Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein S-Glutathionylation Mediates Macrophage Responses to Metabolic Cues from the Extracellular Environment.

AIMS Protein S-glutathionylation, the formation of a mixed disulfide between glutathione and protein thiols, is an oxidative modification that has emerged as a new signaling paradigm, potentially linking oxidative stress to chronic inflammation associated with heart disease, diabetes, cancer, lung disease, and aging. Using a novel, highly sensitive, and selective proteomic approach to identify S-glutathionylated proteins, we tested the hypothesis that monocytes and macrophages sense changes in their microenvironment and respond to metabolic stress by altering their protein thiol S-glutathionylation status. RESULTS We identified over 130 S-glutathionylated proteins, which were associated with a variety of cellular functions, including metabolism, transcription and translation, protein folding, free radical scavenging, cell motility, and cell death. Over 90% of S-glutathionylated proteins identified in metabolically stressed THP-1 monocytes were also found in hydrogen peroxide (H2O2)-treated cells, suggesting that H2O2 mediates metabolic stress-induced protein S-glutathionylation in monocytes and macrophages. We validated our findings in mouse peritoneal macrophages isolated from both healthy and dyslipidemic atherosclerotic mice and found that 52% of the S-glutathionylated proteins found in THP-1 monocytes were also identified in vivo. Changes in macrophage protein S-glutathionylation induced by dyslipidemia were sexually dimorphic. INNOVATION We provide a novel mechanistic link between metabolic (and thiol oxidative) stress, macrophage dysfunction, and chronic inflammatory diseases associated with metabolic disorders. CONCLUSION Our data support the concept that changes in the extracellular metabolic microenvironment induce S-glutathionylation of proteins central to macrophage metabolism and a wide array of cellular signaling pathways and functions, which in turn initiate and promote functional and phenotypic changes in macrophages. Antioxid. Redox Signal. 25, 836-851.
Occupational Noise Exposure and the Risk for Work-Related Injury: A Systematic Review and Meta-analysis

Objectives Occupational noise exposure has been linked to work-related injuries. Strategies to control occupational hazards often rely on dose-response relationships needed to inform policy, but quantitative synthesis of the relevant literature has not been done so far. This study aimed to systematically review the epidemiological literature and to perform meta-analysis of the risk for work-related injury due to occupational noise exposure. Methods PRISMA and MOOSE guidelines were followed. PubMed, ScienceDirect, and Google Scholar were searched up until 15 December 2016 in English, Russian, and Spanish. Reference lists, grey literature, and expert archives were searched as well. The risk of bias was assessed for each study and incorporated into the meta-analysis weights using the quality effects model. Results Overall, 21 studies were included at the qualitative review stage: 9 cross-sectional, 6 case-control, 4 cohort, 1 case-crossover, and 1 ecological. Noise exposure was assessed objectively in 13 studies. Information on occupational injuries was elicited from medical records/registry in 13 studies. Meta-analyses showed RR = 1.22 (95% CI: 1.15, 1.29) (n = 59028) per 5 dB increase in noise exposure (Cochran's Q = 27.26, P < 0.001, I2 = 67%) and RR = 2.16 (95% CI: 1.61, 2.90) (n = 96023) in the most exposed group (>90-95 dB) compared with the least exposed group (Cochran's Q = 180.46, P < 0.001, I2 = 90%). Subgroup analysis with meta-regression revealed an overall robust pooled risk per 5 dB. Conclusions There is a dose-response association between occupational noise exposure and work-related injury risk. However, the quality of evidence is 'very low'; therefore, the magnitude of this association should be interpreted with caution.
Viscoelastic Characterisation of the Temporomandibular Joint Disc in Bovines

Abstract: The aim of this paper was to develop a biomechanical model to reproduce the viscoelastic behaviour of the material of the bovine temporomandibular joint (TMJ) disc, as a substitute material to be applied in subsequent experimental studies of possible human TMJ disorders. As the mechanical properties of the disc change due to different factors, this study is focussed on evaluating its viscoelastic response under compression in stress–relaxation, creep and cycling loading tests, using an equipment that allows us to simulate the real function conditions of the material in a liquid medium at 37 °C. In order to fit the data obtained from the relaxation and creep tests, generalised Maxwell and Kelvin models of eight terms are proposed, leading to Prony’s series of practical interest for subsequent numerical calculations.
Integrating existing natural language processing tools for medication extraction from discharge summaries

