Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduced glomerular size‐ and charge‐selectivity in clinically healthy individuals with microalbuminuria

Abstract. The pathophysiologic mechanism behind microalbuminuria, a potential atherosclerotic risk factor, was explored by measuring fractional clearances of four endogenous plasma proteins of different size and electric charge (albumin, β2‐microglobulin, immunoglobulin G, and immunoglobulin G4). Twenty‐eight clinically healthy individuals with microalbuminuria, defined as a urinary albumin excretion of 6.6–150μg min‐1, and 60 matched control subjects were studied. Fractional immunoglobulin G clearance was higher (geometric means (95% confidence intervals)) 3.0 (2.3–3.9) × 10‐6, n= 28, vs. 2.1 (1.8–2.4) × 10‐6, n= 60; P= 0.02), whereas the ratio immunoglobulin G clearance/immunoglobulin G4 clearance was lower (geometric means (95% confidence intervals)) 1.8 (1.4–2.2), n= 28, vs. 2.3 (2.0–2.5), n= 60; P= 0.03) in microalbuminuric than in normoalbuminuric individuals. Fractional β2‐micro‐globulin clearance was similar in the two groups. Since total IgG and the IgG4 subclass are of similar size and configuration but electrically neutral and negative, respectively; these findings indicate that microalbuminuria is associated with decreased size‐ and charge‐selectivity of the glomerular vessel wall. Hypotheti‐cally, such alterations may reflect generalized vascular abnormalities linking microalbuminuria to athero‐genesis.
Should the diaphragm be evaluated after abdominoplasty?

1. Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italia. a. http://orcid.org/0000-0002-1408-6971 The engine that moves air in and out of the lungs, sometimes referred to as the respiratory pump (or vital pump), relies on skeletal muscles, specifically the respiratory muscles. When the respiratory muscles contract, they create pressure gradients: negative to inhale and positive to exhale. With the exception of the diaphragm, all of the respiratory muscles have a secondary function as postural and chest wall stabilizers, forming and supporting the walls of the chest and abdomen. Quiet breathing is normally achieved by active inspiration, the diaphragm playing the major role, especially when the individual is in the supine position. The other inspiratory muscles contribute to quiet breathing, particularly when the individual is seated or standing. However, when higher levels of ventilation are required (e.g., during exercise) or when there are explosive events, such as coughing and vomiting, the other inspiratory muscles are strongly recruited, together with the expiratory ones. Expiration normally occurs as a passive return to functional residual capacity, and expiratory muscles do not usually contract in healthy subjects at rest. (1,2) Therefore, the diaphragm is the most important respiratory muscle. Diaphragmatic function can be assessed via invasive or noninvasive methods. The invasive methods require the use of esophageal catheters or ionizing radiation and are therefore not routinely used in clinical practice. (3,4) Ultrasound is a well-tolerated, noninvasive modality that allows quantitative measurements of diaphragm thickness and diaphragmatic excursion. When the diaphragm contracts, its normal movement is caudal, creating a piston-like effect to increase abdominal pressure and reduce pleural pressure. M-mode ultrasound allows the amplitude of the excursion of the hemidiaphragms to be quantified. The amplitude of excursion is defined as the maximal distance (from the end-expiratory baseline to the maximum height during inspiration) on the vertical axis of the M-mode ultrasound tracing of the echogenic line running between the liver (or spleen) and the lung, which corresponds to the diaphragm. The portability of an ultrasound device allows that measurement to be made directly at the bedside of patients, even of those who are critically ill. Reduced mobility of the diaphragm can be an indicator of muscle dysfunction. (5-7) Because of the major role played by the diaphragm, its dysfunction can have an impact on survival and quality of life, often being associated with dyspnea, exercise intolerance, and severe sleep disorders, including excessive daytime sleepiness.
Jump higher, run faster: effects of diversified sport participation on talent identification and selection in youth basketball

