Miracle-dz/UniFAR-FTUs huggingface dataset:
Vitally important – does early innate immunity predict recruitment and adult innate immunity?

Abstract The immune system is one of the most important adaptations that has evolved to protect animals from a wide range of pathogens they encounter from early life onwards. During the early developmental period this is particularly true for the innate immunity, as other components of the immune system are, as yet, poorly developed. But innate immunity may not only be crucial for early life survival, but may also have long‐lasting effects, for example if early life immunity reflects the functioning of the immune system as a whole. For this reason, we investigated the importance of four constitutive innate immune parameters (natural antibodies, complement activity, concentrations of haptoglobin, and concentrations of nitric oxide) for recruitment in free‐living great tits. We compared nestling immunity of recruits with nestling immunity of their nonrecruited siblings. We also investigated within individual consistency of these innate immune parameters for those individuals that recruited, which may be taken as a measure of immune capacity. In accordance with previous studies, we found a clear effect of tarsus length and a trend for body mass on the likelihood to recruit. Nevertheless, we found no evidence that higher levels of constitutive innate immunity as a nestling facilitated local recruitment. Furthermore, individual innate immunity was not consistent across life stages, that is to say, nestling immune parameters did not determine, or respectively, reflect adult innate immune parameters. This plasticity in innate immune components may explain why we did not find long‐lasting survival benefits.
Linking HRM Practices and Institutional Setting to Collective Turnover: An Empirical Exploration

The present study addresses the relationship between human resources management (HRM) practices and employee turnover by taking into account the influence of socioeconomic environment. Data was collected at company level with an international sample of 830 companies from 12 countries (Netherlands, Belgium, United Kingdom, Brazil, Switzerland, China, France, Italy, Poland, Germany, South Africa, and Spain). A division into four bundles of human resources (HR) practices is introduced: remunerative, communication, developmental, and well-being practices. The influence of the socioeconomic environment was factored in by including the institutional setting in terms of the level of coordination as a country-level variable. The results showed that collective turnover is related to both a country’s institutional determinants and to company HR practices. Remunerative HR practices may have a negative influence in terms of enhancing turnover, particularly within countries high in coordination. HR well-being practices are the most beneficial practices in terms of reducing employee turnover. Our study adds to our knowledge on the relation between HR practices and turnover from an international perspective. It complements the empirical knowledge on the effectiveness of HRM practices in a cross-national setting and supports the notion that the institutional context should be given more attention when studying HR effectiveness.
Atmospheric Chemistry and Physics Technical Note: Quantitative Long-term Measurements of Voc Concentrations by Ptr-ms – Measurement, Calibration, and Volume Mixing Ratio Calculation Methods

Proton transfer reaction mass spectrometry (PTR-MS) is a technique for online measurements of atmospheric concentrations, or volume mixing ratios, of volatile organic compounds (VOCs). This paper gives a detailed description of our measurement, calibration, and volume mixing ratio calculation methods, which have been designed for long-term stand-alone field measurements by PTR-MS. The PTR-MS instrument has to be calibrated regularly with a gas standard to ensure the accuracy needed in atmospheric VOC measurements. We introduce a novel method for determining an instrument specific relative transmission curve using information obtained from a calibration. This curve enables consistent mixing ratio calculation for VOCs not present in a calibration gas standard. Our method proved to be practical , systematic, and sensitive enough to capture changes in the transmission over time. We also propose a new approach to considering the abundance of H 3 O + H 2 O ions in mixing ratio calculation. The approach takes into account the difference in the transmission efficiencies for H 3 O + and H 3 O + H 2 O ions. To illustrate the functionality of our measurement , calibration, and calculation methods, we present a one-month period of ambient mixing ratio data measured in a boreal forest ecosystem at the SMEAR II station in southern Finland. During the measurement period 27 March– 26 April 2007, the hourly averages of the mixing ratios were 0.051–0.57 ppbv for formaldehyde, 0.19–3.1 ppbv for methanol, 0.038–0.39 ppbv for benzene, and 0.020–1.3 ppbv for monoterpenes. The detection limits for the hourly averages were 0.020, 0.060, 0.0036, and 0.0092 ppbv, respectively .
Local Consolidative Therapy Vs. Maintenance Therapy or Observation for Patients With Oligometastatic Non-Small-Cell Lung Cancer: Long-Term Results of a Multi-Institutional, Phase II, Randomized Study.

