bluuebunny/crossref_metadata_2025 huggingface dataset:
The Screen Project: Guided Direct-To-Consumer Genetic Testing for Breast Cancer Susceptibility in Canada
Authors: Narod Steven A. , Gojska Nicole , Sun Ping , Tryon Angelina , Kotsopoulos Joanne , Metcalfe Kelly , Akbari Mohammad R.
Published: April 2021

There is limited information of the outcomes of direct-to-consumer testing for BRCA1 and BRCA2 mutations. The Screen Project was initiated in 2017 to offer BRCA1 and BRCA2 genetic screening to all Canadians over the age of 18 who wish to know their mutation status. Patients enrolled in the study from 2017 to 2019 and were followed for one year after the receipt of a genetic test result. Study subjects registered online and were sent a saliva sample kit, which was shipped to the reference laboratory. Pre-test genetic counselling and counselling for mutation-negative subjects was optional and at the individual’s discretion. There were 1269 tested individuals between March 2017 and January 2019. A total of 1157 (93%) were women and 87 (7%) were men. Sixty-six percent had a first- or second-degree relative with breast or ovarian cancer. Of the 1269 tested individuals, 30 (2.4%) had a pathogenic mutation in BRCA1 or BRCA2 (20 women and 10 men). Seventy-five percent of the female mutation carriers underwent a bilateral mastectomy and/or salpingo-oophorectomy within a year of receiving a positive result. Genetic counselling was available at no cost to all participants but was requested by only 5% of the non-carriers. The study subjects expressed a high degree of satisfaction with the process.
Prognostic Value of the Neutrophil-to-Lymphocyte Ratio before and after Radiotherapy for Anaplastic Thyroid Carcinoma
Authors: Park Jiyun , Park Jun , Shin Jung-Hee , Oh Young-Lyun , Jung Hyun-Ae , Chung Man-Ki , Choe Jun-Ho , Ahn Yong-Chan , Kim Sun-Wook , Chung Jae-Hoon , Kim Tae-Hyuk , Noh Jae-Myoung
Published: April 2021

The neutrophil–lymphocyte ratio (NLR) is a marker of systemic inflammation, and its elevation has recently been associated with poor survival in many solid cancers. Leukocyte elevation and lymphocyte reduction are associated with a poor response to radiotherapy (RT). This study aimed to assess the prognostic value of NLR before and after RT for anaplastic thyroid carcinoma (ATC). This retrospective study analyzed 40 patients with ATC who received RT with available complete blood cell count data from November 1995 through May 2020 at Samsung Medical Center (Seoul, Korea). Patients were classified into two groups according to the NLR before and after RT. The median overall survival (OS) was 8.9 months (range, 3.5–18.2) in the low NLR group (<3.47) and 5.2 months (range, 2.7–7.5) months in the high NLR group (≥3.47). The association between NLR and OS was also observed in multivariable Cox regression analysis (hazard ratio, 3.18; 95% confidence interval, 1.15–8.85; p = 0.026). The OS curves differed significantly according to post-RT NLR (p = 0.036). A high NLR before and after RT may be significantly associated with poor OS in patients with ATC who receive RT.
Mitochondrial Control of Genomic Instability in Cancer
Authors: Bonora Massimo , Missiroli Sonia , Perrone Mariasole , Fiorica Francesco , Pinton Paolo , Giorgi Carlotta
Published: April 2021

Mitochondria are well known to participate in multiple aspects of tumor formation and progression. They indeed can alter the susceptibility of cells to engage regulated cell death, regulate pro-survival signal transduction pathways and confer metabolic plasticity that adapts to specific tumor cell demands. Interestingly, a relatively poorly explored aspect of mitochondria in neoplastic disease is their contribution to the characteristic genomic instability that underlies the evolution of the disease. In this review, we summarize the known mechanisms by which mitochondrial alterations in cancer tolerate and support the accumulation of DNA mutations which leads to genomic instability. We describe recent studies elucidating mitochondrial responses to DNA damage as well as the direct contribution of mitochondria to favor the accumulation of DNA alterations.
ZINC40099027 Promotes Gastric Mucosal Repair in Ongoing Aspirin-Associated Gastric Injury by Activating Focal Adhesion Kinase
Authors: Oncel Sema , Gupta Rashmi , Wang Qinggang , Basson Marc D.
Published: April 2021

Nonsteroidal anti-inflammatory drugs cause gastric ulcers and gastritis. No drug that treats GI injury directly stimulates mucosal healing. ZINC40099027 (ZN27) activates focal adhesion kinase (FAK) and heals acute indomethacin-induced small bowel injury. We investigated the efficacy of ZN27 in rat and human gastric epithelial cells and ongoing aspirin-associated gastric injury. ZN27 (10 nM) stimulated FAK activation and wound closure in rat and human gastric cell lines. C57BL/6J mice were treated with 300 mg/kg/day aspirin for five days to induce ongoing gastric injury. One day after the initial injury, mice received 900 µg/kg/6 h ZN27, 10 mg/kg/day omeprazole, or 900 µg/kg/6 h ZN27 plus 10 mg/kg/day omeprazole. Like omeprazole, ZN27 reduced gastric injury vs. vehicle controls. ZN27-treated mice displayed better gastric architecture, with thicker mucosa and less hyperemia, inflammation, and submucosal edema, and lost less weight than vehicle controls. Gastric pH, serum creatinine, serum alanine aminotransferase (ALT), and renal and hepatic histology were unaffected by ZN27. Blinded scoring of pFAK-Y-397 immunoreactivity at the edge of ZN27-treated lesions demonstrated increased FAK activation, compared to vehicle-treated lesions, confirming target activation in vivo. These results suggest that ZN27 ameliorates ongoing aspirin-associated gastric mucosal injury by a pathway involving FAK activation. ZN27-derivatives may be useful to promote gastric mucosal repair.
Antiretroviral Drugs Impact Autophagy with Toxic Outcomes
Authors: Cheney Laura , Barbaro John M. , Berman Joan W.
Published: April 2021

