bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Amperometric Microneedle Biosensor for Wearable Levodopa Monitoring of Parkinson’s Disease
Authors: Fang Lu , Ren Hangxu , Mao Xiyu , Zhang Shanshan , Cai Yu , Xu Shiyi , Zhang Yi , Li Lihua , Ye Xuesong , Liang Bo
Published: February 2022

Levodopa (L-Dopa) is considered to be one of the most effective therapies available for Parkinson’s disease (PD) treatment. The therapeutic window of L-Dopa is narrow due to its short half-life, and long-time L-Dopa treatment will cause some side effects such as dyskinesias, psychosis, and orthostatic hypotension. Therefore, it is of great significance to monitor the dynamic concentration of L-Dopa for PD patients with wearable biosensors to reduce the risk of complications. However, the high concentration of interferents in the body brings great challenges to the in vivo monitoring of L-Dopa. To address this issue, we proposed a minimal-invasive L-Dopa biosensor based on a flexible differential microneedle array (FDMA). One working electrode responded to L-Dopa and interfering substances, while the other working electrode only responded to electroactive interferences. The differential current response of these two electrodes was related to the concentration of L-Dopa by eliminating the common mode interference. The differential structure provided the sensor with excellent anti-interference performance and improved the sensor’s accuracy. This novel flexible microneedle sensor exhibited favorable analytical performance of a wide linear dynamic range (0–20 μM), high sensitivity (12.618 nA μM−1 cm−2) as well as long-term stability (two weeks). Ultimately, the L-Dopa sensor displayed a fast response to in vivo L-Dopa dynamically with considerable anti-interference ability. All these attractive performances indicated the feasibility of this FDMA for minimal invasive and continuous monitoring of L-Dopa dynamic concentration for Parkinson’s disease.
Can We Do Better Next Time? Italians’ Response to the COVID-19 Emergency through a Heuristics and Biases Lens
Authors: Misuraca Raffaella , Teuscher Ursina , Scaffidi Abbate Costanza , Ceresia Francesco , Roccella Michele , Parisi Lucia , Vetri Luigi , Miceli Silvana
Published: February 2022

During the outbreak of COVID-19 in Italy, people often failed to adopt behaviors that could have stopped, or at least slowed down, the spread of this deadly disease. We offer cognitive explanations for these decisions, based on some of the most common heuristics and biases that are known to influence human judgment and decision-making, especially under conditions of high uncertainty. Our analysis concludes with the following recommendations: policymakers can and should take advantage of this established science, in order to communicate more effectively and increase the likelihood that people choose responsible actions in a public health crisis.
High-Dose Chemotherapy in Children with Newly Diagnosed Medulloblastoma
Authors: Lafay-Cousin Lucie , Dufour Christelle
Published: February 2022

High-dose chemotherapy with stem cell rescue has been used as an adjuvant therapy or as salvage therapy to treat pediatric patients with brain tumors, and to avoid deleterious side effects of radiotherapy in infants and very young children. Here, we present the most recent trials using high-dose chemotherapy regimens for medulloblastoma in children, and we discuss their contribution to improved survival and describe their toxicity profile and limitations.
Cutaneous Melanoma Systematic Diagnostic Workflows and Integrated Reflectance Confocal Microscopy Assessed with a Retrospective, Comparative Longitudinal (2009–2018) Study
Authors: Pellacani Giovanni , Farnetani Francesca , Chester Johanna , Kaleci Shaniko , Ciardo Silvana , Bassoli Sara , Casari Alice , Longo Caterina , Manfredini Marco , Cesinaro Anna Maria , Giusti Francesca , Iacuzio Antonio , Migaldi Mario
Published: February 2022

Background: The increasing global burden of melanoma demands efficient health services. Accurate early melanoma diagnosis improves prognosis. Objectives: To assess melanoma prevention strategies and a systematic diagnostic-therapeutical workflow (improved patient access and high-performance technology integration) and estimate cost savings. Methods: Retrospective analysis of epidemiological data of an entire province over a 10-year period of all excised lesions suspicious for melanoma (melanoma or benign), registered according to excision location: reference hospital (DP) or other (NDP). A systematic diagnostic-therapeutical workflow, including direct patient access, primary care physician education and high-performance technology (reflectance confocal microscopy (RCM)) integration, was implemented. Impact was assessed with the number of lesions needed to excise (NNE). Results: From 40,832 suspicious lesions excised, 7.5% (n = 3054) were melanoma. There was a 279% increase in the number of melanomas excised (n = 203 (2009) to n = 567 (2018)). Identification precision improved more than 100% (5.1% in 2009 to 12.0% in 2018). After RCM implementation, NNE decreased almost 3-fold at DP and by half at NDP. Overall NNE for DP was significantly lower (NNE = 8) than for NDP (NNE = 20), p < 0.001. Cost savings amounted to EUR 1,476,392.00. Conclusions: Melanoma prevention strategies combined with systematic diagnostic-therapeutical workflow reduced the ratio of nevi excised to identify each melanoma. Total costs may be reduced by as much as 37%.
Roles of Podoplanin in Malignant Progression of Tumor
Authors: Suzuki Hiroyuki , Kaneko Mika K. , Kato Yukinari
Published: February 2022

