Miracle-dz/UniFAR-FTUs huggingface dataset:
Breath Formate Is a Marker of Airway S-Nitrosothiol Depletion in Severe Asthma

Background Children with severe asthma have poor symptom control and elevated markers of airway oxidative and nitrosative stress. Paradoxically, they have decreased airway levels of S-nitrosothiols (SNOs), a class of endogenous airway smooth muscle relaxants. This deficiency results from increased activity of an enzyme that both reduces SNOs to ammonia and oxidizes formaldehyde to formic acid, a volatile carboxylic acid that is more easily detected in exhaled breath condensate (EBC) than SNOs. We therefore hypothesize that depletion of airway SNOs is related to asthma pathology, and breath formate concentration may be a proxy measure of SNO catabolism. Methods and Findings We collected EBC samples from children and adolescents, including 38 with severe asthma, 46 with mild-to-moderate asthma and 16 healthy adolescent controls, and the concentration of ionic constituents was quantified using ion chromatography. The concentrations of EBC components with volatile conjugates were log-normally distributed. Formate was the principal ion that displayed a significant difference between asthma status classifications. The mean EBC formate concentration was 40% higher in samples collected from all asthmatics than from healthy controls (mean = 5.7 µM, mean±standard deviation = 3.1−10.3 µM vs. 4.0, 2.8−5.8 µM, p = 0.05). EBC formate was higher in severe asthmatics than in mild-to-moderate asthmatics (6.8, 3.7−12.3 µM vs. 4.9, 2.8−8.7 µM, p = 0.012). In addition, formate concentration was negatively correlated with methacholine PC20 (r = −0.39, p = 0.002, asthmatics only), and positively correlated with the NO-derived ion nitrite (r = 0.46, p<0.0001) as well as with total serum IgE (r = 0.28, p = 0.016, asthmatics only). Furthermore, formate was not significantly correlated with other volatile organic acids nor with inhaled corticosteroid dose. Conclusions We conclude that EBC formate concentration is significantly higher in the breath of children with asthma than in those without asthma. In addition, amongst asthmatics, formate is elevated in the breath of those with severe asthma compared to those with mild-to-moderate asthma. We suggest that this difference is related to asthma pathology and may be a product of increased catabolism of endogenous S-nitrosothiols.
Expression of m1‐type muscarinic acetylcholine receptors by parvalbumin‐immunoreactive neurons in the primary visual cortex: A comparative study of rat, guinea pig, ferret, macaque, and human

Cholinergic neuromodulation is a candidate mechanism for aspects of arousal and attention in mammals. We have reported previously that cholinergic modulation in the primary visual cortex (V1) of the macaque monkey is strongly targeted toward GABAergic interneurons, and in particular that the vast majority of parvalbumin‐immunoreactive (PV) neurons in macaque V1 express the m1‐type (pirenzepine‐sensitive, Gq‐coupled) muscarinic ACh receptor (m1AChR). In contrast, previous physiological data indicates that PV neurons in rats rarely express pirenzepine‐sensitive muscarinic AChRs. To examine further this apparent species difference in the cholinergic effectors for the primary visual cortex, we have conducted a comparative study of the expression of m1AChRs by PV neurons in V1 of rats, guinea pigs, ferrets, macaques, and humans. We visualize PV‐ and mAChR‐immunoreactive somata by dual‐immunofluorescence confocal microscopy and find that the species differences are profound; the vast majority (>75%) of PV‐ir neurons in macaques, humans, and guinea pigs express m1AChRs. In contrast, in rats only ∼25% of the PV population is immunoreactive for m1AChRs. Our data reveal that while they do so much less frequently than in primates, PV neurons in rats do express Gq‐coupled muscarinic AChRs, which appear to have gone undetected in the previous in vitro studies. Data such as these are critical in determining the species that represent adequate models for the capacity of the cholinergic system to modulate inhibition in the primate cortex. J. Comp. Neurol. 522:986–1003, 2014. © 2013 Wiley Periodicals, Inc.
Comparison of clinical diagnosis with computed tomography in ascertaining type of stroke.