ABSTRACT The aims of this study were to examine the medium-term effects of previous experiences during early stages of sport development on physical capacities of under-13 (U-13) talented basketball players and, to identify variables that discriminated under-14 (U-14) national team training camp selection. Anthropometrical and physical measurements were collected during a basketball training camp. Previous sport experiences (6–10 years), maturity offset, power outputs for jumping and sprinting were determined. A cluster analysis was used to allocate the subjects according to their different levels of sport experiences (more specialized vs. less specialized) to allow creating a dummy variable for the subsequent analysis of the physical variables. A stepwise discriminant analysis was computed to identify the construct that best classifies selected and non-selected players for U-14 national team training camp. The less specialized group outscored more specialized in all physical parameters, irrespectively of gender. The Abalakov Jump Peak Power and Predicted Adult Height (PAH) could successfully discriminate selected from non-selected players for U-14 national team training camp in boys and PAHin girls. The diversified and non-specific sport stimulus during early ages seem to be determinant to the acquisition and development of fundamental movement skills of talented basketball players.
Risks Related to the Use of Non-Steroidal Anti-Inflammatory Drugs in Community-Acquired Pneumonia in Adult and Pediatric Patients

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to alleviate symptoms during community-acquired pneumonia (CAP), while neither clinical data nor guidelines encourage this use. Experimental data suggest that NSAIDs impair neutrophil intrinsic functions, their recruitment to the inflammatory site, and the resolution of inflammatory processes after acute pulmonary bacterial challenge. During CAP, numerous observational data collected in hospitalized children, hospitalized adults, and adults admitted to intensive care units (ICUs) support a strong association between pre-hospital NSAID exposure and a delayed hospital referral, a delayed administration of antibiotic therapy, and the occurrence of pleuropulmonary complications, even in the only study that has accounted for a protopathic bias. Other endpoints have been described including a longer duration of antibiotic therapy and a greater hospital length of stay. In all adult series, patients exposed to NSAIDs were younger and had fewer comorbidities. The mechanisms by which NSAID use would entail a complicated course in pneumonia still remain uncertain. The temporal hypothesis and the immunological hypothesis are the two main emerging hypotheses. Current data strongly support an association between NSAID intake during the outpatient treatment of CAP and a complicated course. This should encourage experts and scientific societies to strongly advise against the use of NSAIDs in the management of lower respiratory tract infections.
Lasers in Surgery and Medicine

Sarathkumar Loganathan, Soundarapandian Santhanakrishnan,* Ravi Bathe, and Muthukumaraswamy Arunachalam Department of Mechanical Engineering, Manufacturing Engineering Section, Indian Institute of Technology Madras, Chennai, 600036, Tamil Nadu, India International Advanced Research Centre for Powder Metallurgy and New Materials (ARCI), Centre for Laser Processing of Materials, Hyderabad, 500005, Telangana, India Department of Periodontics, Tamil Nadu Government Dental College, Chennai, 600003, Tamil Nadu, India
Proficiency Testing of Virus Diagnostics Based on Bioinformatics Analysis of Simulated In Silico High-Throughput Sequencing Data Sets

Quality management and independent assessment of high-throughput sequencing-based virus diagnostics have not yet been established as a mandatory approach for ensuring comparable results. The sensitivity and specificity of viral high-throughput sequence data analysis are highly affected by bioinformatics processing using publicly available and custom tools and databases and thus differ widely between individuals and institutions. ABSTRACT Quality management and independent assessment of high-throughput sequencing-based virus diagnostics have not yet been established as a mandatory approach for ensuring comparable results. The sensitivity and specificity of viral high-throughput sequence data analysis are highly affected by bioinformatics processing using publicly available and custom tools and databases and thus differ widely between individuals and institutions. Here we present the results of the COMPARE [Collaborative Management Platform for Detection and Analyses of (Re-)emerging and Foodborne Outbreaks in Europe] in silico virus proficiency test. An artificial, simulated in silico data set of Illumina HiSeq sequences was provided to 13 different European institutes for bioinformatics analysis to identify viral pathogens in high-throughput sequence data. Comparison of the participants’ analyses shows that the use of different tools, programs, and databases for bioinformatics analyses can impact the correct identification of viral sequences from a simple data set. The identification of slightly mutated and highly divergent virus genomes has been shown to be most challenging. Furthermore, the interpretation of the results, together with a fictitious case report, by the participants showed that in addition to the bioinformatics analysis, the virological evaluation of the results can be important in clinical settings. External quality assessment and proficiency testing should become an important part of validating high-throughput sequencing-based virus diagnostics and could improve the harmonization, comparability, and reproducibility of results. There is a need for the establishment of international proficiency testing, like that established for conventional laboratory tests such as PCR, for bioinformatics pipelines and the interpretation of such results.
mRNA levels can be reduced by antisense oligonucleotides via no-go decay pathway

