bluuebunny/crossref_metadata_2025 huggingface dataset:
Organ-On-A-Chip: A Survey of Technical Results and Problems
Authors: Danku Alex Ede , Dulf Eva-H , Braicu Cornelia , Jurj Ancuta , Berindan-Neagoe Ioana
Published: February 2022

Organ-on-a-chip (OoC), also known as micro physiological systems or “tissue chips” have attracted substantial interest in recent years due to their numerous applications, especially in precision medicine, drug development and screening. Organ-on-a-chip devices can replicate key aspects of human physiology, providing insights into the studied organ function and disease pathophysiology. Moreover, these can accurately be used in drug discovery for personalized medicine. These devices present useful substitutes to traditional preclinical cell culture methods and can reduce the use of in vivo animal studies. In the last few years OoC design technology has seen dramatic advances, leading to a wide range of biomedical applications. These advances have also revealed not only new challenges but also new opportunities. There is a need for multidisciplinary knowledge from the biomedical and engineering fields to understand and realize OoCs. The present review provides a snapshot of this fast-evolving technology, discusses current applications and highlights advantages and disadvantages for biomedical approaches.
Single-Cell Sequencing Unveils the Heterogeneity of Nonimmune Cells in Chronic Apical Periodontitis
Authors: Lin Xinwei , Chi Danlu , Meng Qingzhen , Gong Qimei , Tong Zhongchun
Published: February 2022

Chronic apical periodontitis (CAP) is a unique dynamic interaction between microbial invasions and host defense mechanisms, resulting in infiltration of immune cells, bone absorption, and periapical granuloma formation. To help to understand periapical tissue pathophysiology, we constituted a single-cell atlas for 26,737 high-quality cells from inflammatory periapical tissue and uncovered the complex cellular landscape. The eight types of cells, including nonimmune cells and immune cells, were identified in the periapical tissue of CAP. Considering the key roles of nonimmune cells in CAP, we emphasized osteo-like cells, basal/stromal cells, endothelial cells, and epithelial cells, and discovered their diversity and heterogeneity. The temporal profiling of genomic alterations from common CAP to typical periapical granuloma provided predictions for transcription factors and biological processes. Our study presented potential clues that the shift of inflammatory cytokines, chemokines, proteases, and growth factors initiated polymorphic cell differentiation, lymphangiogenesis, and angiogenesis during CAP.
Blockade of GCH1/BH4 Axis Activates Ferritinophagy to Mitigate the Resistance of Colorectal Cancer to Erastin-Induced Ferroptosis
Authors: Hu Qian , Wei Wanhui , Wu Daiqian , Huang Fengxing , Li Mengting , Li Wenjie , Yin Jingwen , Peng Yanan , Lu Yuanyuan , Zhao Qiu , Liu Lan
Published: February 2022

Ferroptosis, a type of cell death triggered by excessive accumulation of iron-dependent lipid peroxidation, possesses an excellent potential in cancer treatment. However, many colorectal cancer (CRC) cell lines are resistant to ferroptosis induced by erastin and RSL3, the classical ferroptotic inducers. Moreover, the underlying mechanism of resistance remains poorly elucidated. This study sought to discover the major factor contributing to ferroptosis resistance in CRC. The study findings will help design strategies for triggering ferroptosis for application in individualized tumor therapy. Here, we show that tetrahydrobiopterin (BH4) determines the sensitivity of CRC cells to ferroptosis induced by erastin. GTP cyclohydrolase-1 (GCH1) is the first rate-limiting enzyme of BH4. Genetic or pharmacological inhibition of GCH1 decreased BH4 and assisted erastin in cell death induction, lipid peroxidation enhancement, and ferrous iron accumulation. BH4 supplementation completely inhibited ferroptotic features resulting from GCH1 knockdown. Unexpectedly, GCH1 knockdown failed to enhance RSL3-induced cell death in CRC. Mechanistically, GCH1 knockdown drastically activated ferritinophagy during erastin treatment rather than RSL3 treatment. Administration of an autophagy inhibitor reversed erastin resistance in GCH1-knockdown cells. GCH1 inhibitor and erastin co-treatment in vivo synergistically inhibited tumor growth in CRC. Overall, our results identified GCH1/BH4 metabolism as a burgeoning ferroptosis defense mechanism in CRC. Inhibiting GCH1/BH4 metabolism promoted erastin-induced ferroptosis by activating ferritinophagy, suggesting that combining GCH1 inhibitors with erastin in the treatment of CRC is a novel therapeutic strategy.
Brain Regeneration Resembles Brain Cancer at Its Early Wound Healing Stage and Diverges From Cancer Later at Its Proliferation and Differentiation Stages
Authors: Demirci Yeliz , Heger Guillaume , Katkat Esra , Papatheodorou Irene , Brazma Alvis , Ozhan Gunes
Published: February 2022