OBJECTIVE To develop an automated system to extract medications and related information from discharge summaries as part of the 2009 i2b2 natural language processing (NLP) challenge. This task required accurate recognition of medication name, dosage, mode, frequency, duration, and reason for drug administration. DESIGN We developed an integrated system using several existing NLP components developed at Vanderbilt University Medical Center, which included MedEx (to extract medication information), SecTag (a section identification system for clinical notes), a sentence splitter, and a spell checker for drug names. Our goal was to achieve good performance with minimal to no specific training for this document corpus; thus, evaluating the portability of those NLP tools beyond their home institution. The integrated system was developed using 17 notes that were annotated by the organizers and evaluated using 251 notes that were annotated by participating teams. MEASUREMENTS The i2b2 challenge used standard measures, including precision, recall, and F-measure, to evaluate the performance of participating systems. There were two ways to determine whether an extracted textual finding is correct or not: exact matching or inexact matching. The overall performance for all six types of medication-related findings across 251 annotated notes was considered as the primary metric in the challenge. RESULTS Our system achieved an overall F-measure of 0.821 for exact matching (0.839 precision; 0.803 recall) and 0.822 for inexact matching (0.866 precision; 0.782 recall). The system ranked second out of 20 participating teams on overall performance at extracting medications and related information. CONCLUSIONS The results show that the existing MedEx system, together with other NLP components, can extract medication information in clinical text from institutions other than the site of algorithm development with reasonable performance.
Navigational Instruction Generation as Inverse Reinforcement Learning with Neural Machine Translation

Modern robotics applications that involve human-robot interaction require robots to be able to communicate with humans seamlessly and effectively. Natural language provides a flexible and efficient medium through which robots can exchange information with their human partners. Significant advancements have been made in developing robots capable of interpreting free-form instructions, but less attention has been devoted to endowing robots with the ability to generate natural language. We propose a model that enables robots to generate natural language instructions that allow humans to navigate a priori unknown environments. We first decide which information to share with the user according to their preferences, using a policy trained from human demonstrations via inverse reinforcement learning. We then “translate” this information into a natural language instruction using a neural sequence-to-sequence model that learns to generate free-form instructions from natural language corpora. We evaluate our method on a benchmark route instruction dataset and achieve a BLEU score of 72.18% compared to human-generated reference instructions. We additionally conduct navigation experiments with human participants demonstrating that our method generates instructions that people follow as accurately and easily as those produced by humans.
Biogenic oxidized organic functional groups in aerosol particles from a mountain forest site and their similarities to laboratory chamber products

Abstract. Submicron particles collected at Whistler, British Columbia, at 1020 m a.s. l. during May and June 2008 on Teflon filters were analyzed by Fourier transform infrared (FTIR) and X-ray fluorescence (XRF) techniques for organic functional groups (OFG) and elemental composition. Organic mass (OM) concentrations ranged from less than 0.5 to 3.1 μg m−3, with a project mean and standard deviation of 1.3±1.0 μg m−3 and 0.21±0.16 μg m−3 for OM and sulfate, respectively. On average, organic hydroxyl, alkane, and carboxylic acid groups represented 34%, 33%, and 23% of OM, respectively. Ketone, amine and organosulfate groups constituted 6%, 5%, and
Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer

