Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial.

Importance An intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain. Objective To determine whether a higher level of PEEP with alveolar recruitment maneuvers decreases postoperative pulmonary complications in obese patients undergoing surgery compared with a lower level of PEEP. Design, Setting, and Participants Randomized clinical trial of 2013 adults with body mass indices of 35 or greater and substantial risk for postoperative pulmonary complications who were undergoing noncardiac, nonneurological surgery under general anesthesia. The trial was conducted at 77 sites in 23 countries from July 2014-February 2018; final follow-up: May 2018. Interventions Patients were randomized to the high level of PEEP group (n = 989), consisting of a PEEP level of 12 cm H2O with alveolar recruitment maneuvers (a stepwise increase of tidal volume and eventually PEEP) or to the low level of PEEP group (n = 987), consisting of a PEEP level of 4 cm H2O. All patients received volume-controlled ventilation with a tidal volume of 7 mL/kg of predicted body weight. Main Outcomes and Measures The primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including respiratory failure, acute respiratory distress syndrome, bronchospasm, new pulmonary infiltrates, pulmonary infection, aspiration pneumonitis, pleural effusion, atelectasis, cardiopulmonary edema, and pneumothorax. Among the 9 prespecified secondary outcomes, 3 were intraoperative complications, including hypoxemia (oxygen desaturation with Spo2 ≤92% for >1 minute). Results Among 2013 adults who were randomized, 1976 (98.2%) completed the trial (mean age, 48.8 years; 1381 [69.9%] women; 1778 [90.1%] underwent abdominal operations). In the intention-to-treat analysis, the primary outcome occurred in 211 of 989 patients (21.3%) in the high level of PEEP group compared with 233 of 987 patients (23.6%) in the low level of PEEP group (difference, -2.3% [95% CI, -5.9% to 1.4%]; risk ratio, 0.93 [95% CI, 0.83 to 1.04]; P = .23). Among the 9 prespecified secondary outcomes, 6 were not significantly different between the high and low level of PEEP groups, and 3 were significantly different, including fewer patients with hypoxemia (5.0% in the high level of PEEP group vs 13.6% in the low level of PEEP group; difference, -8.6% [95% CI, -11.1% to 6.1%]; P < .001). Conclusions and Relevance Among obese patients undergoing surgery under general anesthesia, an intraoperative mechanical ventilation strategy with a higher level of PEEP and alveolar recruitment maneuvers, compared with a strategy with a lower level of PEEP, did not reduce postoperative pulmonary complications. Trial Registration ClinicalTrials.gov Identifier: NCT02148692.
Tissue-Specific Progenitor and Stem Cells Engineered Mesenchymal Cells Improve Passive ImmuneProtectionAgainst LethalVenezuelanEquine Encephalitis Virus Exposure

Mesenchymal stromal cells (MSCs) arebeingexploitedasgenedeliveryvectors for variousdiseaseand injury therapies. We provide proof-of-concept that engineered MSCs can provide a useful, effective platform for protection against infectious disease. Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne pathogen affecting humans and equines and can be used in bio-warfare. No licensed vaccine or antiviral agent currently exists to combat VEEV infection in humans. Direct antibody administration (passive immunity) is an effective, but short-lived, method of providing immediate protectionagainst apathogen.Wecompared theprotectiveefficacyofhumanumbilical cordperivascular cells (HUCPVCs; a rich source of MSCs), engineered with a transgene encoding a humanized VEEVneutralizing antibody (anti-VEEV), to the purified antibody. In athymic mice, the anti-VEEV antibody had a half-life of 3.7 days, limiting protection to 2 or 3 days after administration. In contrast, engineered HUCPVCs generated protective anti-VEEV serum titers for 21–38 days after a single intramuscular injection. At 109 days after transplantation, 10% of the mice still had circulating anti-VEEV antibody. The mice were protected against exposure to a lethal dose of VEEV by an intramuscular pretreatment injection with engineered HUCPVCs 24 hours or 10 days before exposure, demonstratingboth rapid andprolonged immuneprotection. Thepresent study is the first todescribe engineered MSCs as gene delivery vehicles for passive immunity and supports their utility as antibody delivery vehicles for improved, single-dose prophylaxis against endemic and intentionally disseminated pathogens. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1–10
Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma*

