Miracle-dz/UniFAR-FTUs huggingface dataset:
Bio-Recognition in Spectroscopy-Based Biosensors for *Heavy Metals-Water and Waterborne Contamination Analysis

Microsystems and biomolecules integration as well multiplexing determinations are key aspects of sensing devices in the field of heavy metal contamination monitoring. The present review collects the most relevant information about optical biosensors development in the last decade. Focus is put on analytical characteristics and applications that are dependent on: (i) Signal transduction method (luminescence, colorimetry, evanescent wave (EW), surface-enhanced Raman spectroscopy (SERS), Förster resonance energy transfer (FRET), surface plasmon resonance (SPR); (ii) biorecognition molecules employed (proteins, nucleic acids, aptamers, and enzymes). The biosensing systems applied (or applicable) to water and milk samples will be considered for a comparative analysis, with an emphasis on water as the primary source of possible contamination along the food chain.
The Effect of Computer Gaming on Subsequent Time Perception

Losing track of time upon gaming is a phenomenon often reported by players of computer and video games. However, the few studies addressing this issue show mixed results and do therefore not allow final conclusions about the effect of gaming on time perception. Even less is known about whether and how time distortion continues after a play session. Therefore, the present experiment tested the effect of gaming on the perception of time subsequent to a game session at a LAN party. 40 players produced standard time intervals of 10 s and 60 s before and after having played computer games. Results show a significant increase in time productions after gaming for the short interval, indicating that game-induced time losses continue even after a game session. In contrast, the reverse was true for the longer interval. We discuss how this result may be explained in terms of participants’ motivational states during the experiment counteracting subjective time losses.
CNS cell type–specific gene profiling of P301S tau transgenic mice identifies genes dysregulated by progressive tau accumulation

The microtubule-associated protein tau undergoes aberrant modification resulting in insoluble brain deposits in various neurodegenerative diseases, including frontotemporal dementia (FTD), progressive supranuclear palsy, and corticobasal degeneration. Tau aggregates can form in different cell types of the central nervous system (CNS) but are most prevalent in neurons. We have previously recapitulated aspects of human FTD in mouse models by overexpressing mutant human tau in CNS neurons, including a P301S tau variant in TAU58/2 mice, characterized by early-onset and progressive behavioral deficits and FTD-like neuropathology. The molecular mechanisms underlying the functional deficits of TAU58/2 mice remain mostly elusive. Here, we employed functional genomics (i.e. RNAseq) to determine differentially expressed genes in young and aged TAU58/2 mice to identify alterations in cellular processes that may contribute to neuropathy. We identified genes in cortical brain samples differentially regulated between young and old TAU58/2 mice relative to nontransgenic littermates and by comparative analysis with a dataset of CNS cell type–specific genes expressed in nontransgenic mice. Most differentially-regulated genes had known or putative roles in neurons and included presynaptic and excitatory genes. Specifically, we observed changes in presynaptic factors, glutamatergic signaling, and protein scaffolding. Moreover, in the aged mice, expression levels of several genes whose expression was annotated to occur in other brain cell types were altered. Immunoblotting and immunostaining of brain samples from the TAU58/2 mice confirmed altered expression and localization of identified and network-linked proteins. Our results have revealed genes dysregulated by progressive tau accumulation in an FTD mouse model.
Factors Affecting Korean Physician Job Satisfaction