Gliomas are the most frequent type of brain cancers and characterized by continuous proliferation, inflammation, angiogenesis, invasion and dedifferentiation, which are also among the initiator and sustaining factors of brain regeneration during restoration of tissue integrity and function. Thus, brain regeneration and brain cancer should share more molecular mechanisms at early stages of regeneration where cell proliferation dominates. However, the mechanisms could diverge later when the regenerative response terminates, while cancer cells sustain proliferation. To test this hypothesis, we exploited the adult zebrafish that, in contrast to the mammals, can efficiently regenerate the brain in response to injury. By comparing transcriptome profiles of the regenerating zebrafish telencephalon at its three different stages, i.e., 1 day post-lesion (dpl)-early wound healing stage, 3 dpl-early proliferative stage and 14 dpl-differentiation stage, to those of two brain cancers, i.e., low-grade glioma (LGG) and glioblastoma (GBM), we reveal the common and distinct molecular mechanisms of brain regeneration and brain cancer. While the transcriptomes of 1 dpl and 3 dpl harbor unique gene modules and gene expression profiles that are more divergent from the control, the transcriptome of 14 dpl converges to that of the control. Next, by functional analysis of the transcriptomes of brain regeneration stages to LGG and GBM, we reveal the common and distinct molecular pathways in regeneration and cancer. 1 dpl and LGG and GBM resemble with regard to signaling pathways related to metabolism and neurogenesis, while 3 dpl and LGG and GBM share pathways that control cell proliferation and differentiation. On the other hand, 14 dpl and LGG and GBM converge with respect to developmental and morphogenetic processes. Finally, our global comparison of gene expression profiles of three brain regeneration stages, LGG and GBM exhibit that 1 dpl is the most similar stage to LGG and GBM while 14 dpl is the most distant stage to both brain cancers. Therefore, early convergence and later divergence of brain regeneration and brain cancer constitutes a key starting point in comparative understanding of cellular and molecular events between the two phenomena and development of relevant targeted therapies for brain cancers.
The Nrf2 Pathway in Liver Diseases
Authors: Zhou Jiaming , Zheng Qiuxian , Chen Zhi
Published: February 2022

Oxidative stress is the leading cause of most liver diseases, such as drug-induced liver injury, viral hepatitis, and alcoholic hepatitis caused by drugs, viruses, and ethanol. The Kelch-like ECH-associated protein 1-NFE2-related factor 2 (Keap1-Nrf2) system is a critical defense mechanism of cells and organisms in response to oxidative stress. Accelerating studies have clarified that the Keap1-Nrf2 axis are involved in the prevention and attenuation of liver injury. Nrf2 up-regulation could alleviate drug-induced liver injury in mice. Moreover, many natural Nrf2 activators can regulate lipid metabolism and oxidative stress of liver cells to alleviate fatty liver disease in mice. In virus hepatitis, the increased Nrf2 can inhibit hepatitis C viral replication by up-regulating hemeoxygenase-1. In autoimmune liver diseases, the increased Nrf2 is essential for mice to resist liver injury. In liver cirrhosis, the enhanced Nrf2 reduces the activation of hepatic stellate cells by reducing reactive oxygen species levels to prevent liver fibrosis. Nrf2 plays a dual function in liver cancer progression. At present, a Nrf2 agonist has received clinical approval. Therefore, activating the Nrf2 pathway to induce the expression of cytoprotective genes is a potential option for treating liver diseases. In this review, we comprehensively summarized the relationships between oxidative stress and liver injury, and the critical role of the Nrf2 pathway in multiple liver diseases.
Energy-Saving Synthesis of Functional CoS2/rGO Interlayer With Enhanced Conversion Kinetics for High-Performance Lithium-Sulfur Batteries
Authors: Feng Junan , Li Yahui , Yuan Jinshi , Zhao Yuling , Zhang Jianmin , Wang Fengyun , Tang Jie , Song Jianjun
Published: February 2022

Lithium sulfur (Li-S) battery has exhibited great application potential in next-generation high-density secondary battery systems due to their excellent energy density and high specific capacity. However, the practical industrialization of Li-S battery is still affected by the low conductivity of sulfur and its discharge product (Li2S2/Li2S), the shuttle effect of lithium polysulfide (Li2Sn, 4 ≤ n ≤ 8) during charging/discharging process and so on. Here, cobalt disulfide/reduced graphene oxide (CoS2/rGO) composites were easily and efficiently prepared through an energy-saving microwave-assisted hydrothermal method and employed as functional interlayer on commercial polypropylene separator to enhance the electrochemical performance of Li-S battery. As a physical barrier and second current collector, the porous conductive rGO can relieve the shuttle effect of polysulfides and ensure fast electron/ion transfer. Polar CoS2 nanoparticles uniformly distributed on rGO provide strong chemical adsorption to capture polysulfides. Benefitting from the synergy of physical and chemical constraints on polysulfides, the Li-S battery with CoS2/rGO functional separator exhibits enhanced conversion kinetics and excellent electrochemical performance with a high cycling initial capacity of 1,122.3 mAh g−1 at 0.2 C, good rate capabilities with 583.9 mAh g−1 at 2 C, and long-term cycle stability (decay rate of 0.08% per cycle at 0.5 C). This work provides an efficient and energy/time-saving microwave hydrothermal method for the synthesis of functional materials in stable Li-S battery.
First-Principles Study on the Half-Metallicity of New MXene Materials Nd2NT2 (T = OH, O, S, F, Cl, and Br)
Authors: Yang Kun , Ren Shuning , Huang Haishen , Wu Bo , Shen Guangxian , Zhou Tingyan , Liu Xiaoying
Published: February 2022

