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Considerations about L2- and L1-norm regularizations for ultrasound reverberation characteristics imaging and vectoral Doppler measurement. The L1-norm regularization is applied to ultrasonic reverberation characteristics imaging and vectoral Doppler measurement, of which performances are compared with those of L2-norm regularizations. The L1 regularization yields the sharper image than the L2 regularization. Alternatively, for the Doppler measurement, the L1 regularization yields less accuracy than the L2 regularization. Clinical Relevance- This study will permit us to perform quantitative ultrasonic reverberation characteristics and accurate vectoral Doppler observation.
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Immobilized Stenotrophomonas maltophilia KB2 in Naproxen Degradation. Immobilization is a commonly used method in response to the need to increase the resistance of microorganisms to the toxic effects of xenobiotics. In this study, a plant sponge from Luffa cylindrica was used as a carrier for the immobilization of the Stenotrophomonas maltophilia KB2 strain since such a carrier meets the criteria for high-quality carriers, i.e., low price and biodegradability. The optimal immobilization conditions were established as a temperature of 30 °C, pH 7.2, incubation time of 72 h, and an optical density of the culture of 1.4. The strain immobilized in such conditions was used for the biodegradation of naproxen, and an average rate of degradation of 3.8 µg/hour was obtained under cometabolic conditions with glucose. The obtained results indicate that a microbiological preparation based on immobilized cells on a luffa sponge can be used in bioremediation processes where it is necessary to remove the introduced carrier.
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Comparative efficacy and acceptability of cognitive behavioral therapy delivery formats for insomnia in adults: A systematic review and network meta-analysis. This review compared the efficacy and acceptability of different delivery formats for cognitive behavioral therapy for insomnia (CBT-I) in insomnia. We searched five databases for randomized clinical trials that compared one CBT-I delivery format against another format or control conditions for insomnia in adults. We used pairwise meta-analyses and frequentist network meta-analyses with the random-effects model to synthesize data. A total of 61 unique trials including 11,571 participants compared six CBT-I delivery formats with four control conditions. At post-intervention, with low to high certainty evidence, individual, group, guided self-help, digital assisted, and unguided self-help CBT-I could significantly increase sleep efficiency and total sleep time (TST) and reduce sleep onset latency (SOL), wake after sleep onset (WASO), and insomnia severity compared with treatment as usual (MD range for sleep efficiency: 7.81%-12.45%; MD range for TST: 16.14-33.96 min; MD range for SOL: -22.42 to -13.81 min; MD range for WASO: -40.84 to -19.48 min; MD range for insomnia severity: -6.40 to -3.93) and waitlist (MD range for sleep efficiency: 7.68%-12.32%; MD range for TST: 12.67-30.49 min; MD range for SOL: -19.07 to -10.46 min; MD range for WASO: -47.10 to -19.15 min; MD range for insomnia severity: -7.59 to -5.07). The effects of different CBT-I formats persisted at short-term follow-up (4 wk-6 mo). Individual, group, and digital assisted CBT-I delivery formats would be the more appropriate choices for insomnia in adults, based on post-intervention and short-term effects. Further trials are needed to investigate the long-term effects of different CBT-I formats.
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Clinical Characteristics and Treatment of Adult Idiopathic Carpal Tunnel Syndrome Accompanied with Trigger Digit. To investigate the clinical characteristics and treatment of adult idiopathic carpal tunnel syndrome (CTS) accompanied with trigger digit.
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Experimental study and sensitivity analysis of force behavior in cortical bone milling. Bone milling force is a key factor to be controlled during the orthopedic surgery. Cutting force has significant influence on the breaking of the tools or causing bone cracks. The cutting force depends on machining parameters, cutting tools and the cortical bone tissue. In this paper, rotational speed, feed rate, cutting depth, tool diameter and the osteon orientation are considered as input parameters. For statistical modeling and experimental study, the response surface method was used. Moreover, using the Sobol statistical sensitivity analysis method the effect of each input parameter on the process force is investigated both qualitatively and quantitatively. Results revealed that bone milling force decreases with increasing rotational speed while it increases with feed rate due to an increase in the thickness of the deformed chip as well as an escalation of friction. Moreover, increasing cutting depth due to increased thickness of the deformed chip, increases friction and thus increases cutting force. Additionally, as the diameter of the blade increases, the cutting force increases. Finally, in the perpendicular direction to the osteon, less force is applied to the bone tissue than that of parallel to osteon. Based on Sobol sensitivity analysis, cutting depth (51.4%), feed rate (21.9%), tool rotational speed (19%), milling direction (4.8%) and tool diameter (1.9%) are the most effective respectively. Response optimization was also presented using Derringer algorithm, which provided a minimum cutting force of 3.76 N, when tool diameter of 4 mm, rotational speed of 3000 rpm and feed rate of 100 mm/min and cutting depth of 1 mm were selected in milling perpendicular to the osteon orientation. This research can be used to optimize milling parameters in order to assist robotic surgery and orthopedic tool design.
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Identification of the NAC Transcription Factors and Their Function in ABA and Salinity Response in Nelumbo nucifera . Nelumbo nucifera Gaertn. is an important perennial aquatic herb that has high ornamental, edible, medicinal, and economic value, being widely distributed and used in China. The NAC superfamily (NAM, ATAF1/2, CUC2) plays critical roles in plant growth, development, and response to abiotic and biotic stresses. Though there have been a few reports about NAC genes in lotus, systematic analysis is still relatively lacking. The present study aimed to characterize all the NAC genes in the lotus and obtain better insights on the NnNACs in response to salt stress by depending on ABA signaling. Here, 97 NAC genes were identified by searching the whole lotus genome based on the raw HMM models of the conserved NAM domain and NAC domain. They were characterized by bioinformatics analysis and divided into 18 subgroups based on the phylogenetic tree. Cis-element analysis demonstrated that NAC genes are responsive to biotic and abiotic stresses, light, low temperature, and plant hormones. Meanwhile, NAC genes had tissue expression specificity. qRT-PCR analysis indicated that NAC genes could be upregulated or downregulated by NaCl treatment, ABA, and fluoridone. In addition, NAC016 , NAC025 , and NAC070 , whose encoding genes were significantly induced by NaCl and ABA, were located in the nucleus. Further analysis showed the three NAC proteins had transcriptional activation capabilities. The co-expression network analysis reflected that NAC proteins may form complexes with other proteins to play a role together. Our study provides a theoretical basis for further research to be conducted on the regulatory mechanisms of salinity resistance in the lotus.
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Shigella-associated mild encephalitis with reversible splenial lesion in Hospital Center Delafontaine, Saint-Denis, France: a case report. Mild encephalitis with reversible splenial lesion of the corpus callosum (MERS) is a clinical/radiological syndrome characterized by hyperintense signal changes in the splenium of the corpus callosum visible on diffusion weighted imaging (DWI) in the brain Magnetic Resonance Imaging (MRI) associated with various neurological symptoms. Progression is usually favorable with disappearance of the MRI brain lesion and regression of clinical symptoms over a few days to a few weeks. The exact pathophysiology remains unclear. MERS can be associated with various pathogens.
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Evaluation of Full-Length Versus V4-Region 16S rRNA Sequencing for Phylogenetic Analysis of Mouse Intestinal Microbiota After a Dietary Intervention. The composition of microbial communities is commonly determined by sequence analyses of one of the variable (V) regions in the bacterial 16S rRNA gene. We aimed to assess whether sequencing the full-length versus the V4 region of the 16S rRNA gene affected the results and interpretation of an experiment. To test this, mice were fed a diet without and with the prebiotic inulin and from cecum samples, two primary data sets were generated: (1) a 16S rRNA full-length data set generated by the PacBio platform; (2) a 16S rRNA V4 region data set generated by the Illumina MiSeq platform. A third derived data set was generated by in silico extracting the 16S rRNA V4 region data from the 16S rRNA full-length PacBio data set. Analyses of the primary and derived 16S rRNA V4 region data indicated similar bacterial abundances, and α- and β-diversity. However, comparison of the 16S rRNA full-length data with the primary and derived 16S rRNA V4 region data revealed differences in relative bacterial abundances, and α- and β-diversity. We conclude that the sequence length of 16S rRNA gene and not the sequence analysis platform affected the results and may lead to different interpretations of the effect of an intervention that affects the microbiota.
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Challenges and opportunities to penetrate the blood-brain barrier for brain cancer therapy. Despite significant advances in research, the prognosis for both primary and secondary brain cancers remains poor. The blood-brain barrier (BBB) is a complex and unique semi-permeable membrane that serves as a protective structure to maintain homeostasis within the brain. However, it presents a significant challenge for the delivery of therapeutics into the brain and tumor. Some brain tumors are known to compromise BBB integrity, producing a highly heterogeneous vasculature known as the blood-tumor-barrier (BTB). Identifying strategies to bypass these obstacles to improve the penetrability of anticancer therapeutics has been the focus of research in this area. In this review, we discuss the strategies that have been investigated to evade or alter the cellular and molecular barriers of both the BBB and the BTB and detail the methods currently under preclinical or clinical investigation, including molecular, biological, and physical processes to overcome the BBB or BTB. Increased understanding of the BBB and BTB and the current methods of overcoming these barriers will enable the development of new and more effective treatment strategies for brain tumors.
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Cytokine profile of human limbal myofibroblasts: Key players in corneal antiviral response. Corneal transparency may be compromised by viral infections causing corneal scarring, edema, and neovascularization. Ocular injury results from collateral damage induced by exacerbated immune response in corneal stroma. Myofibroblasts play a key role in this process by producing a disorganized extracellular matrix and inflammatory mediators. However, the immune response profile of myofibroblasts during viral infections is still under study. The aim of this work was to analyze the cytokine profile of human limbal myfibroblasts (HLMs) stimulated with the double-stranded RNA analog polyinosinic:polycytidylic acid (poly I:C) and to identify their signaling pathways.
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Laboratory-Confirmed COVID-19-Associated Hospitalizations Among Adults During SARS-CoV-2 Omicron BA.2 Variant Predominance - COVID-19-Associated Hospitalization Surveillance Network, 14 States, June 20, 2021-May 31, 2022. Beginning the week of March 20–26, 2022, the Omicron BA.2 variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating variant in the United States, accounting for >50% of sequenced isolates.* Data from the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to describe recent COVID-19–associated hospitalization rates among adults aged ≥18 years during the period coinciding with BA.2 predominance (BA.2 period [Omicron BA.2 and BA.2.12.1; March 20–May 31, 2022]). Weekly hospitalization rates (hospitalizations per 100,000 population) among adults aged ≥65 years increased threefold, from 6.9 (week ending April 2, 2022) to 27.6 (week ending May 28, 2022); hospitalization rates in adults aged 18–49 and 50–64 years both increased 1.7-fold during the same time interval. Hospitalization rates among unvaccinated adults were 3.4 times as high as those among vaccinated adults. Among hospitalized nonpregnant patients in this same period, 39.1% had received a primary vaccination series and 1 booster or additional dose; 5.0% had received a primary series and ≥2 boosters or additional doses. All adults should stay up to date† with COVID-19 vaccination, and multiple nonpharmaceutical and medical prevention measures should be used to protect those at high risk for severe COVID-19 illness, irrespective of vaccination status§ (1). Beginning the week of March 20–26, 2022, the Omicron BA.2 variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating variant in the United States, accounting for >50% of sequenced isolates.* Data from the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to describe recent COVID-19–associated hospitalization rates among adults aged ≥18 years during the period coinciding with BA.2 predominance (BA.2 period [Omicron BA.2 and BA.2.12.1; March 20–May 31, 2022]). Weekly hospitalization rates (hospitalizations per 100,000 population) among adults aged ≥65 years increased threefold, from 6.9 (week ending April 2, 2022) to 27.6 (week ending May 28, 2022); hospitalization rates in adults aged 18–49 and 50–64 years both increased 1.7-fold during the same time interval. Hospitalization rates among unvaccinated adults were 3.4 times as high as those among vaccinated adults. Among hospitalized nonpregnant patients in this same period, 39.1% had received a primary vaccination series and 1 booster or additional dose; 5.0% had received a primary series and ≥2 boosters or additional doses. All adults should stay up to date† with COVID-19 vaccination, and multiple nonpharmaceutical and medical prevention measures should be used to protect those at high risk for severe COVID-19 illness, irrespective of vaccination status§ (1).
