Miracle-dz/UniFAR-FTUs huggingface dataset:
Anoctamin 6 is an essential component of the outwardly rectifying chloride channel

Outwardly rectifying chloride channels (ORCC, ICOR) of intermediate single-channel conductance of around 50 pS, are ubiquitously expressed, but have remained a mystery since their description more than 25 y ago. These channels have been shown to be activated on membrane excision and depolarization of the membrane voltage and by cAMP in the presence of the cystic fibrosis transmembrane conductance regulator. We show that anoctamin 6 (Ano6), a member of the recently identified family of putative Cl− channels, is the crucial component of ORCC single-channel and whole-cell currents in airway epithelial cells and Jurkat T lymphocytes. Cystic fibrosis transmembrane conductance regulator augmented ORCC produced by Ano6 in A549 airway epithelial cells. Ano6 is activated during membrane depolarization or apoptosis of Jurkat T lymphocytes and epithelial cells, and is inhibited by 5-nitro-2-(3-phenylpropylamino) benzoic acid, 4,4′-diisothio-cyanostilbene-2,2′-disulfonic acid, or AO1. Ano6 belongs to the basic equipment of any cell type, including colonic surface epithelial cells. It forms the essential component of ORCC and seems to have a role for cell shrinkage and programmed cell death.
Survival in Synovial Sarcoma: A Multivariate Study of Prognostic Factors with Special Emphasis on the Comparison Between Early Death and Long-Term Survival

A retrospective study of 56 patients with synovial sarcoma was done to search for possible prognostic factors affecting survival. In a univariate analysis, age (≥20 years), site (proximal), large tumor size (≥5 cm), mitotic rate of more than 15 per 10 per high-power fields (hpf), high nuclear grade, tumor necrosis of more than 50%, the presence of rhabdoid cells, a small number of mast cells (<20/10 hpf), and a high stage according to the criteria of the American Joint Committee (AJC) staging of soft tissue sarcoma, significantly decreased survival (log-rank test; p < 0.05). Moreover, when comparing the 10-year survival (11 patients) and the deaths within 1 year (12 patients), size, high nuclear grade, presence of rhabdoid cells, tumor necrosis, and stage were all considered to be significant prognostic factors (two-sided chi-square test; p < 0.01). In a multivariate analysis (Cox's model), stage was the only strong predictor of a poor prognosis (p = 0.011). We therefore concluded that large tumor size, high nuclear grade, the presence of rhabdoid cells, extensive tumor necrosis, and a high AJC stage were adverse prognostic factors in synovial sarcoma.
Insurance and quality of care for adults with acute asthma

OBJECTIVE: The relationship between health care insurance and quality of medical care remains incompletely studied. We sought to determine whether type of patient insurance is related to quality of care and subsequent outcomes for patients who arrive in the emergency department (ED) for acute asthma.DESIGN: Using prospectively collected data from the Multicenter Airway Research Collaboration, we compared measures of quality of pre-ED care, acute severity, and short-term outcomes across 4 insurance categories: managed care, indemnity, Medicaid, and uninsured.SETTING AND PARTICIPANTS: Emergency departments at 57 academic medical centers enrolled 1,019 adults with acute asthma.RESULTS: Patients with managed care ranked first and uninsured patients ranked last on all 7 unadjusted quality measures. After controlling for covariates, uninsured patients had significantly lower quality of care than indemnity patients for 5 of 7 measures and had lower initial peak expiratory flow rates than indemnity insured patients. Patients with managed care insurance were more likely than indemnity-insured patients to identify a primary care physician and report using inhaled steroids in the month prior to arrival in the ED. Patients with Medicaid insurance were more likely than indemnity-insured patients to use the ED as their usual source of care for problems with asthma. We found no differences in patient outcomes among the insurance categories we studied.CONCLUSIONS: Uninsured patients had consistently poorer quality of care and than insured patients. Despite differences in indicators of quality of care between types of insurance, we found no differences in short-term patient outcomes by type of insurance.
Crohn's disease-derived monocytes fail to induce Paneth cell defensins