BACKGROUND Cerebrovascular Accident or stroke is a major cause of morbidity and mortality. For any treatment to be contemplated it is important to know whether we are dealing with a bleed or an infarct. This study was carried out to compare clinical diagnosis of stroke with Computed tomography (CT) scan findings in ascertaining the type of stroke (hemorrhagic or ischemic). METHODS This study was carried out at Department of Medicine, Ayub Teaching Hospital, Abbottabad from November 2001 to December 2003. One hundred consecutive patients fulfilling the inclusion criteria presenting with stroke were included. Clinical diagnosis was mainly based on presentation with specific emphasis on speed of onset, presence or absence of underlying cardiovascular diseases and past history of stroke. CT scan brain was carried out in all patients to confirm the diagnosis. The results were compared on case to case basis with CT diagnosis. RESULTS The patients included 71 males and 29 females, with an age range of 20-80 years. Clinically, 43% were suspected to have cerebral infarction, 25% intracerebral bleed and 32% indeterminate. CT scan brain showed 60% cerebral infarction, 27% intracerebral hemorrhages, 9% Space Occupying Lesion and 4% hemorrhagic infarct. CONCLUSION We found that clinical diagnosis in majority of the cases is not as reliable as the CT scan. It can help in diagnosis but cannot confirm it.
Cytotoxic Activity of Mycobacterium ulcerans

Although Mycobacterium ulcerans elicits extensive necrosis of human skin and subcutaneous tissue, the specific cause of the necrosis has never been elucidated. In an attempt to define a toxic substance, 18 strains of M. ulcerans were inoculated into mice, and the progress of each infection was observed and compared with infections of other mycobacteria, including M. cheloni, M. marinum, and M. bovis. Culture filtrates and viable organisms of each of these mycobacteria were inoculated onto tissue culture cells. Inoculation of mouse footpads with M. ulcerans resulted in progressive infections, leading to ulceration and eventual death. Strains of M. cheloni, M. marinum, and M. bovis did not produce progressive infections in the mice. Culture filtrates of M. ulcerans produced severe cytopathogenic effects on tissue cells, but washed, viable organisms of the same strains had no cytopathogenic effect. Culture filtrates and viable organisms of M. cheloni, M. marinum, and M. bovis did not produce a cytopathogenic effect on the tissue cells. Viable organisms of selected strains of M. ulcerans and the culture filtrates of the same strains were inoculated into guinea pig skin. The culture filtrates and the viable organisms both caused focal necrosis and focal inflammation, changes that resemble those in the naturally occurring infection in man. Preliminary purification of the culture filtrate by ultrafiltration indicates that the toxic fraction has a molecular weight of approximately 100,000, and temperature studies indicate that the toxic fraction is heat labile.
The Sample Complexity of Pattern Classification with Neural Networks: The Size of the Weights is More Important than the Size of the Network

Sample complexity results from computational learning theory, when applied to neural network learning for pattern classification problems, suggest that for good generalization performance the number of training examples should grow at least linearly with the number of adjustable parameters in the network. Results in this paper show that if a large neural network is used for a pattern classification problem and the learning algorithm finds a network with small weights that has small squared error on the training patterns, then the generalization performance depends on the size of the weights rather than the number of weights. For example, consider a two-layer feedforward network of sigmoid units, in which the sum of the magnitudes of the weights associated with each unit is bounded by A and the input dimension is n. We show that the misclassification probability is no more than a certain error estimate (that is related to squared error on the training set) plus A/sup 3/ /spl radic/((log n)/m) (ignoring log A and log m factors), where m is the number of training patterns. This may explain the generalization performance of neural networks, particularly when the number of training examples is considerably smaller than the number of weights. It also supports heuristics (such as weight decay and early stopping) that attempt to keep the weights small during training. The proof techniques appear to be useful for the analysis of other pattern classifiers: when the input domain is a totally bounded metric space, we use the same approach to give upper bounds on misclassification probability for classifiers with decision boundaries that are far from the training examples.
The Role of Segmentation in Phonological Processing: An fMRI Investigation

