Miracle-dz/UniFAR-FTUs huggingface dataset:
High-Throughput Multiplexed Transcript Analysis Yields Enhanced Resolution of 5-Hydroxytryptamine2C Receptor mRNA Editing Profiles

RNA editing is a post-transcriptional modification in which adenosine residues are converted to inosine (adenosine-to-inosine editing). Commonly used methodologies to quantify RNA editing levels involve either direct sequencing or pyrosequencing of individual cDNA clones. The limitations of these methods lead to a small number of clones characterized in comparison to the number of mRNA molecules in the original sample, thereby producing significant sampling errors and potentially erroneous conclusions. We have developed an improved method for quantifying RNA editing patterns that increases sequence analysis to an average of more than 800,000 individual cDNAs per sample, substantially increasing accuracy and sensitivity. Our method is based on the serotonin 2C receptor (5-hydroxytryptamine2C; 5HT2C) transcript, an RNA editing substrate in which up to five adenosines are modified. Using a high-throughput multiplexed transcript analysis, we were able to quantify accurately the expression of twenty 5HT2C isoforms, each representing at least 0.25% of the total 5HT2C transcripts. Furthermore, this approach allowed the detection of previously unobserved changes in 5HT2C editing in RNA samples isolated from different inbred mouse strains and dissected brain regions, as well as editing differences in alternatively spliced 5HT2C variants. This approach provides a novel and efficient strategy for large-scale analyses of RNA editing and may prove to be a valuable tool for uncovering new information regarding editing patterns in specific disease states and in response to pharmacological and physiological perturbation, further elucidating the impact of 5HT2C RNA editing on central nervous system function.
Laser Acupuncture Treatment Improves Pain and Functional Status in Patients with Subacromial Impingement Syndrome: A Randomized, Double-Blind, Sham-Controlled Study

Objective The present study aims to determine the effect of laser acupuncture in patients with subacromial impingement syndrome (SAIS). Design Randomized, double-blind, sham-controlled study. Setting Physical medicine and rehabilitation outpatient clinic. Subjects A total 73 patients with SAIS were randomly assigned into a treatment group (n = 36) and a control group (n = 37). Methods The treatment group received laser acupuncture, and the control group received sham laser acupuncture. Eleven acupuncture points (GB 21, LI 4, LI 11, LI 14, LI 15, LI 16, SI 9, SI 10, SI 11, TE 14, and TE 15) were irradiated using a gallium-aluminium-arsenide continuous wave diode-laser, with a wavelength of 850 nm and a power output of 100 mV. The laser acupuncture treatment at each acupuncture point was administered at 4 joules/cm 2 (total dose = 40 joules). All patients were also treated with a hot pack. The patients were assessed at baseline and after 15 sessions of laser treatment. Pain severity and doctor's and patient's global assessments were measured via visual analog scale (VAS). Range of motion (ROM) and functional status were measured using a digital inclinometer and the Shoulder Pain Disability Index, respectively. Results Statistically significant improvements were observed in all parameters in the treatment group. All parameters of pain and functional status in the treatment group were significantly better than those in the control group at week 3. Conclusions To the best of our knowledge, this is the first study that investigates the effect of laser acupuncture in SAIS. The positive results of the present study should lead to further laser acupuncture studies with combinations of different acupuncture points, at different wavelengths, and with long-term follow-up periods.
Heat and mass transfer through outerwear clothing for protection from cold: influence of geometrical, structural and mass characteristics of the textile layers

This paper presents a comprehensive experimental study, conducted on a series of woven and non-woven fabric samples from different materials (cotton, polyester, and polyamide) and 14 three-layer systems of textile materials, used for production of outerwear clothing for protection from cold. Heat and mass transfer properties, related to the thermophysiological comfort of the outerwear clothing, namely conductive thermal resistance, water vapor resistance, relative water vapor permeability, air permeability, accumulative one-way transport of liquids, and overall moisture management capacity, were determined for the system of layers and the compound single layers. The transfer properties of the single layers were presented as a function of their thickness, mass per unit area, and areal porosity. The transfer properties of the system of layers were presented as a function of the thickness, mass per unit area, and bulk density of the systems. Regression analysis was applied to derive regression equations. The results obtained allowed assessment of the existence and trend of the influence, as well as evaluation of the strength of the dependences.
Prognostic and Diagnostic Potential of the Structural Neuroanatomy of Depression