Significance Paneth cell defensins (human α-defensins 5 and 6) are central players in the regulation of the human microbiome in the small intestine, but their regulation remains unclear. Here, we show that healthy monocytes can induce the expression of these defensins via Wnt ligands, especially in patients with Crohn’s disease (CD), who normally display reduced levels of human α-defensin 5 (HD5) and HD6, resulting in impaired host defense and, consequently, mucosal inflammation. However, monocytes from these patients are lacking this defensin-inducing capability, which seems to be based on compromised expression of Wnt ligands. This translational human study demonstrates defective cross-talk between monocytes and Paneth cells in CD with implications for gastrointestinal infections and bone marrow transplantation. Crohn’s disease (CD) is associated with a multitude of genetic defects, many of which likely affect Paneth cell function. Paneth cells reside in the small intestine and produce antimicrobial peptides essential for the host barrier, principally human α-defensin 5 (HD5) and HD6. Patients with CD of the ileum are characterized by reduced constitutive expression of these peptides and, accordingly, compromised antimicrobial barrier function. Here, we present a previously unidentified regulatory mechanism of Paneth cell defensins. Using cultures of human ileal tissue, we showed that the secretome of peripheral blood mononuclear cells (PBMCs) from healthy controls restored the attenuated Paneth cell α-defensin expression characteristic of patients with ileal CD. Analysis of the Wnt pathway in both cultured biopsies and intestinal epithelial cells implicated Wnt ligands driving the PBMC effect, whereas various tested cytokines were ineffective. We further detected another defect in patients with ileal CD, because the PBMC secretomes derived from patients with CD were unable to restore the reduced HD5/HD6 expression. Accordingly, analysis of PBMC subtypes showed that monocytes of patients with CD express significantly lower levels of canonical Wnt ligands, including Wnt3, Wnt3a, Wnt1, and wntless Wnt ligand secretion mediator (Evi/Wls). These studies reveal an important cross-talk between bone marrow-derived cells and epithelial secretory Paneth cells. Defective Paneth cell-mediated innate immunity due to inadequate Wnt ligand stimulation by monocytes provides an additional mechanism in CD. Because defects of Paneth cell function stemming from various etiologies are overcome by Wnt ligands, this mechanism is a potential therapeutic target for this disease.
Deriving Explicit Control Policies for Markov Decision Processes Using Symbolic Regression

In this paper, we introduce a novel approach to optimizing the control of systems that can be modeled as Markov decision processes (MDPs) with a threshold-based optimal policy. Our method is based on a specific type of genetic program known as symbolic regression (SR). We present how the performance of this program can be greatly improved by taking into account the corresponding MDP framework in which we apply it. The proposed method has two main advantages: (1) it results in near-optimal decision policies, and (2) in contrast to other algorithms, it generates closed-form approximations. Obtaining an explicit expression for the decision policy gives the opportunity to conduct sensitivity analysis, and allows instant calculation of a new threshold function for any change in the parameters. We emphasize that the introduced technique is highly general and applicable to MDPs that have a threshold-based policy. Extensive experimentation demonstrates the usefulness of the method.
Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroides dubius): the capacity of adult worms to survive following transplantation to recipient mice

SUMMARY Chronic primary infections with Heligmosomoides polygyrus (Nematospiroides dubius) are still relatively poorly documented, particularly in relation to the role of host resistance in limiting worm survival. In the present work the duration of infection with H. polygyrus was studied in CFLP mice given doses of infective larvae ranging from 50 to 500 L3. The least heavily infected (50 L3) group ceased egg production earliest (week 36) whereas eggs were still detected in the faeces of mice given 500 larvae in week 42. At autopsy (week 42) mice given 50 larvae had virtually lost their entire worm burden with 5 out of 11 mice still harbouring a single worm each. However, all the mice in the group given 500 larvae were still infected, the highest worm burden being 93. The concentration of serum IgGl and specific antibody was highest in mice given 500 larvae, but sera taken from mice with declining worm burdens 19–38 weeks post-infection did not contain detectable host-protective antibody. During the course of infection in CFLP mice, H, polygyrus sustained irreversible changes in its capacity for subsequent survival. Thus, adult worms transferred to naive mice 2, 7, 14, 30 or 36 weeks post-infection did not live longer than worms of a comparable age in the respective donor group. In contrast, primary infection worms taken from jirds in which expulsion is usually completed by 6 weeks post-infection, re-established in mice and survived considerably longer than in the group of donor jirds. These results were discussed in relation to the possible interactions between parasite senility and immunomodulation, and host resistance in limiting primary infections with H. polygyrus in mice and jirds.
The size 1.5 Laryngeal Mask Airway (LMATM) in paediatric anaesthetic practice