Antiretroviral drugs have dramatically improved the morbidity and mortality of people living with HIV (PLWH). While current antiretroviral therapy (ART) regimens are generally well-tolerated, risks for side effects and toxicity remain as PLWH must take life-long medications. Antiretroviral drugs impact autophagy, an intracellular proteolytic process that eliminates debris and foreign material, provides nutrients for metabolism, and performs quality control to maintain cell homeostasis. Toxicity and adverse events associated with antiretrovirals may be due, in part, to their impacts on autophagy. A more complete understanding of the effects on autophagy is essential for developing antiretroviral drugs with decreased off target effects, meaning those unrelated to viral suppression, to minimize toxicity for PLWH. This review summarizes the findings and highlights the gaps in our knowledge of the impacts of antiretroviral drugs on autophagy.
A Quality Improvement Initiative to Reduce Bronchopulmonary Dysplasia in a Level 4 NICU—Golden Hour Management of Respiratory Distress Syndrome in Preterm Newborns
Authors: Dylag Andrew M. , Tulloch Jamey , Paul Karen E. , Meyers Jeffrey M.
Published: April 2021

Background: Prevention of chronic lung disease (CLD) requires a multidisciplinary approach spanning from the delivery room to Neonatal Intensive Care Unit (NICU) discharge. In 2018, a quality improvement (QI) initiative commenced in a level 4 NICU with the goal of decreasing chronic lung disease rates below the Vermont Oxford Network (VON) average of 24%. Methods: Improvement strategies focused on addressing the primary drivers of ventilation strategies, surfactant administration, non-invasive ventilation, medication use, and nutrition/fluid management. The primary outcome was VON CLD, defined as need for mechanical ventilation and/or supplemental oxygen use at 36 weeks postmenstrual age. Statistical process control charts were used to display and analyze data over time. Results: The overall CLD rate decreased from 33.5 to 16.5% following several interventions, a 51% reduction that has been sustained for >18 months. Changes most attributable to this include implementation of the “golden hour” gestational age (GA) based delivery room protocol that encourages early surfactant administration and timely extubation. Fewer infants were intubated across all GA groups with the largest improvement among infants 26–27 weeks GA. Conclusions: Our efforts significantly decreased CLD through GA-based respiratory guidelines and a comprehensive, rigorous QI approach that can be applicable to other teams focused on improvement.
Effect of Annealing Temperature on Microstructure and Resistivity of TiC Thin Films
Authors: Aihaiti Litipu , Tuokedaerhan Kamale , Sadeh Beysen , Zhang Min , Shen Xiangqian , Mijiti Abuduwaili
Published: April 2021

Titanium carbide (TiC) thin films were prepared by non-reactive simultaneous double magnetron sputtering. After deposition, all samples were annealed at different temperatures under high-vacuum conditions. This paper mainly discusses the influence of deposition methods and annealing temperatures on microstructure, surface topography, bonding states and electrical resistivity of TiC films. XRD (X-ray diffraction) results show that TiC thin films can still form crystals without annealing, and the crystallinity of thin films is improved after annealing. The estimated grain size of the TiC films varies from 8.5 nm to 14.7 nm with annealing temperature. It can be seen from SEM (scanning electron microscope) images that surfaces of the films are composed of irregular particles, and when the temperature reaches to 800 °C, the shape of the particles becomes spherical. Growth rate of film is about 30.8 nm/min. Oxygen-related peaks were observed in XPS (X-ray photoelectron spectroscopy) spectra, which is due to the absorption of oxygen atoms on the surface of the film when exposed to air. Raman spectra confirm the formation of TiC crystals and amorphous states of carbon. Resistivity of TiC films decreases monotonically from 666.73 to 86.01 μΩ·cm with the increase in annealing temperature. In brief, the TiC thin films prepared in this study show good crystallinity, thermal stability and low resistivity, which can meet the requirements of metal gate applications.
Improving the Ionic Conductivity of the LLZO–LZO Thin Film through Indium Doping
Authors: Yan Zongkai , Song Yu , Wu Shuai , Wu Yongmin , Song Shipai , Wang Xinyu , Zhu Yanlin , Chen Junsong , Guo Rui , Xiang Yong
Published: April 2021