This work systematically studied the structure, magnetic and electronic properties of the MXene materials Nd2N and Nd2NT2 (T = OH, O, S, F, Cl, and Br) via first-principles calculations based on density functional theory. Results showed that Nd2NT2 (T = OH, O, S, F, Cl, and Br) have half-metallic characteristics whose half-metallic band gap width is higher than 1.70 eV. Its working function ranges from 1.83 to 6.50 eV. The effects of strain on its magnetic and electronic structures were evaluated. Results showed that the structure of Nd2NT2 (T = OH, O, S, and Br) transitions from a ferromagnetic half-metallic semiconductor to a ferromagnetic metallic and ferromagnetic semiconductor under different strains. By contrast, the structures of Nd2NF2 and Nd2NS2 were observed to transition from a half-metallic semiconductor to a ferromagnetic metallic semiconductor under different strains. Calculations of the electronic properties of different proportions of the surface functional groups of Nd2NTx (T = OH, O, and F; x = 0.5, 1(I, II), and 1.5) revealed that Nd2NO1.5 has the characteristics of semiconductors, whereas Nd2NO(II) possesses the characteristics of half-metallic semiconductors. The other structures were observed to exhibit the characteristics of metallic semiconductors. Prediction of Nd2NT2 (T = OH, O, S, F, Cl, and Br) increases the types of lanthanide MXene materials. They are appropriate candidate materials for preparing spintronic devices.
Virtual Screening of Drug-Like Compounds as Potential Inhibitors of the Dengue Virus NS5 Protein
Authors: García-Ariza Leidy L. , Rocha-Roa Cristian , Padilla-Sanabria Leonardo , Castaño-Osorio Jhon C.
Published: February 2022

Dengue virus (DENV) is the causative agent of dengue fever. Annually, there are about 400 million new cases of dengue worldwide, and so far there is no specific treatment against this disease. The NS5 protein is the largest and most conserved viral protein among flaviviruses and is considered a therapeutic target of great interest. This study aims to search drug-like compounds for possible inhibitors of the NS5 protein in the four serotypes of DENV. Using a virtual screening from a ∼642,759-compound database, we suggest 18 compounds with NS5 binding and highlight the best compound per region, in the methyltransferase and RNA-dependent RNA polymerase domains. These compounds interact mainly with the amino acids of the catalytic sites and/or are involved in processes of protein activity. The identified compounds presented physicochemical and pharmacological properties of interest for their use as possible drugs; furthermore, we found that some of these compounds do not affect cell viability in Huh-7; therefore, we suggest evaluating these compounds in vitro as candidates in future research.
Boosting the Electrochemical Performance of PI-5-CA/C-SWCNT Nanohybrid for Sensitive Detection of E. coli O157:H7 From the Real Sample
Authors: Wang Huan , Fan Yanmiao , Yang Qiaoli , Sun Xiaoyu , Liu Hao , Chen Wei , Aziz Ayesha , Wang Shenqi
Published: February 2022

Redox activity is an important indicator for evaluating electrochemical biosensors. In this work, we have successfully polymerized indole-5-carboxylic acid into poly-5-carboxyindole nanomaterials (PI-5-CA), using its superior redox activity, and introduced carboxylated single-walled carbon nanotubes (C-SWCNTs) to synthesize a composite material. Finally, a synthesized composite material was used for the modification of the glass carbon electrode to fabricate the PI-5-CA/C-SWCNTs/GCE-based immunosensor and was successfully applied for the sensitive detection of E. coli O157:H7. The fabricated immunosensor exhibited an outstanding electrocatalytic activity toward the detection of E. coli O157:H7 with a remarkably lowest limit of detection (2.5 CFU/ml, LOD = 3 SD/k, n = 3) and has a wide linear range from 2.98×101 to 2.98×107 CFU/ml. Inspired from the excellent results, the fabricated electrode was applied for the detection of bacteria from real samples (water samples) with a good recovery rate (98.13–107.69%) as well as an excellent stability and specificity. Owing to its simple preparation, excellent performance, and detection time within 30 min, our proposed immunosensor will open a new horizon in different fields for the sensitive detection of bacteria from real samples.
Highly Dispersed CoO Embedded on Graphitized Ordered Mesoporous Carbon as an Effective Catalyst for Selective Fischer–Tropsch Synthesis of C5+ Hydrocarbons
Authors: Bai Jirong , Song Mingyao , Pang Jiazheng , Wang Lingling , Zhang Jianping , Jiang Xiankai , Ni Zhijiang , Wang Zhilei , Zhou Quanfa
Published: February 2022

Herein, we report the high Fischer–Tropsch synthesis performance of the Co-based catalysts supported on graphitized ordered mesoporous carbon (GMC-900) by using a facile strategy. Compared with CMK-3 and active carbon (AC), the obtained GMC-900 by using pollution-free soybean oil as a carbon source exhibited enhanced catalytic performance after loading Co species due to its highly crystallized graphitic structure and uniform dispersion of CoO. As a result, Co/GMC-900 was an effective catalyst with the maximum C5+ selectivity of 52.6%, which much outperformed Co/CMK-3 and Co/AC. This research provides an approach to produce advanced Co-based catalysts with satisfactory performance for efficient Fischer–Tropsch synthesis.
Therapeutic Antibodies Against Shiga Toxins: Trends and Perspectives
Authors: Henrique Izabella de Macedo , Sacerdoti Flavia , Ferreira Raissa Lozzardo , Henrique Camila , Amaral Maria Marta , Piazza Roxane Maria Fontes , Luz Daniela
Published: February 2022

