Miracle-dz/UniFAR-FTUs huggingface dataset:
Procalcitonin and other markers to guide antibiotic use in chronic obstructive pulmonary disease exacerbations in the era of antimicrobial resistance

Purpose of review This review summarizes the latest discoveries regarding the use of clinical indicators and biomarkers to guide antibiotic use in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and it analyzes the advantages and disadvantages of various indicators and markers. Recent findings For AECOPD patients admitted to emergency departments and medical wards, procalcitonin (PCT)-guided antibiotic therapy reduced antibiotic use without adverse outcomes. In contrast, for severe AECOPD patients admitted to ICUs, PCT-guided antibiotic therapy increased the overall mortality in a 3-month follow-up period, and antibiotic use was not decreased. Summary PCT is the most promising biomarker to guide antibiotic use in patients with AECOPD. However, patients with severe AECOPD admitted in ICU may not benefit from PCT-guided antibiotic therapy.
Sensitization of Drug Resistant Cancer Cells: A Matter of Combination Therapy

Cancer drug resistance is an enormous problem. It is responsible for most relapses in cancer patients following apparent remission after successful therapy. Understanding cancer relapse requires an understanding of the processes underlying cancer drug resistance. This article discusses the causes of cancer drug resistance, the current combination therapies, and the problems with the combination therapies. The rational design of combination therapy is warranted to improve the efficacy. These processes must be addressed by finding ways to sensitize the drug-resistant cancers cells to chemotherapy, and to prevent formation of drug resistant cancer cells. It is also necessary to prevent the formation of cancer progenitor cells by epigenetic mechanisms, as cancer progenitor cells are insensitive to standard therapies. In this article, we emphasize the role for the rational development of combination therapy, including epigenetic drugs, in achieving these goals.
Circulating Exosomal miR-20b-5p Is Elevated in Type 2 Diabetes and Could Impair Insulin Action in Human Skeletal Muscle

miRNAs are noncoding RNAs representing an important class of gene expression modulators. Extracellular circulating miRNAs are both candidate biomarkers for disease pathogenesis and mediators of cell-to-cell communication. We examined the miRNA expression profile of total serum and serum-derived exosome-enriched extracellular vesicles in people with normal glucose tolerance or type 2 diabetes. In contrast to total serum miRNA, which did not reveal any differences in miRNA expression, we identified differentially abundant miRNAs in patients with type 2 diabetes using miRNA expression profiles of exosome RNA (exoRNA). To validate the role of these differentially abundant miRNAs on glucose metabolism, we transfected miR-20b-5p, a highly abundant exoRNA in patients with type 2 diabetes, into primary human skeletal muscle cells. miR-20b-5p overexpression increased basal glycogen synthesis in human skeletal muscle cells. We identified AKTIP and STAT3 as miR-20b-5p targets. miR-20b-5p overexpression reduced AKTIP abundance and insulin-stimulated glycogen accumulation. In conclusion, exosome-derived extracellular miR-20b-5p is a circulating biomarker associated with type 2 diabetes that plays an intracellular role in modulating insulin-stimulated glucose metabolism via AKT signaling.
Interferon‐gamma production in Lyme arthritis synovial tissue promotes differentiation of fibroblast‐like synoviocytes into immune effector cells

Lyme arthritis (LA), a late disease manifestation of Borrelia burgdorferi infection, usually resolves with antibiotic therapy. However, some patients develop proliferative synovitis lasting months to several years after spirochetal killing, called postinfectious LA. In this study, we phenotyped haematopoietic and stromal cell populations in the synovial lesion ex vivo and used these findings to generate an in vitro model of LA using patient‐derived fibroblast‐like synoviocytes (FLS). Ex vivo analysis of synovial tissue revealed high abundance of IFNγ‐producing T cells and NK cells. Similar to marked IFNγ responses in tissue, postinfectious LA synovial fluid also had high levels of IFNγ. HLA‐DR‐positive FLS were present throughout the synovial lesion, particularly in areas of inflammation. FLS stimulated in vitro with B. burgdorferi, which were similar to conditions during infection, expressed 68 genes associated primarily with innate immune activation and neutrophil recruitment. In contrast, FLS stimulated with IFNγ, which were similar to conditions in the postinfectious phase, expressed >2,000 genes associated with pathogen sensing, inflammation, and MHC Class II antigen presentation, similar to the expression profile in postinfectious synovial tissue. Furthermore, costimulation of FLS with B. burgdorferi and IFNγ induced greater expression of IL‐6 and other innate immune response proteins and genes than with IFNγ stimulation alone. These results suggest that B. burgdorferi infection, in combination with IFNγ, initiates the differentiation of FLS into a highly inflammatory phenotype. We hypothesise that overexpression of IFNγ by lymphocytes within synovia perpetuates these responses in the postinfectious period, causing proliferative synovitis and stalling appropriate repair of damaged tissue.
The Zebrafish as a Model Host for Invasive Fungal Infections