A solid-state electrolyte with an ionic conductivity comparable to that of a liquid electrolyte is demanded of all-solid-state lithium-ion batteries. Li7La3Zr2O12 (LLZO) is considered to be a promising candidate due to its good thermal stability, high ionic conductivity, and wide electrochemical window. However, the synthesis of a stable cubic-phase LLZO thin film with enhanced densification at a relatively low thermal treatment temperature is yet to be developed. Indium is predicted to be a possible dopant to stabilize the cubic-phase LLZO (c-LLZO). Herein, via a nanolayer stacking process, a LLZO–Li2CO3–In2O3 multilayer solid electrolyte precursor was obtained. After thermal annealing at different temperatures, the effects of indium doping on the formation of c-LLZO and the ionic conductivities of the prepared LLZO–LZO thin film were systematically investigated. The highest ionic conductivity of 9.6 × 10−6 S·cm–1 was obtained at an annealing temperature of 800 °C because the incorporation of indium promoted the formation of c-LLZO and the highly conductive LLZO–LZO interfaces. At the end, a model of LLZO–LZO interface-enhancing ionic conductivity was proposed. This work provides a new approach for the development of low-temperature LLZO-based, solid-state thin-film batteries.
Copy Number Variant Detection with Low-Coverage Whole-Genome Sequencing Represents a Viable Alternative to the Conventional Array-CGH
Authors: Kucharík Marcel , Budiš Jaroslav , Hýblová Michaela , Minárik Gabriel , Szemes Tomáš
Published: April 2021

Copy number variations (CNVs) represent a type of structural variant involving alterations in the number of copies of specific regions of DNA that can either be deleted or duplicated. CNVs contribute substantially to normal population variability, however, abnormal CNVs cause numerous genetic disorders. At present, several methods for CNV detection are applied, ranging from the conventional cytogenetic analysis, through microarray-based methods (aCGH), to next-generation sequencing (NGS). In this paper, we present GenomeScreen, an NGS-based CNV detection method for low-coverage, whole-genome sequencing. We determined the theoretical limits of its accuracy and obtained confirmation in an extensive in silico study and in real patient samples with known genotypes. In theory, at least 6 M uniquely mapped reads are required to detect a CNV with the length of 100 kilobases (kb) or more with high confidence (Z-score > 7). In practice, the in silico analysis required at least 8 M to obtain >99% accuracy (for 100 kb deviations). We compared GenomeScreen with one of the currently used aCGH methods in diagnostic laboratories, which has mean resolution of 200 kb. GenomeScreen and aCGH both detected 59 deviations, while GenomeScreen furthermore detected 134 other (usually) smaller variations. When compared to aCGH, overall performance of the proposed GenemoScreen tool is comparable or superior in terms of accuracy, turn-around time, and cost-effectiveness, thus providing reasonable benefits, particularly in a prenatal diagnosis setting.
Useful Life of Prescribed Fires in a Southern Mediterranean Basin: An Application to Pinus pinaster Stands in the Sierra Morena Range
Authors: Molina Juan Ramón , Ortega Macarena , Rodríguez y Silva Francisco
Published: April 2021

Prescribed fire is a globally relevant fuel treatment for surface fuel management and wildfire hazard reduction. However, Mediterranean ecosystems are adapted to low and moderate fires; hence, the useful life of prescribed fires is limited. Useful life is defined as the effective rotation length of prescribed fires to mitigate fire spread based on critical surface intensity for crown combustion. In this sense, the useful life of a prescribed fire focuses on surface fuel dynamics and its potential fire behavior. In Pinus pinaster stands, the useful life can be established between 0 and 4 years. Canopy base height, time elapsed from the burning, postfire precipitation, and fine fuel moisture content during the burning were identified as the most important variables in postburn fuel dynamics. Other stand characteristics and postfire precipitation can improve the fine fuel and live fuel dynamics models. Our findings support prescribed fires as an effective fuel treatment in the medium term for forest fire prevention, according to stand characteristics and burning implementation conditions. In this sense, forest managers can use the proposed decision tree to identify the useful life of each prescribed fire based on fine fuel moisture content during burning implementation.
TP63 Is Significantly Upregulated in Diabetic Kidney
Authors: Liang Sitai , Nayak Bijaya K. , Vogel Kristine S. , Habib Samy L.
Published: April 2021

The role of tumor protein 63 (TP63) in regulating insulin receptor substrate 1 (IRS-1) and other downstream signal proteins in diabetes has not been characterized. RNAs extracted from kidneys of diabetic mice (db/db) were sequenced to identify genes that are involved in kidney complications. RNA sequence analysis showed more than 4- to 6-fold increases in TP63 expression in the diabetic mice’s kidneys, compared to wild-type mice at age 10 and 12 months old. In addition, the kidneys from diabetic mice showed significant increases in TP63 mRNA and protein expression compared to WT mice. Mouse proximal tubular cells exposed to high glucose (HG) for 48 h showed significant decreases in IRS-1 expression and increases in TP63, compared to cells grown in normal glucose (NG). When TP63 was downregulated by siRNA, significant increases in IRS-1 and activation of AMP-activated protein kinase (AMPK (p-AMPK-Th172)) occurred under NG and HG conditions. Moreover, activation of AMPK by pretreating the cells with AICAR resulted in significant downregulation of TP63 and increased IRS-1 expression. Ad-cDNA-mediated over-expression of tuberin resulted in significantly decreased TP63 levels and upregulation of IRS-1 expression. Furthermore, TP63 knockdown resulted in increased glucose uptake, whereas IRS-1 knockdown resulted in a decrease in the glucose uptake. Altogether, animal and cell culture data showed a potential role of TP63 as a new candidate gene involved in regulating IRS-1 that may be used as a new therapeutic target to prevent kidney complications in diabetes.
Remarkable Population Resilience in a North African Endemic Damselfly in the Face of Rapid Agricultural Transformation
Authors: Khelifa Rassim , Mahdjoub Hayat , Baaloudj Affef , Cannings Robert A. , Samways Michael J.
Published: April 2021

