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CTX-M-Producing Bacteria Isolated from a Highly Polluted River System in Portugal. Enterobacteriaceae resistant to third-generation cephalosporins are a great concern for public health, as these are first-line drugs to treat infections. The production of carbapenemases and extended spectrum beta-lactamases (ESBLs) and/or the overexpression of AmpC β-lactamases are the main mechanisms of resistance to these antibiotics. Among the ESBLs, CTX-M β-lactamases are the most prevalent worldwide. Our aims were to determine the prevalence of cefotaxime-resistant Enterobacteriaceae along a heavily polluted river and characterize bla CTX-M carriers. River water was collected in 11 sites along the main course and tributaries, in two sampling moments. Water quality was evaluated and a collection of cefotaxime-resistant isolates was obtained. bla CTX-M carriers were characterized regarding phylogenetic affiliation, clonality, antibiotic susceptibility, gene diversity, and context. Water presented very low quality in all sites. From 147 cefotaxime-resistant isolates, 46% carried bla CTX-M and were affiliated with Escherichia , Klebsiella , Enterobacter , and Citrobacter . Molecular typing revealed clonal isolates in different sites and over the two years, suggesting survival of the strains in the river or continuous pollution inputs from the same sources. Eight variants of bla CTX-M were found, with bla CTX-M-15 being the most prevalent (52.5%). Sites with a lower water quality showed the highest resistance rates and prevalence of bla CTX-M , suggesting that river water may embody human health risks.
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Catch-up immunisation for migrant children in Melbourne: A qualitative study with providers to determine key challenges. Current models of immunisation service delivery in Australia are not meeting the needs of migrant children, who experience a higher burden of vaccine preventable disease and lower immunisation rates compared to non-migrant children. Understanding the experiences of immunisation providers is critical for designing effective and tailored interventions to improve this service. This study aimed to identify the facilitators and barriers to providers delivering a comprehensive catch-up immunisation service to migrant children in Melbourne, Australia.
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Atheroprone fluid shear stress-regulated ALK1-Endoglin-SMAD signaling originates from early endosomes. Fluid shear stress enhances endothelial SMAD1/5 signaling via the BMP9-bound ALK1 receptor complex supported by the co-receptor Endoglin. While moderate SMAD1/5 activation is required to maintain endothelial quiescence, excessive SMAD1/5 signaling promotes endothelial dysfunction. Increased BMP signaling participates in endothelial-to-mesenchymal transition and inflammation culminating in vascular diseases such as atherosclerosis. While the function of Endoglin has so far been described under picomolar concentrations of BMP9 and short-term shear application, we investigated Endoglin under physiological BMP9 and long-term pathophysiological shear conditions.
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Dosage compensation: A new player in X chromosome upregulation. Dosage balance between sex chromosomes and autosomes can be achieved through diverse mechanisms across vertebrates and invertebrates. A new study discovers a key player that contributes to X chromosome upregulation (XCU) during early mouse development and associates the dysregulation of XCU with human bile duct cancer pathogenesis.
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Epigenetic regulation of aging: implications for interventions of aging and diseases. Aging is accompanied by the decline of organismal functions and a series of prominent hallmarks, including genetic and epigenetic alterations. These aging-associated epigenetic changes include DNA methylation, histone modification, chromatin remodeling, non-coding RNA (ncRNA) regulation, and RNA modification, all of which participate in the regulation of the aging process, and hence contribute to aging-related diseases. Therefore, understanding the epigenetic mechanisms in aging will provide new avenues to develop strategies to delay aging. Indeed, aging interventions based on manipulating epigenetic mechanisms have led to the alleviation of aging or the extension of the lifespan in animal models. Small molecule-based therapies and reprogramming strategies that enable epigenetic rejuvenation have been developed for ameliorating or reversing aging-related conditions. In addition, adopting health-promoting activities, such as caloric restriction, exercise, and calibrating circadian rhythm, has been demonstrated to delay aging. Furthermore, various clinical trials for aging intervention are ongoing, providing more evidence of the safety and efficacy of these therapies. Here, we review recent work on the epigenetic regulation of aging and outline the advances in intervention strategies for aging and age-associated diseases. A better understanding of the critical roles of epigenetics in the aging process will lead to more clinical advances in the prevention of human aging and therapy of aging-related diseases.
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An in vitro and ex vivo wound infection model to test topical and systemic treatment with antibiotics. This study aimed to develop a wound infection model that could be used to test antibiotic-loaded electrospun matrices for the topical treatment of infected skin and compare the effectiveness of this treatment to systemically applied antibiotics.
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Definitive fusion for scoliosis in late juvenile cerebral palsy patients is durable at 5 years postoperatively. Given the challenges associated with managing progressive scoliosis in patients with cerebral palsy (CP), the purpose of this study was to evaluate deformity correction and HRQOL 5 years post-spinal fusion in CP patients who were skeletally immature at the time of surgical correction.
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Clinical course of inflammatory bowel disease and impact on liver disease outcomes in patients with autoimmune sclerosing cholangitis. Autoimmune sclerosing cholangitis (ASC) is a childhood sclerosing cholangitis frequently associated with inflammatory bowel disease (IBD). We describe the IBD phenotype in ASC patients and associated liver disease outcomes.
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Lewis Acid-Relayed Singlet Oxygen Reaction with Enamines: Selective Dimerization of Enamines to Pyrrolin-4-ones. Singlet oxygen ( 1 O 2 )-mediated oxidation represents an attractive strategy for incorporation of oxygen atoms from air under mild and environmentally benign conditions. However, the 1 O 2 reaction with enamine suffers from fragmentation, leading to very unsuccessful transformation. Here, Lewis acid is introduced to intercept [2 + 2] or "ene" reaction intermediates of the 1 O 2 reaction and enables oxidative dimerization of enamines to produce pyrrolin-4-ones in good to excellent yields. Mechanistic studies reveal the formation of the imino ketone intermediate from the interaction of 1 O 2 and enamine, which is able to interact with Lewis acid, relaying the 1 O 2 reaction in enamine chemistry. For the first time, selective cross-dimerization of two different enamines is achieved. Due to the advantages of mild conditions, high chemoselectivity, and up to 99% yield, a promising strategy has been developed for synthesizing aza-heterocycles under ambient conditions, which can be further applied for the synthesis of imidazolone, quinoxaline, and highly functionalized imine.
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HAL-X: Scalable hierarchical clustering for rapid and tunable single-cell analysis. Data clustering plays a significant role in biomedical sciences, particularly in single-cell data analysis. Researchers use clustering algorithms to group individual cells into populations that can be evaluated across different levels of disease progression, drug response, and other clinical statuses. In many cases, multiple sets of clusters must be generated to assess varying levels of cluster specificity. For example, there are many subtypes of leukocytes (e.g. T cells), whose individual preponderance and phenotype must be assessed for statistical/functional significance. In this report, we introduce a novel hierarchical density clustering algorithm (HAL-x) that uses supervised linkage methods to build a cluster hierarchy on raw single-cell data. With this new approach, HAL-x can quickly predict multiple sets of labels for immense datasets, achieving a considerable improvement in computational efficiency on large datasets compared to existing methods. We also show that cell clusters generated by HAL-x yield near-perfect F1-scores when classifying different clinical statuses based on single-cell profiles. Our hierarchical density clustering algorithm achieves high accuracy in single cell classification in a scalable, tunable and rapid manner.
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Impact of plastic pollution on outdoor recreation in the existence of bearing capacity and perspective management. Large-scale increases in plastic waste, greenhouse gas emissions, and fossil fuel depletion all have negative consequences for the environment. Plastic pollution can lead towards negative impacts on outdoor recreational activities. China and the European Union, as world leader in recycling and reuse, are tackling this issue by putting in place measures to counteract this trend for better outdoor recreational activities. As China and EU nations are most attracted by the tourists it is possible that recreational spot can have harmful effects upon wild and human life. So, we analyze the impacts of plastic waste recycling and reuse on outdoor recreation. It is possible to speed up the circular process if industry reduces its resource and energy consumption while also being able to handle plastic waste responsibly, utilize renewable energy sources, generate jobs, and contribute to economic growth, among other things. This research investigates the transition to sustainability in the European Union nations and China between 2000 and 2020 via the prism of resource and energy productivity in the EU nations and China. The Autoregressive Distributed Lag (ARDL) Model, as well as the estimator Driscool Kraay, are employed in this study. There is a statistically significant relationship between plastic recycling and valorization because of plastic pollution leads toward negative impacts on outdoor recreation, as well as resource productivity, according to the data. Increased energy tariffs, insufficient investment in research and development, a lack of job opportunities, and other factors all act as roadblocks to the implementation of circular growth strategies.
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Tri- and Pentacyclic Azaphenothiazine as Pro-Apoptotic Agents in Lung Carcinoma with a Protective Potential to Healthy Cell Lines. The phenothiazine derivatives, tricyclic 10 H -3,6-diazaphenothiazine ( DPT-1 ) and pentacyclic 7-(3'-dimethylaminopropyl)diquinothiazine ( DPT-2 ), have recently been shown to exhibit promising anticancer activities in vitro. In this report, we demonstrated that DPT-1 and DPT-2 could be pro-apoptotic agents in lung carcinoma, the human lung carcinoma A549 and non-small lung carcinoma H1299, in the range of IC 50 = 1.52-12.89 µM, with a protective potential to healthy cell lines BEAS-2B and NHDF. The compounds showed higher activity in the range of the tested concentrations and low cytotoxicity in relation to normal healthy cells than doxorubicin, used as the reference drug. The cytostatic potential of DPT-1 and DPT-2 was demonstrated with the use of MTT assay. Cell cycle analysis via flow cytometry using Annexin-V assay showed the pro-apoptotic and pro-necrotic role of the studied diazaphenothiazines in the cell cycle. DPT-1 and DPT-2 initiated a biological response in the investigated cancer models with a different mechanism and at a different rate. Based on these findings, it can be concluded that DPT-1 and DPT-2 have potential as chemotherapeutic agents.
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Development of a highly efficient prime editor 2 system in plants. Low efficiency has seriously restricted the application of prime editing (PE) systems in plants. In this study, we develop an enhanced plant prime editor 2 system, enpPE2, by stacking various optimization strategies, including updating the PE architecture to PEmax and expressing engineered pegRNA with a structured motif under the control of a composite promoter. In T 0 rice plants, enpPE2 exhibits editing frequencies of 64.58% to 77.08%, which are much higher than the frequencies with unmodified pPE2. Our results indicate that the enpPE2 system provides a robust and powerful tool for the precise modification of plant genomes.
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Tidal volume challenge to predict preload responsiveness in patients with acute respiratory distress syndrome under prone position. Prone position is frequently used in patients with acute respiratory distress syndrome (ARDS), especially during the Coronavirus disease 2019 pandemic. Our study investigated the ability of pulse pressure variation (PPV) and its changes during a tidal volume challenge (TVC) to assess preload responsiveness in ARDS patients under prone position.
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Acute myeloid leukemia with myelodysplasia-related changes and blasts of the mixed T/myeloid phenotype: a case report. A rare but clinically important diagnostic dilemma arises when cases meet the criteria for both acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) and mixed phenotype acute leukemia, especially those that evolve from myelodysplastic syndrome. We describe a 56-year-old male patient who presented with cytopenias and was initially diagnosed with myelodysplastic syndrome with single lineage dysplasia. Nearly 1 year later, this patient progressed to acute leukemia, and his blast cells simultaneously expressed T-lymphoid and myeloid antigens. Cytogenetic analysis showed a 20q deletion, and next-generation sequencing showed mutations of ASXL1, NRAS, PHF6, RUNX1, TP53, and PIGA. He was diagnosed with AML-MRC with blasts of the mixed T/myeloid phenotype according to the latest World Health Organization guidelines. In accordance with the treatment principles of AML-MRC, we chose an AML-like regimen for four cycles, but the patient did not achieve remission. Finally, we adhered to the treatment principles of mixed phenotype acute leukemia, and he achieved remission after a course of ALL-like regimen chemotherapy.