Podoplanin (PDPN) is a cell-surface mucin-like glycoprotein that plays a critical role in tumor development and normal development of the lung, kidney, and lymphatic vascular systems. PDPN is overexpressed in several tumors and is involved in their malignancy. PDPN induces platelet aggregation through binding to platelet receptor C-type lectin-like receptor 2. Furthermore, PDPN modulates signal transductions that regulate cell proliferation, differentiation, migration, invasion, epithelial-to-mesenchymal transition, and stemness, all of which are crucial for the malignant progression of tumor. In the tumor microenvironment (TME), PDPN expression is upregulated in the tumor stroma, including cancer-associated fibroblasts (CAFs) and immune cells. CAFs play significant roles in the extracellular matrix remodeling and the development of immunosuppressive TME. Additionally, PDPN functions as a co-inhibitory molecule on T cells, indicating its involvement with immune evasion. In this review, we describe the mechanistic basis and diverse roles of PDPN in the malignant progression of tumors and discuss the possibility of the clinical application of PDPN-targeted cancer therapy, including cancer-specific monoclonal antibodies, and chimeric antigen receptor T technologies.
Multifaceted Analyses of Isolated Mitochondria Establish the Anticancer Drug 2-Hydroxyoleic Acid as an Inhibitor of Substrate Oxidation and an Activator of Complex IV-Dependent State 3 Respiration
Authors: Mishra Kumudesh , Péter Mária , Nardiello Anna Maria , Keller Guy , Llado Victoria , Fernandez-Garcia Paula , Kahlert Ulf D. , Barasch Dinorah , Saada Ann , Török Zsolt , Balogh Gábor , Escriba Pablo V. , Piotto Stefano , Kakhlon Or
Published: February 2022

The synthetic fatty acid 2-hydroxyoleic acid (2OHOA) has been extensively investigated as a cancer therapy mainly based on its regulation of membrane lipid composition and structure, activating various cell fate pathways. We discovered, additionally, that 2OHOA can uncouple oxidative phosphorylation, but this has never been demonstrated mechanistically. Here, we explored the effect of 2OHOA on mitochondria isolated by ultracentrifugation from U118MG glioblastoma cells. Mitochondria were analyzed by shotgun lipidomics, molecular dynamic simulations, spectrophotometric assays for determining respiratory complex activity, mass spectrometry for assessing beta oxidation and Seahorse technology for bioenergetic profiling. We showed that the main impact of 2OHOA on mitochondrial lipids is their hydroxylation, demonstrated by simulations to decrease co-enzyme Q diffusion in the liquid disordered membranes embedding respiratory complexes. This decreased co-enzyme Q diffusion can explain the inhibition of disjointly measured complexes I–III activity. However, it doesn’t explain how 2OHOA increases complex IV and state 3 respiration in intact mitochondria. This increased respiration probably allows mitochondrial oxidative phosphorylation to maintain ATP production against the 2OHOA-mediated inhibition of glycolytic ATP production. This work correlates 2OHOA function with its modulation of mitochondrial lipid composition, reflecting both 2OHOA anticancer activity and adaptation to it by enhancement of state 3 respiration.
Endoloop-Assisted Polypectomy for a Symptomatic Giant Colonic Polyp in a Pediatric Patient
Authors: Lin Yen-Chung , Chou Jen-Wei , Chen An-Chyi , Wu Shu-Fen , Peng Ching-Tien , Chen Walter , Lin Chien-Heng
Published: February 2022

Colonic polyps are a common cause of persistent bloody stools in pediatric patients. Such polyps are easily diagnosed by a barium study of the lower gastrointestinal tract or by colonoscopy. Polypectomies utilizing electric ligators are generally performed on pediatric patients, and such patients can be easily operated on. However, giant colonic polyps have been reported in pediatric patients. In the past, a laparotomy or laparoscopy would have been performed in some pediatric patients diagnosed with a giant colonic polyp; however, the large size, location, or position of the polyp would sometimes be too large or the location or position of the polyp would make successful operation difficult. In general, larger stumps with large feeding arteries are associated with larger colonic polyps. Therefore, if such a polyp is removed via electric polypectomy alone, there may be a higher risk of post-polypectomy bleeding from its stump. We report a case of a 14-year-old male patient who presented with a 2-month history of bloody stools. A giant juvenile colonic polyp was detected by colonoscopy in the transverse colon. Finally, we successfully removed the giant polyp by using endoloop-assisted polypectomy.
The Use of Virtual Care in Patients with Hematologic Malignancies: A Scoping Review
Authors: Suleman Adam , Vijenthira Abi , Berlin Alejandro , Prica Anca , Rodin Danielle
Published: February 2022

