bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Verification of an Adjustment Factor for Determining the Axial Length Using Optical Biometry in Silicone Oil-Filled Eyes
Authors: Auffarth Gerd U. , Naujokaitis Tadas , Blöck Louise , Daghbashyan Anna , Meis Jan , Augustin Victor A. , Khoramnia Ramin , Yildirim Timur M.
Published: January 2022

The aim of this prospective clinical study was to establish and verify an adaptation for axial length (AL) measurement in silicone oil (SO)-filled pseudophakic eyes with a Scheimpflug and partial coherence interferometry (PCI)-based biometer. The AL was measured with a Pentacam AXL (OCULUS Optikgeräte GmbH, Wetzler, Germany) and IOLMaster 700 (Carl Zeiss Meditec, Jena, Germany). The coefficients of variation (CoV) and the mean systematic difference (95% confidence interval (CI)) between the devices were calculated. After implementing a setting for measuring AL in tamponaded eyes with a Pentacam based on data of 29 eyes, another 12 eyes were examined for verification. The mean AL obtained with the Pentacam was 25.53 ± 1.94 mm (range: 21.70 to 30.76 mm), and with IOLMaster, 24.73 ± 1.97 mm (ranged 20.84 to 29.92 mm), resulting in a mean offset of 0.80 ± 0.08 mm (95% CI: 0.77, 0.83 mm), p < 0.001. The AL values of both devices showed a strong linear correlation (r = 0.999). Verification data confirmed good agreement, with a statistically and clinically non-significant mean difference of 0.02 ± 0.04 (95% CI: −0.01, 0.05) mm, p = 0.134. We implemented a specific adaptation for obtaining reliable AL values in SO-filled eyes with the Pentacam AXL.
Bias Investigation in Artificial Intelligence Systems for Early Detection of Parkinson’s Disease: A Narrative Review
Authors: Paul Sudip , Maindarkar Maheshrao , Saxena Sanjay , Saba Luca , Turk Monika , Kalra Manudeep , Krishnan Padukode R. , Suri Jasjit S.
Published: January 2022

Background and Motivation: Diagnosis of Parkinson’s disease (PD) is often based on medical attention and clinical signs. It is subjective and does not have a good prognosis. Artificial Intelligence (AI) has played a promising role in the diagnosis of PD. However, it introduces bias due to lack of sample size, poor validation, clinical evaluation, and lack of big data configuration. The purpose of this study is to compute the risk of bias (RoB) automatically. Method: The PRISMA search strategy was adopted to select the best 39 AI studies out of 85 PD studies closely associated with early diagnosis PD. The studies were used to compute 30 AI attributes (based on 6 AI clusters), using AP(ai)Bias 1.0 (AtheroPointTM, Roseville, CA, USA), and the mean aggregate score was computed. The studies were ranked and two cutoffs (Moderate-Low (ML) and High-Moderate (MH)) were determined to segregate the studies into three bins: low-, moderate-, and high-bias. Result: The ML and HM cutoffs were 3.50 and 2.33, respectively, which constituted 7, 13, and 6 for low-, moderate-, and high-bias studies. The best and worst architectures were “deep learning with sketches as outcomes” and “machine learning with Electroencephalography,” respectively. We recommend (i) the usage of power analysis in big data framework, (ii) that it must undergo scientific validation using unseen AI models, and (iii) that it should be taken towards clinical evaluation for reliability and stability tests. Conclusion: The AI is a vital component for the diagnosis of early PD and the recommendations must be followed to lower the RoB.
A Survey on Data-Driven Learning for Intelligent Network Intrusion Detection Systems
Authors: Abdelmoumin Ghada , Whitaker Jessica , Rawat Danda B. , Rahman Abdul
Published: January 2022

An effective anomaly-based intelligent IDS (AN-Intel-IDS) must detect both known and unknown attacks. Hence, there is a need to train AN-Intel-IDS using dynamically generated, real-time data in an adversarial setting. Unfortunately, the public datasets available to train AN-Intel-IDS are ineluctably static, unrealistic, and prone to obsolescence. Further, the need to protect private data and conceal sensitive data features has limited data sharing, thus encouraging the use of synthetic data for training predictive and intrusion detection models. However, synthetic data can be unrealistic and potentially bias. On the other hand, real-time data are realistic and current; however, it is inherently imbalanced due to the uneven distribution of anomalous and non-anomalous examples. In general, non-anomalous or normal examples are more frequent than anomalous or attack examples, thus leading to skewed distribution. While imbalanced data are commonly predominant in intrusion detection applications, it can lead to inaccurate predictions and degraded performance. Furthermore, the lack of real-time data produces potentially biased models that are less effective in predicting unknown attacks. Therefore, training AN-Intel-IDS using imbalanced and adversarial learning is instrumental to their efficacy and high performance. This paper investigates imbalanced learning and adversarial learning for training AN-Intel-IDS using a qualitative study. It surveys and synthesizes generative-based data augmentation techniques for addressing the uneven data distribution and generative-based adversarial techniques for generating synthetic yet realistic data in an adversarial setting using rapid review, structured reporting, and subgroup analysis.
Estimation of the Energy Consumption of an All-Terrain Mobile Manipulator for Operations in Steep Vineyards
Authors: Hrabar Ivan , Vasiljević Goran , Kovačić Zdenko
Published: January 2022

