Miracle-dz/UniFAR-FTUs huggingface dataset:
Critical Role of GFRα1 in the Development and Function of the Main Olfactory System

Glial cell line-derived neurotrophic factor (GDNF) and its receptor GFRα1 are prominently expressed in the olfactory epithelium (OE) and olfactory bulb (OB), but their importance for olfactory system development is completely unknown. We have investigated the consequences of GFRα1 deficiency for mouse olfactory system development and function. In the OE, GFRα1 was expressed in basal precursors, immature olfactory sensory neurons (OSNs), and olfactory ensheathing cells (OECs), but was excluded from mature OSNs. The OE of newborn Gfra1 knock-out mice was thinner and contained fewer OSNs, but more dividing precursors, suggesting deficient neurogenesis. Immature OSN axon bundles were enlarged and associated OECs increased, indicating impaired migration of OECs and OSN axons. In the OB, GFRα1 was expressed in immature OSN axons and OECs of the nerve layer, as well as mitral and tufted cells, but was excluded from GABAergic interneurons. In newborn knock-outs, the nerve layer was dramatically reduced, exhibiting fewer axons and OECs. Bulbs were smaller and presented fewer and disorganized glomeruli and a significant reduction in mitral cells. Numbers of tyrosine hydroxylase-, calbindin-, and calretinin-expressing interneurons were also reduced in newborn mice lacking Gfra1. At birth, the OE and OB of Gdnf knock-out mice displayed comparable phenotypes. Similar deficits were also found in adult heterozygous Gfra1+/− mutants, which in addition displayed diminished responses in behavioral tests of olfactory function. We conclude that GFRα1 is critical for the development and function of the main olfactory system, contributing to the development and allocation of all major classes of neurons and glial cells.
Measuring bronchodilation in COPD clinical trials.

AIMS The aim of this study was to compare the variability and sensitivity of impulse oscillometry (R5, X5 and RF), plethysmography (Raw and sGaw) and spirometry (FEV1, FVC and MMEF) in order to determine the most powerful technique for assessing bronchodilation in COPD clinical trials. METHODS Twenty-four patients with COPD had impulse oscillometry, plethysmography and spirometry measured twice 30 mins apart, to determine variability. Then ascending doses of salbutamol (20, 50, 100, 200, 400 and 800 microg) were given and the same measurements made after each dose. Significant changes greater than variability were determined for each performed measurement (expressed as mean percentage improvement with 95% CI). RESULTS Significant effects (P < 0.05) were detected after 20 microg by X5 (18.5% CI 9.8-27.2) RF (11.1% CI 7.2-15.0) and sGaw (21.5% CI 10.1-32.9), and after 50 microg by R5 (16.7% CI 10.8-22.5) and Raw (19.7% CI 13.0-26.4). FEV1 was less sensitive, detecting significant bronchodilation at 100 microg (10.2% CI 7.4-12.9). CONCLUSIONS We conclude that impulse oscillometry and plethysmography should be considered the preferred techniques for measuring bronchodilation in COPD clinical trials.
Metabolomic Profiling of Plasma from Patients with Tuberculosis by Use of Untargeted Mass Spectrometry Reveals Novel Biomarkers for Diagnosis

ABSTRACT Although tuberculosis (TB) is a reemerging disease that affects people in developing countries and immunocompromised populations in developed countries, the current diagnostic methods are far from optimal. Metabolomics is increasingly being used for studies on infectious diseases. We performed metabolome profiling of plasma samples to identify potential biomarkers for diagnosing TB. We compared the plasma metabolome profiles of TB patients (n = 46) with those of community-acquired pneumonia (CAP) patients (n = 30) and controls without active infection (n = 30) using ultrahigh-performance liquid chromatography–electrospray ionization-quadrupole time of flight mass spectrometry (UHPLC-ESI-QTOFMS). Using multivariate and univariate analyses, four metabolites, 12R-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid [12(R)-HETE], ceramide (d18:1/16:0), cholesterol sulfate, and 4α-formyl-4β-methyl-5α-cholesta-8-en-3β-ol, were identified and found to have significantly higher levels in TB patients than those in CAP patients and controls. In a comparison of TB patients and controls, the four metabolites demonstrated area under the receiver operating characteristic curve (AUC) values of 0.914, 0.912, 0.905, and 0.856, sensitivities of 84.8%, 84.8%, 87.0%, and 89.1%, specificities of 90.0%, 86.7%, 86.7%, and 80.0%, and fold changes of 4.19, 26.15, 6.09, and 1.83, respectively. In a comparison of TB and CAP patients, the four metabolites demonstrated AUC values of 0.793, 0.717, 0.802, and 0.894, sensitivities of 89.1%, 71.7%, 80.4%, and 84.8%, specificities of 63.3%, 66.7%, 70.0%, and 83.3%, and fold changes of 4.69, 3.82, 3.75, and 2.16, respectively. 4α-Formyl-4β-methyl-5α-cholesta-8-en-3β-ol combined with 12(R)-HETE or cholesterol sulfate offered ≥70% sensitivity and ≥90% specificity for differentiating TB patients from controls or CAP patients. These novel plasma biomarkers, especially 12(R)-HETE and 4α-formyl-4β-methyl-5α-cholesta-8-en-3β-ol, alone or in combination, are potentially useful for rapid and noninvasive diagnosis of TB. The present findings may offer insights into the pathogenesis and host response in TB.
Role of KatG catalase‐peroxidase in mycobacterial pathogenesis: countering the phagocyte oxidative burst