There is increasing interest from cancer patients and their healthcare providers in the use of virtual care in routine clinical practice. In the setting of hematologic malignancy, where patients often undergo complex and immunodepleting treatments, understanding how to use virtual care safely and effectively is critically important. We aimed to describe the use of virtual care in patients with hematologic malignancies and to examine physician- and patient-reported outcomes in the form of a systematic scoping review. An electronic search of PubMed, Ovid MEDLINE, Elsevier Embase, Scopus, and EBSCO CINAHL was conducted from January 2000 to April 2021. A comprehensive search strategy was used to identify relevant articles, and data were extracted to assess the study design, population, setting, patient characteristics, virtual care platform, and study results. Studies were included if they described the use of virtual care for patients with hematologic malignancies; commentaries were excluded. Fifteen studies met the inclusion criteria after abstract and full-text review. Three studies found that app-based tools were effective in monitoring patient symptoms and triggering alerts for more urgent follow-up. Four studies described the use of phone-based interventions. Five studies found that videoconferencing, with both physicians and oncology nurses, was highly rated by patients. Emerging themes included high levels of patient satisfaction across all domains of virtual care. Provider satisfaction scores were rated lower than patient scores, with concerns about technical issues leading to challenges with virtual care. Four studies found that virtual care allowed providers to promptly respond to patient concerns, especially when patients were experiencing side-effects or had questions about their treatment. Overall, the use of virtual care in patients with hematologic malignancies appears feasible, and resulted in high patient satisfaction. Further research is needed in order to evaluate the optimal method of integrating virtual care into clinical practice.
An Individualized Exercise Intervention for People with Multiple Myeloma—Study Protocol of a Randomized Waitlist-Controlled Trial
Authors: Nicol Jennifer L. , Woodrow Carmel , Cunningham Brent J. , Mollee Peter , Weber Nicholas , Smith Michelle D. , Nicol Andrew J. , Gordon Louisa G. , Hill Michelle M. , Skinner Tina L.
Published: February 2022

People with multiple myeloma (MM) are second only to people with lung cancer for the poorest reported health-related quality of life (HRQoL) of all cancer types. Whether exercise can improve HRQoL in MM, where bone pain and lesions are common, requires investigation. This trial aims to evaluate the efficacy of an exercise intervention compared with control on HRQoL in people with MM. Following baseline testing, people with MM (n = 60) will be randomized to an exercise (EX) or waitlist control (WT) group. EX will complete 12-weeks of supervised (24 sessions) and unsupervised (12 sessions) individualized, modular multimodal exercise training. From weeks 12–52, EX continue unsupervised training thrice weekly, with one optional supervised group-based session weekly from weeks 12–24. The WT will be asked to maintain their current activity levels for the first 12-weeks, before completing the same protocol as EX for the following 52 weeks. Primary (patient-reported HRQoL) and secondary (bone health and pain, fatigue, cardiorespiratory fitness, muscle strength, body composition, disease response, and blood biomarkers) outcomes will be assessed at baseline, 12-, 24- and 52-weeks. Adverse events, attendance, and adherence will be recorded and cost-effectiveness analysis performed. The findings will inform whether exercise should be included as part of standard myeloma care to improve the health of this unique population.
Impact of Macroscopic On-Site Evaluation (MOSE) on Accuracy of Endoscopic Ultrasound-Guided Fine-Needle Biopsy (EUS-FNB) of Pancreatic and Extrapancreatic Solid Lesions: A Prospective Study
Authors: Gaia Silvia , Rizza Stefano , Bruno Mauro , Ribaldone Davide Giuseppe , Maletta Francesca , Sacco Marco , Pacchioni Donatella , Rizzi Felice , Saracco Giorgio Maria , Fagoonee Sharmila , De Angelis Claudio Giovanni
Published: February 2022

This is a prospective and comparative study including 76 consecutive patients performing EUS-FNB for pancreatic and extrapancreatic solid lesions, randomized by alternate allocation to macroscopic on-site evaluation (MOSE) (40 patients) or to a conventional technique (40 patients), with three passes each. MOSE samples were differentiated into score 0: no visible material, score 1: only necrotic or haematic material, score 2: white core tissue ≤ 2 mm, or score 3: white core tissue > 2 mm. The conventional technique consisted in pushing all the needle content into a test tube for evaluation by the pathologist. In both groups, a 22–25 Gauge Franseen-tip needle (Acquire, Boston Scientific Co., Natick, MA, USA) was used. The study evaluated the diagnostic accuracy and adequacy of MOSE compared to the conventional technique and whether MOSE could optimize the number of passes during EUS-FNB. Results: The analysis was performed on 76 patients (38 MOSE, 38 conventional). The overall diagnostic adequacy was 94.7% (72/76) and accuracy was 84.2% (64/76). The diagnostic accuracy was similar in the two groups: MOSE 86.8% (33/38 lesions), vs. conventional 81.6%, 31/38 lesions, p = 0.76). Regarding diagnostic adequacy, the MOSE technique was 97.4% (111/114 passes) compared to 92.1% (105/114 passes) with the conventional technique, p = 0.06. The accuracy increased according to the MOSE score evaluation: it was 43.5%, 65.5% and 78.3% in patients with score 1, score 2, and score 3, respectively. Moreover, if in the first two passes the MOSE score was 2 or 3, the accuracy was 82.6% (20/23), and upon adding a third pass, the accuracy increased to 87% (20/23), which was not significantly different from the general accuracy of the MOSE samples (86.8%) (p = 0.86). Conclusions: The MOSE score showed a comparable diagnostic accuracy to the conventional technique. However, MOSE allows endoscopists to perform an inspective evaluation of the material, tends to perform better than the conventional technique in terms of diagnostic adequacy, and may potentially reduce the number of passes.
Digital Dental Models: Is Photogrammetry an Alternative to Dental Extraoral and Intraoral Scanners?
Authors: Zotti Francesca , Rosolin Luca , Bersani Massimo , Poscolere Andrea , Pappalardo Davide , Zerman Nicoletta
Published: February 2022