This study examines job satisfaction of physicians in Korea and investigates factors affecting their satisfaction. The majority of the past studies tend to cover few minor factors— including stress and occupation professionality or insufficient scale of respondents in particular regions—thus leading to restricted explanations on job satisfaction of the overall physician pool in Korea. This study examines the level of job satisfaction of physicians in Korea and factors affecting their satisfaction by using the ‘2016 Korean Physician Survey (KPS)’ data which included all physicians in Korea. Ordinal logistic regression analysis was conducted in this study in order to identify the factors affecting job satisfaction of physicians in terms of care environment attributes. These attributes included autonomy for care delivery, colleagues/staff/patient relations, income, healthcare resources, social reputation, personal leisure time, administration, restrictions and regulations, and work hours and loads. For the ordinal logistic regression analysis, general socio-demographic attributes, such as gender, age, specialty, job position, type of affiliated healthcare organization, working region, and length of service were controlled beforehand. The result of our measures, the affecting factors of job satisfaction for physicians, include being able to; maintain positive relations with patients through adequate time for consultation and necessary healthcare, have the autonomy to make clinical decisions, have healthy relations with peers and staff, obtain respect from family and society, work in an environment with desirable income and have adequate health resources, and have appropriate work hours and loads for those who facilitate high-quality care. Creating an environment in which physicians can focus on patient-oriented healthcare will contribute to promoting national healthcare.
Human laterality for manipulation and gestural communication: A study of beach-volleyball players during the Olympic Games

ABSTRACT Comparative studies can help understand better brain functional lateralization for manipulation and language. This study investigated and compared, for the first time, human adults’ laterality for manipulation and gestures in a non-experimental social context. We analysed the manual laterality of 48 beach volleyball athletes for four frequently expressed behaviours: a complex throwing action (jump serve) and three gestures (CLAP HAND, PUMP FIST and SLAP HAND-TO-HAND). We evaluated population-level laterality bias for each of the four behaviours separately, compared manual laterality between behaviours and investigated factors influencing gestural laterality. We furthered our between-gestures comparison by taking into account three categories of factors simultaneously: gesture characteristics (sensory modality), interactional context components (positions of interactants and emotional valence), and individual demographic characteristics (age, sex and country). Our study showed that (1) each behaviour considered presented a population-level right-hand bias, (2) differences of laterality between behaviours were probably related to gesture sensory modality and (3) signaller’s laterality was modulated differently in relation to positions of interactants, emotional valence, age and sex. Our results support the literature suggesting that left-hemisphere specialization for manipulation and language (speech and gestures) may have evolved from complex manual activities such as throwing and from gestural communication.
Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic‐ and GPR109a‐mediated mechanisms

Butyrate is a short‐chain fatty acid derived from the metabolism of indigestible carbohydrates by the gut microbiota. Butyrate contributes to gut homeostasis, but it may also control inflammatory responses and host physiology in other tissues. Butyrate inhibits histone deacetylases, thereby affecting gene transcription, and also signals through the metabolite‐sensing G protein receptor (GPR)109a. We produced an mAb to mouse GPR109a and found high expression on podocytes in the kidney. Wild‐type and Gpr109a–/– mice were induced to develop nephropathy by a single injection of Adriamycin and treated with sodium butyrate or high butyrate‐releasing high‐amylose maize starch diet. Butyrate improved proteinuria by preserving podocyte at glomerular basement membrane and attenuated glomerulosclerosis and tissue inflammation. This protective phenotype was associated with increased podocyte‐related proteins and a normalized pattern of acetylation and methylation at promoter sites of genes essential for podocyte function. We found that GPR109a is expressed by podocytes, and the use of Gpr109a–/– mice showed that the protective effects of butyrate depended on GPR109a expression. A prebiotic diet that releases high amounts of butyrate also proved highly effective for protection against kidney disease. Butyrate and GPR109a play a role in the pathogenesis of kidney disease and provide one of the important molecular connections between diet, the gut microbiota, and kidney disease. —Felizardo, R. J. F. , de Almeida, D. C. , Pereira, R. L. , Watanabe, I. K. M. , Doimo, N. T. S. , Ribeiro, W. R. , Cenedeze, M. A. , Hiyane, M. I. , Amano, M. T. , Braga, T. T. , Ferreira, C. M. , Parmigiani, R. B. , Andrade‐Oliveira, V. , Volpini, R. A. , Vinolo, M. A. R. , Mariño, E. , Robert, R. , Mackay, C. R. , Camara, N. O. S. Gut microbial metabolite butyrate protects against proteinuric kidney disease through epigenetic‐ and GPR109a‐mediated mechanisms. FASEB J. 33, 11894–11908 (2019). www.fasebj. org
The Modern Western Diet Rich in Advanced Glycation End-Products (AGEs): An Overview of Its Impact on Obesity and Early Progression of Renal Pathology