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Novel Galactopyranoside Esters: Synthesis, Mechanism, In Vitro Antimicrobial Evaluation and Molecular Docking Studies. One-step direct unimolar valeroylation of methyl α-D-galactopyranoside (MDG) mainly furnished the corresponding 6- O -valeroate. However, DMAP catalyzed a similar reaction that produced 2,6-di- O -valeroate and 6- O -valeroate, with the reactivity sequence as 6-OH > 2-OH > 3-OH,4-OH. To obtain novel antimicrobial agents, 6- O - and 2,6-di- O -valeroate were converted into several 2,3,4-tri- O - and 3,4-di- O -acyl esters, respectively, with other acylating agents in good yields. The PASS activity spectra along with in vitro antimicrobial evaluation clearly indicated that these MDG esters had better antifungal activities than antibacterial agents. To rationalize higher antifungal potentiality, molecular docking was conducted with sterol 14α-demethylase (PDB ID: 4UYL, Aspergillus fumigatus ), which clearly supported the in vitro antifungal results. In particular, MDG ester 7 - 12 showed higher binding energy than the antifungal drug, fluconazole. Additionally, these compounds were found to have more promising binding energy with the SARS-CoV-2 main protease (6LU7) than tetracycline, fluconazole, and native inhibitor N3. Detailed investigation of Ki values, absorption, distribution, metabolism, excretion, and toxicity (ADMET), and the drug-likeness profile indicated that most of these compounds satisfy the drug-likeness evaluation, bioavailability, and safety tests, and hence, these synthetic novel MDG esters could be new antifungal and antiviral drugs.
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[Gestational diabetes mellitus in a hospital in the city of Buenos Aires, Argentina: incidence, treatment, and frequency of screening for reclassification after childbirth]. Gestational diabetes mellitus (GDM) is defined as glucose intolerance diagnosed during pregnancy. This pathology can be associated with maternal and feto-neonatal complications, both in the short and long term. The prevalence of GDM in Argentina (based on the diagnostic criteria of the Latin American Diabetes Association (ALAD), is estimated between 7.5-10% of pregnant women. Information in Argentina on the incidence of GDM is scarce. The objective of this work was to estimate the incidence of GDM, evaluate its treatment and the frequency of screening for postpartum reclassification of diabetes in a population of pregnant women treated at a private hospital in the city of Buenos Aires.
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Effects of High-Frequency Chest Wall Oscillation Expectoration System on Pulmonary Rehabilitation and Cortisol Function in Patients with Severe AECOPD. To investigate the effect of high-frequency chest wall oscillatory expectoration system (HFCWO) on pulmonary rehabilitation and cortisol function in patients with severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
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Preference for experiences: Regulatory focus and the trade-offs between experiential and material purchases. Consumers often make trade-offs between experiential and material purchases, a choice which has important implications for consumers as well as marketers. The current research explores the effect of regulatory focus on such trade-offs. We find that promotion-driven individuals have a higher preference for experiential purchases than people with a prevention focus. This effect is demonstrated with a set of nine studies that utilize different operationalizations of regulatory focus and purchase type, including seven studies in the main text that use experimental data and two studies in the online Supplemental Materials that use real-world data (Instagram and Google Trends). Due to the variable nature of an experiential purchase, promotion-focused individuals are drawn to its numerous upside potentials, whereas prevention-focused people focus on its many downside potentials. Using both the mediation and moderation approaches, we show that the focus of attention on experiential purchases drives the observed effect. Finally, we demonstrate the evidential value of our findings with a p-curve analysis. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Emerging drugs for the treatment of glaucoma: a review of phase II & III trials. Glaucoma is a progressive optic neuropathy and the leading cause of irreversible vision loss. By 2040, the number of individuals with glaucoma is expected to nearly double. The only known modifiable risk factor for glaucoma is intraocular pressure. Topical medications are often used as first-line therapies. Although there are numerous available treatments, there continues to be a need for the development of new medical therapies due to variable response, intolerable side-effect profiles in some patients, and elevated intraocular pressure refractory to other treatments.
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Contribution to the knowledge of the genus Ovipennis Hampson, 1900 with descriptions of two new species from Southern and Southwestern China (Lepidoptera, Erebidae, Arctiinae, Lithosiini). The knowledge of the genus Ovipennis Hampson, 1900 is updated. Nanarsine milani (ern, 2009) is recorded from China and Vietnam for the first time and transferred to the genus Ovipennis based on multilocus molecular phylogenetic and morphological analyses: O. milani (ern, 2009), comb. n. Two new species related to Ovipennis semilutea species-group are described: O. mixta Huang, Zhao, Volynkin Han, sp. n. from Guizhou and Hunan and O. multicornuta Huang, Volynkin, Zhao Han, sp. n. from Sichuan. Adults and genitalia of the aforementioned taxa are illustrated.
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[Sexually transmitted diseases, STD]. Early detection and competent treatment of sexually transmitted diseases (STDs) is essential to maintain or restore the sexual health of those affected and to prevent further transmission. In this context, counselling on Sexually transmitted infections (STI) is of particular importance, both in terms of prevention and rapid diagnosis and treatment. STI are not rare in Germany: syphilis, gonococcal and chlamydial infections even occur with increasing frequency, especially among MSM. At-risk populations (MSM, sex workers, people from high-prevalence regions, partners of STI sufferers) should be offered STI screening. If an STI is present, those affected should also be actively screened for other STIs, and furthermore partners should also be examined for STIs and treated if necessary. Syphilis and other STIs also occur with completely unspecific symptoms. Even asymptomatic infections by gonococci, chlamydia, mycoplasma, HPV, HBV, HCV and HPV can lead to serious complications and late consequences. For STI (HIV, HBV, syphilis), highly effective post-exposure prophylaxis (PEP) is available in some cases.
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Sustainable removal of soil arsenic by naturally-formed iron oxides on plastic tubes. Arsenic (As) pollution in paddy fields is a major threat to rice safety. Existing As remediation techniques are costly, require external chemical addition and degrade soil properties. Here, we report the use of plastic tubes as a recyclable tool to precisely extract As from contaminated soils. Following insertion into flooded paddy soils, polyethylene tube walls were covered by thin but massive Fe coatings of 76.9-367 mg Fe m -2 in 2 weeks, which adsorbed significant amounts of As. The formation of tube-wall Fe oxides was driven by local Fe-oxidizing bacteria with oxygen produced by oxygenic phototrophs (e.g., Cyanobacteria) or diffused from air through the tube wall. The tubes with As-bound Fe oxides can be easily separated from soil and then washed and reused. We tested the As removal efficiency in a pot experiment to remove As from ~ 20 cm depth/40 kg soils in a 2-year experiment and achieved an overall removal efficiency of 152 mg As m -2 soil year -1 , comparable to phytoremediation with the As hyperaccumulator Pteris vittata. The cost of Fe hooks was estimated at 8325 RMB ha -1 year -1 , and the profit of growing rice (around 16080 RMB ha -1 year -1 can be still maintained. The As accumulated in rice tissues was markedly decreased in the treatment (>11.1 %). This work provides a low-cost and sustainable soil remediation method for the targeted removal of As from soils and a useful tool for the study and management of the biogeochemical Fe cycle in paddy soils.
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A 40-Year Litigation Review of Transurethral Surgeries for Benign Prostatic Hyperplasia. To describe litigation patterns of transurethral surgery in the treatment of benign prostatic hyperplasia including verdicts, types of lawsuits, plaintiff claims, and timing of the claims.
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The development of digital ownership in children. The current study examined whether, for children and adults, behaviors that are considered violations of property rights in the case of physical property are likewise viewed as violations in the case of digital property. In this preregistered study (N = 156), 5- to 10-year-old children and adults heard a story about a person who downloaded a digital file (e.g., an e-book that she did not own) onto her personal computer (digital) versus a person who put a physical item (e.g., a book that she did not own) into her bag (physical). Participants were asked to evaluate how okay each behavior is. We found that from 5 years of age children evaluated taking a physical object more negatively than downloading a digital file, which was also the pattern observed in adults. Furthermore, by 9 years of age children were equivalent to adults in their evaluation of downloading digital files. The current study has implications for the development of ownership in children.
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Antibacterial, Antibiofilm, and Antiviral Farnesol-Containing Nanoparticles Prevent Staphylococcus aureus from Drug Resistance Development. Multidrug antimicrobial resistance is a constantly growing health care issue associated with increased mortality and morbidity, and huge financial burden. Bacteria frequently form biofilm communities responsible for numerous persistent infections resistant to conventional antibiotics. Herein, novel nanoparticles (NPs) loaded with the natural bactericide farnesol (FSL NPs) are generated using high-intensity ultrasound. The nanoformulation of farnesol improved its antibacterial properties and demonstrated complete eradication of Staphylococcus aureus within less than 3 h, without inducing resistance development, and was able to 100% inhibit the establishment of a drug-resistant S. aureus biofilm. These antibiotic-free nano-antimicrobials also reduced the mature biofilm at a very low concentration of the active agent. In addition to the outstanding antibacterial properties, the engineered nano-entities demonstrated strong antiviral properties and inhibited the spike proteins of SARS-CoV-2 by up to 83%. The novel FSL NPs did not cause skin tissue irritation and did not induce the secretion of anti-inflammatory cytokines in a 3D skin tissue model. These results support the potential of these bio-based nano-actives to replace the existing antibiotics and they may be used for the development of topical pharmaceutic products for controlling microbial skin infections, without inducing resistance development.
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A case of hepatocellular carcinoma with long-term survival by multidisciplinary treatment for cranial and skeletal muscle metastases. We report a case in which multidisciplinary treatment was effective for hepatocellular carcinoma (HCC) with cranial and skeletal muscle metastases. A 55-year-old male with HCC received sorafenib for lung metastases. He was admitted to our hospital due to the skull metastasis detected by fluorodeoxyglucose positron emission tomography (FDG-PET). The patient underwent resection for skull metastasis. After the surgical treatment, he was treated with sorafenib again. Eight months after craniectomy, FDG-PET showed FDG uptake in the semimembranosus and semitendinosus muscles. Histopathological examination of the muscle biopsy revealed HCC muscle metastasis. Sorafenib treatment was discontinued. The investigational new drug (tegafur-gimeracil-oteracil) and tegafur-uracil were used for the treatment. These treatments proved to be ineffective as the lung metastases enlarged and new metastases appeared on the mediastinal lymph nodes and dura cava. The patient was unable to walk due to the enlarged thigh muscle metastases. Sorafenib was re-administered, which reduced the enlargement of the lung and mediastinal lymph nodes. Dural metastases were treated with resection and radiotherapy. Additional radiation therapy to the thigh muscles relieved the patient from pain experienced during walking. Sorafenib treatment was continued for the next 3 years. The patient survived for 4 years after the skull resection.
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Embryogenic Stem Cell Identity after Protoplast Isolation from Daucus carota and Recovery of Regeneration Ability through Protoplast Culture. Protoplasts are single cells isolated from tissues or organs and are considered a suitable system for cell studies in plants. Embryogenic cells are totipotent stem cells, but their regeneration ability decreases or becomes lost altogether with extension of the culture period. In this study, we isolated and cultured EC-derived protoplasts (EC-pts) from carrots and compared them with non-EC-derived protoplasts (NEC-pts) with respect to their totipotency. The protoplast isolation conditions were optimized, and the EC-pts and NEC-pts were characterized by their cell size and types. Both types of protoplasts were then embedded using the alginate layer (TAL) method, and the resulting EC-pt-TALs and NEC-pt-TALs were cultured for further regeneration. The expression of the EC-specific genes SERK1, WUS, BBM, LEC1, and DRN was analyzed to confirm whether EC identity was maintained after protoplast isolation. The protoplast isolation efficiency for EC-pts was 2.4-fold higher than for NEC-pts (3.5 × 10 6 protoplasts·g -1 FW). In the EC-pt group, protoplasts < 20 µm accounted for 58% of the total protoplasts, whereas in the NEC-pt group, small protoplasts accounted for only 26%. In protoplast culture, the number of protoplasts that divided was 2.6-fold higher for EC-pts than for NEC-pts (7.7 × 10 4 protoplasts·g -1 FW), with a high number of plants regenerated for EC-pt-TALs, whereas no plants were induced by NEC-pt-TAL. Five times more plants were regenerated from EC-pts than from ECs. Regarding the expression of EC-specific genes, WUS and SERK1 expression increased 12-fold, and LEC1 and BBM expression increased 3.6-6.4-fold in isolated protoplasts compared with ECs prior to protoplast isolation (control). These results reveal that the protoplast isolation process did not affect the embryogenic cell identity; rather, it increased the plant regeneration rate, confirming that EC-derived protoplast culture may be an efficient system for increasing the regeneration ability of old EC cultures through the elimination of old and inactivate cells. EC-derived protoplasts may also represent an efficient single-cell system for application in new breeding technologies such as genome editing.