Shiga toxins (Stx) are AB5-type toxins, composed of five B subunits which bind to Gb3 host cell receptors and an active A subunit, whose action on the ribosome leads to protein synthesis suppression. The two Stx types (Stx1 and Stx2) and their subtypes can be produced by Shiga toxin-producing Escherichia coli strains and some Shigella spp. These bacteria colonize the colon and induce diarrhea that may progress to hemorrhagic colitis and in the most severe cases, to hemolytic uremic syndrome, which could lead to death. Since the use of antibiotics in these infections is a topic of great controversy, the treatment remains supportive and there are no specific therapies to ameliorate the course. Therefore, there is an open window for Stx neutralization employing antibodies, which are versatile molecules. Indeed, polyclonal, monoclonal, and recombinant antibodies have been raised and tested in vitro and in vivo assays, showing differences in their neutralizing ability against deleterious effects of Stx. These molecules are in different phases of development for which we decide to present herein an updated report of these antibody molecules, their source, advantages, and disadvantages of the promising ones, as well as the challenges faced until reaching their applicability.
miR-548d-3p Is Up-Regulated in Human Visceral Leishmaniasis and Suppresses Parasite Growth in Macrophages
Authors: Ramos-Sanchez Eduardo Milton , Reis Luiza Campos , Souza Marina de Assis , Muxel Sandra Márcia , Santos Kamila Reis , Lagos Dimitris , Pereira Valéria Rêgo Alves , Brito Maria Edileuza Felinto de , Kaye Paul Martin , Floeter-Winter Lucile Maria , Goto Hiro
Published: February 2022

Visceral leishmaniasis caused by Leishmania (Leishmania) infantum in Latin America progress with hepatosplenomegaly, pancytopenia, hypergammaglobulinemia, and weight loss and maybe lethal mainly in untreated cases. miRNAs are important regulators of immune and inflammatory gene expression, but their mechanisms of action and their relationship to pathogenesis in leishmaniasis are not well understood. In the present study, we sought to quantify changes in miRNAs associated with immune and inflammatory pathways using the L. (L.) infantum promastigote infected- human monocytic THP-1 cell model and plasma from patients with visceral leishmaniasis. We identified differentially expressed miRNAs in infected THP-1 cells compared with non-infected cells using qPCR arrays. These miRNAs were submitted to in silico analysis, revealing targets within functional pathways associated with TGF-β, chemokines, glucose metabolism, inflammation, apoptosis, and cell signaling. In parallel, we identified differentially expressed miRNAs in active visceral leishmaniasis patient plasma compared with endemic healthy controls. In silico analysis of these data indicated different predicted targets within the TGF-β, TLR4, IGF-I, chemokine, and HIF1α pathways. Only a small number of miRNAs were commonly identified in these two datasets, notably with miR-548d-3p being up-regulated in both conditions. To evaluate the potential biological role of miR-548d-3p, we transiently transfected a miR-548d-3p inhibitor into L. (L.) infantum infected-THP-1 cells, finding that inhibition of miR-548d-3p enhanced parasite growth, likely mediated through reduced levels of MCP-1/CCL2 and nitric oxide production. Further work will be required to determine how miR-548d-3p plays a role in vivo and whether it serves as a potential biomarker of progressive leishmaniasis.
Role of ENSO on Conflicts in the Global South
Authors: Roy Shouraseni Sen
Published: February 2022

In recent years, there has been increasing research on the impact of climate change related processes on the occurrence of conflicts in different parts of the world. Analysis of conflicts over extended time periods indicate the possible role of climate change and climate variability on the occurrence of conflicts, particularly in the tropics. With the recent release of the UCDP georeferenced dataset on specific locations of conflicts between 1989 and 2014, we can now examine the temporal patterns of conflicts at a finer spatial resolution. In this study, the role of El Niño Southern Oscillation (ENSO) on the spatio-temporal patterns of conflicts has been analyzed by using a variety of geospatial analysis techniques. The results of the analysis reveal that there were a greater number of conflicts during El Niño years at both the global and continental scale (except North America). In addition, the spatial patterns of conflicts showed greater concentration of intensifying and consecutive hot spots in South and Southeast Asia, the Middle East, and Central and Eastern Africa during El Niño years vs. La Niña years. Specifically, intensifying hot spots of conflicts overlapped with the relatively arid and semi-arid areas of the Global South.
LABKIT: Labeling and Segmentation Toolkit for Big Image Data
Authors: Arzt Matthias , Deschamps Joran , Schmied Christopher , Pietzsch Tobias , Schmidt Deborah , Tomancak Pavel , Haase Robert , Jug Florian
Published: February 2022

We present LABKIT, a user-friendly Fiji plugin for the segmentation of microscopy image data. It offers easy to use manual and automated image segmentation routines that can be rapidly applied to single- and multi-channel images as well as to timelapse movies in 2D or 3D. LABKIT is specifically designed to work efficiently on big image data and enables users of consumer laptops to conveniently work with multiple-terabyte images. This efficiency is achieved by using ImgLib2 and BigDataViewer as well as a memory efficient and fast implementation of the random forest based pixel classification algorithm as the foundation of our software. Optionally we harness the power of graphics processing units (GPU) to gain additional runtime performance. LABKIT is easy to install on virtually all laptops and workstations. Additionally, LABKIT is compatible with high performance computing (HPC) clusters for distributed processing of big image data. The ability to use pixel classifiers trained in LABKIT via the ImageJ macro language enables our users to integrate this functionality as a processing step in automated image processing workflows. Finally, LABKIT comes with rich online resources such as tutorials and examples that will help users to familiarize themselves with available features and how to best use LABKIT in a number of practical real-world use-cases.
Low-Cost Forensics Reveal High Rates of Non-lethal Snaring and Shotgun Injuries in Zambia's Large Carnivores
Authors: White Paula A. , Van Valkenburgh Blaire
Published: February 2022

