Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of insulin signaling may contribute to atrial fibrillation and atrial electrical remodeling in type 1 diabetes

Significance Atrial fibrillation (AF) is prevalent in diabetic patients, yet the basis for AF in diabetes is poorly understood. We have used type 1 diabetic Akita mice to study the effects of insulin on atrial electrophysiology in diabetes. We demonstrate that Akita mice are highly susceptible to AF due to impaired electrical conduction and that insulin treatment can reduce the occurrence of this arrhythmia. Atrial action potential morphology was altered in Akita mice in association with reductions in atrial Na+ current (INa) and repolarizing potassium current. Insulin treatment potently increased atrial INa via distinct chronic and acute effects. These experiments identify antiarrhythmic effects of insulin in type 1 diabetes via potent effects on atrial INa. Atrial fibrillation (AF) is prevalent in diabetes mellitus (DM); however, the basis for this is unknown. This study investigated AF susceptibility and atrial electrophysiology in type 1 diabetic Akita mice using in vivo intracardiac electrophysiology, high-resolution optical mapping in atrial preparations, and patch clamping in isolated atrial myocytes. qPCR and western blotting were used to assess ion channel expression. Akita mice were highly susceptible to AF in association with increased P-wave duration and slowed atrial conduction velocity. In a second model of type 1 DM, mice treated with streptozotocin (STZ) showed a similar increase in susceptibility to AF. Chronic insulin treatment reduced susceptibility and duration of AF and shortened P-wave duration in Akita mice. Atrial action potential (AP) morphology was altered in Akita mice due to a reduction in upstroke velocity and increases in AP duration. In Akita mice, atrial Na+ current (INa) and repolarizing K+ current (IK) carried by voltage gated K+ (Kv1.5) channels were reduced. The reduction in INa occurred in association with reduced expression of SCN5a and voltage gated Na+ (NaV1.5) channels as well as a shift in INa activation kinetics. Insulin potently and selectively increased INa in Akita mice without affecting IK. Chronic insulin treatment increased INa in association with increased expression of NaV1.5. Acute insulin also increased INa, although to a smaller extent, due to enhanced insulin signaling via phosphatidylinositol 3,4,5-triphosphate (PIP3). Our study reveals a critical, selective role for insulin in regulating atrial INa, which impacts susceptibility to AF in type 1 DM.
Improving diagnostic reliability in Chinese medicine

The aim of this thesis was to assess current levels of inter-rater diagnostic agreement in the Chinese Medical (CM) profession and to propose strategies that might improve these levels. Researchers have generally used inappropriate statistical constructs to evaluate inter-rater agreement. A more appropriate weighted chance-removed statistic is employed to determine inter-rater diagnostic agreement with ordinal data. Further, the largest number of raters which have been used in any past study was three. Similarly, no study was located which involved inter-rater diagnostic agreement with subjects drawn from an open population. This is a deficiency in understanding CM inter-rater agreement in a clinical setting. The Diagnostic System of Oriental Medicine (DSOM) format was identified as suitable for use in CM diagnosis by practitioners. This format also enables appropriate statistics to be employed. An experiment was performed in which five experienced practitioners of CM diagnosed 42 subjects using the DSOM as the diagnostic format. Each of the sixteen diagnostic descriptors used to describe a diagnosis with the DSOM were scored 0-5. Substantial chanceremoved weighted agreement of 0.60 ±0.02 was found. The descriptors of DSOM format were edited after examining 60,000 clinical records at the UTS CM outpatient clinic to arrive at the Chinese Medicine Diagnostic Descriptor
The Visceral Adipose Index in Relation to Incidence of Hypertension in Chinese Adults: China Health and Nutrition Survey (CHNS)

