bluuebunny/crossref_metadata_2025 huggingface dataset:
Schisandrin B Diet Inhibits Oxidative Stress to Reduce Ferroptosis and Lipid Peroxidation to Prevent Pirarubicin‐Induced Hepatotoxicity
Authors: Shi Hongwei , Yan Yue , Yang Hong , Pu Peng , Tang Heng
Published: July 2022

Objective. Pirarubicin (THP) is one of anthracycline anticancer drugs. It is widely used in the treatment of various cancers, but its hepatotoxicity cannot be ignored. Schisandrin B (SchB) is a traditional liver‐protecting drug, which has the ability to promote mitochondrial function and upregulate cellular antioxidant defense mechanism. However, whether it can resist THP‐induced hepatotoxicity has not been reported. The purpose of this study was to observe and explore the effect of SchB on THP‐induced hepatotoxicity and its potential mechanism by adding SchB to the diet of rats with THP‐induced hepatotoxicity. Methods. The rat model of THP‐induced hepatotoxicity was established and partly treated with SchB diet. The changes of serum liver function indexes ALT and AST were observed. The histomorphological changes of liver were observed by HE staining. The biomarker levels of oxidative stress in rat serum and liver were measured to observe oxidative stress state. The expressions of ferroptosis‐related protein GPX4 and oxidative stress‐related protein were detected by Western blot. Primary hepatocytes were prepared and cocultured with THP, SchB, and Fer‐1 to detect the production of reactive oxygen species (ROS) and verify the above signal pathways. Results. THP rats showed a series of THP‐induced hepatotoxicity changes, such as liver function damage, oxidative stress, and ferroptosis. SchB diet effectively alleviated these adverse reactions. Further studies showed that SchB had strong antioxidant and antiferroptosis abilities in THP‐induced hepatotoxicity. Conclusion. SchB has obvious protective effect on THP‐induced hepatotoxicity. The mechanism may be closely related to inhibiting oxidative stress and ferroptosis in the liver.
Sentiment Analysis of Tourist Scenic Spots Internet Comments Based on LSTM
Authors: Fu Maozheng , Pan Ling
Published: July 2022

With the win-win development of tourism and the Internet, word-of-mouth ranking of tourist attractions is a valuable reference factor. We try to find a correlation between tourist reviews and taste ranking of tourist attractions. We study the sentiment features of tourist online reviews from the technical perspective of natural language processing, so we propose an improved long short-term memory (LSTM) framework for sentiment feature extraction of travel reviews. We abandon traditional dictionaries and machine learning methods. A deep neural network approach was chosen to decompose multisentiment travel reviews into different morpheme levels for classification. Then, through preprocessing, text sentiment topic detection, and sentiment classification network, an accurate grasp of the sentiment features of reviews is finally achieved. To test the performance of our method, we built a web review database by crawler for experimental validation. Experimental results show that our method maintains more than 90% accuracy in comment sentiment detection, significantly outperforming dictionary methods and machine learning methods.
Blood Pressure Trajectories for 16 Years and the Development of Left Ventricular Hypertrophy and Increased Left Atrial Size: The Korean Genome and Epidemiology Study
Authors: Kim Seong Hwan , Lee Ju-Mi , Lee Seung Ku , Shin Chol , Park Jae-Hyeong
Published: July 2022

Background. Elevated single blood pressure (BP) measurement can be associated with the development of hypertension-mediated target organ damage including left ventricular hypertrophy (LVH) and left atrial (LA) enlargement (LAE). However, long-term patterns of BP and their effects on LVH and LAE are poorly understood. We evaluated the association between the BP trajectories and the presence of LVH and LAE. Methods. We analyzed a total of 2,565 participants (1,267 males, 47.8 ± 6.7 years old) from the first biennial examination (2001-2002) of the Korean Genome and Epidemiology Study. The presence of LVH and LAE was identified by echocardiography performed at the 8th biennial examination (2015-2016). Latent mixture modeling was used to identify trajectories in mid-BP ((systolic BP + diastolic BP)/2) over time. Linear logistic regression was used for assessing BP trajectories with the outcomes. Results. We identified 4 distinct mid-BP trajectories: group 1 (lowest, 20.9%, n = 536), group 2 (36.2%, n = 928), group 3 (32.3%, n = 828), and group 4 (highest, 10.6%, n = 273). Compared with the lowest group, trajectories with elevated mid-BP had greater odds ratios having LVH and LAE by multivariable-adjusted regression models. Adjusted odd ratios for LVH were 2.033 (95% CI = 1.462–2.827,

P
<
0.001

) for group 2, 3.446 (95% CI = 2.475–4.797,

P
<
0.001

) for group 3, and 4.940 (95% CI = 3.318–7.356,

P
<
0.001

) for group 4. Adjusted odd ratios for LAE were 1.200 (95% CI = 0.814–1.769,

P
=
0.358

) for group 2, 1.599 (95% CI = 1.084–2.360,

P
=
0.018

) for group 3, and 1.944 (95% CI = 1.212–3.118,

P
=
0.006

) for group 4. Conclusions. Higher long-term mid-BP was an independent risk factor of cardiac structural changes such as LVH and LAE among middle-aged population.
Relevance Feedback and Deep Neural Network-Based Semantic Method for Query Expansion
Authors: Shukla Abhishek Kumar , Das Sujoy , Kumar Pushpendra , Alam Afroj
Published: July 2022