The aim of this study was to assess the potential effects of palbociclib in combination with letrozole on QTc. PALOMA-2, a phase 3, randomized, double-blind, placebo-controlled trial, compared palbociclib plus letrozole with placebo plus letrozole in postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The study included a QTc evaluation substudy carried out as a definitive QT interval prolongation assessment for palbociclib. Time-matched triplicate ECGs were performed at 0, 2, 4, 6, and 8 h at baseline (Day 0) and on Cycle 1 Day 14. Additional ECGs were collected from all patients for safety monitoring. The QT interval was corrected for heart rate using Fridericia’s correction (QTcF), Bazett’s correction (QTcB), and a study-specific correction factor (QTcS). In total, 666 patients were randomized 2 : 1 to palbociclib plus letrozole or placebo plus letrozole. Of these, 125 patients were enrolled in the QTc evaluation substudy. No patients in the palbociclib plus letrozole arm of the substudy (N=77) had a maximum postbaseline QTcS or QTcF value of ≥ 480 ms, or a maximum increase from clock time-matched baseline for QTcS or QTcF values of ≥ 60 ms. The upper bounds of the one-sided 95% confidence interval for the mean change from time-matched baseline for QTcS, QTcF, and QTcB at all time points and at steady-state Cmax following repeated administration of 125 mg palbociclib were less than 10 ms. Palbociclib, when administered with letrozole at the recommended therapeutic dosing regimen, did not prolong the QT interval to a clinically relevant extent.
The effect of green tea ointment on episiotomy pain and wound healing in primiparous women: A randomized, double‐blind, placebo‐controlled clinical trial

The delayed healing of episiotomy wound and its associated pain is a major problem in obstetrics. Because green tea has analgesic and wound‐healing properties, the present study was conducted to determine the effect of green tea ointment on episiotomy pain and wound‐healing. The green tea extract was also standardized by measuring its Phenolic and flavonoid compounds, antioxidant activity, and one of its active components, that is, Epigallocatechin gallate. The present clinical trial was conducted on 99 primiparous women visiting Afzalipour Hospital in Kerman in 2015. The subjects were randomly divided into 3 groups, including a green tea ointment group, a placebo ointment group, and a routine care group. The 2 ointment groups smeared 2 cm of the green tea or placebo ointments onto their sutured area twice daily for a total of 10 days. The severity of pain was assessed in the subjects using the visual pain scale and wound‐healing using the Redness, Edema, Ecchymosis, Discharge, Approximation (REEDA) scale before the intervention and on the 5th and 10th days after delivery. To standardize the extract, Epigallocatechin gallate was measured by high‐performance liquid chromatography (HPLC). Phenolic and flavonoid compounds, as well as antioxidant activity of the extract were also determined by spectrometry methods. Before the intervention, no significant differences were observed between the 3 groups in terms of their personal and obstetric details (p > .05), the severity of pain (p = .118), and the REEDA score (p = .212). On the 5th and 10th days after delivery, the severity of pain was significantly lower in the green tea group than in the other 2 groups (p < .0001). The mean REEDA score on the 5th and 10th days showed a better and faster healing in the green tea group compared to the other 2 groups (p < .0001). Total content of phenolic and flavonoids contents of green tea were 74.2 mg/g Gallic acid equivalent and 16.3 mg/g Rutin equivalent, respectively, and its antioxidant capacity was 46% of b‐carotene. Green tea ointment appears to be effective in relieving episiotomy pain and improving wound‐healing in this study. Further studies are recommended to be conducted on the effectiveness and safety of the different doses of green tea ointment.
The kinesin motor protein Kif7 is required for T-cell development and normal MHC expression on thymic epithelial cells (TEC) in the thymus

Kif7 is a ciliary kinesin motor protein that regulates mammalian Hedgehog pathway activation through influencing structure of the primary cilium. Here we show that Kif7 is required for normal T-cell development, despite the fact that T-cells lack primary cilia. Analysis of Kif7-deficient thymus showed that Kif7-deficiency increases the early CD44+CD25+CD4-CD8- thymocyte progenitor population but reduces differentiation to CD4+CD8+ double positive (DP) cell. At the transition from DP to mature T-cell, Kif7-deficiency selectively delayed maturation to the CD8 lineage. Expression of CD5, which correlates with TCR signal strength, was reduced on DP and mature CD4 and CD8 cells, as a result of thymocyte-intrinsic Kif7-deficiency, and Kif7-deficient T-cells from radiation chimeras activated less efficiently when stimulated with anti-CD3 and anti-CD28 in vitro. Kif7-deficient thymocytes showed higher expression of the Hedgehog target gene Ptch1 than WT, but were less sensitive to treatment with recombinant Shh, and Kif7-deficient T-cell development was refractory to neutralisation of endogenous Hh proteins, indicating that Kif7-deficient thymocytes were unable to interpret changes in the Hedgehog signal. In addition, Kif7-deficiency reduced cell-surface MHCII expression on thymic epithelial cells.
Maintenance of somatic tissue regeneration with age in short‐ and long‐lived species of sea urchins