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Application of Grey Lotka-Volterra Model in Water-Economy-Industry-Technology Innovation System in Beijing-Tianjin-Hebei Region. With the proposal of China's high-quality development strategy, how to promote regional stability and coordinated development based on a deep understanding of the main contradictions and changes in China's society has become the focus of research. High-quality development is a brand-new coordinated development concept, which aims to optimize the economic structure, transform the development model, enhance the development momentum, and take innovation as the primary driving force. How to promote the coordinated development of this region has become a hot issue considered by scholars. The Beijing-Tianjin-Hebei region is the capital economic circle of China, and the purpose of this study is to promote the coordinated and stable development of the region. On this premise, this paper firstly adopts the composite Grey Lotka-Volterra (GLV) model and Fractional GM(1,1) (FGM(1,1)) model to research Water Resources system-Economic System-Industrial System-Technology Innovation System in the Beijing-Tianjin-Hebei region. Secondly, by analyzing the research data, it is found that the relationship between the system is very complex, and the stability calculation results are all below 0. Then, the analysis of the research results shows that there is no obvious coordination among the three regions, and they have not yet reached a state of mutual promotion and stable and coordinated development. Finally, four suggestions are put forward for the coordinated development of the Beijing-Tianjin-Hebei region. This can not only provide direction for the future development of the region but also have reference significance for the development of other regions. Further, accelerate the coordination and unity of all factors of production in China and promote China's development at a deeper and higher level.
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The Impact of Frailty on Traumatic Brain Injury Outcomes: An Analysis of 691 821 Nationwide Cases. Frailty, a decline in physiological reserve, prognosticates poorer outcomes for several neurosurgical conditions. However, the impact of frailty on traumatic brain injury outcomes is not well characterized.
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Effects of antibiotics and metals on lung and intestinal microbiome dysbiosis after sub-chronic lower-level exposure of air pollution in ageing rats. We investigated the effects of antibiotics, drugs, and metals on lung and intestinal microbiomes after sub-chronic exposure of low-level air pollution in ageing rats. Male 1.5-year-old Fischer 344 ageing rats were exposed to low-level traffic-related air pollution via whole-body exposure system for 3 months with/without high-efficiency particulate air (HEPA) filtration (gaseous vs. particulate matter with aerodynamic diameter of ≤2.5 µm (PM 2.5 ) pollution). Lung functions, antibiotics, drugs, and metals in lungs were examined and linked to lung and fecal microbiome analyses by high-throughput sequencing analysis of 16 s ribosomal (r)DNA. Rats were exposed to 8.7 μg/m 3 PM 2.5 , 10.1 ppb NO 2 , 1.6 ppb SO 2 , and 23.9 ppb O 3 in average during the study period. Air pollution exposure decreased forced vital capacity (FVC), peak expiratory flow (PEF), forced expiratory volume in 20 ms (FEV 20 ), and FEF at 25∼75% of FVC (FEF 25-75 ). Air pollution exposure increased antibiotics and drugs (benzotriazole, methamphetamine, methyl-1 H-benzotriazole, ketamine, ampicillin, ciprofloxacin, pentoxifylline, erythromycin, clarithromycin, ceftriaxone, penicillin G, and penicillin V) and altered metals (V, Cr, Cu, Zn, and Ba) levels in lungs. Fusobacteria and Verrucomicrobia at phylum level were increased in lung microbiome by air pollution, whereas increased alpha diversity, Bacteroidetes and Proteobacteria and decreased Firmicutes at phylum level were occurred in intestinal microbiome. Lung function decline was correlated with increasing antibiotics, drugs, and metals in lungs as well as lung and intestinal microbiome dysbiosis. The antibiotics, drugs, and Cr, Co, Ca, and Cu levels in lung were correlated with lung and intestinal microbiome dysbiosis. The lung microbiome was correlated with intestinal microbiome at several phylum and family levels after air pollution exposure. Our results revealed that antibiotics, drugs, and metals in the lung caused lung and intestinal microbiome dysbiosis in ageing rats exposed to air pollution, which may lead to lung function decline.
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The Impact of Social Supports on the Excessive Alcohol Use of the Middle-Aged Adults in South Korea: Do All Types of Social Supports Have Positive Effects on Excessive Alcohol Users? The purpose of the study is to discuss the necessity of interventions on excessive alcohol use among middle-aged adult Koreans and attempt to investigate the effect of social supports including family support and friend support on excessive alcohol use. To achieve these goals, a self-administered online survey was conducted on middle-aged adult Koreans from 40 to 59 years old sampled through the convenience allocation extraction method, with responses of a total of 767 samples analyzed. The results from the analysis was that the support of the family reduced excessive alcohol use, whereas the support of friends provoked excessive alcohol use. Based on these results, the necessity of a distinction in the different types of social supports for interventions in excessive alcohol use was revealed. In addition, several practical and political implications for the alleviation of excessive alcohol use among middle-aged adults are recommended.
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Generation of an induced pluripotent stem cell line (ZJULLi003-A) from a hypertrophic cardiomyopathy patient carrying MYH7/c.4384G > A mutation. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited cardiovascular disease characterized by left ventricular hypertrophy and cardiomyocyte disarray. In this study, a skin biopsy was obtained from a HCM patient, who carried a missense mutation (c.4384G > A; p.E1462K) in the myosin heavy chain 7 (MYH7) gene. The skin fibroblasts were subsequently reprogrammed with a non-integrated Sendai viral method to generate a patient-specific induced pluripotent stem cell (iPSC) line. The generated iPSC line showed typical morphology and normal karyotype, expressed pluripotency markers, and was capable to differentiate into three germ layers.
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The effectiveness of dry needling in patients with chronic low back pain: a prospective, randomized, single-blinded study. Dry needling (DN) is a standard procedure for treating musculoskeletal disorders. However, there are no clear recommendations for using DN in low back pain (LBP). Therefore, this study aimed to assess the effectiveness of the novel DN program for reducing pain intensity and improving functional efficiency in patients with chronic LBP. A group of 40 patients with chronic LBP due to the L5-S1 discopathy were eligible and randomized into experimental (n = 20) and control (n = 20) groups. The DN program was performed for the experimental group according to the Five Regulatory Systems (FRS) concept. The control group received sham therapy using placebo needles. DN sessions were performed twice a week for 4 weeks. A single needling application lasted 60 min. Both groups received standard treatment and physical exercise of LBP for 1 month. Subjective pain was measured by a visual analog scale (VAS), functional efficiency was assessed with the Oswestry Disability Index (ODI), and the lower spine range of motion was measured with the Schober test. There were significant differences in pain reduction (VAS) in both groups (p < 0.001). The strongest analgesic effect in the DN group yielded 6.45 points immediately after the therapy, 6.2 points after 1 month, and 6 points after 3 months. The DN group scored higher VAS reduction than the control group (p < 0.001). There were significant differences in the functional state (ODI) in the experimental group (p < 0.001). There was a significant ODI decrease by 18.1 points, after 1 month by 18.9 points, and after 3 months by 17.6 points. No significant differences were found in the control group (p > 0.05). Intergroup differences were observed in the functional efficiency in ODI in all measurement time-points (p < 0.001). There were significant differences in the range of motion (Schober test) in the DN group (main effect: p < 0.001). For all measurements, differences (p < 0.001) were observed in favor of DN compared to the control. In conclusion, DN program according to the FRS concept stands for the novel treatment method supplemented by an exercise program, effectively reducing pain and improving functional efficiency in LBP patients.
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The Development of iDPC-STEM and Its Application in Electron Beam Sensitive Materials. The main aspects of material research: material synthesis, material structure, and material properties, are interrelated. Acquiring atomic structure information of electron beam sensitive materials by electron microscope, such as porous zeolites, organic-inorganic hybrid perovskites, metal-organic frameworks, is an important and challenging task. The difficulties in characterization of the structures will inevitably limit the optimization of their synthesis methods and further improve their performance. The emergence of integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM), a STEM characterization technique capable of obtaining images with high signal-to-noise ratio under lower doses, has made great breakthroughs in the atomic structure characterization of these materials. This article reviews the developments and applications of iDPC-STEM in electron beam sensitive materials, and provides an outlook on its capabilities and development.
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The Role of Depressive Disorders in Autonomic Cardiovascular Dysregulation in Fibromyalgia. Previous research revealed aberrances in autonomic cardiovascular regulation in fibromyalgia, which may be relevant to symptoms genesis and the increased risk of cardiovascular disorders in individuals with fibromyalgia. This study investigated the role of comorbid depression in autonomic cardiovascular dysregulations in fibromyalgia.
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Essential services: Quantifying the contributions of America's pharmacists in COVID-19 clinical interventions. As the COVID-19 pandemic spread across the United States, America's pharmacists and their teammates expanded their clinical services to help their communities from every practice setting: community and ambulatory care, inpatient, long-term care, academia, public health, and many others.
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Relationships between Plasma Concentrations of Testosterone and Dihydrotestosterone and Geriatric Depression Scale Scores in Men and Women Aged 60-65 Years-A Multivariate Approach with the Use of Quade's Test. The potential role of testosterone and dihydrotestosterone in the pathogenesis of depression in older subjects is poorly recognized and understood. The current study examines the symptoms of depression in males and females at the age of 60-65 using a short version (15 questions) of the Geriatric Depression Scale (GDS) questionnaire. Blood plasma levels of androgens were estimated by LC/MS/MS. Total GDS score calculated for males were not found to be significantly associated with plasma levels of testosterone or dihydrotestosterone. Older men with higher plasma testosteronemia were more likely to report being in good spirits most of the time, but more willing to stay at home than undertake outside activities. The men with higher plasma levels of dihydrotestosterone also perceived themselves as being in good spirits most of the time. Older men with higher testosterone were more likely to report having more problems with their memory than others. No significant associations were found between plasma levels of androgens and GDS scores in older women; however, some tendencies suggest that testosterone and dihydrotestosterone may act as antidepressants in older women.
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Global patterns and rates of habitat transitions across the eukaryotic tree of life. The successful colonization of new habitats has played a fundamental role during the evolution of life. Salinity is one of the strongest barriers for organisms to cross, which has resulted in the evolution of distinct marine and non-marine (including both freshwater and soil) communities. Although microbes represent by far the vast majority of eukaryote diversity, the role of the salt barrier in shaping the diversity across the eukaryotic tree is poorly known. Traditional views suggest rare and ancient marine/non-marine transitions but this view is being challenged by the discovery of several recently transitioned lineages. Here, we investigate habitat evolution across the tree of eukaryotes using a unique set of taxon-rich phylogenies inferred from a combination of long-read and short-read environmental metabarcoding data spanning the ribosomal DNA operon. Our results show that, overall, marine and non-marine microbial communities are phylogenetically distinct but transitions have occurred in both directions in almost all major eukaryotic lineages, with hundreds of transition events detected. Some groups have experienced relatively high rates of transitions, most notably fungi for which crossing the salt barrier has probably been an important aspect of their successful diversification. At the deepest phylogenetic levels, ancestral habitat reconstruction analyses suggest that eukaryotes may have first evolved in non-marine habitats and that the two largest known eukaryotic assemblages (TSAR and Amorphea) arose in different habitats. Overall, our findings indicate that the salt barrier has played an important role during eukaryote evolution and provide a global perspective on habitat transitions in this domain of life.
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Derivable genetic programming for two-dimensional colloidal materials. We describe a method for deriving surface functionalization patterns for colloidal systems that can induce self-assembly into any chosen periodic symmetry at a planar interface. The result is a sequence of letters, s ∈ {A,T,C,G}, or a gene, that describes the perimeter of the colloidal object and programs its self-assembly. This represents a genome that is finite and can be exhaustively enumerated. These genes derive from symmetry, which may be topologically represented by two-dimensional parabolic orbifolds; since these orbifolds are surfaces that may be derived from first principles, this represents an ab initio route to colloid functionality. The genes are human readable and can be employed to easily design colloidal units. We employ a biological (genetic) analogy to demonstrate this and illustrate their connection to the designs of Maurits Cornelis (M. C.) Escher.
