Miracle-dz/UniFAR-FTUs huggingface dataset:
Accumulation of Advanced Glycation End Products, Measured as Skin Autofluorescence, in Renal Disease

Abstract: Advanced glycation end products (AGEs) accumulate during renal failure and dialysis. Kidney transplantation is thought to reverse this accumulation by restoring renal function. Using a noninvasive and validated autofluorescence reader, we evaluated AGE levels in 285 transplant recipients (mean age, 52 years; range, 41 to 60 years), 32 dialysis patients (mean age, 56 years; range, 43 to 65 years), and 231 normal control subjects (mean age, 51 years; range, 40 to 65 years). Measurements in transplant recipients were performed for a mean of 73 months (range, 32 to 143 months) after transplantation. Dialysis patients were on dialysis therapy for a mean of 42 months (range, 17 to 107 months). Fluorescence was significantly increased in dialysis patients compared with normal control subjects (2.8 vs. 2.0 arbitrary units [a.u.], P < .0001). Although fluorescence levels were significantly decreased in transplant recipients compared with dialysis patients (2.5 vs. 2.8 a.u., P < .0001), fluorescence in transplant recipients was higher than in controls (2.5 vs. 2.0 a.u., P < .0001). In transplant recipients, fluorescence correlated positively with the duration of dialysis prior to transplantation (R= 0.21, P < .0001), and negatively with creatinine clearance (R=−0.34, P < .0001). No correlation was found between time after transplantation and fluorescence in transplant recipients (R=−0.10, P= .10). Fluorescence in dialysis patients was positively correlated with duration of dialysis (R= 0.36, P= .042). Our results, like those of others, suggest that kidney transplantation does not fully correct increased AGE levels found in dialysis patients. The increased AGE levels in kidney transplant recipients cannot be explained by the differences in renal function alone. The availability of a simple, noninvasive method (AGE‐Reader) to measure AGE accumulation may be used to monitor AGE accumulation in a clinical setting as well as in a study setting.
Can attention to the intestinal microbiota improve understanding and treatment of anorexia nervosa?

ABSTRACT Anorexia nervosa (AN) is characterized by severe dietary restriction or other weight loss behaviors and exhibits the highest mortality rate of any psychiatric disorder. Therapeutic renourishment in AN is founded primarily on clinical opinion and guidelines, with a weak evidence base. Genetic factors do not fully account for the etiology of AN, and non-genetic factors that contribute to the onset and persistence of this disease warrant investigation. Compelling evidence that the intestinal microbiota regulates adiposity and metabolism, and more recently, anxiety behavior, provides a strong rationale for exploring the role of this complex microbial community in the onset, maintenance of, and recovery from AN. This review explores the relationship between the intestinal microbiota and AN and a potential role for this enteric microbial community as a therapy for this severe illness.
Cuticular hydrocarbons corroborate the distinction between lowland and highland Natal fruit fly (Tephritidae, Ceratitis rosa) populations

Abstract The cuticular hydrocarbons (CHs) and morphology of two Ceratitis rosa Karsch (Diptera: Tephritidae) populations, putatively belonging to two cryptic taxa, were analysed. The chemical profiles were characterised by two-dimensional gas chromatography with mass spectrometric detection. CHs of Ceratitis rosa that originated from the lowlands and highlands of Kenya comprised of n-alkanes, monomethylalkanes, dimethylalkanes and unsaturated hydrocarbons in the range of the carbon backbone from C14 to C37. Hydrocarbons containing C29, C31, C33 and C35 carbon atoms predominated in these two populations. 2-Methyltriacontane was the predominant compound in both populations. Quantitative differences in the distribution of hydrocarbons of different chain lengths, mainly the C22, C32, C33 and C34 compounds of these two populations, were observed despite indistinct qualitative differences in these hydrocarbons. Morphological analyses of male legs confirmed that the flies belong to different morphotypes of Ceratitis rosa previously labelled as R1 and R2 for lowland and highland populations, respectively. A statistical analysis of the CH compositions of the putative R1 and R2 species showed distinct interspecific identities, with several CHs specific for each of the lowland and highland populations. This study supports a hypothesis that the taxon Ceratitis rosa consists of at least two biological species.
Lung epithelial Na channel subunits are differentially regulated during development and by steroids.