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Flow cytometry lyophilised-reagent tube for quantifying peripheral blood neutrophil myeloperoxidase expression in myelodysplastic syndromes (MPO-MDS-Develop): protocol for a diagnostic accuracy study. Suspicion of myelodysplastic syndromes (MDS) is the most common reason for bone marrow aspirate in elderly patients. Peripheral blood neutrophil myeloperoxidase expression quantified by flow cytometric analysis might rule out MDS for up to 35% of patients referred for suspected disease, without requiring bone marrow aspiration. Yet laboratory-developed liquid antibody cocktails have practical limitations, because of lack of standardisation and poor stability. This research project aims to estimate the level of agreement and comparative accuracy between a single-use flow cytometry tube of lyophilised reagents (BD Lyotube Stain 468) and its laboratory-developed liquid reagent counterpart in quantifying peripheral blood neutrophil myeloperoxidase expression, among adult patients referred for suspected MDS.
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Intervertebral disc cell chondroptosis elicits neutrophil response in Staphylococcus aureus spondylodiscitis. To understand the pathophysiology of spondylodiscitis due to Staphylococcus aureus , an emerging infectious disease of the intervertebral disc (IVD) and vertebral body with a high complication rate, we combined clinical insights and experimental approaches. Clinical data and histological material of nine patients suffering from S. aureus spondylodiscitis were retrospectively collected at a single center. To mirror the clinical findings experimentally, we developed a novel porcine ex vivo model mimicking acute S. aureus spondylodiscitis and assessed the interaction between S. aureus and IVD cells within their native environment. In addition, the inflammatory features underlying this interaction were assessed in primary human IVD cells. Finally, mirroring the clinical findings, we assessed primary human neutrophils for their ability to respond to secreted inflammatory modulators of IVD cells upon the S. aureus challenge. Acute S. aureus spondylodiscitis in patients was characterized by tissue necrosis and neutrophil infiltration. Additionally, the presence of empty IVD cells' lacunae was observed. This was mirrored in the ex vivo porcine model, where S. aureus induced extensive IVD cell death, leading to empty lacunae. Concomitant engagement of the apoptotic and pyroptotic cell death pathways was observed in primary human IVD cells, resulting in cytokine release. Among the released cytokines, functionally intact neutrophil-priming as well as broad pro- and anti-inflammatory cytokines which are known for their involvement in IVD degeneration were found. In patients as well as ex vivo in a novel porcine model, S. aureus IVD infection caused IVD cell death, resulting in empty lacunae, which was accompanied by the release of inflammatory markers and recruitment of neutrophils. These findings offer valuable insights into the important role of inflammatory IVD cell death during spondylodiscitis and potential future therapeutic approaches.
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Effects of Serum LDL-C, CysC, and D-D in Patients with Coronary Atherosclerotic Heart Disease. To investigate the effects of low-density lipoprotein cholesterol (LDL-C) and serum cystatin C (CysC) combined with D-dimer (D-D) on patients with coronary atherosclerotic heart disease (CHD).
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[Early urethral catheter removal after robot-assisted radical prostatectomy]. Robot-assisted radical prostatectomy (RARP) is a widely used treatment method for patients with clinically localized prostate cancer. Posterior reconstruction of urethrovesical anastomosis (UVA) is one of the techniques that provides early recovery of urinary continence after surgery. Changes in the technique of performing posterior reconstruction of UVA may contribute to further improvement of functional results.
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TB in the elderly: clinical features and outcomes. BACKGROUND: TB in low-incidence countries is characterised by changes in age distribution towards larger numbers of cases among the elderly. OBJECTIVES: To investigate clinical features and outcomes of TB treatment in older patients and identify predictors of poor outcome. METHODS: Multicentre retrospective study of new TB cases from 53 hospitals included in the registry of the Integrated Tuberculosis Research Programme of the Spanish Society of Pulmonology and Thoracic Surgery ( Sociedad Española de Neumología y Cirugía Torácica ) between 2006 and 2020. RESULTS: We identified 731 patients aged ≥75 years from a cohort of 7,505 patients with TB. In the elderly, weight loss, disseminated disease and normal X-rays or infiltrates without cavitation were more common. All-cause mortality was 16% (5% of deaths due to TB). The elderly had higher rates of toxicity (6.7%) and hospital admissions (36%). In the multivariate analysis of predictors of TB mortality in ≥75-year-olds, only weight, age and treatment with non-standard regimens remained significant. CONCLUSIONS: TB in older patients needs more attention and remains a challenge because of a lack of specific clinical and radiological features. Standard treatment is effective, although mortality is higher than in young patients. Low weight, non-standard regimens and age are significant predictors of TB mortality.
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Ellagic Acid Increases Stress Resistance via Insulin/IGF-1 Signaling Pathway in Caenorhabditis elegans . Ellagic acid is a natural polyphenol found in various fruits and vegetables. Numerous studies have shown that ellagic acid has beneficial effects on human health. In this study, we investigated the stress resistant action of ellagic acid in Caenorhabditis elegans ( C. elegans ). Notably, 50 μM ellagic acid prolonged the lifespan of C. elegans by 36.25%, 36.22%, 155.1%, and 79.07% under ultraviolet radiation stress, heat stress, oxidative stress, and Pseudomonas aeruginosa infection stress, respectively. Furthermore, the mechanism by which ellagic acid reduces the damage caused by ultraviolet radiation in C. elegans was explored. Ellagic acid could significantly induce the nucleus translocation of DAF-16 and, thereby, activate a series of target genes to resist ultraviolet radiation stress. Moreover, ellagic acid also significantly increased the expression of SOD-3 by 3.61 times and the activity of superoxide dismutase by 3.70 times to clean out harmful reactive oxygen species in C. elegans exposed to ultraviolet radiation stress. In both daf-16 mutant and daf-2 ; daf-16 double-mutant worms exposed to ultraviolet radiation, ellagic acid could no longer prolong their lifespan. These results indicate that ellagic acid plays an important role in resisting ultraviolet radiation stress in C. elegans, probably in an insulin/IGF-1 signaling pathway-dependent way.
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Exploration of critical thinking and self-regulated learning in online learning during the COVID-19 pandemic. An in-depth analysis of today's online biochemistry learning is required to ensure better learning in the future. As a skill that students need to enter the world of work, critical thinking remains a goal in higher education. To develop critical thinking, students need to self-regulate by developing their self-regulated learning (SRL). This study aims to analyze students' critical thinking and SRL during online biochemistry learning. The research sample comprises 54 University of Mataram students. The data on critical thinking and SRL were gathered using tests and questionnaires. Supporting data were collected from observations on the Moodle platform, which was used as a learning tool during the learning process, and free-response data. The results revealed low average scores for three components of the students' critical thinking in online biochemistry learning, namely hypothesis testing, developing conclusions and argument analysis. Among the indicators, metacognitive skill had the highest average score and help seeking had the lowest average score in the SRL measurement. Students' low critical thinking in online biochemistry learning may be caused by a lack of student-student interaction.
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Effects of current treatments for trauma survivors with posttraumatic stress disorder on reducing a negative self-concept: a systematic review and meta-analysis. <b>Background:</b> A negative self-concept is characterised by dysfunctional cognitions about the self and has been suggested to be a key factor involved in the development and maintenance of posttraumatic stress disorder (PTSD). In addition, the current definitions of PTSD according to DSM-5 and the new ICD-11 diagnosis of Complex PTSD (CPTSD) include aspects of negative self-concept in their diagnostic criteria. <b>Objective:</b> The aim of this meta-analysis was to synthesise the currently available evidence on the effects of psychological interventions for PTSD on negative self-concept. <b>Methods:</b> PubMed, PsychINFO, PSYNDEX, PTSDpubs and Cochrane Library were searched for randomised controlled trials (RCTs) of psychological treatments for PTSD symptoms in adults, published up to February 2021. A systematic review and meta-analysis were conducted, with risk of bias assessed by the Cochrane Risk of Bias Assessment Tool. <b>Results:</b> A total of 25 RCTs (<i>N</i> = 2585) were included in the meta-analysis. Results showed that psychological interventions significantly improve a negative self-concept with a moderate to large controlled effect size (<i>k</i> = 30, <i>g</i> = 0.67, 95% CI [0.31, 1.02], <i>p</i> &lt; .001) at post-treatment. Heterogeneity between studies was large but could not be accounted for by moderators included in the current analysis, i.e. different types of interventions (e.g. with vs. without a cognitive restructuring component, trauma-focused vs. not). <b>Conclusions:</b> Current treatments for PTSD are effective in reducing a negative self-concept. However, more research is needed to identify moderators of this effect and identify interventions that are most effective for reducing negative self-concept.
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Genomic characteristics of two most widely used BCG vaccine strains: Danish 1331 and Pasteur 1173P2. Bacillus Calmette-Guérin (BCG) refers to a group of vaccine strains with unique genetic characteristics. BCG is the only available vaccine for preventing tuberculosis (TB). Genetic and biochemical variations among the BCG vaccine strains have been considered as one of the significant parameters affecting the variable protective efficacy of the vaccine against pulmonary tuberculosis. To track genetic variations, here two vaccine strains (Danish 1331 and Pasteur 1173P2) popularly used according to the BCG World Atlas were subjected to a comparative analysis against the Mycobacterium tuberculosis H37Rv, Mycobacterium bovis AF2122/97, and Mycobacterium tuberculosis variant bovis BCG str. Pasteur 1173P2 reference genomes. Besides, the presence or absence of the experimentally verified human T cell epitopes was examined.
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Alginate/polyvinyl alcohol films for wound healing: Advantages and challenges. The skin is the largest organ in the human body and its physical integrity must be maintained for body homeostasis and to prevent the entry of pathogenic microorganisms. Sodium alginate (SA) and polyvinyl alcohol (PVA) are two polymers widely used in films for wound dressing applications. Furthermore, blends between SA and PVA improve physical, mechanical and biological properties of the final wound healing material when compared to the individual polymers. Different drugs have been incorporated into SA/PVA-based films to improve wound healing activity. It is noteworthy that SA/PVA films can be crosslinked with Ca 2+ or other agents, which improves physicochemical and biological properties. Thus, SA/PVA associations are promising for the biomedical field, as a potential alternative for wound treatment. This review focuses on the main techniques for obtaining SA/PVA films, their physical-chemical characterization, drug incorporation, and the advantages and challenges of these films for wound healing.