A heterogeneous robotic system that can perform various tasks in the steep vineyards of the Mediterranean region was developed and tested as part of the HEKTOR—Heterogeneous Autonomous Robotic System in Viticulture and Mariculture—project. This article describes the design of hardware and an easy-to-use method for evaluating the energy consumption of the system, as well as, indirectly, its deployment readiness level. The heterogeneous robotic system itself consisted of a flying robot—a light autonomous aerial robot (LAAR)—and a ground robot—an all-terrain mobile manipulator (ATMM), composed of an all-terrain mobile robot (ATMR) platform and a seven-degree-of-freedom (DoF) torque-controlled robotic arm. A formal approach to describe the topology and parameters of selected vineyards is presented. It is shown how Google Earth data can be used to make an initial estimation of energy consumption for a selected vineyard. On this basis, estimates of energy consumption were made for the tasks of protective spraying and bud rubbing. The experiments were conducted in two different vineyards, one with a moderate slope and the other with a much steeper slope, to evaluate the proposed estimation method.
Responses of Larix principis-rupprechtii Radial Growth to Climatic Factors at Different Elevations on Guancen Mountain, North-Central China
Authors: Wang Jiachuan , Li Shuheng , Guo Yili , Yang Qi , Ren Rui , Han Yijie
Published: January 2022

Larix principis-rupprechtii is an important afforestation tree species in the North China alpine coniferous forest belt. Studying the correlations and response relationships between Larix principis-rupprechtii radial growth and climatic factors at different elevations is helpful for understanding the growth trends of L. principis-rupprechtiind its long-term sensitivity and adaptability to climate change. Pearson correlation, redundancy (RDA), and sliding analysis were performed to study the correlations and dynamic relationships between radial growth and climatic factors. The main conclusions are as follows: (1) The three-elevation standard chronologies all exhibited high characteristic values, contained rich climate information and were suitable for tree-ring climatological analyses. (2) Both temperature and precipitation restricted low-elevation L. principis-rupprechtii radial growth, while monthly maximum temperatures mainly affected mid-high-elevation L. principis-rupprechtii radial growth. (3) Mid-elevation L. principis-rupprechtii radial growth responded to climate factors with a “lag effect” and was not restricted by spring and early summer drought. (4) Long-term sliding analysis showed that spring temperatures and winter precipitation were the main climatic factors restricting L. principis-rupprechtii growth under warming and drying climate trends at different elevations. The tree-ring width index and Palmer drought severity index (PDSI) were positively correlated, indicating that L. principis-rupprechtii growth is somewhat restricted by drought. These results provide a reference and guidance for L. principis-rupprechtii management and sustainable development in different regions under warming and drying background climate trends.
Quantifying Drought Resistance of Drylands in Northern China from 1982 to 2015: Regional Disparity in Drought Resistance
Authors: Wei Maohong , Li Hailing , Akram Muhammad Adnan , Dong Longwei , Sun Ying , Hu Weigang , Gong Haiyang , Zhao Dongmin , Xiong Junlan , Yao Shuran , Sun Yuan , Hou Qingqing , Zhang Yahui , Wang Xiaoting , Xie Shubin , Deng Yan , Zhang Liang , Degen Abraham Allan , Ran Jinzhi , Deng Jianming
Published: January 2022

Drylands are expected to be affected by greater global drought variability in the future; consequently, how dryland ecosystems respond to drought events needs urgent attention. In this study, the Normalized Vegetation Index (NDVI) and Standardized Precipitation and Evaporation Index (SPEI) were employed to quantify the resistance of ecosystem productivity to drought events in drylands of northern China between 1982 and 2015. The relationships and temporal trends of resistance and drought characteristics, which included length, severity, and interval, were examined. The temporal trends of resistance responded greatest to those of drought length, and drought length was the most sensitive and had the strongest negative effect with respect to resistance. Resistance decreased with increasing drought length and did not recover with decreasing drought length in hyper-arid regions after 2004, but did recover in arid and semi-arid regions from 2004 and in dry sub-humid regions from 1997. We reason that the regional differences in resistance may result from the seed bank and compensatory effects of plant species under drought events. In particular, this study implies that the ecosystem productivity of hyper-arid regions is the most vulnerable to drought events, and the drought–resistance and drought–recovery interactions are likely to respond abnormally or even shift under ongoing drought change.
Three Millennia of Vegetation, Land-Use, and Climate Change in SE Sicily
Authors: Michelangeli Fabrizio , Di Rita Federico , Celant Alessandra , Tisnérat-Laborde Nadine , Lirer Fabrizio , Magri Donatella
Published: January 2022

This study presents the first Late Holocene marine pollen record (core ND2) from SE Sicily. It encompasses the last 3000 years and is one of the most detailed records of the south-central Mediterranean region in terms of time resolution. The combined approach of marine palynology and historical ecology, supported by independent palaeoclimate proxies, provides an integrated regional reconstruction of past vegetational dynamics in relation to rapid climatic fluctuations, historical socio-economic processes, and past land-use practices, offering new insights into the vegetation history of SE Sicily. Short-term variations of sparse tree cover in persistently open landscapes reflect rapid hydroclimatic changes and historical land-use practices. Four main phases of forest reduction are found in relation to the 2.8 ka BP event, including the Late Antique Little Ice Age, the Medieval Climate Anomaly, and the Little Ice Age, respectively. Forest recovery is recorded during the Hellenistic and Roman Republican Periods, the Early Middle Ages, and the last century. Agricultural and silvicultural practices, as well as stock-breeding activities, had a primary role in shaping the current vegetational landscape of SE Sicily.
Stand Composition, Tree-Related Microhabitats and Birds—A Network of Relationships in a Managed Forest
Authors: Piechnik Łukasz , Holeksa Jan , Ledwoń Mateusz , Kurek Przemysław , Szarek-Łukaszewska Grażyna , Żywiec Magdalena
Published: January 2022