PURPOSE Our previously published findings reported that local consolidative therapy (LCT) with radiotherapy or surgery improved progression-free survival (PFS) and delayed new disease in patients with oligometastatic non-small-cell lung cancer (NSCLC) that did not progress after front-line systemic therapy. Herein, we present the longer-term overall survival (OS) results accompanied by additional secondary end points. PATIENTS AND METHODS This multicenter, randomized, phase II trial enrolled patients with stage IV NSCLC, three or fewer metastases, and no progression at 3 or more months after front-line systemic therapy. Patients were randomly assigned (1:1) to maintenance therapy or observation (MT/O) or to LCT to all active disease sites. The primary end point was PFS; secondary end points were OS, toxicity, and the appearance of new lesions. All analyses were two sided, and P values less than . 10 were deemed significant. RESULTS The Data Safety and Monitoring Board recommended early trial closure after 49 patients were randomly assigned because of a significant PFS benefit in the LCT arm. With an updated median follow-up time of 38.8 months (range, 28.3 to 61.4 months), the PFS benefit was durable (median, 14.2 months [95% CI, 7.4 to 23.1 months] with LCT v 4.4 months [95% CI, 2.2 to 8.3 months] with MT/O; P = .022). We also found an OS benefit in the LCT arm (median, 41.2 months [95% CI, 18.9 months to not reached] with LCT v 17.0 months [95% CI, 10.1 to 39.8 months] with MT/O; P = .017). No additional grade 3 or greater toxicities were observed. Survival after progression was longer in the LCT group (37.6 months with LCT v 9.4 months with MT/O; P = .034). Of the 20 patients who experienced progression in the MT/O arm, nine received LCT to all lesions after progression, and the median OS was 17 months (95% CI, 7.8 months to not reached). CONCLUSION In patients with oligometastatic NSCLC that did not progress after front-line systemic therapy, LCT prolonged PFS and OS relative to MT/O.
Convolutional neural networks automate detection for tracking of submicron-scale particles in 2D and 3D

Significance The increasing availability of powerful light microscopes capable of collecting terabytes of high-resolution 2D and 3D videos in a single day has created a great demand for automated image analysis tools. Tracking the movement of nanometer-scale particles (e.g., virus, proteins, and synthetic drug particles) is critical for understanding how pathogens breach mucosal barriers and for the design of new drug therapies. Our advancement is to use an artificial neural network that provides, first and foremost, substantially improved automation. Additionally, our method improves accuracy compared with current methods and reproducibility across users and laboratories. Particle tracking is a powerful biophysical tool that requires conversion of large video files into position time series, i.e., traces of the species of interest for data analysis. Current tracking methods, based on a limited set of input parameters to identify bright objects, are ill-equipped to handle the spectrum of spatiotemporal heterogeneity and poor signal-to-noise ratios typically presented by submicron species in complex biological environments. Extensive user involvement is frequently necessary to optimize and execute tracking methods, which is not only inefficient but introduces user bias. To develop a fully automated tracking method, we developed a convolutional neural network for particle localization from image data, comprising over 6,000 parameters, and used machine learning techniques to train the network on a diverse portfolio of video conditions. The neural network tracker provides unprecedented automation and accuracy, with exceptionally low false positive and false negative rates on both 2D and 3D simulated videos and 2D experimental videos of difficult-to-track species.
Clinical advances of siRNA therapeutics

Small interfering RNA (siRNA) enables efficient target gene silencing by employing a RNA interference (RNAi) mechanism, which can compromise gene expression and regulate gene activity by cleaving mRNA or repressing its translation. Twenty years after the discovery of RNAi in 1998, ONPATTRO™ (patisiran) (Alnylam Pharmaceuticals, Inc.), a lipid formulated siRNA modality, was approved for the first time by United States Food and Drug Administration and the European Commission in 2018. With this milestone achievement, siRNA therapeutics will soar in the coming years. Here, we review the discovery and the mechanisms of RNAi, briefly describe the delivery technologies of siRNA, and summarize recent clinical advances of siRNA therapeutics.
Determinants of Non-Vaccination against Pandemic 2009 H1N1 Influenza in Pregnant Women: A Prospective Cohort Study