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Physical and psychological intimate partner violence: Relations with child threat appraisals and internalizing and externalizing symptoms. This study examined whether interparental physical and psychological intimate partner violence (IPV) have additive effects on child threat appraisals and internalizing and externalizing symptoms, and whether relations between psychological IPV and child difficulties differ when physical IPV has occurred, as compared to when it has not occurred. Participants were 531 children (51% male) aged 7-10 years and their mothers. Children reported on IPV, and on their threat appraisals; children and mothers both reported on child internalizing and externalizing symptoms. Families participated in three assessments spaced 6 months apart. Results indicated that physical and psychological IPV had additive effects on child threat appraisals and child reports of disruptive behavior problems, but not on other measures of child internalizing or externalizing symptoms. Results of moderator analyses indicated that relations between psychological IPV and mothers' reports of child internalizing symptoms, and between psychological IPV and child reports of disruptive behavior problems were stronger when physical IPV had occurred. Notably, psychological IPV was also associated with child threat appraisals, anxiety symptoms, and disruptive behavior problems even in the absence of physical IPV. The findings suggest that in child and family research and service settings, when aspects of the interparental relationship are relevant, the risks posed by psychological IPV should be considered. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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[Constructing resonance in a polluted area: the case of 'Rolando da Piazzola' (Veneto Region, Northern Italy)]. Environmental pollution in the site of the high school 'Rolando da Piazzola' in Piazzola sul Brenta (Padua, Veneto Region, Northern Italy) was discovered by chance in 2020. Since then, investigations on the environmental damage have been ongoing, while the school is anyway working. The purpose of this article is twofold. On the one hand, to narrate the stratification uses in the area from 1891 to nowadays: a story accounting for both the processing of chemical fertilizers at the origin of pollution and its oblivion between the 1960s and 1980s. On the other hand, to shed light on such forgotten memories by recovering last-century narratives and current voices on the past, thus providing a first assessment of a work in progress. The industrial legacy and the sudden change of use of the area itself exhibit a 'cognitive dissonance' between the harmfulness of the place, known to the population since the factory was active, and the inertia of top-down projects, passed in the name of interests and variously conceived notion of development. Such dissonance is now to be grasped by the school, in the light of an ecological view. The participatory reasoning on the environmental and health risks alludes to the civic mission of the school and calls for a syntonic relationship with the territory. These operations require a resonance inside and outside the institute, which has still not been found. What is at stake is the need to reconnect the memory between generations and the relationships between human and non-human entities (i.e., the environment). On these basis, it would be possible to build some scientific citizenship that can face uncertainty without paralyzing effect, but in a new, transparent, and horizontal narrative about the sense of a place and of itself.
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Effect of a Lifestyle Intervention on Cardiometabolic Health Among Emerging Adults: A Randomized Clinical Trial. The prevalence of obesity has increased substantially among emerging adults, yet no previous large-scale behavioral weight loss trials have been conducted among this age group.
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The Bacterial ClpXP-ClpB Family Is Enriched with RNA-Binding Protein Complexes. In the matrix of bacteria/mitochondria/chloroplasts, Lon acts as the degradation machine for soluble proteins. In stress periods, however, proteostasis and survival depend on the strongly conserved Clp/Hsp100 family. Currently, the targets of ATP-powered unfoldases/disaggregases ClpB and ClpX and of peptidase ClpP heptameric rings are still unclear. Trapping experiments and proteome profiling in multiple organisms triggered confusion, so we analyzed the consistency of ClpP-trap targets in bacteria. We also provide meta-analyses of protein interactions in humans, to elucidate where Clp family members are enriched. Furthermore, meta-analyses of mouse complexomics are provided. Genotype-phenotype correlations confirmed our concept. Trapping, proteome, and complexome data retrieved consistent coaccumulation of CLPXP with GFM1 and TUFM orthologs. CLPX shows broad interaction selectivity encompassing mitochondrial translation elongation, RNA granules, and nucleoids. CLPB preferentially attaches to mitochondrial RNA granules and translation initiation components; CLPP is enriched with them all and associates with release/recycling factors. Mutations in CLPP cause Perrault syndrome, with phenotypes similar to defects in mtDNA/mtRNA. Thus, we propose that CLPB and CLPXP are crucial to counteract misfolded insoluble protein assemblies that contain nucleotides. This insight is relevant to improve ClpP-modulating drugs that block bacterial growth and for the treatment of human infertility, deafness, and neurodegeneration.
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SMART-LAMP: A Smartphone-Operated Handheld Device for Real-Time Colorimetric Point-of-Care Diagnosis of Infectious Diseases via Loop-Mediated Isothermal Amplification. Nucleic acid amplification diagnostics offer outstanding features of sensitivity and specificity. However, they still lack speed and robustness, require extensive infrastructure, and are neither affordable nor user-friendly. Thus, they have not been extensively applied in point-of-care diagnostics, particularly in low-resource settings. In this work, we have combined the loop-mediated isothermal amplification (LAMP) technology with a handheld portable device (SMART-LAMP) developed to perform real-time isothermal nucleic acid amplification reactions, based on simple colorimetric measurements, all of which are Bluetooth-controlled by a dedicated smartphone app. We have validated its diagnostic utility regarding different infectious diseases, including Schistosomiasis, Strongyloidiasis, and COVID-19, and analyzed clinical samples from suspected COVID-19 patients. Finally, we have proved that the combination of long-term stabilized LAMP master mixes, stored and transported at room temperature with our developed SMART-LAMP device, provides an improvement towards true point-of-care diagnosis of infectious diseases in settings with limited infrastructure. Our proposal could be easily adapted to the diagnosis of other infectious diseases.
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Comprehensive analysis of intratumoural heterogeneity of somatic copy number alterations in diffuse glioma reveals clonality-dependent prognostic patterns. Intratumoural heterogeneity (ITH) has been implicated in tumour growth and progression as well as therapy resistance. However, the extent of ITH of somatic copy number alterations (ITH-SCNAs) as a result of tumour evolution and its influence on clinical outcomes in diffuse glioma (DG) remain poorly understood.
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Comfrey polysaccharides modulate the gut microbiota and its metabolites SCFAs and affect the production performance of laying hens. Effects of dietary supplementation of comfrey polysaccharides (CPs) on production performance, egg quality, and microbial composition of cecum in laying hens were evaluated. A total of 240 laying hens were allocated into 4 groups with 6 replicates per group. The laying hens were fed diets containing CPs at levels of 0, 0.5, 1.0, and 1.5 %, respectively. The results showed that the egg production rate increased by 5.97 %, the egg mass improved by 6.71 %, and the feed conversion rate reduced by 5.43 % in the 1.0 % supplementation group of CPs compared with those in the control group. The digestibility of ash, crude fat, and phosphorus was notably improved by the addition of CPs at 1.0 % (P < 0.05). The relative abundances of Bacteroidetes at the phylum level, Bacteroidaceae, Rikenellaceae, and Prevotellaceae at the family level were increased by CPs (P < 0.05). The relative abundances of Bacteroides, Megamonas, Rikenellaceae_RC9_gut_group, [Ruminococcus]_torques_group, Methanobrevibacter, Desulfovibrio, Romboutsia, Alistipes, and Intestinimonas at the genus level were increased by CPs (P < 0.05). Dietary supplementation of CPs could enhance the production performance of laying hens, which might be related to the improvement of nutrient digestibility and microbial community modulations in the cecum. Therefore, CPs have potential application value as prebiotics in laying hens.
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Recursive Decomposition Network for Deformable Image Registration. Deformation decomposition serves as a good solution for deformable image registration when the deformation is large. Current deformation decomposition methods can be categorized into cascade-based methods and pyramid-based methods. However, cascade-based methods suffer from heavy computational burdens and long inference time due to their structures of repeated subnetworks, while the effectiveness of pyramid-based methods is constrained by their limited numbers of resolution levels. In this paper, to address both the insufficient and inefficient decomposition problems in current deformation decomposition methods, we propose a recursive decomposition network (RDN) to offer a novel solution for deformable image registration. Stage-wise recursion can efficiently decompose a large deformation into different pyramid estimation stages without using repeated subnetworks like in cascade-based methods. Level-wise recursion can sufficiently decompose the deformation inside each resolution level instead of only one-time estimation like in pyramid-based methods. Extensive experiments and ablation studies on two representative datasets validate the effectiveness and efficiency of our proposed RDN.
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Pooled screening of CAR T cells identifies diverse immune signaling domains for next-generation immunotherapies. Chimeric antigen receptors (CARs) repurpose natural signaling components to retarget T cells to refractory cancers but have shown limited efficacy in persistent, recurrent malignancies. Here, we introduce "CAR Pooling," a multiplexed approach to rapidly identify CAR designs with clinical potential. Forty CARs with signaling domains derived from a range of immune cell lineages were evaluated in pooled assays for their ability to stimulate critical T cell effector functions during repetitive stimulation that mimics long-term tumor antigen exposure. Several domains were identified from the tumor necrosis factor (TNF) receptor family that have been primarily associated with B cells. CD40 enhanced proliferation, whereas B cell-activating factor receptor (BAFF-R) and transmembrane activator and CAML interactor (TACI) promoted cytotoxicity. These functions were enhanced relative to clinical benchmarks after prolonged antigen stimulation, and CAR T cell signaling through these domains fell into distinct states of memory, cytotoxicity, and metabolism. BAFF-R CAR T cells were enriched for a highly cytotoxic transcriptional signature previously associated with positive clinical outcomes. We also observed that replacing the 4-1BB intracellular signaling domain with the BAFF-R signaling domain in a clinically validated B cell maturation antigen (BCMA)-specific CAR resulted in enhanced activity in a xenotransplant model of multiple myeloma. Together, these results show that CAR Pooling is a general approach for rapid exploration of CAR architecture and activity to improve the efficacy of CAR T cell therapies.
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Agreement between the laboratory-based and non-laboratory-based WHO cardiovascular risk charts: a cross-sectional analysis of a national health survey in Peru. To determine the agreement between the cardiovascular disease (CVD) risk predictions computed with the WHO non-laboratory-based model and laboratory-based model in a nationally representative sample of Peruvian adults.
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Fair Facial Attribute Classification via Causal Graph-Based Attribute Translation. Recent studies have raised concerns regarding racial and gender disparity in facial attribute classification performance. As these attributes are directly and indirectly correlated with the sensitive attribute in a complex manner, simple disparate treatment is ineffective in reducing performance disparity. This paper focuses on achieving counterfactual fairness for facial attribute classification. Each labeled input image is used to generate two synthetic replicas: one under factual assumptions about the sensitive attribute and one under counterfactual. The proposed causal graph-based attribute translation generates realistic counterfactual images that consider the complicated causal relationship among the attributes with an encoder-decoder framework. A causal graph represents complex relationships among the attributes and is used to sample factual and counterfactual facial attributes of the given face image. The encoder-decoder architecture translates the given facial image to have sampled factual or counterfactual attributes while preserving its identity. The attribute classifier is trained for fair prediction with counterfactual regularization between factual and corresponding counterfactual translated images. Extensive experimental results on the CelebA dataset demonstrate the effectiveness and interpretability of the proposed learning method for classifying multiple face attributes.
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Autotaxin Has a Negative Role in Systemic Inflammation. The pathogenesis of sepsis involves complex interactions and a systemic inflammatory response leading eventually to multiorgan failure. Autotaxin (ATX, ENPP2) is a secreted glycoprotein largely responsible for the extracellular production of lysophosphatidic acid (LPA), which exerts multiple effects in almost all cell types through its at least six G-protein-coupled LPA receptors (LPARs). Here, we investigated a possible role of the ATX/LPA axis in sepsis in an animal model of endotoxemia as well as in septic patients. Mice with 50% reduced serum ATX levels showed improved survival upon lipopolysaccharide (LPS) stimulation compared to their littermate controls. Similarly, mice bearing the inducible inactivation of ATX and presenting with &gt;70% decreased ATX levels were even more protected against LPS-induced endotoxemia; however, no significant effects were observed upon the chronic and systemic transgenic overexpression of ATX. Moreover, the genetic deletion of LPA receptors 1 and 2 did not significantly affect the severity of the modelled disease, suggesting that alternative receptors may mediate LPA effects upon sepsis. In translation, ATX levels were found to be elevated in the sera of critically ill patients with sepsis in comparison with their baseline levels upon ICU admission. Therefore, the results indicate a role for ATX in LPS-induced sepsis and suggest possible therapeutic benefits of pharmacologically targeting ATX in severe, systemic inflammatory disorders.