Aging in many animals is characterized by a failure to maintain tissue homeostasis and the loss of regenerative capacity. In this study, the ability to maintain tissue homeostasis and regenerative potential was investigated in sea urchins, a novel model to study longevity and negligible senescence. Sea urchins grow indeterminately, regenerate damaged appendages and reproduce throughout their lifespan and yet different species are reported to have very different life expectancies (ranging from 4 to more than 100 years). Quantitative analyses of cell proliferation and apoptosis indicated a low level of cell turnover in tissues of young and old sea urchins of species with different lifespans (Lytechinus variegatus, Strongylocentrotus purpuratus and Mesocentrotus franciscanus). The ability to regenerate damaged tissue was maintained with age as assessed by the regrowth of amputated spines and tube feet (motor and sensory appendages). Expression of genes involved in cell proliferation (pcna), telomere maintenance (tert) and multipotency (seawi and vasa) was maintained with age in somatic tissues. Immunolocalization of the Vasa protein to areas of the tube feet, spines, radial nerve, esophagus and a sub‐population of circulating coelomocytes suggests the presence of multipotent cells that may play a role in normal tissue homeostasis and the regenerative potential of external appendages. The results indicate that regenerative potential was maintained with age regardless of lifespan, contrary to the expectation that shorter lived species would invest less in maintenance and repair.
Table 2 The risk factors and suggestions for the management of NIV failure based on timing

Background: Identifying the predictors of noninvasive ventilation (NIV) failure has attracted significant interest because of the strong link between failure and poor outcomes. However, very little attention has been paid to the timing of the failure. This narrative review focuses on the causes of NIV failure and risk factors and potential remedies for NIV failure, based on the timing factor. Results: The possible causes of immediate failure (within minutes to <1 h) are a weak cough reflex, excessive secretions, hypercapnic encephalopathy, intolerance, agitation, and patient-ventilator asynchrony. The major potential interventions include chest physiotherapeutic techniques, early fiberoptic bronchoscopy, changing ventilator settings, and judicious sedation. The risk factors for early failure (within 1 to 48 h) may differ for hypercapnic and hypoxemic respiratory failure. However, most cases of early failure are due to poor arterial blood gas (ABGs) and an inability to promptly correct them, increased severity of illness, and the persistence of a high respiratory rate. Despite a satisfactory initial response, late failure (48 h after NIV) can occur and may be related to sleep disturbance. Conclusions: Every clinician dealing with NIV should be aware of these risk factors and the predicted parameters of NIV failure that may change during the application of NIV. Close monitoring is required to detect early and late signs of deterioration, thereby preventing unavoidable delays in intubation.
High-throughput analysis of sulfatides in cerebrospinal fluid using automated extraction and UPLC-MS/MS[S]

Sulfatides (STs) are a group of glycosphingolipids that are highly expressed in brain. Due to their importance for normal brain function and their potential involvement in neurological diseases, development of accurate and sensitive methods for their determination is needed. Here we describe a high-throughput oriented and quantitative method for the determination of STs in cerebrospinal fluid (CSF). The STs were extracted using a fully automated liquid/liquid extraction method and quantified using ultra-performance liquid chromatography coupled to tandem mass spectrometry. With the high sensitivity of the developed method, quantification of 20 ST species from only 100 μl of CSF was performed. Validation of the method showed that the STs were extracted with high recovery (90%) and could be determined with low inter- and intra-day variation. Our method was applied to a patient cohort of subjects with an Alzheimer’s disease biomarker profile. Although the total ST levels were unaltered compared with an age-matched control group, we show that the ratio of hydroxylated/nonhydroxylated STs was increased in the patient cohort. In conclusion, we believe that the fast, sensitive, and accurate method described in this study is a powerful new tool for the determination of STs in clinical as well as preclinical settings.
Utility of a repeat renal biopsy in lupus nephritis: a single centre experience