Abstract Antisense technology can reduce gene expression via the RNase H1 or RISC pathways and can increase gene expression through modulation of splicing or translation. Here, we demonstrate that antisense oligonucleotides (ASOs) can reduce mRNA levels by acting through the no-go decay pathway. Phosphorothioate ASOs fully modified with 2′-O-methoxyethyl decreased mRNA levels when targeted to coding regions of mRNAs in a translation-dependent, RNase H1-independent manner. The ASOs that activated this decay pathway hybridized near the 3′ end of the coding regions. Although some ASOs induced nonsense-mediated decay, others reduced mRNA levels through the no-go decay pathway, since depletion of PELO/HBS1L, proteins required for no-go decay pathway activity, decreased the activities of these ASOs. ASO length and chemical modification influenced the efficacy of these reagents. This non-gapmer ASO-induced mRNA reduction was observed for different transcripts and in different cell lines. Thus, our study identifies a new mechanism by which mRNAs can be degraded using ASOs, adding a new antisense approach to modulation of gene expression. It also helps explain why some fully modified ASOs cause RNA target to be reduced despite being unable to serve as substrates for RNase H1.
The insulin‐like growth factor binding protein‐3 and its death receptor in pancreatic ductal adenocarcinoma poor prognosis

Insulin‐like growth factor binding protein‐3 (IGFBP‐3) and its newly discovered death receptor (IGFBP‐3R) have been reported to involve in a wide variety of cancers. However, their role in pancreatic ductal adenocarcinoma (PDAC) has not been elucidated yet. Here, 478 pancreatic cancers were screened for primary PDAC tumors. The samples were evaluated using quantitative reverse‐transcriptase polymerase chain reaction, western blotting, and immunohistochemistry staining. The results indicated that relative IGFBP‐3 mRNA expression and its protein level were reduced stage dependently in the PDAC tumors (p < .001 and p < .05, respectively). The subcellular distribution of IGFBP‐3 was mainly nuclear only in Stage 0 + 1 (about 150% compared to adjacent normal tissues [p < .05]). The value for IGFBP‐3R messenger RNA (mRNA) and protein were also reduced in tumors in compared to adjacent normal pancreatic tissues (p < .05). The Kaplan–Meier analysis also showed that mRNA expression of IGFBP‐3 and IGFBP‐3R was positively associated with survival, (p = .001). In addition, there is a strong association between low expression of IGFBP‐3 and tumor size (p = .032), the lymphatic invasion (p = .001), the TNM (tumor, node, metastasis) staging (p = .001), tumor differentiation (p = .001), and PNI status (p = .021). Down‐regulation of IGFBP‐3R was also correlated with the tumor size (p = .01), the lymphatic invasion (p = .012) TNM staging (p = .001), tumor differentiation (p = .021) and PNI status (p = .038). In conclusion, IGFBP‐3 and its receptor were down‐regulated and their expression was associated with poor prognosis of PDAC.
Aspergillus fumigatus enhances human NK cell activity by regulating M1 macrophage polarization

The progression of disease caused by fungal infection is closely associated with the human immune system. Macrophages and natural killer cells (NK cells) are two important types of innate immune cells that serve an important role in anti-infection immunity. There has been limited research into the interactions between fungi and macrophages. In the present in vitro study, reverse transcription-quantitative PCR, ELISA and flow cytometry were performed to reveal that the interaction between macrophages and NK cells, regulated by Aspergillus fumigatus conidia, induced macrophages to polarize into M1 macrophages by secreting large quantities of tumor necrosis factor-α, interleukin-18 and Galectin-9. In addition, when NK cells were co-cultured with the conidia of A. fumigatus-stimulated M1 macrophages, they exhibited increased activation levels and secretion of interferon-γ (IFN-γ). It was further demonstrated via antibody neutralization and gene silencing experiments that galectin-9 served an important role in the interaction between macrophages and NK cells regulated by A. fumigatus. In conclusion, it was demonstrated that A. fumigatus induced the polarization of macrophages into M1 macrophages by secreting Galectin-9, which then promoted NK cell activity and IFN-γ secretion. The results provided improved understanding of the role of innate immune cells in invasive fungal infections. The present study also provided novel insight into the study of macrophages and NK cells in inflammatory infections caused by A. fumigatus and potential strategies to control the progression of inflammation.
Magnitude and modifiers of the weekend effect in hospital admissions: a systematic review and meta-analysis

