Miracle-dz/UniFAR-FTUs huggingface dataset:
Duration of Hospitalization and Lung Function Deterioration as Predictors of Future Chronic Obstructive Pulmonary Disease Exacerbations.

and CMV amend the intense respiratory muscle contractions. Accordingly, IL-6 and IL-10 levels after CMV are significantly lower compared with the levels before intubation. This effect is not observed in both control groups, excluding any drugor intubationrelated effect as the reason for the decrease in cytokine levels. Thus, the source of the augmented plasma IL-6 and IL-10 levels during AECOPD above the value observed after 6 hours of CMV could be the strenuously contracting respiratory muscles. The functional roles of respiratory muscle–derived IL-6 and IL-10 are not definitely established. Muscle-derived IL-6 might be signaling that the energy stores within the respiratory muscles are reaching critically low levels (glycogen depletion) and stimulate glycogenolysis in the liver to make glucose available to the strenuously contracting energy-depleted respiratory muscles (8). Thus, after attenuation of strenuous muscular contractions secondary to CMV application, IL-6 is being down-regulated, as the respiratory muscles are no longer energy depleted. Both IL-6 and IL-10 might be produced within the respiratory muscles secondary to oxidative stress development because of strenuous contractions (3, 5). Preliminary results from our laboratory suggest these cytokines are also affecting the control of breathing (9). Eotaxin and EGF are expressed in the COPD lung and are increased in AECOPD (11, 12). Increased bronchoalveolar lavage and plasma eotaxin (eosinophil chemotactic factor) during AECOPD may indicate airway eosinophilia, whereas the activation of the EGF receptor leads to gene expression for mucus secretion. The attenuation of the large negative swings in pleural pressure, and consequently the relief of lung stress after CMV, lead to decreased eotaxin and EGF levels in AECOPD. In conclusion, application of CMV in patients with AECOPD leads to decreased plasma levels for circulating IL-6, IL-10, eotaxin, and EGF. The origin of the augmented level of these cytokines during AECOPD could partly be the strenuously contracting respiratory muscles and/or the mechanically stressed lung. n
Improving sedimentation stability of magnetorheological fluids using an organic molecular particle coating

A key goal for implementation of magnetorheological fluids (MRFs) is to minimize sedimentation or to increase suspension stability. In this study, a series of MRF samples were synthesized by suspending carbonyl iron particles (CIPs), which had different organic molecules and auxiliaries grafted onto their surface, in silicone oil. The magnetorheology of these MRF samples was measured using a magneto-rheometer, and their sedimentation behaviors were quantitatively evaluated using a thermal conductivity sedimentation measurement method. The effect of these coatings on the stability of the MRFs was analyzed. Results show that all of the MRFs exhibit good MR effects and that the surface modification does not greatly weaken the MR effect. Suspension stability was substantially improved by grafting organic molecular structures onto the surface of the CIPs, and the sedimentation rate was influenced by the organic molecule structure. Compared to the uncoated CIPs, when the organic molecule was changed from octyl acyl ethylenediamine triacetate (C7H15COED3A) to lauryl acyl ethylenediamine triacetate (C11H23COED3A) and stearyl acyl ethylenediamine triacetate (C17H35COED3A), the sedimentation rate decreased by 53.9% to 64.2% and 75.1%, respectively. The mechanisms of how organic molecular structure affects the stability of MRFs are discussed.
Neuronal RARβ Signaling Modulates PTEN Activity Directly in Neurons and via Exosome Transfer in Astrocytes to Prevent Glial Scar Formation and Induce Spinal Cord Regeneration

Failure of axonal regeneration in the central nervous system (CNS) is mainly attributed to a lack of intrinsic neuronal growth programs and an inhibitory environment from a glial scar. Phosphatase and tensin homolog (PTEN) is a major negative regulator of neuronal regeneration and, as such, inhibiting its activity has been considered a therapeutic target for spinal cord (SC) injuries (SCIs). Using a novel model of rat cervical avulsion, we show that treatment with a retinoic acid receptor β (RARβ) agonist results in locomotor and sensory recovery. Axonal regeneration from the severed roots into the SC could be seen by biotinylated dextran amine labeling. Light micrographs of the dorsal root entry zone show the peripheral nervous system (PNS)–CNS transition of regrown axons. RARβ agonist treatment also resulted in the absence of scar formation. Mechanism studies revealed that, in RARβ-agonist-treated neurons, PTEN activity is decreased by cytoplasmic phosphorylation and increased secretion in exosomes. These are taken up by astrocytes, resulting in hampered proliferation and causing them to arrange in a normal-appearing scaffold around the regenerating axons. Attribution of the glial modulation to neuronal PTEN in exosomes was demonstrated by the use of an exosome inhibitor in vivo and PTEN siRNA in vitro assays. The dual effect of RARβ signaling, both neuronal and neuronal–glial, results in axonal regeneration into the SC after dorsal root neurotmesis. Targeting this pathway may open new avenues for the treatment of SCIs. SIGNIFICANCE STATEMENT Spinal cord injuries (SCIs) often result in permanent damage in the adult due to the very limited capacity of axonal regeneration. Intrinsic neuronal programs and the formation of a glial scar are the main obstacles. Here, we identify a single target, neuronal retinoic acid receptor β (RARβ), which modulates these two aspects of the postinjury physiological response. Activation of RARβ in the neuron inactivates phosphatase and tensin homolog and induces its transfer into the astrocytes in small vesicles, where it prevents scar formation. This may open new therapeutic avenues for SCIs.
Differentiation of femur bone from surrounding soft tissue using laser-induced breakdown spectroscopy as a feedback system for smart laserosteotomy