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Novel Amoxicillin-Loaded Sericin Biopolymeric Nanoparticles: Synthesis, Optimization, Antibacterial and Wound Healing Activities. Infected wounds are a major threat among diabetic patients. Technological advancements are currently increasing the number of new adjunctive therapies that may be potent agents for speeding recovery, lowering the amputation rate and limiting infection recurrences. A novel formula with promising antibacterial activity, namely sericin/propolis/Amoxicillin nanoparticles, was assessed as a potent treatment of infected wounds in normal and diabetic rats. Skin wound healing efficiency was assessed through wound healing scorings, bacterial load assessment and histological examinations. It was revealed that upon using sericin/propolis/Amoxicillin nanoparticles, complete wound healing was successfully achieved after 10 and 15 days postinjury for nondiabetic and diabetic rats, respectively. However, the bacterial load in the induced infected wounds was extremely low (0-10 CFU/mL) after 15 days post-treatment. The histological studies revealed that the dermis was more organized with new matrix deposition, and mature collagen fibers were observed among the treated animal groups. The present study is the first preclinical study which reported the importance of silk sericin in the form of nano-sericin/propolis loaded with Amoxicillin as an effective treatment against bacterial wound infections.
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Humoral and adaptive immune responses to the SARS-CoV-2 vaccine. Vaccines against SARS-CoV-2 ameliorate infection and adverse outcomes from SARS-CoV-2. Elicitation of high affinity and durable protective antibody responses is a hallmark of a successful humoral immune response to vaccination. To assess the relevance of serum levels of SARS-CoV-2 specific antibodies and to further characterize the immune response to SARS-CoV-2 vaccines, we report i) the levels of spike-binding and neutralizing antibodies to SARS-COV-2 in the sera of 30 healthy volunteers at nine months after the second vaccination dose of mRNA vaccine and one month after the booster dose; ii) the levels of IFN-γ production by blood T cells exposed to SARS-CoV-2 spike antigen (Wuhan, Alpha B.1.1.7, Delta B.1.617.2, and Omicron B1.1.529 variants); and iii) the specific phenotype of T cells related with exposure to SARS-CoV-2 spike antigen. We observed that the booster dose induced increased humoral and adaptive immune responses and led to early activation of the memory CD8+ T subset.
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Baicalein exhibits differential effects and mechanisms towards disruption of α-synuclein fibrils with different polymorphs. Parkinson's disease (PD) is the second most common neurodegenerative diseases with no cure yet and its major hallmark is α-synuclein fibrillary aggregates. The crucial role of α-synuclein aggregation in PD makes it an attractive target for potential disease-modifying therapies. Disaggregation of α-synuclein fibrils is considered as one of the promising therapeutic strategies to treat PD. The wild type (WT) and mutant α-synuclein fibrils exhibit different polymorphs and provide therapeutic targets for PD. Recent experiments reported that a flavonoid baicalein can disrupt WT α-synuclein fibrils. However, the underlying disruptive mechanism remains largely elusive, and whether BAC is capable of disrupting mutant α-synuclein fibrils is also unknown. Herein, we performed microsecond molecular dynamics simulations on cryo-EM-determined WT and two familial PD-associated mutant (E46K and H50Q) α-synuclein fibrils with and without baicalein. We find that baicalein destructs WT fibril by disrupting E46-K80 salt-bridge and β-sheets, and by remodeling the inter-protofilament interface. And baicalein can also damage E46K and H50Q mutant fibrils, but to different extents and via different mechanisms. The E46K fibril disruption is initiated from E61-K80 salt-bridge and N-terminal β-sheet, while the H50Q fibril disruption starts from the inter-protofilament interface and N-terminal β-sheet. These results reveal that disruptive effects and modes of baicalein on α-synuclein fibrils are polymorphism-dependent. This study suggests that baicalein may be a potential drug candidate to disrupt both WT and E46K/H50Q mutant α-synuclein fibrils and alleviate the pathological process of PD.
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Integrated disease surveillance and response in humanitarian context: South Sudan experience. decades of instability continue to impact the implementation of the Integrated Disease Surveillance and Response (IDSR) strategy. The study reviewed the progress and outcomes of rolling out IDSR in South Sudan.
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A taxonomic revision of the dirt ants, Basiceros Schulz, 1906 (Hymenoptera, Formicidae). The ant genus Basiceros is an exclusively Neotropical group known for its cryptic habits. Based on a recent molecular phylogenetic framework, a comprehensive revisionary study of the genus is presented. Nine species are recognized, two of which are described as new (Basiceros browni sp. nov. and Basiceros tumucumaquensis sp. nov.). Basiceros redux (Donisthorpe 1939) is transferred to the genus Octostruma (O. reducta comb. nov.). As part of this revisionary work, taxonomic keys and images to all species and castes are provided. Castes and sexes (including larvae, males, and intercastes) are described for the first time for several Basiceros species. New records considerably expand the distributional range for most species. Natural history data and comments on character plasticity and convergence are also included.
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Higher fasting blood glucose was associated with worse in-hospital clinical outcomes in patients with primary intracerebral hemorrhage: From a large-scale nationwide longitudinal registry. Studies that investigated the relationship between fasting blood glucose (FBG) and intracerebral hemorrhage (ICH) outcomes were insufficient.
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Subjective and objective difficulty of emotional facial expression perception from dynamic stimuli. This study aimed to discover predictors of subjective and objective difficulty in emotion perception from dynamic facial expressions. We used a multidimensional emotion perception framework, in which observers rated the perceived emotion along a number of dimensions instead of choosing from traditionally-used discrete categories of emotions. Data were collected online from 441 participants who rated facial expression stimuli in a novel paradigm designed to separately measure subjective (self-reported) and objective (deviation from the population consensus) difficulty. We targeted person-specific (sex and age of observers and actors) and stimulus-specific (valence and arousal values) predictors of those difficulty scores. Our findings suggest that increasing age of actors makes emotion perception more difficult for observers, and that perception difficulty is underestimated by men in comparison to women, and by younger and older adults in comparison to middle-aged adults. The results also yielded an increase in the objective difficulty measure for female observers and female actors. Stimulus-specific factors-valence and arousal-exhibited quadratic relationships with subjective and objective difficulties: Very positive and very negative stimuli were linked to reduced subjective and objective difficulty, whereas stimuli of very low and high arousal were linked to decreased subjective but increased objective difficulty. Exploratory analyses revealed low relevance of person-specific variables for the prediction of difficulty but highlighted the importance of valence in emotion perception, in line with functional accounts of emotions. Our findings highlight the need to complement traditional emotion recognition paradigms with novel designs, like the one presented here, to grasp the "big picture" of human emotion perception.
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Persistent symptoms are diverse and associated with health concerns and impaired quality of life in patients with paediatric coeliac disease diagnosis after transition to adulthood. To investigate the prevalence and associated factors of persistent symptoms despite a strict gluten-free diet in adult patients with coeliac disease diagnosed in childhood.
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Transcriptome Dynamics Underlying Magnesium Deficiency Stress in Three Founding Saccharum Species. Modern sugarcane cultivars were generated through interspecific crossing of the stress resistance Saccharum spontaneum and the high sugar content Saccharum officinarum which was domesticated from Saccharum robustum . Magnesium deficiency (MGD) is particularly prominent in tropical and subtropical regions where sugarcane is grown, but the response mechanism to MGD in sugarcane remains unknown. Physiological and transcriptomic analysis of the three founding Saccharum species under different magnesium (Mg) levels was performed. Our result showed that MGD decreased chlorophyll content and photosynthetic efficiency of three Saccharum species but led to increased starch in leaves and lignin content in roots of Saccharum robustum and Saccharum spontaneum . We identified 12,129, 11,306 and 12,178 differentially expressed genes (DEGs) of Saccharum officinarum , Saccharum robustum and Saccharum spontaneum , respectively. In Saccharum officinarum , MGD affected signal transduction by up-regulating the expression of xylan biosynthesis process-related genes. Saccharum robustum, responded to the MGD by regulating the expression of transcription and detoxification process-related genes. Saccharum spontaneum , avoids damage from MGD by regulating the expression of the signing transduction process and the transformation from growth and development to reproductive development. This novel repertoire of candidate genes related to MGD response in sugarcane will be helpful for engineering MGD tolerant varieties.
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Percutaneous Transhepatic Treatment of Benign Bile Duct Strictures Using Retrievable Covered Stents: Long-Term Outcomes in 148 Patients. To investigate the long-term outcomes of percutaneous treatment of benign biliary strictures using temporary placement of a retrievable expanded polytetrafluoroethylene (PTFE) covered stent.
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MPN-304 Analysis of Clinical and Hematological Characteristics of Primary Myelofibrosis in the Young Patients From the Republic of Moldova: A Single-Institution Experience. Over the last several decades, we have observed an increase in the number of young patients with myeloproliferative neoplasms. The lack of information about clinic-hematological manifestations and outcomes requires a boost of common efforts between specialists.
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Anti-Inflammatory Effects of GLP-1R Activation in the Retina. Glucagon-like peptide-1 (GLP-1) is an incretin hormone, mainly produced by enteroendocrine L cells, which participates in the regulation of glucose homeostasis, and in reduction in body weight by promoting satiety. Actions of GLP-1 are mediated by activation of its receptor GLP-1R, which is widely expressed in several tissues including the retina. The effects of GLP-1R activation are useful in the management of type 2 diabetes mellitus (T2DM). In addition, the activation of GLP-1R has anti-inflammatory effects in several organs, suggesting that it may be also useful in the treatment of inflammatory diseases. Inflammation is a common element in the pathogenesis of several ocular diseases, and the protective effects of treatment with GLP-1 emerged also in retinal diseases. In this review we highlight the anti-inflammatory effects of GLP-1R activation in the retina. Firstly, we summarized the pathogenic role of inflammation in ocular diseases. Then, we described the pleiotropic effects of GLP-1R activation on the cellular components of the retina which are mainly involved in the pathogenesis of inflammatory retinal diseases: the retinal ganglion cells, retinal pigment epithelial cells and endothelial cells.
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Electrocardiogram Parameters That Affect the Success Rate of Radiofrequency Ablation in Patients with Outflow Tract Ventricular Premature Complexes. The objectives of this study are to assess the efficacy of radiofrequency catheter ablation (RFCA) in patients with outflow tract (OT) ventricular premature complexes (VPCs) and to explore the electrocardiographic (ECG) features of initially successful procedures.
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Sex-specific Regulation of Prolactin Secretion by Pituitary Bradykinin Receptors. Sex differences in the control of prolactin secretion are well documented. Sex-related differences in intrapituitary factors regulating lactotroph function have recently attracted attention. Sex differences in prolactinoma development are well documented in clinic, prolactinomas being more frequent in women but more aggressive in men, for poorly understood reasons. Kallikrein, the enzyme releasing kinins has been found in the pituitary, but there is no information on pituitary kinin receptors and their function. In the present work, we characterized pituitary bradykinin receptors (BRs) at the messenger RNA and protein levels in 2 mouse models of prolactinoma, Drd2 receptor gene inactivation and hCGβ gene overexpression, in both males and females, wild type or genomically altered. BR B2 (B2R) accounted for 97% or more of total pituitary BRs in both models, regardless of genotype, and was present in lactotrophs, somatotrophs, and gonadotrophs. Male pituitaries displayed higher level of B2R than females, regardless of genotype. Pituitary B2R gene expression was downregulated by estrogen in both males and females but only in females by dopamine. Activation of B1R or B2R by selective pharmacological agonists induced prolactin release in male pituitaries but inhibited prolactin secretion in female pituitaries. Increased B2R content was observed in pituitaries of mutated animals developing prolactinomas, compared to their respective wild-type controls. The present study documents a novel sex-related difference in the control of prolactin secretion and suggests that kinins are involved, through B2R activation, in lactotroph function and prolactinoma development.