Background Depression is experienced as a persistent low mood or anhedonia accompanied by behavioural and cognitive disturbances which impair day to day functioning. However, the diagnosis is largely based on self-reported symptoms, and there are no neurobiological markers to guide the choice of treatment. In the present study, we examined the prognostic and diagnostic potential of the structural neural correlates of depression. Methodology and Principal Findings Subjects were 37 patients with major depressive disorder (mean age 43.2 years), medication-free, in an acute depressive episode, and 37 healthy individuals. Following the MRI scan, 30 patients underwent treatment with the antidepressant medication fluoxetine or cognitive behavioural therapy (CBT). Of the patients who subsequently achieved clinical remission with antidepressant medication, the whole brain structural neuroanatomy predicted 88.9% of the clinical response, prior to the initiation of treatment (88.9% patients in clinical remission (sensitivity) and 88.9% patients with residual symptoms (specificity), p = 0.01). Accuracy of the structural neuroanatomy as a diagnostic marker though was 67.6% (64.9% patients (sensitivity) and 70.3% healthy individuals (specificity), p = 0.027). Conclusions and Significance The structural neuroanatomy of depression shows high predictive potential for clinical response to antidepressant medication, while its diagnostic potential is more limited. The present findings provide initial steps towards the development of neurobiological prognostic markers for depression.
Relationship of response and survival in patients with relapsed and refractory multiple myeloma treated with pomalidomide plus low-dose dexamethasone in the MM-003 trial randomized phase III trial (NIMBUS)

Abstract Relapsed/refractory multiple myeloma (RRMM) patients have poor overall survival (OS). Pomalidomide plus low-dose dexamethasone (POM + LoDEX) significantly extends OS in RRMM vs. high-dose dexamethasone. Survival of patients with stable disease (SD) was compared to patients with progressive disease (PD) or ≥ partial response (≥PR) at cycles (C) 3, 5, and 7. Among 302 patients randomized to POM + LoDEX, at C3 19.2% achieved ≥ PR, 38.4% SD, and 14.6% PD. Patients with SD at C3 (17.4%) and C5 (13.6%) showed improved responses at C7. Median OS from randomization by response at C3 was 22.4 months for ≥ PR (n = 58, HR 0.66; 95% CI 0.40–1.08, p = 0.0976 vs. SD), 16.2 months for SD (n = 116), and 6.3 months for PD (n = 44, HR 3.43; 95% CI 2.23–5.27, p < 0.0001 vs. SD). Similar patterns were observed for C5 and C7. Results show that POM + LoDEX should be a standard treatment after lenalidomide and bortezomib, including in SD patients.
PKC-ALDH2 Pathway Plays a Novel Role in Adipocyte Differentiation

The ALDH2 gene encodes the mitochondrial aldehyde dehydrogenase 2 (ALDH2), a critical enzyme involved in ethanol clearance through acetaldehyde metabolism. ALDH2 also catalyzes the metabolism of other bioreactive aldehydes, including propionaldehyde, butyraldehyde, and 4-hydroxykenals (4-HNE). Increased levels of 4-HNE in adipose tissue positively correlate with obesity and insulin resistance. However, it remains unclear whether ALDH2 is involved in regulation of adipocyte differentiation. Here, we found that ALDH2 protein levels were lower in white adipose tissue of high-fat diet-fed mice and ob/ob mice relative to lean mice. Knockdown of ALDH2 expression in 3T3-L1 preadipocytes caused an increase in intracellular 4-HNE, thereby attenuated adipocyte differentiation. By contrast, an ALDH2 activator, Alda-1, significantly accelerated adipogenesis, which was accompanied by an increase in adipogenic gene expression. Consistently, adipogenesis was reduced when protein kinase C ε (PKCε), an ALDH2 phosphorylating activator, was silenced in 3T3-L1 preadipocytes, whereas treatment with a PKCε agonist in 3T3-L1 preadipocytes enhanced adipogenesis. Whole-genome microarray profiling of Alda-1-treated cells demonstrated several upregulated transcripts encoding proteins involved in metabolism and the majority of these transcripts are for proteins involved in PPAR signaling pathways. Furthermore, PKCε-ALDH2 interaction alleviates 4-HNE induced aberrant PPARγ regulation on adipogenesis. Taken together, these results demonstrate that ALDH2 activation enhances adipogenesis and signaling pathways involving PPARγ. Thus, activation of PKCε-ALDH2 regulatory axis may be a therapeutic target for treating obesity and type 2 diabetes.
Human Stem Cell-Derived Neurons: A System to Study Human Tau Function and Dysfunction