Background In October 2009, the French government organized a national-wide, free of charge vaccination campaign against pandemic H1N1 influenza virus, especially targeting pregnant women, a high risk group for severe illness. The study objective was to evaluate pandemic flu vaccine uptake and factors associated with non-vaccination in a population of pregnant women. Methodology/Principal Findings In a prospective cohort conducted in 3 maternity hospitals in Paris, 882 pregnant women were randomly included between October 12, 2009 and February 3, 2010, with the aim to study characteristics of pandemic influenza during pregnancy. At inclusion, socio-demographic, medical, obstetrical factors and those associated with a higher risk of flu exposition and disease-spreading were systematically collected. Pandemic flu vaccine uptake was checked until delivery. 555 (62.9%) women did not get vaccinated. Determinants associated with non-vaccination in a multivariate logistic regression were: geographic origin (Sub-Saharan African origin, adjusted Odd Ratio aOR = 5.4[2.3–12.7], North African origin, aOR = 2.5[1.3–4.7] and Asian origin, aOR = 2.1[1.7–2.6] compared to French and European origin) and socio-professional categories (farmers, craftsmen and tradesmen, aOR = 2.3[2.0–2.6], intermediate professionals, aOR = 1.3[1.0–1.6], employees and manual workers, aOR = 2.5[1.4–4.4] compared to managers and intellectual professionals). The probability of not receiving pandemic flu vaccine was lower among women vaccinated against seasonal flu in the previous 5 years (aOR = 0.6[0.4–0.8]) and among those who stopped smoking before or early during pregnancy (aOR = 0.6[0.4–0.8]). Number of children less than 18 years old living at home, work in contact with children or in healthcare area, or professional contact with the public, were not associated with a higher vaccine uptake. Conclusions/Significance In this cohort of pregnant women, vaccine coverage against pandemic 2009 A/H1N1 flu was low, particularly in immigrant women and those having a low socio-economic status. To improve its effectiveness, future vaccination campaign for pregnant women should be more specifically tailored for these populations.
Real life outcomes of patients aged ≥75 years old with acute promyelocytic leukemia: experience of the PETHEMA registry

Abstract Acute promyelocytic leukemia is infrequent among patients aged ≥75 years old, a population that is rarely eligible for clinical protocols. This study aims to analyze the treatment strategies and clinical outcomes of very old APL patients reported to the international PETHEMA registry. Between 1997 and 2017, among 2501 APL cases registered 120 were ≥75 years old. Treatment approaches were: AIDA regimen, 79 patients; ATRA alone, 23; 16, supportive care (SC) and 2, other strategies. Patients treated with AIDA were younger, had better ECOG and lower leukocytes. Complete remission (CR) was achieved in 65% of AIDA-group vs. 45% in the ATRA-group, being infections followed by bleeding the most frequent causes of induction death. Patients in CR after AIDA showed 3-year DFS of 73%. Our real-life series of very old APL patients provides a reference basis for future treatment strategies aiming to improve clinical outcomes in this challenging population.
Simulating Star Formation and Feedback in Galactic Disk Models

We use a high-resolution grid-based hydrodynamics method to simulate the multiphase interstellar medium (ISM) in a quiescent Milky Way-sized disk galaxy. The models are global and three-dimensional, and they include a treatment of star formation and feedback. We examine the formation of gravitational instabilities and show that a form of the Toomre instability criterion can successfully predict where star formation will occur. Two common prescriptions for star formation are investigated. The first is based on cosmological simulations and has a relatively low threshold for star formation but also enforces a comparatively low efficiency. The second only permits star formation above a number density of 103 cm-3 but adopts a high efficiency. We show that both methods can reproduce the observed slope of the relationship between star formation and gas surface density (although at too high a rate for our adopted parameters). A run that includes feedback from Type II supernovae is successful at driving gas out of the plane, most of which falls back onto the disk. This feedback also substantially reduces the star formation rate. Finally, we examine the density and pressure distribution of the ISM and show that there is a rough pressure equilibrium in the disk, but with a wide range of pressures at a given location (and even wider for the case including feedback).
Humans and Chimpanzees Display Opposite Patterns of Diversity in Arylamine N-Acetyltransferase Genes