Forest ecosystems contain many tree-related microhabitats (TreMs), which are used by various groups of organisms. Birds use TreMs for shelter, foraging and breeding. The abundance and variability of TreMs is related to tree stand composition and age. Over the last few centuries there has been a drastic decline in the structural and biological diversity of temperate forests over large areas of the Northern Hemisphere. These changes have reduced the diversity and quantity of TreMs. In this study we showed the relationships between stand composition, the abundance of TreMs, and the species richness of birds in a managed forest. We focused on TreMs that are important to birds: woodpecker breeding cavities, rot holes, dead branches, broken treetops, and perennial polypores. Our study was performed in a managed lowland temperate forest. In 94 plots (10 ha each) we made bird surveys and inventoried the stand composition and TreMs. Our results show that the tree stand composition of a managed forest affects the abundance of TreMs. The share of deciduous trees in the stand favors the occurrence of such TreMs as dead branches, rot holes and perennial polypores. The overall richness of bird species and the species richness of primary cavity nesters depended on the total basal area of oak, hornbeam and birch, whereas the species richness of secondary cavity nesters increased with the total basal area of birch and oak.
Elucidating Hexanucleotide Repeat Number and Methylation within the X-Linked Dystonia-Parkinsonism (XDP)-Related SVA Retrotransposon in TAF1 with Nanopore Sequencing
Authors: Lüth Theresa , Laβ Joshua , Schaake Susen , Wohlers Inken , Pozojevic Jelena , Jamora Roland Dominic G. , Rosales Raymond L. , Brüggemann Norbert , Saranza Gerard , Diesta Cid Czarina E. , Schlüter Kathleen , Tse Ronnie , Reyes Charles Jourdan , Brand Max , Busch Hauke , Klein Christine , Westenberger Ana , Trinh Joanne
Published: January 2022

Background: X-linked dystonia-parkinsonism (XDP) is an adult-onset neurodegenerative disorder characterized by progressive dystonia and parkinsonism. It is caused by a SINE-VNTR-Alu (SVA) retrotransposon insertion in the TAF1 gene with a polymorphic (CCCTCT)n domain that acts as a genetic modifier of disease onset and expressivity. Methods: Herein, we used Nanopore sequencing to investigate SVA genetic variability and methylation. We used blood-derived DNA from 96 XDP patients for amplicon-based deep Nanopore sequencing and validated it with fragment analysis which was performed using fluorescence-based PCR. To detect methylation from blood- and brain-derived DNA, we used a Cas9-targeted approach. Results: High concordance was observed for hexanucleotide repeat numbers detected with Nanopore sequencing and fragment analysis. Within the SVA locus, there was no difference in genetic variability other than variations of the repeat motif between patients. We detected high CpG methylation frequency (MF) of the SVA and flanking regions (mean MF = 0.94, SD = ±0.12). Our preliminary results suggest only subtle differences between the XDP patient and the control in predicted enhancer sites directly flanking the SVA locus. Conclusions: Nanopore sequencing can reliably detect SVA hexanucleotide repeat numbers, methylation and, lastly, variation in the repeat motif.
Understanding the Quadruple Flutes of Teotihuacan, Mexico
Authors: Both Arnd Adje
Published: January 2022

This paper presents the results of a study on the quadruple flutes (multiple pipes) from the UNESCO World Heritage Centre of Teotihuacan, Mexico, based on a thorough examination of the fragmented, restored and partly reconstructed archaeological finds and the manufacture and subsequent test of a series of playable reproductions with a refined reconstructive design. For the latter, organological features, such as the diameter, number and position of the fingerholes/tone holes and the length of the individual pipes of the restored finds are challenged and a new design is proposed that might be closer to the original construction of the Teotihuacan instruments. The study reveals a better understanding of the particular construction, acoustics and musical possibilities of the Teotihuacan quadruple flutes.
Correction: Yang et al. Influence of Relief Degree of Land Surface on Street Network Complexity in China. ISPRS Int. J. Geo-Inf. 2021, 10, 705
Authors: Yang Nai , Jiang Le , Chao Yi , Li Yang , Liu Pengcheng
Published: January 2022

In the original publication [...]
A Pricing Model for Urban Rental Housing Based on Convolutional Neural Networks and Spatial Density: A Case Study of Wuhan, China
Authors: Shen Hang , Li Lin , Zhu Haihong , Li Feng
Published: January 2022

