bluuebunny/crossref_metadata_2025 huggingface dataset:
An ECG Classification Method Based on Multi-Task Learning and CoT Attention Mechanism
Authors: Geng Quancheng , Liu Hui , Gao Tianlei , Liu Rensong , Chen Chao , Zhu Qing , Shu Minglei
Published: March 2023

Electrocardiogram (ECG) is an efficient and simple method for the diagnosis of cardiovascular diseases and has been widely used in clinical practice. Because of the shortage of professional cardiologists and the popularity of electrocardiograms, accurate and efficient arrhythmia detection has become a hot research topic. In this paper, we propose a new multi-task deep neural network, which includes a shared low-level feature extraction module (i.e., SE-ResNet) and a task-specific classification module. Contextual Transformer (CoT) block is introduced in the classification module to dynamically model the local and global information of ECG feature sequence. The proposed method was evaluated on public CPSC2018 and PTB-XL datasets and achieved an average F1 score of 0.827 on the CPSC2018 dataset and an average F1 score of 0.833 on the PTB-XL dataset.
Knowledge, Opinions, and Practices of Oral Cancer Prevention among Palestinian Practicing Dentists: An Online Cross-Sectional Questionnaire
Authors: Shadid Rola Muhammed , Habash Ghassan
Published: March 2023

Oral-health professionals play a critical role in the early recognition and prevention of oral cancer; however, most patients are diagnosed in the advanced stages that demonstrate poor prognosis. Therefore, this study aimed to investigate the knowledge, opinions, and clinical practices of practicing dentists related to oral cancer prevention and oral mucosal screening in Palestine. This research used an online cross-sectional questionnaire design. Practicing dentists in Palestine completed the 44-item questionnaire encompassing the following four sections: (a) personal data (6 items); (b) oral cancer knowledge (21 items); (c) opinions and beliefs related to oral cancer (10 items); and (d) clinical practices related to oral cancer (7 items). The questionnaire was sent to all eligible participants (N = 650) between July and September of 2022. The response rate was 39.1% (N = 254). About 70.1% of the respondents had poor knowledge of oral cancer and its risk factors, and almost 84.3% had positive opinions related to oral cancer prevention and oral mucosal screening. Concerning the clinical practices, only 29.9% routinely examined their patients every time their patients visited. More experienced dentists showed significantly more positive opinions and better clinical practices related to oral cancer prevention and screening; however, they had significantly lower knowledge scores compared with the younger dentists (p < 0.05). Inadequate training was the most reported perceived boundary against routine oral cancer screening. Palestinian dentists appeared to have positive opinions related to oral cancer prevention and oral mucosal screening. However, the assessment of the knowledge and clinical practices revealed deficiencies in this regard.
Modeling a Metamorphic Aquifer through a Hydro-Geophysical Approach: The Gap between Field Data and System Complexity
Authors: Chidichimo Francesco , De Biase Michele , Muto Francesco , Straface Salvatore
Published: March 2023

The productivity of metamorphic aquifers is generally lower than that of the more common alluvial and carbonates ones. However, in some Mediterranean areas, such as the Calabria region (Italy), water scarcity combined with the presence of extensive metamorphic water bodies requires the development of further studies to characterize the hydrodynamic properties of these groundwater systems in order to achieve their sustainable exploitation. The interest in this goal becomes even greater if climate change effects are considered. The purpose of this study was to provide the geological-structural and hydrogeological numerical modeling of a metamorphic aquifer, using direct and indirect data measurement, in a large area of the Sila Piccola in Calabria. The hydrodynamic characterization of the crystalline-metamorphic aquifer, constituted by granite and metamorphic rocks, is extremely complex. The MODFLOW-2005 groundwater model was used to simulate flow phenomena in the aquifer, obtaining hydraulic conductivity values of 2.7 × 10−6 m/s, which turned out to be two orders of magnitude higher than those obtained from the interpretation of the slug-tests performed in the study area. The mathematical model was also able to estimate the presence of a lateral recharge from a neighboring deep aquifer providing a significant water supply to the system under investigation.
A Management Method of Multi-Granularity Dimensions for Spatiotemporal Data
Authors: Cao Wen , Liu Wenhao , Tong Xiaochong , Wang Jianfei , Peng Feilin , Tian Yuzhen , Zhu Jingwen
Published: March 2023

To understand the complex phenomena in social space and monitor the dynamic changes in people’s tracks, we need more cross-scale data. However, when we retrieve data, we often ignore the impact of multi-scale, resulting in incomplete results. To solve this problem, we proposed a management method of multi-granularity dimensions for spatiotemporal data. This method systematically described dimension granularity and the fuzzy caused by dimension granularity, and used multi-scale integer coding technology to organize and manage multi-granularity dimensions, and realized the integrity of the data query results according to the correlation between the different scale codes. We simulated the time and band data for the experiment. The experimental results showed that: (1) this method effectively solves the problem of incomplete query results of the intersection query method. (2) Compared with traditional string encoding, the query efficiency of multiscale integer encoding is twice as high. (3) The proportion of different dimension granularity has an impact on the query effect of multi-scale integer coding. When the proportion of fine-grained data is high, the advantage of multi-scale integer coding is greater.
Lupin, a Unique Legume That Is Nodulated by Multiple Microsymbionts: The Role of Horizontal Gene Transfer
Authors: Msaddak Abdelhakim , Mars Mohamed , Quiñones Miguel A. , Lucas M. Mercedes , Pueyo José J.
Published: March 2023