The zebrafish has become a widely accepted model host for studies of infectious disease, including fungal infections. The species is genetically tractable, and the larvae are transparent and amenable to prolonged in vivo imaging and small molecule screening. The aim of this review is to provide a thorough introduction into the published studies of fungal infection in the zebrafish and the specific ways in which this model has benefited the field. In doing so, we hope to provide potential new zebrafish researchers with a snapshot of the current toolbox and prior results, while illustrating how the model has been used well and where the unfulfilled potential of this model can be found.
Prevalence, awareness, control and determinants of hypertension among primary health care professional nurses in Eastern Cape, South Africa

Background Nurses in primary health care settings are key stakeholders in the diagnosis and management of hypertensive patients. Unfortunately, the working conditions of nurses predispose them to stress, long hours of work, shift duties and unhealthy diets, which are drivers of hypertension. Yet nurses are often overlooked in health screening exercises, primarily because they are assumed to be informed and ‘healthy’. Aim This study examined the prevalence, awareness, control and determinants of hypertension among professional primary health care nurses in the Eastern Cape Province of South Africa. Setting This was a cross-sectional survey of 203 professional nurses working at 41 primary health care facilities of the Eastern Cape Province. Methods A modified WHO STEPwise questionnaire was used for data collection during face-to-face interviews. The information obtained included demographic information, behavioural lifestyles, anthropometric and blood pressure (BP) measurements. Hypertension is defined as an average of two BP ≥ 140/90 mmHg or self-reported history of antihypertensive medication use. Results The prevalence of hypertension was 52%. Of this, 41% were unaware of their hypertension status. Of those who were aware and on treatment, only 38.1% had a controlled blood pressure. After adjusting for confounders (for physical activity, dietary practices, parity, income and alcohol use), only age and duration of practice were independent predictors of hypertension among the study population. Conclusion There is a high prevalence of hypertension among the study participants. There is an unexpected low rate of awareness and suboptimal control of blood pressure among the participants. Age is the significant predictor of hypertension among professional nurses in Eastern Cape Province, South Africa. There is an urgent need for the implementation of an effective workplace health programme for nurses in the province.
Relational cost analysis for functional-imperative programs

Relational cost analysis aims at formally establishing bounds on the difference in the evaluation costs of two programs. As a particular case, one can also use relational cost analysis to establish bounds on the difference in the evaluation cost of the same program on two different inputs. One way to perform relational cost analysis is to use a relational type-and-effect system that supports reasoning about relations between two executions of two programs. Building on this basic idea, we present a type-and-effect system, called ARel, for reasoning about the relative cost of array-manipulating, higher-order functional-imperative programs. The key ingredient of our approach is a new lightweight type refinement discipline that we use to track relations (differences) between two mutable arrays. This discipline combined with Hoare-style triples built into the types allows us to express and establish precise relative costs of several interesting programs which imperatively update their data. We have implemented ARel using ideas from bidirectional type checking.
Phase IIa, placebo-controlled, randomised study of lutikizumab, an anti-interleukin-1α and anti-interleukin-1β dual variable domain immunoglobulin, in patients with erosive hand osteoarthritis