Because the alpha-subunit of the rat lung epithelial Na channel (rENaC) is not expressed until late fetal gestation, the developmental immaturity of alpha-rENaC may be involved in the premature fetal lung's inability to mount a Na-absorptive response to appropriate agonists. As previous work has shown that the beta- and gamma-rENaC subunits of the Na channel are required for maximal alpha-rENaC activity, we determined their developmental expression in the fetal lung. In addition, because thyroid and corticosteroid therapy can mature the in vivo fetal lamb lung's ability to transport Na, we wished to determine whether such treatment increased the expression of alpha-, beta-, and gamma-rENaC. Lungs were harvested from normal rat fetuses of 17 through 22 days gestation (term = 22 days), normal rat pups during the first week of life, and adult rats. Initial expression of alpha-rENaC was detected at 19 days gestation and progressively increased in utero. beta- and gamma-rENaC mRNA were not detected until 21 and 22 days gestation, and then only at very low levels. During the first week after birth, the levels of alpha-rENaC declined, whereas beta- and gamma-rENaC mRNA levels increased. This pre- and postnatal pattern of alpha-rENaC expression correlates with the endogenous glucocorticosteroid levels in the fetus and the rat pup's early postnatal corticosteroid resistance. Combined or separate treatment of pregnant rats (16 through 22 days gestational age) with thyroid-releasing hormone (TRH) and/or dexamethasone (Dex) for 48 h showed that Dex, but not TRH, could increase fetal lung alpha-rENaC mRNA levels. (ABSTRACT TRUNCATED AT 250 WORDS)
Efficacy of a Dual-ring Wound Protector for Prevention of Surgical Site Infections After Pancreaticoduodenectomy in Patients With Intrabiliary Stents: A Randomized Clinical Trial

Objective: To evaluate the efficacy of a dual-ring wound protector for preventing incisional surgical site infection (SSI) among patients with preoperative biliary stents undergoing pancreaticoduodenectomy (PD). Methods and analysis: This study was a parallel, dual-arm, double-blind randomized controlled trial. Adult patients with a biliary stent undergoing elective PD at 2 tertiary care institutions were included (February 2013 to May 2016). Patients were randomly assigned to receive a surgical dual-ring wound protector or no wound protector, and also the current standard of care. The main outcome measure was incisional SSI, as defined by the Centers for Disease Control and Prevention criteria, within 30 days of the index operation. Results: A total of 107 patients were recruited (mean age 67.2 years; standard deviation 12.9; 65% male). No significant differences were identified between the intervention and control groups (age, sex, body mass index, preoperative comorbidities, American Society of Anesthesiologists class, prestent cholangitis). There was a significant reduction in the incidence of incisional SSI in the wound protector group (21.1% vs 44.0%; relative risk reduction 52%; P = 0.010). Patients with completed PD also displayed a decrease in incisional SSI with use of the wound protector compared with those palliated surgically (27.3% vs 48.7%; P = 0.04). Multivariate analysis did not identify any significant modifying factor relationships (estimated blood loss, duration of surgery, hospital site, etc.) (P > 0.05). Conclusion: Among adult patients with intrabiliary stents, the use of a dual-ring wound protector during PD significantly reduces the risk of incisional SSI.
Characteristics of Hospitalised Patients at the Lowest and Highest Ends of the Body Mass Index Spectrum