Lupin is a high-protein legume crop that grows in a wide range of edaphoclimatic conditions where other crops are not viable. Its unique seed nutrient profile can promote health benefits, and it has been proposed as a phytoremediation plant. Most rhizobia nodulating Lupinus species belong to the genus Bradyrhizobium, comprising strains that are phylogenetically related to B. cytisi, B. hipponenese, B. rifense, B. iriomotense/B. stylosanthis, B. diazoefficiens, B. japonicum, B. canariense/B. lupini, and B. retamae/B. valentinum. Lupins are also nodulated by fast-growing bacteria within the genera Microvirga, Ochrobactrum, Devosia, Phyllobacterium, Agrobacterium, Rhizobium, and Neorhizobium. Phylogenetic analyses of the nod and nif genes, involved in microbial colonization and symbiotic nitrogen fixation, respectively, suggest that fast-growing lupin-nodulating bacteria have acquired their symbiotic genes from rhizobial genera other than Bradyrhizobium. Horizontal transfer represents a key mechanism allowing lupin to form symbioses with bacteria that were previously considered as non-symbiotic or unable to nodulate lupin, which might favor lupin’s adaptation to specific habitats. The characterization of yet-unstudied Lupinus species, including microsymbiont whole genome analyses, will most likely expand and modify the current lupin microsymbiont taxonomy, and provide additional knowledge that might help to further increase lupin’s adaptability to marginal soils and climates.
Immuno-Stimulating Activity of 1,25-Dihydroxyvitamin D in Blood Cells from Five Healthy People and in Blasts from Five Patients with Leukemias and Pre-Leukemic States
Authors: Marchwicka Aleksandra , Nowak Kuba , Satyr Anastasiia , Wołowiec Dariusz , Marcinkowska Ewa
Published: March 2023

(1) Hematological malignancies are characterized by an immortalization, uncontrolled proliferation of blood cells and their differentiation block, followed by the loss of function. The primary goal in the treatment of leukemias is the elimination of rapidly proliferating leukemic cells (named blasts). However, chemotherapy, which removes proliferating blasts, also prevents the remaining immune cells from being activated. Acute leukemias affect elderly people, who are often not fit to survive aggressive chemotherapy. Therefore, there is a need of milder treatment, named differentiation therapy, which might simulate the immune system of the patient. 1,25-Dihydroxyvitamin D, or low-calcemic analogs of this compound, were proposed as supporting therapy in acute leukemias. (2) Bone marrow blasts from patients with hematological malignancies, and leukocytes from healthy volunteers were ex vivo exposed to 1,25-dihydroxyvitamin D, and then their genomes and transcriptomes were investigated. (3) Our analysis indicates that 1,25-dihydroxyvitamin D regulates in blood cells predominantly genes involved in immune response, such as CAMP (cathelicidin antimicrobial peptide), CP (ceruloplasmin), CXCL9 (C-X-C motif chemokine ligand 9), CD14 (CD14 molecule) or VMO1 (vitelline membrane outer layer 1 homolog). This concerns blood cells from healthy people, as well as blasts from patients with hematological malignancies. In addition, in one patient, 1,25-dihydroxyvitamin D significantly downregulated transcription of genes responsible for cell division and immortalization. (4) In conclusion, the data presented in this paper suggest that addition of 1,25-dihydroxyvitamin D to the currently available treatments would stimulate immune system, inhibit proliferation and reduce immortal potential of blasts.
Role of Muscarinic Acetylcholine Receptors in Intestinal Epithelial Homeostasis: Insights for the Treatment of Inflammatory Bowel Disease
Authors: Uwada Junsuke , Nakazawa Hitomi , Muramatsu Ikunobu , Masuoka Takayoshi , Yazawa Takashi
Published: March 2023

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is an intestinal disorder that causes prolonged inflammation of the gastrointestinal tract. Currently, the etiology of IBD is not fully understood and treatments are insufficient to completely cure the disease. In addition to absorbing essential nutrients, intestinal epithelial cells prevent the entry of foreign antigens (micro-organisms and undigested food) through mucus secretion and epithelial barrier formation. Disruption of the intestinal epithelial homeostasis exacerbates inflammation. Thus, the maintenance and reinforcement of epithelial function may have therapeutic benefits in the treatment of IBD. Muscarinic acetylcholine receptors (mAChRs) are G protein-coupled receptors for acetylcholine that are expressed in intestinal epithelial cells. Recent studies have revealed the role of mAChRs in the maintenance of intestinal epithelial homeostasis. The importance of non-neuronal acetylcholine in mAChR activation in epithelial cells has also been recognized. This review aimed to summarize recent advances in research on mAChRs for intestinal epithelial homeostasis and the involvement of non-neuronal acetylcholine systems, and highlight their potential as targets for IBD therapy.
Molecular Basis of Unequal Alternative Splicing of Human SCD5 and Its Alteration by Natural Genetic Variations
Authors: Orosz Gabriella , Szabó Luca , Bereti Szanna , Zámbó Veronika , Csala Miklós , Kereszturi Éva
Published: March 2023

Alternative splicing (AS) is a major means of post-transcriptional control of gene expression, and provides a dynamic versatility of protein isoforms. Cancer-related AS disorders have diagnostic, prognostic and therapeutic values. Changes in the expression and AS of human stearoyl-CoA desaturase-5 (SCD5) are promising specific tumor markers, although the transcript variants (TVs) of the gene have not yet been confirmed. Our in silico, in vitro and in vivo study focuses on the distribution of SCD5 TVs (A and B) in human tissues, the functionality of the relevant splice sites, and their modulation by certain single-nucleotide variations (SNVs). An order of magnitude higher SCD5A expression was found compared with SCD5B. This unequal splicing is attributed to a weaker recognition of the SCD5B-specific splicing acceptor site, based on predictions confirmed by an optimized minigene assay. The pronounced dominance of SCD5A was largely modified (rs1430176385_A, rs1011850309_A) or even inverted (rs1011850309_C) by natural SNVs at the TV-specific splice sites. Our results provide long missing data on the proportion of SCD5 TVs in human tissues and reveal mutation-driven changes in SCD5 AS, potentially affecting tumor-associated reprogramming of lipid metabolism, thus having prognostic significance, which may be utilized for novel and personalized therapeutic approaches.
Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review
Authors: Twarowski Bartosz , Herbet Mariola
Published: March 2023