Machine learning techniques have been widely used in almost every area of arts, science, and technology for the last two decades. Document analysis and query expansion also use machine learning techniques at a broad scale for information retrieval tasks. The state-of-the-art models like the Bo1 model, Bo2 model, KL divergence model, and chi-square model are probabilistic, and they work on DFR-based retrieval models. These models are much focused on term frequency and do not care about the semantic relationship among the terms. The proposed model applies the semantic method to find the semantic similarity among the terms to expand the query. The proposed method uses the relevance feedback method that selects a user-assisted most relevant document from top “k” initially retrieved documents and then applies deep neural network technique to select the most informative terms related to original query terms. The results are evaluated at FIRE 2011 ad hoc English test collection. The mean average precision of the proposed method is 0.3568. The proposed method also compares the state-of-the-art models. The proposed model observed 19.77% and 8.05% improvement on the mean average precision (MAP) parameter with respect to the original query and Bo1 model, respectively.
Research on Computer-Aided Product Design Technology
Authors: Song Wei
Published: July 2022

As globalization picks up speed, product innovation—the driving force behind business growth and market competition—becomes increasingly important for advancing product design technology. Computer-aided technology is one of the key components of product design, including issues with scientific analysis, creative thinking, problem-solving, and handling conflicts. Product design technology is gaining more and more attention. Computer-aided technology is now a trendy topic that is being studied by many academics due to the quick growth of computer technology. However, most of them focus on the product information model and solution and do not start from the technical methods and innovation of product design, resulting in many problems in the later solution and information description. Therefore, this paper studies product technology problems based on computer-aided technology and briefly explains the CAI technology-driven technology and the establishment of integrated process model. In this model, the assembly information model diagram is constructed to analyze the conflicts and problems in the assembly model, and then, the CAI-driven integrated innovation technology is called to complete the assembly model design. Conflicts in the assembly design can be minimized by using this paradigm. Finally, the qualitative examination of product design reveals that brainstorming is the process that uses the least amount of energy. The shafting assembly system is reviewed and examined at the same time, and the assembly accuracy accounts for the highest 35 percent of the system, completely indicating the extraordinary impact of computer-aided product design.
Network Pharmacology and Molecular Docking on the Molecular Mechanism of Jiawei-Huang Lian-Gan Jiang Decoction in the Treatment of Colorectal Adenomas
Authors: Ji Shuangshuang , Long Sidan , Yang Yang , Liu Zihao , Wang Rui , Zhang Huifen , Zhang Shuxin
Published: July 2022

Purpose. Jiawei-Huang Lian-Gan Jiang decoction (JWHLGJD) was developed to treat and prevent the patients with colorectal adenomas (CRA) in China. This study is aimed to discover JWHLGJD’s active compounds and demonstrate mechanisms of JWHLGJD against CRA through network pharmacology and molecular docking techniques. Methods. All the components of JWHLGJD were retrieved from the pharmacology database of Traditional Chinese Medicine Systems Pharmacology (TCMSP). The GeneCards database, the Online Mendelian Inheritance in Man database (OMIM), the DrugBank database, and PharmGKB were used to obtain the genes matching the targets. Cytoscape created the compound-target network. The network of target protein-protein interactions (PPI) was constructed using the STRING database. Gene Ontology (GO) functional and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways involved in the targets were analyzed by using the DAVID database. Cytoscape created the component-target-pathway (C-T-P) network. AutoDock Vina software was used to verify the molecular docking of JWHLGJD components and key targets. Core genes linked with survival and tumor microenvironment were analyzed through the Kaplan–Meier plotter and TIMER 2.0 databases, respectively. Results. Compound-target network mainly contained 38 compounds and 130 targets of the JWHLGJD associated with CRA. TP53, MAPK1, JUN, HSP90AA1, and AKT1 were identified as core targets by the PPI network. KEGG pathway shows that the pathways in cancer, lipids, and atherosclerosis, PI3K-Akt signaling pathway and MAPK signaling pathway, are the most relevant pathways to CRA. The C-T-P network suggests that the active component in JWHLGJD is capable of regulating target genes of these related pathways. The results of molecular docking showed that berberine and stigmasterol were the top two compounds of JWHLGJD, which had high affinity with TP53 and MAPK1, respectively. And, MAPK1 exerted a more significant effect on the prognosis of adenocarcinoma, for it was highly associated with various immune cells. Conclusion. Findings in this study provided light on JWHLGJD’s active components, prospective targets, and molecular mechanism. It also gave a potential way to uncovering the scientific underpinning and therapeutic mechanism of traditional Chinese medicine (TCM) formulas.
The Mixed Teaching Mode of Preschool Education Major in the Era of “Internet Plus”
Authors: Li Xiao
Published: July 2022