Background: The recently introduced size 1.5 laryngeal mask airway (LMATM) is specifically designed for use in children weighing 5–10 kg. Methods: We prospectively evaluated its use in 68 patients, mean age 8.7 months, who were undergoing a variety of routine surgical procedures.
Prevalence and aetiology of clinical mastitis on dairy farms in Devon

Nliss NIilnc is also at the Nale Vetciinarv dCentre, The Laurcrls, Station1 Road, liverton, Devon EX\ 1 6 4LF THERE have beennonatioinal surveys of the aetiology ofclinicalmastitis in the UK in the past decade (Booth 1997). Many authors have suggested that the pattern of disease has changed over the past 20 years (WN7ilesmith and others 1986, Erskine and others 1988, Booth 1993). Strcptococcus idris anid other envTironmental pathogenis, such as Esclwtricliti coli, have been reported to be more prevalent than the contagious pathogenis, forcxample, Staphylococculs au rcus and StrL'ptococclbs ago/laictiac, as causes of clinicalmastitis in recent years (AInon1 1982, 1989, 1993, 2000,WNTilesmith anid others 1986, Erskine and others 1988, Booth 1993, Bradley and Greenl 2001). A survey was conductd from October 1 999 to February 2001 to confirm the importance of environmental pathogenls in dairy herds in mid-Devon. Devon ison1e of the 10 cooInties in Great Britain that has a density ofmzore than 60 dairy cowsTs per square mile. One hundred and thirty farmswere included in the study. 'IThe average herd size on the farms studied was 94 cowvs (ranige 30 to 346). The majority of herds (69 per cent) were composed of Holstein l'riesiani cowNTs. In afturther 16 per cent of herds there were mainly HolsteinFriesian cowvswith a small niumber of other breeds,including pedigree Holstein, Ayrshire, Jersey, brown swviss, Meuse-RhinecIjssel and Simmenital-Friesiani cross. The remainiing herds wvere BritishFriesian (9 per cent), pedigree Holstein (4 per cent), Guernsey ( 1 percent) and Ayrshire ( I
Neuromagnetic Localization of CMV Generators Using Incomplete and Full-Head Biomagnetometer

Contingent magnetic variation (CMV) data were recorded in three healthy male subjects using a 2 x 37 biomagnetometer system. The experiment was repeated for one of the subjects using a 151 whole-head biomagnetometer; the same auditory GO/NOGO choice reaction time paradigm as in the first experiment was used, extended to include repetitions of identical runs and additional control conditions. Magnetic field tomography was applied to the averaged data of each subject, for each run and condition (e.g., GO/NOGO). An independent estimate of the current density in the brain was obtained every few milliseconds. The slow components were emphasized by integrating the square of the current density vector, pixel by pixel, revealing in each subject activity in the auditory cortex, sensorimotor cortex, inferior prefrontal area, and posterior inferior parietal area. The intersubject variability was large, but looking across subjects the auditory and sensorimotor cortex (which were best covered by the two probes) were consistently identified in each subject as contributing to the generation of the early and late slow CMV components. These findings were confirmed by the whole-head single-subject experiment, in which slow activity was also identified in the supplementary motor area (SMA) and posterior cingulate cortex (PCC), areas very likely missed in the first experiment because of the limited view of the twin system. The PCC and particularly the SMA activations were substantially reduced when identical runs were repeated.
Heroin self-administration and extinction increases prelimbic cortical astroglia-synapse proximity and alters dendritic spine morphometrics that are reversed by N-acetylcysteine