Alzheimer’s disease is one of the most commonly diagnosed cases of senile dementia in the world. It is an incurable process, most often leading to death. This disease is multifactorial, and one factor of this is inflammation. Numerous mediators secreted by inflammatory cells can cause neuronal degeneration. Neuritis may coexist with other mechanisms of Alzheimer’s disease, contributing to disease progression, and may also directly underlie AD. Although much has been established about the inflammatory processes in the pathogenesis of AD, many aspects remain unexplained. The work is devoted in particular to the pathomechanism of inflammation and its role in diagnosis and treatment. An in-depth and detailed understanding of the pathomechanism of neuroinflammation in Alzheimer’s disease may help in the development of diagnostic methods for early diagnosis and may contribute to the development of new therapeutic strategies for the disease.
Myokine Musclin Is Critical for Exercise-Induced Cardiac Conditioning
Authors: Harris Matthew P. , Zeng Shemin , Zhu Zhiyong , Lira Vitor A. , Yu Liping , Hodgson-Zingman Denice M. , Zingman Leonid V.
Published: March 2023

This study investigates the role and mechanisms by which the myokine musclin promotes exercise-induced cardiac conditioning. Exercise is one of the most powerful triggers of cardiac conditioning with proven benefits for healthy and diseased hearts. There is an emerging understanding that muscles produce and secrete myokines, which mediate local and systemic “crosstalk” to promote exercise tolerance and overall health, including cardiac conditioning. The myokine musclin, highly conserved across animal species, has been shown to be upregulated in response to physical activity. However, musclin effects on exercise-induced cardiac conditioning are not established. Following completion of a treadmill exercise protocol, wild type (WT) mice and mice with disruption of the musclin-encoding gene, Ostn, had their hearts extracted and exposed to an ex vivo ischemia-reperfusion protocol or biochemical studies. Disruption of musclin signaling abolished the ability of exercise to mitigate cardiac ischemic injury. This impaired cardioprotection was associated with reduced mitochondrial content and function linked to blunted cyclic guanosine monophosphate (cGMP) signaling. Genetic deletion of musclin reduced the nuclear abundance of protein kinase G (PKGI) and cyclic adenosine monophosphate (cAMP) response element binding (CREB), resulting in suppression of the master regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), and its downstream targets in response to physical activity. Synthetic musclin peptide pharmacokinetic parameters were defined and used to calculate the infusion rate necessary to maintain its plasma level comparable to that observed after exercise. This infusion was found to reproduce the cardioprotective benefits of exercise in sedentary WT and Ostn-KO mice. Musclin is essential for exercise-induced cardiac protection. Boosting musclin signaling might serve as a novel therapeutic strategy for cardioprotection.
Photodegradable by Yellow-Orange Light degFusionRed Optogenetic Module with Autocatalytically Formed Chromophore
Authors: Chernov Konstantin G. , Manoilov Kyrylo Yu. , Oliinyk Olena S. , Shcherbakova Daria M. , Verkhusha Vladislav V.
Published: March 2023

Optogenetic systems driven by yellow-orange light are required for the simultaneous regulation of several cellular processes. We have engineered the red fluorescent protein FusionRed into a 26 kDa monomeric optogenetic module, called degFusionRed. Unlike other fluorescent protein-based optogenetic domains, which exhibit light-induced self-inactivation by generating reactive oxygen species, degFusionRed undergoes proteasomal degradation upon illumination with 567 nm light. Similarly to the parent protein, degFusionRed has minimal absorbance at 450 nm and above 650 nm, making it spectrally compatible with blue and near-infrared-light-controlled optogenetic tools. The autocatalytically formed chromophore provides degFusionRed with an additional advantage over most optogenetic tools that require the binding of the exogenous chromophores, the amount of which varies in different cells. The degFusionRed efficiently performed in the engineered light-controlled transcription factor and in the targeted photodegradation of the protein of interest, demonstrating its versatility as the optogenetic module of choice for spectral multiplexed interrogation of various cellular processes.
Physiological and Functional Effects of Dominant Active TCRα Expression in Transgenic Mice
Authors: Kalinina Anastasiia A. , Ziganshin Rustam Kh. , Silaeva Yulia Yu. , Sharova Nina I. , Nikonova Margarita F. , Persiyantseva Nadezda A. , Gorkova Tatiana G. , Antoshina Elena E. , Trukhanova Lubov S. , Donetskova Almira D. , Komogorova Victoria V. , Litvina Marina M. , Mitin Alexander N. , Zamkova Maria A. , Bruter Alexandra V. , Khromykh Ludmila M. , Kazansky Dmitry B.
Published: March 2023