With the progress of network information technology, many industries have experienced changes and upgrades, and the combination with Internet technology has created many new development opportunities. In addition, in recent years, with the increase of the number of students, the gap between teachers in the field of education is very large, and the demand for preschool teachers is gradually increasing. According to this actual situation, the society has higher and higher requirements for the overall quality of kindergarten teachers. Therefore, it is necessary to use “Internet plus” to realize the reform of preschool education. The application of “Internet plus” in the field of preschool education not only combines the educational resource network of preschool education with preschool education but also is a brand-new reform method. Preschool teachers should make full use of the technical means of network information to form a new teaching system. And innovative teaching methods are often used, which makes the construction of mixed teaching mode of preschool education in China develop rapidly. The mixed teaching mode of preschool education can not only share preschool education resources but also promote the communication between kindergarten and parents. However, there are some problems that affect the development of the blended teaching model of preschool education in China, so it is necessary to take effective strategies to promote the process of the blended teaching model of preschool education.
On the Space of Locally Sobolev-Slobodeckij Functions
Authors: Behzadan A. , Holst M.
Published: July 2022

The study of certain differential operators between Sobolev spaces of sections of vector bundles on compact manifolds equipped with rough metric is closely related to the study of locally Sobolev functions on domains in the Euclidean space. In this paper, we present a coherent rigorous study of some of the properties of locally Sobolev-Slobodeckij functions that are especially useful in the study of differential operators between sections of vector bundles on compact manifolds with rough metric. The results of this type in published literature generally can be found only for integer order Sobolev spaces

W

m
,
p

or Bessel potential spaces

H

s

. Here, we have presented the relevant results and their detailed proofs for Sobolev-Slobodeckij spaces

W

s
,
p

where

s

does not need to be an integer. We also develop a number of results needed in the study of differential operators on manifolds that do not appear to be in the literature.
[Retracted] Identification and Classification of Prostate Cancer Identification and Classification Based on Improved Convolution Neural Network
Authors: Tyagi Shobha , Tyagi Neha , Choudhury Amarendranath , Gupta Gauri , Zahra Musaddak Maher Abdul , Rahin Saima Ahmed
Published: July 2022

Prostate cancer is one of the most common cancers in men worldwide, second only to lung cancer. The most common method used in diagnosing prostate cancer is the microscopic observation of stained biopsies by a pathologist and the Gleason score of the tissue microarray images. However, scoring prostate cancer tissue microarrays by pathologists using Gleason mode under many tissue microarray images is time‐consuming, susceptible to subjective factors between different observers, and has low reproducibility. We have used the two most common technologies, deep learning, and computer vision, in this research, as the development of deep learning and computer vision has made pathology computer‐aided diagnosis systems more objective and repeatable. Furthermore, the U‐Net network, which is used in our study, is the most extensively used network in medical image segmentation. Unlike the classifiers used in previous studies, a region segmentation model based on an improved U‐Net network is proposed in our research, which fuses deep and shallow layers through densely connected blocks. At the same time, the features of each scale are supervised. As an outcome of the research, the network parameters can be reduced, the computational efficiency can be improved, and the method’s effectiveness is verified on a fully annotated dataset.
Small Extracellular Vesicles from Inflamed Adipose Derived Stromal Cells Enhance the NF-κB-Dependent Inflammatory/Catabolic Environment of Osteoarthritis
Authors: Cavallo Carola , Merli Giulia , Zini Nicoletta , D’Adamo Stefania , Cattini Luca , Guescini Michele , Grigolo Brunella , Di Martino Alessandro , Santi Spartaco , Borzì Rosa Maria , Filardo Giuseppe
Published: July 2022

The last decade has seen exponentially growing efforts to exploit the effects of adipose derived stromal cells (ADSC) in the treatment of a wide range of chronic degenerative diseases, including osteoarthritis (OA), the most prevalent joint disorder. In the perspective of developing a cell-free advanced therapy medicinal product, a focus has been recently addressed to the ADSC secretome that lends itself to an allogeneic use and can be further dissected for the selective purification of small extracellular vesicles (sEVs). sEVs can act as “biological drug carriers” to transfer information that mirror the pathophysiology of the providing cells. This is important in the clinical perspective where many OA patients are also affected by the metabolic syndrome (MetS). ADSC from MetS OA patients are dysfunctional and “inflammatory” primed within the adipose tissue. To mimic this condition, we exposed ADSC to IL-1β, and then we investigated the effects of the isolated sEVs on chondrocytes and synoviocytes, either cultured separately or in co-culture, to tease out the effects of these “IL-1β primed sEVs” on gene and protein expression of major inflammatory and catabolic OA markers. In comparison with sEVs isolated from unstimulated ADSC, the IL-1β primed sEVs were able to propagate NF-κB activation in bystander joint cells. The effects were more prominent on synoviocytes, possibly because of a higher expression of binding molecules such as CD44. These findings call upon a careful characterization of the “inflammatory fingerprint” of ADSC to avoid the transfer of an unwanted message as well as the development of in vitro “preconditioning” strategies able to rescue the antiinflammatory/anticatabolic potential of ADSC-derived sEVs.
New Idea of College Music Teaching Mode Based on Numerical Deconstruction and Scientific Calculation
Authors: Liu Yao
Published: July 2022