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Historical mercury contamination in a major Latin American industrial and port complex: The case of the Santos estuary, Southeastern Brazil. The present study determined total mercury (Hg) in four 210 Pb dated sediment cores to assess the historical anthropogenic Hg accumulation in the Santos estuary, Southeastern Brazil. Background levels were identified using the deepest sections of the cores, corresponding to pre-industrial ages. Mercury distribution in the sediment cores (0.02-2.64 mg kg -1 ) presented a large spatial and temporal variation. Contamination is highest in the upper estuary and indicates that the industrial hub, especially a chlor-alkali plant is the primary source of Hg. A contaminant trap effect is observed in this area associated with high fine sediment accumulation and Hg fluxes. The contamination pattern indicates that the regions not affected by direct inputs are influenced by reworking, resuspension, and transport of contaminated sediments by tidal flows. The Hg enrichment in the upper layers of the sediment cores demonstrates that the environmental actions fulfilled in the 1980s were insufficient to control Hg pollution in the Santos estuary.
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The Impact of Improved Oral Care Methods on the Oral Health of Patients Undergoing Transoral Mechanical Ventilation. To explore the effects of improved oral care on the number of oropharyngeal bacteria and the incidence of ventilator-associated pneumonia in patients undergoing mechanical ventilation through oral endotracheal intubation by improving conventional oral care methods and operating procedures and to evaluate the quality of improved oral care and effect.
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Inhibitory role of microRNA-484 in kidney stone formation by repressing calcium oxalate crystallization via a VDR/FoxO1 regulator axis. Kidney stones are regarded as common malignant diseases in the developed world. As a result, significant research examining their formation is ongoing, with microRNAs (miRs) recently being linked with kidney stone formation. Here, we aim to define the potential role of miR-484 in regulating renal tubular epithelial cell (RTEC) viability and the attachment of calcium oxalate (CaOx) crystals to RTECs via vitamin D receptor (VDR)/forkhead box protein O1 (FoxO1) axis. The pathological condition of CaOx crystallization was induced and examined in Sprague-Dawley rats, while RTECs were isolated and cultured in vitro. Loss- and gain-function assays were performed to study the effects that miR-484, VDR, and FoxO1 on RTEC functions and CaOx crystallization in vitro and on kidney stone formation in vivo. The interaction between miR-484 and VDR was confirmed by dual-luciferase reporter gene assays. Downregulation of miR-484 and FoxO1 as well as overexpression of VDR were identified in kidney stone modelled rats. VDR was confirmed as a target gene of miR-484, while knockdown of VDR upregulated the FoxO1 expression. miR-484 overexpression or VDR suppression reduced RTEC cytotoxicity and crystal attachment to RTECs in vitro and reduced the CaOx crystallization in vivo. Taken together, these findings suggest that miR-484 overexpression may be a potential inhibitor of RTEC proliferation and CaOx crystallization through a VDR/FoxO1 regulatory axis, providing a novel therapeutic target for the treatment of kidney stone.
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Safety and Feasibility of Steerable Radiofrequency Ablation in Combination with Cementoplasty for the Treatment of Large Extraspinal Bone Metastases. Radiofrequency ablation (RFA) and cementoplasty, individually and in concert, has been adopted as palliative interventional strategies to reduce pain caused by bone metastases and prevent skeletal related events. We aim to evaluate the feasibility and safety of a steerable RFA device with an articulating bipolar extensible electrode for the treatment of extraspinal bone metastases.
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[Characteristics of older people who have an intention to work as assistance personnel for long-term care or childcare]. Objectives With the rapid progress of aging society and decreasing population, there is a shortage of workers in various areas, which has become a serious problem especially in the welfare field, for long-term care and childcare. As one of the countermeasures, some efforts are being made to hire people who are living independent daily lives, as auxiliary personnel, and have them take charge of non-specialized peripheral work of the facilities. The purpose of this study was to examine the characteristics of older adults who have an intention to work as auxiliary personnel in the welfare field.Methods A self-response questionnaire survey was conducted from October to November 2019 for 374 members of "REPRINTS" who are picture-book reading volunteers, aged 60 years or more, and are living in the capital area. There were 295 valid responses. We performed logistic regression analysis using the presence or absence of intention to work for long-term care assistance and for childcare assistance as the dependent variables. The missing values were supplemented by the multiple imputation method (10 files were created).Results The results of analysis revealed that 24.9% of the respondents had an intention to work for long-term care assistance, and 36.6% for childcare assistance. From the results of logistic regression analysis, it was found that among those intending to work in long-term care assistance, participants involved in lifelong learning activities had significantly higher intention to work (OR: 2.98, 95%CI: 1.40-6.34). Among those intending to work in childcare assistance, those with a high subjective sense of health had a significantly higher intention to work (OR: 2.41, 95%CI: 1.01-5.76).Conclusion The intention of work for childcare assistance was higher than that for long-term care assistance. A notable characteristic of older people willing to work as assistants in the welfare field is that those who participate in lifelong learning activities would be willing to actively work for long-term care assistance, and those with high subjective health would be willing to actively work for childcare assistance. By focusing on the older people with these characteristics, we may be able to contribute to identifying the those among them who want to work as assistant personnel.
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Young children with autism show atypical prefrontal cortical responses to humanoid robots: An fNIRS study. Previous behavioral studies have found that children with autism spectrum disorder (ASD) show greater interest in humanoid robots than in humans. However, the neural mechanism underlying this is not clear. This study compared brain activation patterns between children with ASD and neurotypical children while they watched videos with robots and humans.
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Assembling a safe and effective toolbox for integrated flea control and plague mitigation: Fipronil experiments with prairie dogs. Plague, a widely distributed zoonotic disease of mammalian hosts and flea vectors, poses a significant risk to ecosystems throughout much of Earth. Conservation biologists use insecticides for flea control and plague mitigation. Here, we evaluate the use of an insecticide grain bait, laced with 0.005% fipronil (FIP) by weight, with black-tailed prairie dogs (BTPDs, Cynomys ludovicianus). We consider safety measures, flea control, BTPD body condition, BTPD survival, efficacy of plague mitigation, and the speed of FIP grain application vs. infusing BTPD burrows with insecticide dusts. We also explore conservation implications for endangered black-footed ferrets (Mustela nigripes), which are specialized predators of Cynomys.
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SCFAs Ameliorate Chronic Postsurgical Pain-Related Cognition Dysfunction via the ACSS2-HDAC2 Axis in Rats. Patients with chronic postsurgical pain (CPSP) frequently exhibit comorbid cognitive deficits. Recent observations have emphasized the critical effects of gut microbial metabolites, like short-chain fatty acids (SCFAs), in regulating cognitive function. However, the underlying mechanisms and effective interventions remain unclear. According to hierarchical clustering and 16S rRNA analysis, over two-thirds of the CPSP rats had cognitive impairment, and the CPSP rats with cognitive impairment had an aberrant composition of gut SCFA-producing bacteria. Then, using feces microbiota transplantation, researchers identified a causal relationship between cognitive-behavioral and microbic changes. Similarly, the number of genera that generated SCFAs was decreased in the feces from recipients of cognitive impairment microbiota. Moreover, treatment with the SCFAs alleviated the cognitive-behavioral deficits in the cognitively compromised pain rats. Finally, we observed that SCFA supplementation improved histone acetylation and abnormal synaptic transmission in the medial prefrontal cortex (mPFC), hippocampal CA1, and central amygdala (CeA) area via the ACSS2 (acetyl-CoA synthetase2)-HDAC2 (histone deacetylase 2) axis. These findings link pain-related cognition dysfunction, gut microbiota, and short-chain fatty acids, shedding fresh insight into the pathogenesis and therapy of pain-associated cognition dysfunction.
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A long noncoding RNA influences the choice of the X chromosome to be inactivated. X chromosome inactivation (XCI) is the process of silencing one of the X chromosomes in cells of the female mammal which ensures dosage compensation between the sexes. Although theoretically random in somatic tissues, the choice of which X chromosome is chosen to be inactivated can be biased in mice by genetic element(s) associated with the so-called X-controlling element ( Xce ). Although the Xce was first described and genetically localized nearly 40 y ago, its mode of action remains elusive. In the approach presented here, we identify a single long noncoding RNA (lncRNA) within the Xce locus, Lppnx, which may be the driving factor in the choice of which X chromosome will be inactivated in the developing female mouse embryo. Comparing weak and strong Xce alleles we show that Lppnx modulates the expression of Xist lncRNA , one of the key factors in XCI, by controlling the occupancy of pluripotency factors at Intron1 of Xist . This effect is counteracted by enhanced binding of Rex1 in DxPas34 , another key element in XCI regulating the activity of Tsix lncRNA, the main antagonist of Xist, in the strong but not in the weak Xce allele. These results suggest that the different susceptibility for XCI observed in weak and strong Xce alleles results from differential transcription factor binding of Xist Intron 1 and DxPas34 , and that Lppnx represents a decisive factor in explaining the action of the Xce .
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Aquabots. Soft robots, made from elastomers, easily bend and flex, but deformability constraints severely limit navigation through and within narrow, confined spaces. Using aqueous two-phase systems we print water-in-water constructs that, by aqueous phase-separation-induced self-assembly, produce ultrasoft liquid robots, termed aquabots, comprised of hierarchical structures that span in length scale from the nanoscopic to microsciopic, that are beyond the resolution limits of printing and overcome the deformability barrier. The exterior of the compartmentalized membranes is easily functionalized, for example, by binding enzymes, catalytic nanoparticles, and magnetic nanoparticles that impart sensitive magnetic responsiveness. These ultrasoft aquabots can adapt their shape for gripping and transporting objects and can be used for targeted photocatalysis, delivery, and release in confined and tortuous spaces. These biocompatible, multicompartmental, and multifunctional aquabots can be readily applied to medical micromanipulation, targeted cargo delivery, tissue engineering, and biomimetics.
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Interictal discharges delay target-directed eye movements and impair attentional set-shifting in children with epilepsy. The theory of transient cognitive impairment in epilepsy posits that lapses in attention result from ephemeral disruption of attentional circuitry by interictal events. Eye movements are intimately associated with human attention and can be monitored in real time using eye-tracking technologies. Here, we sought to characterize the associations between interictal epileptiform discharges (IEDs), gaze, and attentional behavior in children with epilepsy.
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Feasibility and safety of a novel 3D-printed biodegradable biliary stent in an in vivo porcine model: a preliminary study. To assess the feasibility and safety of a novel 3D-printed biodegradable biliary stent using polycaprolactone (PCL) in an in vivo porcine model. In this animal study using domestic pigs, biodegradable radiopaque biliary stents made of polycaprolactone (PCL) and barium sulfate were produced using 3D printing and surgically inserted into the common bile duct (CBD) of pigs (stent group, n = 12). Another five pigs were allocated to the control group that only underwent resection and anastomosis of the CBD without stent insertion. To check the position and status of the stents and stent-related complications, follow-up computed tomography (CT) was performed every month. The pigs were sacrificed 1 or 3 months after surgery, and their excised CBD specimens were examined at both the macroscopic and microscopic levels. Three pigs (one in the stent group and two in the control group) died within one day after surgery and were excluded from further analysis; the remaining 11 in the stent group and 3 in the control group survived the scheduled follow-up period (1 month, 5 and 1; and 3 months, 6 and 2 in stent and control groups, respectively). In all pigs, no clinical symptoms or radiologic evidence of biliary complications was observed. In the stent group (n = 11), stent migration (n = 1 at 3 months; n = 2 at 1 month) and stent fracture (n = 3 at 2 months) were detected on CT scans. Macroscopic evaluation of the stent indicated no significant change at 1 month (n = 3) or fragmentation with discoloration at 3 months (n = 5). On microscopic examination of CBD specimens, the tissue inflammation score was significantly higher in the stent group than in the control group (mean ± standard deviation (SD), 5.63 ± 2.07 vs. 2.00 ± 1.73; P = 0.039) and thickness of fibrosis of the CBD wall was significantly higher than that of the control group (0.46 ± 0.12 mm vs. 0.21 ± 0.05 mm; P = 0.012). Despite mild bile duct inflammation and fibrosis, 3D-printed biodegradable biliary stents showed good feasibility and safety in porcine bile ducts, suggesting their potential for use in the prevention of postoperative biliary strictures.