Hypertension is the most crucial single contributor to global burden of disease and mortality, while weight loss as a non-pharmacological strategy is recommended to reduce blood pressure. This study aims to examine the association between visceral adipose index (VAI) and hypertension in Chinese adults. Data were collected from the China Health and Nutrition Survey (CHNS), consisting of 8374 apparently healthy participants aged ≥18 years in the 2009 CHNS for cross-sectional analysis, and 4275 participants at entry from 2009 to 2011 for cohort analysis. Height, weight, waist circumference, blood pressure (BP), and blood lipid were measured. Information of population characteristics, smoking status, alcohol consumption, physical activity, and diet were determined by validated questionnaire. Higher VAI scores were significantly associated with higher BP levels and higher risk of hypertension after adjustment with potential confounders (all p-trend < 0.001). The adjusted hazard ratio of hypertension was 1.526 (95%CI: 1.194, 1.952; p-trend < 0.01) for participants in the highest quartile of VAI scores when compared with those in the lowest quartile after adjustment for age, physical activity, antihypertensive medication, total energy intake, salt intake, and other major lifestyle factors. VAI scores were significantly, longitudinally associated with hypertension development among apparently healthy Chinese adults.
GLP-1 Notch—LAG-1 CSL control of the germline stem cell fate is mediated by transcriptional targets lst-1 and sygl-1

Stem cell systems are essential for the development and maintenance of polarized tissues. Intercellular signaling pathways control stem cell systems, where niche cells signal stem cells to maintain the stem cell fate/self-renewal and inhibit differentiation. In the C. elegans germline, GLP-1 Notch signaling specifies the stem cell fate, employing the sequence-specific DNA binding protein LAG-1 to implement the transcriptional response. We undertook a comprehensive genome-wide approach to identify transcriptional targets of GLP-1 signaling. We expected primary response target genes to be evident at the intersection of genes identified as directly bound by LAG-1, from ChIP-seq experiments, with genes identified as requiring GLP-1 signaling for RNA accumulation, from RNA-seq analysis. Furthermore, we performed a time-course transcriptomics analysis following auxin inducible degradation of LAG-1 to distinguish between genes whose RNA level was a primary or secondary response of GLP-1 signaling. Surprisingly, only lst-1 and sygl-1, the two known target genes of GLP-1 in the germline, fulfilled these criteria, indicating that these two genes are the primary response targets of GLP-1 Notch and may be the sole germline GLP-1 signaling protein-coding transcriptional targets for mediating the stem cell fate. In addition, three secondary response genes were identified based on their timing following loss of LAG-1, their lack of a LAG-1 ChIP-seq peak and that their glp-1 dependent mRNA accumulation could be explained by a requirement for lst-1 and sygl-1 activity. Moreover, our analysis also suggests that the function of the primary response genes lst-1 and sygl-1 can account for the glp-1 dependent peak protein accumulation of FBF-2, which promotes the stem cell fate and, in part, for the spatial restriction of elevated LAG-1 accumulation to the stem cell region.
Prepare to adapt: blood supply and transfusion support during the first 2 weeks of the 2019 novel coronavirus (COVID‐19) pandemic affecting Washington State

The first coronavirus (COVID‐19) case was reported in United States in the state of Washington, approximately 3 months after the outbreak in Wuhan, China. Three weeks later, the US federal government declared the pandemic a national emergency. The number of confirmed COVID‐19 positive cases increased rather rapidly and changed routine daily activities of the community.
miRNA expression can classify pediatric thyroid lesions and increases the diagnostic yield of mutation testing

Genetic alterations in multiple cell signaling pathways are involved in the molecular pathogenesis of thyroid cancer. Oncogene mutation testing and gene‐expression profiling are routinely used for the preoperative risk management of adult thyroid nodules. In this study, we evaluated the potential value of miRNA biomarkers for the classification of pediatric thyroid lesions.
Health Care Costs at End-of-Life for Patients with Idiopathic Pulmonary Fibrosis: Evaluation of a Pilot Multidisciplinary Clinic.