Objective To assess the efficacy, safety, pharmacokinetics and pharmacodynamics of the anti-interleukin (IL)-1α/β dual variable domain immunoglobulin lutikizumab (ABT-981) in erosive hand osteoarthritis (HOA). Methods Patients with ≥1 erosive and ≥3 tender and/or swollen hand joints were randomised to placebo or lutikizumab 200 mg subcutaneously every 2 weeks for 24 weeks. The primary endpoint was change in Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain subdomain score from baseline to 16 weeks. At baseline and week 26, subjects had bilateral hand radiographs and MRI of the hand with the greatest number of baseline tender and/or swollen joints. Continuous endpoints were assessed using analysis of covariance models, with treatment and country as main factors and baseline measurements as covariates. Results Of 132 randomised subjects, 1 received no study drug and 110 completed the study (placebo, 61/67 (91%); lutikizumab, 49/64 (77%)). AUSCAN pain was not different among subjects treated with lutikizumab versus placebo at week 16 (least squares mean difference, 1.5 (95% CI –1.9 to 5.0)). Other clinical and imaging endpoints were not different between lutikizumab and placebo. Lutikizumab significantly decreased serum high-sensitivity C reactive protein levels, IL-1α and IL-1β levels, and blood neutrophils. Lutikizumab pharmacokinetics were consistent with phase I studies and not affected by antidrug antibodies. Injection site reactions and neutropaenia were more common in the lutikizumab group; discontinuations because of adverse events occurred more frequently with lutikizumab (4/64) versus placebo (1/67). Conclusion Despite adequate blockade of IL-1, lutikizumab did not improve pain or imaging outcomes in erosive HOA compared with placebo.
Pressure‐induced mesenchymal stem cell osteogenesis is dependent on intermediate filament remodeling

Macroscale loading of bone generates a complex local mechanical microenvironment that drives osteogenesis and bone mechanoadaptation. One such mechanical stimulus generated is hydrostatic pressure (HP); however, the effect of HP on mesenchymal stem cells (MSCs) and the mechanotransduction mechanisms utilized by these cells to sense this stimulus are yet to be fully elucidated. In this study, we demonstrate that cyclic HP is a potent mediator of cytoskeletal reorganization and increases in osteogenic responses in MSCs. In particular, we demonstrate that the intermediate filament (IF) network undergoes breakdown and reorganization with centripetal translocation of IF bundles toward the perinuclear region. Furthermore, we show for the first time that this IF remodeling is required for loading‐induced MSC osteogenesis, revealing a novel mechanism of MSC mechanotransduction. In addition, we demonstrate that chemical disruption of IFs with withaferin A induces a similar mechanism of IF breakdown and remodeling as well as a subsequent increase in osteogenic gene expression in MSCs, exhibiting a potential mechanotherapeutic effect to enhance MSC osteogenesis. This study therefore highlights a novel mechanotransduction mechanism of pressure‐induced MSC osteogenesis involving the understudied cytoskeletal structure, the IF, and demonstrates a potential new therapy to enhance bone formation in bone‐loss diseases such as osteoporosis. —Stavenschi, E. , Hoey, D. A. Pressure‐induced mesenchymal stem cell osteogenesis is dependent on intermediate filament remodeling. FASEB J. 33, 4178–4187 (2019). www.fasebj. org
Molecular genotyping, diversity studies and high-resolution molecular markers unveiled by microsatellites in Giardia duodenalis

Background Giardia duodenalis (synonyms G. lamblia and G. intestinalis) is an enteric protozoan parasite of a wide range of mammalian hosts, including humans and various domestic and wild animals. There is considerable genetic variability in G. duodenalis and isolates of this parasite have been divided into eight genetic assemblages. Microsatellites markers can be used to discriminate isolates with a high level of sensitivity. This study was conducted to identify and characterize genomic microsatellites (simple sequence repeats—SSRs), sequences of one- to six-nucleotide motifs repeated in tandem, present in the available genomes of G. duodenalis and to develop new markers that can serve as a tool for detection and for characterizing the genetic diversity of this parasite. Methodology/ Principal findings For each genetic assemblage, polymorphism levels for the microsatellite markers were evaluated. After performing the analysis using the MISA and SciRoKo software, 1,853 simple sequence repeats (SSRs) were identified. In all the genomes, trinucleotide repeats were the most common class followed by tetranucleotide. Many of the SSR loci are assemblage-specific, and 36 SSR loci shared among all the genomes were identified. Together with hypothetical proteins, variant-specific surface proteins represented nearly half of the annotated SSR loci. The results regarding the most common repeat among the SSRs led us to infer that positive selection occurred to avoid frameshift mutations. Additionally, based on inter- and intra-genetic assemblages polymorphism analyses, we unveiled previously undetected genetic variation, indicating that the microsatellite markers we developed are useful molecular tools for epidemiological inferences based on population genetics patterns and processes. Conclusions There is increasing demand for the development of new molecular markers and for the characterization of pathogens at a higher resolution level. In this study, we present 60 G. duodenalis microsatellites markers that exhibited high polymerase chain reaction (PCR) amplification efficiency among the different genetic assemblages. Twenty of these markers presented nucleotide sequence polymorphisms and may be used as a genotyping tool. The monomorphic markers can be used for the detection of the parasite at the species and genetic assemblage level. These polymorphic markers revealed a genetic diversity that was previously undetectable, thus they can be considered valuable molecular tools for high resolution markers in future studies investigating Giardia and may also be used for epidemiological inferences based on populations genetics patterns and processes.
N-(2-(Dimethylamino)Ethyl)-4-18F-Fluorobenzamide: A Novel Molecular Probe for High-Contrast PET Imaging of Malignant Melanoma

