa infection were investigated. Methods. Eighty-six (86) P. aeruginosa isolates were collected from different clinical specimens and were confirmed using different biochemical tests. The formation of biofilm was investigated by using a crystal violet assay. Also, EP genes were identified by the PCR method. Results. Based on the results, gentamicin-resistant (n = 50, 66.29%) and ciprofloxacin-resistant (n = 61, 69.66%) strains were the most frequent and colistin (n = 1, 1.12%) and ceftazidime (n = 12, 7.86%) resistant strains were the least prevalent. Furthermore, 22 isolates (31.42%) were MDR, and 11 isolates (12.35%) were XDR strains. Also, 19 isolates (22.47%) were classified as strong biofilm, 29 isolates (21.34%) as moderate biofilm, and 3 (11.23%) isolates as weak biofilm producers. The distribution of the EP genes was as follows: mexA (n = 44, 34.83%), mexB (n = 33, 32.58%), oprM (n = 59, 29.21%), oprD (n = 61, 30.33%), tetA (n = 22, 25.58%), tetR (n = 19, 22.09%), and emrE (n = 21, 24.41%). However, there was a strong significant association between biofilm formation and EPs in P. aeruginosa. Conclusions. In this study, we suggested that the presence of a multidrug resistance efflux pump, MexEF-OprN, significantly reduced P. aeruginosa pathogenicity. In contrast, the presence of the MexAB-OprM and MexCD-OprJ pumps did not affect virulence.
Antibacterial Activity of 2-Picolyl-polypyridyl-Based Ruthenium (II/III) Complexes on Non-Drug-Resistant and Drug-Resistant Bacteria
Authors: Matshwele James T. P. , Odisitse Sebusi , Mapolelo Daphne , Leteane Melvin , Julius Lebogang G. , Nkwe David O. , Nareetsile Florence
Published: May 2021

A new hexadentate 2-picolyl-polypyridyl-based ligand (4, 4'-(butane-1, 4-diylbis(oxy))bis(N, N-bis(pyridin-2-ylmethyl)aniline)) (2BUT) (1) and its corresponding Ru(II/III) complexes were synthesized and characterized, followed by assessment of their possible bioactive properties towards drug-resistant and non-drug-resistant bacteria. Spectroscopic characterization of the ligand was done using proton NMR, FTIR, and ESI-MS, which showed that the ligand was successfully synthesized. The Ru(II/III) complexes were characterized by FTIR, UV/Vis, elemental analysis, proton NMR, ESI-MS, and magnetic susceptibility studies. The analysis of ESI-MS data of the complexes showed that they were successfully synthesized. Empirical formulae derived from elemental analysis of the complexes also indicated successful synthesis and relative purity of the complexes. The important functional groups of the ligands could be observed after complexation using FTIR. Magnetic susceptibility data and electronic spectra indicated that both complexes adopt a low spin configuration. The disc diffusion assay was used to test the compounds for antibiotic activity on two bacteria species and their drug-resistant counterparts. The compounds displayed antibiotic activity towards the two non-drug-resistant bacteria. As for the drug-resistant organisms, only [Ru2(2BUT)(DMF)2(DPA)2](BH4)43 and 2, 2-dipyridylamine inhibited the growth of MRSA. Gel electrophoresis DNA cleavage studies showed that the ligands had no DNA cleaving properties while all the complexes denatured the bacterial DNA. Therefore, the complexes may have DNA nuclease activity towards the bacterial genomic material.
The “Dark Side” of Pneumoperitoneum and Laparoscopy
Authors: Umano Giuseppina Rosaria , Delehaye Giulia , Noviello Carmine , Papparella Alfonso
Published: May 2021

Laparoscopic surgery has been one of the most common procedures for abdominal surgery at pediatric age during the last few decades as it has several advantages compared to laparotomy, such as shorter hospital stays, less pain, and better cosmetic results. However, it is associated with both local and systemic modifications. Recent evidence demonstrated that carbon dioxide pneumoperitoneum might be modulated in terms of pressure, duration, temperature, and humidity to mitigate and modulate these changes. The aim of this study is to review the current knowledge about animal and human models investigating pneumoperitoneum-related biological and histological impairment. In particular, pneumoperitoneum is associated with local and systemic inflammation, acidosis, oxidative stress, mesothelium lining abnormalities, and adhesion development. Animal studies reported that an increase in pressure and time and a decrease in humidity and temperature might enhance the rate of comorbidities. However, to date, few studies were conducted on humans; therefore, this research field should be further investigated to confirm in experimental models and humans how to improve laparoscopic procedures in the spirit of minimally invasive surgeries.
[Retracted] Genome‐Wide Screening Identifies Prognostic Long Noncoding RNAs in Hepatocellular Carcinoma
Authors: Feng Yujie , Hu Xiao , Ma Kai , Zhang Bingyuan , Sun Chuandong
Published: May 2021

Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis. Therefore, there is an urgent call for the investigation of novel biomarkers in HCC. In the present study, we identified 6 upregulated lncRNAs in HCC, including LINC01134, RHPN1‐AS1, NRAV, CMB9‐22P13.1, MKLN1‐AS, and MAPKAPK5‐AS1. Higher expression of these lncRNAs was correlated to a more advanced cancer stage and a poorer prognosis in HCC patients. Enrichment analysis revealed that these lncRNAs played a crucial role in HCC progression, possibly through a series of cancer‐related biological processes, such as cell cycle, DNA replication, histone acetyltransferase complex, fatty acid oxidation, and lipid modification. Moreover, competing endogenous RNA (ceRNA) network analysis revealed that these lncRNAs could bind to certain miRNAs to promote HCC progression. Loss‐of‐function assays indicated that silencing of RHPN1‐AS1 significantly suppressed HCC proliferation and migration. Though further validations are still needed, these identified lncRNAs could serve as valuable potential biomarkers for HCC prognosis.
HDL Improves Cholesterol and Glucose Homeostasis and Reduces Atherosclerosis in Diabetes-Associated Atherosclerosis
Authors: Di Bartolo Belinda A. , Cartland Siân P. , Genner Scott , Manuneedhi Cholan Pradeep , Vellozzi Melissa , Rye Kerry-Anne , Kavurma Mary M.
Published: May 2021

Background and Aims. Apolipoprotein A-I (ApoA-I), the main component of high-density lipoprotein (HDL), not only promotes reverse cholesterol transport (RCT) in atherosclerosis but also increases insulin secretion in pancreatic β-cells, suggesting that interventions which raise HDL levels may be beneficial in diabetes-associated cardiovascular disease (CVD). Previously, we showed that TNF-related apoptosis-inducing ligand (TRAIL) deletion in Apolipoprotein Eknockout (Apoe-/-) mice results in diabetes-accelerated atherosclerosis in response to a “Western” diet. Here, we sought to identify whether reconstituted HDL (rHDL) could improve features of diabetes-associated CVD in Trail-/-Apoe-/- mice. Methods and Results. Trail-/-Apoe-/- and Apoe-/- mice on a “Western” diet for 12 weeks received 3 weekly infusions of either PBS (vehicle) or rHDL (containing ApoA-I (20 mg/kg) and 1-palmitoyl-2-linoleoyl phosphatidylcholine). Administration of rHDL reduced total plasma cholesterol, triglyceride, and glucose levels in Trail-/-Apoe-/- but not in Apoe-/- mice, with no change in weight gain observed. rHDL treatment also improved glucose clearance in response to insulin and glucose tolerance tests. Immunohistological analysis of pancreata revealed increased insulin expression/production and a reduction in macrophage infiltration in mice with TRAIL deletion. Furthermore, atherosclerotic plaque size in Trail-/-Apoe-/- mice was significantly reduced associating with increased expression of the M2 macrophage marker CD206, suggesting HDL's involvement in the polarization of macrophages. rHDL also increased vascular mRNA expression of RCT transporters, ABCA1 and ABCG1, in Trail-/-Apoe-/- but not in Apoe-/- mice. Conclusions. rHDL improves features of diabetes-associated atherosclerosis in mice. These findings support the therapeutic potential of rHDL in the treatment of atherosclerosis and associated diabetic complications. More studies are warranted to understand rHDL’s mechanism of action.
Tacrolimus Protects Podocytes from Apoptosis via Downregulation of TRPC6 in Diabetic Nephropathy
Authors: Ma Ruixia , Wang Ying , Xu Yan , Wang Rui , Wang Xianghua , Yu Ning , Li Minghui , Zhou Yan
Published: May 2021

Podocyte injury plays an important role in diabetic nephropathy (DN), and apoptosis is one of its mechanisms. The transient receptor potential channel 6 (TRPC6) is expressed in podocytes and mediates podocyte injury induced by high glucose levels. Tacrolimus is a novel immunosuppressive agent that is reported to play an important role in podocyte protection. The purpose of this study was to investigate the potential mechanism of podocyte protection by tacrolimus in a type 2 diabetic mellitus (T2DM) rat model and in immortalized mouse podocytes (MPC5). Transmission electron microcopy was used to evaluate renal injury morphology. After treatment with FK506, we measured 24-hour urinary albumin-to-creatinine ratios and creatinine clearance rates as well as major biochemical parameters such as glucose, insulin, serum creatinine, urea nitrogen, total cholesterol, triglycerides, alanine transaminase, and aspartate aminotransferase. Nephrin and TRPC6 protein expression and podocyte apoptotic rates in vivo and in vitro were measured using immunohistochemical staining, TUNEL assays, and flow cytometry, respectively. Western blot was used to measure expression of cleaved-caspase-3 and bax/bcl-2. Exposed to high glucose (HG), DM rats exhibited disrupted biochemical conditions and impaired podocyte structure. Decreased expression of nephrin and increased expression of TRPC6, cleaved-caspase-3, and bax/bcl-2 ratios were found in podocytes, along with higher apoptotic percentage, while tacrolimus intervention counteracted the effect of HG on podocytes. Our results suggest that tacrolimus protects podocytes during the progression of type 2 diabetic nephropathy, possibly ameliorating podocyte apoptosis by downregulating the expression of TRPC6.
Asymptomatic Familial Multiple Cerebral Cavernous Malformation in a 73-Year-Old Woman
Authors: Dzefi-Tettey Klenam , Edzie Emmanuel Kobina Mesi , Gorleku Philip Narteh , Kusodzi Henry , Asemah Abdul Raman
Published: May 2021