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An observational study of the effects of smoking cessation earlier on the clinical characteristics and course of acute exacerbations of chronic obstructive pulmonary disease. Previous studies have focused on the negative effects of continued smoking on chronic obstructive pulmonary disease (COPD). However, few studies have investigated the positive effects of long-term smoking cessation on patients suffering from acute exacerbations of COPD.
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Shikonin derivatives cause apoptosis and cell cycle arrest in human chondrosarcoma cells via death receptors and MAPK regulation. Although chondrosarcoma is the second most common primary malignant bone tumor, treatment options are limited due to its extensive resistance to a chemo- and radiation therapy. Since shikonin has shown potent anticancer activity in various types of cancer cells, it represents a promising compound for the development of a new therapeutic approach.
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Cerium/polyacrylic acid modified porphyrin metal-organic framework as fluorescence and photothermal sensor for ascorbic acid measurement. A fluorescence and photothermal dual-signal assay was developed for the determination of ascorbic acid (AA). Cerium/polyacrylic acid modified porphyrin metal-organic frameworks (PCN-224@PAA-Ce MOFs) exhibit oxidase-like activity and can effectively oxidize 3,3 ', 5,5 '-tetramethylbenzidine (TMB) from colorless substrates to blue substrates (oxTMB). The absorption spectrum of oxTMB overlaps with the emission spectrum of PCN-224@PAA-Ce, resulting in quenching of fluorescence emission of PCN-224@PAA-Ce. oxTMB, as an excellent photothermal agent, converts the optical signal into the thermal signal (temperature increasing) driven by 808 nm laser. In the presence of AA, the blue oxTMB was reduced to colorless TMB, which led to the fluorescence recovery of PCN-224@PAA-Ce and at the same time, the photothermal signal was changed with the temperature decreasing under the driving of 808 nm laser. The detection limits (LOD) of fluorescence/photothermal dual-mode AA sensor strategies were as low as 0.73 μM and 1.4 μM, respectively. Rapid analysis of ascorbic acid was accomplished with the present procedure, AA in vitamin C tablets and human serum samples were validated.
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Short-Term Efficacy and Safety of Open Conjunctiva Ab Externo XEN45 Gel Stent Implantation in Glaucoma Patients. We examined the safety and efficacy of the open conjunctiva ab externo approach for XEN45 gel stent implantation. There was a significant reduction in intraocular pressure (IOP) and number of glaucoma medications at 12 months follow-up.
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Impact of the COVID-19 Pandemic on Elective and Emergency Surgical Procedures in a University Hospital. to assess the impact of the COVID-19 pandemic on abdominal wall hernia repair surgeries and cholecystectomy in a referral center hospital.
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Estimation of nitrous oxide emissions from rice paddy fields using the DNDC model: a case study of South Korea. The Denitrification-Decomposition (DNDC)-Rice is a mechanistic model which is widely used for the simulation and estimation of greenhouse gas emissions [nitrous oxide (N 2 O)] from soils under rice cultivation. N 2 O emissions from paddy fields in South Korea are of high importance for their cumulative effect on climate. The objective of this study was to estimate the N 2 O emissions and biogeochemical factors involved in N 2 O emissions such as ammonium (NH 4 + ) and nitrate (NO 3 - ) using the DNDC model in the rice-growing regions of South Korea. N 2 O emission was observed at every application of fertilizer and during end-season drainage at different rice-growing regions in South Korea. Maximum NH 4 + and NO 3 - were observed at 0-10 cm depth of soil. NH 4 + increased at each fertilizer application and no change in NO 3 - was observed during flooding. NH 4 + decreased and NO 3 - increased simultaneously at end-season drainage. Minimum and maximum cumulative N 2 O emissions were observed at Chungcheongbuk-do and Jeju-do regions of South Korea, respectively. The simulated average cumulative N 2 O emission in rice paddies of South Korea was 1.37 kg N 2 O-N ha -1 season -1 . This study will help in calculating the total nitrogen emissions from agriculture land of South Korea and the World.
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Intra-bone marrow injection of magnesium isoglyrrhizinate inhibits inflammation and delays osteoarthritis progression through the NF-κB pathway. Osteoarthritis (OA) presents cartilage damage in addition to chronic inflammation. However, self-recovery of damaged cartilage in an inflammatory environment is not possible. Mesenchymal stem cells (MSCs) in the bone marrow are a source of regenerative repair of damaged cartilage. To date, whether intra-luminal administration of the bone marrow can delay the progression of OA is still unknown. This study, therefore, aimed to explore the role of intra-bone marrow injection of Magnesium isoglycyrrhizinate (MgIG) in delaying the OA progression and to investigate the underlying mechanism.
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Recent Developments to Cope the Antibacterial Resistance via β-Lactamase Inhibition. Antibacterial resistance towards the β-lactam (BL) drugs is now ubiquitous, and there is a major global health concern associated with the emergence of new β-lactamases (BLAs) as the primary cause of resistance. In addition to the development of new antibacterial drugs, β-lactamase inhibition is an alternative modality that can be implemented to tackle this resistance channel. This strategy has successfully revitalized the efficacy of a number of otherwise obsolete BLs since the discovery of the first β-lactamase inhibitor (BLI), clavulanic acid. Over the years, β-lactamase inhibition research has grown, leading to the introduction of new synthetic inhibitors, and a few are currently in clinical trials. Of note, the 1, 6-diazabicyclo [3,2,1]octan-7-one (DBO) scaffold gained the attention of researchers around the world, which finally culminated in the approval of two BLIs, avibactam and relebactam, which can successfully inhibit Ambler class A, C, and D β-lactamases. Boronic acids have shown promise in coping with Ambler class B β-lactamases in recent research, in addition to classes A, C, and D with the clinical use of vaborbactam. This review focuses on the further developments in the synthetic strategies using DBO as well as boronic acid derivatives. In addition, various other potential serine- and metallo- β-lactamases inhibitors that have been developed in last few years are discussed briefly as well. Furthermore, binding interactions of the representative inhibitors have been discussed based on the crystal structure data of inhibitor-enzyme complex, published in the literature.
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Mutagenesis of high-efficiency heterotrophic nitrifying-aerobic denitrifying bacterium Rhodococcus sp. strain CPZ 24. Breeding high-efficiency heterotrophic nitrifying-aerobic denitrifying (SND) bacteria is important for the removal of biological nitrogen in wastewater treatment. In this study, a high-efficiency SND mutant strain, ΔRhodococcus sp. CPZ 24, was obtained by ultraviolet-diethyl sulfate compound mutagenesis. The maximum nitrification and denitrification rates were 3.77 and 1.37 mg·L -1 ·h -1 , respectively 30.30 % and 17.10 % higher than those of wild bacteria. Biolog technology and network model analysis revealed that ΔCPZ 24 significantly improved the utilisation ability and metabolic activity of organic carbon sources. Furthermore, the expression levels of the nitrogen removal function genes nxrA, nosZ, amoA, and norB in strain ΔCPZ 24 increased significantly. In actual sewage, mutant bacteria ΔCPZ 24 have a 95.05 % ammonia-nitrogen degradation rate and a 96.67 % nitrate-nitrogen degradation rate. These results suggested that UV-DES compound mutation was a successful strategy to improve the nitrogen removal performance of SND bacteria in wastewater treatment.
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A refined chronology for the Middle and early Upper Paleolithic sequence of Riparo Mochi (Liguria, Italy). The Riparo Mochi rock shelter, located on the Ligurian coast of Italy, is one of the most important early Upper Paleolithic sites on the Mediterranean rim. Its ∼10-m-deep stratigraphy comprises a Mousterian sequence, followed by various development stages of the Upper Paleolithic. A series of radiometric dates on marine shells bearing traces of human modification has provided a chronological framework for the final Mousterian and the Proto-Aurignacian of the site. Based on modeling results, the end of the Mousterian was dated between 44.0 and 41.8 ka cal BP (68% probability) and the beginning of the Proto-Aurignacian between 42.7 and 41.6 ka cal BP (68% probability). However, these estimates were based on a limited number of radiocarbon ages in the Mousterian levels. Here, we report new dating of the Mochi sequence using luminescence techniques, along with new radiocarbon measurements. The combination of these results using a Bayesian modeling approach allows for the first time the establishment of a more precise timing for the Mousterian occupation at the site. We show that Mousterian groups were already present at Riparo Mochi by at least 65 ka and continued to occupy the site for another 20 ka. The transition to the earliest Upper Paleolithic at the site is centered around 44.3-41.1 ka (95.4% probability), providing our best age estimate for the beginning of the Early Upper Paleolithic and the establishment of modern human groups in the Balzi Rossi. The sequence continues upward with a more evolved Aurignacian phase and a Gravettian phase starting at ∼26 ka or earlier.
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ICT Tools for Registry Research: A Market Survey. Registries in health research are complex systems requiring a diverse infrastructure with information and communications technology tools (ICT tools) for manifold tasks. Those tools should support not only data management but also several core and accompanying processes. Recent trends in registry research also need to be taken into account. Thirty-five vendors, suppliers, and experts were included in a survey on ICT tools for registries and cohorts. Information from 28 tools was available for a preliminary analysis. In comparison to 2015 and 2018, coverage of core processes such as registry development or data analysis and utilization increased from below 40% to 39% and higher. Recording patient-reported information and linkage to other data collections was well covered. However, near-patient trends were less supported. The market offers a rich selection of commercial and non-commercial ICT tools for registry research. Due to the manifold offers available from the market, in-house developed software should be an absolute exception.
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Comprehensive analysis of pyroptotic gene prognostic signatures associated with tumor immune microenvironment and genomic mutation in breast cancer. Breast cancer is becoming a tumor with the highest morbidity rate, and inflammation-induced cell death namely pyroptosis reportedly plays dual roles in cancers. However, the specific mechanism between pyroptosis and the clinical prognosis of breast cancer patients is indistinct. Hence, novel pyroptosis-related biomarkers and their contributing factors deserve further exploration to predict the prognosis in breast cancer.
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Genome-wide analysis of the B-box gene family in the sweetpotato wild ancestor Ipomoea trifida and determination of the function of IbBBX28 in the regulation of flowering time of Arabidopsis. B-box (BBX) proteins constitute a class of transcription factors that play vital roles in the regulation of photoperiod flowering, photomorphogenesis, and the response to biotic and abiotic stresses. In this paper, a total of 32 BBX genes were identified in Ipomoea trifida, a wild ancestor of sweetpotato. Chromosome localization analysis showed that these 32 ItfBBX genes were distributed unevenly across 12 chromosomes. The ItfBBX gene family members were classified into five groups according to their phylogenetic relationships and structural features. Predictions of cis-elements revealed that the promoter sequences of the ItfBBX genes contain light response, stress response, hormone response and other elements. Synteny analysis revealed evidence of 26 segmental duplication events and only one tandem duplication event. Tissue-specific and abiotic stress-response expression profiles were analysed, and the results were confirmed via RT-qPCR. Overall, ItfBBX genes may play vital roles in the stress response. We chose IbBBX28 for further study and revealed that IbBBX28 negatively regulates the flowering time of IbBBX28-overexpressing Arabidopsis under long-day conditions. Our study provides references for characterizing the function of BBX genes in sweetpotato.
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Activation of AMP-activated protein kinase ablated the formation of aortic dissection by suppressing vascular inflammation and phenotypic switching of vascular smooth muscle cells. Aortic dissection (AD) is a fatal vascular disease in absence of effective pharmaceutical therapy. Adenosine monophosphate-activated protein kinase α (AMPKα) plays a critical role in various cardiovascular diseases. Whether AMPKα is involved in the pathogenesis of aortic dissection remains unknown. We aimed to determine whether activation of AMPKα prevents the formation of AD.
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Laboratory platform for monitoring SARS-CoV-2 based on surveillance of influenza and other respiratory viruses in Peru. In Peru, the COVID-19 pandemic demonstrated the usefulness of having a structured laboratory surveillance system that has been operational for 22 years, based on influenza surveillance; initially in the form of sentinel units, and later strengthened and innovated, with its own resources and with external support, to provide quality information. Biotechnological advances have been implemented for diagnostic confirmation and the capacity of the national laboratory network has been expanded, maintaining efficiency, considering the diverse and complex realities of each region, and overcoming difficulties regarding communication and articulation between institutions. It is necessary to consolidate this system, with collaborative and coordinated work between its components, boosting its effectiveness and timeliness and promoting genomic surveillance of new viruses and variants, as is currently the case with SARS-CoV-2.