A T cell receptor (TCR) consists of α- and β-chains. Accumulating evidence suggests that some TCRs possess chain centricity, i.e., either of the hemi-chains can dominate in antigen recognition and dictate the TCR’s specificity. The introduction of TCRα/β into naive lymphocytes generates antigen-specific T cells that are ready to perform their functions. Transgenesis of the dominant active TCRα creates transgenic animals with improved anti-tumor immune control, and adoptive immunotherapy with TCRα-transduced T cells provides resistance to infections. However, the potential detrimental effects of the dominant hemi-chain TCR’s expression in transgenic animals have not been well investigated. Here, we analyzed, in detail, the functional status of the immune system of recently generated 1D1a transgenic mice expressing the dominant active TCRα specific to the H2-Kb molecule. In their age dynamics, neither autoimmunity due to the random pairing of transgenic TCRα with endogenous TCRβ variants nor significant disturbances in systemic homeostasis were detected in these mice. Although the specific immune response was considerably enhanced in 1D1a mice, responses to third-party alloantigens were not compromised, indicating that the expression of dominant active TCRα did not limit immune reactivity in transgenic mice. Our data suggest that TCRα transgene expression could delay thymic involution and maintain TCRβ repertoire diversity in old transgenic mice. The detected changes in the systemic homeostasis in 1D1a transgenic mice, which are minor and primarily transient, may indicate variations in the ontogeny of wild-type and transgenic mouse lines.
Multifaceted Roles of Aquaporins in the Pathogenesis of Alzheimer’s Disease
Authors: Yamada Kaoru
Published: March 2023

The central nervous system is highly dependent on water, and disturbances in water homeostasis can have a significant impact on its normal functions. The regulation of water balance is, at least in part, carried out via specialized water channels called aquaporins. In the central nervous system, two major aquaporins (AQPs), AQP1 and AQP4, and their potential involvements have been long implicated in the pathophysiology of many brain disorders such as brain edema and Neuromyelitis optica. In addition to these diseases, there is growing attention to the involvement of AQPs in the removal of waste products in Alzheimer’s disease (AD). This indicates that targeting fluid homeostasis is a novel and attractive approach for AD. This review article aims to summarize recent knowledge on the pathological implications of AQPs in AD, discussing unsolved questions and future prospects.
Genome-Wide CRISPR Screens Reveal ZATT as a Synthetic Lethal Target of TOP2-Poison Etoposide That Can Act in a TDP2-Independent Pathway
Authors: Park Jeong-Min , Zhang Huimin , Nie Litong , Wang Chao , Huang Min , Feng Xu , Tang Mengfan , Chen Zhen , Xiong Yun , Lee Namsoo , Li Siting , Yin Ling , Hart Traver , Chen Junjie
Published: March 2023

Etoposide (ETO) is an anticancer drug that targets topoisomerase II (TOP2). It stabilizes a normally transient TOP2–DNA covalent complex (TOP2cc), thus leading to DNA double-strand breaks (DSBs). Tyrosyl-DNA phosphodiesterases two (TDP2) is directly involved in the repair of TOP2cc by removing phosphotyrosyl peptides from 5′-termini of DSBs. Recent studies suggest that additional factors are required for TOP2cc repair, which include the proteasome and the zinc finger protein associated with TDP2 and TOP2, named ZATT. ZATT may alter the conformation of TOP2cc in a way that renders the accessibility of TDP2 for TOP2cc removal. In this study, our genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screens revealed that ZATT also has a TDP2-independent role in promoting cell survival following ETO treatment. ZATT KO cells showed relatively higher ETO sensitivity than TDP2-KO cells, and ZATT/TDP2 DKO cells displayed additive hypersensitivity to ETO treatment. The study using a series of deletion mutants of ZATT determined that the N-terminal 1–168 residues of ZATT are required for interaction with TOP2 and this interaction is critical to ETO sensitivity. Moreover, depletion of ZATT resulted in accelerated TOP2 degradation after ETO or cycloheximide (CHX) treatment, suggesting that ZATT may increase TOP2 stability and likely participate in TOP2 turnover. Taken together, this study suggests that ZATT is a critical determinant that dictates responses to ETO treatment and targeting. ZATT is a promising strategy to increase ETO efficacy for cancer therapy.
Cadherin-11-Interleukin-6 Signaling between Cardiac Fibroblast and Cardiomyocyte Promotes Ventricular Remodeling in a Mouse Pressure Overload-Induced Heart Failure Model
Authors: Fang Guojian , Li Yingze , Yuan Jiali , Cao Wei , Song Shuai , Chen Long , Wang Yuepeng , Wang Qunshan
Published: March 2023

Heart failure is a serious and life-threatening disease worldwide. Cadherin-11 (Cad-11) is highly expressed in the heart and closely associated with inflammation. There is currently limited understanding on how Cad-11 contributes to cardiac remodeling and its underline molecular mechanism. We found an increased expression of Cad-11 in biopsy heart samples from heart failure patients, suggesting a link between Cad-11 and heart failure. To determine the role of Cad-11 in cardiac remodeling, Cad-11-deficient mice were used in a well-established mouse transverse aortic constriction (TAC) model. Loss of Cad11 greatly improved pressure overload-induced LV structural and electrical remodeling. IL (interleukin)-6 production was increased following TAC in WT mice and this increase was inhibited in cadherin-11−/− mice. We further tested the effect of IL-6 on myocyte hypertrophy and fibrosis in a primary culture system. The addition of hCad-11-Fc to cultured cardiac fibroblasts increased IL-6 production and fibroblast cell activation, whereas neutralizing IL-6 with an IL-6 antibody resulted in alleviating the fibroblast activation induced by hCad-11-Fc. On the other hand, cardiomyocytes were promoted to cardiomyocyte hypertrophy when cultured in condition media collected from cardiac fibroblasts stimulated by hCad-11-Fc.Similarly, neutralizing IL-6 prevented cardiomyocyte hypertrophy. Finally, we found that MAPKs and CaMKII–STAT3 pathways were activated in both hCad-11-Fc stimulated fibroblasts and cardiomyocytes treated with hCad-11-Fc stimulated fibroblast condition medium. IL-6 neutralization inhibited such MAPK and CaMKII-STAT3 signaling activation. These data demonstrate that Cad-11 functions in pressure overload-induced ventricular remodeling through inducing IL-6 secretion from cardiac fibroblasts to modulate the pathophysiology of neighboring cardiomyocytes.
Nitrite Reductase Activity of Ferrous Nitrobindins: A Comparative Study
Authors: De Simone Giovanna , di Masi Alessandra , Tundo Grazia R. , Coletta Massimo , Ascenzi Paolo
Published: March 2023