Reactive nitrogen species (RNS) play an essential role in host defence against Mycobacterium tuberculosis (MTB) in the mouse model of tuberculosis (TB), as evidenced by the increased susceptibility of mice deficient in the inducible isoform of nitric oxide synthase (NOS2). In contrast, the role of reactive oxygen species (ROS) in protection against MTB is less clear, and mice defective in the ROS‐generating phagocyte NADPH oxidase (Phox) are relatively resistant. This suggests that MTB might possess efficient mechanisms to evade or counter the phagocyte oxidative burst, effectively masking the impact of this host defence mechanism. In order to assess the role of ROS detoxification pathways in MTB virulence, we generated a katG null mutant of MTB, deficient in the KatG catalase‐peroxidase‐peroxynitritase, and evaluated the mutant's ability to replicate and persist in macrophages and mice. Although markedly attenuated in wild‐type C57Bl/6 mice and NOS2–/– mice, the ΔkatG MTB strain was indistinguishable from wild‐type MTB in its ability to replicate and persist in gp91Phox–/– mice lacking the gp91 subunit of NADPH oxidase. Similar observations were made with murine bone marrow macrophages infected ex vivo: growth of the ΔkatG MTB strain was impaired in macrophages from C57Bl/6 and NOS2–/– mice, but indistinguishable from wild‐type MTB in gp91Phox–/– macrophages. These results indicate that the major role of KatG in MTB pathogenesis is to catabolize the peroxides generated by the phagocyte NADPH oxidase; in the absence of this host antimicrobial mechanism, KatG is apparently dispensable.
Pattern matrix design of PDMA for 5G UL applications

In this paper, a multiple parameters weighted fractional Fourier transform (MP-WFRFT) and constellation scrambling (CS) method based physical layer (PHY) security system is proposed. The proposed scheme is executed by two steps. In the first step, MP-WFRFT, implemented as the constellation beguiling (CB) method, is applied to change the signal's identity. In the second step the additional pseudo random phase information, regarded as the encryption key, is attached to the original signal to enhance the security. Typically, the pseudo random phase information can be removed effectively by the legitimate receiver. In contrast to the cryptography based encryption algorithms and the conventional PHY secrecy techniques, the main contribution of the proposed scheme is concentrated on the variation in signal's characteristics. Simulation results show that the proposed scheme can prevent the exchanging signal from eavesdroppers' classification or inception. Moreover, the proposed scheme can guarantee the BER performance at a tolerate increasing in computational complexity for the legitimate receivers.
Predictors of treatment preference for mandibular fracture.