Although laserosteotomes have become generally accepted devices in surgical applications, they still suffer from a lack of information about the type of tissue currently being ablated; as a result, critical structures of the body under or near the focal spot of the laser beam are prone to inadvertent ablation. The lack of information about the properties of the ablated tissue can be solved by connecting the laserosteotome to an optical detection setup which can differentiate various types of tissues, especially bone from connective soft tissues. This study examines the applicability of laser-induced breakdown spectroscopy (LIBS) as a potential technique to differentiate bone from surrounding soft tissue (fat and muscle). In this experiment, fresh porcine femur bone, muscle, and fat were used as hard and soft tissue samples. The beam of a nanosecond frequency–doubled Nd:YAG laser was used to ablate the tissue samples and generate the plasma. The plasma light emitted from the ablated spot, which corresponds to the recombination spectra of ionized atoms and molecules, was gathered with a collection optic (including a reflective light collector and a fiber optic) and sent to an Echelle spectrometer for resolving the atomic composition of the ablated sample. Afterwards, Discriminant Function Analysis (DFA) based on the ratio of the intensity of selected peak pairs was performed to classify three sample groups (bone, muscle, and fat). Lastly, the sensitivity, specificity, and accuracy of the proposed method were calculated. Sensitivity and specificity of 100 % and 99 % were achieved, respectively, to differentiate bone from surrounding soft tissue.
Understanding GSS use by executive groups

GSSs have the potential to help autocratic groups significantly improve their decision making processes. However, the same autocratic power t8ructms seem to rliscourage GSS use. Ifthis is true, the overall effectiveness of GSS for groups will be very limited. Ur&xtunately, not enough is known about why groups use or don’t use GSSs (Kraemer and King, 1988). This is particularly true of executive groups, who may he key to the diffusion of GSS
Resting State Cortical Oscillations of Patients With Parkinson Disease and With and Without Subthalamic Deep Brain Stimulation: A Magnetoencephalography Study

Purpose: In this study, we investigate the modification to cortical oscillations of patients with Parkinson disease (PD) by subthalamic deep brain stimulation (STN-DBS). Methods: Spontaneous cortical oscillations of patients with PD were recorded with magnetoencephalography during on and off subthalamic nucleus deep brain stimulation states. Several features such as average frequency, average power, and relative subband power in regions of interest were extracted in the frequency domain, and these features were correlated with Unified Parkinson Disease Rating Scale III evaluation. The same features were also investigated in patients with PD without surgery and healthy controls. Results: Patients with Parkinson disease without surgery compared with healthy controls had a significantly lower average frequency and an increased average power in 1 to 48 Hz range in whole cortex. Higher relative power in theta and simultaneous decrease in beta and gamma over temporal and occipital were also observed in patients with PD. The Unified Parkinson Disease Rating Scale III rigidity score correlated with the average frequency and with the relative power of beta and gamma in frontal areas. During subthalamic nucleus deep brain stimulation, the average frequency increased significantly when stimulation was on compared with off state. In addition, the relative power dropped in delta, whereas it rose in beta over the whole cortex. Through the course of stimulation, the Unified Parkinson Disease Rating Scale III rigidity and tremor scores correlated with the relative power of alpha over left parietal. Conclusions: Subthalamic nucleus deep brain stimulation improves the symptoms of PD by suppressing the synchronization of alpha rhythm in somatomotor region.
Effect of selective LRRK2 kinase inhibition on nonhuman primate lung