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COVID-19 Symptoms and Deaths among Healthcare Workers, United States. We evaluated whether demographics and COVID-19 symptoms predicted COVID-19 deaths among healthcare workers (HCWs) in the United States by comparing COVID-19 deaths in HCWs with 3 control groups (HCW nondeaths, non-HCW deaths, and non-HCW nondeaths) using a case-control design. We obtained patient-level data of 33 variables reported during January 1, 2020-October 12, 2021, in all US states. We used logistic regression analysis while controlling for confounders. We found that persons who were >50 years of age, male, Black, or Asian experienced significantly more deaths than matched controls. In addition, HCWs who died had higher risks for the most severe clinical indicators. We also found that the most indicative symptoms were preexisting medical conditions, shortness of breath, fever, cough, and gastrointestinal symptoms. In summary, minority, male, and older HCWs had greater risk for COVID-19 death. Severe clinical indicators and specific symptoms may predict COVID-19-related deaths among HCWs.
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Long drives and red tape: mapping rural veteran access to primary care using causal-loop diagramming. Rural veterans experience more challenges than their urban peers in accessing primary care services, which can negatively impact their health and wellbeing. The factors driving this disparity are complex and involve patient, clinic, health system, community and policy influences. Federal policies over the last decade have relaxed requirements for some veterans to receive primary care services from community providers through their VA benefits, known as community care.
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The correlation of plasma atherogenic index and obesity in patients with familial Mediterranean fever. The plasma atherogenic index (PAI) is associated with cardiovascular diseases. This study evaluated the relationship between PAI and obesity in patients with familial Mediterranean fever (FMF) and its advantage over conventional lipid components in predicting obesity.
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HClO-Activated Near-Infrared Fluorogenic Aza-BODIPY-Bisferrocene Triad with High Turn-on Ratio for In Vivo Biosensing. Optically monitoring hypochlorous acid (HClO) in living body favors diagnosis and study of inflammatory diseases. However, this has been hampered by limited strategies to develop highly fluorogenic tools in the deep-penetration near-infrared spectrum. Herein, a near-infrared aza-BODIPY-bisferrocene triad Fc 2 -CBDP that unexpectedly achieves an exceptionally sensitive and selective fluorescence turn-on (>220-fold) response toward HClO through single-ferrocene oxidation and boron-alkynyl hydrolysis cascade is reported. Mechanism insight shows that Fc 2 -CBDP features "enhanced charge transfer"-caused quenching due to intramolecular bisferrocene electronic coupling, which is decoupled in the reaction with HClO. The utility of Fc 2 -CBDP for intracellular HClO imaging is evaluated and, more importantly, in vivo high-contrast deep-tissue imaging of lymphatic inflammation and colitis is realized. This work provides new insights into both HClO and ferrocene chemistry, and extends the reach of fluorogenic strategies in the near-infrared biosensing.
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Athletes' Mesenchymal Stem Cells Could Be the Best Choice for Cell Therapy in Omicron-Infected Patients. New severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Omicron, contains 32 mutations that have caused a high incidence of breakthrough infections or re-infections. These mutations have reduced vaccine protection against Omicron and other new emerging variants. This highlights the need to find effective treatment, which is suggested to be stem cell-based therapy. Stem cells could support respiratory epithelial cells and they could restore alveolar bioenergetics. In addition, they can increase the secretion of immunomodulatory cytokines. However, after transplantation, cell survival and growth rate are low because of an inappropriate microenvironment, and stem cells face ischemia, inflammation, and oxidative stress in the transplantation niche which reduces the cells' survival and growth. Exercise-training can upregulate antioxidant, anti-inflammatory, and anti-apoptotic defense mechanisms and increase growth signaling, thereby improving transplanted cells' survival and growth. Hence, using athletes' stem cells may increase stem-cell therapy outcomes in Omicron-affected patients.
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Recent advances in medicinal and edible homologous polysaccharides: Extraction, purification, structure, modification, and biological activities. 110 kinds of traditional Chinese medicines can be used for medicine and food from Chinese pharmacopoeia in 2021. With the deepening of research in recent years, medicinal and edible homologous (MEH) traditional Chinese medicines have great development and application prospects in many fields. Polysaccharides are one of the major and representative pharmacologically active macromolecules in traditional Chinese medicines with MEH. Moreover, traditional Chinese medicines with MEH have become the main source of natural polysaccharides with safety, high efficiency, and low side effects. Increasing researches have confirmed that MEH polysaccharides (MEHPs) have multiple biological activities both in vitro and in vivo methods, such as antioxidant, immunomodulatory, anti-tumor, anti-aging, anti-inflammatory, hypoglycemic, hypolipidemic activities, and regulating intestinal flora. Additionally, different raw materials, extraction, purification, and chemical modification methods result in differences in the structure and biological activities of MEHPs. The purpose of the present review is to provide comprehensively and systematically reorganized information in the extraction, purification, structure, modification, biological activities, and potential mechanism of MEHPs to support their therapeutic effects and health functions. New valuable insights and theoretical basis for the future researches and developments regarding MEHPs were proposed in the fields of medicine and food.
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Recruitment of clathrin to intracellular membranes is sufficient for vesicle formation. The formation of a clathrin-coated vesicle (CCV) is a major membrane remodeling process that is crucial for membrane traffic in cells. Besides clathrin, these vesicles contain at least 100 different proteins although it is unclear how many are essential for the formation of the vesicle. Here, we show that intracellular clathrin-coated formation can be induced in living cells using minimal machinery and that it can be achieved on various membranes, including the mitochondrial outer membrane. Chemical heterodimerization was used to inducibly attach a clathrin-binding fragment 'hook' to an 'anchor' protein targeted to a specific membrane. Endogenous clathrin assembled to form coated pits on the mitochondria, termed MitoPits, within seconds of induction. MitoPits are double-membraned invaginations that form preferentially on high curvature regions of the mitochondrion. Upon induction, all stages of CCV formation - initiation, invagination, and even fission - were faithfully reconstituted. We found no evidence for the functional involvement of accessory proteins in this process. In addition, fission of MitoPit-derived vesicles was independent of known scission factors including dynamins and dynamin-related protein 1 (Drp1), suggesting that the clathrin cage generates sufficient force to bud intracellular vesicles. Our results suggest that, following its recruitment, clathrin is sufficient for intracellular CCV formation.
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Localized intensification of arsenic methylation within landfill leachate-saturated zone. Leachate-saturated zone (LSZ) of landfills is a complicated biogeochemical hotspot due to the continuous input of electron donors and acceptors from the top refuse layer with leachate migration. In this study, the methylation behavior of the arsenic (As) was investigated. The results indicate that As-methylation processes are influenced by temperature fields in LSZ. The dimethylarsinic acid biotransformation capability can be enhanced with an increase in temperature. Microbial diversity, quantification of functional gene (arsM), and co-occurrence network analysis further characterized the drivers of As methylation in LSZ. As-biogeochemical cycle pathways, as well as As-functional gene distribution among different temperature fields, were modeled on the basis of KEGG annotation. Binning analysis was further employed to assemble As-methylated metagenomes, enabling the identification of novel species for As methylation in landfills. Then, 87 high-quality draft metagenome-assembled genomes (MAGs) were reconstructed from LSZ refuse samples; nearly 15 % (13 of 87) belonged to putative As-methylates functional MAGs. Combined with the model of the As-biogeochemical cycle, nine putative functional species could complete methylation processes alone. The findings of this study highlighted the temperature influence on the As-methylation behavior in LSZ and could facilitate the management of As contamination in landfills.
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New take on the post-take ward round: a quality improvement project undertaken in a district general hospital. A patient's first encounter with a consultant clinician, known as the post-take ward round (PTWR), is a pivotal encounter at the start of their hospital journey. It is a chance for a review of history, examination and investigations, formulation of preliminary diagnosis and management plan. High-quality patient care is reliant on effective communication of clinical information between teams, and the PTWR record is an integral part of this handover of information across different clinicians, medical teams and wards.Consensus of consultant opinion allowed for the formation of a standard against which the quality of PTWR documentation could be measured. This project aimed to assess and improve compliance with the devised standard.Following a survey of referrals made to the medical team after the move to electronic record keeping, it was found that important information was being missed from PTWR records. For example, of the 446 records analysed, only 34% had a documented potential discharge date (PDD) and 20% had a documented escalation plan. Analysis showed overall compliance to core criteria was 63%.Several changes within the department of acute medicine were trialled, including the introduction of a checklist, prompt cards for clinical staff to carry and finally the implementation of an electronic form for PTWR records.Over the course of several cycles of data collection, compliance with core criteria improved from 63% to 86%. Most notably, improvement was seen in documentation of social history (42%-87%), frailty score (0%-63%), PDD (41%-81%) and escalation plan (21%-66%).This work demonstrates the value of development of a standard for PTWR documentation, and of a proforma. The actions taken in this hospital may be of benefit to other medical departments.
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Robust Template Matching Using Multiple-Layered Absent Color Indexing. Color is an essential feature in histogram-based matching. This can be extracted as statistical data during the comparison process. Although the applicability of color features in histogram-based techniques has been proven, position information is lacking during the matching process. We present a conceptually simple and effective method called multiple-layered absent color indexing (ABC-ML) for template matching. Apparent and absent color histograms are obtained from the original color histogram, where the absent colors belong to low-frequency or vacant bins. To determine the color range of compared images, we propose a total color space (TCS) that can determine the operating range of the histogram bins. Furthermore, we invert the absent colors to obtain the properties of these colors using threshold hT. Then, we compute the similarity using the intersection. A multiple-layered structure is proposed against the shift issue in histogram-based approaches. Each layer is constructed using the isotonic principle. Thus, absent color indexing and multiple-layered structure are combined to solve the precision problem. Our experiments on real-world images and open data demonstrated that they have produced state-of-the-art results. Moreover, they retained the histogram merits of robustness in cases of deformation and scaling.
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Dearth of electrophysiology fellows: perspectives from cardiology fellows-in-training. Over the last 6 years, there has been a high percentage of unfilled cardiac electrophysiology (EP) training spots each year. The authors aimed to investigate potential explanations for the unfilled positions based on a survey from the current Fellows-In-Training (FITs).
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B-Box Transcription Factor FaBBX22 Promotes Light-Induced Anthocyanin Accumulation in Strawberry ( Fragaria × ananassa ). B-box transcription factors (TFs) play a vital role in light-induced anthocyanin accumulation. Here, the FaBBX22 gene encoding 287 amino acids B-box TF was isolated from the cultivated strawberry variety 'Benihoppe' and characterized functionally. The expression analysis showed that FaBBX22 was expressed in the roots, stems, leaves, flowers and fruits, and its transcription level was upregulated under the red- or blue-light irradiation. FaBBX22 was localized in the nucleus and showed trans-acting activity in yeast cells. Ectopic overexpression of FaBBX22 in Arabidopsis enhanced the accumulation of anthocyanin. Additionally, we obtained transgenic strawberry calli that overexpressed the FaBBX22 gene, and strawberry calli coloration assays showed that FaBBX22 increased anthocyanin accumulation by upregulating the expression of anthocyanin biosynthetic genes ( FaPAL , FaANS , FaF3'H , FaUFGT1 ) and transport gene FaRAP in a light-dependent manner. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation assays indicated that FaBBX22 interacted with FaHY5. Furthermore, mutation of the 70th Asp residue in FaBBX22 protein to an Ala residue disrupted the interaction between FaBBX22 and FaHY5. Further, a transient expression assay demonstrated that the co-expression of FaBBX22 and FaHY5 could strongly promote anthocyanin accumulation in strawberry fruits. Collectively, these results revealed the positive regulatory role of FaBBX22 in light-induced anthocyanin accumulation.