Cerebral cavernous malformations (CCMs) are dilated blood vessels which can develop sporadically or in familial form and are the commonest malformations of blood vessels in the spinal cord and brain. The familial form is an autosomal dominant gene mutation disorder. This condition can be diagnosed with magnetic resonance imaging (MRI) and computed tomography (CT) scan, but the modality of choice is MRI because of its high sensitivity. We report a case of a 73-year-old woman with an asymptomatic multiple familial cerebral cavernous malformation (FCCM) which was previously misdiagnosed as multiple cerebral metastases on CT scan. A brain MRI performed correctly diagnosed her condition as FCCM based on the typical MRI appearances. In order not to misdiagnose brain lesions like CCM on CT scan, for cerebral metastases in resource-poor settings, radiologists must recommend advanced imaging modalities like MRI for further evaluation, thereby avoiding unnecessary invasive surgical biopsies.
The Future Burden of Head and Neck Cancers Attributable to Modifiable Behaviors in Australia: A Pooled Cohort Study
Authors: Laaksonen Maarit A. , Canfell Karen , MacInnis Robert J. , Banks Emily , Byles Julie E. , Giles Graham G. , Magliano Dianna J. , Shaw Jonathan E. , Hirani Vasant , Gill Tiffany K. , Mitchell Paul , Cumming Robert G. , Salagame Usha , Vajdic Claire M.
Published: May 2021

Background:

Estimates of future burden of cancer attributable to current modifiable causal exposures can guide cancer prevention. We quantified future head and neck cancer burden in Australia attributable to individual and joint causal exposures, and assessed whether these burdens differ between population subgroups.

Methods:

We estimated the strength of the associations between exposures and head and neck cancer using adjusted proportional hazards models from pooled data from seven Australian cohorts (N = 367,058) linked to national cancer and death registries and estimated exposure prevalence from the 2017 to 2018 Australian National Health Survey. We calculated population attributable fractions (PAF) with 95% confidence intervals (CI), accounting for competing risk of death, and compared PAFs for population subgroups.

Results:

Contemporary levels of current and former smoking contribute 30.6% (95% CI, 22.7%–37.8%), alcohol consumption exceeding two standard drinks per day 12.9% (95% CI, 7.6%–17.9%), and these exposures jointly 38.5% (95% CI, 31.1%–45.0%) to the future head and neck cancer burden. Alcohol-attributable burden is triple and smoking-attributable burden is double for men compared with women. Smoking-attributable burden is also at least double for those consuming more than two alcoholic drinks daily or doing less than 150 minutes of moderate or 75 minutes of vigorous activity weekly, and for those aged under 65 years, unmarried, with low or intermediate educational attainment or lower socioeconomic status, compared with their counterparts.

Conclusions:

Two-fifths of head and neck cancers in Australia are preventable by investment in tobacco and alcohol control.

Impact:

Targeting men and other identified high-burden subgroups can help to reduce head and neck cancer burden disparities.
Defining the Energetic Basis for a Conformational Switch Mediating Ligand-Independent Activation of Mutant Estrogen Receptors in Breast Cancer
Authors: Mayne Christopher G. , Toy Weiyi , Carlson Kathryn E. , Bhatt Trusha , Fanning Sean W. , Greene Geoffrey L. , Katzenellenbogen Benita S. , Chandarlapaty Sarat , Katzenellenbogen John A. , Tajkhorshid Emad
Published: May 2021

Although most primary estrogen receptor (ER)–positive breast cancers respond well to endocrine therapies, many relapse later as metastatic disease due to endocrine therapy resistance. Over one third of these are associated with mutations in the ligand-binding domain (LBD) that activate the receptor independent of ligand. We have used an array of advanced computational techniques rooted in molecular dynamics simulations, in concert with and validated by experiments, to characterize the molecular mechanisms by which specific acquired somatic point mutations give rise to ER constitutive activation. By comparing structural and energetic features of constitutively active mutants and ligand-bound forms of ER-LBD with unliganded wild-type (WT) ER, we characterize a spring force originating from strain in the Helix 11–12 loop of WT-ER, opposing folding of Helix 12 into the active conformation and keeping WT-ER off and disordered, with the ligand-binding pocket open for rapid ligand binding. We quantify ways in which this spring force is abrogated by activating mutations that latch (Y537S) or relax (D538G) the folded form of the loop, enabling formation of the active conformation without ligand binding. We also identify a new ligand-mediated hydrogen-bonding network that stabilizes the active, ligand-bound conformation of WT-ER LBD, and similarly stabilizes the active conformation of the ER mutants in the hormone-free state.