Background: 3D models are nowadays part of daily clinical practice. Photogrammetry is a brand-new method for transforming small objects into 3D models while keeping their original shape and size. The aim of this study was to evaluate the accuracy, in terms of precision and trueness, of a digital dental model acquired with photogrammetry compared with those obtained using extraoral scanners and intraoral scanners, starting from the same plaster model. Methods: A plaster model was converted into a digital model using photogrammetry, an extraoral scanner and an intraoral scanner. Different references were measured twice at a distance of 30 min for each model, on the digital models using the software Blender and on the plaster model using a calibre. The Interclass Correlation Coefficient was calculated for each pair of measurements. A volumetric analysis was performed by superimposing the digital models. The coefficient of variation was calculated. A two-way ANOVA test was conducted. Results: For each reference, the coefficient of variation was less than 3%, and the two ANOVA tests resulted in a non-significant value in both cases (p > 0.05). The volumetric analysis demonstrated good agreement between the models derived from the different acquisition methods. Conclusions: Photogrammetry seems to be a good method for acquiring digital models starting from a plaster model, all the methods tested seem to be good for obtaining an accurate three-dimensional digital model. Other studies are needed to evaluate clinical efficacy.
Driver Cardiovascular Disease Detection Using Seismocardiogram
Authors: Uskovas Gediminas , Valinevicius Algimantas , Zilys Mindaugas , Navikas Dangirutis , Frivaldsky Michal , Prauzek Michal , Konecny Jaromir , Andriukaitis Darius
Published: February 2022

This article deals with the treatment and application of cardiac biosignals, an excited accelerometer, and a gyroscope in the prevention of accidents on the road. Previously conducted studies say that the seismocardiogram is a measure of cardiac microvibration signals that allows for detecting rhythms, heart valve opening and closing disorders, and monitoring of patients’ breathing. This article refers to the seismocardiogram hypothesis that the measurements of a seismocardiogram could be used to identify drivers’ heart problems before they reach a critical condition and safely stop the vehicle by informing the relevant departments in a nonclinical manner. The proposed system works without an electrocardiogram, which helps to detect heart rhythms more easily. The estimation of the heart rate (HR) is calculated through automatically detected aortic valve opening (AO) peaks. The system is composed of two micro-electromechanical systems (MEMSs) to evaluate physiological parameters and eliminate the effects of external interference on the entire system. The few digital filtering methods are discussed and benchmarked to increase seismocardiogram efficiency. As a result, the fourth adaptive filter obtains the estimated HR = 65 beats per min (bmp) in a still noisy signal (SNR = −11.32 dB). In contrast with the low processing benefit (3.39 dB), 27 AO peaks were detected with a 917.56-ms peak interval mean over 1.11 s, and the calculated root mean square error (RMSE) was 0.1942 m/s2 when the adaptive filter order is 50 and the adaptation step is equal to 0.933.
Uncertainty and Sensitivity Analysis of a Dry Cask for Spent Nuclear Fuel
Authors: Angelucci Michela , Paci Sandro , Feria Francisco , Herranz Luis Enrique
Published: February 2022

Nuclear safety relies to a good extent on thoroughly validated codes. However, code predictions are affected by uncertainties that need to be quantified for a more accurate evaluation of safety margins. In this regard, the present paper proposes a preliminary uncertainty and sensitivity analysis of the thermal behavior of a concrete-based dry cask for spent nuclear fuel storage, employing the MELCOR code and a series of MATLAB scripts. As thermal behavior is of utmost importance for the fulfillment of United States Nuclear Regulatory Commission (USNRC) safety requirements, the Peak Cladding Temperature (PCT) has been addressed as the key Figure of Merit (FOM). Variables related to the main heat transfer mechanisms have been selected as input parameters for the uncertainty quantification, whereas heat source and heat sink, namely decay power and external air temperature, have been dealt with in a separate sensitivity analysis. The results show that the selected parameters have a weak influence on the PCT, whereas it is strongly related to the decay power and external air temperature values. In any case, PCT stays below the regulatory threshold even under the considered off-normal conditions.
Heat and Light Stability of Pumpkin-Based Carotenoids in a Photosensitive Food: A Carotenoid-Coloured Beverage
Authors: Atencio Sharmaine , Verkempinck Sarah H. E. , Reineke Kai , Hendrickx Marc , Van Loey Ann
Published: February 2022

This study aimed to evaluate carotenoid degradation kinetics in a beverage coloured with pumpkin juice concentrate during storage at dark and illuminated conditions at four temperatures (10, 20, 35 and 45 °C). Carotenoids were quantified by HPLC-DAD, and kinetic parameters for carotenoid degradation were estimated by one-step nonlinear regression analysis. During dark storage, degradation kinetics was modelled by fractional conversion (all-trans-β-carotene) and zero-order equations (all-trans-antheraxanthin, all-trans-lutein, all-trans-violaxanthin and all-trans-neoxanthin). Storage of samples in a climatic chamber with intense light intensity (1875–3000 lux) accelerated the carotenoid losses. At illuminated conditions, degradation followed a first-order (all-trans-lutein, all-trans-violaxanthin and all-trans-neoxanthin) and fractional conversion model (all-trans-β-carotene and all-trans-antheraxanthin). Carotenoid degradation followed an Arrhenius temperature-dependency, with Ea values lower than 50 kJ/mol. Degradation was shown to be mainly by oxidative reactions. Packaging under minimal oxygen conditions, use of antioxidants (e.g., ascorbic acid), and proper choice of light sources at retail shelves may be considered to optimize the pigment retention in a carotenoid-coloured beverage during storage.
Pharmacogenetics of Drugs Used in the Treatment of Cancers
Authors: Franczyk Beata , Rysz Jacek , Gluba-Brzózka Anna
Published: February 2022