Glioblastoma is an aggressive brain tumor, thus early detection and immunotherapy may improve survival. This study includes large-scale analyses of the peptidome of the plasma-soluble HLA molecules of Glioblastoma patients and healthy controls, and the membranal HLA of the patients' tumors. These HLA peptidomes contain many HLA peptides derived from tumor antigens, providing potential opportunities for early diagnosis, and possibly also for personalized immunotherapy. The results emphasize the usefulness of the plasma-soluble HLA peptidomes as a source for biomarkers. Graphical Abstract Highlights The plasma-soluble HLA peptidome of Glioblastoma contains many tumor antigens. This sHLA peptidome may serve as a rich source for disease biomarkers. The sHLA peptidomes are highly correlated with the tumor's membranal HLA peptidomes. The HLA peptidomes differ significantly from the proteomes of the tumors. Glioblastoma multiforme (GBM) is the most aggressive brain tumor with poor prognosis to most patients. Immunotherapy of GBM is a potentially beneficial treatment option, whose optimal implementation may depend on familiarity with tumor specific antigens, presented as HLA peptides by the GBM cells. Further, early detection of GBM, such as by a routine blood test, may improve survival, even with the current treatment modalities. This study includes large-scale analyses of the HLA peptidome (immunopeptidome) of the plasma-soluble HLA molecules (sHLA) of 142 plasma samples, and the membranal HLA of GBM tumors of 10 of these patients' tumor samples. Tumor samples were fresh-frozen immediately after surgery and the plasma samples were collected before, and at multiple visits after surgery. In total, this HLA peptidome analysis involved 52 different HLA allotypes and resulted in the identification of more than 35,000 different HLA peptides. Strong correlations were observed in the signal intensities and in the repertoires of identified peptides between the tumors and plasma-soluble HLA peptidomes of the individual patients, whereas low correlations were observed between these HLA peptidomes and the tumors' proteomes. HLA peptides derived from Cancer/Testis Antigens (CTAs) were selected based on their presence among the HLA peptidomes of the patients and absence of expression of their source genes from any healthy and essential human tissues, except from immune-privileged sites. Additionally, peptides were selected as potential biomarkers if their levels in the plasma-sHLA peptidome were significantly reduced after the removal of tumor mass. The CTAs identified among the analyzed HLA peptidomes provide new opportunities for personalized immunotherapy and for early diagnosis of GBM.
Altered Gray Matter Volume and White Matter Integrity in Sensorineural Hearing Loss Patients: A VBM and TBSS Study.

OBJECTIVE The purpose of the present study was to detect structural changes in the brains of patients with sensorineural hearing loss (SNHL) by combining voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS). METHODS Thirty-five patients with SNHL (mean age: 39.72 ± 1.81 yr) and 23 age-matched control subjects (mean age: 39.83 ± 1.96 yr) were assessed using three-dimensional, T1-weighted imaging, and diffusion tensor imaging. TBSS and VBM analyses were performed to evaluate grey matter (GM) volume changes and white matter (WM) alternations, as measured by mean diffusivity (MD), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD). RESULTS VBM showed decreased GM volume in patients with SNHL in the fusiform gyrus of the right temporal lobe and right middle occipital gyrus. TBSS revealed WM integrity changes, including decreased FA and RD and increased RD in several WM regions. However, MD showed no significant difference between patients with SNHL and age-matched controls. CONCLUSION Patients with SNHL showed smaller GM volume and WM integrity changes in several regions.
An Investigation into the design of an Interface for Interaction with a Virtual Environment representing a four-dimensional object