With the development of urbanization and the expansion of floating populations, rental housing has become an increasingly common living choice for many people, and housing rental prices have attracted great attention from individuals, enterprises and the government. The housing rental prices are principally estimated based on structural, locational and neighborhood variables, among which the relationships are complicated and can hardly be captured entirely by simple one-dimensional models; in addition, the influence of the geographic objects on the price may vary with the increase in their quantities. However, existing pricing models usually take those structural, locational and neighborhood variables as one-dimensional inputs into neural networks, and often neglect the aggregated effects of geographical objects, which may lead to fluctuating rental price estimations. Therefore, this paper proposes a rental housing price model based on the convolutional neural network (CNN) and the synthetic spatial density of points of interest (POIs). The CNN can efficiently extract the complex characteristics among the relevant variables of housing, and the two-dimensional locational and neighborhood variables, based on the synthetic spatial density, effectively reflect the aggregated effects of the urban facilities on rental housing prices, thereby improving the accuracy of the model. Taking Wuhan, China, as the study area, the proposed method achieves satisfactory and accurate rental price estimations (coefficient of determination (R2) = 0.9097, root mean square error (RMSE) = 3.5126) in comparison with other commonly used pricing models.
Seipin Deficiency as a Model of Severe Adipocyte Dysfunction: Lessons from Rodent Models and Teaching for Human Disease
Authors: Magré Jocelyne , Prieur Xavier
Published: January 2022

Obesity prevalence is increasing worldwide, leading to cardiometabolic morbidities. Adipocyte dysfunction, impairing white adipose tissue (WAT) expandability and metabolic flexibility, is central in the development of obesity-related metabolic complications. Rare syndromes of lipodystrophy characterized by an extreme paucity of functional adipose tissue should be considered as primary adipocyte dysfunction diseases. Berardinelli-Seip congenital lipodystrophy (BSCL) is the most severe form with a near absence of WAT associated with cardiometabolic complications such as insulin resistance, liver steatosis, dyslipidemia, and cardiomyopathy. Twenty years ago, mutations in the BSCL2 gene have been identified as the cause of BSCL in human. BSCL2 encodes seipin, an endoplasmic reticulum (ER) anchored protein whose function was unknown back then. Studies of seipin knockout mice or rats demonstrated how seipin deficiency leads to severe lipodystrophy and to cardiometabolic complications. At the cellular levels, seipin is organized in multimers that are particularly enriched at ER/lipid droplet and ER/mitochondria contact sites. Seipin deficiency impairs both adipocyte differentiation and mature adipocyte maintenance. Experiments using adipose tissue transplantation in seipin knockout mice and tissue-specific deletion of seipin have provided a large body of evidence that liver steatosis, cardiomyopathy, and renal injury, classical diabetic complications, are all consequences of lipodystrophy. Rare adipocyte dysfunctions such as in BSCL are the key paradigm to unravel the pathways that control adipocyte homeostasis. The knowledge gathered through the study of these pathologies may bring new strategies to maintain and improve adipose tissue expandability.
Novel Mechanism by a Bis-Pyridinium Fullerene Derivative to Induce Apoptosis by Enhancing the MEK-ERK Pathway in a Reactive Oxygen Species-Independent Manner in BCR-ABL-Positive Chronic Myeloid Leukemia-Derived K562 Cells
Authors: Sumi Kazuya , Tago Kenji , Nakazawa Yosuke , Takahashi Kyoko , Ohe Tomoyuki , Mashino Tadahiko , Funakoshi-Tago Megumi
Published: January 2022

In the treatment of breakpoint cluster region-Abelson (BCR-ABL)-positive chronic myeloid leukemia (CML) using BCR-ABL inhibitors, the appearance of a gatekeeper mutation (T315I) in BCR-ABL is a serious issue. Therefore, the development of novel drugs that overcome acquired resistance to BCR-ABL inhibitors by CML cells is required. We previously demonstrated that a bis-pyridinium fullerene derivative (BPF) induced apoptosis in human chronic myeloid leukemia (CML)-derived K562 cells partially through the generation of reactive oxygen species (ROS). We herein show that BPF enhanced the activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase (MEK-ERK) pathway in a ROS-independent manner. BPF-induced apoptosis was attenuated by trametinib, suggesting the functional involvement of the MEK-ERK pathway in apoptosis in K562 cells. In addition, the constitutive activation of the MEK-ERK pathway by the enforced expression of the BRAFV600E mutant significantly increased the sensitivity of K562 cells to BPF. These results confirmed for the first time that BPF induces apoptosis in K562 cells through dual pathways—ROS production and the activation of the MEK-ERK pathway. Furthermore, BPF induced cell death in transformed Ba/F3 cells expressing not only BCR-ABL but also T315I mutant through the activation of the MEK-ERK pathway. These results indicate that BPF is as an effective CML drug that overcomes resistance to BCR-ABL inhibitors.
DNA Methylation and Non-Coding RNAs during Tissue-Injury Associated Pain
Authors: Irfan Jahanzaib , Febrianto Muhammad Rizki , Sharma Anju , Rose Thomas , Mahmudzade Yasamin , Di Giovanni Simone , Nagy Istvan , Torres-Perez Jose Vicente
Published: January 2022

While about half of the population experience persistent pain associated with tissue damages during their lifetime, current symptom-based approaches often fail to reduce such pain to a satisfactory level. To provide better patient care, mechanism-based analgesic approaches must be developed, which necessitates a comprehensive understanding of the nociceptive mechanism leading to tissue injury-associated persistent pain. Epigenetic events leading the altered transcription in the nervous system are pivotal in the maintenance of pain in tissue injury. However, the mechanisms through which those events contribute to the persistence of pain are not fully understood. This review provides a summary and critical evaluation of two epigenetic mechanisms, DNA methylation and non-coding RNA expression, on transcriptional modulation in nociceptive pathways during the development of tissue injury-associated pain. We assess the pre-clinical data and their translational implication and evaluate the potential of controlling DNA methylation and non-coding RNA expression as novel analgesic approaches and/or biomarkers of persistent pain.
SiMYB19 from Foxtail Millet (Setaria italica) Confers Transgenic Rice Tolerance to High Salt Stress in the Field
Authors: Xu Chengjie , Luo Mingzhao , Sun Xianjun , Yan Jiji , Shi Huawei , Yan Huishu , Yan Rongyue , Wang Shuguang , Tang Wensi , Zhou Yongbin , Wang Chunxiao , Xu Zhaoshi , Chen Jun , Ma Youzhi , Jiang Qiyan , Chen Ming , Sun Daizhen
Published: January 2022