Nitrobindins (Nbs) are all-β-barrel heme proteins spanning from bacteria to Homo sapiens. They inactivate reactive nitrogen species by sequestering NO, converting NO to HNO2, and promoting peroxynitrite isomerization to NO3−. Here, the nitrite reductase activity of Nb(II) from Mycobacterium tuberculosis (Mt-Nb(II)), Arabidopsis thaliana (At-Nb(II)), Danio rerio (Dr-Nb(II)), and Homo sapiens (Hs-Nb(II)) is reported. This activity is crucial for the in vivo production of NO, and thus for the regulation of blood pressure, being of the utmost importance for the blood supply to poorly oxygenated tissues, such as the eye retina. At pH 7.3 and 20.0 °C, the values of the second-order rate constants (i.e., kon) for the reduction of NO2− to NO and the concomitant formation of nitrosylated Mt-Nb(II), At-Nb(II), Dr-Nb(II), and Hs-Nb(II) (Nb(II)-NO) were 7.6 M−1 s−1, 9.3 M−1 s−1, 1.4 × 101 M−1 s−1, and 5.8 M−1 s−1, respectively. The values of kon increased linearly with decreasing pH, thus indicating that the NO2−-based conversion of Nb(II) to Nb(II)-NO requires the involvement of one proton. These results represent the first evidence for the NO2 reductase activity of Nbs(II), strongly supporting the view that Nbs are involved in NO metabolism. Interestingly, the nitrite reductase reactivity of all-β-barrel Nbs and of all-α-helical globins (e.g., myoglobin) was very similar despite the very different three-dimensional fold; however, differences between all-α-helical globins and all-β-barrel Nbs suggest that nitrite reductase activity appears to be controlled by distal steric barriers, even though a more complex regulatory mechanism can be also envisaged.
Multiplexed Fluorescence Plate Reader In Situ Protein Expression Assay in Apoptotic HepG2 Cells
Authors: Jakabfi-Csepregi Rita , Kovács Gábor L. , Kaltenecker Péter , Kőszegi Tamás
Published: March 2023

Instead of Western blot being considered as a gold standard for intracellular protein expression assays, we developed a novel multiplexed high throughput (180 tests/day) in situ manual protein expression method directly in 96-well plates using 25,000–100,000 cells/well after formaldehyde fixation and Triton X 100 permeabilization. HepG2 cells were treated with ochratoxin A (OTA) and staurosporine (STP) to induce apoptosis. Antioxidant and apoptotic cell signaling protein expression were studied by various rabbit primary antibodies and HRP labeled secondary antibodies. The HRP labeled immune complexes were developed by H2O2/Ampliflu Red fluorogenic reagent and measured in a plate reader. Our assay can simultaneously quantify 22 protein antigens in one plate with 4 technical replicates with an interassay imprecision of <10% CV. The fluorescence signals are referred to total intracellular protein contents in the wells and given as fluorescence/protein ratio FPR, expressed as % of the controls (FPR %). OTA caused a dose–response increase (p < 0.05–p < 0.001) in SOD2, CAT, ALB, CASP3,7,9, BCL2, BAX, Nf-kB, phospho-Erk1/2/Erk1/2, phospho-Akt/Akt, phospho-p38/p38, and phospho-PPARg/PPARg levels while phospho-AMPK/AMPK ratios decreased (p < 0.05–p < 0.001). On the contrary, STP induced a dose–response decrease (p < 0.05–p < 0.001) in CASP3,7,9, BAX, BCL2, Nf-kB and phospho-Erk1/2/Erk1/2 expression while B-ACT, phospho-Akt/Akt, phospho-p38/p38 and phospho-PPARg/PPARg ratios increased.
Generating Paraphrase Using Simulated Annealing for Citation Sentences
Authors: Ilyas Ridwan , Khodra Masayu , Munir Rinaldi , Mandala Rila , Widyantoro Dwi
Published: March 2023

The paraphrase generator for citation sentences is used to produce several sentence alternatives to avoid plagiarism. Furthermore, the generation results need to pay attention to semantic similarity and lexical divergence standards. This study proposed the StoPGEN model as an algorithm for generating citation paraphrase sentences with stochastic output. The generation process is guided by an objective function using a simulated annealing algorithm to maintain the properties of semantic similarity and lexical divergence. The objective function is created by combining the two factors that maintain these properties. This study combined METEOR and PINC Scores in a linear weighting function that can be adjusted for its value tendency in one of the matrix functions. The dataset of citation sentences that had been labeled with paraphrases was used to test StoPGEN and other models for comparison. The StoPGEN model, with the citation sentences dataset, produced a BLEU score of 55.37, outperforming the bidirectional LSTM method with a value of 28.93. StoPGEN was also tested using Quora data by changing the language source in the architecture section resulting in a BLEU score of 22.37, outperforming UPSA 18.21. In addition, the qualitative evaluation results of the citation sentence generation based on respondents obtained an acceptance value of 50.80.
How Metal Nuclearity Impacts Electrocatalytic H2 Production in Thiocarbohydrazone-Based Complexes
Authors: Papadakis Michael , Barrozo Alexandre , Delmotte Léa , Straistari Tatiana , Shova Sergiu , Réglier Marius , Krewald Vera , Bertaina Sylvain , Hardré Renaud , Orio Maylis
Published: March 2023