Implications:

Our investigations provide deep insight into the energetic basis for the structural mechanisms of receptor activation through mutation, exemplified here with ER in endocrine-resistant metastatic breast cancers, with potential application to other dysregulated receptor signaling due to driver mutations.
Local Anti–PD-1 Delivery Prevents Progression of Premalignant Lesions in a 4NQO-Oral Carcinogenesis Mouse Model
Authors: Shi Yewen , Xie Tong-xin , Leach David G. , Wang Bingbing , Young Simon , Osman Abdullah A. , Sikora Andrew G. , Ren Xiaoyong , Hartgerink Jeffrey D. , Myers Jeffrey N. , Rangel Roberto
Published: May 2021

Although the principle of systemic treatment to prevent the progression of oral premalignant lesions (OPL) has been demonstrated, there remains a lack of consensus about an optimal approach that balances clinical efficacy with toxicity concerns. Recent advances in cancer therapy using approaches targeting the tumor immune microenvironment (TIME) including immune-checkpoint inhibitors indicate that these agents have significant clinically activity against different types of cancers, including oral cancer, and therefore they may provide an effective oral cancer prevention strategy for patients with OPLs. Our past work showed that systemic delivery of a monoclonal antibody to the programmed death receptor 1 (PD-1) immune checkpoint can inhibit the progression of OPLs to oral cancer in a syngeneic murine oral carcinogenesis model. Here we report a novel approach of local delivery of a PD-1 immune-checkpoint inhibitor loaded using a hydrogel, which significantly reduces the progression of OPLs to carcinomas. In addition, we detected a significant infiltration of regulatory T cells associated with oral lesions with p53 mutation, and a severe loss of expression of STING, which correlated with a decreased infiltration of dendritic cells in the oral lesions. However, a single local dose of PD-1 inhibitor was found to restore stimulator of interferon response cGAMP interactor 1 (STING) and CD11c expression and increase the infiltration of CD8+ T cells into the TIME irrespective of the p53 mutational status. Overall, we provide evidence for the potential clinical value of local delivery of biomaterials loaded with anti–PD-1 antibodies to prevent malignant progression of OPLs.

Prevention Relevance:

Oral cancer is an aggressive disease, with an overall survival rate of 50%. Preinvasive histologic abnormalities such as tongue dysplasia represent an early stage of oral cancer; however, there are no treatments to prevent oral carcinoma progression. Here, we combined biomaterials loaded with an immunotherapeutic agent preventing oral cancer progression.
Impact of Patient Adherence to Stool-Based Colorectal Cancer Screening and Colonoscopy Following a Positive Test on Clinical Outcomes
Authors: Fendrick A. Mark , Fisher Deborah A. , Saoud Leila , Ozbay A. Burak , Karlitz Jordan J. , Limburg Paul J.
Published: May 2021

Colorectal cancer–screening models commonly assume 100% adherence, which is inconsistent with real-world experience. The influence of adherence to initial stool-based screening [fecal immunochemical test (FIT), multitarget stool DNA (mt-sDNA)] and follow-up colonoscopy (after a positive stool test) on colorectal cancer outcomes was modeled using the Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model. Average-risk individuals without diagnosed colorectal cancer at age 40 undergoing annual FIT or triennial mt-sDNA screening from ages 50 to 75 were simulated. Primary analyses incorporated published mt-sDNA (71%) or FIT (43%) screening adherence, with follow-up colonoscopy adherence ranging from 40% to 100%. Secondary analyses simulated 100% adherence for stool-based screening and colonoscopy follow-up (S1), published adherence for stool-based screening with 100% adherence to colonoscopy follow-up (S2), and published adherence for both stool-based screening and colonoscopy follow-up after positive mt-sDNA (73%) or FIT (47%; S3). Outcomes were life-years gained (LYG) and colorectal cancer incidence and mortality reductions (per 1,000 individuals) versus no screening. Adherence to colonoscopy follow-up after FIT had to be 4%–13% higher than mt-sDNA to reach equivalent LYG. The theoretical S1 favored FIT versus mt-sDNA (LYG 316 vs. 297; colorectal cancer incidence reduction 68% vs. 64%; colorectal cancer mortality reduction 76% vs. 72%). The more realistic S2 and S3 favored mt-sDNA versus FIT (S2: LYG 284 vs. 245, colorectal cancer incidence reduction 61% vs. 50%, colorectal cancer mortality reduction 69% vs. 59%; S3: LYG 203 vs. 113, colorectal cancer incidence reduction 43% vs. 23%, colorectal cancer mortality reduction 49% vs. 27%, respectively). Incorporating realistic adherence rates for colorectal cancer screening influences modeled outcomes and should be considered when assessing comparative effectiveness.