Pharmacogenomics is based on the understanding of the individual differences in drug use, the response to drug therapy (efficacy and toxicity), and the mechanisms underlying variable drug responses. The identification of DNA variants which markedly contribute to inter-individual variations in drug responses would improve the efficacy of treatments and decrease the rate of the adverse side effects of drugs. This review focuses only on the impact of polymorphisms within drug-metabolizing enzymes on drug responses. Anticancer drugs usually have a very narrow therapeutic index; therefore, it is very important to use appropriate doses in order to achieve the maximum benefits without putting the patient at risk of life-threatening toxicities. However, the adjustment of the appropriate dose is not so easy, due to the inheritance of specific polymorphisms in the genes encoding the target proteins and drug-metabolizing enzymes. This review presents just a few examples of such polymorphisms and their impact on the response to therapy.
Petrifyin’: Canonical Counter-Discourse in Two Caribbean Women’s Medusa Poems
Authors: Zapkin Phillip
Published: February 2022

This essay utilizes Helen Tiffin’s idea of canonical counter-discourse to read the Medusa poems of Shara McCallum and Dorothea Smartt, two female Caribbean poets. Essentially, canonical counter-discourse involves authors rewriting works or giving voice to peripheral/silenced characters from the literary canon to challenge inequalities upheld by power structures such as imperialism and patriarchy. McCallum’s and Smartt’s poems represent Medusa to reflect their own concerns as women of color from Jamaica and Barbados, respectively. McCallum’s “Madwoman as Rasta Medusa” aligns the titular character from her book Madwoman with Medusa to express Madwoman’s righteous anger at the “wanton” and “gravalicious” ways of a Babylon addressed in second person. Smartt’s series of Medusa poems from Connecting Medium explore the pain of hair and skin treatments Black women endure to try and meet Euro-centric beauty standards, as well as the struggles of immigrants, particularly people of color. Both poets claim Medusa as kindred, empowering Medusa as a figure with agency—which she is denied in the Greco-Roman sources—and simultaneously legitimizing both Caribbean literature and the poets’ feminist and post-colonial protests by linking them to the cultural capital of the classics.
Physiological and Psychological Effects of Volatile Organic Compounds from Dried Common Rush (Juncus effusus L. var. decipiens Buchen.) on Humans
Authors: Sun Minkai , Nakashima Taisuke , Yoshimura Yuri , Honden Akiyoshi , Nakagawa Toshinori , Nakashima Yu , Kawaguchi Makoto , Takamori Yukimitsu , Koshi Yoshitaka , Sawada Rimpei , Nishida Shinsuke , Ohnuki Koichiro , Shimizu Kuniyoshi
Published: February 2022

This study compared the participants’ physiological responses and subjective evaluations of air scented with different concentrations of common rush (Juncus effusus L. var. decipiens Buchen.) (30 g and 15 g, with fresh air as a control). We asked 20 participants to complete a series of visual discrimination tasks while inhaling two different air samples. We evaluated (1) brain activity, (2) autonomic nervous activity, and (3) blood pressure and pulse rate, (4) in combination with self-evaluation. In addition, we quantified the concentrations of volatile organic compounds. The participants reported the scent to be sour, pungent, and smelly; this impression was likely caused by hexanal and acetic acid. Although the self-evaluations showed that participants did not enjoy the scent, their alpha amplitudes of electroencephalogram and parasympathetic nervous activity were increased, suggesting that participants were relaxed in this atmosphere. Moreover, a lower concentration resulted in a greater induction of relaxation. While the air was not pleasant-smelling, the volatile organic compounds present had a positive psychophysiological impact.
Renoprotective Effects of Mangiferin: Pharmacological Advances and Future Perspectives
Authors: Akter Sumaya , Moni Akhi , Faisal Golam Mahbub , Uddin Muhammad Ramiz , Jahan Nourin , Hannan Md Abdul , Rahman Asadur , Uddin Md Jamal
Published: February 2022

Both acute and chronic kidney diseases substantially contribute to the morbidities and mortality of patients worldwide. The existing therapeutics, which are mostly developed from synthetic sources, present some unexpected effects in patients, provoking researchers to explore potential novel alternatives. Natural products that have protective effects against various renal pathologies could be potential drug candidates for kidney diseases. Mangiferin is a natural polyphenol predominantly isolated from Mangifera indica and possesses multiple health benefits against various human ailments, including kidney disease. The main objective of this review is to update the renoprotective potentials of mangiferin with underlying molecular pharmacology and to highlight the recent development of mangiferin-based therapeutics toward kidney problems. Literature published over the past decade suggests that treatment with mangiferin attenuates renal inflammation and oxidative stress, improves interstitial fibrosis and renal dysfunction, and ameliorates structural alteration in the kidney. Therefore, mangiferin could be used as a multi-target therapeutic candidate to treat renal diseases. Although mangiferin-loaded nanoparticles have shown therapeutic promise against various human diseases, there is limited information on the targeted delivery of mangiferin in the kidney. Further research is required to gain insight into the molecular pharmacology of mangiferin targeting kidney diseases and translate the preclinical results into clinical use.
Murine Beta-Amyloid (1–42) Oligomers Disrupt Endothelial Barrier Integrity and VEGFR Signaling via Activating Astrocytes to Release Deleterious Soluble Factors
Authors: Yue Qian , Zhou Xinhua , Zhang Zaijun , Hoi Maggie Pui Man
Published: February 2022