Background: Recent findings established that underweight (UW) and extremely obese (EO) people were over-represented in the inpatient cohort of one Australian tertiary hospital. This study aimed to describe the characteristics of these patients and identify if differences existed between this subset and the remaining cohort. Method: Single-centre retrospective case-note review of patients previously identified as being UW or EO during a 2015 prospective point prevalence study, and comparison with those who had “closer-to-normal-weight” body mass index (BMI). Results: Forty eight patient notes were reviewed (33 UW; 15 EO). The majority of UW patients were admitted under General Medicine with cancer-related illness, whereas EO patients were admitted across specialties, most commonly with a cardiovascular condition. The most frequent past medical history for both groups was a cardiovascular disorder. Compared to patients in all other BMI categories, there was no higher risk of prolonged hospital length of stay in either patient group (p = 0.94). Underweight patients had significantly higher age-adjusted Charlson co-morbidity index scores compared to the EO group (p = 0.01), and although not statistically significant, there was higher frequency of mortality (in-hospital, 28-day and 1-year post-discharge) in those UW (p = 0.54; p = 1; p = 1 respectively). Both groups demonstrated higher rates of hospital re-admission within 28 days of discharge than those reported for this hospital as a whole. Conclusion: Data presented adds to the limited evidence relating to health outcomes for patients at either end of the BMI spectrum. Decreasing hospital re-admission frequency in these groups might result in considerable cost savings in the future.
MiR-323 Inhibits Prostate Cancer Vascularization Through Adiponectin Receptor

Background/Aims: The current treatments fail to provide satisfactory cure for aggressive prostate cancers (PCs). Hence, further comprehension of PC metastasis is highly appreciated for improving the levels of therapy. We have previously shown that Adiponectin reduces the levels of vascular endothelial growth factor A (VEGF-A) in PCs to suppress tumor-associated neovascularization, possibly through AMPK/mTor signaling. Here, we studied the regulation of Adiponectin signaling in PCs. Methods: We analyzed the levels and correlation of Adiponectin receptor 1 (AdipoR1) and microRNA-323 (miR-323) in the PC specimen, compared to the paired normal prostate tissue. We analyzed the binding of miR-323 to the 3'UTR of AdipoR1 mRNA and its effects on AdipoR1 translation by bioinformatics analysis and by luciferase-reporter assay, respectively. We modified miR-323 levels in PC cells, and examined the effects on the expression of AdipoR1 and VEGF-A, as well as on vessel formation in a human umbilical vein endothelial cells (HUVECs) transwell collagen gel assay. Results: We detected significantly lower levels of AdipoR1 and significantly higher levels of miR-323 in PC specimen. Moreover, the levels of AdipoR1 and miR-323 are inversely correlated. Moreover, miR-323 was found to bind to the 3'UTR of AdipoR1 mRNA to inhibit its translation. Overexpression of miR-323 in PC cells decreased AdipoR1 protein levels, whereas inhibition of miR-323 increased AdipoR1 protein levels, without affecting AdipoR1 transcripts. Moreover, overexpression of miR-323 increased the levels of VEGF-A and the vessel formation by HUVECs, while inhibition of miR-323 decreased the levels of VEGF-A and the vessel formation by HUVECs. Conclusion: Our data demonstrate that miR-323 may increase VEGF-A-mediated cancer vascularization in PC cells through AdipoR1 suppression.
Molecular Identification of a Novel Candidate Sorting Receptor Purified from Human Brain by Receptor-associated Protein Affinity Chromatography*