Phonological processes map sound information onto higher levels of language processing and provide the mechanisms by which verbal information can be temporarily stored in working memory. Despite a strong convergence of data suggesting both left lateralization and distributed encoding in the anterior and posterior perisylvian language areas, the nature and brain encoding of phonological subprocesses remain ambiguous. The present study used functional magnetic resonance imaging (fMRT) to investigate the conditions under which anterior (lateral frontal) areas are activated during speech-discrimination tasks that differ in segmental processing demands. In two experiments, subjects performed same/ different judgments on the first sound of pairs of words. In the first experiment, the speech stimuli did not require overt segmentation of the initial consonant from the rest of the word, since the different pairs only varied in the phonetic voicing of the initial consonant (e.g., dip-tip). In the second experiment, the speech stimuli required segmentation since different pairs both varied in initial consonant voicing and contained different vowels and final consonants (e.g., dip-ten). These speech conditions were compared to a tone-discrimination control condition. Behavioral data showed that subjects were highly accurate in both experiments, but revealed different patterns of reaction-time latencies between the two experiments. The imaging data indicated that whereas both speech conditions showed superior temporal activation when compared to tone discrimination, only the second experiment showed consistent evidence of frontal activity. Taken together, the results of Experiments 1 and 2 suggest that phonological processing per se does not necessarily recruit frontal areas. We postulate that frontal activation is a product of segmentation processes in speech perception, or alternatively, working memory demands required for such processing.
Detection of tuberculosis drug resistance: a comparison by Mycobacterium tuberculosis MLPA assay versus Genotype®MTBDRplus

BACKGROUND To cope with the emergence of multidrug-resistant tuberculosis (MDR-TB), new molecular methods that can routinely be used to screen for a wide range of drug resistance related genetic markers in the Mycobacterium tuberculosis genome are urgently needed. OBJECTIVE To evaluate the performance of multiplex ligaton-dependent probe amplification (MLPA) against Genotype® MTBDRplus to detect resistance to isoniazid (INHr) and rifampicin (RIFr). METHOD 96 culture isolates characterised for identification, drug susceptibility testing (DST) and sequencing of rpoB, katG, and inhA genes were evaluated by the MLPA and Genotype®MTBDRplus assays. RESULTS With sequencing as a reference standard, sensitivity (SE) to detect INHr was 92.8% and 85.7%, and specificity (SP) was 100% and 97.5%, for MLPA and Genotype®MTBDRplus, respectively. In relation to RIFr, SE was 87.5% and 100%, and SP was 100% and 98.8%, respectively. Kappa value was identical between Genotype®MTBDRplus and MLPA compared with the standard DST and sequencing for detection of INHr [0.83 (0.75-0.91)] and RIFr [0.93 (0.88-0.98)]. CONCLUSION Compared to Genotype®MTBDRplus, MLPA showed similar sensitivity to detect INH and RIF resistance. The results obtained by the MLPA and Genotype®MTBDRplus assays indicate that both molecular tests can be used for the rapid detection of drug-resistant TB with high accuracy. MLPA has the added value of providing information on the circulating M. tuberculosis lineages.
Relationship Among Pain Catastrophizing, Depressed Mood, and Outcomes Across Physical Therapy Treatments

Background Pain catastrophizing and emotional distress can act as prognostic factors for pain and disability. Research on how these variables interact within individuals and over time is in an early stage. Understanding various patterns of prognostic factors and how these factors change during treatment is important for developing treatments targeting important factors. Objective The primary aim of this study was to investigate relationships between pain catastrophizing and depressed mood in people seeking primary care for musculoskeletal pain. An additional aim was to relate these patterns of prognostic factors to outcomes during a 6-month period. Design The design was prospective; data were obtained at baseline and at follow-up. Methods Forty-two physical therapists taking part in an educational program recruited, from their clinical practices in primary care, consecutive patients who were currently experiencing a pain problem. Patients received various physical therapy interventions between baseline and follow-up. Results On the basis of patterns of scoring for pain catastrophizing and depressed mood, 4 subgroups of participants were found. Belonging to a subgroup with elevated levels of either pain catastrophizing or depressed mood at baseline was related to the absence of improvement and elevated levels of disability after physical therapy interventions. Furthermore, elevated levels of both variables were related to the highest levels of disability. Limitations The analyses relied on self-report. Neither treatment content nor pain-related fear was measured. The sample was a mixture of participants reporting acute pain and subacute pain. Conclusions The results stress the importance of assessing and targeting prognostic factors. Moreover, the results suggest the need to tailor treatments to match patterns of prognostic factors and the need to target depressed mood and pain catastrophizing in physical therapy interventions.
A 1.2-V CMOS complex bandpass filter with a tunable center frequency