Among the many genes involved in the metabolism of therapeutic drugs, human arylamine N-acetyltransferases (NATs) genes have been extensively studied, due to their medical importance both in pharmacogenetics and disease epidemiology. One member of this small gene family, NAT2, is established as the locus of the classic human acetylation polymorphism in drug metabolism. Current hypotheses hold that selective processes favoring haplotypes conferring lower NAT2 activity have been operating in modern humans’ recent history as an adaptation to local chemical and dietary environments. To shed new light on such hypotheses, we investigated the genetic diversity of the three members of the NAT gene family in seven hominid species, including modern humans, Neanderthals and Denisovans. Little polymorphism sharing was found among hominids, yet all species displayed high NAT diversity, but distributed in an opposite fashion in chimpanzees and bonobos (Pan genus) compared to modern humans, with higher diversity in Pan species at NAT1 and lower at NAT2, while the reverse is observed in humans. This pattern was also reflected in the results returned by selective neutrality tests, which suggest, in agreement with the predicted functional impact of mutations detected in non-human primates, stronger directional selection, presumably purifying selection, at NAT1 in modern humans, and at NAT2 in chimpanzees. Overall, the results point to the evolution of divergent functions of these highly homologous genes in the different primate species, possibly related to their specific chemical/dietary environment (exposome) and we hypothesize that this is likely linked to the emergence of controlled fire use in the human lineage.
A Viral microRNA Cluster Regulates the Expression of PTEN, p27 and of a bcl-2 Homolog

The Epstein-Barr virus (EBV) infects and transforms B-lymphocytes with high efficiency. This process requires expression of the viral latent proteins and of the 3 miR-BHRF1 microRNAs. Here we show that B-cells infected by a virus that lacks these non-coding RNAs (Δ123) grew more slowly between day 5 and day 20, relative to wild type controls. This effect could be ascribed to a reduced S phase entry combined with a moderately increased apoptosis rate. Whilst the first phenotypic trait was consistent with an enhanced PTEN expression in B-cells infected with Δ123, the second could be explained by very low BHRF1 protein and RNA levels in the same cells. Indeed, B-cells infected either by a recombinant virus that lacks the BHRF1 protein, a viral bcl-2 homolog, or by Δ123 underwent a similar degree of apoptosis, whereas knockouts of both BHRF1 microRNAs and protein proved transformation-incompetent. We find that that the miR-BHRF1-3 seed regions, and to a lesser extent those of miR-BHRF1-2 mediate these stimulatory effects. After this critical period, B-cells infected with the Δ123 mutant recovered a normal growth rate and became more resistant to provoked apoptosis. This resulted from an enhanced BHRF1 protein expression relative to cells infected with wild type viruses and correlated with decreased p27 expression, two pro-oncogenic events. The upregulation of BHRF1 can be explained by the observation that large BHRF1 mRNAs are the source of BHRF1 protein but are destroyed following BHRF1 microRNA processing, in particular of miR-BHRF1-2. The BHRF1 microRNAs are unlikely to directly target p27 but their absence may facilitate the selection of B-cells that express low levels of this protein. Thus, the BHRF1 microRNAs allowed a time-restricted expression of the BHRF1 protein to innocuously expand the virus B-cell reservoir during the first weeks post-infection without increasing long-term immune pressure.
Protein tyrosine phosphatase 1B regulates the activity of retinal pigment epithelial cells