Agriculture can be pervasive in its effect on wild nature, affecting various types of natural habitats, including lotic ecosystems. Here, we assess the extent of agricultural expansion on lotic systems in Northern Africa (Algeria, Tunisia, and Morocco) and document its overlap with the distribution of an endemic damselfly, Platycnemis subdilatata Selys, using species distribution modeling. We found that agricultural land cover increased by 321% in the region between 1992 and 2005, and, in particular, the main watercourses experienced an increase in agricultural land cover from 21.4% in 1992 to 78.1% in 2005, together with an increase in the intensity of 226% in agricultural practices. We used capture–mark–recapture (CMR) surveys in terrestrial habitats surrounding a stream bordered by grassland and cropland in northeastern Algeria to determine demographic parameters and population size, as well as cropland occupancy. CMR modeling showed that the recapture and survival probabilities had an average of 0.14 (95%CI: 0.14–0.17) and 0.86 (0.85–0.87), respectively. We estimated a relatively large population of P. subdilatata (~1750 individuals) in terrestrial habitats. The occupancy of terrestrial habitats by adults was spatially structured by age. Our data suggest that P. subdilatata has survived agricultural expansion and intensification better than other local odonate species, mainly because it can occupy transformed landscapes, such as croplands and grasslands.
Non Alcoholic Fatty Liver Disease Is Positively Associated with Increased Glycated Haemoglobin Levels in Subjects without Diabetes
Authors: Zupo Roberta , Castellana Fabio , Panza Francesco , Castellana Marco , Lampignano Luisa , Cincione Raffaele Ivan , Triggiani Vincenzo , Giannelli Gianluigi , Dibello Vittorio , Sardone Rodolfo , De Pergola Giovanni
Published: April 2021

Screening for non-alcoholic fatty liver disease (NAFLD) is key step for primary management of fatty liver in the clinical setting. Excess weight subjects carry a greater metabolic risk even before exhibiting pathological patterns, including diabetes. We characterized the cross-sectional relationship between routine circulating biomarkers and NAFLD in a large sample of diabetes-free subjects with overweight or obesity, to elucidate any independent relationship. A population sample of 1232 consecutive subjects with a body mass index of at least 25 kg/m2, not receiving any drug or supplemental therapy, was studied. Clinical data and routine biochemistry were analyzed. NAFLD was defined using the validated fatty liver index (FLI), classifying subjects with a score ≥ 60% as at high risk. Due to extreme skewing of variables of interest, resampling matching for age and sex was performed. Our study population was characterized by a majority of females (69.90%) and a prevalence of NAFLD in males (88.90%). As a first step, propensity score matching was explicitly performed to balance the two groups according to the FLI cut-off. Based on the resulting statistical trajectories, corroborated even after data matching, we built two logistic regression models on the matched population (N = 732) to verify any independent association. We found that each unit increase of FT3 implicated a 50% increased risk of NAFLD (OR 1.506, 95%CI 1.064 to 2.131). When including glycated haemoglobin (HbA1c) in the model, free-triiodothyronine (FT3) lost significance (OR 1.557, 95%CI 0.784 to 3.089) while each unit increase in HbA1c (%) indicated a significantly greater NAFLD risk, by almost two-fold (OR 2.32, 95%CI 1.193 to 4.512). Glucose metabolism dominates a key pathway along the hazard trajectories of NAFLD, turned out to be key biomarker in monitoring the risk of fatty liver in diabetes-free overweight subjects. Each unit increase in HbA1c (%) indicated a significantly greater NAFLD risk, by almost two-fold, in our study.
Frailty in Acute and Chronic Coronary Syndrome Patients Entering Cardiac Rehabilitation
Authors: Giallauria Francesco , Di Lorenzo Anna , Venturini Elio , Pacileo Mario , D’Andrea Antonello , Garofalo Umberto , De Lucia Felice , Testa Crescenzo , Cuomo Gianluigi , Iannuzzo Gabriella , Gentile Marco , Nugara Cinzia , Sarullo Filippo M , Marinus Nastasia , Hansen Dominique , Vigorito Carlo
Published: April 2021

Worldwide population ageing is partly due to advanced standard of care, leading to increased incidence and prevalence of geriatric syndromes such as frailty and disability. Hence, the age at the onset of acute coronary syndromes (ACS) keeps growing as well. Moreover, ageing is a risk factor for both frailty and cardiovascular disease (CVD). Frailty and CVD in the elderly share pathophysiological mechanisms and associated conditions, such as malnutrition, sarcopenia, anemia, polypharmacy and both increased bleeding/thrombotic risk, leading to a negative impact on outcomes. In geriatric populations ACS is associated with an increased frailty degree that has a negative effect on re-hospitalization and mortality outcomes. Frail elderly patients are increasingly referred to cardiac rehabilitation (CR) programs after ACS; however, plans of care must be tailored on individual’s clinical complexity in terms of functional capacity, nutritional status and comorbidities, cognitive status, socio-economic support. Completing rehabilitative intervention with a reduced frailty degree, disability prevention, improvement in functional state and quality of life and reduction of re-hospitalization are the goals of CR program. Tools for detecting frailty and guidelines for management of frail elderly patients post-ACS are still debated. This review focused on the need of an early identification of frail patients in elderly with ACS and at elaborating personalized plans of care and secondary prevention in CR setting.
Cognitive Dysfunction in a Mouse Model of Cerebral Ischemia Influences Salivary Metabolomics
Authors: To Masahiro , Sugimoto Masahiro , Saruta Juri , Yamamoto Yuko , Sakaguchi Wakako , Kawata Akira , Matsuo Masato , Tsukinoki Keiichi
Published: April 2021