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Pediatric inborn errors of immunity causing hemophagocytic lymphohistiocytosis: Case report and review of the literature. Inborn errors of immunity are a group of genetic disorders caused by mutations that affect the development and/or function of several compartments of the immune system, predisposing patients to infections, autoimmunity, allergy and malignancies. In this regard, mutations that affect proteins involved in trafficking, priming, docking, or membrane fusion will impair the exocytosis of lytic granules of effector NK and cytotoxic T lymphocytes. This may predispose patients to hemophagocytic lymphohistiocytosis, a life-threatening immune disorder characterized by systemic lymphocyte and macrophage activation, and increased levels of cytokines, which lead to an uncontrolled hyperinflammation state and progressive multiorgan damage. In this review, we will describe a clinical case and recent advances in inborn errors of immunity predisposing to hemophagocytic lymphohistiocytosis. Summary sentence: Review of recent advances in inborn errors of immunity predisposing to hemophagocytic lymphohistiocytosis.
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GPNMB confers risk for Parkinson's disease through interaction with α-synuclein. Many risk loci for Parkinson's disease (PD) have been identified by genome-wide association studies (GWASs), but target genes and mechanisms remain largely unknown. We linked the GWAS-derived chromosome 7 locus (sentinel single-nucleotide polymorphism rs199347) to GPNMB through colocalization analyses of expression quantitative trait locus and PD risk signals, confirmed by allele-specific expression studies in the human brain. In cells, glycoprotein nonmetastatic melanoma protein B (GPNMB) coimmunoprecipitated and colocalized with α-synuclein (aSyn). In induced pluripotent stem cell-derived neurons, loss of GPNMB resulted in loss of ability to internalize aSyn fibrils and develop aSyn pathology. In 731 PD and 59 control biosamples, GPNMB was elevated in PD plasma, associating with disease severity. Thus, GPNMB represents a PD risk gene with potential for biomarker development and therapeutic targeting.
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GW842166X Alleviates Osteoarthritis by Repressing LPS-mediated Chondrocyte Catabolism in Mice. To explore the role and underlying mechanism of GW842166X on osteoarthritis and osteoarthritis-associated abnormal catabolism.
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Perspectives on the mechanism of pyroptosis after intracerebral hemorrhage. Intracerebral hemorrhage (ICH) is a highly harmful neurological disorder with high rates of mortality, disability, and recurrence. However, effective therapies are not currently available. Secondary immune injury and cell death are the leading causes of brain injury and a poor prognosis. Pyroptosis is a recently discovered form of programmed cell death that differs from apoptosis and necrosis and is mediated by gasdermin proteins. Pyroptosis is caused by multiple pathways that eventually form pores in the cell membrane, facilitating the release of inflammatory substances and causing the cell to rupture and die. Pyroptosis occurs in neurons, glial cells, and endothelial cells after ICH. Furthermore, pyroptosis causes cell death and releases inflammatory factors such as interleukin (IL)-1β and IL-18, leading to a secondary immune-inflammatory response and further brain damage. The NOD-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) pathway plays the most critical role in pyroptosis after ICH. Pyroptosis can be inhibited by directly targeting NLRP3 or its upstream molecules, or directly interfering with caspase-1 expression and GSDMD formation, thus significantly improving the prognosis of ICH. The present review discusses key pathological pathways and regulatory mechanisms of pyroptosis after ICH and suggests possible intervention strategies to mitigate pyroptosis and brain dysfunction after ICH.
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Quantitative Pharmacodynamic Characterization of Resistance versus Heteroresistance of Colistin in E. coli Using a Semimechanistic Modeling of Killing Curves. Heteroresistance corresponds to the presence, in a bacterial isolate, of an initial small subpopulation of bacteria characterized by a significant reduction in their sensitivity to a given antibiotic. Mechanisms of heteroresistance versus resistance are poorly understood. The aim of this study was to explore heteroresistance in mcr -positive and mcr -negative Escherichia coli strains exposed to colistin by use of modeling killing curves with a semimechanistic model. We quantify, for a range of phenotypically (susceptibility based on MIC) and genotypically (carriage of mcr -1 or mcr -3 or mcr -negative) different bacteria, a maximum killing rate ( E max ) of colistin and the corresponding potency (EC 50 ), i.e., the colistin concentrations corresponding to E max /2. Heteroresistant subpopulations were identified in both mcr -negative and mcr -positive E. coli as around 0.06% of the starting population. Minority heteroresistant bacteria, both for mcr -negative and mcr -positive strains, differed from the corresponding dominant populations only by the maximum killing rate of colistin (differences for E max by a factor of 12.66 and 3.76 for mcr -negative and mcr -positive strains, respectively) and without alteration of their EC 50 s. On the other hand, the resistant mcr -positive strains are distinguished from the mcr -negative strains by differences in their EC 50 , which can reach a factor of 44 for their dominant population and 22 for their heteroresistant subpopulations. It is suggested that the underlying physiological mechanisms differ between resistance and heteroresistance, with resistance being linked to a decrease in the affinity of colistin for its site of action, whereas heteroresistance would, rather, be linked to an alteration of the target, which will be more difficult to be further changed or destroyed.
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Developmental neurotoxicity of acrylamide and its metabolite glycidamide in a human mixed culture of neurons and astrocytes undergoing differentiation in concentrations relevant for human exposure. Neural stem cells (NSCs) derived from human induced pluripotent stem cells were used to investigate effects of exposure to the food contaminant acrylamide (AA) and its main metabolite glycidamide (GA) on key neurodevelopmental processes. Diet is an important source of human AA exposure for pregnant women, and AA is known to pass the placenta and the newborn may also be exposed through breast feeding after birth. The NSCs were exposed to AA and GA (1 ×10 -8 - 3 ×10 -3 M) under 7 days of proliferation and up to 28 days of differentiation towards a mixed culture of neurons and astrocytes. Effects on cell viability was measured using Alamar Blue™ cell viability assay, alterations in gene expression were assessed using real time PCR and RNA sequencing, and protein levels were quantified using immunocytochemistry and high content imaging. Effects of AA and GA on neurodevelopmental processes were evaluated using endpoints linked to common key events identified in the existing developmental neurotoxicity adverse outcome pathways (AOPs). Our results suggest that AA and GA at low concentrations (1 ×10 -7 - 1 ×10 -8 M) increased cell viability and markers of proliferation both in proliferating NSCs (7 days) and in maturing neurons after 14-28 days of differentiation. IC 50 for cell death of AA and GA was 5.2 × 10 -3 M and 5.8 × 10 -4 M, respectively, showing about ten times higher potency for GA. Increased expression of brain derived neurotrophic factor (BDNF) concomitant with decreased synaptogenesis were observed for GA exposure (10 -7 M) only at later differentiation stages, and an increased number of astrocytes (up to 3-fold) at 14 and 21 days of differentiation. Also, AA exposure gave tendency towards decreased differentiation (increased percent Nestin positive cells). After 28 days, neurite branch points and number of neurites per neuron measured by microtubule-associated protein 2 (Map2) staining decreased, while the same neurite features measured by βIII-Tubulin increased, indicating perturbation of neuronal differentiation and maturation.
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Lymphadenectomy Benefits Small Cell Carcinoma of Ovary: A Population-Based Analysis. Small cell carcinoma of the ovary (SCCO) is a rare type of ovarian cancer with high aggressiveness. The optimal treatment modality remains elusive. This study aims to comprehensively investigate the survival impact of clinical characteristics and treatments including lymphadenectomy in SCCO. A retrospective cohort study was performed and included patients from the Surveillance, Epidemiology, and End Results (SEER) database. Data collected included demographics, therapeutic details, and pathologic characteristics. Propensity-score matching analysis (PSM) was carried out to balance baseline variables between SCCO and non-SCCO. Cox regression, Kaplan-Meier, and stratified analyses were conducted before and after PSM. After filtering, 80 records on SCCO and 39,662 records on non-SSCO were obtained. Patients with SCCO were more prone to present unilateral tumor (57.6% and 85.0%, p < 0.001), larger tumor size (>15 cm: 9.5% and 32.5%; 10-15 cm: 13.2% vs. 22.5%, p < 0.001), younger age (59.1 ± 14.91 vs. 37.2 ± 19.05; p < 0.001), single status (17.0% vs. 45.0%; p < 0.001), single malignant tumor in a lifetime (76.1% vs. 87.5%; p = 0.0244), and pathologic grade IV diseases (14.5% vs. 40.0%; p < 0.001) compared with non-SCCO. After balancing the baseline clinical characteristics with a 1:4 ratio PSM, a total of matched 72 patients with SCCO and 254 patients with non-SCCO were identified. The survival rate of SCCO was distinctly inferior to non-SCCO, particularly in FIGO I, II, and III stages. Lymphadenectomy was performed in 37 (51.39%) SCCO patients, of whom 12 (32.43%) were found to have pathologically positive lymph nodes. Lymphadenectomy was linked to favorable overall survival in SCCO, particularly in the advanced stage, and was also an independent prognostic factor, whereas lymphadenectomy did not reveal an edge in matched non-SCCO. There was a pronounced survival benefit for SCCO when at least 10 or more nodes were resected. Lymphadenectomy in a non-stage-dependent way should be considered and deserves further clinical validation to promote the overall survival in SCCO.
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Effort-based decision making and self-reported apathy in frequent cannabis users and healthy controls: A replication and extension. Amotivational syndrome is a term used to refer to lack of motivation and passive personality related to chronic cannabis use. Given mixed findings, the current study aimed to replicate and extend previous research on frequent cannabis use, motivated behavior, and self-reported apathy.
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Incidental Os Odontoideum in an Adolescent Athlete With Sports-Related Concussion. Sports-related concussion (SRC) is a frequent injury in the adolescent population with presentation including a wide array of signs and symptoms. There are no universally agreed upon guidelines for when to pursue advanced imaging, such as magnetic resonance imaging (MRI), in the workup of SRCs in the adolescent population. Our experience indicates that MRI rarely contributes to management. This case report highlights a rare finding of os odontoideum on MRI imaging in an adolescent female soccer player in the setting of treatment of an SRC that altered the course of her clinical management.
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Double jeopardy: How lower levels of support during COVID-19 exacerbated the relationship between loneliness and distress. While the relationship between loneliness and psychological distress is well documented, the mechanisms underlying this relationship are less clear. One factor known to be related to loneliness as well as psychological distress, is social support, with some studies suggesting that support-both received and provided-can serve as a mechanism to reduce the distress associated with loneliness. In this paper we examine the mediating role of both aspects of support in the relationship between loneliness and psychological distress in the COVID-19 context. We used a multi-country dataset collected at two timepoints during the pandemic; the first during the early stages ( N = 6,842, 11 countries) and the second collected for a subset of countries ( N = 1,299, 3 countries) 3 months later. Across all eleven countries, results revealed significant positive associations between loneliness and distress. Furthermore, using longitudinal data, we investigated the directionality of this relationship and found that increased loneliness over time was associated with increased psychological distress. The data also showed that both feeling unsupported and feeling unable to provide support to others mediated this relationship. These findings point to the need to facilitate people's ability to draw effective social support and help others-particularly at times when social connectedness is threatened-as a way of alleviating the psychological distress that commonly presents with loneliness.
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Total Synthesis of Darobactin A. The collaborative total synthesis of darobactin A, a recently isolated antibiotic that selectively targets Gram-negative bacteria, has been accomplished in a convergent fashion with a longest linear sequence of 16 steps from d-Garner's aldehyde and l-serine. Scalable routes toward three non-canonical amino acids were developed to enable the synthesis. The closure of the bismacrocycle was realized through sequential, halogen-selective Larock indole syntheses, where the proper order of cyclizations proved crucial for the formation of the desired atropisomer of the natural product.
