Is the quantity of circulatory cell-free DNA in human plasma and serum samples associated with gender, age and frequency of blood donations?

Circulatory cell-free DNA (cf-DNA) is increased in a variety of clinical pathologic conditions; therefore, these markers could be widely used as markers for detecting and monitoring several disorders. To better understand the biology of this molecule, we analysed the relationship between the level of circulatory cf-DNA and physiological parameters such as gender, age and frequency of blood donations. Paired plasma and serum samples were obtained from 87 blood donors and 50 healthy adults who had never donated blood. Cf-DNA was extracted from plasma and serum samples using the MagNA Pure LC Instrument. Quantity determination of circulatory cf-DNA was performed by TaqMan real-time PCR for the ubiquitous GAPDH gene. Our data showed that the concentration of cf-DNA in serum was about eightfold higher than that in plasma. Regarding the level of these circulatory species, no significant differences were observed between the age-matched men and women and gender-matched, different-age cohorts, except in women who were older than 60years of age. Frequent blood donations did not increase the circulatory species. Circulatory cf-DNA in plasma and serum samples is not correlated with human gender and human age except in women who are older than 60years of age. Frequent blood donation did not affect the quantity of circulatory cf-DNA. The explanation for the latter most likely is the short half-life time of free fetal DNA in maternal circulatio

Growth and Geometry Split in Light of the DES-Y3 Survey

We test the smooth dark energy paradigm using Dark Energy Survey (DES) Year 1 and Year 3 weak lensing and galaxy clustering data. Within the $\Lambda$CDM and $w$CDM model we separate the expansion and structure growth history by splitting $\Omega_\mathrm{m}$ (and $w$) into two meta-parameters that allow for different evolution of growth and geometry in the Universe. We consider three different combinations of priors on geometry from CMB, SNIa, BAO, BBN that differ in constraining power but have been designed such that the growth information comes solely from the DES weak lensing and galaxy clustering. For the DES-Y1 data we find no detectable tension between growth and geometry meta-parameters in both the $\Lambda$CDM and $w$CDM parameter space. This statement also holds for DES-Y3 cosmic shear and 3x2pt analyses. For the combination of DES-Y3 galaxy-galaxy lensing and galaxy clustering (2x2pt) we measure a tension between our growth and geometry meta-parameters of 2.6$\sigma$ in the $\Lambda$CDM and 4.48$\sigma$ in the $w$CDM model space, respectively. We attribute this tension to residual systematics in the DES-Y3 RedMagic galaxy sample rather than to new physics. We plan to investigate our findings further using alternative lens samples in DES-Y3 and future weak lensing and galaxy clustering datasets.Comment: 19 pages, 14 figures, to be submitte

Desarrollo y validación de una escala PLEs desde la perspectiva del alumno y el aprendizaje en la educación terciaria

The study's goal is to create and validate a Personal Learning Environment Scale (PLEs) from the learner and learning perspective (named PLEsS-LL) to ensure effective learning in Chinese tertiary education. 657 undergraduates participated in the study after completing scale development steps. Six factors were extracted from the PLEsS-LL using Exploratory Factor Analysis (EFA). Confirmatory Factor Analysis (CFA) supported the six-factor scale with 22 items. Furthermore, the PLEsS-LL was redesigned as a questionnaire to assess learners' readiness for PLE learning. The findings indicated that participants were comfortable learning in PLEs in general. They were mostly positive in terms of learning motivation and problem-solving abilities. They did, however, report less confidence in self-directed learning. Meanwhile, male participants outperformed female participants in all categories except learning motivation. The reasons were explained, and suggestions for future PLE design were made. The PLEsS-LL could be used as a resource or guide for learner preparation in the PLE context in higher education around the world.El objetivo del estudio es crear y validar una Escala de Entornos Personales de Aprendizaje (PLEsS) desde la perspectiva del alumno y el aprendizaje (llamada PLEsS-LL) para garantizar un aprendizaje efectivo en la educación terciaria china. 657 estudiantes universitarios participaron en el estudio después de completar los pasos de desarrollo de escala. Se extrajeron seis factores del PLEsS-LL mediante Análisis Factorial Exploratorio (EFA). El Análisis Factorial Confirmatorio (AFC) apoyó la escala de seis factores con 22 ítems.  Además, el PLEsS-LL fue rediseñado como un cuestionario para evaluar la preparación de los alumnos para el aprendizaje PLE. Los hallazgos indicaron que los participantes se sentían cómodos al aprender en PLE en general. En su mayoría fueron positivos en términos de motivación de aprendizaje y habilidades para resolver problemas. Sin embargo, informaron menos confianza en el aprendizaje autodirigido. Mientras tanto, los participantes masculinos superaron a las participantes femeninas en todas las categorías, excepto en la motivación de aprendizaje. Se explicaron las razones y se hicieron sugerencias para el diseño futuro de PLE. El PLEsS-LL podría utilizarse como un recurso o guía para la preparación del alumno en el contexto de los PLEs en la educación superior de todo el mundo