Vascular dementia, caused by cerebrovascular disease, is associated with cognitive impairment and reduced hippocampal metabolite levels. Specifically, cognitive impairment can be induced by decreased hippocampal brain-derived neurotrophic factor (BDNF) expression. The development of low or non-invasive biomarkers to characterize these diseases is an urgent task. Disturbance of metabolic pathways has been frequently observed in cognitive impairment, and salivary molecules also showed the potentials to reflect cognitive impairment. Therefore, we evaluated salivary metabolic profiles associated with altered hippocampal BDNF expression levels in a cerebral ischemia mouse model using metabolomic analyses. The effect of tacrine (a cholinesterase inhibitor) administration was also examined. The arteries of ICR mice were occluded with aneurysm clips to generate the cerebral ischemia model. Learning and memory performance was assessed using the elevated plus maze (EPM) test. Hippocampal and blood BDNF levels were quantified using an enzyme-linked immunosorbent assay. Glutamate decarboxylase 1 (GAD1) mRNA expression, is associated with cognitive impairment, was quantified by a real-time polymerase chain reaction. The EPM test revealed impaired spatial working memory in the cerebral ischemia mouse model; tacrine administration ameliorated this memory impairment. Cerebral ischemia suppressed GAD1 expression by decreasing hippocampal BDNF expression. In total, seven salivary metabolites, such as trimethylamine N-oxide and putrescine, were changed by cognitive impairment and tacrine administration. Our data suggest that salivary metabolite patterns were associated with cognitive function.
The Relationship between Hospital Volume and In-Hospital Mortality of Severely Injured Patients in Dutch Level-1 Trauma Centers
Authors: Sewalt Charlie , Venema Esmee , van Zwet Erik , van Ditshuizen Jan , Schuit Stephanie , Polinder Suzanne , Lingsma Hester , den Hartog Dennis ,   on behalf of LTR Research Group
Published: April 2021

Centralization of trauma centers leads to a higher hospital volume of severely injured patients (Injury Severity Score (ISS) > 15), but the effect of volume on outcome remains unclear. The aim of this study was to determine the association between hospital volume of severely injured patients and in-hospital mortality in Dutch Level-1 trauma centers. A retrospective observational cohort study was performed using the Dutch trauma registry. All severely injured adults (ISS > 15) admitted to a Level-1 trauma center between 2015 and 2018 were included. The effect of hospital volume on in-hospital mortality was analyzed with random effects logistic regression models with a random intercept for Level-1 trauma center, adjusted for important demographic and injury characteristics. A total of 11,917 severely injured patients from 13 Dutch Level-1 trauma centers was included in this study. Hospital volume varied from 120 to 410 severely injured patients per year. Observed mortality rates varied between 12% and 24% per center. After case-mix correction, no statistically significant differences between low- and high-volume centers were demonstrated (adjusted odds ratio 0.97 per 50 extra patients per year, 95% Confidence Interval 0.90–1.04, p = 0.44). The variation in hospital volume of the included Level-1 trauma centers was not associated with the outcome of severely injured patients. Our results suggest that well-organized trauma centers with a similar organization of care could potentially achieve comparable outcomes.
Treatment Efficacy with a Novel Hyaluronic Acid-Based Hydrogel for Osteoarthritis of the Knee
Authors: Russu Octav Marius , Pop Tudor Sorin , Feier Andrei Marian , Trâmbițaș Cristian , Incze-Bartha Zsuzsanna , Borodi Paul Gabriel , Gergely István , Zuh Sándor-György
Published: April 2021

Background: Prior trials investigating the treatment of symptomatic osteoarthritis (OA) with hyaluronic-acid-derived products injections have provided optimistic results. The study was directed to assess the effectiveness of an innovative hyaluronic-acid-based hydrogel (Hymovis®) in the treatment of symptomatic knee OA. Methods: A prospective, single-center, clinical trial was performed. Thirty-five patients with degenerative knee OA were included. Inclusion criteria were: age between 45–80, radiographic Kellgren grade II or III osteoarthritis, minimum 35 mm score on the Visual Analogue Scale (VAS), pain for at least 6 months and agreement to participate in the study. Patients received two injections at a one-week interval. The evaluator assessed the patients using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and VAS. Evaluation was performed before, at 2 and 6 months after the injections. Results: A significant improvement on the WOMAC Index pain subscale was observed at 6 months after the injection. At two months, pain subscale score decreased from 10.34 to 9.34. At six months, a significant decrement in pain parameters compared to baseline was observed (from 10.34 to 7.72; p = 0.0004). Median points on VAS significantly ameliorated after 6 months (from 74.2 to 57.3 cm; p < 0.0001). Regarding physical function, a statistically significant difference compared to baseline was observed at the end of the study (from 29.74 to 25.18; p = 0.0025). WOMAC Index stiffness component did not differ from baseline at any time during follow-up. Conclusions: Pain relief installed with a delayed on-set but had a prolonged duration. The novel hyaluronic acid-based hydrogel (Hymovis®) had effective results, particularly after six months post-injections and offers a therapeutic advancement in the treatment of moderate to severe osteoarthritis.
Forests to the Foreigners: Large-Scale Land Acquisitions in Gabon
Authors: Legault Danielle , Cochrane Logan
Published: April 2021