Clinical and preclinical studies indicate that adaptations in corticostriatal neurotransmission significantly contribute to heroin relapse vulnerability. In animal models, heroin self-administration and extinction produce cellular adaptations in both neurons and astrocytes within the nucleus accumbens (NA) core that are required for cue-induced heroin seeking. Specifically, decreased glutamate clearance and reduced association of perisynaptic astrocytic processes with NAcore synapses allow glutamate release from prelimbic (PrL) cortical terminals to engage synaptic and structural plasticity in NAcore medium spiny neurons. Normalizing astroglial glutamate homeostasis with drugs like the antioxidant N-acetylcysteine (NAC) prevents cue-induced heroin seeking. Surprisingly, little is known about heroin-induced alterations in astrocytes or pyramidal neurons projecting to the NAcore in the PrL cortex (PrL-NAcore). Here, we observed increased complexity of the glial fibrillary acidic protein (GFAP) cytoskeletal arbor and increased association of the astroglial plasma membrane with synaptic markers following heroin SA and extinction training in the PrL cortex. Repeated treatment with NAC during extinction reversed both the enhanced astroglial complexity and synaptic association. In PrL-NAcore neurons, heroin SA and extinction decreased apical tuft dendritic spine density and enlarged dendritic spine head diameter in male Sprague-Dawley rats. Repeated NAC treatment during extinction prevented decreases in spine density but not dendritic spine head expansion. Moreover, heroin SA and extinction increased co-registry of the GluA1 subunit of AMPA receptors in both the dendrite shaft and spine heads of PrL-NAcore neurons. Interestingly, accumulation of GluA1 immunoreactivity in spine heads was further potentiated by NAC treatment during extinction. Taken together, our data reveal circuit-level adaptations in cortical dendritic spine morphology potentially linked to heroin-induced alterations in astrocyte complexity and association at synapses. Additionally, these data demonstrate, for the first time, that NAC reverses PrL cortical heroin SA and extinction-induced adaptations in both astrocytes and corticostriatal neurons.
Increased urinary excretion of thromboxane B 2 and 2 , 3-dinor-TxB 2 in cyclosporin A nephrotoxicity

Increased urinary excretion of thromboxane B2 and 2,3-dinor-TxB2 in cyclosporin A nephrotoxlcity. Cyclosporin A (CsA) administration to rats is associated with a selective increase in urinary excretion of immunoreactive thromboxane B2 (i-TxB2), the stable breakdown product of TxA2. The exaggerated synthesis of TxA2 may play a role in the reduction of glomerular filtration rate (GFR) observed both in animals and humans undergoing CsA treatment. The present study was designed to get further insight into the origin of the abnormal i-TxB2 urinary excretion. Rats given orally CsA (50 mg/kg/day) for 30 days had a significant increase in the urinary excretion of both 2,3-dinor-TxB2 and TxB2 measured by technique of capillary column gas chromatography-negative ion chemical ionization mass spectrometry (HRGCNICIMS). Urinary TxB2 is more likely to reflect the renal synthesis of the parent compound, whereas 2,3-dinor-TxB2 is considered to reflect the amount of TxB2 formed in the circulation. Experiments in isolated perfused kidney (IPK) taken from animals given CsA for 30 days showed a lower percentage increase in urinary TxB2 over vehicle treated animals. Moreover in IPK the ratio 2,3-dinor-TxB2/TxB2 was lower than in vivo. The amount of i-TxB2 detectable in serum of animals given CsA was not different from that of control animals. In contrast, isolated glomeruli taken from rats given CsA had an increase in their TxA2 synthesis measured as i-TxB2 in the supernatants. Ultrastructural studies on kidney specimens from animals given CsA showed a focal glomerular endothelial damage together with a marked infiltration of blood borne cells of monocyte-macrophage type in the glomerular tuft. In contrast, kidney specimens taken from IPK preparations were devoid of inflammatory cells. In vitro CsA did not interfere with platelet arachidonic acid (AA) metabolism as shown by a normal i-TxB2 generation in vitro by rat platelet-rich plasma (PRP) exposed to CsA and then challenged with AA or ADP. Similarly isolated glomeruli and isolated proximal tubules from normal rats when challenged with CsA in vitro converted AA into TxA2 normally. It is suggested that the cause of the increased urinary excretion or 2,3-dinor-TxB2 is the consequence of intrarenal platelet and macrophage activation, probably triggered by the endothelial damage. The parallel increase in the urinary excretion of unmetabolized TxB2 is likely to reflect a concomitant activation of resident renal cell AA metabolism induced by CsA.
Neurophysiological characteristics of human leg muscle action potentials evoked by transcutaneous magnetic stimulation of the spine