ReactIE: Enhancing Chemical Reaction Extraction with Weak Supervision

Structured chemical reaction information plays a vital role for chemists engaged in laboratory work and advanced endeavors such as computer-aided drug design. Despite the importance of extracting structured reactions from scientific literature, data annotation for this purpose is cost-prohibitive due to the significant labor required from domain experts. Consequently, the scarcity of sufficient training data poses an obstacle to the progress of related models in this domain. In this paper, we propose ReactIE, which combines two weakly supervised approaches for pre-training. Our method utilizes frequent patterns within the text as linguistic cues to identify specific characteristics of chemical reactions. Additionally, we adopt synthetic data from patent records as distant supervision to incorporate domain knowledge into the model. Experiments demonstrate that ReactIE achieves substantial improvements and outperforms all existing baselines.Comment: Findings of ACL 2023, Short Pape

Functional Profiling of Transcription Factor Genes in Neurospora crassa.

Regulation of gene expression by DNA-binding transcription factors is essential for proper control of growth and development in all organisms. In this study, we annotate and characterize growth and developmental phenotypes for transcription factor genes in the model filamentous fungus Neurospora crassa We identified 312 transcription factor genes, corresponding to 3.2% of the protein coding genes in the genome. The largest class was the fungal-specific Zn2Cys6 (C6) binuclear cluster, with 135 members, followed by the highly conserved C2H2 zinc finger group, with 61 genes. Viable knockout mutants were produced for 273 genes, and complete growth and developmental phenotypic data are available for 242 strains, with 64% possessing at least one defect. The most prominent defect observed was in growth of basal hyphae (43% of mutants analyzed), followed by asexual sporulation (38%), and the various stages of sexual development (19%). Two growth or developmental defects were observed for 21% of the mutants, while 8% were defective in all three major phenotypes tested. Analysis of available mRNA expression data for a time course of sexual development revealed mutants with sexual phenotypes that correlate with transcription factor transcript abundance in wild type. Inspection of this data also implicated cryptic roles in sexual development for several cotranscribed transcription factor genes that do not produce a phenotype when mutated