Background The role of repeat renal biopsy in lupus nephritis (LN) to guide treatment or predict prognosis has been controversial. We assessed glomerular and tubulointerstitial histological characteristics of serial renal biopsies, correlations with clinical variables and the impact on subsequent management. Methods Out of a large single-centre cohort of 270 biopsy-proven LN patients, 66 (24%) had serial biopsies. LN classes based on glomerular pathology were defined according to the International Society of Nephrology/Renal Pathology Society 2003 classification, while tubulointerstitial pathologies were evaluated using the revised Austin's semi-quantitative scoring system. Results LN class transitions from proliferative (III and IV) to non-proliferative classes (II and V) were uncommon (n = 4, 7.7%), while non-proliferatives frequently switched to proliferative classes (n = 12, 63.2%) and were more likely to receive increased immunosuppression (P = 0.040). Biochemical or serological variables could not predict these histopathological transitions. Tubulointerstitial score (mean ± standard deviation) progressed from 2.69 ± 2.03 on reference to 3.78 ± 2.03 on repeat biopsy (P = 0.001). Serum creatinine levels correlated with the degree of tubular atrophy on both reference (r = 0.33, P = 0.048) and repeat biopsy (r = 0.56, P < 0.001), and with interstitial scarring (r = 0.60, P < 0.001) on repeat biopsy. Greater interstitial inflammation on reference biopsy was associated with advanced interstitial scarring on repeat biopsies (r = 0.385, P = 0.009). Conclusions Repeat renal biopsy is an important tool to guide management, in particular in those with initial class II or V who flare. Although class transitions cannot be predicted by clinical parameters, serum creatinine level correlates with the degree of tubulointerstitial damage.
Solving Systems of Linear Equations: Locally and Asynchronously

We consider approximating a single component of the solution to a system of linear equations $Ax = b$, where $A$ is an invertible real matrix and $b \in \mathbb{R}^n$. If $A$ is either diagonally dominant or positive definite, we can equivalently solve for $x_i$ in $x = Gx + z$ for some $G$ and $z$ such that spectral radius $\rho(G) < 1$. Existing algorithms either focus on computing the full vector $x$ or use Monte Carlo methods to estimate a component $x_i$ under the condition $\|G\|_{\infty} < 1$. We consider the setting where $n$ is large, yet $G$ is sparse, i.e., each row has at most $d$ nonzero entries. We present synchronous and asynchronous randomized variants of a local algorithm which relies on the Neumann series characterization of the component $x_i$, and allows us to limit the sparsity of the vectors involved in the computation, leading to improved convergence rates. Both variants of our algorithm produce an estimate $\hat{x}_i$ such that $|\hat{x}_i - x_i| \leq \epsilon \|x\|_2$, and we provide convergence guarantees when $\|G\|_2 < 1$. We prove that the synchronous local algorithm uses at most $O(\min(d \epsilon^{\ln(d)/\ln(\|G\|_2)}, dn\ln(\epsilon)/\ln(\|G\|_2)))$ multiplications. The asynchronous local algorithm adaptively samples one coordinate to update among the nonzero coordinates of the current iterate in each time step. We prove with high probability that the error contracts by a time varying factor in each step, guaranteeing that the algorithm converges to the correct solution. With probability at least $1 - \delta$, the asynchronous randomized algorithm uses at most $O(\min(d (\epsilon \sqrt{\delta/5})^{-d/(1-\|G\|_2)}, -dn \ln (\epsilon \sqrt{\delta})/(1-\|G\|_2)))$ multiplications. Thus our algorithms obtain an approximation for $x_i$ in constant time with respect to the size of the matrix when $d = O(1)$ and $1/(1-\|G\|_2) = O(1)$ as a function of $n$.