In the context of rapid social development, education has also faced many challenges in the market. As an important part of higher education, music courses have important value and effect on the cultivation of students’ healthy psychological quality. Correct and effective music teaching can effectively guide students’ music theory knowledge and aesthetic awareness and promote students’ personal future development. However, the learning of theoretical knowledge in music courses is often abstract and boring. In the actual teaching process, problems such as unsatisfactory teaching effect of teachers and low learning interest and enthusiasm of students are often caused by the single teaching mode. Based on numerical analysis and scientific computing, this paper studies the new ideas of college music teaching mode. Under the guidance of scientific educational theory, numerical analysis and scientific calculation are integrated into the teaching of music curriculum theory, and abstract music theory knowledge is concretized to guide students to learn knowledge in a more intuitive way. In the practice of college music teaching mode based on numerical analysis and scientific computing, the method proposed in this paper can effectively improve students’ learning effect and learning enthusiasm. And through the questionnaire survey, it is found that more than 80% of the students are satisfied with this teaching mode, and 62.5% of the students hope to continue to use this teaching mode in the learning process. It is feasible to apply it in practical teaching.
Using Imagination to Integrate Contextual Effects in a Cue-Reactivity Paradigm in Patients with Alcohol Use Disorder: A Functional Magnetic Resonance Imaging Pilot Study
Authors: Fey Werner , Conring Frauke , Federspiel Andrea , Steiner Leonie , Moggi Franz , Stein Maria
Published: July 2022

Introduction: In individuals with alcohol use disorder (AUD), the brain areas underlying cue-induced reactions (e.g., cingulum, striatum, thalamus) and altered activation of these regions have been identified by functional neuroimaging. Neuronal responses to a complex alcohol-related context are yet to investigate. To better understand contextual effects as well as the interplay of cue-induced neural reactions and context exposure, the present study implemented an imagination procedure during functional magnetic resonance imaging (fMRI). Methods: Thirteen patients with AUD and 13 healthy controls completed two rounds of a cue-reactivity paradigm inside an MRI scanner. Two individualized imagination tasks were conducted before each of the two cue reactivity tasks. A 2 (group) × 2 (imagination) × 2 (picture-type) analysis of variance (ANOVA) was performed. Results: The ANOVA revealed a main effect for imagination with higher activation in bilateral thalamus and right caudate nucleus and an interaction effect between imagination and group in right thalamus and left caudate nucleus, due to the patient group reacting stronger during alcohol-related imagination. These structures are involved in relaying sensory information and habit learning. No main or interaction effects of picture type were observed. Conclusions: These results support the view that context effects alter the neural responses in thalamus and nucleus caudatus in patients with AUD, and that imagination tasks are suited to incorporate contextual influences in neurophysiological research designs. Future research needs to investigate whether the failure to observe a picture-type effect was due to limited statistical power and omission to individualize picture set, or whether an imagination procedure interferes with the evocation of picture-type effects.
Mutational Screening for Mitochondrial tRNA Genes in 100 Women with Pre-Eclampsia
Authors: Zhou Baohua , Chu Xuelian , Zhang Caijuan , Liang Xiufeng
Published: July 2022

Introduction: Impairment of mitochondrial function caused by pathogenic mitochondrial DNA (mtDNA) mutations has been found to be associated with pre-eclampsia (PE). However, the underlying mechanism of PE remains poorly undetermined. The aim of this study is to evaluate the relationship between mitochondrial tRNA (mt-tRNA) variants and PE. Methods: The mt-tRNA variants in a cohort of 100 pregnant women with PE and 100 healthy subjects were examined by PCR-Sanger sequencing. Moreover, the phylogenetic conservation analysis, mitochondrial haplogroup analysis, and pathogenicity scoring system were used to assess the potential pathogenicity of these tRNA variants. Results: We identified five possible pathogenic mt-tRNA variants: tRNAPhe A608G, tRNAIle A4263G, tRNAAla T5587C, tRNALeu(CUN) G12294C, and tRNAPro G15995A. We noticed that these variants were not detected in control subjects and occurred at the positions which were extremely conserved. Alternations in tRNA structure caused by these variants may lead to the failures in tRNA metabolism, which may subsequently lead to the impairment of mitochondrial translation as well as the respiratory chain functions. Thus, mt-tRNA variants may be involved in the pathogenesis of PE. Conclusion: Taken together, our data indicated that variants in mt-tRNA genes were the important contributors to PE; screening for mt-tRNA variants was recommended for early detection and prevention of PE.
Oncologic Rehabilitation in the COVID-19 Pandemic: The Situation in Clinics
Authors: Rick Oliver , Hoffmann Wilfried , Steimann Monika Anna
Published: July 2022

Background: Oncological rehabilitation is an important pillar in the treatment of cancer patients. Due to the COVID-19 pandemic, this form of therapy is particularly challenged, as it relies heavily on group therapies. The aim of the study was to find out what impact the pandemic has had on oncological rehabilitation so far and how the rehabilitation clinics have dealt with it. Methods: A web-based survey was used to collect data from 14 oncological rehabilitation clinics on the impact of the COVID-19 pandemic on occupancy, staffing trends, and hygiene measures for the observation period from March 1, 2020, to February 28, 2021. The data were compared with the same period 1 year earlier. In addition, the compensatory measures taken with regard to therapy were recorded. Results: While only 15,272 patients were rehabilitated in the period under review, 21,257 patients were rehabilitated in the same period 1 year earlier. This corresponds to a decrease in occupancy of 28%. Three clinics were affected by temporary closures due to the pandemic. In 39% of the clinics, screening tests for patients had already been started for more than 8 months, while this was also offered to staff in only 23% of the clinics. With regard to changes in the therapeutic offer, more physiotherapeutic small groups with a reduced number of participants were used. This was also used in the area of sports therapy and education offers by 73% and 60% of the clinics, respectively. Overall, 92% of the participants assumed an economic recovery at the time of the survey. Conclusion: Despite a considerable decrease in occupancy in the oncological rehabilitation clinics, the therapies could be changed and carried out in a hygiene-compliant manner. Screening tests were offered at an early stage for patients as well as somewhat delayed for staff. The data show that pandemic-consistently changes in oncological rehabilitation are possible and that supply chains can be maintained.
A Retroperitoneal Mass Encasing the Renal Hilum Presenting as a Parapelvic Tumor: A Case Report with Laparoscopic Resection Approach
Authors: Nikoobakht Mohammad Reza , Inanloo Seyed Hassan , Mohammadi Abdolreza , Hosseini Seyed Reza , Nazarpour Mohammad Javad , Lotfi Mohammad , Esamaeil Panah Shima , Bahoush Masoud , Aghamir Seyed Mohammad Kazem
Published: July 2022