Five methods of mapping the input from a six-degrees-of-freedom input device to the set of rotations available in four-dimensional space are evaluated with respect to how well they can be used to perform four-dimensional target aquisition tasks. Also evaluated are the user's opinions of the methods of interaction. Two of the five interaction methods perform significantly better than the rest allowing some general results to be drawn.
A Multiagent Traffic Management Framework for Cooperative Intelligent Transportation Systems

—The rapid growth experienced by many cities has created huge pressures on their traffic and transport systems. One common solution consists of increasing the number of roads available, but is not always the most appropriate. The application of Information and Communications Technologies enabling more efficient and effective use of the existing transport infrastructure is necessary (also known as Intelligent Transportation Systems). Furthermore, cooperation between vehicles and infrastructure is currently studied under the name of Cooperative Intelligent Transportation Systems. This paper proposes a traffic management framework based on agents that enable users to make better use of traffic and transport infrastructure by cooperating with infrastructure. We also propose a parallel algorithm to determine the K-routes for the drivers.
Effect of Load Capacitance and Input Transition Time on FinFET Inverter Capacitances

FinFETs are poised to replace conventional MOSFETs at sub-22-nm technology nodes mainly due to their relatively planar compatible fabrication process. It is well known that FinFET device parasitics are critical for the propagation delay and power dissipation. However, a quantitative understanding of device parasitics for circuit design is yet to be attained. We report a new extension transistor-induced capacitance shielding (ETICS) phenomenon. In this phenomenon, the FinFET extension region forms a transistor, which shields gate-extension fringing field capacitance. Due to this phenomenon, we observe a strong dependence of effective values of FinFET logic gate capacitances on transition times of their terminal voltages, which is unlike the conventional transistors. We show that delay estimation methods need to be modified considering ETICS for efficient FinFET circuit design.
Facile Synthesis of Monodispersed α-Ni(OH)2 Microspheres Assembled by Ultrathin Nanosheets and Its Performance for Oxygen Evolution Reduction

Electrocatalytic water splitting is an efficient route to generate renewable energy sources, in which the noble metal materials are usually used as electrocatalysts. But the high price and scarcity of these catalysts impede their large-scale applications. Ni-based materials are considered to be the most suitable catalytic materials to substitute these noble metal materials. In this paper, the monodispersed α-Ni(OH)2 microspheres assembled by ultrathin nanosheets were synthesized by a facile solvothermal method. This method was surfactant-free and no any precipitator was used. The as-obtained products were well characterized by X-ray diffraction (XRD), field emission scanning electron microscope (FESEM), transmission electron microscope (TEM), thermal gravimetric (TG) analysis, and X-ray photoelectron spectroscopy (XPS). The results of N2 adsorption/desorption isotherm indicate that the BET surface area of the products was 169.94 m2g-1, and the pore-size distribution centered at 3.5 nm. Then, the electrochemical properties were evaluated by linear sweep voltammetry (LSV) in 1 M KOH. At a current density of 10 mA cm2, the overpotential for the α-Ni(OH)2-MS is 320mV, and the Tafel slope is 98.7 mV dec-1, indicating its excellent reaction kinetics for an efficient catalyst toward oxygen evolution reaction (OER).
Structure and functional characterization of 4-hydroxyphenylacetate 3-hydroxylase from Escherichia coli.

Hydroxylation of phenols into polyphenols, valuable chemical and pharmaceutical products, is a challenging reaction. The search for green synthetic processes has led to considering microorganisms as well as pure hydroxylases as catalysts for phenol hydroxylation. Here we report the structural and functional characterization of the FAD-dependent 4-hydroxyphenylacetate 3-monooxygenase from Escherichia coli, named HpaB. We show that this enzyme enjoys a relatively broad substrate specificity, allowing conversion of a number of non-natural phenolic compounds such as tyrosol, hydroxymandelic acid, coumaric acid, hydroxybenzoic acid and its methyl ester and phenol into the corresponding catechols. The reaction can be carried out using a simple chemical assay based on formate as the electron donor and the organometallic complex [Cp*Rh(bpy)(H2O)]2+ as the catalyst for FAD reduction. The availability of a crystal structure of HpaB in complex with FAD 1.8 Å resolution opens the possibility of rational tuning of the substrate specificity and the activity of this interesting class of phenol hydroxylases.
Probiotics Lactobacillus reuteri Abrogates Immune Checkpoint Blockade-Associated Colitis by Inhibiting Group 3 Innate Lymphoid Cells