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How Does Government Efficiency Affect Health Outcomes? The Empirical Evidence from 156 Countries. This paper uses the unbalanced panel data of 156 countries during the period of 2002 to 2018 to explore the possible impact of government efficiency on health outcomes. Firstly, we used the fixed-effect model to examine the relationship between government efficiency and health outcomes and found that the increase in government efficiency can significantly improve health outcomes. Then, a series of robustness checks were carried out, which confirmed the reliability of the above result. Thirdly, this paper conducted a heterogeneity analysis from the perspective of life cycle. Fourthly, this paper investigated the mechanisms of the impact of government efficiency on health outcomes from the perspectives of economic growth, health innovation, education and corruption control. Finally, this paper studied the moderating effects of the ruling party's ideology and democracy on the relationship between government efficiency and health outcomes. The findings of this study provide some references for governments to improve health outcomes.
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A new droplet digital PCR assay: improving detection of paucibacillary smear-negative pulmonary tuberculosis. Smear-negative pulmonary TB (PTB) is difficult to diagnose. Current diagnosis and treatment monitoring methods have inherent limitations. Droplet digital PCR (ddPCR) is a new technique with high sensitivity. This study presents a novel ddPCR for rapid and sensitive identification of Mycobacterium tuberculosis (MTB).
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Comparison between the Right and Left Distal Radial Access for Patients Undergoing Coronary Procedures: A Propensity Score Matching Analysis. Distal radial access for coronary procedures decreases hemostasis time, prevents radial occlusion, and improves patient comfort compared to conventional transradial access. Initially described for left distal radial access (lDRA), the right distal radial access (rDRA) is feasible. However, there are no comparative studies to date. This study aimed to evaluate the impact of the access site on vascular access and procedural performance.
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A novel fluorescent probe for real-time imaging of thionitrous acid under inflammatory and oxidative conditions. Thionitrous acid (HSNO), a crosstalk intermediate of two crucial gasotransmitters nitric oxide and hydrogen sulfide, plays a critical role in redox regulation of cellular signaling and functions. However, real-time and facile detection of HSNO with high selectivity and sensitivity remains highly challenging. Herein we report a novel fluorescent probe (SNP-1) for HSNO detection. SNP-1 has a simple molecular structure, but showing strong fluorescence, a low detection limit, a broad linear detection range (from nanomolar to micromolar concentrations), ultrasensitivity, and high selectivity for HSNO in both aqueous media and cells. Benefiting from these unique features, SNP-1 could effectively visualize changes of HSNO levels in mouse models of acute ulcerative colitis and renal ischemia/reperfusion injury. Moreover, the good correlation between colonic HSNO levels and disease activity index demonstrated that HSNO is a promising new diagnostic agent for acute ulcerative colitis. Therefore, SNP-1 can serve as a useful fluorescent probe for precision detection of HSNO in various biological systems, thereby facilitating mechanistic studies, therapeutic assessment, and high-content drug screening for corresponding diseases.
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Risk assessment models for venous thromboembolism in pregnancy and in the puerperium: a systematic review. To assess the comparative accuracy of risk assessment models (RAMs) to identify women during pregnancy and the early postnatal period who are at increased risk of venous thromboembolism (VTE).
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Pathogenic strategies and immune mechanisms to necrotrophs: Differences and similarities to biotrophs and hemibiotrophs. Pathogenesis in plant diseases is complex comprising diverse pathogen virulence and plant immune mechanisms. These pathogens cause damaging plant diseases by deploying specialized and generic virulence strategies that are countered by intricate resistance mechanisms. The significant challenges that necrotrophs pose to crop production are predicted to increase with climate change. Immunity to biotrophs and hemibiotrophs is dominated by intracellular receptors that recognize specific effectors and activate resistance. These mechanisms play only minor roles in resistance to necrotrophs. Pathogen- or host-derived conserved pattern molecules trigger immune responses that broadly contribute to plant immunity. However, certain pathogen or host-derived immune elicitors are enriched by the virulence activities of necrotrophs. Different plant hormones modulate systemic resistance and cell death that have differential impacts on resistance to pathogens of different lifestyles. Knowledge of mechanisms that contribute to resistance to necrotrophs has expanded. Besides toxins and cell wall degrading enzymes that dominate the pathogenesis of necrotrophs, other effectors with subtle contributions are being identified.
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Positron Emission Tomography reveals age-associated hypothalamic microglial activation in women. In rodents, hypothalamic inflammation plays a critical role in aging and age-related diseases. Hypothalamic inflammation has not previously been assessed in vivo in humans. We used Positron Emission Tomography (PET) with a radiotracer sensitive to the translocator protein (TSPO) expressed by activated microglia, to assess correlations between age and regional brain TSPO in a group of healthy subjects (n = 43, 19 female, aged 23-78), focusing on hypothalamus. We found robust age-correlated TSPO expression in thalamus but not hypothalamus in the combined group of women and men. This pattern differs from what has been described in rodents. Prominent age-correlated TSPO expression in thalamus in humans, but in hypothalamus in rodents, could reflect evolutionary changes in size and function of thalamus versus hypothalamus, and may be relevant to the appropriateness of using rodents to model human aging. When examining TSPO PET results in women and men separately, we found that only women showed age-correlated hypothalamic TSPO expression. We suggest this novel result is relevant to understanding a stark sex difference in human aging: that only women undergo loss of fertility-menopause-at mid-life. Our finding of age-correlated hypothalamic inflammation in women could have implications for understanding and perhaps altering reproductive aging in women.
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Temperature dependence studies of tissue-mimicking phantoms for ultra-wideband microwave breast tumor detection. Microwave imaging (MWI) systems are being investigated for breast cancer diagnostics as an alternative to conventional x-ray mammography and breast ultrasound. This work aims at a next generation of tissue-mimicking phantoms modelling the temperature-dependent dielectric properties of breast tissue over a large frequency bandwidth. Such phantoms can be used to develop a novel kind of MWI systems that exploit the temperature-dependent permittivity of tissue as a natural contrast agent. Due to the higher water content in tumor tissue, a temperature increase leads to a different change in the complex permittivity compared to surrounding tissue. This will generate a tumor dominated scattering response when the overall tissue temperature increases by a few degrees, e.g. through the use of microwave hyperthermia systems. In that case a differential diagnostic image can be calculated between microwave measurements at reference (around 37 °C) and elevated temperature conditions. This work proposes the design and characterization of agar-oil-glycerin phantoms for fatty, glandular, skin and tumor tissue. The characterization includes measurements with an open-ended coaxial probe and a network analyzer for the frequency range from 50 MHz to 20 GHz in a temperature-controlled environment covering the temperature range from 25 °C to 46 °C. The phantoms show an unique temperature response over the considered frequency bandwidth leading to significant changes in the real and imaginary part of the complex permittivity. Comparative studies with porcine skin and fat tissue show a qualitative agreement.
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Arterial Stiffness and Endothelial Function are Comparable in Young Healthy Vegetarians and Omnivores. Vegetarians (VEG) are reported to have lower body weight, blood pressure (BP), and cardiovascular disease (CVD) risk compared with omnivores (OMN), yet the mechanisms remain unclear. A vegetarian diet may protect the vascular endothelium, reducing the risk of atherosclerosis and CVD. This cross-sectional study compared vascular function between OMN and VEG. We hypothesized that VEG would have greater vascular function compared with OMN. Fifty-eight normotensive young healthy adults participated (40 women [W]/18 men [M]; 28 OMN [15W/13M] and 30 VEG [25W/5M]; 26 ± 7 years; BP: 112 ± 11/67 ± 8 mm Hg). Arterial stiffness, assessed by carotid-to-femoral pulse wave velocity (OMN: 5.6 ± 0.8 m/s, VEG: 5.3 ± 0.8 m/s; P = .17) and wave reflection assessed by aortic augmentation index (OMN: 6.9 ± 12.3%, VEG: 8.8 ± 13.5%; P = .57) were not different between groups. However, central pulse pressure (OMN: 32 ± 5; VEG: 29 ± 5 mm Hg; P = .048) and forward wave reflection were greater in omnivores (OMN: 26 ± 3; VEG: 24 ± 3 mm Hg; P = .048). Endothelial-dependent dilation measured by brachial artery flow-mediated dilation was not different between groups (OMN: 6.0 ± 2.9%, VEG: 6.9 ± 3.3%; P = .29). Percent change in femoral blood flow from baseline during passive leg movement, another assessment of nitric oxide-mediated endothelial dilation, was similar between groups (OMN: 203 ± 88 mL/min, VEG: 253 ± 192 mL/min; P = .50). These data suggest that in healthy young adults, normotensive VEG do not have significantly improved vascular function compared with OMN; however, they have a lower central pulse pressure and forward wave amplitude which may lower the risk of future CVD.
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Remote Intraoperative Neural Response Telemetry: Technique and Results in Cochlear Implant Surgery. Present results with remote intraoperative neural response telemetry (NRT) during cochlear implantation (CI) and its usefulness in overcoming the inefficiency of in person NRT.
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Hidden codes in mRNA: Control of gene expression by m 6 A. Information in mRNA has largely been thought to be confined to its nucleotide sequence. However, the advent of mapping techniques to detect modified nucleotides has revealed that mRNA contains additional information in the form of chemical modifications. The most abundant modified nucleotide is N 6 -methyladenosine (m 6 A), a methyl modification of adenosine. Although early studies viewed m 6 A as a dynamic and tissue-specific modification, it is now clear that the mRNAs that contain m 6 A and the location of m 6 A in those transcripts are largely universal and are influenced by gene architecture, i.e., the size and location of exons and introns. m 6 A can affect nuclear processes such as splicing and epigenetic regulation, but the major effect of m 6 A on mRNAs is to promote degradation in the cytoplasm. m 6 A marks a functionally related cohort of mRNAs linked to certain biological processes, including cell differentiation and cell fate determination. m 6 A is also enriched in other cohorts of mRNAs and can therefore affect their respective cellular processes and pathways. Future work will focus on understanding how the m 6 A pathway is regulated to achieve control of m 6 A-containing mRNAs.
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Factors associated with vision loss in Black or Hispanic patients 1 year after standalone or combined Ahmed glaucoma valve surgery. To determine factors associated with vision loss 1 year after Ahmed glaucoma valve (AGV) surgery in Black or Hispanic patients, who bear disproportionate glaucoma burdens yet have been underrepresented in pivotal trials.
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Trends in suicide deaths before and after the COVID-19 outbreak in Korea. We investigated the effect of the coronavirus disease-2019 (COVID-19) pandemic on suicide trends in Korea via a time-series analysis. We used Facebook Prophet to generate forecasting models based on the monthly numbers of suicide deaths in Korea between 1997 and 2018, validated the models by comparison with the 2019 numbers, and predicted the numbers of suicides in 2020. We compared the expected and observed numbers of suicides during the COVID-19 pandemic. The total numbers of suicides during the COVID-19 pandemic did not deviate from projections based on the pre-pandemic period. However, the number of suicides among women and those under the age of 34 years significantly exceeded the expected level. The COVID-19 pandemic did not increase the overall suicide rate significantly. However, suicides among women and young people increased, suggesting that the pandemic might drive more members of these groups to suicide. Further studies are needed to verify the long-term impact of the COVID-19 pandemic on suicide.