Retroperitoneal masses are a rare condition that may be discovered incidentally in routine abdominal imaging. These lesions are commonly asymptomatic but may be associated with intestinal obstruction and rarely presented with acute abdomen. They may originate from the retroperitoneal organs, including the genitourinary or gastrointestinal tract, or originate primarily from retroperitoneal space, such as retroperitoneal fat, muscle, nervous system, and lymphatic system. The malignant masses are more common than benign masses, and sarcoma is the most malignant tumor in this space. We present a case with the hilar lesion of the left kidney that was managed with laparoscopic resection. The laparoscopy revealed that the mass completely enclosed the left renal hilum, but the mass was excised without any complication. The final pathologic report revealed a benign mesenteric cyst. Although most of the retroperitoneal mass had a malignant etiology, in cystic lesions in the renal hilar area, the benign mesenteric cyst may keep in mind the differential diagnosis of a mass in this anatomic region.
The Effects of Rearing in a Shelved Environment on Behavioral and Physiological Markers of Welfare in Rats (Rattus norvegicus)
Authors: Bigelow Logan J. , Pope Emily K. , Knight Jennifer B. , Rock Jessica E. , MacLeod Sarah K. , Bernard Paul B.
Published: July 2022

Early-life experiences are critical modifiers of development. An important component of early-life experience is the nature of maternal interactions, which can be modified by stress. During rearing, mothers are typically allocated to single-level cages where they are readily accessible to pups, a potentially stressful scenario not reflective of nature. Accordingly, mothers regularly removed from the rearing environment interact differently with their offspring, leading to long-term changes in offspring physiology and behavior. Such changes commonly include modifications within the hypothalamic-pituitary-adrenal axis, of which corticosterone is a major component. Modifications in the hypothalamic-pituitary-adrenal axis may also be manifested through changes in affective behavior and assessed via tests such as the open field and elevated plus maze as well as via ultrasonic vocalization (USV) analysis. As a means of assessing the impact of rearing in a shelved environment, we allocated mothers to standard single-level cages or cages with an integrated shelf, which allowed the mother to temporarily escape pups. While there were no differences in fecal cortico­sterone, behavior in the elevated plus maze, or USVs, male rats reared in standard cages weighed more, and all standard single-level housed rats spent more time in the center of the open field. The observed differences indicate that allocating nursing mothers to shelved environments throughout the postnatal period has long-lasting effects on offspring behavior that must be considered when establishing dam enrichment protocols.
Ist die Ergänzung der Basistherapie mit tiefdosiertem Prednisolon bei älteren Patienten mit rheumatoider Arthritis vertretbar? Resultate der randomisiert-kontrollierten GLORIA-Studie
Authors: Mihai Carina
Published: July 2022

Background: Low-dose glucocorticoid (GC) therapy is widely used in rheumatoid arthritis (RA) but the balance of benefit and harm is still unclear. Subjects and methods: The GLORIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) pragmatic double-blind randomised trial compared 2 years of prednisolone, 5 mg/day, to placebo in patients aged 65+ with active RA. We allowed all cotreatments except long-term open label GC and minimised exclusion criteria, tailored to seniors. Benefit outcomes included disease activity (disease activity score; DAS28, coprimary) and joint damage (Sharp/van der Heijde, secondary). The other coprimary outcome was harm, expressed as the proportion of patients with ≥1 adverse event (AE) of special interest. Such events comprised serious events, GC-specific events and those causing study discontinuation. Longitudinal models analysed the data, with one-sided testing and 95% confidence limits (95% CL). Results: We randomised 451 patients with established RA and mean 2.1 comorbidities, age 72, disease duration 11 years and DAS28 4.5. 79% were on disease-modifying treatment, including 14% on biologics. 63% prednisolone versus 61% placebo patients completed the trial. Discontinuations were for AE (both, 14%), active disease (3 vs 4%) and for other (including covid pandemic-related disease) reasons (19 vs 21%); mean time in study was 19 months. Disease activity was 0.37 points lower on prednisolone (95% CL 0.23, p < 0.0001); joint damage progression was 1.7 points lower (95% CL 0.7, p = 0.003). 60% versus 49% of patients experienced the harm outcome, adjusted relative risk 1.24 (95% CL 1.04, p = 0.02), with the largest contrast in (mostly non-severe) infections. Other GC-specific events were rare. Conclusion: Add-on low-dose prednisolone has beneficial long-term effects in senior patients with established RA, with a trade-off of 24% increase in patients with mostly non-severe AE; this suggests a favourable balance of benefit and harm. Trial registration number: NCT02585258.
O fundamento lógico do normativismo da gramática grega e sua relação com a ausência da inovação e mudança linguísticas como objeto de estudo teórico
Authors: Vitral Lorenzo
Published: July 2022