Receptor-associated protein (RAP) is an endoplasmic reticulum/Golgi protein involved in the processing of receptors of the low density lipoprotein receptor family. A ∼95-kDa membrane glycoprotein, designated gp95/sortilin, was purified from human brain extracts by RAP affinity chromatography and cloned in a human cDNA library. The gene maps to chromosome 1p and encodes an 833-amino acid type I receptor containing an N-terminal furin cleavage site immediately preceding the N terminus determined in the purified protein. Gp95/sortilin is expressed in several tissues including brain, spinal cord, and testis. Gp95/sortilin is not related to the low density lipoprotein receptor family but shows intriguing homologies to established sorting receptors: a 140-amino acid lumenal segment of sortilin representing a hitherto unrecognized type of extracellular module shows extensive homology to corresponding segments in each of the two lumenal domains of yeast Vps10p, and the extreme C terminus of the cytoplasmic tail of sortilin contains the casein kinase phosphorylation consensus site and an adjacent dileucine sorting motif that mediate assembly protein-1 binding and lysosomal sorting of the mannose-6-phosphate receptors. Expression of a chimeric receptor containing the cytoplasmic tail of gp95/sortilin demonstrates evidence that the tail conveys colocalization with the cation-independent mannose6-phosphate receptor in endosomes and the Golgi compartment.
Advances in and Limitations of Up-and-down Methodology: A Précis of Clinical Use, Study Design, and Dose Estimation in Anesthesia Research

Sequential design methods for binary response variables exist for determination of the concentration or dose associated with the 50% point along the dose–response curve; the up-and-down method of Dixon and Mood is now commonly used in anesthesia research. There have been important developments in statistical methods that (1) allow the design of experiments for the measurement of the response at any point (quantile) along the dose–response curve, (2) demonstrate the risk of certain statistical methods commonly used in literature reports, (3) allow the estimation of the concentration or dose—the target dose—associated with the chosen quantile without the assumption of the symmetry of the tolerance distribution, and (4) set bounds on the probability of response at this target dose. This article details these developments, briefly surveys current use of the up-and-down method in anesthesia research, reanalyzes published reports using the up-and-down method for the study of the epidural relief of pain during labor, and discusses appropriate inferences from up-and-down method studies.
Heterodimerization of TLR2 with TLR1 or TLR6 expands the ligand spectrum but does not lead to differential signaling

TLR are primary triggers of the innate immune system by recognizing various microorganisms through conserved pathogen‐associated molecular patterns. TLR2 is the receptor for a functional recognition of bacterial lipopeptides (LP) and is up‐regulated during various disorders such as chronic obstructive pulmonary disease and sepsis. This receptor is unique in its ability to form heteromers with TLR1 or TLR6 to mediate intracellular signaling. According to the fatty acid pattern as well as the assembling of the polypeptide tail, LP can signal through TLR2 in a TLR1‐ or TLR6‐dependent manner. There are also di‐ and triacylated LP, which stimulate TLR1‐deficient cells and TLR6‐deficient cells. In this study, we investigated whether heterodimerization evolutionarily developed to broaden the ligand spectrum or to induce different immune responses. We analyzed the signal transduction pathways activated through the different TLR2 dimers using the three LP, palmitic acid (Pam)octanoic acid (Oct)2C‐(VPGVG)4VPGKG, fibroblast‐stimulating LP‐1, and Pam2C‐SK4. Dominant‐negative forms of signaling molecules, immunoblotting of MAPK, as well as microarray analysis indicate that all dimers use the same signaling cascade, leading to an identical pattern of gene activation. We conclude that heterodimerization of TLR2 with TLR1 or TLR6 evolutionarily developed to expand the ligand spectrum to enable the innate immune system to recognize the numerous, different structures of LP present in various pathogens. Thus, although mycoplasma and Gram‐positive and Gram‐negative bacteria may activate different TLR2 dimers, the development of different signal pathways in response to different LP does not seem to be of vital significance for the innate defense system.
Massive MIMO for Wireless Sensing With a Coherent Multiple Access Channel