Prevention Relevance:

Adherence rates for initial colorectal cancer screening by FIT or mt-sDNA and for colonoscopy follow-up of a positive initial test influence the comparative effectiveness of these screening strategies. Using adherence rates based on published data for stool-based testing and colonoscopy follow-up yielded superior outcomes with an mt-sDNA versus FIT-screening strategy.
IL11: A Specific Repressor of Tumor-Specific CD4+ T Cells
Authors: van der Burg Sjoerd H.
Published: May 2021

CD4+ T helper 1 (Th1) cells have a key role in tumor immunity by producing effector cytokines that orchestrate the tumoricidal effects of cytotoxic T lymphocytes, natural killer cells, and macrophages and directly exert tumor growth control via the induction of tumor cell senescence and inhibition of angiogenesis. In this issue, Huynh and colleagues report a new role for IL11 in fostering tumor outgrowth by suppressing the effector mechanisms of intratumoral CD4+ Th1 cells.

See related article by Huynh et al., p. 735.
Treatment Strategy for Patients with HR-Positive HER2-Negative Metastatic Breast Cancer That Progressed on CDK4/6 Inhibitors
Authors: Hayama Shouko , Nakamura Rikiya , Miyaki Toshiko , Itami Makiko , Yamamoto Naohito
Published: May 2021

Background/Aims: The study aim was to evaluate if mTOR inhibitors can be considered as a treatment option for HR+ HER2− metastatic breast cancer (MBC) after progression on CDK4/6 inhibitors in clinical practice. Methods: We retrospectively collected the clinicopathological data of patients with HR+ HER2− MBC treated with CDK4/6 inhibitors and subsequent therapies at our institution between 2014 and 2020. The patients were divided into 3 groups according to the type of subsequent treatment: (A) exemestane plus everolimus, (B) endocrine monotherapy, and (C) chemotherapy. Overall survival (OS) was estimated by using the Kaplan-Meier method and compared by using the log-rank test. The efficacy and adverse events (AEs) of each subsequent treatment were assessed by using Fisher’s exact tests. Results: Eighty-six patients (34 in group A, 20 in group B, 32 in group C) were included. The most common endocrine therapy in group B was fulvestrant (40%). The major chemotherapy regimen in group C was eribulin (25%). The median OS times after stopping CDK4/6 inhibitors were 34.5 months (95% confidence interval, 17.2 to NA), 13.6 months (3.9 to NA), and 19.5 months (18.8 to NA) in group A, group B, and group C, respectively. The only significant difference in OS was observed between group A and group B (20.9 months; p = 0.003). There was no difference in the incidence of grade 3 AEs between groups A and C or in the frequency of treatment discontinuation because of AEs among the 3 groups. Conclusion: Our study shows that mTOR inhibitors might be an effective treatment option for patients with HR+ HER2− MBC previously treated with CDK4/6 inhibitors.
Animal Models in Pharmacology: A Brief History Awarding the Nobel Prizes for Physiology or Medicine
Authors: Jota Baptista Catarina V. , Faustino-Rocha Ana I. , Oliveira Paula A.
Published: May 2021

Background: The Nobel Prize of Physiology or Medicine (NPPM) has recognized the work of 222 scientists from different nationalities, from 1901 until 2020. From the total, 186 award researchers used animal models in their projects, and 21 were attributed to scientists and projects directly related to Pharmacology. In the most recent years, genetics is a dominant scientific area, while at the beginning of the 20th century, most of the studies were more related to anatomy, cytology, and physiology. Summary: Mammalian models were used in 144 NPPM projects, being rodents the most used group of species. Moreover, 92 researchers included domestic species in their work. The criteria used to choose the species, the number of animals used and the experimental protocol is always debatable and dependent on the scientific area of the study; however, the 3R’s principle can be applied to most scientific fields. Independently of the species, the animal model can be classified in different types and criteria, depending on their ecology, genetics, and mode of action. Key-Messages: The use of animal models in NPPM awarded projects, namely in Pharmacology, illustrates their importance, need and benefit to improve scientific knowledge and create solutions. In the future, with the contribute of technology, it might be possible to refine the use of animal models in pharmacology studies.
Bottlenecks in the Acute Stroke Care System during the COVID-19 Pandemic in Catalonia
Authors: Ramos-Pachón Anna , García-Tornel Álvaro , Millán Mònica , Ribó Marc , Amaro Sergi , Cardona Pere , Martí-Fàbregas Joan , Roquer Jaume , Silva Yolanda , Ustrell Xavier , Purroy Francisco , Gómez-Choco Manuel , Zaragoza-Brunet José , Cánovas David , Krupinski Jurek , Sala Natalia Mas , Palomeras Ernest , Cocho Dolores , Redondo Laura , Repullo Carmen , Sanjurjo Eduardo , Carrión Dolors , López Mercè , Almendros M.Cruz , Barceló Miquel , Monedero Jordi , Catena Esther , Rybyeba Maria , Diaz Gloria , Jiménez-Fàbrega Xavier , Solà Silvia , Hidalgo Verónica , Pueyo Maria Jesus , Pérez de la Ossa Natàlia , Urra Xabier ,   for the Catalan Stroke Code and Reperfusion Consortium (Cat-SCR)
Published: May 2021