O objetivo deste trabalho é demonstrar, numa perspectiva historiográfica, que o caráter normativista, amplamente reconhecido, da gramática tradicional na sua vertente grega não se deve somente ao trabalho filológico de preservação ou padronização dos textos clássicos. Essa tarefa foi, na verdade, precedida, tomando Aristóteles como o primeiro sistematizador do conhecimento filosófico de sua época, pela busca de uma linguagem capaz de realizar o trabalho ontológico fundamental da metafísica. A eliminação aristotélica da ambiguidade e da intencionalidade na busca da linguagem precisa e a fundação da metafísica num período em que os estudos da linguagem ainda não se constituíram como disciplina autônoma desfavoreceram por completo a inovação ou a mudança linguística como um objeto de estudo legítimo.
Unfolded Protein Response Differentially Modulates the Platelet Phenotype
Authors: Jain Kanika , Tyagi Tarun , Du Jing , Hu Xiaoyue , Patell Kanchi , Martin Kathleen A. , Hwa John
Published: July 2022

Background:

Unfolded protein response (UPR) is a multifaceted signaling cascade that alleviates protein misfolding. Although well studied in nucleated cells, UPR in absence of transcriptional regulation has not been described. Intricately associated with cardiovascular diseases, platelets, despite being anucleate, respond rapidly to stressors in blood. We investigate the UPR in anucleate platelets and explore its role, if any, on platelet physiology and function.

Methods:

Human and mouse platelets were studied using a combination of ex vivo and in vivo experiments. Platelet lineage-specific knockout mice were generated independently for each of the 3 UPR pathways, PERK (protein kinase RNA [PKR]-like endoplasmic reticulum kinase), XBP1 (X-binding protein), and ATF6 (activating transcription factor 6). Diabetes patients were prospectively recruited, and platelets were evaluated for activation of UPR under chronic pathophysiological disease conditions.

Results:

Tunicamycin induced the IRE1α (inositol-requiring enzyme-1alpha)-XBP1 pathway in human and mouse platelets, while oxidative stress predominantly activated the PERK pathway. PERK deletion significantly increased platelet aggregation and apoptosis and phosphorylation of PLCγ2, PLCβ3, and p38 MAPK. Deficiency of XBP1 increased platelet aggregation, with higher PLCβ3 and PKCδ activation. ATF6 deletion mediated a relatively modest effect on platelet phenotype with increased PKA (protein kinase A). Platelets from diabetes patients exhibited a positive correlation between disease severity, platelet activation, and protein aggregation, with only IRE1α-XBP1 activation. Moreover, IRE1α inhibition increased platelet aggregation, while clinically approved chemical chaperone, sodium 4-phenylbutyrate reduced the platelet hyperactivation.

Conclusions:

We show for the first time, that UPR activation occurs in platelets and can be independent of genomic regulation, with selective induction being specific to the source and severity of stress. Each UPR pathway plays a key role and can differentially modulate the platelet activation pathways and phenotype. Targeting the specific arms of UPR may provide a new antiplatelet strategy to mitigate thrombotic risk in diabetes and other cardiovascular diseases.
Community-Based, Cluster-Randomized Pilot Trial of a Cardiovascular Mobile Health Intervention: Preliminary Findings of the FAITH! Trial
Authors: Brewer LaPrincess C. , Jenkins Sarah , Hayes Sharonne N. , Kumbamu Ashok , Jones Clarence , Burke Lora E. , Cooper Lisa A. , Patten Christi A.
Published: July 2022

Background:

African Americans continue to have suboptimal cardiovascular health (CVH) based on the American Heart Association Life’s Simple 7 (LS7), 7 health-promoting behaviors and biological risk factors (eg, physical activity, blood pressure). Innovative, community-level interventions in partnership with trusted institutions such as African American churches are potential means to improve CVH in this population.

Methods:

Using a community-based participatory research approach, the FAITH! Trial (Fostering African American Improvement in Total Health) rigorously assessed the feasibility and preliminary efficacy of a refined, community-informed, mobile health intervention (FAITH! App) for promoting CVH among African Americans in faith communities using a cluster randomized controlled trial. Participants from 16 churches in Rochester and Minneapolis-St Paul, MN, were randomized to receive the FAITH! App (immediate intervention) or were assigned to a delayed intervention comparator group. The 10-week intervention core features included culturally relevant and LS7-focused education modules, diet/physical activity self-monitoring, and a group sharing board. Data were collected via electronic surveys and health assessments. Primary outcomes were average change in mean LS7 score (continuous measure of CVH ranging from poor to ideal [0–14 points]) from baseline to 6 months post-intervention (using generalized estimating equations) and app engagement/usability (by the Health Information Technology Usability Evaluation Scale; range, 0–5).