We consider the detection and estimation of a zero-mean Gaussian signal in a wireless sensor network with a coherent multiple access channel, when the fusion center (FC) is configured with a large number of antennas and the wireless channels between the sensor nodes and FC experience Rayleigh fading. For the detection problem, we study the Neyman-Pearson (NP) detector and energy detector (ED) and find optimal values for the sensor transmission gains. For the NP detector, which requires channel state information (CSI), we show that detection performance remains asymptotically constant with the number of FC antennas if the sensor transmit power decreases proportionally with the increase in the number of antennas. Performance bounds show that the benefit of multiple antennas at the FC disappears as the transmit power grows. The results of the NP detector are also generalized to the linear minimum mean-squared error estimator. For the ED, which does not require CSI, we derive optimal gains that maximize the deflection coefficient of the detector, and we show that a constant deflection can be asymptotically achieved if the sensor transmit power scales as the inverse square root of the number of FC antennas. Unlike the NP detector, for high sensor power, the multi-antenna ED is observed to empirically have significantly better performance than the single-antenna implementation. A number of simulation results are included to validate the analysis.
An interior-point method for topology identification and optimal design of noisy networks

We consider the problem of optimal topology identification and design of the corresponding edge weights for stochastically-forced undirected networks. By introducing $\ell_1$-regularization into the optimal control formulation aimed at minimizing the steady-state variance amplification, this problem can be cast as a semidefinite program. Standard interior-point method solvers can be used to efficiently compute the optimal solution for small and medium size networks. In this paper, we develop a customized algorithm, based on infeasible primal-dual interior-point method, that is well-suited for large problems. The search direction is obtained using the direct method based on Cholesky factorization and an inexact iterative method based on the preconditioned conjugate gradients (PCG). We illustrate that both of these significantly outperform the general-purpose solvers and that the PCG method can solve the problems with hundreds of thousands of edges in the controller graph in several minutes, on a PC. We also exploit structure of connected resistive networks and demonstrate how additional edges can be systematically added in order to minimize the total effective resistance.
Breakdown of Diazotized Proteins and Synthetic Substrates by Rumen Bacterial Proteases

Several different kinds of substrate were used to investigate the proteolytic activity of rumen bacteria and of proteases released from rumen bacteria by blending (“coat proteases”). These substrates included diazotized feed proteins and diazotized soluble and insoluble pure proteins. It was concluded that, while solubility was an important factor, the secondary and tertiary structure of a protein had a major influence on its rate of digestion. The resistance of elastin congo red to digestion indicated that similar fibrous proteins in plant material might resist proteolytic attack by rumen bacteria. Coat proteases had a broad specificity, including several exo- and endopeptidase activities, as determined by using synthetic peptide substrates.
Structural characterization of a mixed-linkage glucan deficient mutant reveals alteration in cellulose microfibril orientation in rice coleoptile mesophyll cell walls

The CELLULOSE SYNTHASE-LIKE F6 (CslF6) gene was previously shown to mediate the biosynthesis of mixed-linkage glucan (MLG), a cell wall polysaccharide that is hypothesized to be tightly associated with cellulose and also have a role in cell expansion in the primary cell wall of young seedlings in grass species. We have recently shown that loss-of-function cslf6 rice mutants do not accumulate MLG in most vegetative tissues. Despite the absence of a structurally important polymer, MLG, these mutants are unexpectedly viable and only show a moderate growth compromise compared to wild type. Therefore these mutants are ideal biological systems to test the current grass cell wall model. In order to gain a better understanding of the role of MLG in the primary wall, we performed in-depth compositional and structural analyses of the cell walls of 3 day-old rice seedlings using various biochemical and novel microspectroscopic approaches. We found that cellulose content as well as matrix polysaccharide composition was not significantly altered in the MLG deficient mutant. However, we observed a significant change in cellulose microfibril bundle organization in mesophyll cell walls of the cslf6 mutant. Using synchrotron source Fourier Transform Mid-Infrared (FTM-IR) Spectromicroscopy for high-resolution imaging, we determined that the bonds associated with cellulose and arabinoxylan, another major component of the primary cell walls of grasses, were in a lower energy configuration compared to wild type, suggesting a slightly weaker primary wall in MLG deficient mesophyll cells. Taken together, these results suggest that MLG may influence cellulose deposition in mesophyll cell walls without significantly affecting anisotropic growth thus challenging MLG importance in cell wall expansion.