Malignant melanoma is an aggressive and serious form of skin cancer, with prognosis and treatment outcome depending heavily on the clinical stage of the disease at the time of diagnosis. Here, we synthesized a novel 18F-labeled benzamide derivative to target melanoma and then evaluated its biologic characteristics in small-animal models. Methods: N-(2-(dimethylamino)ethyl)-4-18F-fluorobenzamide (18F-DMFB) was synthesized by reaction of N-succinimidyl 4-18F-fluorobenzoate with N,N-dimethylethylenediamine. The binding affinity of 18F-DMFB was measured in B16F10 (mouse melanoma) cells with or without l-tyrosine. Small-animal PET imaging with 18F-DMFB was performed on B16F10 xenograft and metastasis mouse models. Results: The overall non–decay-corrected radiochemical yield of 18F-DMFB was approximately 10%–15%. Uptake of 18F-DMFB was melanin-specific, as cellular uptake in B16F10 increased more than 18-fold in the presence of l-tyrosine. Biodistribution studies revealed that 18F-DMFB accumulated, and was retained, in B16F10 xenografts for 120 min (10, 30, 60, and 120 min: 9.24, 10.80, 13.0, and 10.59 percentage injected dose/g, respectively) after radiotracer injection. Liver uptake of 18F-DMFB decreased from 10 to 120 min and showed fast clearance (10, 30, 60, and 120 min: 11.19, 5.7, 2.47, and 0.4 percentage injected dose/g). Furthermore, 18F-DMFB allowed visualization of metastatic lesions immediately after injection and was retained in lesions for over 60 min, with a high tumor-to-background ratio. Conclusion: 18F-DMFB demonstrated a high melanin-targeting ability and tumor-specific tumor uptake in both primary and metastatic lesions in animal models bearing malignant melanoma. 18F-DMFB may be a potential PET imaging agent for melanoma.
The Health Risks of Obesity Have Not Been Exaggerated.

T here is public health concern regarding the prevalence of overweight (body mass index [BMI] Q25 kgIm) and obesity (BMI Q30 kgIm) in the United States and other countries throughout the world. The prevalence of obesity in the United States is 35.0% for men and 40.4% based on 2013 to 2014 national survey data (1), with the overall prevalence of obesity increasing in adults from 30.5% in 1999 to 2000 to 37.7% in 2013 to 2014 (2). Of additional concern is the prevalence of class 3 obesity (BMI Q40 kgIm), with data from 2013 to 2014 in the United States demonstrating a prevalence of 5.5% for men and 9.9% for women. Since 2005, there has been a trend for an increase in the prevalence of both obesity and class 3 obesity, which significantly increased for women, but not for men (1). These trends and prevalence rates of obesity are of concern because of the demonstrated association between obesity and many negative health consequences.
Task assignment for Eco-friendly Mobile Crowdsensing