Advanced glycation end-products (AGEs) are an assorted group of molecules formed through covalent bonds between a reduced sugar and a free amino group of proteins, lipids, and nucleic acids. Glycation alters their structure and function, leading to impaired cell function. They can be originated by physiological processes, when not counterbalanced by detoxification mechanisms, or derive from exogenous sources such as food, cigarette smoke, and air pollution. Their accumulation increases inflammation and oxidative stress through the activation of various mechanisms mainly triggered by binding to their receptors (RAGE). So far, the pathogenic role of AGEs has been evidenced in inflammatory and chronic diseases such as chronic kidney disease, cardiovascular disease, and diabetic nephropathy. This review focuses on the AGE-induced kidney damage, by describing the molecular players involved and investigating its link to the excess of body weight and visceral fat, hallmarks of obesity. Research regarding interventions to reduce AGE accumulation has been of great interest and a nutraceutical approach that would help fighting chronic diseases could be a very useful tool for patients’ everyday lives.
Human Tumor-Infiltrating Dendritic Cells: From In Situ Visualization to High-Dimensional Analyses

The interaction between tumor cells and the immune system is considered to be a dynamic process. Dendritic cells (DCs) play a pivotal role in anti-tumor immunity owing to their outstanding T cell activation ability. Their functions and activities are broad ranged, triggering different mechanisms and responses to the DC subset. Several studies identified in situ human tumor-infiltrating DCs by immunostaining using a limited number of markers. However, considering the heterogeneity of DC subsets, the identification of each subtype present in the immune infiltrate is essential. To achieve this, studies initially relied on flow cytometry analyses to provide a precise characterization of tumor-associated DC subsets based on a combination of multiple markers. The concomitant development of advanced technologies, such as mass cytometry or complete transcriptome sequencing of a cell population or at a single cell level, has provided further details on previously identified populations, has unveiled previously unknown populations, and has finally led to the standardization of the DCs classification across tissues and species. Here, we review the evolution of tumor-associated DC description, from in situ visualization to their characterization with high-dimensional technologies, and the clinical use of these findings specifically focusing on the prognostic impact of DCs in cancers.
Nurses’ practice of integration of HIV prevention and sexual and reproductive health services in Ntcheu District, Malawi

Background Nurses play a critical role in their practice of integrating human immunodeficiency virus (HIV) prevention and sexual and reproductive services to combat the spread of HIV and promote family planning in resource-constrained countries like Malawi. Objectives The purpose of this study was to determine and describe the nurses’ practice of integration of HIV prevention and sexual and reproductive health (SRH) services as a strategy to effectively combat the spread of HIV and promote family planning in Malawi. Methods A descriptive qualitative case study was used. The research question was: How do nurses practise the integration of family planning and HIV prevention services in Ntcheu District, Malawi? Qualitative data were collected using semi-structured interviews from a sample of 10 participants. Manual data analysis, using the five steps for interpretive content analysis, was used to analyse data. Results Five themes were identified as (1) facilitation of access and acceptability of comprehensive HIV and family planning services, (2) educating and counselling patients, (3) early detection of HIV among women of child-bearing age, (4) professional benefits of integrating family planning and HIV prevention services and (5) resentment of integration of family planning and HIV prevention services. Conclusion The nurses’ practice of integration of HIV prevention and SRH services has more benefits for both nurses and patients as a strategy to combat the spread of HIV and promote family planning in a resource-constrained country like Malawi.
The Impact of Radiotherapy Facility Volume on the Survival and Guideline Concordance of Patients With Muscle-invasive Bladder Cancer Receiving Bladder-preservation Therapy