Salt stress is a major threat to crop quality and yield. Most experiments on salt stress-related genes have been conducted at the laboratory or greenhouse scale. Consequently, there is a lack of research demonstrating the merit of exploring these genes in field crops. Here, we found that the R2R3-MYB transcription factor SiMYB19 from foxtail millet is expressed mainly in the roots and is induced by various abiotic stressors such as salt, drought, low nitrogen, and abscisic acid. SiMYB19 is tentatively localized to the nucleus and activates transcription. It enhances salt tolerance in transgenic rice at the germination and seedling stages. SiMYB19 overexpression increased shoot height, grain yield, and salt tolerance in field- and salt pond-grown transgenic rice. SiMYB19 overexpression promotes abscisic acid (ABA) accumulation in transgenic rice and upregulates the ABA synthesis gene OsNCED3 and the ABA signal transduction pathway-related genes OsPK1 and OsABF2. Thus, SiMYB19 improves salt tolerance in transgenic rice by regulating ABA synthesis and signal transduction. Using rice heterologous expression analysis, the present study introduced a novel candidate gene for improving salt tolerance and increasing yield in crops grown in saline-alkali soil.
The Roles of IL-22 and Its Receptor in the Regulation of Inflammatory Responses in the Brain
Authors: Lee Dahae , Jo Hyejung , Go Cheolhyeon , Jang Yoojin , Chu Naghyung , Bae Suhyun , Kang Dongmin , Kim Yejin , Kang Jae Seung
Published: January 2022

Interleukin (IL)-22 is a potent mediator of inflammatory responses. The IL-22 receptor consists of the IL-22Rα and IL-10Rβ subunits. Previous studies have shown that IL-22Rα expression is restricted to non-hematopoietic cells in the skin, pancreas, intestine, liver, lung, and kidney. Although IL-22 is involved in the development of inflammatory responses, there have been no reports of its role in brain inflammation. Here, we used RT-PCR, Western blotting, flow cytometry, immunohistochemical, and microarray analyses to examine the role of IL-22 and expression of IL-22Rα in the brain, using the microglial cell line, hippocampal neuronal cell line, and inflamed mouse brain tissue. Treatment of BV2 and HT22 cells with recombinant IL-22 increased the expression levels of the pro-inflammatory cytokines IL-6 and TNF-α, as well as cyclooxygenase (COX)-2 and prostaglandin E2. We also found that the JNK and STAT3 signaling pathways play an important role in IL-22-mediated increases in inflammatory mediators. Microarray analyses revealed upregulated expression of inflammation-related genes in IL-22-treated HT22 cells. Finally, we found that IL-22Rα is spontaneously expressed in the brain and is upregulated in inflamed mouse brain. Overall, our results demonstrate that interaction of IL-22 with IL-22Rα plays a role in the development of inflammatory responses in the brain.
Molecular Mechanisms of lncRNAs in the Dependent Regulation of Cancer and Their Potential Therapeutic Use
Authors: García-Padilla Carlos , Dueñas Ángel , García-López Virginio , Aránega Amelia , Franco Diego , Garcia-Martínez Virginio , López-Sánchez Carmen
Published: January 2022

Deep whole genome and transcriptome sequencing have highlighted the importance of an emerging class of non-coding RNA longer than 200 nucleotides (i.e., long non-coding RNAs (lncRNAs)) that are involved in multiple cellular processes such as cell differentiation, embryonic development, and tissue homeostasis. Cancer is a prime example derived from a loss of homeostasis, primarily caused by genetic alterations both in the genomic and epigenetic landscape, which results in deregulation of the gene networks. Deregulation of the expression of many lncRNAs in samples, tissues or patients has been pointed out as a molecular regulator in carcinogenesis, with them acting as oncogenes or tumor suppressor genes. Herein, we summarize the distinct molecular regulatory mechanisms described in literature in which lncRNAs modulate carcinogenesis, emphasizing epigenetic and genetic alterations in particular. Furthermore, we also reviewed the current strategies used to block lncRNA oncogenic functions and their usefulness as potential therapeutic targets in several carcinomas.
Silencing of ATP Synthase β Impairs Egg Development in the Leafhopper Scaphoideus titanus, Vector of the Phytoplasma Associated with Grapevine Flavescence Dorée
Authors: Ripamonti Matteo , Cerone Luca , Abbà Simona , Rossi Marika , Ottati Sara , Palmano Sabrina , Marzachì Cristina , Galetto Luciana
Published: January 2022