The impact of snaring and human-wildlife conflict (HWC) on large carnivore populations is of growing concern, and yet few empirical data are available. Mortality is the metric most often used, but non-lethal injuries that impact fitness are also important threats. However, because non-lethal injuries to wild carnivores are difficult to detect, they have received little study. Using straightforward forensic examination of the skulls of trophy-hunted lions and leopards from Luangwa Valley (LV) and Greater Kafue Ecosystem (GKE), Zambia, we identified non-lethal injuries consisting of snare damage to teeth and shotgun pellets in skulls. Wire snare entanglement can cause permanent, diagnostic damage to carnivore teeth when individuals bite and pull on the wire. Shotguns are used by poachers, as well as during HWCs to drive off carnivores perceived as threats. Carnivores struck by shotgun pellets can suffer non-lethal, but potentially toxic injuries such as pellets embedded in their skulls. Because poaching and HWC are generally more prevalent near human settlements, we predicted a higher incidence of anthropogenic injuries to carnivores in Luangwa where the human population is larger and more concentrated along protected area edges than Kafue. Contrary to expectation, anthropogenic injuries were more prevalent among lions and leopards in Kafue than Luangwa. Notably, definitive evidence of snare entanglement greatly surpassed previous estimates for these regions. Overall, 37% (41 in 112) of adult male lions (29% in Luangwa, 45% in Kafue) and 22% (10 in 45) of adult male leopards (17% in Luangwa, 26% in Kafue) examined had survived being snared at some point in their lifetime. Among adult male lions, 27% (30 in 112) had old shotgun pellet injuries to their skulls. Our procedure of forensic examination of carnivore skulls and teeth, some of which can be applied to live-captured animals, allows for improved detection of cryptic, non-lethal anthropogenic injuries. Further, our methods represent a consistent and economical way to track changes in the frequency of such injuries over time and between regions, thereby providing a direct measure of the effectiveness of conservation programs that seek to reduce poaching and HWC.
Combined Lifestyle Factors and Risk of All-Cause and Cause-Specific Mortality Among Participants in the Linxian Nutrition Intervention Trial: A Cohort, Observational Study
Authors: Fan Jin-hu , Wang Jian-bing , Yang Huan , Dawsey Sanford M. , Taylor Philip R. , Qiao You-lin , Abnet Christian C.
Published: February 2022

Background

Several studies have indicated that combinations of lifestyle and dietary factors are associated with risk of total mortality and death from cardiovascular disease and cancer, but limited data are available from long-term follow-up studies in China.

Methods

This study was a observational cohort study. We prospectively examined the associations of combined lifestyle factors and risk of total and cause-specific mortality in the Linxian General Population Nutrition Intervention Trial (NIT) cohort that included 29,584 healthy adults. A points system method was used to calculate a combined risk score of five lifestyle factors, including smoking, alcohol drinking, body mass index, vegetable intake and fruit intake. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results

Overall, adjusted hazard ratios for mortality increased progressively with an increasing combined risk score. Compared to individuals with a score of zero or one, HRs (95%CIs) for a score of five or above were 1.59 (1.44–1.75) for all-cause mortality, 1.67 (1.48–1.88) for heart disease, 1.69 (1.52–1.88) for stroke, and 1.34 (1.21, 1.47) for cancer. This association for mortality was seen consistently, regardless of gender and age at baseline.

Conclusions

A higher combined risk score was positively associated with risk of total, heart disease, stroke, and cancer mortality. These findings could provide further evidence for the idea that healthy lifestyle is the optimal way to reduce the risk of premature death, and encourage behavior change.
Why Are Women Predisposed to Intracranial Aneurysm?
Authors: Fréneau Milène , Baron-Menguy Céline , Vion Anne-Clémence , Loirand Gervaise
Published: February 2022

Intracranial aneurysm (IA) is a frequent and generally asymptomatic cerebrovascular abnormality characterized as a localized dilation and wall thinning of intracranial arteries that preferentially arises at the arterial bifurcations of the circle of Willis. The devastating complication of IA is its rupture, which results in subarachnoid hemorrhage that can lead to severe disability and death. IA affects about 3% of the general population with an average age for detection of rupture around 50 years. IAs, whether ruptured or unruptured, are more common in women than in men by about 60% overall, and more especially after the menopause where the risk is double-compared to men. Although these data support a protective role of estrogen, differences in the location and number of IAs observed in women and men under the age of 50 suggest that other underlying mechanisms participate to the greater IA prevalence in women. The aim of this review is to provide a comprehensive overview of the current data from both clinical and basic research and a synthesis of the proposed mechanisms that may explain why women are more prone to develop IA.
Case Report: Optical Coherence Tomography Usage for Treatment of the Chronically Lost Stent in the Left Main Coronary Artery
Authors: Krcmar Tomislav , Grgic Romic Ivana , Tomulic Vjekoslav , Jakljevic Tomislav , Bastiancic Luka , Zeljkovic Ivan
Published: February 2022