The objectives of this study were to establish the neurophysiological properties of the compound muscle action potentials (CMAPs) evoked by transcutaneous magnetic stimulation of the spine (tsMSS) and the effects of tsMSS on the soleus H‐reflex. In semi‐prone seated subjects with trunk semi‐flexed, the epicenter of a figure‐of‐eight magnetic coil was placed at Thoracic 10 with the handle on the midline of the vertebral column. The magnetic stimulator was triggered by monophasic single pulses of 1 ms, and the intensity ranged from 90% to 100% of the stimulator output across subjects. CMAPs were recorded bilaterally from ankle and knee muscles at the interstimulus intervals of 1, 3, 5, 8, and 10 s. The CMAPs evoked were also conditioned by posterior tibial and common peroneal nerve stimulation at a conditioning‐test (C‐T) interval of 50 ms. The soleus H‐reflex was conditioned by tsMSS at the C‐T intervals of 50, 20, −20, and −50 ms. The amplitude of the CMAPs was not decreased when evoked at low stimulation frequencies, excitation of group I afferents from mixed peripheral nerves in the leg affected the CMAPs in a non‐somatotopical neural organization pattern, and tsMSS depressed soleus H‐reflex excitability. These CMAPs are likely due to orthodromic excitation of nerve motor fibers and antidromic depolarization of different types of afferents. The latency of these CMAPs may be utilized to establish the spine‐to‐muscle conduction time in central and peripheral nervous system disorders in humans. tsMSS may constitute a non‐invasive modality to decrease spinal reflex hyperexcitability and treat hypertonia in neurological disorders. Bioelectromagnetics 34:200–210, 2013. © 2012 Wiley Periodicals, Inc.
Dietary L-glutamine does not improve lymphocyte metabolism or function in exercise-trained rats.

Decreased glutamine availability is proposed as a mechanism for changes in immune function with intense exhaustive exercise. Less is known about the immunomodulatory effects of regular nonexhaustive exercise. To determine the effects of low intensity regular exercise and dietary glutamine supplementation on plasma glutamine concentrations, lymphocyte metabolism, and immune function, male (278 +/- 5 g) and female (182 +/- 1 g) Sprague-Dawley Buffalo rats were fed nutritionally complete casein-based semi-purified diets +/- 2% w/w glutamine. Rats were trained (21 d), as confirmed by higher (P < 0.05) succinate dehydrogenase activity in soleus muscle, to swim 2 or 4 h.d-1 or remained sedentary. Exercise lowered plasma concentrations of tryptophan, glutamate, methionine, alanine, threonine, aspartate, asparagine, and ornithine and increased the lysine concentration (P < 0.05). Neither diet nor exercise altered plasma glutamine concentrations, lymphocyte phenotypes in spleen, or the in vitro rates of splenocyte energy metabolism (production of glucose and glutamine metabolites or ATP concentrations in the incubation media). Compared with nonsupplemented rats, splenic cytolytic activity (lysis of 51Cr labeled YAC-1 cells) was reduced (P < 0.05) in the glutamine-supplemented exercising group. Under these conditions, glutamine supplementation does not appear to provide any added benefit to the exercise-trained animal.
Improved undetected error probability model for JTEC and JTEC-SQED coding schemes

The undetected error probability is an important measure to assess the communication reliability provided by any error coding scheme. Two error coding schemes namely, Joint crosstalk avoidance and Triple Error Correction (JTEC) and JTEC with Simultaneous Quadruple Error Detection (JTEC-SQED), provide both crosstalk reduction and multi-bit error correction/detection features. The available undetected error probability model yields an upper bound value which does not give accurate estimation on the reliability provided. This paper presents an improved mathematical model to estimate the undetected error probability of these two joint coding schemes. According to the decoding algorithm the errors are classified into patterns and their decoding result is checked for failures. The probabilities of the failing patterns are used to build the new models. The improved models have less than 1% error with respect to the simulation results and reflect in up to 60% higher mean time to failure as compared to available models.