LRRK2 kinase inhibitors, under development for Parkinson’s disease, have an effect on type II pneumocytes in nonhuman primate lung, suggesting that pulmonary toxicity may be a critical safety liability. A lung phenotype for LRRK2 inhibitors Human genetic evidence implicates leucine-rich repeat kinase 2 (LRRK2) as a high-priority drug target for Parkinson’s disease. However, the benefit and risk of inhibiting the kinase activity of LRRK2 is unknown and is currently untested in humans. Using two selective LRRK2 kinase inhibitors, Fuji et al. report a safety liability in nonhuman primates characterized by morphological changes in lung. These results are consistent with observations in mice lacking LRRK2. These safety observations offer a cautionary note for pharmacological modulation of LRRK2 in humans. Inhibition of the kinase activity of leucine-rich repeat kinase 2 (LRRK2) is under investigation as a possible treatment for Parkinson’s disease. However, there is no clinical validation as yet, and the safety implications of targeting LRRK2 kinase activity are not well understood. We evaluated the potential safety risks by comparing human and mouse LRRK2 mRNA tissue expression, by analyzing a Lrrk2 knockout mouse model, and by testing selective brain-penetrating LRRK2 kinase inhibitors in multiple species. LRRK2 mRNA tissue expression was comparable between species. Phenotypic analysis of Lrrk2 knockout mice revealed morphologic changes in lungs and kidneys, similar to those reported previously. However, in preclinical toxicity assessments in rodents, no pulmonary or renal changes were induced by two distinct LRRK2 kinase inhibitors. Both of these kinase inhibitors induced abnormal cytoplasmic accumulation of secretory lysosome-related organelles known as lamellar bodies in type II pneumocytes of the lung in nonhuman primates, but no lysosomal abnormality was observed in the kidney. The pulmonary change resembled the phenotype of Lrrk2 knockout mice, suggesting that this was LRRK2-mediated rather than a nonspecific or off-target effect. A biomarker of lysosomal dysregulation, di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP), was also decreased in the urine of Lrrk2 knockout mice and nonhuman primates treated with LRRK2 kinase inhibitors. Our results suggest a role for LRRK2 in regulating lysosome-related lamellar bodies and that pulmonary toxicity may be a critical safety liability for LRRK2 kinase inhibitors in patients.
Antibiotic-resistant Gram-negative Bacteremia in Pediatric Oncology Patients—Risk Factors and Outcomes

Background: Infection with antibiotic-resistant (AR) Gram-negative (GN) bacteria is associated with increased morbidity and mortality. The aim of this study was to determine risk factors and outcomes associated with GN bacteremia with acquired resistance to antibiotics used in the empiric treatment of febrile neutropenia in pediatric oncology patients at our institution. Methods: All episodes of GN bacteremia in oncology patients at the Royal Children’s Hospital Melbourne, from 2003 to 2010 were retrospectively reviewed. Information regarding age, diagnosis, phase of treatment, inpatient status, previous AR GN infection, treatment with inotropes or ventilatory support, admission to intensive care unit, and hospital and intensive care unit length of stay were obtained from electronic records. Results: A total of 280 episodes of GN bacteremia in 210 patients were identified. Of these, 42 episodes in 35 patients were caused by an AR GN organism. Factors independently associated with AR GN bacteremia were high-intensity chemotherapy (odds ratio 3.7, 95% confidence interval: 1.2–11.4), hospital-acquired bacteremia (odds ratio 4.3, 95% confidence interval: 2.0–9.6) and isolation of AR GN bacteria from any site within the preceding 12 months (odds ratio 9.9, 95% confidence interval: 3.8–25.5). Episodes of AR GN bacteremia were associated with longer median hospital length of stay (23.5 days versus 14.0 days; P = 0.0007), longer median intensive care unit length of stay (3.8 days versus 1.6 days; P = 0.02) and a higher rate of invasive ventilation (15% versus 5.2%; P = 0.03). No significant difference in infection-related or all-cause mortality between the 2 groups was identified. Conclusions: In pediatric oncology patients, AR GN bacteremia is associated with an increased rate of adverse outcomes and is more likely in patients who have received high-intensity chemotherapy, have been in hospital beyond 48 hours and who have had previous AR GN infection or colonization.
Value of hepatic subcapsular flow by color Doppler ultrasonography in the diagnosis of biliary atresia

Diagnosis of biliary atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis (NC), is challenging. Ultrasonography is a helpful investigation when evaluating NC. The aim was to determine the value of color Doppler ultrasound, particularly hepatic subcapsular flow, as a possible tool in early discrimination of BA from other causes of NC.
Total tumor volume predicts risk of recurrence following liver transplantation in patients with hepatocellular carcinoma