Acute adverse outcomes of a stent loss during percutaneous coronary intervention (PCI) are well described, however, data on long-term consequences are scarce, especially with intravascular imaging. We report a case of a coronary stent loss in the left main and ostial left circumflex artery (LCx) bifurcation and its migration into the LCx ostium during PCI procedures. This rare complication, which was not immediately noticed, was verified and successfully resolved 5 months after using optical coherence tomography and right trans-radial access. Considering the infrequency of this complication, few cases have been reported, however, our case has several distinct specificities. We aim to encourage the crushing technique in cases of chronic stent loss when the retrieval is not an option and highlight the optical coherence tomography (OCT) value in imaging and evaluation of similar complex settings.
Short-Term Supplementation With Fermented Red Clover Extract Reduces Vascular Inflammation in Early Post-menopausal Women
Authors: Wickham Kate A. , Nørregaard Line B. , Oxfeldt Mikkel , Cheung Stephen S. , Gliemann Lasse , Hansen Mette , Hellsten Ylva
Published: February 2022

The decline in estrogen at menopause poses a critical challenge to cardiovascular and metabolic health. Recently, a growing interest in the role of phytoestrogens, with a particular focus on isoflavones, has emerged as they can bind to estrogen receptors and may mimic the roles of endogenous estrogen. Fermented red clover extract (RC) contains isoflavones with superior bioavailability compared to non-fermented isoflavones, however little is known regarding the impact of isoflavones on cardiovascular and metabolic health. We assessed markers of vascular health in plasma and skeletal muscle samples obtained from healthy but sedentary early post-menopausal women (n = 10; 54 ± 4 years) following 2 weeks of twice daily treatment with placebo (PLA) or RC (60 mg isoflavones per day). The two interventions were administered using a randomized, double-blind, crossover design with a two-week washout period. Plasma samples were utilized for assessment of markers of vascular inflammation. There was a statistically significant reduction (~5.4%) in vascular cell adhesion molecule 1 (VCAM-1) following 2 weeks of RC supplementation compared to PLA (p = 0.03). In contrast, there was no effect of RC supplementation compared to PLA on skeletal muscle estrogen receptor content and enzymes related to vascular function, and angiogenesis. Supplementation with RC reduces vascular inflammation in early post-menopausal women and future studies should address the long-term impact of daily supplementation with RC after menopause.
Targeted Delivery for Cardiac Regeneration: Comparison of Intra-coronary Infusion and Intra-myocardial Injection in Porcine Hearts
Authors: Vekstein Andrew M. , Wendell David C. , DeLuca Sophia , Yan Ruorong , Chen Yifan , Bishawi Muath , Devlin Garth W. , Asokan Aravind , Poss Kenneth D. , Bowles Dawn E. , Williams Adam R. , Bursac Nenad
Published: February 2022

Background

The optimal delivery route to enhance effectiveness of regenerative therapeutics to the human heart is poorly understood. Direct intra-myocardial (IM) injection is the gold standard, however, it is relatively invasive. We thus compared targeted IM against less invasive, catheter-based intra-coronary (IC) delivery to porcine myocardium for the acute retention of nanoparticles using cardiac magnetic resonance (CMR) imaging and viral vector transduction using qPCR.

Methods

Ferumoxytol iron oxide (IO) nanoparticles (5 ml) were administered to Yorkshire swine (n = 13) by: (1) IM via thoracotomy, (2) catheter-based IC balloon-occlusion (BO) with infusion into the distal left anterior descending (LAD) coronary artery, (3) IC perforated side-wall (SW) infusion into the LAD, or (4) non-selective IC via left main (LM) coronary artery infusion. Hearts were harvested and imaged using at 3T whole-body MRI scanner. In separate Yorkshire swine (n = 13), an adeno-associated virus (AAV) vector was similarly delivered, tissue harvested 4–6 weeks later, and viral DNA quantified from predefined areas at risk (apical LV/RV) vs. not at risk in a potential mid-LAD infarct model. Results were analyzed using pairwise Student's t-test.

Results

IM delivery yielded the highest IO retention (16.0 ± 4.6% of left ventricular volume). Of the IC approaches, BO showed the highest IO retention (8.7 ± 2.2% vs. SW = 5.5 ± 4.9% and LM = 0%) and yielded consistent uptake in the porcine distal LAD territory, including the apical septum, LV, and RV. IM delivery was limited to the apex and anterior wall, without septal retention. For the AAV delivery, the BO was most efficient in the at risk territory (Risk: BO = 6.0 × 10−9, IM = 1.4 × 10−9, LM = 3.2 × 10−10 viral copies per μg genomic DNA) while all delivery routes were comparable in the non-risk territory (BO = 1.7 × 10−9, IM = 8.9 × 10−10, LM = 1.2 × 10−9).