Introduction: The COVID-19 pandemic resulted in significant healthcare reorganizations, potentially striking standard medical care. We investigated the impact of the COVID-19 pandemic on acute stroke care quality and clinical outcomes to detect healthcare system’s bottlenecks from a territorial point of view. Methods: Crossed-data analysis between a prospective nation-based mandatory registry of acute stroke, Emergency Medical System (EMS) records, and daily incidence of COVID-19 in Catalonia (Spain). We included all stroke code activations during the pandemic (March 15–May 2, 2020) and an immediate prepandemic period (January 26–March 14, 2020). Primary outcomes were stroke code activations and reperfusion therapies in both periods. Secondary outcomes included clinical characteristics, workflow metrics, differences across types of stroke centers, correlation analysis between weekly EMS alerts, COVID-19 cases, and workflow metrics, and impact on mortality and clinical outcome at 90 days. Results: Stroke code activations decreased by 22% and reperfusion therapies dropped by 29% during the pandemic period, with no differences in age, stroke severity, or large vessel occlusion. Calls to EMS were handled 42 min later, and time from onset to hospital arrival increased by 53 min, with significant correlations between weekly COVID-19 cases and more EMS calls (rho = 0.81), less stroke code activations (rho = −0.37), and longer prehospital delays (rho = 0.25). Telestroke centers were afflicted with higher reductions in stroke code activations, reperfusion treatments, referrals to endovascular centers, and increased delays to thrombolytics. The independent odds of death increased (OR 1.6 [1.05–2.4], p 0.03) and good functional outcome decreased (mRS ≤2 at 90 days: OR 0.6 [0.4–0.9], p 0.015) during the pandemic period. Conclusion: During the COVID-19 pandemic, Catalonia’s stroke system’s weakest points were the delay to EMS alert and a decline of stroke code activations, reperfusion treatments, and interhospital transfers, mostly at local centers. Patients suffering an acute stroke during the pandemic period had higher odds of poor functional outcome and death. The complete stroke care system’s analysis is crucial to allocate resources appropriately.
Decreased Time on the Nondominant One-Leg Standing Test Associated with Repeated Falls in Older Residents with Healthy Aging, Mild Cognitive Impairment, and Dementia: The Wakuya Project
Authors: Kumai Keiichi , Kumai Mika , Takada Junko , Oonuma Jiro , Nakamura Kei , Meguro Kenichi
Published: May 2021

Introduction: The aim of this study is to clarify the association between repeated falls and the dominant/nondominant side in the open-eyed one-leg standing (OLS) test among people who are healthy or have mild cognitive impairment (MCI) or dementia in a community setting. We recruited 180 participants from 39 areas in the town of Wakuya. Methods: This is a cross-sectional study. Participants were classified into 3 Clinical Dementia Rating (CDR) groups, i.e., CDR 0 (healthy, n = 71), CDR 0.5 (MCI, n = 85), and CDR 1+ (n = 23), and they were investigated for motor function (grip strength, 6-m normal gait speed, timed up and go test, and OLS test) and falls during the past year. Results: Subjects with a CDR of 0.5 had higher rates of single and repeated falls (13.0 and 23.4%, respectively) than the CDR 0 group (12.1 and 4.5%, respectively), as did those in CDR 1+ group (15.0 and 30.0%). For the CDR 0.5 group, the frequency of falls was negatively (biologically meaningful direction) correlated with the left OLS time. No significant correlations with falls were found for other motor function tests. Another analysis separating the CDR 0.5 group into 2 subgroups (repeated falls vs. no or a single fall) also showed that the left OLS time was lower in subjects with repeated falls. Conclusion: People with MCI who had fallen repeatedly in the year before the assessment had a significantly lower left OLS time compared to those who had not fallen or had had 1 fall with MCI. None of the other physical measures were associated with past repeat falls including OLS on the dominant right side. No such findings were noted in the CDR 0 and CDR 0+ groups.
The impact of integration of solar farms on the power losses, voltage profile and short circuit level in the distribution system
Authors: Alzyoud Abdallah R , Dalabeeh Ali S , Al-Rawashdeh Ayman Y. , Al-Mofleh Anwar , Allabadi Ahmad , Almomani Tamadher , Hindi Ayman
Published: May 2021