BACKGROUND Patient treatment preferences do not necessarily remain stable over time. OBJECTIVE This study focuses on predictors of patient treatment choice and on the extent to which patients are willing to take risks by choosing surgical versus nonsurgical treatment for mandibular fracture. METHODS Surveys of African-American and Hispanic adults receiving treatment at King/Drew Medical Center for either a mandibular fracture (n = 98) or third-molar removal (n = 105) were used to investigate patterns of patient preference over the course of a 4-month study period using generalized estimating equations controlling for age, gender, income, and fracture versus third-molar patient. The study examined the effects of symptom rating and a"standard gamble" measure reflecting a patient's willingness to accept scarring or nerve damage. This analysis is based on 169 patients who participated in four waves of data collection. RESULTS The most salient predictor of patient treatment was the standard gamble measure at 1-month follow-up. Subjects with higher risk tolerance were more likely to select surgery versus jaw wiring. A higher likelihood of choosing surgery was associated with higher income and greater symptom severity. Fracture patients were more likely to select surgery compared with third-molar patients. CONCLUSIONS The significance of symptom severity 1-month post-surgery raises an important issue regarding the healing process. Moreover, the significance of standard gamble as a predictor of treatment choice for mandibular fracture should encourage other researchers to use this measure of willingness to accept risk when studying acute conditions such as jaw fracture.
Localization of relaxin receptors in arteries and veins, and region‐specific increases in compliance and bradykinin‐mediated relaxation after in vivo serelaxin treatment

Relaxin is a potent vasodilator of small resistance arteries and modifies arterial compliance in some systemic vascular beds, yet receptors for relaxin, such as RXFP1, have only been localized to vascular smooth muscle. This study first aimed to localize RXFP1 in rat arteries and veins from different organ beds and determine whether receptors are present in endothelial cells. We then tested the hypothesis that region‐specific vascular effects of relaxin may be influenced by the cellular localization of RXFP1 within different blood vessels. The aorta, vena cava, mesenteric artery, and vein had significantly higher (P<0.05) RXFP1 immunostaining in endothelial cells compared with vascular smooth muscle, whereas the femoral artery and vein and small pulmonary arteries had higher (P<0.01) RXFP1 immunostaining in the vascular smooth muscle. Male rats were treated subcutaneously with recombinant human relaxin‐2 (serelaxin; 4 μg/h) for 5 d; vasodilation and compliance in mesenteric and femoral arteries and veins were compared with placebo controls. Serelaxin significantly (P=0.04) reduced wall stiffness and increased volume compliance in mesenteric arteries but not in the other vessels examined. This was associated with changes in geometrical properties, and not compositional changes in the extracellular matrix. Serelaxin treatment had no effect on acetylcholine‐mediated relaxation but significantly (P< 0.001) enhanced bradykinin (BK)‐mediated relaxation in mesenteric arteries, involving enhanced nitric oxide but not endothelium‐derived hyperpolarization or vasodilatory prostanoids. In conclusion, there is differential distribution of RXFP1 on endothelial and smooth muscle across the vasculature. In rats, mesenteric arteries exhibit the greatest functional response to chronic serelaxin treatment. —Jelinic, M. , Leo, C‐H. , Post Uiterweer, E. P., Sandow, S. L. , Gooi, J. H. , Wlodek, M. E. , Conrad, K. P., Parkington, H. , Tare, M. , Parry, L. J. Localization of relaxin receptors in arteries and veins, and region‐specific increases in compliance and bradykinin‐mediated relaxation after in vivo serelaxin treatment. FASEB J. 28, 275–287 (2014). www.fasebj. org
Muscle fatigability and depressive symptoms in later life

Fatigability is the degree to which performance decreases during a specific activity of a given intensity and duration. Depression is known to heighten subjective fatigue, but whether its association with physical fatigability is unknown. Further, whether fatigability is a precursor or risk factor for the development of subsequent depressive symptoms is also unclear.
A national retinal screening programme for diabetes in Scotland

The Health Technology Board Scotland (HTBS) have issued recommendations for eye screening in patients with diabetes. These are based on evidence‐based clinical studies. Evidence‐based studies do not answer all the practical issues, and some conclusions have thus been extrapolated from the known evidence base. Other factors such as patient issues, organizational issues and cost effectiveness have also been incorporated into the recommendations. HTBS recommend single‐field digital retinal photography. Retinal photography best addresses the issues of adequate sensitivity and accountable quality assurance. Non‐mydriatic photography is recommended, followed by immediate use of dilating eye drops if it is unsuccessful, followed by slit‐lamp examination if both of these approaches fail. An independent grading scheme has been established, which is similar to the ‘Global’, and compatible with the National Screening Committee (NSC) grading scheme. The rationale for these recommendations, and debate behind some of the decisions, is laid out in this article.
Effect of rabeprazole and omeprazole on the onset of gastro-oesophageal reflux disease symptom relief during the first seven days of treatment