RATIONALE Even though Idiopathic pulmonary fibrosis (IPF) is a disease with high morbidity and mortality and no cure, palliative care is rarely implemented, leading to high symptom burden and unmet care needs. In 2012 we implemented a Multidisciplinary Collaborative (MDC) care model linking clinic and community multidisciplinary teams to provide an early-integrated palliative approach, focusing on early symptom management and advanced care planning (ACP). OBJECTIVES This study evaluates the differences in resource utilization and associated costs of end-of-life care between early-integrated palliative and conventionally treated IPF patients. METHODS Using administrative health data, we identified all patients in Alberta who presented to hospital with an IPF diagnosis between Jan 1, 2012 and Dec 31, 2018 and died within this timeframe. We compared 3 groups of patients: those who received (1) MDC care (our clinic patients), (2) specialist care (SC; respirologist), and (3) non-specialist care (NSC; no contact with a respiratory clinic). The primary outcomes were health care resource utilization and costs in the year before death. RESULTS Of 2,768 patients across three groups, MDC patients were over 3 times more likely to have received anti-fibrotic therapies over SC patients (OR=3.0; 95%CI 1.8-5.2), almost twice as likely to receive pulmonary rehab (OR=1.9; 95%CI 1.1-3.4) and 36% more likely to receive opiates (OR=1.4; 95%CI 0.8-2.3) in the last year of life. The median total health care costs in the last 3 months of life were approximately $7,700 CDN lower for MDC patients compared to those receiving specialist care, driven primarily by fewer hospitalizations and ED visits. MDC patients were also less likely to die in hospital (44.9% MDC vs 64.9% SC vs 66.8% NSC, p<0.001) and had the highest rates of no hospitalization in the last year of life. CONCLUSIONS An integrated palliative approach in IPF is associated with improvements in the quality of end-of-life care and reduction in costs. Transformation of care models is required to deliver a palliative approach in IPF. Multidisciplinary collaborative teams within such models can address the high burden of unmet needs for symptom management, advance care planning (ACP) and community support in this complex population.
The Role of Fnr Paralogs in Controlling Anaerobic Metabolism in the Diazotroph Paenibacillus polymyxa WLY78

The members of the nitrogen-fixing Paenibacillus spp. have great potential to be used as a bacterial fertilizer in agriculture. However, the functions of the fnr gene(s) in nitrogen fixation and other metabolisms in Paenibacillus spp. are not known. Here, we found that in P. polymyxa WLY78, Fnr1 and Fnr3 were responsible for regulation of numerous genes in response to changes in oxygen levels, but Fnr5 and Fnr7 exhibited little effect. Fnr1 and Fnr3 indirectly or directly regulated many types of important metabolism, such as nitrogen fixation, Fe uptake, respiration, and electron transport. This study not only reveals the function of the fnr genes of P. polymyxa WLY78 in nitrogen fixation and other metabolisms but also will provide insight into the evolution and regulatory mechanisms of fnr in Paenibacillus. ABSTRACT Fnr is a transcriptional regulator that controls the expression of a variety of genes in response to oxygen limitation in bacteria. Genome sequencing revealed four genes (fnr1, fnr3, fnr5, and fnr7) coding for Fnr proteins in Paenibacillus polymyxa WLY78. Fnr1 and Fnr3 showed more similarity to each other than to Fnr5 and Fnr7. Also, Fnr1 and Fnr3 exhibited high similarity with Bacillus cereus Fnr and Bacillus subtilis Fnr in sequence and structures. Both the aerobically purified His-tagged Fnr1 and His-tagged Fnr3 in Escherichia coli could bind to the specific DNA promoter. Deletion analysis showed that the four fnr genes, especially fnr1 and fnr3, have significant impacts on growth and nitrogenase activity. Single deletion of fnr1 or fnr3 led to a 50% reduction in nitrogenase activity, and double deletion of fnr1 and fnr3 resulted to a 90% reduction in activity. Genome-wide transcription analysis showed that Fnr1 and Fnr3 indirectly activated expression of nif (nitrogen fixation) genes and Fe transport genes under anaerobic conditions. Fnr1 and Fnr3 inhibited expression of the genes involved in the aerobic respiratory chain and activated expression of genes responsible for anaerobic electron acceptor genes. IMPORTANCE The members of the nitrogen-fixing Paenibacillus spp. have great potential to be used as a bacterial fertilizer in agriculture. However, the functions of the fnr gene(s) in nitrogen fixation and other metabolisms in Paenibacillus spp. are not known. Here, we found that in P. polymyxa WLY78, Fnr1 and Fnr3 were responsible for regulation of numerous genes in response to changes in oxygen levels, but Fnr5 and Fnr7 exhibited little effect. Fnr1 and Fnr3 indirectly or directly regulated many types of important metabolism, such as nitrogen fixation, Fe uptake, respiration, and electron transport. This study not only reveals the function of the fnr genes of P. polymyxa WLY78 in nitrogen fixation and other metabolisms but also will provide insight into the evolution and regulatory mechanisms of fnr in Paenibacillus.
Development of Rapid Word-Object Associations in Relation to Expressive Vocabulary: Shared Commonalities in Infants and Toddlers with and without Williams Syndrome.