A 4th-order complex bandpass filter (BPF) with a tunable center frequency is designed and fabricated in a 0.13 /spl mu/m CMOS technology. The transfer function is changeable dynamically. The passband center frequency can be set to 0 Hz, 1 MHz, 1.5 MHz and 2 MHz so that the filter can work as a complex BPF in the receiver path and as a LPF in the transmit path. An opamp-RC filter is used to obtain a wide dynamic range. The filter operates with the supply voltage as low as 1.2 V. The input referred noise for 1.4 MHz band width is 53 /spl mu/Vrms. IIP3 and the image rejection ratio at 1.5 MHz is 25.2 dBm and 52 dB, respectively.
A NIMA-related kinase, Cnk2p, regulates both flagellar length and cell size in Chlamydomonas

The cycle of ciliogenesis and ciliary disassembly is coordinated with cell division. In the unicellular alga Chlamydomonas, the two flagella are maintained at constant and equal length during interphase, and are reabsorbed prior to mitosis. We report that the NIMA-related kinase, Cnk2p, is an axonemal protein that affects flagellar length via effects on disassembly rate and also plays a role in the cellular assessment of size prior to committing to mitosis. This is the second NIMA-related kinase shown to affect ciliary function and cell cycle progression in Chlamydomonas. We speculate that members of the NIMA family have evolved nuanced roles to coordinate cilia/cell cycle regulation.
Robust decentralized actuator fault detection and estimation for large-scale systems using a sliding mode observer

In this paper, robust decentralized actuator fault detection and estimation is considered for a class of non-linear large-scale systems. A sliding mode observer is proposed together with an appropriate coordinate transformation to find the sliding mode dynamics. Then, based on the features of the observer, a decentralized fault estimation strategy is proposed using an equivalent output error injection, and a decentralized reconstruction scheme follows by further exploiting the structure of the uncertainty which is allowed to have non-linear bounds. The estimation and reconstruction signals only depend on the available measured information and thus the proposed strategy can work on-line. The theoretical results which have been obtained are applied to an automated highway system. Simulation shows the feasibility and effectiveness of the proposed scheme.
Aggression recognition using overlapping speech

Automatic recognition of negative affect and aggression is key in many safety critical domains such as surveillance and health care. In this paper we explore the potential of overlapping speech for predicting aggression levels. As a first step we consider 3 categories of overlapping speech based on literature. Having an annotation of these overlap categories, we examine whether overlapping speech is a good feature for predicting aggression by using it in classification together with a set of acoustic features typically used for this purpose. Next, we explore if this fine categorization of overlap is necessary in predicting aggression levels or a more coarse representation is sufficient. Finally, we check the additive values of automatically predicted overlapping speech for aggression recognition. The experiments are performed on a dataset of dyadic interactions between professional aggression training actors (actors) and naive participants (students) interacting freely based on short role descriptions. Our findings show that overlapping speech is a key feature for predicting aggression levels, that discriminating only severe cases of overlap is a sufficient feature and that automatically predicted overlap is improving aggression recognition as well.
Ovarian Steroid Regulation of Estrogen and Progesterone Receptor Messenger Ribonucleic Acid in the Anteroventral Periventricular Nucleus of the Rat