Conclusions

Direct IM injection has the highest local retention, while IC delivery with balloon occlusion and distal infusion is the most effective IC delivery technique to target therapeutics to a heart territory most in risk from an infarct.
Generational Perspectives on Technology's Role in Mental Health Care: A Survey of Adults With Lived Mental Health Experience
Authors: Woerner Molly , Sams Nichole , Rivera Nales Cristian , Gorstein Tara , Johnson Morgan , Mosser Brittany A. , Areán Patricia A.
Published: February 2022

Introduction

Personal technology (e.g., smartphones, wearable health devices) has been leveraged extensively for mental health purposes, with upwards of 20,000 mobile applications on the market today and has been considered an important implementation strategy to overcome barriers many people face in accessing mental health care. The main question yet to be addressed is the role consumers feel technology should play in their care. One underserved demographic often ignored in this discussion are people over the age of 60. The population of adults 60 and older is predicted to double by 2,050 signaling a need to address how older adults view technology for their mental health care.

Objective

The objective of this study is to better understand why digital mental health tools are not as broadly adopted as predicted, what role people with lived mental health experience feel technology should play in their care and how those results compare across age groups.

Method

In a mixed-methods approach, we analyzed results from a one-time cross-sectional survey that included 998 adults aged 18–83 with lived experience of mental health concerns recruited from Prolific, an online research platform. We surveyed participant's use of technology including their perspectives on using technology in conjunction with their mental health care. We asked participants about their previous use of digital mental health tools, their treatment preferences for mental health care, and the role technology should play in their mental health care.

Results

Across all age groups, respondents had favorable views of using digital mental health for managing mental health care. However, older adults rated their acceptability of digital mental health tools lower than middle-aged and younger adults. When asked what role technology should play in mental health care in an open-ended response, most participants responded that technology should play a complementary role in mental health care (723/954, 75.8%).

Conclusion

Digital mental health is seen as a valuable care management tool across all age groups, but preferences for its role in care remain largely administrative and supportive. Future development of digital mental health should reflect these preferences.
The Huapinghsu Channel/Mienhua Canyon System as a Sediment Conduit Transporting Sediments From Offshore North Taiwan to the Southern Okinawa Trough
Authors: Chiang Cheng-Shing , Yu Ho-Shing , Noda Atsushi , TuZino Taqumi
Published: February 2022

By examining bathymetric and seismic reflection data in the shelf-slope region offshore northeast of Taiwan, the morphology of the Huapinghsu Channel/Mienhua Canyon System was refined and the occurrence of axial incision in the major erosional trough of the Mienhua Canyon was identified. The Huapinghsu Channel extends from its head at a water depth of 120 m seaward across the shelf-slope region and merges with the Mienhua Canyon before finally emptying into the Southern Okinawa Trough. This review with a new idea illustrates this channel/canyon system as a sediment conduit transporting sediments from western Taiwan rivers to the Southern Okinawa Trough. Within the proximal reach of the Mienhua Canyon, in situ suspended particles were found associated with bottom nepheloid layers, which transport resuspended particles along the canyon course, and eventually into the Southern Okinawa Trough even during sea-level highstand. The shelf area around the channel head is subject to the influence of frequent occurrences of large typhoons and seasonal migrations of oceanic currents. Numerical examinations indicate that the flow velocities related with large waves or currents satisfy the critical values to the threshold of the motion of fine sand, implying gravity flows occur around the channel head, sweep unconsolidated sediments in the channel head, or even incise the channel floor at the present day. In this paper, sea level changes from the Last Glacial Maximum (LGM, ∼21 ka BP) to the present and sediment input to the head of the Huapinghsu Channel head are considered the major factors in the control of the Huapinghsu Channel/Mienhua Canyon system, which functions as a sediment conduit in the study area. Tectonics and climate are the minor factors that contribute to shelf sediment transport to the Southern Okinawa Trough via this channel/canyon system.
Structural Evolution and Motion Characteristics of a Hard Roof During Thickening Coal Seam Mining
Authors: Zhang Xiangyang , Zhao Xiangyang , Luo Lei
Published: February 2022

This study combined theoretical analysis, physical simulation, and numerical simulation to discuss the influences of the structural evolution and motion characteristics of a hard roof during thickening coal seam mining on working face pressure. Results showed that during the mining of the thickening coal seam with a hard roof, the settlement curve of low-level strata was a stepwise wave slope, and the settlement curve of high-level strata shifted from a “V-shaped” distribution pattern to a parabola under the full mining of the coal seam. When the mining thickness was relatively small, the mining space expanded with the increase in mining thickness due to the “masonry beam” structure formed by the low-level, sub-critical overlying strata. The low-level critical strata formed a “composite cantilever beam” structure with a hard immediate roof after advancing into the caving zone. After complete recovery, the overlying strata were in a steady-movement state, and the plastic failure zone of the overlying strata of the thickening coal seam presented obvious distribution characteristics of longitudinal and transverse partitions. This study provides theoretical reference for coal seam mining under similar geological conditions.
Simulation of Rapid Intensification of Super Typhoon Lekima (2019). Part II: The Critical Role of Cloud-Radiation Interaction of Asymmetric Convection
Authors: Huang Qijun , Ge Xuyang , Bi Mingyu
Published: February 2022