Immune checkpoint blockade (ICB) immunotherapy increases antitumor immunity by blocking cytotoxic-T-lymphocyte-associated protein 4 (CTLA-4) or programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and displays robust clinical responses in various cancers. However, ICB immunotherapy also triggers severe inflammatory side effects, known as immune-related adverse effects (irAEs). One of the most common toxicities is immune checkpoint blockade-associated colitis (ICB associated colitis). The exact mechanism of ICB associated colitis remains to be explored. Here, we combined ICB (anti–CTLA-4 and anti-PD-1) treatment with a standard colitis model, in which a more severe form of colitis is induced in mice, to recapitulate the clinical observations in patients receiving combined ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) therapy, during which colitis is the most frequent complication encountered. We found that the composition of the gut microbiota changed in ICB associated colitis. Principal component analysis of the gut microbiome showed an obvious reduction in the abundance of Lactobacillus in severe ICB associated colitis. Lactobacillus depletion completely by vancomycin augmented the immunopathology of ICB. Furthermore, we found that the ICB toxicity could be totally eliminated via the administration of a widely available probiotic Lactobacillus reuteri (L.reuteri). Oral administration of L. reuteri therapeutically inhibited the development and progression of colitis, thus ameliorating the loss of body weight and inflammatory status induced by ICB treatment. Mechanistically, the protective effect of L. reuteri was associated with a decrease in the distribution of group 3 innate lymphocytes (ILC3s) induced by ICB associated colitis. In conclusion, our study highlights the immunomodulatory mechanism of the gut microbiota and suggests that manipulating the gut microbiota by administrating L. reuteri can mitigate the autoimmunity induced by ICB, thus allowing ICB immunotherapy to stimulate the desired immune response without an apparent immunopathology.
Intravenous versus inhalational techniques for rapid emergence from anaesthesia in patients undergoing brain tumour surgery

Early and rapid emergence from anaesthesia after brain tumour surgery allows prompt neurological assessment and early detection of complications that require immediate intervention. Many different classes of drugs have been used during neurosurgical anaesthesia. The systematic review determined the effects of intravenous compared with inhalational anaesthetic drugs for rapid emergence from anaesthesia in patients undergoing brain tumour surgery.
Management of Hypertension in CAKUT: Protective Factor for CKD

Patients with congenital kidney and urinary tract abnormalities (CAKUT) will often develop end-stage renal disease at some point and the need for renal replacement therapy is associated with high rates of morbidity and mortality. Hence, efforts to slow the progression of the disease are essential. Hypertension has been proven to be an independent risk factor for faster decline of glomerular filtration rate in renal patients, but studies involving only children with CAKUT are scarce. We performed a literature review to explore the association of hypertension with faster chronic kidney disease progression in children with CAKUT and also treatment options in this condition. A recent study reported an annual decline in GFR of 1.8 ml/min/1.73 m2 among hypertensive patients with non-glomerular CKD, compared with 0.8 ml/min/1.73 m2 in normotensive children. A multicenter prospective cohort in Brazil showed that a 1-unit increase in systolic blood pressure Z-score was associated with a 1.5-fold higher risk of disease progression. Since renin-angiotensin-aldosterone system activation is the most important mechanism of hypertension in these children, the first-line therapy involves the use of inhibitors of this axis, including angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers type I, which also promote an anti-fibrotic effect. Recent studies have shown a good safety profile for use in patients with chronic kidney disease and also in those with solitary kidneys. Hypertension is an independent risk factor for kidney disease progression and should be promptly managed for renal protection, especially among patients with CAKUT, the primary cause of chronic kidney disease in the pediatric population.
RNA-Seq Revealed Novel Non-proliferative Retinopathy Specific Circulating MiRNAs in T2DM Patients