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Fibroblast Growth Factor 23 and Risk of New Onset Heart Failure With Preserved or Reduced Ejection Fraction: The PREVEND Study. Background The role of fibroblast growth factor 23 (FGF23) in the development of new-onset heart failure (HF) with reduced (HFrEF) or preserved ejection fraction (HFpEF) in the general population is unknown. Therefore, we set out to investigate associations of C-terminal FGF23 with development of new-onset HF and, more specifically, with HFrEF or HFpEF in a large, prospective, population-based cohort. Methods and Results We studied 6830 participants (aged 53.8±12.1 years; 49.7% men; estimated glomerular filtration rate, 93.1±15.7 mL/min per 1.73 m 2 ) in the community-based PREVEND (Prevention of Renal and Vascular End-Stage Disease) study who were free of HF at baseline. Cross-sectional multivariable linear regression analysis showed that ferritin (standardized β, -0.24; P <0.001) and estimated glomerular filtration rate (standardized β, -0.13; P <0.001) were the strongest independent correlates of FGF23. Multivariable Cox proportional hazard regression was used to study the association between baseline FGF23 and incident HF, HFrEF (ejection fraction ≤40%) or HFpEF (ejection fraction ≥50%). After median follow-up of 7.4 [IQR 6.9-7.9] years, 227 individuals (3.3%) developed new-onset HF, of whom 132 had HFrEF and 88 had HFpEF. A higher FGF23 level was associated with an increased risk of incident HF (fully adjusted hazard ratio, 1.29 [95% CI, 1.06-1.57]) and with an increased risk of incident HFrEF (fully adjusted hazard ratio, 1.31 [95% CI, 1.01-1.69]). The association between FGF23 and incident HFpEF lost statistical significance after multivariable adjustment (hazard ratio, 1.22 [95% CI, 0.87-1.71]). Conclusions Higher FGF23 is independently associated with new-onset HFrEF in analyses fully adjusted for cardiovascular risk factors and other potential confounders. The association between FGF23 and incident HFpEF lost statistical significance upon multivariable adjustment.
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Teaching Radiographic Caries Detection and Treatment Planning: A Seminar Using an Audience Response System. This study presents a seminar model for teaching radiographic caries detection and treatment planning at the Faculty of Dentistry, University of Oslo. The seminar is based partly on an audience response system (ARS) and uses patient cases to focus on caries risk assessment and treatment planning. This paper describes the seminar design, implementation, learning outcomes, and observational study of variability in caries registrations and students' attitudes to use of ARS. Dental and dental hygiene students participate in two seminar modules. Module 1 aims to develop and increase individual student skills in radiographic caries lesion detection, scoring, and differential diagnosis. Students perform trial registrations on bitewings using an ARS with anonymous live polling, and scorings are discussed in plenum. Students then perform individual registrations on 12 bitewing pairs. Using digital scoring, students detect and grade caries lesions on all approximal and occlusal tooth surfaces. After the session, students use the ARS to repeat scorings on selected tooth surfaces, and results are again discussed in plenum. Module 2 involves group exercises on 4 patient cases that are later presented with plenary discussions. In total, 1,624 caries registrations performed by 150 students attending the seminar between 2016 and 2018 were assessed for variability between students. As expected, variations in caries registrations were observed between students, mostly related to restored surfaces or tooth surfaces that were otherwise difficult to register. In 2022, 63 dental and dental hygiene students attending the seminar answered a questionnaire about use of ARS. The responses were scored using a five-point Likert scale. Overall, no significant difference in satisfaction with the ARS-based module was observed between dental and dental hygiene students (χ2 test, p &gt; 0.05). The majority of the students were positive toward the use of ARS (94%), but some disagreed on the role of ARS in usefulness for understanding the seminar content (3.2%), and in increasing their confidence in radiographic registration of caries (3.2%). The ARS-based module provides a positive learning environment that ensures student anonymity, interactivity, and engagement, and combined with the other seminar module gives students basic skills in caries detection and treatment planning.
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Field-based versus laboratory-based estimates of muscle quality index in adolescents with and without Down syndrome. Low muscle quality index (MQI) is a potential risk of developing functional impairments in older people. However, considering that individuals with Down syndrome (DS) present with a faster decline in biological aging, an investigation on MQI in individuals with DS is necessary. The aims of this present cross-sectional study were to compare (1) MQI between adolescents with and without DS and (2) evaluate laboratory versus field-based estimates of MQI.
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Association of desphospho-uncarboxylated matrix gla protein with incident cardiovascular disease and all-cause mortality: Results from the prospective Bruneck Study. Matrix Gla protein (MGP), a vitamin K-dependent protein, is a potent inhibitor of vascular calcification. Desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K insufficiency, has been shown to predict cardiovascular disease (CVD) and all-cause mortality in high-risk populations. Whether the increased risk associated with dp-ucMGP also applies to the general, and especially, the elderly population has not yet been fully elucidated.
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Environmental Interventions for Asthma. Exposure and sensitization to environmental factors play a fundamental role in asthma development and is strongly associated with asthma morbidity. While hereditary factors are critical determinants of asthma, exposures to environmental factors are implicated in the phenotypic expression of asthma and have been strongly associated in the risk of its development. Significant interest has thus been geared toward potentially modifiable environmental exposures which may lead to the development of asthma. Allergen exposure, in particular indoor allergens, plays a significant role in the pathogenesis of asthma, and remediation is a primary component of asthma management. In the home, multifaceted and multitargeted environmental control strategies have been shown to reduce home exposures and improve asthma outcomes. In addition to the home environment, assessment of the school, daycare, and workplace environments of patients with asthma is necessary to ensure appropriate environmental control measures in conjunction with medical care. This article will discuss the role of the environment on asthma, review targeted environmental therapy, and examine environmental control measures to suppress environmental exposures in the home and school setting.
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Improving the ischemia-reperfusion injury in vascularized composite allotransplantation: Clinical experience and experimental implications. Long-time ischemia worsening transplant outcomes in vascularized composite allotransplantation (VCA) is often neglected. Ischemia-reperfusion injury (IRI) is an inevitable event that follows reperfusion after a period of cold static storage. The pathophysiological mechanism activates local inflammation, which is a barrier to allograft long-term immune tolerance. The previous publications have not clearly described the relationship between the tissue damage and ischemia time, nor the rejection grade. In this review, we found that the rejection episodes and rejection grade are usually related to the ischemia time, both in clinical and experimental aspects. Moreover, we summarized the potential therapeutic measures to mitigate the ischemia-reperfusion injury. Compare to static preservation, machine perfusion is a promising method that can keep VCA tissue viability and extend preservation time, which is especially beneficial for the expansion of the donor pool and better MHC-matching.
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Exploring the lived experience of renal cachexia for individuals with end-stage renal disease and the interrelated experience of their carers: Study protocol. Renal cachexia is an important consideration in the person-centred care that is needed in end-stage renal disease (ESRD). However, given that clinical guidelines relating to renal cachexia are largely absent, this is an unmet care need. To inform guidelines and future renal service planning, there is an urgency to understand individuals' experiences of renal cachexia and the interrelated experiences of the carers in their lives. We report here the protocol for an interpretative phenomenological study which will explore this lived experience. A purposive sampling strategy will recruit individuals living with ESRD who have cachexia and their carers. A maximum of 30 participants (15 per group) dependent on saturation will be recruited across two nephrology directorates, within two healthcare trusts in the United Kingdom. Individuals with renal cachexia undergoing haemodialysis will be recruited via clinical gatekeepers and their carers will subsequently be invited to participate in the study. Participants will be offered the opportunity to have a face-to-face, virtual or telephone interview. Interviews will be audio-recorded, transcribed verbatim and analysed using interpretative phenomenological analysis. NVivo, will be used for data management. Ethical approval for this study was granted by the Office for Research Ethics Committees Northern Ireland (REC Reference: 22/NI/0107). Scientific evidence tends to focus on measurable psychological, social and quality of life outcomes but there is limited research providing in-depth meaning and understanding of the views of individuals with renal disease who are experiencing renal cachexia. This information is urgently needed to better prepare healthcare providers and in turn support individuals with ESRD and their carers. This study will help healthcare providers understand what challenges individuals with ESRD, and their carers face in relation to cachexia and aims to inform future clinical practice guidelines and develop supportive interventions which recognise and respond to the needs of this population.
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Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain-Barre Syndrome. AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolic and immune functions mainly through the inhibition of the mechanistic target of rapamycin (mTOR)-dependent anabolic pathways and the activation of catabolic processes such as autophagy. The AMPK/mTOR signaling pathway and autophagy markers were analyzed by immunoblotting in blood mononuclear cells of 20 healthy control subjects and 23 patients with an acute demyelinating form of Guillain-Barré syndrome (GBS). The activation of the liver kinase B1 (LKB1)/AMPK/Raptor signaling axis was significantly reduced in GBS compared to control subjects. In contrast, the phosphorylated forms of mTOR activator AKT and mTOR substrate 4EBP1, as well as the levels of autophagy markers LC3-II, beclin-1, ATG5, p62/sequestosome 1, and NBR1 were similar between the two groups. The downregulation of LKB1/AMPK signaling, but not the activation status of the AKT/mTOR/4EBP1 pathway or the levels of autophagy markers, correlated with higher clinical activity and worse outcomes of GBS. A retrospective study in a diabetic cohort of GBS patients demonstrated that treatment with AMPK activator metformin was associated with milder GBS compared to insulin/sulphonylurea therapy. In conclusion, the impairment of the LKB1/AMPK pathway might contribute to the development/progression of GBS, thus representing a potential therapeutic target in this immune-mediated peripheral polyneuropathy.
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Characteristics of Retracted Research Articles About COVID-19 vs Other Topics. This cross-sectional study compares the author and journal characteristics of retracted articles on COVID-19 with retracted articles from other topics.
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Secondary Electrons in Gold Nanoparticle Clusters and Their Role in Therapeutic Ratio: The Outcome of a Monte Carlo Simulation Study. Gold nanoparticles (GNPs) are used in proton therapy radio-sensitizers to help increase the dose of radiation to targeted tumors by the emission of secondary electrons. Thus, this study aimed to investigate the link between secondary electron yields produced from a nanoshell of GNPs and dose absorption according to the distance from the center of the nanoparticles by using a Monte Carlo model. Microscopic evaluation was performed by modeling the interactions of secondary electrons in a phase-space file (PSF), where the number of emitted electrons was calculated within a spherical GNP of 15 nm along with the absorbed dose near it. Then, the Geant4-DNA physics list was used to facilitate the tracking of low-energy electrons down to an energy below 50 eV in water. The results show a remarkable change in the number of secondary electrons, which can be compared at concentrations less than and greater than 5 mg/mL, with increased secondary electron production exhibited around NPs within a distance of 10-100 nm from the surface of all nanospheres. It was found that there was a steep dose enhancement drop-off up to a factor of dose enhancement factor (DFE) ≤ 1 within a short distance of 100 nm from the surface of the GNPs, which revealed that the dose enhancement existed locally at nanometer distances from the GNPs. Overall, our results indicate that the physical interactions of protons with GNP clusters should not be considered as being directly responsible for the radio-sensitization effect, but should be regarded as playing a major role in NP properties and concentrations, which has a subsequent impact on local dose enhancement.
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Quarantine preparedness - the missing factor in COVID-19 behaviour change? Qualitative insights from Australia. A key feature of the global public health response to contain and slow the spread of COVID-19 has been community-based quarantine and self-isolation. As part of The Optimise Study, this research sought to understand the factors that influence people's ability to undertake home-based quarantine and isolation to contain the spread of COVID-19.
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Rac1 as a therapeutic anticancer target: Promises and limitations. Small molecule inhibitors of GTPases are increasingly considered for the treatment of multiple human pathologies. The GTPase Rac1 (Ras-related C3 botulinum toxin substrate 1) plays major roles in vital cellular processes, notably in the control cell motility and dynamic, the regulation of oxidative stress, and in inflammatory and immune surveillance. As such, Rac1 is viewed as a potential target to combat cancers but also diverse inflammatory, metabolic, neurodegenerative, respiratory, cardiovascular, viral, and parasitic diseases. Potent and selective Rac1 inhibitors have been identified and designed, such as compounds GYS32661 and MBQ-167 both in preclinical development for the treatment of advanced solid tumors. The pleiotropic roles and ubiquitous expression of the protein can be viewed as limitations for anticancer approaches. However, the frequent overexpression and/or hyperactivation of the Rac1 in difficult-to-treat chemoresistant cancers, make Rac1 an attractive target in oncology. The key roles of Rac1 in multiple cellular pathways, together with its major implications in carcinogenesis, tumor proliferation and metastasis, support the development of small molecule inhibitors. The challenge is high and the difficulty shall not be underestimated, but the target is innovative and promising in combination with chemo- and/or immuno-therapy. Opportunities and challenges associated with the targeting of Rac1 are discussed.