This paper introduces a study of utilizing solar energy farm that is integrated with the national grid based on intensive data availability of solar energy in Jordan. The study discusses the impact and the ability of integrating solar farms into the national grid of Jordan. The study considerd different cases and, various power system studies for connection points of solar farms to medium voltage networks. Among these studies are short circuit level, voltage profile and power losses. The main objective of the study is to analyze impacts of integration of solar farms on distribution systems of the chosen areas. Photovoltaic (PV) system with varying penetration levels are integrated at different locations (connection points) into the distribution network. Calculations are performed and models are built using actual data obtained from the Jordanian power grid with PV interconnection. The effect of the short circuit level, voltage profile and power losses in the distribution system are also analyzed. Finally, the most suitable method of connecting the solar farm to the national power network is recommended.
Outage performance users located outside D2D coverage area in downlink cellular network
Authors: Nguyen Thanh-Luan , Do Dinh-Thuan
Published: May 2021

Device-to-device (D2D) communication has been proposed to employ the proximity between two devices to enhance the overall spectrum utilization of a crowded cellular network. With the help of geometric probability tools, this framework considers the performance of cellular users under spatial separation with the D2D pair is investigated. The measurement results and analytical expression of outage probability show that the proposed frameworks improve the outage performance at a high signal-tonoise ratio (SNR) at the base station. Results also interpret that the distances between nodes in the D2D-assisted network make slight impacts on the performance of the cellular user.
VHDL design and FPGA implementation of direct torque control for induction machines
Authors: Lotfi Elhabib , Elharoussi Mustapha , Abdelmounim Elhassane
Published: May 2021

This paper presents a VHDL design and an FPGA implementation of a direct torque controller (DTC) used to order induction machines (IM). The use of FPGA at high sampling frequency reduces the torque ripple while maintaining the classical DTC control structure. We have adopted a modular approach, by dividing the global entity into a set of elementary blocks designed and implemented separately. The performances of this command are to reduce the torque ripple to 0.01 Nm and the flux ripple to 0.01 wb with a circuit implementing DTC control of 3,256 LEs of complexity and 64 latency clock cycles. To evaluate the performance of our FPGA circuit implementing DTC controller, we have performed a co-simulation platform based on MATLAB/Simulink and Modelsim programs. MATLAB/Simulink was used to simulate the dynamics of the induction machine associated with its inverter and the proposed DTC control strategy was executed under the modelsim software using the VHDL fixed point. We have operated our circuit FPGA in the loop in a speed variation platform of induction machine and we have obtained the following performances: A zero overrun, response time at speeds of 300 ms and a zero static error as required in the specifications.
Secure message transmission scheme in wireless sensor networks
Authors: Ameen Kameran Ali , Mahmood Baban Ahmed , Najm Aldeen Taher Yalmaz
Published: May 2021

Wireless sensor networks (WSNs) have been the subject of intensive research in the past few years and the backbone of most maximum present information technology. WSNs have been employed in various applications such as track monitoring battlegrounds in military fields and patients’ medical requirements in the civilian field. The wireless sensor networks are always randomly distributed in an open area (hostile), pervasive environment, and open media channel. Thus, WSNs are vulnerable to several species of attacks. Moreover, messages may be easily intercepted or altered because the transmission is not secure, hence effective key management scheme is strongly needed to reduce the risks. Cryptography methods are a crucial aspect of WSNs to reach security goals. In this paper, we propose an efficient and secure message transmission scheme that combines the Knapsack algorithm with the Diffie-Hellmann process to encrypt messages. The results and analysis show that the proposed scheme is efficient and it achieves most of the security goals providing high privacy and security. It is also resilient against some of the well-known attacks.
Mobile health monitoring based studies for diabetes mellitus: a review
Authors: AlShorman Omar , Masadeh Mahmoud Saleh , AlShorman Buthaynah
Published: May 2021

Diabetes as a chronic disease is considered to be a serious problem not only for diabetic patients but also for caregivers, families and countries. Hazardously, as an example, 16% of the Middle East population died every year because of diabetes as it is reported by World Health Organization (WHO). Therefore, it is crucial to utilize the recent advances and technologies to find the best instrument for diabetes monitoring and management. Recently, mobile health (mHealth) technologies have a vital role in the healthcare industrial world. Undoubtedly, mHealth technologies are used to manage, track, monitor, diagnose, and prevent chronic diseases including, diabetes. Certainly, the main advantages of mHealth include a real-time and continuous monitoring with high reliability, accessibility, and availability. In addition to that, mHealth is considered to be a fast, accurate, simple, cheap, comfortable, and safe technology. Hence, the proposed study aims to review existing mHealth studies for managing, diagnosing, tracking, detecting, and predicting diabetic mellitus. Moreover, challenges and future trends of this emerging topic are also discussed.
Comparative analysis of augmented datasets performances of age invariant face recognition models
Authors: Okokpujie Kennedy , Noma-Osaghae Etinosa , John Samuel Ndueso , Ndujiuba Charles , Okokpujie Imhade Princess
Published: May 2021