Background Intracellular filamentous deposits containing microtubule-associated protein tau constitute a defining characteristic of many neurodegenerative disorders. Current experimental models to study tau pathology in vitro do not usually recapitulate the tau expression pattern characteristic of adult human brain. In this study, we have investigated whether human embryonic stem cell-derived neurons could be a good model to study human tau distribution, function and dysfunction. Methodology/Principal Findings Using RT-PCR, immunohistochemistry, western blotting and cell transfections we have investigated whether all 6 adult human brain tau isoforms are expressed in neurons derived from human embryonic and fetal stem cells and whether 4 repeat tau over-expression alone, or with the F3 tau repeat fragment, (amino acid 258–380 of the 2N4R tau isoform with the ΔK280 mutation) affects tau distribution. We found that the shortest 3 repeat tau isoform, similarly to human brain, is the first to be expressed during neuronal differentiation while the other 5 tau isoforms are expressed later. Over expression of tau with 4 repeats affects tau cellular distribution and the short tau F3 fragment appears to increase tau phosphorylation but this effect does not appear to be toxic for the cell. Conclusions Our results indicate that human embryonic stem cell-derived neurons express all 6 tau isoforms and are a good model in which to study tau physiology and pathology.
Foraminiferal Mg/Ca increase in the Caribbean during the Pliocene: Western Atlantic Warm Pool formation, salinity influence, or diagenetic overprint?

We constructed a high‐resolution Mg/Ca record on the planktonic foraminifer Globigerinoides sacculifer in order to explore the change in sea surface temperature (SST) due to the shoaling of the Isthmus of Panama as well as the impact of secondary factors like diagenesis and large salinity fluctuations. The study covers the latest Miocene and the early Pliocene (5.6–3.9 Ma) and was combined with δ18O to isolate changes in sea surface salinity (SSS). Before 4.5 Ma, SSTMg/Ca and SSS show moderate fluctuations, indicating a free exchange of surface ocean water masses between the Pacific and the Atlantic. The increase in δ18O after 4.5 Ma represents increasing salinities in the Caribbean due to the progressive closure of the Panamanian Gateway. The increase in Mg/Ca toward values of maximum 7 mmol/mol suggests that secondary influences have played a significant role. Evidence of crystalline overgrowths on the foraminiferal tests in correlation with aragonite, Sr/Ca, and productivity cyclicities indicates a diagenetic overprint on the foraminiferal tests. Laser ablation inductively coupled plasma–mass spectrometry analyses, however, do not show significantly increased Mg/Ca ratios in the crystalline overgrowths, and neither do calculations based on pore water data conclusively result in significantly elevated Mg/Ca ratios in the crystalline overgrowths. Alternatively, the elevated Mg/Ca ratios might have been caused by salinity as the δ18O record of Site 1000 has been interpreted to represent large fluctuations in SSS, and cultivating experiments have shown an increase in Mg/Ca with increasing salinity. We conclude that the Mg/Ca record <4.5 Ma can only reliably be considered for paleoceanographical purposes when the minimum values, not showing any evidence of secondary influences, are used, resulting in a warming of central Caribbean surface water masses after 4.5 Ma of ∼2°C.
Association between different Non-Invasively Derived Thresholds with Lactate Threshold during graded incremental exercise