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Simultaneous Occurrence of Chicken Pox and Herpes Zoster with Facial Nerve Palsy in Immunocompetent Patient. Patients who earlier suffered from chicken pox may develop herpes zoster (HZ) due to reactivation in dorsal root ganglia. The occurrence of both clinical conditions at the same time is sporadic. Unusual presentation and a belligerent course are seen in immunocompromised hosts. The presence of both HZ and chicken pox in immunocompetent patients is infrequent and incoherent with the present understanding of pathogenesis. Here, we present a case of HZ involving the maxillary division of the right trigeminal nerve with simultaneous occurrence of varicella-zoster and right peripheral facial nerve palsy.
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Analysis of risk factors affecting union and refracture after combined surgery for congenital pseudarthrosis of the tibia: a retrospective study of 255 cases. Congenital pseudarthrosis of the tibia (CPT) is a rare disease occurring in children. The aim of this study is to identify the factors affecting bone union and re-fracture after surgery for CPT and to provide reliable evidence for clinics.
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Copper removal from aqueous solution using chemical precipitation and adsorption by Himalayan Pine Forest Residue as Biochar. This research deals with the use of pine residue biochar as an adsorbent for the removal of copper from aqueous solution which is a major component of printed circuit boards from E-waste. Biochar was produced from pine residue such as bark, cone and needle through pyrolysis, and the effect of temperature on biochar properties was assessed. The biochar yield of about 33% and maximum surface area of 368 m 2 /g was obtained at pyrolysis temperature of 650°C. FTIR analysis revealed the existence of C-O, O-H and C = C functional groups on the surface of biochars. The point of zero charge of pine biochars were in the range 5.55 to 5.75. Batch adsorption studies revealed maximum copper adsorption capacity of 60-81 mg/g at near neutral pH. The batch adsorption data fitted well with Langmuir isotherm and followed the pseudo-second order kinetics. Adsorption of copper onto the biochar surface mainly followed physisorption which was reversible in nature. Desorption study revealed that pine biochar could be reused up to three cycles. Column adsorption data fitted well with Thomas model. These investigations revealed that the pine residue, which otherwise results in adverse environmental impacts, can be converted into useful resource like biochar as a heavy metal adsorbent.
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OARD: Open annotations for rare diseases and their phenotypes based on real-world data. Diagnosis for rare genetic diseases often relies on phenotype-driven methods, which hinge on the accuracy and completeness of the rare disease phenotypes in the underlying annotation knowledgebase. Existing knowledgebases are often manually curated with additional annotations found in published case reports. Despite their potential, real-world data such as electronic health records (EHRs) have not been fully exploited to derive rare disease annotations. Here, we present open annotation for rare diseases (OARD), a real-world-data-derived resource with annotation for rare-disease-related phenotypes. This resource is derived from the EHRs of two academic health institutions containing more than 10 million individuals spanning wide age ranges and different disease subgroups. By leveraging ontology mapping and advanced natural-language-processing (NLP) methods, OARD automatically and efficiently extracts concepts for both rare diseases and their phenotypic traits from billing codes and lab tests as well as over 100 million clinical narratives. The rare disease prevalence derived by OARD is highly correlated with those annotated in the original rare disease knowledgebase. By performing association analysis, we identified more than 1 million novel disease-phenotype association pairs that were previously missed by human annotation, and >60% were confirmed true associations via manual review of a list of sampled pairs. Compared to the manual curated annotation, OARD is 100% data driven and its pipeline can be shared across different institutions. By supporting privacy-preserving sharing of aggregated summary statistics, such as term frequencies and disease-phenotype associations, it fills an important gap to facilitate data-driven research in the rare disease community.
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Anthelmintic resistance of horse strongyle nematodes to fenbendazole in Lithuania. Control of strongyle infections presents a global challenge for horse practitioners due to the development of anthelmintic resistance (AR), however comprehensive information on AR in Lithuania is still lacking. The aim of this study was to assess the current situation of fenbendazole (FBZ) AR in horses at stable level in Lithuania.
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Emergency department-based, nurse-initiated, serious illness conversation intervention for older adults: a protocol for a randomized controlled trial. Visits to the emergency department (ED) are inflection points in patients' illness trajectories and are an underutilized setting to engage seriously ill patients in conversations about their goals of care. We developed an intervention (ED GOAL) that primes seriously ill patients to discuss their goals of care with their outpatient clinicians after leaving the ED. The aims of this study are (i) to test the impact of ED GOAL administered by trained nurses on self-reported, advance care planning (ACP) engagement after leaving the ED and (ii) to evaluate whether ED GOAL increases self-reported completion of serious illness conversation and other patient-centered outcomes.
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Water reduces iron toxicity. An 86-year-old man presented to the emergency room with vomiting and melena. The patient was hemodynamically stable and remained alert and orientated. According to his family, ingestion of a pack of disposable hand warmers, which he mistook for black sesame powder, occurred 17 h prior to admission. Before ingestion, he mixed the powder with warm water. Physical examination revealed no thermal injury of the oral mucosa with no abdominal pain or tenderness. An abdominal plain film showed multiple scattered radiopaque material with zonal distribution over the right abdomen. An intravenous 500-mg deferoxamine challenge test showed no vin rosé urine discoloration. Serial serum iron levels remained within the normal range. The patient remained clinically stable with no medical complications. He was discharged 3 days after admission. The hand warmers consisted of iron powder (50% w/w), sodium chloride, activated charcoal, and nontoxic vermiculite: a potential risk for intestinal thermal injury. In this case, the water added beforehand rapidly terminated the iron oxidation reaction. This explained the lack of thermal injury. Ferric oxide is poorly absorbed by the digestive tract and explained the absence of iron intoxication. Therefore, clinicians should clarify the method of ingestion. If a hand warmer has been premixed with water, less mucosa injury can be expected with a lower risk of iron intoxication. This report also provided evidence that abdominal plain films can be used to confirm the ingestion of iron and monitor its elimination.
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Clonal distribution and antimicrobial resistance of methicillin-susceptible and -resistant Staphylococcus aureus strains isolated from broiler farms, slaughterhouses, and retail chicken meat. Colonization of food-producing animals by antimicrobial-resistant Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), has become a serious public health problem worldwide. In the current study, clonal diversities of livestock-associated S. aureus isolates collected from broiler farms, slaughterhouses, and retail chicken meat were examined. Two-hundred S. aureus isolates (43 MRSA and 157 methicillin-susceptible S. aureus [MSSA] isolates) were analyzed to determine 1) the genotypes of the isolates (multilocus sequence, agr, and spa types), 2) the methicillin resistance phenotype and staphylococcal cassette chromosome mec (SCCmec) types, 3) the antimicrobial resistance profiles, and 4) the mutational changes in gyrA, gyrB, parC, and parE in fluoroquinolone-resistant isolates. Fifteen different sequence types (STs) of MSSA strains displaying a relatively high degree of genetic diversity were detected in broiler farms, slaughterhouses, and retail chicken meat. In contrast to MSSA, 2 dominant genetic lineages of MRSA (ST692-SCCmecV with t2249 spa type, and ST188-SCCmecIVa with spa type t189) were found in healthy broilers. The high prevalence of ST692 and ST188 in healthy broilers is associated with high levels of multiple antimicrobial-resistance phenotypes, particularly fluoroquinolone resistance. All fluoroquinolone-resistant isolates carried double point mutations in gyrA (S84L) and parC (S80F), regardless of STs or methicillin resistance. Notably, only the ST188 lineage carried an additional third mutation in gyrB (D494N), correlating with enhanced ciprofloxacin minimum inhibitory concentration values versus the strains with double mutations. These results provide important insights into the genetic diversity of antimicrobial-resistant S. aureus strains associated with the chicken meat production chain, including healthy broilers, in Korea.
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Site-specific characteristics of bone and progenitor cells in control and ovariectomized rats. One-third of postmenopausal women experience at least one osteoporotic bone fracture in their lifetime that occurs spontaneously or from low-impact events. However, osteoporosis-associated jaw bone fractures are extremely rare. It was also observed that jaw bone marrow stem cells (BMSCs) have a higher capacity to form mineralized tissues than limb BMSCs. At present, the underlying causes and mechanisms of variations between jaw bone and limb bone during postmenopause are largely unknown. Thus, the objective of the current study was to examine the site-specific effects of estrogen deficiency using comprehensive analysis of bone quantity and quality, and its association with characterization of cellular components of bone. Nine rats (female, 6 months old) for each bilateral sham and ovariectomy (OVX) surgery were obtained and maintained for 2 months after surgery. A hemi-mandible and a femur from each rat were characterized for parameters of volume, mineral density, cortical and trabecular morphology, and static and dynamic mechanical analysis. Another set of 5 rats (female, 9 months old) was obtained for assays of BMSCs. Following cytometry to identify BMSCs, bioassays for proliferation, and osteogenic, adipogenic, chondrogenic differentiation, and cell mitochondrial stress tests were performed. In addition, mRNA expression of BMSCs was analyzed. OVX decreased bone quantity and quality (mineral content, morphology, and energy dissipation) of femur while those of mandible were not influenced. Cellular assays demonstrated that mandible BMSCs showed greater differentiation than femur BMSCs. Gene ontology pathway analysis indicated that the mandibular BMSCs showed most significant differential expression of genes in the regulatory pathways of osteoblast differentiation, SMAD signaling, cartilage development, and glucose transmembrane transporter activity. These findings suggested that active mandibular BMSCs maintain bone formation and mineralization by balancing the rapid bone resorption caused by estrogen deficiency. These characteristics likely help reduce the risk of osteoporotic fracture in postmenopausal jawbone.
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Survival after hospital discharge in patients hospitalized for acute coronavirus disease 2019: data on 2586 patients from a tertiary center registry. To assess the long-term survival after hospital discharge of patients hospitalized due to coronavirus disease 2019 (COVID-19).
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Complexity-biodiversity relationships on marine urban structures: reintroducing habitat heterogeneity through eco-engineering. Urbanization is leading to biodiversity loss through habitat homogenization. The smooth, featureless surfaces of many marine urban structures support ecological communities, often of lower biodiversity, distinct from the complex natural habitats they replace. Eco-engineering (design for ecological co-benefits) seeks to enhance biodiversity and ecological functions on urban structures. We assessed the benefits to biodiversity of retrofitting four types of complex habitat panels to an intertidal seawall at patch (versus flat control panels) and site (versus unmodified control seawalls and reference rocky shores) scales. Two years after installation, patch-scale effects of complex panels on biodiversity ranged from neutral to positive, depending on the protective features they provided, though all but one design (honeycomb) supported unique species. Water-retaining features (rockpools) and crevices, which provided moisture retention and cooling, increased biodiversity and supported algae and invertebrates otherwise absent. At the site scale, biodiversity benefits ranged from neutral at the high- and mid-intertidal to positive at the low-intertidal elevation. The results highlight the importance of matching eco-engineering interventions to the niche of target species, and environmental conditions. While species richness was greatest on rockpool and crevice panels, the unique species supported by other panel designs highlights that to maximize biodiversity, habitat heterogeneity is essential. This article is part of the theme issue 'Ecological complexity and the biosphere: the next 30 years'.
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Changes in trace metal concentrations throughout the phosphogypsum lifecycle. Phosphogypsum (PG) samples from four distinct sources in the Southeastern US were analyzed to explore the variation in total metal content between newly generated (fresh) PG and PG disposed of in phosphogypsum stacks for different lengths of time (stack). Fresh PG exhibited greater total metal concentrations relative to stack PG, including those identified in the literature as important from a risk assessment perspective (As, Cd, Co, Cr, Cu, Pb, and Zn). The pH varied between fresh and stack PG, with some stack samples exhibiting lower pH than fresh samples, however the relationship between pH and age of sample was not linear. Stack samples with pH values similar to fresh samples possessed lower concentrations of total inorganic metals than fresh samples suggesting that process water drainage and stack location play an important role in the reusability of PG as they can affect the pH of stack PG and total inorganic metal concentrations. Overall observations show that stacking PG for three or more years prior to beneficial reuse provides a construction material with lower total metal concentrations than fresh PG.
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