For the past decade, the land rush discourse has analyzed foreign investment in land and agriculture around the world, with Africa being a continent of particular focus due to the scale of acquisitions that have taken place. Gabon, a largely forested state in Central Africa, has been neglected in the land rush conversations, despite having over half of its land allocated to forestry, agriculture, and mining concessions. This paper draws on existing evidence and contributes new empirical data through expert interviews to fill this critical knowledge gap. We situate Gabon’s historic relationship with land, establishing the intrinsic relationship between colonial land tenure systems and present-day land rights. Our findings analyze the macro context of investors and investments, as well as the impacts related to rural–urban linkages and infrastructure development into the forests, civil society, human–environment relationships, and certification programs. While challenges continue to be experienced, the promise of Gabon’s first national land use plan—the use of sustainable concessions and mandatory forestry certification—offers a unique opportunity for Gabon to transition towards a future that better benefits its population while also protecting its natural resources.
Enhancing Properties of Soft Magnetic Materials: A Study into Hot Isostatic Pressing and Sintering Atmosphere Influences
Authors: Romero Ana , Morales Angel L. , Herranz Gemma
Published: April 2021

Soft magnetic materials are characterized by achieving a high magnetic induction value in the presence of a small magnetic field. Common applications of these materials, such as transformers or sensors, are in constant evolution and new requirements are becoming more demanding. Nickel and its alloys are employed as smart materials taking advantage of their superior magnetoelastic properties. A metal injection molding (MIM) technique provides high-quality complex-shaped parts with a good density and controlled impurity levels, which are necessary for these applications, by carefully adjusting the sintering stage. Previous investigations have established a sintering cycle for pure nickel consisting of 1325 ∘C for 12 h within an N2-5%H2 atmosphere. Nevertheless, microstructural, mechanical and magnetoelastic responses can still be greatly enhanced. In this context, the effects of hot isostatic pressing (HIP), and sintering atmosphere have been investigated. The application of an adequate HIP treatment leads to significant improvements in comparison to the reference sintering process. It achieves almost complete densification while increasing field-dependent elastic modulus from 8.1% up to 9.6%. Additionally, the sintering atmosphere has been proven to be a key factor in reducing impurities and hence facilitating magnetic domain motion. Three different atmospheres have been studied: N2-5%H2 (with a higher gas flow), N2-10%H2-0.1%CH4 and low vacuum. Minimum carbon contents have been registered using more reducing atmospheres (N2-5%H2 and N2-10%H2-0.1%CH4) which has led to values of field-dependent elastic modulus higher than 10%. This value is 2.5 times higher than that obtained when nickel parts are processed via conventional techniques. Moreover, although minimizing carbon content has been shown to be easier and more beneficial than achieving complete densification, both strategies could be used in combination to improve and maximize magnetoelastic performance.
Friction Stir Welding of AA2099-T83 and AA2060-T8E30 Aluminium Alloys with New Cr-Free Surface Treatments and Sealant Application
Authors: Aldanondo Egoitz , Vivas Javier , Álvarez Pedro , Hurtado Iñaki , Karanika Alexandra
Published: April 2021

The feasibility for friction stir welding (FSW) surface-treated AA2099-T83 aluminium extrusions with AA2060-T8E30 aluminium sheets in the overlap configuration and using a sealant at the interface was investigated in this work. New Cr-free surface treatments such as thin film sulphuric acid anodising (TFSAA) and sol–gel were applied to the parent materials, and a sealant was applied before applying the FSW process. FSW welds were produced using several combinations of surface treatments and sealant application with no significant influence on FSW process stability and performance. The metallographic examination of the welds showed that a good protection of the crevice was achieved with some sealant accumulation at the edges of the overlapping region. The microstructural analysis showed no sealant remnants but the presence of some oxide remnants in the stir zone (SZ) of the welds, especially in the TFSAA treated parent material cases. However, these remnants did not show any significant effect in the static pull-out strength of the joints and failures at the most stressed zone of the AA2099-T83 extrusions outside the FSW weld region were consistently obtained.
Identification and Speed Estimation of a Moving Object in an Indoor Application Based on Visible Light Sensing of Retroreflective Foils
Authors: Weiss Andreas Peter , Wenzl Franz Peter
Published: April 2021

Identification and sensing are two of the main tasks a wireless sensor node has to perform in an Internet of Things (IoT) environment. Placing active powered nodes on objects is the most usual approach for the fulfillment of these functions. With the expected massive increase of connected things, there are several issues on the horizon that hamper the further deployment of this approach in an energy efficient, sustainable way, like the usage of environmentally hazardous batteries or accumulators, as well as the required electrical energy for their operation. In this work, we propose a novel approach for performing the tasks of identification and sensing, applying visible light sensing (VLS) based on light emitting diode (LED) illumination and utilizing retroreflective foils mounted on a moving object. This low cost hardware is combined with a self-developed, low complex software algorithm with minimal training effort. Our results show that successful identification and sensing of the speed of a moving object can be achieved with a correct estimation rate of 99.92%. The used foils are commercially available and pose no threat to the environment and there is no need for active sensors on the moving object and no requirement of wireless radio frequency communication. All of this is achievable whilst undisturbed illumination is still provided.
The Design, Simulation and Fabrication of an Omnidirectional Inertial Switch with Rectangular Suspension Spring
Authors: Chen Wenguo , Wang Rui , Wang Huiying , Sun Shulei
Published: April 2021