Mobile crowdsensing is a sensing paradigm such that mobile users need to move to task locations to perform sensing tasks. In this paper, we focus on studying the task assignment problem of eco-friendly mobile crowdsensing which aims to minimize carbon emissions while meeting various resource limits including task deadlines and transportation constraints. We first describe the eco-friendly mobile crowdsensing system model and formulate the task assignment problem. Then we divide the problem into two subproblems including selection of best transportation type and user-task matching. We model the user-task matching as unbalanced minimum-cost bipartite matching, transform the problem into balanced maximum-weight bipartite matching, and use Kuhn-Munkres algorithm to obtain the optimal solution. Extensive simulations are conducted and the results show the efficiency and effectiveness of our proposed solution.
Role of host genetics and heat‐tolerant algal symbionts in sustaining populations of the endangered coral Orbicella faveolata in the Florida Keys with ocean warming

Identifying which factors lead to coral bleaching resistance is a priority given the global decline of coral reefs with ocean warming. During the second year of back‐to‐back bleaching events in the Florida Keys in 2014 and 2015, we characterized key environmental and biological factors associated with bleaching resilience in the threatened reef‐building coral Orbicella faveolata. Ten reefs (five inshore, five offshore, 179 corals total) were sampled during bleaching (September 2015) and recovery (May 2016). Corals were genotyped with 2bRAD and profiled for algal symbiont abundance and type. O. faveolata at the inshore sites, despite higher temperatures, demonstrated significantly higher bleaching resistance and better recovery compared to offshore. The thermotolerant Durusdinium trenchii (formerly Symbiondinium trenchii) was the dominant endosymbiont type region‐wide during initial (78.0% of corals sampled) and final (77.2%) sampling; >90% of the nonbleached corals were dominated by D. trenchii. 2bRAD host genotyping found no genetic structure among reefs, but inshore sites showed a high level of clonality. While none of the measured environmental parameters were correlated with bleaching, 71% of variation in bleaching resistance and 73% of variation in the proportion of D. trenchii was attributable to differences between genets, highlighting the leading role of genetics in shaping natural bleaching patterns. Notably, D. trenchii was rarely dominant in O. faveolata from the Florida Keys in previous studies, even during bleaching. The region‐wide high abundance of D. trenchii was likely driven by repeated bleaching associated with the two warmest years on record for the Florida Keys (2014 and 2015). On inshore reefs in the Upper Florida Keys, O. faveolata was most abundant, had the highest bleaching resistance, and contained the most corals dominated by D. trenchii, illustrating a causal link between heat tolerance and ecosystem resilience with global change.
YÖNETİCİLİKTE AŞİL SENDROMU VE MESLEKİ TÜKENMİŞLİK İLİŞKİSİ

fakat kendilerine diger insanlar kadar guven duymayan, daha zayif hisseden insanlarin yasadiklari korkuya verilen isimdir. Bu kisiler gercekte basarilidirlar ama kendilerini basarili gormezler bu yuzden daha fazla calisir daha fazla yorulurlar. Kendisine buyuk hedefler koyan ve bu hedeflere ulasmadiginda da hayal kirikligi yasayan insanlar, kendilerini yorgun, bitkin, enerjisi tukenmis hissederler. Buradan hareketle bu calismanin amaci, farkli sektorlerde yonetici pozisyonunda calisanlarin gizli basarisizlik korkusu ile mesleki tukenmislik duzeyleri arasindaki iliskiyi, demografik degiskenler de goz onunde bulundurularak ortaya koymaktir. Verilerin analizi icin SPSS Programi kullanilmis ve egitim, saglik, bankacilik sektorlerinde calisan 151 yoneticiye anket uygulanmistir. Arastirma sonucunda, yoneticilerin yas, sektor ve calisma yili degiskenleri haric demografik ozellikleri ile gizli basarisizlik korkusu ve mesleki tukenmislikleri arasinda pek fazla anlamli bir iliski bulunmamis; buna karsilik gizli basarisizlik korkusu ile mesleki tukenmislik arasinda anlamli bir iliski bulunmustur. Elde edilen bulgular mesleki tukenmislik ile gizli basarisizlik korkusu arasinda anlamli bir iliski oldugunu gostermektedir. Buna karsilik yoneticilerin yas ve sektor degiskeni haric demografik ozellikleri ile gizli basarisizlik korkusu ve mesleki tukenmislikleri arasinda pek fazla anlamli bir iliski bulunmamistir. Katilimcilarin yasa gore tukenmislik duzeyleri arasinda anlamli bir farklilik bulunmamisken; gizli basarisizlik korkusu duzeyleri yas degiskenine gore farklilik gostermistir.