In this study, super typhoon Lekima (2019) with an atypical rapid intensification (RI) episode is investigated by conducting a pair of experiments. In the control experiment, the model reproduces reasonably well the evolution characteristics of convective activity and intensity changes. That is, active downshear-left convection moved counterclockwise to the upshear flank. In the sensitivity experiment without the cloud-radiation feedback (CRF), the simulation fails to capture the observed upshear deep convection and the RI process. Our analyses suggest that the cloud–radiation interaction acts as positive feedback between the tilting-induced convective asymmetry (TCA) and outflow channel. On the one hand, the radiative process will induce upper (lower) cooling (warming) above (within) the cloud anvil of the outflow layer. This thermodynamical pattern locally destabilizes the upper troposphere and is conducive to enhance the deep convection. On the other hand, the enhanced deep convection provides the energy source to promote the upper divergent flows. The stronger divergent flow acts efficiently to block the vertical wind shear (VWS) and leads to a stronger outflow channel. This CRF assists in the development of a thicker and more radially extensive outflow than that CRF-off simulation. This study further confirms the outflow blocking effect, which gains insights on the evolution of upshear-left asymmetric convection and its role in the atypical RI event.
The Antarctic Marginal Ice Zone and Pack Ice Area in CMEMS GREP Ensemble Reanalysis Product
Authors: Iovino Doroteaciro , Selivanova Julia , Masina Simona , Cipollone Andrea
Published: February 2022

Global ocean reanalyses provide consistent and comprehensive records of ocean and sea ice variables and are therefore of pivotal significance for climate studies, particularly in data-sparse regions such as Antarctica. Here, for the first time, we present the temporal and spatial variability of sea ice area in the ensemble of global ocean reanalyses produced by the Copernicus Marine Environment Monitoring Service (CMEMS) for the period 1993–2019. The reanalysis ensemble robustly reproduces observed interannual and seasonal variability, linear trend, as well as record highs and lows. While no consensus has been reached yet on the physical source of Antarctic-wide ice changes, our study also emphasizes the importance of understanding the different responses of ice classes, marginal ice zone (MIZ) and pack ice, to climate changes. Modifications of the distribution of MIZ and pack ice have implications for the level of air/sea exchanges and for the marine ecosystem. Analysis of the spatial and temporal variability of ice classes can provide further insights on long-term trends and help to improve predictions of future changes in Antarctic sea ice. We assess the ability of the reanalysis ensemble to adequately capture variability in space and time of the MIZ and pack ice area, and conclude that it can provide consistent estimates of recent changes in the Antarctic sea ice area. Our results show that the Antarctic sea ice area agrees well with satellite estimates, and the hemispheric and regional sea ice area variability are properly reproduced on seasonal and interannual time scales. Although the ensemble reanalysis product tends to slightly overestimate MIZ in summer, results show that it properly represents the variability of MIZ minima and maxima as well as its interannual variability during the growing and melting seasons. Our results confirm that Global Reanalysis Ensemble Product is able to reproduce the observed substantial regional variability, in regions covered by marginal ice.
The Early Cretaceous Zaduo Granite, Eastern Qiangtang Terrane (China)—An Attempt to Constrain its Paleolatitude and Tectonic Implications
Authors: Fu Qiang , Yan Maodu , Dekkers Mark J. , Guan Chong , de Boer Rosa A. , Yu Liang , Xu Wanlong , Li Bingshuai , Shen Miaomiao , Zhang Jingyu , Xu Zunbo
Published: February 2022

The Eastern Qiangtang Terrane is an orogenic-like belt around the Eastern Himalayan syntaxis (EHS). The deformation history of this terrane must be known to understand how the EHS region responded to the Lhasa-Qiangtang collision and the closure of the Bangong-Nujiang Ocean (BNO). Here, we present a new paleomagnetic investigation on an Early Cretaceous granite (∼126 Ma) in the Zaduo area, Eastern Qiangtang Terrane. Petrographic observations reflect crystallization from primary melts with only limited subsequent alteration (chloritization of biotite). Magnetite appears to be the dominant carrier of the characteristic remanent magnetization (ChRM) based on stepwise demagnetization of the natural remanent magnetization, supplemented by detailed rock magnetic measurements, including magnetization versus temperature, and acquisition curves of the isothermal and anhysteretic remanent magnetization. End-member modeling of those acquisition curves helped to constrain the paleomagnetic analysis. The inconsistent demagnetization behavior between alternating field (AF) demagnetization at high levels and thermal demagnetization was attributed to the development of gyroremanent magnetization in the AF demagnetization generated by fine-grained single domain magnetite. The ChRM directions from 92 granite samples in geographic coordinates yield an average of declination (Dg) of 2.6° and inclination (Ig) of 38.6° (precision parameter k = 51.4, and 95% confidence cone α95 = 2.1°). The amount of tilting of the granite is poorly constrained which makes proper correction rather tedious. We compared the expected bedding attitudes (Strikeexp = 43.1°, Dipexp = 46.1°) derived from published data (Huang et al., 1992;Tong et al., 2015) with the average observed bedding attitudes (Strikeobs = 54°, Dipobs = 32°) of the Middle-Upper Jurassic sandstones of the Yanshiping Group that was intruded by the Early Cretaceous granite. The discrepancy between the expected and measured bedding attitudes implies that the strata of the Yanshiping Group in the Zaduo area were already tilted prior to the intrusion of the ∼126 Ma Zaduo granite, which was attributed to the Lhasa-Qiangtang collision and the closure of the BNO. The collision led to a series of geological events, such as the tilting of the strata, the ophiolite emplacement, the development of a peripheral foreland basin, and the magmatic activity gap. The tilting/folding of the strata was generally delayed by the layer parallel shortening processes during the early stages of the deformation, thus suggesting an older Lhasa-Qiangtang collision (i.e., >126 Ma).