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Improving Clinical Documentation Compliance Pre-Gastrointestinal Endoscopy Procedures Through the Use of an Endoscopy Checklist. Production pressure in endoscopy units, to avoid procedural delays, can lead to documentation gaps that pose a patient safety risk. Fast-paced, high-volume endoscopy units within a 673-bed academic medical center, incomplete and illegible documentation were identified during a 2018 Joint Commission survey. Pre-procedure safety checklists help ensure accurate clinical handovers. Checklists promote team communication that includes the patient to have complete and relevant information to perform a safe procedure and speak up to identify discrepancies. An endoscopy-specific safety checklist was used by the procedural team immediately pre-procedure. This quality improvement project used Plan Do Study Act cycles to incorporate changes suggested by users. Chart audits were conducted pre- and post-pilot. The results showed significant improvements in physician documentation completeness and legibility, suggesting the checklist prompted clarification of documentation and communication between the nurse and the physician. Nursing assessment saw a 27.1% improvement, suggesting clarification of clinical handover between the admitting and procedural nurses. Improved communication was perceived by staff. This project showed how a standardized tool to promote team communication and clarification of discrepancies pre-procedure can contribute to prevention of errors.
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mTORC1 Activity in Psoriatic Lesions Is Mediated by Aberrant Regulation through the Tuberous Sclerosis Complex. In the basal, proliferative layer of healthy skin, the mTOR complex 1 (mTORC1) is activated, thus regulating proliferation while preventing differentiation. When cells leave the proliferative, basal compartment, mTORC1 signaling is turned off, which allows differentiation. Under inflammatory conditions, this switch is hijacked by cytokines and prevents proper differentiation. It is currently unknown how mTORC1 is regulated to mediate these effects on keratinocyte differentiation. In other tissues, mTORC1 activity is controlled through various pathways via the tuberous sclerosis complex (TSC). Thus, we investigated whether the TS complex is regulated by proinflammatory cytokines and contributes to the pathogenesis of psoriasis. TNF-α as well as IL-1β induced the phosphorylation of TSC2, especially on S939 via the PI3-K/AKT and MAPK pathway. Surprisingly, increased TSC2 phosphorylation could not be detected in psoriasis patients. Instead, TSC2 was strongly downregulated in lesional psoriatic skin compared to non-lesional skin of the same patients or healthy skin. In vitro inflammatory cytokines induced dissociation of TSC2 from the lysosome, followed by destabilization of the TS complex and degradation. Thus, we assume that in psoriasis, inflammatory cytokines induce strong TSC2 phosphorylation, which in turn leads to its degradation. Consequently, chronic mTORC1 activity impairs ordered keratinocyte differentiation and contributes to the phenotypical changes seen in the psoriatic epidermis.
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Genetically predicted higher educational attainment decreases the risk of stroke: a multivariable Mendelian randomization study. The causal association between educational attainment (EA) and stroke remains unclear. Hence, a novel multivariable Mendelian randomization (MVMR) approach was applied to solve this issue.
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Comprehensive Process Mapping and Qualitative Interviews to Inform Implementation of Rapid Linkage to HIV Care Programs in a Mid-Sized Urban Setting in the Southern United States. Rapid antiretroviral therapy (ART) initiation, in which people living with HIV start ART within days of diagnosis, is a key component of the US Ending the HIV Epidemic initiative.
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Design of Optimization Algorithm for Configuration of Amateur Sports Training Equipment in Smart City Community. Community amateur sports training equipment is necessary to ensure the development of national fitness activities. It is found that the design concept of community public sports space in China is not perfect, the structural layout is not reasonable, the stock space is not optimized, and the resource allocation is not balanced. In particular, there is a lack of indoor fitness facilities and sports venues in the community, and the people's "fitness where to go" is still a difficult problem. In the smart city construction, the resource integration and optimization of community amateur sports training facilities have also been further developed. Considering various influencing factors, this paper establishes a location model of community amateur sports training facilities with the least total cost and convenience. Aiming at the practical optimization problem with high complexity, an improved adaptive weight multiobjective particle swarm optimization (PSO) model is proposed. These parameters in the algorithm were adjusted dynamically, which balanced the overall search ability and partial improvement ability of the PSO algorithm and completed the optimal scheduling of community amateur sports training equipment configuration while ensuring the optimal global solution. Experimental results show that the algorithm's efficiency and searching ability have been further promoted. It also has an excellent performance in solving the complex location problem of community amateur sports training facilities.
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Feasibility and acceptability of a novel telepsychiatry-delivered precision prescribing intervention for anxiety and depression. Major Depressive Disorder and Generalized Anxiety Disorder are pervasive and debilitating conditions, though treatment is often inaccessible and based on trial-and-error prescribing methods. The present observational study seeks to describe the use of a proprietary precision prescribing algorithm piloted during routine clinical practice as part of Brightside's telepsychiatry services. The primary aim is to determine the feasibility and acceptability of implementing this intervention. Secondary aims include exploring remission and symptom improvement rates.
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Global impact of the first year of COVID-19 vaccination: a mathematical modelling study. The first COVID-19 vaccine outside a clinical trial setting was administered on Dec 8, 2020. To ensure global vaccine equity, vaccine targets were set by the COVID-19 Vaccines Global Access (COVAX) Facility and WHO. However, due to vaccine shortfalls, these targets were not achieved by the end of 2021. We aimed to quantify the global impact of the first year of COVID-19 vaccination programmes.
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The conformations and basal conformational dynamics of translocation factor SecDF vary with translocon SecYEG interaction. The general secretory, or Sec, system is a primary protein export pathway from the cytosol of Escherichia coli and all eubacteria. Integral membrane protein complex SecDF is a translocation factor that enhances polypeptide secretion, which is driven by the Sec translocase, consisting of translocon SecYEG and ATPase SecA. SecDF is thought to utilize a proton gradient to effectively pull precursor proteins from the cytoplasm into the periplasm. Working models have been developed to describe the structure and function of SecDF, but important mechanistic questions remain unanswered. Atomic force microscopy (AFM) is a powerful technique for studying the dynamics of single-molecule systems including membrane proteins in near-native conditions. The sharp tip of the AFM provides direct access to membrane-external protein conformations. Here, we acquired AFM images and kymographs (∼100 ms resolution) to visualize SecDF protrusions in near-native supported lipid bilayers and compared the experimental data to simulated AFM images based on static structures. When studied in isolation, SecDF exhibited a stable and compact conformation close to the lipid bilayer surface, indicative of a resting state. Interestingly, upon SecYEG introduction, we observed changes in both SecDF conformation and conformational dynamics. The population of periplasmic protrusions corresponding to an intermediate form of SecDF, which is thought to be active in precursor protein handling, increased more than ninefold. In conjunction, our dynamics measurements revealed an enhancement in the transition rate between distinct SecDF conformations when the translocon was present. Together, this work provides a novel vista of basal-level SecDF conformational dynamics in near-native conditions.
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Study on the Pakistan stock market using a new stock crisis prediction method. A Stock market collapse occurs when stock prices drop by more than 10% across all main indexes. Predicting a stock market crisis is difficult because of the increased volatility in the stock market. Stock price drops can be triggered by a variety of factors, including corporate results, geopolitical tensions, financial crises, and pandemic events. For scholars and investors, predicting a crisis is a difficult endeavor. We developed a model for the prediction of stock crisis using Hybridized Feature Selection (HFS) approach. Firstly, we went for the suggestion of the HFS method for the removal of stock's unnecessary financial attributes. The Naïve Bayes approach, on the other hand, is used for the classification of strong fundamental stocks. In the third step, Stochastic Relative Strength Index (StochRSI) is employed to identify a stock price bubble. In the fourth step, we identified the stock market crisis point in stock prices through moving average statistics. The fifth is the prediction of stock crises by using deep learning algorithms such as Gated Recurrent Unit (GRU) and Long-Short Term Memory (LSTM). Root Mean Square Error (RMSE), Mean Squared Error (MSE) and Mean Absolute Error (MAE) are implemented for assessing the performance of the models. The HFS-based GRU technique outperformed the HFS-based LSTM method to anticipate the stock crisis. To complete the task, the experiments used Pakistan datasets. The researchers can look at additional technical factors to forecast when a crisis would occur in the future. With a new optimizer, the GRU approach may be improved and fine-tuned even more.
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Starch and whey protein isolate films including an aroma compound stabilized by nanocellulose. Bergamot essential oil (BO) shows biological activities and is widely used as a flavoring for food products; however, its application in foods is limited because of the low stability and solubility in water. This study aimed to prepare whey protein isolate (WPI) and starch (S) films, including nanocellulose based BO nanoemulsions, potentially enhancing BO functionality. BO nanoemulsion was obtained by using a nanocellulose dispersion (2 mg/mL) including 3 mM CaCl2 with a ratio of 2/8 (v/v, BO/nanocellulose dispersion) and then suitably dispersed (2%, w/w) in the WPI and S film-forming solutions to obtain film samples. The water vapor permeability (WVP), mechanical and optical properties and BO's release from those obtained films were studied. The WVP (p<0.05) and tensile strength (p>0.05) of films were improved, whereas opacity increased with the addition of BO nanoemulsion (p<0.05). The release of BO from S films was faster than in WPI films. These results showed that nanocellulose could be used as carriers for essential oils such as BO to enhance its functionality within bio-polymeric matrices intended to be used as relevant carriers of aroma compounds.
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Glioblastoma cell motility depends on enhanced oxidative stress coupled with mobilization of a sulfurtransferase. Cell motility is critical for tumor malignancy. Metabolism being an obligatory step in shaping cell behavior, we looked for metabolic weaknesses shared by motile cells across the diverse genetic contexts of patients' glioblastoma. Computational analyses of single-cell transcriptomes from thirty patients' tumors isolated cells with high motile potential and highlighted their metabolic specificities. These cells were characterized by enhanced mitochondrial load and oxidative stress coupled with mobilization of the cysteine metabolism enzyme 3-Mercaptopyruvate sulfurtransferase (MPST). Functional assays with patients' tumor-derived cells and -tissue organoids, and genetic and pharmacological manipulations confirmed that the cells depend on enhanced ROS production and MPST activity for their motility. MPST action involved protection of protein cysteine residues from damaging hyperoxidation. Its knockdown translated in reduced tumor burden, and a robust increase in mice survival. Starting from cell-by-cell analyses of the patients' tumors, our work unravels metabolic dependencies of cell malignancy maintained across heterogeneous genomic landscapes.
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EXPLORE B: A prospective, long-term natural history study of patients with acute hepatic porphyria with chronic symptoms. One-year data from EXPLORE Part A showed high disease burden and impaired quality of life (QOL) in patients with acute hepatic porphyria (AHP) with recurrent attacks. We report baseline data of patients who enrolled in EXPLORE Part B for up to an additional 3 years of follow-up. EXPLORE B is a long-term, prospective study evaluating disease activity, pain intensity, and QOL in patients with AHP with ≥1 attack in the 12 months before enrollment or receiving hemin or gonadotropin-releasing hormone prophylaxis. Data were evaluated in patients with more (≥3 attacks or on prophylaxis treatment) or fewer (<3 attacks and no prophylaxis treatment) attacks. Patients in the total population (N = 136), and more (n = 110) and fewer (n = 26) attack subgroups, reported a median (range) of 3 (0-52), 4 (0-52), and 1 (0-2) acute attacks, respectively, in the 12 months prior to the baseline visit. Pain, mood/sleep, digestive/bladder, and nervous system symptoms were each experienced by ≥80% of patients; most received hemin during attacks. Almost three-quarters of patients reported chronic symptoms between attacks, including 85% of patients with fewer attacks. Pain intensity was comparable among both attack subgroups; most patients required pain medication. All groups had diminished QOL on the EuroQol visual analog scale and the European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 versus population norms. Patients with AHP with recurrent attacks, even those having fewer attacks, experience a high disease burden, as evidenced by chronic symptoms between attacks and impaired QOL.