Objective To examine the magnitude of the weekend effect, defined as differences in patient outcomes between weekend and weekday hospital admissions, and factors influencing it. Design A systematic review incorporating Bayesian meta-analyses and meta-regression. Data sources We searched seven databases including MEDLINE and EMBASE from January 2000 to April 2015, and updated the MEDLINE search up to November 2017. Eligibility criteria: primary research studies published in peer-reviewed journals of unselected admissions (not focusing on specific conditions) investigating the weekend effect on mortality, adverse events, length of hospital stay (LoS) or patient satisfaction. Results For the systematic review, we included 68 studies (70 articles) covering over 640 million admissions. Of these, two-thirds were conducted in the UK (n=24) or USA (n=22). The pooled odds ratio (OR) for weekend mortality effect across admission types was 1.16 (95% credible interval 1.10 to 1.23). The weekend effect appeared greater for elective (1.70, 1.08 to 2.52) than emergency (1.11, 1.06 to 1.16) or maternity (1.06, 0.89 to 1.29) admissions. Further examination of the literature shows that these estimates are influenced by methodological, clinical and service factors: at weekends, fewer patients are admitted to hospital, those who are admitted are more severely ill and there are differences in care pathways before and after admission. Evidence regarding the weekend effect on adverse events and LoS is weak and inconsistent, and that on patient satisfaction is sparse. The overall quality of evidence for inferring weekend/weekday difference in hospital care quality from the observed weekend effect was rated as ‘very low’ based on the Grading of Recommendations, Assessment, Development and Evaluations framework. Conclusions The weekend effect is unlikely to have a single cause, or to be a reliable indicator of care quality at weekends. Further work should focus on underlying mechanisms and examine care processes in both hospital and community. Prospero registration number CRD42016036487
A Quantitative and Qualitative Analysis of Electronic Prescribing Incidents Reported by Community Pharmacists

Abstract Background Electronic prescribing (e-prescribing) technology was introduced as an alternative to handwritten prescriptions allowing health care professionals to send prescriptions directly to pharmacies. While the technology has many advantages, such as improving pharmacy workflow and reducing medication errors, some limitations have been realized. Objective The objective of this study was to examine the frequency, type, and contributing factors of e-prescribing quality-related incidents reported to two national error-reporting databases in the United States. Methods This was a retrospective analysis of voluntarily reports of e-prescribing quality-related incidents. A quantitative and qualitative analysis was conducted of incidents reported between 2011 and 2015 to the Pharmacy Quality Commitment (PQC) and the Pharmacy Provider e-prescribing Experience Reporting Portal (PEER) databases. For the qualitative analysis, events were combined from the PQC and PEER portal and a 10% random sample of events were analyzed. Results A total of 589 events were reported to the PEER Portal. Of these, problems with patient directions were the most frequent incident type (n = 210) of which 10% (n = 21) reached the patient. Quantity selection (n = 158) and drug selection (n = 96) were the next most frequently reported events, 20% of which reached the patient. The PQC system received 550 reports. The most frequent event type reported to this system was incorrect directions (23.3%, n = 128) followed by incorrect prescriber (17%), incorrect drug (15%), and incorrect strength (12%). The most common theme in the qualitative analysis was a perceived increased likelihood of patient receiving incorrect drug therapy due to e-prescribing. Another theme identified included confusion and frustration of pharmacy personnel as result of e-prescription quality-related events. Conclusion The use of qualitative and quantitative incident data revealed that patient directions and quantity selection were the most common quality issues with e-prescribing. In turn, this may increase the likelihood of patients receiving incorrect drug therapy.
Adenylyl cyclase-associated protein 1-targeted nanoparticles as a novel strategy for the treatment of metastatic non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is one of the most fatal cancers worldwide. Adenylyl cyclase-associated protein 1 (CAP1) belongs to a family of cyclase-associated proteins that are involved in the development of cancerous tumors. A previous study by our group confirmed the association between CAP1, lung cancer and the metastasis of cancer cells. In the present study, poly(lactic-polyglycolic acid; PLGA)/CAP1-small interfering (si)RNA nanoparticles were prepared and delivered into A549 cells. The performance of PLGA/siCAP1-siRNA nanoparticles for siRNA delivery was measured based on the results of migration assay and animal experiments. The multifunctional nanoparticles were determined to be capable of inhibiting CAP1 expression, which reduced NSCLC metastasis in vitro and in vivo. Therefore, the findings of the current study highlighted the potential use of PLGA/siCAP1-siRNA nanoparticles for the treatment of NSCLC metastasis.
Effect of the Environment on the Sport Performance