Criteria for the selection of candidates for liver transplantation in the presence of hepatocellular carcinoma (HCC) should accurately predict posttransplant recurrence while not excluding excessive numbers of patients from candidacy. Existing criteria are challenged by the limited accuracy of radiological assessment. The total tumor volume (TTV) was calculated by the addition of the volume of each individual tumor. A preliminary analysis was carried out on HCC patient data from the Alberta Liver Transplant Program (52 patients) and then validated on the populations of the Universities of Toronto and Colorado programs (154 and 82 patients). A TTV cutoff of 115 cm3 was chosen on the basis of the risk of recurrence with use of a receiver operating characteristic curve. Radiology correlated more closely to pathology with TTV than with Milan and University of California at San Francisco (UCSF) criteria (91% versus 69% and 75% of patients, P < 0.0001). Although more patients met qualifying criteria for transplant with TTV (28%‐53% more than Milan and 16%‐26% more than UCSF), no deterioration of outcome was demonstrated in an analysis of patients within TTV ≤ 115 cm3 in comparison with those meeting Milan or UCSF classifications at all institutions. Patients with TTV > 115 cm3 experienced more recurrences and lower patient survival in the Alberta and Colorado series (P < 0.05). When TTV with a cutoff of 115 cm3 is used for candidate selection, the accuracy of pretransplant radiological assessment is enhanced, with posttransplant outcomes not different from those achieved with Milan and UCSF classifications despite a more inclusive patient population. Liver Transpl 14:1107–1115, 2008. © 2008 AASLD.
The spaying of bitches

The spaying operation, or ovariohysterectomy, involves a general anaesthetic, with removal of the ovaries and the entire uterus down to the level of the cervix, via an incision in the midline of the abdomen of the bitch. Unwanted pups are prevented this removes the problems associated with finding homes or increasing the stray population. No false pregnancy false pregnancy is very common in bitches, and can occur after each season. It may result in distress to the bitch and anguish to the owner. A bitch undergoing a false pregnancy may produce milk, lose her appetite and become quite aggressive. Phantom pregnancies may become more severe with each season. Pyometra and other womb and ovarian diseases are avoided unspayed bitches can develop pyometra (a pus filled womb) late in life which then requires life–saving surgery. Spaying a healthy bitch does not involve the risks of spaying an older bitch with complications from the pyometra. Reduced risk of mammary tumours the relative risk of mammary tumours increases progressively with each season. The earlier the bitch is spayed, the lower the risk. No oestrus oestrus (season or “heat”) occurs about every six months in entire bitches. During this time bitches have to be kept away from other dogs and walked under close supervision. To prevent the perpetuation of genetic defects. Castration of Dogs:
Indices and Applications in High-Throughput Sequencing

Recent advances in sequencing technology allow to produce billions of base pairs per day in the form of reads of length 100 bp an longer and current developments promise the personal $1,000 genome in a couple of years. The analysis of these unprecedented amounts of data demands for efficient data structures and algorithms. One such data structures is the substring index, that represents all substrings or substrings up to a certain length contained in a given text. In this thesis we propose 3 substring indices, which we extend to be applicable to millions of sequences. We devise internal and external memory construction algorithms and a uniform framework for accessing the generalized suffix tree. Additionally we propose different index-based applications, e.g. exact and approximate pattern matching and different repeat search algorithms. Second, we present the read mapping tool RazerS, which aligns millions of single or paired-end reads of arbitrary lengths to their potential genomic origin using either Hamming or edit distance. Our tool can work either lossless or with a user-defined loss rate at higher speeds. Given the loss rate, we present a novel approach that guarantees not to lose more reads than specified. This enables the user to adapt to the problem at hand and provides a seamless tradeoff between sensitivity and running time. We compare RazerS with other state-of-the-art read mappers and show that it has the highest sensitivity and a comparable performance on various real-world datasets. At last, we propose a general approach for frequency based string mining, which has many applications, e.g. in contrast data mining. Our contribution is a novel and lightweight algorithm that is faster and uses less memory than the best available algorithms. We show its applicability for mining multiple databases with a variety of frequency constraints. As such, we use the notion of entropy from information theory to generalize the emerging substring mining problem to multiple databases. To demonstrate the improvement of our algorithm we compared to recent approaches on real-world experiments of various string domains, e.g. natural language, DNA, or protein sequences.
Use of residue pairs in protein sequence‐sequence and sequence‐structure alignments

Two new sets of scoring matrices are introduced: H2 for the protein sequence comparison and T2 for the protein sequence–structure correlation. Each element of H2 or T2 measures the frequency with which a pair of amino acid types in one protein, k‐residues apart in the sequence, is aligned with another pair of residues, of given amino acid types (for H2) or in given structural states (for T2), in other structurally homologous proteins. There are four types, corresponding to the k‐values of 1 to 4, for both H2 and T2. These matrices were set up using a large number of structurally homologous protein pairs, with little sequence homology between the pair, that were recently generated using the structure comparison program SHEBA.