Objective. Gastro-oesophageal reflux disease (GORD) symptoms have a significant impact on patients’ well-being. Onset of symptom relief is therefore an important consideration in GORD treatment. The primary objective was to compare the efficacy of rabeprazole (20 mg) and omeprazole (20 mg) regarding onset of heartburn control during the first 7 days of treatment in patients with erosive oesophagitis. Secondary objectives included maintenance of sustained heartburn control, control of other GORD symptoms (e.g. acid regurgitation, epigastric pain, dysphagia), effect on quality of life, patient satisfaction with treatment, and adverse events. Material and methods. In this multicentre, randomized, parallel-group, double-blind, comparative study, performed in Europe and Iceland, patients with endoscopically confirmed erosive oesophagitis were randomized to receive once-daily treatment with rabeprazole 20 mg (n=358) or omeprazole 20 mg (n=359) for 7 days. Symptoms were recorded (scored on a 5-point Likert scale) twice daily by the patients on their diary cards. Results. Median time to reach heartburn control was 1.5 days for both the rabeprazole and omeprazole groups (p<0.43). The results were similar between treatments for other study parameters. Both treatments were well tolerated. Conclusions. Unlike previous studies, no significant differences were found between treatments with rabeprazole (20 mg) and omeprazole (20 mg) in this study. Further studies are needed to evaluate the potential benefit of fast-acting proton-pump inhibitors, such as rabeprazole, with respect to onset of symptom control in erosive GORD.
Calcium–calmodulin‐dependent protein kinase II phosphorylation modulates PSD‐95 binding to NMDA receptors

At the postsynaptic membrane of excitatory synapses, NMDA‐type receptors are bound to scaffolding and signalling proteins that regulate the strength of synaptic transmission. The cytosolic tails of the NR2A and NR2B subunits of NMDA receptor bind to calcium–calmodulin‐dependent protein kinase II (CaMKII) and to members of the MAGUK family such as PSD‐95. In particular, although NR2A and NR2B subunits are highly homologous, the sites of their interaction with CaMKII as well as the regulation of this binding differ. We identified PSD‐95 phosphorylation as a molecular mechanism responsible for the dynamic regulation of the interaction of both PSD‐95 and CaMKII with the NR2A subunit. CaMKII‐dependent phosphorylation of PSD‐95 occurs both in vitro, in GST‐PSD‐95 fusion proteins phosphorylated by purified active CaMKII, and in vivo, in transfected COS‐7 as well as in cultured hippocampal neurons. We identified Ser73 as major phosphorylation site within the PDZ1 domain of PSD‐95, as confirmed by point mutagenesis experiments and by using a phospho‐specific antibody. PSD‐95 Ser73 phosphorylation causes NR2A dissociation from PSD‐95, while it does not interfere with NR2B binding to PSD‐95. These results identify CaMKII‐dependent phosphorylation of the PDZ1 domain of PSD‐95 as a mechanism regulating the signalling transduction pathway downstream NMDA receptor.
Barriers to Information Access across Languages on the Internet: Network and Language Effects

This paper investigates the role of language in accessing information on the Internet. We combined data about website visitors through log-file analysis with data about web-hosts and links obtained from a crawler. Results suggest that language may represent a double barrier: first, the number of native speakers determines the number of web-hosts, and hence the amount of information and the interconnectedness of information sources. Second, to access information on a particular website the languages offered are an even more important factor than network effects: non-native speakers and links from websites in other languages are always underrepresented. Our results are in line with the Information Foraging Theory, the Revised Hierarchy Model, network and market theories, and emphasize the role of language on the Internet. Insight into these processes is helpful when website translation represents important investment decisions, or when aiming to diminish the digital divide.
Prognostic Factor Analysis for Management of Chronic Neck Pain: Can We Predict the Severity of Neck Pain with Lateral Cervical Curvature?