Scaphoideus titanus (Hemiptera: Cicadellidae) is the natural vector of Flavescence dorée phytoplasma, a quarantine pest of grapevine with severe impact on European viticulture. RNA interference (RNAi) machinery components are present in S. titanus transcriptome and injection of ATP synthase β dsRNAs into adults caused gene silencing, starting three days post injection (dpi) up to 20 dpi, leading to decrease cognate protein. Silencing of this gene in the closely related leafhopper Euscelidiusvariegatus previously showed female sterility and lack of mature eggs in ovaries. Here, alteration of developing egg morphology in S. titanus ovaries as well as overexpression of hexamerin transcript (amino acid storage protein) and cathepsin L protein (lysosome proteinase) were observed in dsATP-injected females. To evaluate RNAi-specificity, E.variegatus was used as dsRNA-receiving model-species. Different doses of two sets of dsRNA-constructs targeting distinct portions of ATP synthase β gene of both species induced silencing, lack of egg development, and female sterility in E. variegatus, indicating that off-target effects must be evaluated case by case. The effectiveness of RNAi in S. titanus provides a powerful tool for functional genomics of this non-model species and paves the way toward RNAi-based strategies to limit vector population, despite several technical and regulatory constraints that still need to be overcome to allow open field application.
Accumulation of Cytochrome b558 at the Plasma Membrane: Hallmark of Oxidative Stress in Phagocytic Cells
Authors: Owusu Stephenson B. , Dupré-Crochet Sophie , Bizouarn Tania , Houée-Levin Chantal , Baciou Laura
Published: January 2022

Neutrophils play a very key role in the human immune defense against pathogenic infections. The predominant players in this role during the activation of neutrophils are the release of cytotoxic agents stored in the granules and secretory vesicles and the massive production of reactive oxygen species (ROS) initiated by the enzyme NADPH oxidase. In addition, in living organisms, cells are continuously exposed to endogenous (inflammations, elevated neutrophil presence in the vicinity) and exogenous ROS at low and moderate levels (travels by plane, radiotherapy, space irradiation, blood banking, etc.). To study these effects, we used ROS induced by gamma radiation from low (0.2 Gy) to high (25 Gy) dose levels on PLB-985 cells from a myeloid cell line differentiated to neutrophil-like cells that are considered a good alternative to neutrophils. We determined a much longer lifetime of PLB-985 cells than that of neutrophils, which, as expected, decreased by increasing the irradiation dose. In the absence of any secondary stimulus, a very low production of ROS is detected with no significant difference between irradiated and non-irradiated cells. However, in phagocytosing cells, irradiation doses above 2 Gy enhanced oxidative burst in PLB-985 cells. Whatever the irradiation dose, NADPH oxidase devoid of its cytosolic regulatory units is observed at the plasma membrane in irradiated PLB-985 cells. This result is different from that observed for irradiated neutrophils in which irradiation also induced a translocation of regulatory subunits suggesting that the signal transduction mechanism or pathway operate differently in both cells.
Multiphoton Bleaching of Red Fluorescent Proteins and the Ways to Reduce It
Authors: Drobizhev Mikhail , Molina Rosana S. , Franklin Jacob
Published: January 2022

Red fluorescent proteins and biosensors built upon them are potentially beneficial for two-photon laser microscopy (TPLM) because they can image deeper layers of tissue, compared to green fluorescent proteins. However, some publications report on their very fast photobleaching, especially upon excitation at 750–800 nm. Here we study the multiphoton bleaching properties of mCherry, mPlum, tdTomato, and jREX-GECO1, measuring power dependences of photobleaching rates K at different excitation wavelengths across the whole two-photon absorption spectrum. Although all these proteins contain the chromophore with the same chemical structure, the mechanisms of their multiphoton bleaching are different. The number of photons required to initiate a photochemical reaction varies, depending on wavelength and power, from 2 (all four proteins) to 3 (jREX-GECO1) to 4 (mCherry, mPlum, tdTomato), and even up to 8 (tdTomato). We found that at sufficiently low excitation power P, the rate K often follows a quadratic power dependence, that turns into higher order dependence (K~Pα with α > 2) when the power surpasses a particular threshold P*. An optimum intensity for TPLM is close to the P*, because it provides the highest signal-to-background ratio and any further reduction of laser intensity would not improve the fluorescence/bleaching rate ratio. Additionally, one should avoid using wavelengths shorter than a particular threshold to avoid fast bleaching due to multiphoton ionization.
A Comparative Study of Users versus Non-Users’ Behavioral Intention towards M-Banking Apps’ Adoption
Authors: Saprikis Vaggelis , Avlogiaris Giorgos , Katarachia Androniki
Published: January 2022

The banking sector has been considered as one of the primary adopters of Information and Communications Technologies. Especially during the last years, they have invested a lot into the digital transformation of their business process. Concerning their retail customers, banks realized very early the great potential abilities to provide value added self-services functions via mobile devices, mainly smartphones to them; thus, they have invested a lot into m-banking apps’ functionality. Furthermore, the COVID-19 pandemic has brought out different ways for financial transactions and even more mobile users have taken advantage of m-banking app services. Thus, the purpose of this empirical paper is to investigate the determinants that impact individuals on adopting or not m-banking apps. Specifically, it examines two groups of individuals, users (adopters) and non-users (non-adopters) of m-banking apps, and aims to reveal if there are differences and similarities between the factors that impact them on adopting or not this type of m-banking services. To our knowledge, this is the second scientific attempt where these two groups of individuals have been compared on this topic. The paper proposes a comprehensive conceptual model by extending Venkatech’s et al. (2003) Unified Theory of Acceptance and Use of Technology (UTAUT) with ICT facilitators (i.e., reward and security) and ICT inhibitors (i.e., risk and anxiety), as well as the recommendation factor. However, this study intends to fill the research gap by investigating and proving for the first time the impact of social influence, reward and anxiety factors on behavioral intention, the relationship between risk and anxiety and the impact of behavioral intention on recommendation via the application of Confirmatory Factor Analysis and Structural Equation Modeling (SEM) statistical techniques. The results reveal a number of differences regarding the factors that impact or not these two groups towards m-banking app adoption; thus, it provides new insights regarding m-banking app adoption in a slightly examined scientific field. Thus, the study intends to assist the banking sector in better understanding their customers with the aim to formulate and apply customized m-business strategies and increase not only the adoption of m-banking apps but also the level of their further use.
Analgesia Nociception Index-Guided Remifentanil versus Standard Care during Propofol Anesthesia: A Randomized Controlled Trial
Authors: Sabourdin Nada , Burey Julien , Tuffet Sophie , Thomin Anne , Rousseau Alexandra , Al-Hawari Mossab , Taconet Clementine , Louvet Nicolas , Constant Isabelle
Published: January 2022