Transgenic mouse models of Alzheimer’s disease (AD) overexpress mutations of the human amyloid protein precursor (APP) and presenilin-1 (PSEN1) genes, which are known causes of amyloid pathology in familial AD. However, animal models for studying AD in the context of aging and age-related co-morbidities, such as blood–brain barrier (BBB) disruptions, are lacking. More recently, aged and progeroid mouse models have been proposed as alternatives to study aging-related AD, but the toxicity of murine amyloid-beta protein (Aβ) is not well defined. In this study, we aimed to study the potential toxicity of murine Aβ on brain endothelial cells and astrocytes, which are important components of the BBB, using mouse brain endothelial cells (bEnd.3) and astrocytes (C8-D1A). Murine-soluble Aβ (1–42) oligomers (sAβO42) (10 µM) induced negligible injuries in an endothelial monolayer but induced significant barrier disruptions in a bEnd.3 and C8-D1A co-culture. Similar results of endothelial perturbation were observed in a bEnd.3 monolayer treated with astrocyte-conditioned medium (ACM) generated by astrocytes exposed to sAβO42 (ACM-sAβO42), while additional exogenous sAβO42 did not cause further damage. Western blot analysis showed that ACM-sAβO42 altered the basal activities of vascular endothelial growth factor receptor 2 (VEGFR2), eNOS, and the signaling of the MEK/ERK and Akt pathways in bEnd.3. Our results showed that murine sAβO42 was moderately toxic to an endothelial and astrocyte co-culture. These damaging effects on the endothelial barrier were induced by deleterious soluble factors released from astrocytes, which disrupted endothelial VEGFR2 signaling and perturbed cell survival and barrier stabilization.
Regulatory T Cell Apoptosis during Preeclampsia May Be Prevented by Gal-2
Authors: Meister Sarah , Hahn Laura , Beyer Susanne , Mannewitz Mareike , Perleberg Carolin , Schnell Konstantin , Anz David , Corradini Stefanie , Schmoeckel Elisa , Mayr Doris , Hasbargen Uwe , Zati Zehni Alaleh , Mahner Sven , Jeschke Udo , Kolben Thomas
Published: February 2022

There are several open questions to be answered regarding the pathophysiology of the development of preeclampsia (PE). Numerous factors are involved in its genesis, such as defective placentation, vascular impairment, and an altered immune response. The activation of the adaptive and innate immune system represents an immunologic, particularity during PE. Proinflammatory cytokines are predominantly produced, whereas immune regulatory and immune suppressive factors are diminished in PE. In the present study, we focused on the recruitment of regulatory T cells (Tregs) which are key players in processes mediating immune tolerance. To identify Tregs in the decidua, an immunohistochemical staining of FoxP3 of 32 PE and 34 control placentas was performed. A clearly reduced number of FoxP3-positive cells in the decidua of preeclamptic women could be shown in our analysis (p = 0.036). Furthermore, CCL22, a well-known Treg chemoattractant, was immunohistochemically evaluated. Interestingly, CCL22 expression was increased at the maternal-fetal interface in PE-affected pregnancies (psyncytiotrophoblast = 0.035, pdecidua = 0.004). Therefore, the hypothesis that Tregs undergo apoptosis at the materno-fetal interface during PE was generated, and verified by FoxP3/TUNEL (TdT-mediated dUTP-biotin nick end labeling) staining. Galectin-2 (Gal-2), a member of the family of carbohydrate-binding proteins, which is known to be downregulated during PE, seems to play a pivotal role in T cell apoptosis. By performing a cell culture experiment with isolated Tregs, we could identify Gal-2 as a factor that seems to prevent the apoptosis of Tregs. Our findings point to a cascade of apoptosis of Tregs at the materno-fetal interface during PE. Gal-2 might be a potential therapeutic target in PE to regulate immune tolerance.
Advances in Neuromodulation for Chronic Pain
Authors: Moens Maarten , Goudman Lisa
Published: February 2022

In the past decade, neuromodulation as a treatment option for pain took a huge interest in innovating and developing more effective paradigms to conquer chronic pain syndromes [...]
Understanding the Settling Processes of Dredged Sediment Disposed in Open Waters through Experimental Tests and Numerical Simulations
Authors: Ding Wei , Lu Chuanteng , Xie Qiancheng , Luo Xiaofeng , Zhang Gongjin
Published: February 2022

During dredging for subsea tunnels and pipelines, the dredged soil is typically dumped in a designated area. Understanding the settling behaviors of the dumped particles is essential for an accurate prediction of the resulting morphology. This study dealt with the settling processes in the open-water column by means of experimental tests and numerical simulations. Both quiescent and ambient current conditions were taken into account. Particular attention was paid to the induced flow patterns, descent sediment movement features and the resulting topography. Regarding the diffusion width and settling velocity, three key effect factors, i.e., dumped volume, particle size and ambient flow strength, were considered. The results show that the dumped sediment in the water forms a particle cloud, and two vortices with opposite rotations occur on both sides of the cloud. During settlement, three stages corresponding to convective descent, dynamic collapse and passive diffusion are observed. Most of the descending sediment is incorporated in a spherical vortex, resembling an upside-down mushroom cloud, and some sediment is also contained in an irregular trailing stem. The dumped particles exhibit initial acceleration, and then they slow down to converge to a fixed value. Subjected to the ambient currents, the initial acceleration phase is prolonged, and the vortex is somewhat distorted; the particle cloud is also advected downstream with a velocity roughly equal to the ambient current.
Mechanical Behavior of the Rock-Concrete Interface for a Bridge Anchorage Structure Using Discrete Element Method
Authors: Cui Zhen , Zhang Maochu , Sheng Qian
Published: February 2022