Results:

Of 85 enrolled participants (randomized to immediate [N=41] and delayed [control] intervention [N=44] groups), 76 and 68 completed surveys/health assessments at baseline and 6 months post-intervention, respectively (80% retention rate with assessments at both baseline and 6-month time points); immediate intervention [N=30] and control [N=38] groups). At baseline, the majority of participants (mean age [SD], 54.2 [12.3] years, 71% female) had <4-year college education level (39/66, 59%) and poor CVH (44% in poor category; mean LS7 score [SD], 6.8 [1.9]). The mean LS7 score of the intervention group increased by 1.9 (SD 1.9) points compared with 0.7 (SD 1.7) point in the control group (both
P
<0.0001) at 6 months. The estimated difference of this increase between the groups was 1.1 (95% CI, 0.6–1.7;
P
<0.0001). App engagement/usability was overall high (100% connection to app; >75% completed weekly diet/physical activity tracking; Health Information Technology Usability Evaluation Scale, mean [SD], 4.2 [0.7]).

Conclusions:

On the basis of preliminary findings, the refined FAITH! App appears to be an efficacious mobile health tool to promote ideal CVH among African Americans.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03777709.
Racial and Ethnic Differences in All-Cause and Cardiovascular Disease Mortality: The MESA Study
Authors: Post Wendy S. , Watson Karol E. , Hansen Spencer , Folsom Aaron R. , Szklo Moyses , Shea Steven , Barr R. Graham , Burke Gregory , Bertoni Alain G. , Allen Norrina , Pankow James S. , Lima Joao A.C. , Rotter Jerome I. , Kaufman Joel D. , Johnson W. Craig , Kronmal Richard A. , Diez-Roux Ana V. , McClelland Robyn L.
Published: July 2022

Background:

Despite improvements in population health, marked racial and ethnic disparities in longevity and cardiovascular disease (CVD) mortality persist. This study aimed to describe risks for all-cause and CVD mortality by race and ethnicity, before and after accounting for socioeconomic status (SES) and other factors, in the MESA study (Multi-Ethnic Study of Atherosclerosis).

Methods:

MESA recruited 6814 US adults, 45 to 84 years of age, free of clinical CVD at baseline, including Black, White, Hispanic, and Chinese individuals (2000–2002). Using Cox proportional hazards modeling with time-updated covariates, we evaluated the association of self-reported race and ethnicity with all-cause and adjudicated CVD mortality, with progressive adjustments for age and sex, SES (neighborhood SES, income, education, and health insurance), lifestyle and psychosocial risk factors, clinical risk factors, and immigration history.

Results:

During a median of 15.8 years of follow-up, 22.8% of participants (n=1552) died, of which 5.3% (n=364) died of CVD. After adjusting for age and sex, Black participants had a 34% higher mortality hazard (hazard ratio [HR], 1.34 [95% CI, 1.19–1.51]), Chinese participants had a 21% lower mortality hazard (HR, 0.79 [95% CI, 0.66–0.95]), and there was no mortality difference in Hispanic participants (HR, 0.99 [95% CI, 0.86–1.14]) compared with White participants. After adjusting for SES, the mortality HR for Black participants compared with White participants was reduced (HR, 1.16 [95% CI, 1.01–1.34]) but still statistically significant. With adjustment for SES, the mortality hazards for Chinese and Hispanic participants also decreased in comparison with White participants. After further adjustment for additional risk factors and immigration history, Hispanic participants (HR, 0.77 [95% CI, 0.63–0.94]) had a lower mortality risk than White participants, and hazard ratios for Black participants (HR, 1.08 [95% CI, 0.92–1.26]) and Chinese participants (HR, 0.81 [95% CI, 0.60–1.08]) were not significantly different from those of White participants. Similar trends were seen for CVD mortality, although the age- and sex-adjusted HR for CVD mortality for Black participants compared with White participants was greater than all-cause mortality (HR, 1.72 [95% CI, 1.34–2.21] compared with HR, 1.34 [95% CI, 1.19–1.51]).

Conclusions:

These results highlight persistent racial and ethnic differences in overall and CVD mortality, largely attributable to social determinants of health, and support the need to identify and act on systemic factors that shape differences in health across racial and ethnic groups.
US Surveillance of Acute Ischemic Stroke Patient Characteristics, Care Quality, and Outcomes for 2019
Authors: Ziaeian Boback , Xu Haolin , Matsouaka Roland A. , Xian Ying , Khan Yosef , Schwamm Lee S. , Smith Eric E. , Fonarow Gregg C.
Published: July 2022

Background:

The United States lacks a timely and accurate nationwide surveillance system for acute ischemic stroke (AIS). We use the Get With The Guidelines-Stroke registry to apply poststratification survey weights to generate national assessment of AIS epidemiology, hospital care quality, and in-hospital outcomes.

Methods:

Clinical data from the Get With The Guidelines-Stroke registry were weighted using a Bayesian interpolation method anchored to observations from the national inpatient sample. To generate a US stroke forecast for 2019, we linearized time trend estimates from the national inpatient sample to project anticipated AIS hospital volume, distribution, and race/ethnicity characteristics for the year 2019. Primary measures of AIS epidemiology and clinical care included patient and hospital characteristics, stroke severity, vital and laboratory measures, treatment interventions, performance measures, disposition, and clinical outcomes at discharge.