We compared lactate threshold (TLac) with non-invasive markers of an aerobic-anaerobic transition; namely, ventilatory (VT) and tissue saturation index (TSIT) thresholds. While identification of a breakpoint in blood lactate concentration ([BLa]) is common for determination of an aerobic-anaerobic transition, non-invasive measures, VT and NIRS, have also received attention as a means of determining this critical exercise intensity. We hypothesised that one or other of these non-invasive measures would have a strong association with TLac. Thirty-one (n=31) competitive male athletes (mean ± SD, age 29±9 yr, height 1.81±0.1 m, body mass 77.7±10.0 kg) performed graded incremental cycling to volitional exhaustion. Heart rate, TSI and gas exchange data were measured throughout and [BLa] was determined at fixed intervals. Threshold detection involved a segmented linear regression analysis minimising the squared sum of the residuals to determine TLac, TSIT and VT. Workload and HR at TLac, VT and TSIT were analysed using repeated measures ANOVA and correlation assessed using Pearson’s and interclass correlation coefficients. Thresholds at TSIT and TLac were not significantly different (255±35 vs. 249±30 W, P>0.05), suggesting that limitations in O2 delivery could be closely linked to an aerobic-anaerobic transition. However, poor correlation (r=0.55, ICC=0.54 and 95%LoA of +67 and −54 W) suggested other factors may exert an influence. Mean VT occurred at a significantly higher workload than TLac (271 ±35 vs 249±30 W, P<0.001). Consequently, VT proved less useful, giving an indication of when an aerobic-anaerobic transition had already occurred. In conclusion, non-invasive markers of the aerobic transition are not concurrent with TLac.
The Climatic Niche Diversity of Malagasy Primates: A Phylogenetic Perspective

Background Numerous researchers have posited that there should be a strong negative relationship between the evolutionary distance among species and their ecological similarity. Alternative evidence suggests that members of adaptive radiations should display no relationship between divergence time and ecological similarity because rapid evolution results in near-simultaneous speciation early in the clade's history. In this paper, we performed the first investigation of ecological diversity in a phylogenetic context using a mammalian adaptive radiation, the Malagasy primates. Methodology/Principal Findings We collected data for 43 extant species including: 1) 1064 species by locality samples, 2) GIS climate data for each sampling locality, and 3) the phylogenetic relationships of the species. We calculated the niche space of each species by summarizing the climatic variation at localities of known occurrence. Climate data from all species occurrences at all sites were entered into a principal components analysis. We calculated the mean value of the first two PCA axes, representing rainfall and temperature diversity, for each species. We calculated the K statistic using the Physig program for Matlab to examine how well the climatic niche space of species was correlated with phylogeny. Conclusions/Significance We found that there was little relationship between the phylogenetic distance of Malagasy primates and their rainfall and temperature niche space, i.e., closely related species tend to occupy different climatic niches. Furthermore, several species from different genera converged on a similar climatic niche. These results have important implications for the evolution of ecological diversity, and the long-term survival of these endangered species.
Investigating knowledge levels of university students about infertility.

Objective The aim of this study was to determine the knowledge levels of university students about infertility and investigate the differences in knowledge levels according to sociodemographic variables and some lifestyle factors. Material and methods The sample of the study consisted of 9693 undergraduate students (5002 females, 4691 males) from 12 regions. Regions were determined according to Statistical Region Units Classification-1 criteria. Infertility Knowledge Test (IKT) was used as a data collection tool. Results It was found that university students' IKT scores significantly differed according to gender (p<0.01); age (p<0.05); body mass index (p<0.05); reproductive health education status (p<0.001), presence of infertile individuals around (p<0.001); having sexual intercourse (p<0.001); smoking (p<0.001) and alcohol consumption frequency (p<0.05). Conclusion University students' lack of knowledge about family planning, effects of age and sexual intercourse timing on infertility was remarkable. However, it was determined that the knowledge level of infertility risk factors related to substance use and body mass index was high. It is believed that increasing the level of knowledge about infertility among individuals will positively effect their awareness of risk factors and facilitate their search for timely medical assistance. Sexual health education can be effective in increasing university students' knowledge of infertility.
Phylogenetic Constraints Do Not Explain the Rarity of Nitrogen-Fixing Trees in Late-Successional Temperate Forests