Purpose To determine whether protein tyrosine phosphatase 1B (PTP1B) is expressed in rat retinal pigment epithelium (RPE) cells, to evaluate whether inhibition of PTP1B contributes to initiation of RPE cells into an active state, and to investigate the signaling pathways involved in this process. Methods Rat retinas were detached by trans-scleral injection of 1.4% sodium hyaluronate into the subretinal space. Immunocytochemistry evaluated the expression of PTP1B in RPE cells located at normal and detached retinas. From the cultured RPE cells treated with TCS-401, cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetracolium bromide assay, and the protein expression levels of cyclin A and cyclin D1 were determined. The effect of TCS-401 on cell differentiation was confirmed by immunostaining for α-smooth muscle actin and by western blot. Cell migration activity and PTP1B signaling mechanism were determined. Migration Assay was used to evaluate cell migration activity. PTP1B signaling mechanism was determined by use of PD98059 and LY294002. Results PTP1B was expressed in the RPE layer of the normal retina. After retinal detachment, weak immunolabeling of PTP1B was seen in the RPE cells. TCS-401 promoted the proliferation and expression of cyclin A and cyclin D1 in RPE cells. TCS-401 induced RPE cells to differentiate toward better contractility and motility. A migration assay proved that inhibiting PTP1B improved the migratory activity of RPE cells. TCS-401 activated extracellular signal-regulated kinase (Erk) and protein kinase B (Akt) phosphorylation. Pretreatment with PD98059 and LY294002 abolished TCS-401-induced activation of Erk, Akt, cell proliferation, and cell migration. Conclusions PTP1B may be involved in regulating the active state of RPE cells. The inhibition of PTP1B promoted the proliferation, myofibroblast differentiation, and migration of RPE cells, and MEK/Erk and PI3K/Akt signaling pathways played important roles in the proliferation and migration process.
Effects of Intestinal Microbial–Elaborated Butyrate on Oncogenic Signaling Pathways

The intestinal microbiota is well known to have multiple benefits on human health, including cancer prevention and treatment. The effects are partially mediated by microbiota-produced short chain fatty acids (SCFAs) such as butyrate, propionate and acetate. The anti-cancer effect of butyrate has been demonstrated in cancer cell cultures and animal models of cancer. Butyrate, as a signaling molecule, has effects on multiple signaling pathways. The most studied effect is its inhibition on histone deacetylase (HDAC), which leads to alterations of several important oncogenic signaling pathways such as JAK2/STAT3, VEGF. Butyrate can interfere with both mitochondrial apoptotic and extrinsic apoptotic pathways. In addition, butyrate also reduces gut inflammation by promoting T-regulatory cell differentiation with decreased activities of the NF-κB and STAT3 pathways. Through PKC and Wnt pathways, butyrate increases cancer cell differentiation. Furthermore, butyrate regulates oncogenic signaling molecules through microRNAs and methylation. Therefore, butyrate has the potential to be incorporated into cancer prevention and treatment regimens. In this review we summarize recent progress in butyrate research and discuss the future development of butyrate as an anti-cancer agent with emphasis on its effects on oncogenic signaling pathways. The low bioavailability of butyrate is a problem, which precludes clinical application. The disadvantage of butyrate for medicinal applications may be overcome by several approaches including nano-delivery, analogue development and combination use with other anti-cancer agents or phytochemicals.
Kinetic Evaluation of Dye Decolorization by Fenton Processes in the Presence of 3-Hydroxyanthranilic Acid

The fungal metabolite 3-hydroxyanthranilic acid (3-HAA) was used as a redox mediator with the aim of increasing dye degradation by Fenton oxidative processes (Fe2+/H2O2, Fe3+/H2O2). Its Fe3+-reducing activity can enhance the generation of reactive oxygen species as HO● radicals. Initially, the influence of 3-HAA on decolorization kinetics of five dyes (methylene blue, chromotrope 2R, methyl orange, phenol red, and safranin T) was investigated using decolorization data from a previous work conducted by the present research group. Fe3+-containing reaction data were well fitted with first-order and mainly second-order kinetic models, whereas the BMG (Behnajady, Modirshahla and Ghanbary) model obtained optimal fit to Fe2+. Improvements in kinetic parameters (i.e., apparent rate constants and maximum oxidation capacity) were observed with the addition of 3-HAA. In another set of experiments, a decrease in apparent activation energy was observed due to introducing 3-HAA into reactions containing either Fe2+ or Fe3+ in order to decolorize phenol red at different temperatures. This indicates that the redox mediator decreases the energy barrier so as to allow reactions to occur. Thus, based on recent experiments and the reaction kinetics models evaluated herein, pro-oxidant properties have been observed for 3-HAA in Fenton processes.