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Nanoparticles of naturally occurring PPAR-γ inhibitor betulinic acid ameliorates bone marrow adiposity and pathological bone loss in ovariectomized rats via Wnt/β-catenin pathway. Postmenopausal osteoporosis is one of the world's biggest yet unnoticed health issues. After ovariectomy, declined estrogen level significantly contributes to the elevation of bone marrow adiposity and bone loss leading to osteoporosis. Therapeutics to prevent osteoporosis addressing various aspects are now in short supply. In this study we made an approach to synthesize nanoparticles of naturally occurring PPAR-γ inhibitor, betulinic acid (BA/NPs) and tested the same in altered bone metabolisms developed after ovariectomy.
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Enhanced dewaterability of lake dredged sediments by electrochemical oxidation of peroxydisulfate on BDD anode. Dredged sediments, as a product of mitigating endogenous pollution of rivers and lakes, cause severe environmental pollution without suitable disposal. To reduce dredged sediments, the electrochemical oxidation (EO) of peroxydisulfate (PS) on a boron-doped diamond (BDD) anode (EO/BDD-PS) was utilized to enhance the dewaterability of the dredged sediments. The soluble chemical oxygen demand increased in the EO/BDD-PS system, and more than 70.0% of the specific resistance to filtration was reduced by EO/BDD-PS within 20 min. The optimal conditions were determined to be as follows: current density, 30 mA cm -2 ; PS dosage 4 g L -1 ; and initial pH, 6.96. After treatment with EO/BDD-PS, the electronegativity of the sludge flocs was alleviated and the particle size increased from 7.61 to 10.64 μm. Furthermore, proteins and polysaccharides were degraded, and tightly bound extracellular polymeric substances (TB-EPS) and loosely bound EPS (LB-EPS) were effectively transported to soluble EPS (S-EPS). Furthermore, humification of organic matter occurred in S-EPS and LB-EPS when the dredged sediment was treated with EO/BDD-PS. Dominant hydroxyl radicals (•OH) and sulfate radicals (SO 4 • - ) were generated in the EO/BDD-PS system. Moreover, the efficiency of the filtrate as an electrolyte decreased slightly after recycling five times. Therefore, this method may be economical for enhancing the dewaterability of dredged sediments.
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An anti-scratch flexible SERS substrate for pesticide residue detection on the surface of fruits and vegetables. We propose an anti-scratch flexible surface-enhanced Raman scattering substrate with arrayed nanocavity microstructures fabricated by colloidal lithography. The nanocavity microstructure of the substrate can well protect the inner gold nanoparticles during wipe sampling. The prepared flexible substrate was able to detect 4-aminothiophenol (4-ATP) with a concentration down to 1 fM. Furthermore, the substrate was used to detect 6-BA residues on the surface of apples and bean sprouts through wipe sampling, which shows great potential in the field of rapid on-site detection, especially in the detection of pesticide residues on the surface of fruits and vegetables.
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Marine Cyanobacteria as Sources of Lead Anticancer Compounds: A Review of Families of Metabolites with Cytotoxic, Antiproliferative, and Antineoplastic Effects. The marine environment is highly diverse, each living creature fighting to establish and proliferate. Among marine organisms, cyanobacteria are astounding secondary metabolite producers representing a wonderful source of biologically active molecules aimed to communicate, defend from predators, or compete. Studies on these molecules' origins and activities have been systematic, although much is still to be discovered. Their broad chemical diversity results from integrating peptide and polyketide synthetases and synthases, along with cascades of biosynthetic transformations resulting in new chemical structures. Cyanobacteria are glycolipid, macrolide, peptide, and polyketide producers, and to date, hundreds of these molecules have been isolated and tested. Many of these compounds have demonstrated important bioactivities such as cytotoxicity, antineoplastic, and antiproliferative activity with potential pharmacological uses. Some are currently under clinical investigation. Additionally, conventional chemotherapeutic treatments include drugs with a well-known range of side effects, making anticancer drug research from new sources, such as marine cyanobacteria, necessary. This review is focused on the anticancer bioactivities of metabolites produced by marine cyanobacteria, emphasizing the identification of each variant of the metabolite family, their chemical structures, and the mechanisms of action underlying their biological and pharmacological activities.
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[Investigation of the Performance of Organic Contaminant Degradation by Fe 2+ /PDS Under Environmentally Relevant pH Conditions]. Peroxydisulfate (PDS) activation by Fe 2+ has proven to be a promising method to abate emerging organic contaminants by generating reactive oxidation species. Nevertheless, this process may only achieve good decontamination performance under acidic conditions, which has markedly limited its application in real practice. To address this issue, we comprehensively investigated the performance of the Fe 2+ /PDS process toward some probe contaminants at different pH levels and explored the potential change in reactive oxidative species and the influence of oxygen. Both SO 4 - · and Fe(Ⅳ) were identified to be involved in the Fe 2+ /PDS process, and the types of these oxidative species did not change with varying pH values. Although dissolved oxygen could compete with PDS for Fe 2+ , especially at high pH values, this competition process was not the major reason for the declined performance of the Fe 2+ /PDS process, since 37.6%-100% of PDS could also be activated with the presence of oxygen. Instead, the overdosing of Fe 2+ could greatly inhibit carbamazepine removal, indicating that the nonproductive consumption of reactive oxidants by Fe 2+ should account for the declined performance of Fe 2+ /PDS under environmentally relevant pH conditions. Accordingly, the feasibility of applying zero-valent iron and sulfidated zero-valent iron was further evaluated, and the formation of corrosion products was characterized using X-ray absorption fine structure spectroscopy. All these findings will improve our understanding about the Fe 2+ /PDS process and thus facilitate its application.
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Establishment and assessment of rodent models of medication-related osteonecrosis of the jaw (MRONJ). Medication-related osteonecrosis of the jaw (MRONJ) is primarily associated with administering antiresorptive or antiangiogenic drugs. Despite significant research on MRONJ, its pathogenesis and effective treatments are still not fully understood. Animal models can be used to simulate the pathophysiological features of MRONJ, serving as standardized in vivo experimental platforms to explore the pathogenesis and therapies of MRONJ. Rodent models exhibit excellent effectiveness and high reproducibility in mimicking human MRONJ, but classical methods cannot achieve a complete replica of the pathogenesis of MRONJ. Modified rodent models have been reported with improvements for better mimicking of MRONJ onset in clinic. This review summarizes representative classical and modified rodent models of MRONJ created through various combinations of systemic drug induction and local stimulation and discusses their effectiveness and efficiency. Currently, there is a lack of a unified assessment system for MRONJ models, which hinders a standard definition of MRONJ-like lesions in rodents. Therefore, this review comprehensively summarizes assessment systems based on published peer-review articles, including new approaches in gross observation, histological assessments, radiographic assessments, and serological assessments. This review can serve as a reference for model establishment and evaluation in future preclinical studies on MRONJ.
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Secure access control using updateable attribute keys. In the era of cloud computing, the technique of access control is vital to protect the confidentiality and integrity of cloud data. From the perspective of servers, they should only allow authenticated clients to gain the access of data. Specifically, the server will share a communication channel with the client by generating a common session key. It is thus regarded as a symmetric key for encrypting data in the current channel. An access control mechanism using attribute-based encryptions is most flexible, since the decryption privilege can be granted to the ones who have sufficient attributes. In the paper, the authors propose a secure access control consisting of the attributed-based mutual authentication and the attribute-based encryption. The most appealing property of our system is that the attribute keys associated with each user is periodically updatable. Moreover, we will also show that our system fulfills the security of fuzzy selective-ID assuming the hardness of Decisional Modified Bilinear Diffie-Hellman (DMBDH) problem.
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Targeting the RNA G-Quadruplex and Protein Interactome for Antiviral Therapy. In recent years, G-quadruplexes (G4s), types of noncanonical four-stranded nucleic acid structures, have been identified in many viruses that threaten human health, such as HIV and Epstein-Barr virus. In this context, G4 ligands were designed to target the G4 structures, among which some have shown promising antiviral effects. In this Perspective, we first summarize the diversified roles of RNA G4s in different viruses. Next, we introduce small-molecule ligands developed as G4 modulators and highlight their applications in antiviral studies. In addition to G4s, we comprehensively review the medical intervention of G4-interacting proteins from both the virus (N protein, viral-encoded helicases, severe acute respiratory syndrome-unique domain, and Epstein-Barr nuclear antigen 1) and the host (heterogeneous nuclear ribonucleoproteins, RNA helicases, zinc-finger cellular nucelic acid-binding protein, and nucleolin) by inhibitors as an alternative way to disturb the normal functions of G4s. Finally, we discuss the challenges and opportunities in G4-based antiviral therapy.
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Dietary Exposure to United States Food and Drug Administration-Approved Synthetic Food Colors in Children, Pregnant Women, and Women of Childbearing Age Living in the United States. The Food and Drug Administration (FDA) regulates artificial food colors (AFCs) in the United States. Exposure to AFCs has raised concerns about adverse behavioral effects in children. We quantified AFC exposure in women of childbearing age, pregnant women, and children and compared them to FDA and World Health Organization acceptable daily intakes (ADIs). We estimated the "typical" and "high" single-day and two-day average dietary exposure to each AFC (mg/kg/day) based on laboratory measurements and food consumption data from the 2015-2016 National Health and Nutrition Examination Survey (NHANES). We also examined whether AFC intake differed by income, education, and ethnicity. Exposure tended to be higher in children and the highest AFC exposure was found for Red No. 40. Children's mean and 95th percentile FD&C Red No. 3 estimated intakes exceeded the ADIs in some instances. Juice drinks, soft drinks, icings, and ice cream cones were major foods contributing to children's (&lt;16 years old) AFC exposure. AFC intake was higher in participants with lower incomes and education and of African American ethnicity. The findings indicate widespread AFC exposure including in very young children. Research is needed on the sociodemographic determinants of exposure and AFC toxicokinetics to better describe the absorption and organ-specific exposure.
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Evaluation of post laparoscopic cholecystectomy pain after subcutaneous injection of lidocaine at port site versus lidocaine spray on gallbladder bed after cholecystectomy: a randomized controlled trial. The efficacy of intraperitoneal (IP) and incisional use of local anesthesia in laparoscopic cholecystectomy is a promising subject regarding post-operative pain control. In this study, we aim to compare these methods using lidocaine as the local anesthetic.
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The effects of messaging on long COVID expectations: An online experiment. We examined whether varying information about long COVID would affect expectations about the illness.
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Genetic Analysis of Pheochromocytoma and Paraganglioma Complicating Cyanotic Congenital Heart Disease. Pheochromocytoma and paraganglioma (PPGL) may appear as a complication of cyanotic congenital heart disease (CCHD-PPGL) with frequent EPAS1 mutations, suggesting a close link between EPAS1 mutations and tissue hypoxia in CCHD-PPGL pathogenesis.
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Development and Pilot Evaluation of a Decision Aid for Small Kidney Masses. To develop and pilot test a patient decision aid (DA) describing small kidney masses and risks and benefits of treatment for the masses.
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Inequalities in food acquisition according to the social profiles of the head of households in Brazil. Brazil is characterized by strong social inequalities and differences in access to quality food and sufficient quantities of it, which represent a violation of the human right to adequate food. The aim was to assess food expenditures according to the social profiles of the head of the households. Data from the cross-sectional Brazilian Household Budget Survey (2017/2018) were used with a nationally representative sample of household survey participants (n=52,917). Poisson regression was used to estimate prevalence ratios (PR) to assess the association of different social profiles with the acquisition of food. The profile characterized by woman self-classified as white, with a higher education, which characteristics were positively and significantly associated with more acquisition of fruits (PR=1.22; CI95% 1.09-1.36) and vegetables and greens (PR=1.24; CI95% 1.09-1.41). Black women with low education levels showed a negative association with the consumption of soda (PR=0.53; CI95% 0.45-0.62), and prepared food (PR=0.52; CI95% 0.37-0.74). The results reveal great inequalities in the purchase of food between the social profiles of the heads of the family.
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