The clinical benefits to be expected from intraoperative nociception monitors are currently under investigation. Among these devices, the Analgesia Nociception-Index (ANI) has shown promising results under sevoflurane anesthesia. Our study investigated ANI-guided remifentanil administration under propofol anesthesia. We hypothesized that ANI guidance would result in reduced remifentanil consumption compared with standard management. This prospective, randomized, controlled, single-blinded, bi-centric study included women undergoing elective gynecologic surgery under target-controlled infusion of propofol and remifentanil. Patients were randomly assigned to an ANI or Standard group. In the ANI group, remifentanil target concentration was adjusted by 0.5 ng mL−1 steps every 5 min according to the ANI value. In the Standard group, remifentanil was managed according to standard practice. Our primary objective was to compare remifentanil consumption between the groups. Our secondary objectives were to compare the quality of anesthesia, postoperative analgesia and the incidence of chronic pain. Eighty patients were included. Remifentanil consumption was lower in the ANI group: 4.4 (3.3; 5.7) vs. 5.8 (4.9; 7.1) µg kg−1 h−1 (difference = −1.4 (95% CI, −2.6 to −0.2), p = 0.0026). Propofol consumption was not different between the groups. Postoperative pain scores were low in both groups. There was no difference in morphine consumption 24 h after surgery. The proportion of patients reporting pain 3 months after surgery was 18.8% in the ANI group and 30.8% in the Standard group (difference = −12.0 (95% CI, −32.2 to 9.2)). ANI guidance resulted in lower remifentanil consumption compared with standard practice under propofol anesthesia. There was no difference in short- or long-term postoperative analgesia.
On the Use of Hemadsorption with CytoSorb in Patients with Septic Shock. Comment on Kogelmann et al. First Evaluation of a New Dynamic Scoring System Intended to Support Prescription of Adjuvant CytoSorb Hemoadsorption Therapy in Patients with Septic Shock. J. Clin. Med. 2021, 10, 2939
Authors: Supady Alexander , Lepper Philipp M. , Duerschmied Daniel , Wengenmayer Tobias
Published: January 2022

With great interest we read the article by Klaus Kogelmann and co-authors on the “First Evaluation of a New Dynamic Scoring System Intended to Support Prescription of Adjuvant CytoSorb Hemoadsorption Therapy in Patients with Septic Shock” [...]
Comparative Analysis of Root Canal Dentin Removal Capacity of Two NiTi Endodontic Reciprocating Systems for the Root Canal Treatment of Primary Molar Teeth. An In Vitro Study
Authors: Faus-Llácer Vicente , Pulido Ouardi Dalia , Faus-Matoses Ignacio , Ruiz-Sánchez Celia , Zubizarreta-Macho Álvaro , Ortiz Anabella María Reyes , Faus-Matoses Vicente
Published: January 2022

The objective of the present study was to evaluate and compare the dentin removal capacity of Endogal Kids and Reciproc Blue NiTi alloy endodontic reciprocating systems for root canal treatments in primary second molar teeth via a micro-computed tomography (micro-CT) scan. Materials and Methods: Sixty root canal systems in fifteen primary second molar teeth were chosen and classified into one of the following study groups: A: EK3 Endogal Kids (n = 30) (EDG) and B. R25 Reciproc Blue (n = 30) (RB). Preoperative and postoperative micro-CT scans were uploaded into image processing software to analyze the changes in the volume of root canal dentin using a mathematical algorithm that enabled progressive differentiation between neighboring pixels after defining and segmenting the root canal systems in both micro-CT scans. Volumetric variations in the root canal system and the root canal third were calculated using a t-test for independent samples or a nonparametric Mann–Whitney–Wilcoxon test. Results: Statistically significant differences (p = 0.0066) in dentin removal capacity were found between the EDG (2.89 ± 1.26 mm3) and RB (1.22 ± 0.58 mm3) study groups for the coronal root canal third; however, no statistically significant differences were found for the middle (p = 0.4864) and apical (p = 0.6276) root canal thirds. Conclusions: Endogal and Reciproc Blue NiTi endodontic reciprocating systems showed similar capacity for the removal of root canal dentin, except for the coronal root canal third, in which the Reciproc Blue NiTi endodontic reciprocating system preserved more root canal dentin tissue.
New Candidates for Biomarkers and Drug Targets of Ischemic Stroke—A First Dynamic LC-MS Human Serum Proteomic Study
Authors: Turek-Jakubowska Aleksandra , Dębski Janusz , Jakubowski Maciej , Szahidewicz-Krupska Ewa , Gawryś Jakub , Gawryś Karolina , Janus Agnieszka , Trocha Małgorzata , Doroszko Adrian
Published: January 2022