Objectives: Higher facility surgical volume predicts for improved outcomes in patients with muscle-invasive bladder cancer (MIBC) who undergo radical cystectomy. We investigated the association between facility radiotherapy (RT) case volume and overall survival (OS) for patients with MIBC who received bladder-preserving RT, and the relationship with adherence to National Comprehensive Cancer Network (NCCN) guidelines for bladder preservation. Methods: The National Cancer Database was used to identify patients diagnosed with nonmetastatic MIBC from 2004 to 2015 and received RT at the reporting center. Facility case volume was defined as the total MIBC patients treated with RT during the period. Facilities were stratified into high-volume facility (HVF) or low-volume facility at the 80th percentile of RT case volume. OS was assessed using Kaplan-Meier analysis. Rates of compliance with NCCN guidelines regarding the use of transurethral resection of the bladder tumor before RT, planned use of concurrent chemotherapy, and total RT dose were compared. Cox proportional hazard model was used to evaluate predictors of OS. Results: There were 7562 patients included. No differences in age, Charlson-Deyo score, T stage, or node-positive rates were observed between groups. HVFs exhibited greater compliance with NCCN guidelines for bladder preservation (P<0.0001). Treatment at an HVF was associated with the improved OS for all patients (P=0.001) and for the subset of patients receiving NCCN-recommended RT doses (P=0.0081). Volume was an independent predictor of OS (P=0.002). Conclusions: Treatment at an HVF is associated with improved OS and greater guideline-concordant management among patients with MIBC.
How words impact on pain

The wording used before and during painful medical procedures might significantly affect the painfulness and discomfort of the procedures. Two theories might account for these effects: the motivational priming theory (Lang, 1995, American Psychologist, 50, 372) and the theory of neural networks (Hebb, 1949, The organization of behavior. New York, NY: Wiley; Pulvermuller, 1999, Behavioral and Brain Sciences, 22, 253; Pulvermüller and Fadiga, 2010, Nature Reviews Neuroscience, 11, 351).
Congenital Diaphragmatic Hernia: State of the Art in Translating Experimental Research to the Bedside

Abstract Congenital diaphragmatic hernia (CDH) is a devastating disease that still carries a high mortality and morbidity rate. Poor outcomes for fetuses and infants with CDH are mainly related to pulmonary hypoplasia (PH) and pulmonary vascular remodeling that leads to pulmonary hypertension (PHTN). Over the last five decades, research efforts have focused on modeling CDH not only to study the pathophysiology of the diaphragmatic defect, pulmonary hypoplasia, and pulmonary hypertension, but also to identify therapies that would promote lung growth and maturation, and correct vascular remodeling. As CDH is a multifactorial condition whose etiology remains unknown, there is not a single model of CDH, rather several ones that replicate different aspects of this disease. While small animals like the mouse and the rat have mainly been used to uncover biological pathways underlying the diaphragmatic defect and poor lung growth, larger animals like the lamb and the rabbit models have been instrumental for pursuing medical and surgical interventions. Overall, the use of animal models has indeed advanced our knowledge on CDH and helped us test innovative therapeutic options. For example, the lamb model of CDH has been the paradigm for testing fetal surgical procedures, including tracheal occlusion, which has been translated to clinical use. In this review, we outline the induction protocols of CDH in animals with the use of chemicals, dietary changes, genetic alterations, and surgical maneuvers, and we describe the studies that have translated experimental results to the bedside.
The crystal structure of AcrR from Mycobacterium tuberculosis reveals a one‐component transcriptional regulation mechanism

Transcriptional regulator proteins are closely involved in essential survival strategies in bacteria. AcrR is a one‐component allosteric repressor of the genes associated with lipid transport and antibiotic resistance. When fatty acid ligands bind to the C‐terminal ligand‐binding cavity of AcrR, a conformational change in the N‐terminal operator‐binding region of AcrR is triggered, which releases the repressed DNA and initiates transcription. This paper focuses on the structural transition mechanism of AcrR of Mycobacterium tuberculosis upon DNA and ligand binding. AcrR loses its structural integrity upon ligand‐mediated structural alteration and bends toward the promoter DNA in a more compact form, initiating a rotational motion. Our functional characterization of AcrR and description of the ligand‐ and DNA‐recognition mechanism may facilitate the discovery of new therapies for tuberculosis.
The wolf of hypomethylating agent failure: what comes next?