Traditionally, the numerical simulation work of a bridge gravity anchorage structure is performed with a continuous method, such as the finite element method (FEM). However, since the rock mass and gravity anchorage structure are assumed to be continuous in the FEM, the interaction between the rock mass foundation and the concrete of the anchorage is not frequently considered. This paper aims to investigate the problem of the interaction between the rock mass foundation and the concrete of the anchorage. The discrete element method (DEM), which has been verified to be suitable for the modelling of contact problems of discrete blocks, is introduced in this paper to simulate the mechanical behavior of the rock-concrete system of the gravity anchorage structure and its rock mass foundation. Based on the in-situ scale model test for a bridge, the mechanical behavior of the rock-concrete interface was discussed with the DEM method. With the calibrated DEM model, the displacement of the foundation rock mass, contact stresses, and yield state on the rock-concrete interface were numerically investigated. The anti-sliding effect of the keyway and the step at the bottom of the gravity anchorage structure was analyzed. The results show that the anchorage deformation under the design conditions is basically characterized by the rigid rotation around the keyway of platform #2, and that such rotation subsequently affects the anti-shear capacity of the entire gravity anchorage to a large extent. The anchorage scale model could remain stable under the design lateral load such that the rock-concrete interface would remain intact and sufficient shear resistance could be provided by the keyway and steps.
Retinal Microcirculation Changes in Crohn’s Disease Patients under Biologics, a Potential Biomarker of Severity: A Pilot Study
Authors: Debourdeau Eloi , Chamard Chloé , Carriere Isabelle , Plat Julien , Villain Max , Boivineau Lucile , Altwegg Romain , Daien Vincent
Published: February 2022

Crohn’s disease (CD) is associated with increased cardiovascular risk and the retinal microcirculation is a reflection of the systemic microcirculation. Is the retinal microcirculation altered in relation to the severity of Crohn’s disease? This cross-sectional case-controlled study was conducted in a university hospital center from November 2020 to February 2021. We prospectively included patients with moderate (biologic therapy) or severe (biologic therapy + peri-anal disease and/or digestive resection) CD and age- and sex-matched controls. Individuals with diabetes, renal disease, cardiovascular disease, ophthalmological history or poor quality images were excluded. All participants underwent OCT angiography (OCT-A) imaging (Optovue, Fremont, CA). Analysis of covariance was used. 74 CD patients (33 moderate, 41 severe) and 74 controls (66 (44.6%) men; mean (SD) age 44 (14) years) were included. Compared with the controls, the severe CD patients showed a significantly reduced mean foveal avascular zone area (p = 0.001), superficial macular capillary plexus vessel density (p = 0.009) and parafoveal thickness (p < 0.001), with no difference in mean superficial capillary flow index (p = 0.06) or deep macular capillary plexus vessel density (p = 0.67). The mean foveal avascular zone was significantly lower in the severe than the moderate CD patients (p = 0.010). OCT-A can detect alterations in retinal microcirculation in patients with severe versus moderate CD and versus age- and sex-matched controls.
Preliminary Acceptability of a Home-Based Peripheral Blood Collection Device for Viral Load Testing in the Context of Analytical Treatment Interruptions in HIV Cure Trials: Results from a Nationwide Survey in the United States
Authors: Dubé Karine , Eskaf Shadi , Hastie Elizabeth , Agarwal Harsh , Henley Laney , Roebuck Christopher , Carter William B. , Dee Lynda , Taylor Jeff , Mapp Derrick , Campbell Danielle M. , Villa Thomas J. , Peterson Beth , Lynn Kenneth M. , Lalley-Chareczko Linden , Hiserodt Emily , Kim Sukyung , Rosenbloom Daniel , Evans Brad R. , Anderson Melanie , Hazuda Daria J. , Shipley Lisa , Bateman Kevin , Howell Bonnie J. , Mounzer Karam , Tebas Pablo , Montaner Luis J.
Published: February 2022

Frequent viral load testing is necessary during analytical treatment interruptions (ATIs) in HIV cure-directed clinical trials, though such may be burdensome and inconvenient to trial participants. We implemented a national, cross-sectional survey in the United States to examine the acceptability of a novel home-based peripheral blood collection device for HIV viral load testing. Between June and August 2021, we distributed an online survey to people with HIV (PWH) and community members, biomedical HIV cure researchers and HIV care providers. We performed descriptive analyses to summarize the results. We received 73 survey responses, with 51 from community members, 12 from biomedical HIV cure researchers and 10 from HIV care providers. Of those, 51 (70%) were cisgender men and 50 (68%) reported living with HIV. Most (>80% overall) indicated that the device would be helpful during ATI trials and they would feel comfortable using it themselves or recommending it to their patients/participants. Of the 50 PWH, 42 (84%) indicated they would use the device if they were participating in an ATI trial and 27 (54%) also expressed a willingness to use the device outside of HIV cure studies. Increasing sensitivity of viral load tests and pluri-potency of the device (CD4 count, chemistries) would augment acceptability. Survey findings provide evidence that viral load home testing would be an important adjunct to ongoing HIV cure-directed trials involving ATIs. Survey findings may help inform successful implementation and uptake of the device in the context of personalized HIV care.
Horizon Scan of Transboundary Concerns Impacting Snow Leopard Landscapes in Asia
Authors: Sultan Hameeda , Rashid Wajid , Shi Jianbin , Rahim Inam ur , Nafees Mohammad , Bohnett Eve , Rashid Sajid , Khan Muhammad Tariq , Shah Izaz Ali , Han Heesup , Ariza-Montes Antonio
Published: February 2022