(1) Background: The aim of this dynamic-LC/MS-human-serum-proteomic-study was to identify potential proteins-candidates for biomarkers of acute ischemic stroke, their changes during acute phase of stroke and to define potential novel drug-targets. (2) Methods: A total of 32 patients (29–80 years) with acute ischemic stroke were enrolled to the study. The control group constituted 29 demographically-matched volunteers. Subjects with stroke presented clinical symptoms lasting no longer than 24 h, confirmed by neurological-examination and/or new cerebral ischemia visualized in the CT scans (computed tomography). The analysis of plasma proteome was performed using LC-MS (liquid chromatography–mass spectrometry). (3) Results: Ten proteins with significantly different serum concentrations between groups volunteers were: complement-factor-B, apolipoprotein-A-I, fibronectin, alpha-2-HS-glycoprotein, alpha-1B-glycoprotein, heat-shock-cognate-71kDa protein/heat-shock-related-70kDa-protein-2, thymidine phosphorylase-2, cytoplasmic-tryptophan-tRNA-ligase, ficolin-2, beta-Ala-His-dipeptidase. (4) Conclusions: This is the first dynamic LC-MS study performed on a clinical model which differentiates serum proteome of patients in acute phase of ischemic stroke in time series and compares to control group. Listed proteins should be considered as risk factors, markers of ischemic stroke or potential therapeutic targets. Further clinical validation might define their exact role in differential diagnostics, monitoring the course of the ischemic stroke or specifying them as novel drug targets.
Prognostic Benefit of New Drugs for HFrEF: A Systematic Review and Network Meta-Analysis
Authors: Pagnesi Matteo , Baldetti Luca , Aimo Alberto , Inciardi Riccardo , Tomasoni Daniela , Vizzardi Enrico , Vergaro Giuseppe , Emdin Michele , Lombardi Carlo
Published: January 2022

Background: The new heart failure (HF) therapies of sodium-glucose cotransporter 2 inhibitors (SGLT2i), vericiguat, and omecamtiv mecarbil do not act primarily through the neuro-hormonal blockade, but have shown clinical benefits in patients with HF with reduced ejection fraction (HFrEF). However, their respective efficacies remain unclear. Our aim was to evaluate the relative efficacy of new drugs for HFrEF. Methods: We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing SGLT2i, vericiguat, omecamtiv mecarbil, and placebo in HFrEF patients. The primary endpoint was the composite of cardiovascular death (CVD) or HF hospitalization (CVD-HF); secondary endpoints were CVD, all-cause death, and HF hospitalization (HFH). Results: Twelve RCTs (n = 23,861 patients) were included. A significant reduction in CVD-HF was observed with SGLT2i compared with placebo (risk ratio (RR) 0.77, 95% confidence interval (CI) 0.71–0.83), vericiguat (RR 0.84, 95% CI 0.75–0.93), and omecamtiv mecarbil (RR 0.80, 95% CI 0.72–0.88). No significant difference was observed between vericiguat and omecamtiv mecarbil (RR 0.95, 95% CI 0.87–1.04). SGLT2i were superior to placebo and omecamtiv mecarbil for all individual secondary endpoints (CVD, all-cause death, and HFH), and also to vericiguat for HFH. SGLT2i ranked as the most effective therapy for all endpoints, and vericiguat, omecamtiv mecarbil, and placebo ranked as the second, third, and last options, respectively, for the primary endpoint. Conclusions: In patients with HFrEF on standard-of-care therapy, SGLT2i therapy was associated with a reduced risk of CVD-HF compared to placebo, vericiguat, and omecamtiv mecarbil. Furthermore, SGLT2i were superior to placebo and omecamtiv mecarbil for CVD, all-cause death, and HFH, and also to vericiguat for HFH.
Elevated Perinatal Depression during the COVID-19 Pandemic: A National Study among Jewish and Arab Women in Israel
Authors: Alfayumi-Zeadna Samira , Bina Rena , Levy Drorit , Merzbach Rachel , Zeadna Atif
Published: January 2022

This study assessed prevalence of perinatal depression symptoms (PNDS) during the COVID-19 pandemic among Arab and Jewish women in Israel and identified COVID-19-related risk factors for PNDS, while comparing Arab and Jewish women. Sample included 730 perinatal women (604 Jewish and 126 Arab) aged 19–45 years, who filled out an online self-report questionnaire. The questionnaire assessed several areas: perinatal experiences and exposure to COVID-19, social support, and financial and emotional impact. PNDS was measured by the Edinburgh Postnatal Depression Scale (EPDS). Prevalence of PNDS (EPDS ≥ 10) in the entire study population was 40.0%. Prevalence among Arab women was significantly higher compared to Jewish women (58% vs. 36%, PV < 0.001). Higher PNDS were significantly associated with anxiety symptoms (GAD ≥ 10) (PV < 0.001), stress related to COVID-19 (PV < 0.001), adverse change in delivery of healthcare services (PV = 0.025), and unemployment (PV = 0.002). PNDS has elevated more than twofold during COVID-19 in Israel. Such high rates of PNDS may potentially negatively impact women, and fetal and child health development. This situation requires special attention from public health services and policy makers to provide support and mitigation strategies for pregnant and postpartum women in times of health crises.