An omnidirectional inertial switch with rectangular spring is proposed in this paper, and the prototype has been fabricated by surface micromachining technology. To evaluate the threshold consistency and stability of omnidirectional inertia switch, the stiffness of rectangular suspension springs is analyzed. The simulation result shows that the coupling stiffness of the rectangular spring suspension system in the non-sensitive direction is a little more than that in the sensitive direction, which indicated that the omnidirectional switching system’s stability is reinforced, attributed to the design of rectangular springs. The dynamic response simulation shows that the threshold of the omnidirectional inertial switch using the rectangular suspension spring has high consistency in the horizontal direction. The prototype of an inertial switch is fabricated and tested successfully. The testing results indicate even threshold distribution in the horizontal direction. The threshold acceleration of the designed inertial switch is about 58 g in the X direction and 37 g in the Z direction; the contact time is about 18 μs.
Review of Design Considerations for Brain-on-a-Chip Models
Authors: Cameron Tiffany , Bennet Tanya , Rowe Elyn , Anwer Mehwish , Wellington Cheryl , Cheung Karen
Published: April 2021

In recent years, the need for sophisticated human in vitro models for integrative biology has motivated the development of organ-on-a-chip platforms. Organ-on-a-chip devices are engineered to mimic the mechanical, biochemical and physiological properties of human organs; however, there are many important considerations when selecting or designing an appropriate device for investigating a specific scientific question. Building microfluidic Brain-on-a-Chip (BoC) models from the ground-up will allow for research questions to be answered more thoroughly in the brain research field, but the design of these devices requires several choices to be made throughout the design development phase. These considerations include the cell types, extracellular matrix (ECM) material(s), and perfusion/flow considerations. Choices made early in the design cycle will dictate the limitations of the device and influence the end-point results such as the permeability of the endothelial cell monolayer, and the expression of cell type-specific markers. To better understand why the engineering aspects of a microfluidic BoC need to be influenced by the desired biological environment, recent progress in microfluidic BoC technology is compared. This review focuses on perfusable blood–brain barrier (BBB) and neurovascular unit (NVU) models with discussions about the chip architecture, the ECM used, and how they relate to the in vivo human brain. With increased knowledge on how to make informed choices when selecting or designing BoC models, the scientific community will benefit from shorter development phases and platforms curated for their application.
Metasediments Covering Ophiolites in the HP Internal Belt of the Western Alps: Review of Tectono-Stratigraphic Successions and Constraints for the Alpine Evolution
Authors: Tartarotti Paola , Martin Silvana , Festa Andrea , Balestro Gianni
Published: April 2021

Ophiolites of the Alpine belt derive from the closure of the Mesozoic Tethys Ocean that was interposed between the palaeo-Europe and palaeo-Adria continental plates. The Alpine orogeny has intensely reworked the oceanic rocks into metaophiolites with various metamorphic imprints. In the Western Alps, metaophiolites and continental-derived units are distributed within two paired bands: An inner band where Alpine subduction-related high-pressure (HP) metamorphism is preserved, and an outer band where blueschist to greenschist facies recrystallisation due to the decompression path prevails. The metaophiolites of the inner band are hugely important not just because they provide records of the prograde tectonic and metamorphic evolution of the Western Alps, but also because they retain the signature of the intra-oceanic tectono-sedimentary evolution. Lithostratigraphic and petrographic criteria applied to metasediments associated with HP metaophiolites reveal the occurrence of distinct tectono-stratigraphic successions including quartzites with marbles, chaotic rock units, and layered calc schists. These successions, although sliced, deformed, and superposed in complex ways during the orogenic stage, preserve remnants of their primary depositional setting constraining the pre-orogenic evolution of the Jurassic Tethys Ocean.
Re–Os and Sr Isotopic Study of Permian–Triassic Sedimentary Rocks from the Himalaya: Shale Chronology and Carbonate Diagenesis
Authors: Mandal Anirban , Tripathy Gyana Ranjan , Goswami Vineet , Ackerman Lukáš , Parcha Suraj K. , Chandra Rakesh
Published: April 2021

Sedimentary rocks from the Himalayas are well-preserved archives of the Neo-Tethys oceanic conditions. In this contribution, Re–Os isotopic systematics of black shales from the Gungri Formation, Spiti valley and siltstones from the Khunamuh Formation, Guryul Ravine have been investigated to constrain their depositional ages. The Re–Os isochron for the Gungri shales yields a depositional age of 255 ± 22 Ma (2σ; n = 8; MSWD (Mean Square Weighted Deviation) = 5.7), consistent with available biostratigraphic information. The initial 187Os/188Os ratio (0.60 ± 0.13) is similar to that reported for the Late Permian shales, indicating the connection of the Neo-Tethys with the global ocean. In contrast, the Re–Os systematic is found to be non-isochronous for the Guryul Ravine section, a proximal site with a strong influence of seismic/Tsunami events. Global compilation of 187Re/188Os ratios in Late Permian shales and bathymetric distribution of the Re/Os ratios point to strong role of Re/Os uptake by macroalgae, in addition to oceanic pH and redox state, in regulating the Re–Os systematic in shales. The 87Sr/86Sr ratios for the Induan carbonates from the Spiti (0.71551–0.71837) are higher than to that expected for the Lower Triassic ocean (~0.707). Co-variations of Sr and 87Sr/86Sr with Mn concentrations establish the diagenetic alteration of these carbonates.
Empirical Study on Reduction Behavior and Metallurgical Properties of Vanadia–Titania Magnetite in Blast Furnace
Authors: He Zhanwei , Hu Xiaojun , Lan Mo , Liu Jianxing , Cheng Gongjin , Xue Xiangxin , Chou Kouchih
Published: April 2021