Thiocarbohydrazone-based catalysts feature ligands that are potentially electrochemically active. From the synthesis point of view, these ligands can be easily tailored, opening multiple strategies for optimization, such as using different substituent groups or metal substitution. In this work, we show the possibility of a new strategy, involving the nuclearity of the system, meaning the number of metal centers. We report the synthesis and characterization of a trinuclear nickel-thiocarbohydrazone complex displaying an improved turnover rate compared with its mononuclear counterpart. We use DFT calculations to show that the mechanism involved is metal-centered, unlike the metal-assisted ligand-centered mechanism found in the mononuclear complex. Finally, we show that two possible mechanisms can be assigned to this catalyst, both involving an initial double reduction of the system.
Intranasal Fentanyl for Acute Pain Management in Children, Adults and Elderly Patients in the Prehospital Emergency Service and in the Emergency Department: A Systematic Review
Authors: Serra Sossio , Spampinato Michele Domenico , Riccardi Alessandro , Guarino Mario , Pavasini Rita , Fabbri Andrea , De Iaco Fabio
Published: March 2023

This systematic review examined the efficacy and safety of intranasal fentanyl (INF) for acute pain treatment in children, adults, and the elderly in prehospital emergency services (PHES) and emergency departments (ED). ClinicalTrials.gov, LILACS, PubMed, SCOPUS, EMBASE, Google Scholar and Cochrane databases were consulted until 31 December 2022. A total of 23 studies were included: 18 in children (1 PHES, 17 ED), 5 in adults (1 PHES, 4 ED) and 1 in older people (1 PHES subgroup analysis). In children, INF was effective in both settings and as effective as the comparator drugs, with no differences in adverse events (AEs); one randomised controlled trial (RCT) showed that INF was more effective than the comparator drugs. In adults, one study demonstrated the efficacy of INF in the PHES setting, one study demonstrated the efficacy of INF in the ED setting, two RCTs showed INF to be less effective than the comparator drugs and one RCT showed INF to be as effective as the comparator, with no difference in AEs reported. In older people, one study showed effective pain relief and no AEs. In summary, INF appears to be effective and safe in children and adults in PHES and ED. More high-quality studies are needed, especially in PHES and older people.
Immediate and Long-Term Effectiveness of Proprioceptive Neuromuscular Facilitation and Static Stretching on Joint Range of Motion, Flexibility, and Electromyographic Activity of Knee Muscles in Older Adults
Authors: Zaidi Sahar , Ahamad Asfak , Fatima Anam , Ahmad Irshad , Malhotra Deepak , Al Muslem Wafa Hashem , Abdulaziz Sahar , Nuhmani Shibili
Published: March 2023

Introduction and Objective: Previously, various stretching techniques were compared to study their effects on the different physiological parameters of hamstring muscles in the elderly population. There is no research that compares the immediate and long-term effects of proprioceptive neuromuscular facilitation-contract–relax (PNF-CR) and static stretching (SS) techniques on knee range of motion (ROM), hamstring flexibility, and knee flexor muscle EMG activity in the elderly. This study intends to compare the same. Methods: A total of 30 males aged 55–75 years were randomly assigned into the PNF-CR group (n = 10), SS group (n = 10), and control group (n = 10). The PNF-CR group received four trials of the contract–relax technique, the SS group received passive stretching of an 80 s duration by the therapist, and the control group received no intervention. A total of 12 sessions were given during the four-week period. Knee range of motion, electromyographic activity of the biceps femoris, and the sit-and-reach test were taken for the dominant side thrice: pre-intervention, immediately after stretching, and after the training period. Results: A statistically significant difference was observed in the maximum voluntary isometric contraction (MVIC) of biceps femoris between the PNF and the control groups (p = 0.01) after four weeks of intervention. The knee ROM and hamstring flexibility for the PNF group showed significant improvement immediately post-test (p = 0.01) and after four weeks of training (p = 0.07 and p = 0.001). SS showed significant results for both ROM and flexibility after four weeks of intervention (p = 0.001), and significant immediate post-test improvements were seen for ROM only (p = 0.007). Conclusions: PNF stretching has an immediate, as well as long-term, effect on knee ROM and hamstring flexibility, whereas it has only a long-term effect on muscle electromyographic activity. SS has an immediate, as well as long-term, effect on knee ROM and only a long-term effect on hamstring flexibility, without any immediate or long-term effects on muscle electromyographic activity.
Hand and Wrist Involvement in Seropositive Rheumatoid Arthritis, Seronegative Rheumatoid Arthritis, and Psoriatic Arthritis—The Value of Classic Radiography
Authors: Żelnio Ewa , Taljanovic Mihra , Mańczak Małgorzata , Sudoł-Szopińska Iwona
Published: March 2023