Background Symbiotic nitrogen (N)-fixing trees are rare in late-successional temperate forests, even though these forests are often N limited. Two hypotheses could explain this paradox. The ‘phylogenetic constraints hypothesis’ states that no late-successional tree taxa in temperate forests belong to clades that are predisposed to N fixation. Conversely, the ‘selective constraints hypothesis’ states that such taxa are present, but N-fixing symbioses would lower their fitness. Here we test the phylogenetic constraints hypothesis. Methodology/Principal Findings Using U.S. forest inventory data, we derived successional indices related to shade tolerance and stand age for N-fixing trees, non-fixing trees in the ‘potentially N-fixing clade’ (smallest angiosperm clade that includes all N fixers), and non-fixing trees outside this clade. We then used phylogenetically independent contrasts (PICs) to test for associations between these successional indices and N fixation. Four results stand out from our analysis of U.S. trees. First, N fixers are less shade-tolerant than non-fixers both inside and outside of the potentially N-fixing clade. Second, N fixers tend to occur in younger stands in a given geographical region than non-fixers both inside and outside of the potentially N-fixing clade. Third, the potentially N-fixing clade contains numerous late-successional non-fixers. Fourth, although the N fixation trait is evolutionarily conserved, the successional traits are relatively labile. Conclusions/Significance These results suggest that selective constraints, not phylogenetic constraints, explain the rarity of late-successional N-fixing trees in temperate forests. Because N-fixing trees could overcome N limitation to net primary production if they were abundant, this study helps to understand the maintenance of N limitation in temperate forests, and therefore the capacity of this biome to sequester carbon.
Deep Semantic Face Deblurring

In this paper, we present an effective and efficient face deblurring algorithm by exploiting semantic cues via deep convolutional neural networks (CNNs). As face images are highly structured and share several key semantic components (e.g., eyes and mouths), the semantic information of a face provides a strong prior for restoration. As such, we propose to incorporate global semantic priors as input and impose local structure losses to regularize the output within a multi-scale deep CNN. We train the network with perceptual and adversarial losses to generate photo-realistic results and develop an incremental training strategy to handle random blur kernels in the wild. Quantitative and qualitative evaluations demonstrate that the proposed face deblurring algorithm restores sharp images with more facial details and performs favorably against state-of-the-art methods in terms of restoration quality, face recognition and execution speed.
An investigation on 4-aminobenzoic acid modified polyvinyl chloride/graphene oxide and PVC/graphene oxide based nanocomposite membranes

We synthesized graphene oxide (GO) using a modified Hummer’s method, and then blended it into polyvinyl chloride (PVC) and amino-functional PVC (PVC-4ABA) matrices. GO was added to 0.5 g PVC at 0.01, 0.05, 0.1 and 0.5 g. The PVC/GO matrix was modified using 4-aminobenzoic acid (4ABA) at 0.01, 0.05, 0.1 and 0.5 g per 0.5 g PVC. This gave four amino-functional PVC/GO series and one PVC/GO series nanocomposite membranes that were prepared by a solution blending route. The filler and the modifier (4ABA) content effect on the PVC membrane properties were investigated. Fourier transform infrared spectroscopy confirmed the GO functional groups and PVC modification with 4ABA. According to scanning electron microscopy, a unique two-way layered structure was observed for modified PVC and GO composites. XRD explained the conformation of PVC/GO and modified PVC/GO nanocomposites. GO crystallite size and its interlayer distance between sheets were also studied. The XRD peak at 2θ = 10.8° with interlayer spacing of 0.81 nm was calculated with the Bragg equation. GO particle size was calculated (Scherrer formula) as 7.78 nm. XRD results revealed fine interaction between modified PVC and GO compared with unmodified PVC composites. Glass transition temperature (Tg) of non-modified PVC/GO nanocomposite was 202℃, whereas modified nanocomposite with similar GO loading had Tg equal to 212℃. Higher filler content gave better hydrophilic membranes as determined by solvent content, porosity, and shrinkage ratio. PVC-4ABA-0.5/GO 0.5 membrane with a low contact angle (25°) is a fine option for water purification. The overall results suggest that the higher modifier concentrations developed better interaction between the nanofiller and PVC.