The loss of permeability affects the reduction of the ferrous burden in the cohesive zone of a blast furnace (BF). Vanadia–titania magnetite (VTM) burden of various chemical compositions have different metallurgical properties. The reduction and softening-melting-dripping properties of different kinds of VTM were investigated. The results showed that the core of sinter or pellet is indirectly reduced to wustite and (Fe,Ti)Ox, and the periphery contains interlinked metallic iron and CaSiO3 in the cohesive zone. Wustite and (Fe,Ti)Ox are directly reduced in the melting-dripping zone. The aggregate (Fe, V, Cr) present in the non-dripping causes a loss of valuable components. With the increase in TiO2 content, the substrate phase of molten slag changes from melilite to titanaugite, and the mass of dripping decreases gradually. In addition, the permeability index S increased and the melting zone widened, which indicates that the increase in TiO2 content negatively affected the melting-dripping performance. The mass of the dripping is directly proportional to the pellet ratio. Considering the adverse effect of TiO2 on softening-melting-dripping properties, it is recommended that high TiO2 VTM is smelted while mixed with ordinary ores or with an increased pellet ratio in the burden structure.
Natural Product Inhibition and Enzyme Kinetics Related to Phylogenetic Characterization for Bacterial Peptidyl-tRNA Hydrolase 1
Authors: Strange D. Scott , Gaffin Steven S. , Holloway W. Blake , Kinsella Meredyth D. , Wisotsky Jacob N. , McFeeters Hana , McFeeters Robert L.
Published: April 2021

With the relentless development of drug resistance and re-emergence of many pathogenic bacteria, the need for new antibiotics and new antibiotic targets is urgent and growing. Bacterial peptidyl-tRNA hydrolase, Pth1, is emerging as a promising new target for antibiotic development. From the conserved core and high degree of structural similarity, broad-spectrum inhibition is postulated. However, Pth1 small-molecule inhibition is still in the earliest stages. Focusing on pathogenic bacteria, herein we report the phylogenetic classification of Pth1 and natural product inhibition spanning phylogenetic space. While broad-spectrum inhibition is found, narrow-spectrum and even potentially clade-specific inhibition is more frequently observed. Additionally reported are enzyme kinetics and general in vitro Pth1 solubility that follow phylogenetic boundaries along with identification of key residues in the gate loop region that appear to govern both. The studies presented here demonstrate the sizeable potential for small-molecule inhibition of Pth1, improve understanding of Pth enzymes, and advance Pth1 as a much-needed novel antibiotic target.
Ursolic Acid Lactone Obtained from Eucalyptus tereticornis Increases Glucose Uptake and Reduces Inflammatory Activity and Intracellular Neutral Fat: An In Vitro Study
Authors: Balcazar Norman , Betancur Laura I. , Muñoz Diana L. , Cabrera Frankly J. , Castaño Adriana , Echeverri Luis F. , Acin Sergio
Published: April 2021

Obesity has a strong relationship to insulin resistance and diabetes mellitus, a chronic metabolic disease that alters many physiological functions. Naturally derived drugs have aroused great interest in treating obesity, and triterpenoids are natural compounds with multiple biological activities and antidiabetic mechanisms. Here, we evaluated the bioactivity of ursolic acid lactone (UAL), a lesser-known triterpenoid, obtained from Eucalyptus tereticornis. We used different cell lines to show for the first time that this molecule exhibits anti-inflammatory properties in a macrophage model, increases glucose uptake in insulin-resistant muscle cells, and reduces triglyceride content in hepatocytes and adipocytes. In 3T3-L1 adipocytes, UAL inhibited the expression of genes involved in adipogenesis and lipogenesis, enhanced the expression of genes involved in fat oxidation, and increased AMP-activated protein kinase phosphorylation. The range of biological activities demonstrated in vitro indicates that UAL is a promising molecule for fighting diabetes.
The Art of Designing DNA Nanostructures with CAD Software
Authors: Glaser Martin , Deb Sourav , Seier Florian , Agrawal Amay , Liedl Tim , Douglas Shawn , Gupta Manish K. , Smith David M.
Published: April 2021

Since the arrival of DNA nanotechnology nearly 40 years ago, the field has progressed from its beginnings of envisioning rather simple DNA structures having a branched, multi-strand architecture into creating beautifully complex structures comprising hundreds or even thousands of unique strands, with the possibility to exactly control the positions down to the molecular level. While the earliest construction methodologies, such as simple Holliday junctions or tiles, could reasonably be designed on pen and paper in a short amount of time, the advent of complex techniques, such as DNA origami or DNA bricks, require software to reduce the time required and propensity for human error within the design process. Where available, readily accessible design software catalyzes our ability to bring techniques to researchers in diverse fields and it has helped to speed the penetration of methods, such as DNA origami, into a wide range of applications from biomedicine to photonics. Here, we review the historical and current state of CAD software to enable a variety of methods that are fundamental to using structural DNA technology. Beginning with the first tools for predicting sequence-based secondary structure of nucleotides, we trace the development and significance of different software packages to the current state-of-the-art, with a particular focus on programs that are open source.