The hand and wrist are among the most common anatomical areas involved in rheumatic diseases, especially seropositive and seronegative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). The purpose of this study was to identify the most differentiating radiographic characteristics of PsA, seropositive RA, and seronegative RA, particularly in the early stages. A retrospective analysis of radiographic hand findings was performed on 180 seropositive RA patients (29 males, 151 females, mean age at the point of acquisition of the analyzed radiograph of 53.4 y/o, SD 12.6), 154 PsA patients (45 males, 109 females, age median of 48.1 y/o, SD 12.4), and 36 seronegative RA patients (4 males, 32 females, age median of 53.1 y/o, SD 17.1) acquired during the period 2005–2020. Posterior–anterior and Nørgaard views were analyzed in all patients. The radiographs were evaluated for three radiographic findings: type of symmetry (asymmetric/bilateral/changes in corresponding joint compartments/‘mirror-image’ symmetry), anatomic location (e.g., wrist, metacarpophalangeal (MCP), proximal interphalangeal (PIP), distal interphalangeal (DIP) joints), and type of lesions (e.g., juxta-articular osteoporosis, bone cysts, erosions, proliferative bone changes). The study showed that symmetric distribution of lesions defined as ‘lesions present in corresponding compartments’ was more suggestive of seropositive or seronegative RA than PsA. Lesions affecting the PIP joints, wrist, or styloid process of the radius; juxta-articular osteoporosis, joint space narrowing, joint subluxations, or dislocations were more common in patients with seropositive RA than in those with PsA, whereas DIP joints’ involvement and proliferative bone changes were more likely to suggest PsA than seropositive RA. Lesions in PIP, MCP, and wrist joints, as well as erosions, advanced bone damage, joint subluxations, dislocations, and joint space narrowing, were more common in seropositive RA patients than in seronegative RA patients. The ulnar styloid was more commonly affected in seronegative RA patients than in PsA patients. The study confirmed that types of bone lesions and their distribution in the hands and wrists can be useful in differentiating seropositive RA from PsA and suggests that seronegative RA varies in radiological presentation from seropositive RA and PsA.
Risk Assessment of Bauxite Maritime Logistics Based on Improved FMECA and Fuzzy Bayesian Network
Authors: Sun Jiachen , Wang Haiyan , Wang Mengmeng
Published: March 2023

Because of the many limitations of the traditional failure mode effect and criticality analysis (FMECA), an integrated risk assessment model with improved FMECA, fuzzy Bayesian networks (FBN), and improved evidence reasoning (ER) is proposed. A new risk characterization parameter system is constructed in the model. A fuzzy rule base system based on the confidence structure is constructed by combining fuzzy set theory with expert knowledge, and BN reasoning technology is used to realize the importance ranking of the hazard degree of maritime logistics risk events. The improved ER based on weight distribution and matrix analysis can effectively integrate the results of risk event assessment and realize the hazard evaluation of the maritime logistics system from the overall perspective. The effectiveness and feasibility of the model are verified by carrying out a risk assessment on the maritime logistics of importing bauxite to China. The research results show that the priority of risk events in the maritime logistics of bauxite are “pirates or terrorist attacks” and “workers’ riots or strikes” in sequence. In addition, the bauxite maritime logistics system is at a medium- to high-risk level as a whole. The proposed model is expected to provide a systematic risk assessment model and framework for the engineering field.
Determination of Current and Future Extreme Sea Levels at the Local Scale in Port-Bouët Bay (Côte d’Ivoire)
Authors: Kouakou Marcel , Bonou Frédéric , Gnandi Kissao , Djagoua Eric , Idrissou Mouhamed , Abunkudugu Asaa
Published: March 2023

The Port-Bouët Bay shoreline is threatened by extreme sea level (ESL) events, which result from the combination of storm tide, wave run-up, and sea level rise (SLR). This study provides comprehensive scenarios of current and future ESLs at the local scale along the bay to understand the evolution of the phenomenon and promote local adaptation. The methodological steps involve first reconstructing historical storm tide and wave run-up data using a hydrodynamic model (D-flow FM) and the empirical model of Stockdon et al. Second, the Generalized Pareto Distribution (GPD) model fitted to the Peaks-Over-Thresholds (POT) method is applied to the data to calculate extreme return levels. Third, we combine the extreme storm tide and wave run-up using the joint probability method to obtain the current ESLs. Finally, the current ESLs are integrated with recent SLR projections to provide future ESL estimates. The results show that the current ESLs are relatively high, with 100-year return levels of 4.37 m ± 0.51, 4.97 m ± 0.57, and 4.48 m ± 0.5 at Vridi, Petit-Bassam, and Sogefiha respectively. By end-century, under the SSP1-2.6, SSP2-4.5, and SSP5-8.5 scenarios, the future SLR is expected to increase the current ESLs by 0.49 m, 0.62 m, and 0.84 m, respectively. This could lead to a more frequent occurrence of the current 100-year return period, happening once every 2 years by 2100, especially under SSP5-8.5. The developed SLR scenarios can be used to assess the potential coastal flood risk in the study area for sustainable and effective coastal management and planning.
Ras2 Is Responsible for the Environmental Responses, Melanin Metabolism, and Virulence of Botrytis cinerea
Authors: Li Hua , Shen Xuemei , Wu Wenjia , Zhang Wanyu , Wang Yousheng
Published: March 2023