Alessandro Pezzoli, Elena Cristofori, Matteo Moncalero, Fiorella Giacometto and Andrea Boscolo 1 DIATI, Politecnico di Torino, C.so Duca degli Abruzzi 24, Torino, Italy MeteoSport Sport Psychology Research Unit – Motor Science Research Centre – School of Motor and Sport Sciences, University of Turin, P.zza Bernini 12, Torino, Italy DIST, Politecnico di Torino, Viale Mattioli 39, Castello del Valentino, Torino, Italy DICAM, Alma Mater Studiorum, Universita di Bologna, Via Terraccini 28, Bologna, Italy Ospedale Cottolengo Piccola Casa della Divina Provvidenza, Via S. Giuseppe Cottolengo 14, 10152 – Torino, ITALY alessandro.pezzoli@polito.it, elena.crisotofori@polito.it, matteo.moncalero@unibo.it, fiorella.giacometto@libero.it, andrea.b@atleticom.it
Histological Evidence of Diabetic Kidney Disease Precede Clinical Diagnosis

Background: In the absence of a histological diagnosis, persistent albuminuria is globally accepted as the main diagnostic criteria for diabetic kidney disease (DKD). Methods: In the present retrospective study, we evaluated data from an Italian cohort of 42 deceased diabetic donors (mainly with type 2 diabetes). Using the kidney biopsies obtained at the time of donation to evaluate single or double allocation based on Karpinski score, we determined the prevalence of histological lesions attributable to diabetes. Results: All 42 donors presented with proteinuria in the normal range and an estimated glomerular filtration rate (eGFR) (chronic kidney disease [CKD]-EPI) >60 mL/min/1.73 m2. A kidney biopsy was available for 36 patients; of these, one was not interpretable and 32 showed histopathological lesions consistent with DKD and encompassing all histological classes. Thus, we found a relatively high proportion of histologically proven DKD that had been clinically undiagnosed, as none of the patient had significant proteinuria and eGFR <60 mL/min/1.73 m2. Conclusions: The data we present here support the need to implement routine kidney biopsies in normoalbuminuric diabetic subjects in the early stages of CKD. Such strategy may help to improve risk stratification in diabetic patients and guide therapeutic decisions during the early stages of the disease.
The Ecological Role of the Mammalian Mesocarnivore

Large mammalian carnivores are ecologically important because relatively few individuals can cause strong predation-driven direct effects or fear-driven indirect effects that can ripple through communities and, ultimately, influence ecosystem structure and function. Most mammalian carnivores are not large, however, but are small to midsized species collectively termed “mesocarnivores. ” Mesocarnivores are more numerous and more diverse than larger carnivores, and often reside in closer proximity to humans, yet we know little about how they influence communities and ecosystems. In this article we review the ecological role of the mesocarnivore and present examples where mesocarnivores drive community structure and function in roles similar to, or altogether different from, their larger brethren. Together, these examples substantiate the need for an assessment of the ecological role of mammalian carnivores beyond an examination of only the largest species. In particular, we emphasize the need to study the trophic penetrance of mesocarnivores and examine how ecological context modulates their functional role.