haematologica | 2019; 104(8) 1505 report demonstrated that the use of insecticide to impregnate bed nets and screening for parasites in blood reduced the malaria risk in children on iron supplementation. Moreover, recent data demonstrate that iron deficiency negatively impacts on immunological responses to diphtheria vaccine leaving children insufficiently protected against such infections (N Stoffel, Zurich, oral presentation, Bioiron Meeting 2019). Thus, this study by Armitage and co-workers is an important step forward to gain more insights into the relative contribution of different regulatory mechanisms on circulating biomarker concentrations such as hepcidin and how this impacts on predicting therapeutic efficacy and the risk:benefit ratio of iron supplementation in a primary care setting. Future studies will have to clarify the optimal timing and dose of iron supplementation to children, whether or not a continuous administration via dietary iron fortification or a once daily or once every other day application is preferable. It will also be necessary to identify those children who might be at risk of unwanted effects of iron supplementation mainly arising from an increased morbidity and mortality from infections. Finally, we await further information on the impact of iron supplementation on growth and mental development, functionality of the immune system, efficacy of preventive measures such as vaccination, and the consequences of iron-mediated alterations of the intestinal microbiota on children’s health.
Therapeutically relevant engraftment of a CRISPR-Cas9–edited HSC-enriched population with HbF reactivation in nonhuman primates

CRISPR-Cas9–edited hematopoietic stem cells produce long-term engraftment and fetal hemoglobin reactivation in nonhuman primates. Enriching stem cells for gene editing Gene editing using CRISPR-Cas9 offers the potential of targeted treatment for a variety of genetic diseases. These include inherited abnormalities of β hemoglobin, which can be indirectly targeted by increasing the amount of healthy fetal hemoglobin even without fully correcting the disease-causing mutation. Humbert et al. used CRISPR-based gene editing to modify hematopoietic stem cells from nonhuman primates, introducing a naturally occurring mutation that increases the amount of fetal hemoglobin. The authors successfully applied this method to a highly enriched population of stem cells in the primate model, suggesting the potential for translating this efficient editing technique to human patients. Reactivation of fetal hemoglobin (HbF) is being pursued as a treatment strategy for hemoglobinopathies. Here, we evaluated the therapeutic potential of hematopoietic stem and progenitor cells (HSPCs) edited with the CRISPR-Cas9 nuclease platform to recapitulate naturally occurring mutations identified in individuals who express increased amounts of HbF, a condition known as hereditary persistence of HbF. CRISPR-Cas9 treatment and transplantation of HSPCs purified on the basis of surface expression of the CD34 receptor in a nonhuman primate (NHP) autologous transplantation model resulted in up to 30% engraftment of gene-edited cells for >1 year. Edited cells effectively and stably reactivated HbF, as evidenced by up to 18% HbF-expressing erythrocytes in peripheral blood. Similar results were obtained by editing highly enriched stem cells, defined by the markers CD34+CD90+CD45RA−, allowing for a 10-fold reduction in the number of transplanted target cells, thus considerably reducing the need for editing reagents. The frequency of engrafted, gene-edited cells persisting in vivo using this approach may be sufficient to ameliorate the phenotype for a number of genetic diseases.
Control of biofouling on pearl oysters Pinctada imbricata using wax and Chinese herbs

Abstract Biofouling poses severe challenges to pearl oyster Pinctada imbricata culture in China, and controlling it is both labor- and capital-intensive. The antifouling properties of wax, and wax mixed with Chinese herbs, sprayed onto pearl oyster shell surfaces during peak biofouling seasons were evaluated. Pearl oysters coated with three wax treatments (plain wax, Chinaberry seed extract, Chinese honeylocust fruit extract) and a control (no treatment), were cultured in nets for up to 60 days. Mortality rate, fouling organism and pearl-oyster weights, and shell height are reported for individual oysters on each of six sampling dates. With the exception of oysters submerged for 12 days, all oysters were significantly affected by treatment type and submersion duration. Fouling weight increased more rapidly over time in the control-treatment oysters. Wax-based coatings deterred fouling-organism settlement on oysters for at least 2 months during the intensive fouling season, reducing mortality and not adversely effecting growth.