Results:

We estimate 552 476 patients with AIS were admitted in 2019 to US hospitals. Median age was 71 (interquartile range, 60–81), 48.8% female. Atrial fibrillation was diagnosed in 22.6%, 30.2% had prior stroke/transient ischemic attack, and 36.4% had diabetes. At baseline, 46.4% of patients with AIS were taking antiplatelet agents, 19.2% anticoagulants, and 46.3% cholesterol-reducers. Mortality was 4.4%, and only 52.3% were able to ambulate independently at discharge. Performance nationally on AIS achievement measures were generally higher than 95% for all measures but the use of thrombolytics within 3 hours of early stroke presentations (81.9%). Additional quality measures had lower rates of receipt: dysphagia screening (84.9%), early thrombolytics by 4.5 hours (79.7%), and statin therapy (80.6%).

Conclusions:

We provide timely, reliable, and actionable US national AIS surveillance using Bayesian interpolation poststratification weights. These data may facilitate more targeted quality improvement efforts, resource allocation, and national policies to improve AIS care and outcomes.
Application of Microwave Space-Based Environmental Monitoring (SBEM) Data for Operational Tropical Cyclone Intensity Estimation at the Joint Typhoon Warning Center
Authors: Howell Brian , Egan Sean , Fine Caitlin
Published: July 2022

The Joint Typhoon Warning Center (JTWC) utilized new space-based environmental monitoring (SBEM) data alongside traditional data to adjust JTWC tropical cyclone (TC) intensity and structure estimates during production of the official 2019 Best Track dataset. Intensity estimates from multiple platforms such as Advanced Microwave Scanning Radiometer-2 (AMSR2), the Soil Moisture Active Passive (SMAP) and Soil Moisture and Ocean Salinity (SMOS) radiometers, and synthetic aperture radar (SAR), along with objective Dvorak and satellite consensus algorithms, not only aided the poststorm best track (BT) process, but also provided robust data that supported real-time analysis and forecasting. This summary attempts to communicate with the TC community the extent to which these new data affected the 2019 official BT data, how JTWC utilized these new data in the poststorm BT process, and provide examples of how these data influenced forecaster decision-making in real time. This paper makes no attempt to validate the accuracy of the wind speed estimates from these methods (SAR, SMAP/SMOS, or AMSR2) and does not outline the entirety of the JTWC process for determining TC intensity, but it does outline, briefly, the impact of these new datasets on the final JTWC BT intensity estimates and on real-time analysis. These methodologies are valuable sources of cyclone intensity estimates in an otherwise data-sparse area of responsibility, and in many cases provide critical data not captured by traditional methods alone, which are detailed further in this summary.
An Ensemble Forecasting Method for Dealing with the Combined Effects of the Initial and Model Errors and a Potential Deep Learning Implementation
Authors: Duan Wansuo , Ma Junjie , Vannitsem Stéphane
Published: July 2022

In this paper, a new nonlinear forcing singular vector (NFSV) approach is proposed to provide mutually independent optimally combined modes of initial perturbations and model perturbations (C-NFSVs) in ensemble forecasts. The C-NFSVs are a group of optimally growing structures that take into account the impact of the interaction between the initial errors and the model errors effectively, generalizing the original NFSV for simulations of the impact of the model errors. The C-NFSVs method is tested in the context of the Lorenz-96 model to demonstrate its potential to improve ensemble forecast skills. This method is compared with the orthogonal conditional nonlinear optimal perturbations (O-CNOPs) method for estimating only the initial uncertainties and the orthogonal NFSVs (O-NFSVs) for estimating only the model uncertainties. The results demonstrate that when both the initial perturbations and model perturbations are introduced in the forecasting system, the C-NFSVs are much more capable of achieving higher ensemble forecasting skills. The use of a deep learning approach as a remedy for the expensive computational costs of the C-NFSVs is evaluated. The results show that learning the impact of the C-NFSVs on the ensemble provides a useful and efficient alternative for the operational implementation of C-NFSVs in forecasting suites dealing with the combined effects of the initial errors and the model errors.

Significance Statement

A new ensemble forecasting method for dealing with combined effects of initial errors and model errors, i.e., the C-NFSVs, is proposed, which is an extension of the NFSV approach for simulating the model error effects in ensemble forecasts. The C-NFSVs provide mutually independent optimally combined modes of initial perturbations and model perturbations. This new method is tested for generating ensemble forecasts in the context of the Lorenz-96 model, and there are indications that the optimally growing structures may provide reliable ensemble forecasts. Furthermore, it is found that a hybrid dynamical–deep learning approach could be a potential avenue for real-time ensemble forecasting systems when perturbations combine the impact of the initial and the model errors.
Compulsory vaccination against SARS-CoV-2 in health care professionals in Italy: Bioethical-legal issues
Authors: Cioffi Andrea , Cecannecchia Camilla
Published: July 2022

On 17 March 2022, the Italian Council of Ministers, by means of Press Release No. 67, sanctioned the extension of the vaccine obligation against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for health workers until 31 December 2022. Healthcare workers who do not demonstrate that they have adequate vaccination coverage will be suspended from work and will not be paid. Recently, the Council of Administrative Justice of Sicily has identified possible contrasts between the vaccine obligation of health professionals and numerous constitutional principles, paving the way for an interesting bioethical-legal debate on the subject. The aim of this article is to examine the possible profiles of unconstitutionality of the measure of the Italian Government and to identify medico-legal and bioethical issues potentially related to the vaccine obligation for health professionals in a context of resolution of the emergency phase related to the coronavirus disease 2019 (COVID-19) pandemic.