The high-altitude region of Asia is prone to natural resource degradation caused by a variety of natural and anthropogenic factors that also threaten the habitat of critical top predator species, the snow leopard (Panthera uncia). The snow leopard’s landscape encompasses parts of the twelve Asian countries and is dominated by pastoral societies within arid mountainous terrain. However, no investigation has assessed the vulnerability and pathways towards long-term sustainability on the global snow leopard landscape scale. Thus, the current study reviewed 123 peer-reviewed scientific publications on the existing knowledge, identified gaps, and proposed sustainable mitigation options for the longer term and on larger landscape levels in the range countries. The natural resource degradation in this region is caused by various social, economic, and ecological threats that negatively affect its biodiversity. The factors that make the snow leopard landscapes vulnerable include habitat fragmentation through border fencing, trade corridor infrastructure, non-uniform conservation policies, human–snow leopard conflict, the increasing human population, climatic change, land use and cover changes, and unsustainable tourism. Thus, conservation of the integrated Socio-Ecological System (SES) prevailing in this region requires a multi-pronged approach. This paper proposes solutions and identifies the pathways through which to implement these solutions. The prerequisite to implementing such solutions is the adoption of cross-border collaboration (regional cooperation), the creation of peace parks, readiness to integrate transnational and cross-sectoral conservation policies, a focus on improving livestock management practices, a preparedness to control human population growth, a readiness to mitigate climate change, initiating transboundary landscape-level habitat conservation, adopting environment-friendly trade corridors, and promoting sustainable tourism. Sustainable development in this region encompasses the political, social, economic, and ecological landscapes across the borders.
Changes in the Structure of Crop Production in Slovakia after 2004 Using an Example of Selected Crops
Authors: Némethová Jana , Vilinová Katarína
Published: February 2022

Spatial changes in the structure of crop production have the potential to impact economics and food security in Slovakia. The objective of this study was to analyze the modification of harvested areas, the production and yields of selected crops—cereals, oilseeds, and perennial forages—and their food and non-food use from 2004 to 2020. The results indicated that an increase in the cultivation of large-scale crops (cereals and oilseeds) has occurred at the expense of crops produced for food. Changes in the structure of plant production indicate negative risk factor that reduce the competitiveness of the agricultural sector and threaten Slovakia’s food security. Moran’s global and Moran’s local autocorrelation index were used in the synthesis of the findings. A spatial autocorrelation analysis of the harvest areas of selected crops was used as a practical approach to locate statistically significant areas with high or low crop harvest. This manifested itself as positive spatial autocorrelation.
Association of the DNA Methyltransferase and Folate Cycle Enzymes’ Gene Polymorphisms with Coronary Restenosis
Authors: Timizheva Kalima B. , Ahmed Abdulbary A. M. , Ait Aissa Amira , Aghajanyan Anna V. , Tskhovrebova Leyla V. , Azova Madina M.
Published: February 2022

Background: In recent years, the interest in genetic predisposition studies for coronary artery disease and restenosis has increased. Studies show that polymorphisms of genes encoding folate cycle and homocysteine metabolism enzymes significantly contribute to atherogenesis and endothelial dysfunction. The purpose of this study was to examine some SNPs of genes coding for folate cycle enzymes and DNA methyltransferases as risk factors for in-stent restenosis. Methods: The study included 113 patients after stent implantation and 62 patients without signs of coronary artery disease at coronary angiography as the control group. Real-time PCR and RFLP-PCR were applied to genotype all participants for MTHFR rs1801133, MTHFR rs1801131, MTR rs1805087, MTRR rs1801394, DNMT1 rs8101626, DNMT3B rs1569686, and DNMT3B rs2424913 gene polymorphisms. Statistical data processing was carried out using the R language and the SPSS Statistics 20 software. Results: Statistically significant differences in the DNMT3B gene polymorphisms were found between patients with and without in-stent restenosis. An association of TT rs1569686 and TT rs2424913 genotypes with the development of restenosis was revealed. The TT rs1569686 genotype was more frequent in the patients under the age of 65 years and in the subgroup of patients with post-12-month restenosis, as was the minor GG genotype for MTR rs1805087. The homozygous TT genotype for MTHFR rs1801133 was significantly more frequent in the subgroup over 65 years old. The frequencies of the heterozygous genotype for the MTRR gene and the minor GG homozygotes for the DNMT1 gene were significantly higher in the subgroup with in-stent restenosis under 65 years old. Conclusions: The results of this study could be used for a comprehensive risk assessment of ISR development, determining the optimal tactics and an individual approach in the treatment of patients with coronary artery disease before or after percutaneous coronary interventions, including homocysteine-lowering treatment in patients with hyperhomocysteinemia and a high risk of in-stent restenosis.