Background: Diabetic retinopathy (DR) is a common diabetes complication and was considered as the major cause of blindness among young adults. MiRNAs are a group of small non-coding RNAs regulating the expression of target genes and have been reported to be associated with the development of DR in a variety of molecular mechanisms. In this study, we aimed to identify miRNAs that are differentially expressed (DE) in the serum of DR patients. Methods: We recruited 21 type 2 diabetes mellitus (T2DM) inpatients of Chinese Han ancestry, consisting of 10 non-proliferative DR patients (DR group) and 11 non-DR T2DM patients (NDR group). MiRNA was extracted from fasting peripheral serum and quantified by RNA-seq. The expression levels of miRNA were evaluated and compared between the two groups, with adjustments made for age differences. The validated target genes of miRNAs were subjected to a pathway analysis. We also constructed a weighted polygenic risk score using the DE miRNA and evaluated its predictive power. Results: Five miRNAs were DE between DR and NDR groups (p-Value ≤ 0.01, LFC ≥ 2 or LFC ≤-2). These included miR-4448, miR-338-3p, miR-190a-5p, miR-485-5p, and miR-9-5p. In total, these miRNAs were validated to regulate 55 target genes. Four target genes were found to overlap with the NAD metabolism, sirtuin, and aging pathway, which was thought to control the vascular growth and morphogenesis. The predictive power of our polygenic risk score was apparently high (AUC = 0.909). However, it needs to be interpreted with caution. Conclusion: In this study, we discovered novel DR-specific miRNAs in human serum samples. These circulating miRNAs may represent the pathological changes in the retina in response to diabetes and may serve as non-invasive biomarkers for early DR risk prediction.
Co-enhance bioactive of polymer scaffold with mesoporous silica and nano-hydroxyapatite

Abstract Mesoporous silica Santa Barbara Amorphous-15 (SBA15) and nano-hydroxyapatite (nHA) were introduced in poly-l-lactic acid (PLLA) scaffold fabricated by selective laser sintering to co-enhance the bioactivity. On the one hand, the active elements silicon and calcium released respectively by the degradation of SBA15 and nHA were favorable for stimulating cell response. On the other hand, the hydrated silica gel layer derived from SBA15 could adsorb calcium ions released from nHA, thereby co-promoting apatite nucleation and growth. The experimental results showed that the formation of bone-like apatite on the scaffold was accelerated under simulated body fluid, indicating a good biomineralization capacity. Moreover, the scaffold demonstrated a good cell response in promoting the attachment of cell and the expression of alkaline phosphatase activity. Besides, SBA15 and nHA not only improved the hydrophilicity of the scaffold (the water contact angle changed from 107.4° to 57.8°), but also retarded the pH reduction by neutralizing the acidic hydrolysate of PLLA. These results indicated that the PLLA-SBA15-nHA scaffold may be potential candidates for bone repair.
Document segmentation via oblique cuts

This paper presents a novel solution for the layout segmentation of graphical elements in Business Intelligence documents. We propose a generalization of the recursive X-Y cut algorithm, which allows for cutting along arbitrary oblique directions. An intermediate processing step consisting of line and solid region removal is also necessary due to presence of decorative elements. The output of the proposed segmentation is a hierarchical structure which allows for the identification of primitives in pie and bar charts. The algorithm was tested on a database composed of charts from business documents. Results are very promising.
Occurrence of nodular gill disease in farmed brown trout (Salmo trutta L.).

1 Department of Comparative Biomedicine and Food Science, University of Padova, Legnaro, Italy 4 2 Department of Veterinary Medical Sciences, Alma Mater Studiorum University of Bologna, Ozzano d’Emilia, Italy 5 3 Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy 6 4 Fondazione Edmund Mach, San Michele all’Adige, Italy 7 5 Skretting Italia, Mozzecane, Italy 8 9