The popularity of face recognition systems has increased due to their non-invasive method of image acquisition, thus boasting the widespread applications. Face ageing is one major factor that influences the performance of face recognition algorithms. In this study, the authors present a comparative study of the two most accepted and experimented face ageing datasets (FG-Net and morph II). These datasets were used to simulate age invariant face recognition (AIFR) models. Four types of noises were added to the two face ageing datasets at the preprocessing stage. The addition of noise at the preprocessing stage served as a data augmentation technique that increased the number of sample images available for deep convolutional neural network (DCNN) experimentation, improved the proposed AIFR model and the trait aging features extraction process. The proposed AIFR models are developed with the pre-trained Inception-ResNet-v2 deep convolutional neural network architecture. On testing and comparing the models, the results revealed that FG-Net is more efficient over Morph with an accuracy of 0.15%, loss function of 71%, mean square error (MSE) of 39% and mean absolute error (MAE) of -0.63%.
Automatic limit switch calibrator for control valve at steam turbine of a geothermal power plant
Authors: Megantoro Prisma , Latif Abdul , Aji Pramudita Brahmantya , Vigneshwaran P.
Published: May 2021

Measurement of fluid level in steam valves should require precise values. The instrument designed in this article is used to find out how precise the limit switch is used as an indicator control valve at certain points. The measurement technique will be implemented on a control valve on the geothermal power plant. This device is using the Arduino Due board as a data processor and modified the data signal of the vernier caliper to measure the valve opening. The TFT LCD layer is used to display the measurement and calibration results. The test results of this device indicate that this device has an accuracy level of more than 99%.
Evaluation of scratch and pre-trained convolutional neural networks for the classification of Tomato plant diseases
Authors: Ihsan Aquil Mohammad Amimul , Wan Ishak Wan Hussain
Published: May 2021

Plant diseases are a major cause of destruction and death of most plants and especially trees. However, with the help of early detection, this issue can be solved and treated appropriately. A timely and accurate diagnosis is critical in maintaining the quality of crops. Recent innovations in the field of deep learning (DL), especially in convolutional neural networks (CNNs) have achieved great breakthroughs across different applications such as the classification of plant diseases. This study aims to evaluate scratch and pre-trained CNNs in the classification of tomato plant diseases by comparing some of the state-of-the-art architectures including densely connected convolutional network (Densenet) 120, residual network (ResNet) 101, ResNet 50, ReseNet 30, ResNet 18, squeezenet and Vgg.net. The comparison was then evaluated using a multiclass statistical analysis based on the F-Score, specificity, sensitivity, precision, and accuracy. The dataset used for the experiments was drawn from 9 classes of tomato diseases and a healthy class from PlantVillage. The findings show that the pretrained Densenet-120 performed excellently with 99.68% precision, 99.84% F-1 score, and 99.81% accuracy, which is higher compared to its non-trained based model showing the effectiveness of using a combination of a CNN model with fine-tuning adjustment in classifying crop diseases.
Amazigh-Sys: Intelligent system for recognition of amazigh words
Authors: Ammari Rachid , Zenkouar Lahbib
Published: May 2021

Amazigh-sys is an intelligent morphological analysis system for Amazigh language based on xerox’s finite-state transducer (XFST). Our system can process simultaneously five lexical units. This paper begins with the development of Amazigh lexicon (AMAlex) for attested nouns, verbs, pronouns, prepositions, and adverbs and the characteristics relating to each lemma. A set of rules are added to define the inflectional behavior and morphosyntactic links of each entry as well as the relationship between the different lexical units. The use of finite-state technology ensures the bidirectionality of our system (analysis and generation). Amazigh-sys is the first general morphological analysis system for Amazigh based on xerox finite state able to process and recognize all lexical units and ensures a high recognition rate of input words. This contribution facilitates the implementation of other applications related to the automatic processing of the Amazigh language.
EEG signal classification for drowsiness detection using wavelet transform and support vector machine
Authors: Br. Pasaribu Novie Theresia , Halim Timotius , Ratnadewi Ratnadewi , Prijono Agus
Published: May 2021

There are several categories to detect and measure driver drowsiness such as physiological methods, subjective methods and behavioral methods. The most objective method for drowsiness detection is the physiological method. One of the physiological methods used is an electroencephalogram (EEG). In this research wavelet transform is used as a feature extraction and using support vector machine (SVM) as a classifier. We proposed an experiment of retrieval data which is designed by using modified-EAR and EEG signal. From the SVM training process, with the 5-fold cross validation, Quadratic kernel has the highest accuracy 84.5% then others. In testing Driving-2 process 7 respondents were detected as drowsiness class, and 3 respondents were detected as awake class. In the testing of Driving-3 process, 6 respondents were detected as drowsiness class, and 4 respondents were detected as awake class. 