Early dark energy constraints with late-time expansion marginalization

Early dark energy (EDE) is an extension to the $\Lambda$CDM model, proposed to reduce the tension between the measurements of the Hubble constant $H_0$ from the cosmic microwave background (CMB) and from the local cosmic distance ladder. However, this model increases the $S_8$ tension between CMB and large scale structure measurements. Analyses of galaxy clustering and lensing correlation functions report a decreased preference for EDE and its effect on the Hubble tension. Smooth dark energy models affect growth of structure through the background expansion. In this work, we study the inclusion of a general, smooth late-time dark energy modification in combination with EDE and obtain constraints on EDE marginalized over the late-time expansion. We assess the impact on the $S_8$ and Hubble tensions. In order to generalize the late expansion, we use a late dark energy fluid model with a piecewise constant equation of state $w(z)$ over 3, 5 and 10 redshift bins in the window $z \in [0,3]$. We show that, when analyzing ACT and Planck CMB data combined with Pantheon supernovae, BAO from 6dF, SDSS and BOSS, Planck 2018 CMB lensing and Dark Energy Survey cosmic shear and clustering data, the inclusion of a general smooth dark energy modification at late times has no significant effect on $S_8$ and EDE parameter constraints. Using the aforementioned datasets, the EDE fraction constraint with late-time expansion marginalization is $f_\mathrm{EDE} = 0.067^{+0.019}_{-0.027}$ using 3 redshift bins, with similar results for 5 and 10 redshift bins. This work shows that in order to solve simultaneously the Hubble and $S_8$ tensions, one needs a mechanism for increasing the clustering of matter at late times different from a simple change in the background evolution of late dark energy. [Abridged]Comment: 22 pages, 9 figure

Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment

Interstitial fibrosis plays a key role in the development and progression of heart failure. Here, we show that an enzyme that crosslinks collagen—Lysyl oxidase-like 2 (Loxl2)—is essential for interstitial fibrosis and mechanical dysfunction of pathologically stressed hearts. In mice, cardiac stress activates fibroblasts to express and secrete Loxl2 into the interstitium, triggering fibrosis, systolic and diastolic dysfunction of stressed hearts. Antibody-mediated inhibition or genetic disruption of Loxl2 greatly reduces stress-induced cardiac fibrosis and chamber dilatation, improving systolic and diastolic functions. Loxl2 stimulates cardiac fibroblasts through PI3K/AKT to produce TGF-β2, promoting fibroblast-to-myofibroblast transformation; Loxl2 also acts downstream of TGF-β2 to stimulate myofibroblast migration. In diseased human hearts, LOXL2 is upregulated in cardiac interstitium; its levels correlate with collagen crosslinking and cardiac dysfunction. LOXL2 is also elevated in the serum of heart failure (HF) patients, correlating with other HF biomarkers, suggesting a conserved LOXL2-mediated mechanism of human HF

Constraining Baryonic Physics with DES Y1 and Planck data -- Combining Galaxy Clustering, Weak Lensing, and CMB Lensing

We constrain cosmology and baryonic feedback scenarios with a joint analysis of weak lensing, galaxy clustering, cosmic microwave background (CMB) lensing, and their cross-correlations (so-called 6$\times$2) using data from the Dark Energy Survey (DES) Y1 and the Planck satellite mission. Noteworthy features of our 6$\times$2 pipeline are: We extend CMB lensing cross-correlation measurements to a band surrounding the DES Y1 footprint (a $\sim 25\%$ gain in pairs), and we develop analytic covariance capabilities that account for different footprints and all cross-terms in the 6$\times$2 analysis. We also measure the DES Y1 cosmic shear two-point correlation function (2PCF) down to $0.^\prime 25$, but find that going below $2.^\prime 5$ does not increase cosmological information due to shape noise. We model baryonic physics uncertainties via the amplitude of Principal Components (PCs) derived from a set of hydro-simulations. Given our statistical uncertainties, varying the first PC amplitude $Q_1$ is sufficient to model small-scale cosmic shear 2PCF. For DES Y1+Planck 6$\times$2 we find $S_8=0.799\pm0.016$, comparable to the 5$\times$2 result of DES Y3+SPT/Planck $S_8=0.773\pm0.016$. Combined with our most informative cosmology priors -- baryon acoustic oscillation (BAO), big bang nucleosynthesis (BBN), type Ia supernovae (SNe Ia), and Planck 2018 EE+lowE, we measure $S_8=0.817\pm 0.011$. Regarding baryonic physics constraints, our 6$\times$2 analysis finds $Q_1=2.8\pm1.8$. Combined with the aforementioned priors, it improves the constraint to $Q_1=3.5\pm1.3$. For comparison, the strongest feedback scenario considered in this paper, the cosmo-OWLS AGN ($\Delta T_\mathrm{heat}=10^{8.7}$ K), corresponds to $Q_1=5.84$.Comment: 24 pages, 13 figures, comments are welcome