The anteroventral periventricular nucleus of the preoptic region (AVPV) represents a key site for hormonal feedback on gonadotropin secretion. It plays a critical role in the neural control of luteinizing hormone secretion and contains high densities of neurons that express receptors for estrogen and progesterone. In this study in situ hybridization was used to examine the expression of mRNAs encoding the estrogen (ER) and progesterone (PR) receptors in the AVPV during the estrous cycle. ER gene expression fluctuated during the cycle with the lowest levels of ER mRNA observed in animals killed on the afternoon of proestrus, and the highest levels present in animals killed during metestrus. This apparent inverse relationship between circulating levels of estradiol (E2) and ER mRNA levels in AVPV neurons was supported by the observation that treatment of ovariectomized rats with E2 suppressed expression of ER mRNA in the AVPV. The influence of progesterone (P4) on ER expression was less pronounced, but a significant increase in ER mRNA in the AVPV was detected 3 h after treatment with P4. In contrast, PR mRNA levels were highest in the AVPV during diestrus and lowest on the morning of proestrus suggesting that PR expression in the AVPV is regulated in a complex manner that may reflect the combined regulatory effects of E2 and P4. E2 treatment caused a dramatic induction of PR mRNA in the AVPV, but P4 did not affect PR mRNA expression acutely, although PR mRNA appears to be attenuated in the AVPV 27 h after P4 treatment. These findings suggest that ovarian steroid hormones regulate ER and PR gene expression in the AVPV during the estrous cycle, which may represent molecular events that contribute to cyclic changes in the responsiveness of AVPV neurons to steroid hormones.
Enhanced primary care items. Their use in diabetes management.

BACKGROUND The Enhanced Primary Care (EPC) items for care planning and case conferencing provide an opportunity for better quality care for people with chronic disease. OBJECTIVE To explore the use of the EPC items in the structured care of diabetes based on evidenced based guidelines in general practice. DISCUSSION Care planning and case conferencing are useful, especially in the structured care of patients who have poor control. The achievement of better health outcome for these patients depends upon a patient oriented and structured approach in collaboration with other health professionals. This needs to be supported by systems within the practice, Division and local community.
Noise Reduction in Arterial Spin Labeling Based Functional Connectivity Using Nuisance Variables

Arterial Spin Labeling (ASL) perfusion image series have recently been utilized for functional connectivity (FC) analysis in healthy volunteers and children with autism spectrum disorders (ASD). Noise reduction by using nuisance variables has been shown to be necessary to minimize potential confounding effects of head motion and physiological signals on BOLD based FC analysis. The purpose of the present study is to systematically evaluate the effectiveness of different noise reduction strategies (NRS) using nuisance variables to improve perfusion based FC analysis in two cohorts of healthy adults using state of the art 3D background-suppressed (BS) GRASE pseudo-continuous ASL (pCASL) and dual-echo 2D-EPI pCASL sequences. Five different NRS were performed in healthy volunteers to compare their performance. We then compared seed-based FC analysis using 3D BS GRASE pCASL in a cohort of 12 children with ASD (3f/9m, age 12.8 ± 1.3 years) and 13 typically developing (TD) children (1f/12m; age 13.9 ± 3 years) in conjunction with NRS. Regression of different combinations of nuisance variables affected FC analysis from a seed in the posterior cingulate cortex (PCC) to other areas of the default mode network (DMN) in both BOLD and pCASL data sets. Consistent with existing literature on BOLD-FC, we observed improved spatial specificity after physiological noise reduction and improved long-range connectivity using head movement related regressors. Furthermore, 3D BS GRASE pCASL shows much higher temporal SNR compared to dual-echo 2D-EPI pCASL and similar effects of noise reduction as those observed for BOLD. Seed-based FC analysis using 3D BS GRASE pCASL in children with ASD and TD children showed that noise reduction including physiological and motion related signals as nuisance variables is crucial for identifying altered long-range connectivity from PCC to frontal brain areas associated with ASD. This is the first study that systematically evaluated the effects of different NRS on ASL based FC analysis. 3D BS GRASE pCASL is the preferred ASL sequence for FC analysis due to its superior temporal SNR. Removing physiological noise and motion parameters is critical for detecting altered FC in neurodevelopmental disorders such as ASD.