Objective Although little is known about its origins, neck pain may be related to several associated anatomical pathologies. We aimed to characterize the incidence and features of chronic neck pain and analyze the relationship between neck pain severity and its affecting factors. Methods Between March 2012 and July 2013, we studied 216 patients with chronic neck pain. Initially, combined tramadol (37.5 mg) plus acetaminophen (325 mg) was administered orally twice daily (b.i.d.) to all patients over a 2-week period. After two weeks, patients were evaluated for neck pain during an outpatient clinic visit. If the numeric rating scale of the patient had not decreased to 5 or lower, a cervical medial branch block (MBB) was recommended after double-dosed previous medication trial. We classified all patients into two groups (mild vs. severe neck pain group), based on medication efficacy. Logistic regression tests were used to evaluate the factors associated with neck pain severity. Results A total of 198 patients were included in the analyses, due to follow-up loss in 18 patients. While medication was successful in reducing pain in 68.2% patients with chronic neck pain, the remaining patients required cervical MBB. Lateral cervical curvature, such as a straight or sigmoid type curve, was found to be significantly associated with the severity of neck pain. Conclusion We managed chronic neck pain with a simple pharmacological management protocol followed by MBB. We should keep in mind that it may be difficult to manage the patient with straight or sigmoid lateral curvature only with oral medication.
What automated age estimation of hand and wrist MRI data tells us about skeletal maturation in male adolescents

Abstract Background: Age estimation of individuals is important in human biology and has various medical and forensic applications. Recent interest in MR-based methods aims to investigate alternatives for established methods involving ionising radiation. Automatic, software-based methods additionally promise improved estimation objectivity. Aim: To investigate how informative automatically selected image features are regarding their ability to discriminate age, by exploring a recently proposed software-based age estimation method for MR images of the left hand and wrist. Subjects and methods: One hundred and two MR datasets of left hand images are used to evaluate age estimation performance, consisting of bone and epiphyseal gap volume localisation, computation of one age regression model per bone mapping image features to age and fusion of individual bone age predictions to a final age estimate. Results: Quantitative results of the software-based method show an age estimation performance with a mean absolute difference of 0.85 years (SD = 0.58 years) to chronological age, as determined by a cross-validation experiment. Qualitatively, it is demonstrated how feature selection works and which image features of skeletal maturation are automatically chosen to model the non-linear regression function. Conclusion: Feasibility of automatic age estimation based on MRI data is shown and selected image features are found to be informative for describing anatomical changes during physical maturation in male adolescents.
Pasteurization Procedures for Donor Human Milk Affect Body Growth, Intestinal Structure, and Resistance against Bacterial Infections in Preterm Pigs.

Background: Holder pasteurization (HP) destroys multiple bioactive factors in donor human milk (DM), and UV-C irradiation (UVC) is potentially a gentler method for pasteurizing DM for preterm infants.Objective: We investigated whether UVC-treated DM improves gut maturation and resistance toward bacterial infections relative to HP-treated DM.Methods: Bacteria, selected bioactive components, and markers of antioxidant capacity were measured in unpasteurized donor milk (UP), HP-treated milk, and UVC-treated milk (all from the same DM pool). Fifty-seven cesarean-delivered preterm pigs (91% gestation; ratio of males to females, 30:27) received decreasing volumes of parental nutrition (average 69 mL · kg-1 · d-1) and increasing volumes of the 3 DM diets (n = 19 each, average 89 mL · kg-1 · d-1) for 8-9 d. Body growth, gut structure and function, and systemic bacterial infection were evaluated.Results: A high bacterial load in the UP (6×105 colony forming units/mL) was eliminated similarly by HP and UVC treatments. Relative to HP-treated milk, both UVC-treated milk and UP showed greater activities of lipase and alkaline phosphatase and concentrations of lactoferrin, secretory immunoglobulin A, xanthine dehydrogenase, and some antioxidant markers (all P < 0.05). The pigs fed UVC-treated milk and pigs fed UP showed higher relative weight gain than pigs fed HP-treated milk (5.4% and 3.5%), and fewer pigs fed UVC-treated milk had positive bacterial cultures in the bone marrow (28%) than pigs fed HP-treated milk (68%) (P < 0.05). Intestinal health was also improved in pigs fed UVC-treated milk compared with those fed HP-treated milk as indicated by a higher plasma citrulline concentration (36%) and villus height (38%) (P < 0.05) and a tendency for higher aminopeptidase N (48%) and claudin-4 (26%) concentrations in the distal intestine (P < 0.08). The gut microbiota composition was similar among groups except for greater proportions of Enterococcus in pigs fed UVC-treated milk than in pigs fed UP and those fed HP-treated milk in both cecum contents (20% and 10%) and distal intestinal mucosa (24% and 20%) (all P < 0.05). Conclusions: UVC is better than HP treatment in preserving bioactive factors in DM. UVC-treated milk may induce better weight gain, intestinal health, and resistance against bacterial infections as shown in preterm pigs as a model for DM-fed preterm infants.