Using Chinese Version of MYMOP in Chinese Medicine Evaluation: Validity, Responsiveness and Minimally Important Change

<p>Abstract</p> <p>Background</p> <p>Measure Yourself Medical Outcome Profile (MYMOP) is a patient generated outcome instrument applicable in the evaluation of both allopathic and complementary medicine treatment. This study aims to adapt MYMOP into Chinese, and to assess its validity, responsiveness and minimally important change values in a sample of patients using Chinese medicine (CM) services.</p> <p>Methods</p> <p>A Chinese version of MYMOP (CMYMOP) is developed by forward-backward-forward translation strategy, expert panel assessment and pilot testing amongst patients. 272 patients aged 18 or above with subjective symptoms in the past 2 weeks were recruited at a CM clinic, and were invited to complete a set of questionnaire containing CMYMOP and SF-36. Follow ups were performed at 2^ndand 4^thweek after consultation, using the same set of questionnaire plus a global rating of change question. Criterion validity of CMYMOP was assessed by its correlation with SF-36 at baseline, and responsiveness was evaluated by calculating the Cohen effect size (ES) of change at two follow ups. Minimally important difference (MID) values were estimated via anchor based method, while minimally detectable difference (MDC) figures were calculated by distribution based method.</p> <p>Results</p> <p>Criterion validity of CMYMOP was demonstrated by negative correlation between CMYMOP Profile scores and all SF-36 domain and summary scores at baseline. For responsiveness between baseline and 4^thweek follow up, ES of CMYMOP Symptom 1, Activity and Profile reached the moderate change threshold (ES>0.5), while Symptom 2 and Wellbeing reached the weak change threshold (ES>0.2). None of the SF-36 scores reached the moderate change threshold, implying CMYMOP's stronger responsiveness in CM setting. At 2^ndweek follow up, MID values for Symptom 1, Symptom 2, Wellbeing and Profile items were 0.894, 0.580, 0.263 and 0.516 respectively. For Activity item, MDC figure of 0.808 was adopted to estimate MID.</p> <p>Conclusions</p> <p>The findings support the validity and responsiveness of CMYMOP for capturing patient centred clinical changes within 2 weeks in a CM clinical setting. Further researches are warranted (1) to estimate Activity item MID, (2) to assess the test-retest reliability of CMYMOP, and (3) to perform further MID evaluation using multiple, item specific anchor questions.</p

Progressive Shifts in the Gut Microbiome Reflect Prediabetes and Diabetes Development in a Treatment-Naive Mexican Cohort.

Type 2 diabetes (T2D) is a global epidemic that affects more than 8% of the world\u27s population and is a leading cause of death in Mexico. Diet and lifestyle are known to contribute to the onset of T2D. However, the role of the gut microbiome in T2D progression remains uncertain. Associations between microbiome composition and diabetes are confounded by medication use, diet, and obesity. Here we present data on a treatment-naive cohort of 405 Mexican individuals across varying stages of T2D severity. Associations between gut bacteria and more than 200 clinical variables revealed a defined set of bacterial genera that were consistent biomarkers of T2D prevalence and risk. Specifically, gradual increases in blood glucose levels, beta cell dysfunction, and the accumulation of measured T2D risk factors were correlated with the relative abundances of four bacterial genera. In a cohort of 25 individuals, T2D treatment-predominantly metformin-reliably returned the microbiome to the normoglycemic community state. Deep clinical characterization allowed us to broadly control for confounding variables, indicating that these microbiome patterns were independent of common T2D comorbidities, like obesity or cardiovascular disease. Our work provides the first solid evidence for a direct link between the gut microbiome and T2D in a critically high-risk population. In particular, we show that increased T2D risk is reflected in gradual changes in the gut microbiome. Whether or not these T2D-associated changes in the gut contribute to the etiology of T2D or its comorbidities remains to be seen