Ras proteins are monomeric G proteins that are ubiquitous in fungal cells and play important roles in fungal growth, virulence, and environmental responses. Botrytis cinerea is a phytopathogenic fungus that infects various crops. However, under specific environmental conditions, the overripe grapes infected by B. cinerea can be used to brew valuable noble rot wine. As a Ras protein, the role of Bcras2 in the environmental responses of B. cinerea is poorly understood. In this study, we deleted the Bcras2 gene using homologous recombination and examined its functions. Downstream genes regulated by Bcras2 were explored using RNA sequencing transcriptomics. It was found that ΔBcras2 deletion mutants showed significantly reduced growth rate, increased sclerotia production, decreased resistance to oxidative stress, and enhanced resistance to cell wall stress. Additionally, Bcras2 deletion promoted the expression of melanin-related genes in sclerotia and decreased the expression of melanin-related genes in conidia. The above results indicate that Bcras2 positively regulates growth, oxidative stress resistance, and conidial melanin-related genes expression, and negatively regulates sclerotia production, cell wall stress resistance and sclerotial melanin-related genes expression. These results revealed previously unknown functions of Bcras2 in environmental responses and melanin metabolism in B. cinerea.
Baseline CTC Count as a Predictor of Long-Term Outcomes in High-Risk Prostate Cancer
Authors: Cieślikowski Wojciech A. , Milecki Piotr , Świerczewska Monika , Ida Agnieszka , Kasperczak Michał , Jankowiak Agnieszka , Nowicki Michał , Pantel Klaus , Alix-Panabières Catherine , Zabel Maciej , Antczak Andrzej , Budna-Tukan Joanna
Published: March 2023

The aim of the present study was to verify whether the baseline circulating tumor cell (CTC) count might serve as a predictor of overall survival (OS) and metastasis-free survival (MFS) in patients with high-risk prostate cancer (PCa) during a follow-up period of at least 5 years. CTCs were enumerated using three different assay formats in 104 patients: the CellSearch® system, EPISPOT assay and GILUPI CellCollector. A total of 57 (55%) patients survived until the end of the follow-up period, with a 5 year OS of 66% (95% CI: 56–74%). The analysis of univariate Cox proportional hazard models identified a baseline CTC count ≥ 1, which was determined with the CellSearch® system, a Gleason sum ≥ 8, cT ≥ 2c and metastases at initial diagnosis as significant predictors of a worse OS in the entire cohort. The CTC count ≥ 1 was also the only significant predictor of a worse OS in a subset of 85 patients who presented with localized PCa at the baseline. The baseline CTC number did not affect the MFS. In conclusion, the baseline CTC count can be considered a determinant of survival in high-risk PCa and also in patients with a localized disease. However, determining the prognostic value of the CTC count in patients with localized PCa would optimally require longitudinal monitoring of this parameter.
Lower Extremity Nerve Conduction Abnormalities in Vietnamese Patients with Type 2 Diabetes: A Cross-Sectional Study on Peripheral Neuropathy and Its Correlation with Glycemic Control and Renal Function
Authors: Tung Do Dinh , Minh Nui Nguyen , Nguyen Hanh Thi , Nguyen Thi Phi Nga , Nguyen Thi Huong Lan , Nguyen Duc Long , Pham Dung Thuy Nguyen , Tran Toan Quoc , Nguyen Duong Thanh , Nguyen Linh Phuong
Published: March 2023

Peripheral neuropathy is a common complication of type 2 diabetes mellitus (T2DM) that results in nerve conduction abnormalities. This study aimed to investigate the parameters of nerve conduction in lower extremities among T2DM patients in Vietnam. A cross-sectional study was conducted on 61 T2DM patients aged 18 years and older, diagnosed according to the American Diabetes Association’s criteria. Data on demographic characteristics, duration of diabetes, hypertension, dyslipidemia, neuropathy symptoms, and biochemical parameters were collected. Nerve conduction parameters were measured in the tibial and peroneal nerves, including peripheral motor potential time, response amplitude M, and motor conduction speed, as well as sensory conduction in the shallow nerve. The study found a high rate of peripheral neuropathy among T2DM patients in Vietnam, with decreased conduction rate, motor response amplitude, and nerve sensation. The incidence of nerve damage was highest in the right peroneal nerve and left peroneal nerve (86.7% for both), followed by the right tibial nerve and left tibial nerve (67.2% and 68.9%, respectively). No significant differences were found in the rate of nerve defects between different age groups, body mass index (BMI) groups, or groups with hypertension or dyslipidemia. However, a statistically significant association was found between the rate of clinical neurological abnormalities and the duration of diabetes (p < 0.05). Patients with poor glucose control and/or decreased renal function also had a higher incidence of nerve defects. The study highlights the high incidence of peripheral neuropathy among T2DM patients in Vietnam and the association between nerve conduction abnormalities and poor glucose control and/or decreased renal function. The findings underscore the importance of early diagnosis and management of neuropathy in T2DM patients to prevent serious complications.
Correction: Zanetti et al. Agritourism and Farms Diversification in Italy: What Have We Learnt from COVID-19? Land 2022, 11, 1215
Authors: Zanetti Barbara , Verrascina Milena , Licciardo Francesco , Gargano Giuseppe
Published: March 2023

In the original publication [...]
Tumor Area Highlighting Using T2WI, ADC Map, and DWI Sequence Fusion on bpMRI Images for Better Prostate Cancer Diagnosis
Authors: Teică Rossy Vlăduț , Șerbănescu Mircea-Sebastian , Florescu Lucian Mihai , Gheonea Ioana Andreea
Published: March 2023

Prostate cancer is the second most common cancer in men worldwide. The results obtained in magnetic resonance imaging examinations are used to decide the indication, type, and location of a prostate biopsy and contribute information about the characterization or aggressiveness of detected cancers, including tumor progression over time. This study proposes a method to highlight prostate lesions with a high and very high risk of being malignant by overlaying a T2-weighted image, apparent diffusion coefficient map, and diffusion-weighted image sequences using 204 pairs of slices from 80 examined patients. It was reviewed by two radiologists who segmented suspicious lesions and labeled them according to the prostate imaging-reporting and data system (PI-RADS) score. Both radiologists found the algorithm to be useful as a “first opinion”, and they gave an average score on the quality of the highlight of 9.2 and 9.3, with an agreement of 0.96.