Associative word learning, i.e., associating a word with an object, is an important building block of early word learning for TD infants. The present study investigated the development of word-object associations by TD infants and infants and toddlers with Williams syndrome (WS), a rare genetic disorder associated with delayed language and cognitive development. The specific reasons for the language delays are unknown. We investigated whether their early language delay could be related to differences in how word-object associations are formed. Fifty-nine 11- to 14-month-old TD infants and thirty-one 12- to 35-month-olds with WS were tested on a modified version of the "switch" task (Werker, Cohen, Lloyd, Casasola, & Stager, 1998) using phonetically dissimilar words and novel objects. Infants were classified as word-learners or novice word-learners based on their expressive vocabularies (greater than 10 words versus. 10 words or fewer). We found similar developmental patterns across both populations: Expressive vocabulary size classification was an important index of the development of word-object associations. Moreover, the development of word-object associations evidenced a domain-general progression from independent (processing objects separately from words) to integrated (processing associations between words and objects). As a group, word-learners formed word-object associations, but novice word-learners did not; instead, they focused primarily on the objects. Findings build on previous research suggesting that although early language acquisition is delayed in infants with WS, infants and toddlers with and without WS share a common developmental pattern and set of mechanisms in early word learning.
ALTERED MERISTEM PROGRAM1 regulates leaf identity independently of miR156-mediated translational repression

ABSTRACT In Arabidopsis, loss of the carboxypeptidase ALTERED MERISTEM PROGRAM1 (AMP1) produces an increase in the rate of leaf initiation, an enlarged shoot apical meristem and an increase in the number of juvenile leaves. This phenotype is also observed in plants with reduced levels of miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors, suggesting that AMP1 might promote SPL activity. However, we found that the amp1 mutant phenotype is only partially corrected by elevated SPL gene expression, and that amp1 has no significant effect on SPL transcript levels, or on the level or the activity of miR156. Although AMP1 has been reported to promote miRNA-mediated translational repression, amp1 did not prevent the translational repression of the miR156 target SPL9 or the miR159 target MYB33. These results suggest that AMP1 regulates vegetative phase change downstream of, or in parallel to, the miR156/SPL pathway, and that it is not universally required for miRNA-mediated translational repression. Summary: Loss of the carboxypeptidase AMP1 does not interfere with the function of miR156 or miR159, suggesting that AMP1 is not universally required for miRNA-mediated translational repression in Arabidopsis.
Long noncoding RNA ILF3-AS1 regulates myocardial infarction via the miR-212-3p/SIRT1 axis and PI3K/Akt signaling pathway.

OBJECTIVE Myocardial infarction (MI) is a serious cardiac disease due to its high incidence and mortality worldwide. Long noncoding RNAs (lncRNAs) have been found to play an essential role in the pathological progress of various cardiovascular diseases. ILF3-AS1 is a newly identified lncRNA, and many studies have demonstrated that ILF3-AS1 affects the development of various malignancies. However, the biological function of ILF3-AS1 and its underlying mechanism in MI are still unknown. In the present study, the function of ILF3-AS1 and the possible mechanisms against hypoxia-induced apoptosis in H9c2 cells were investigated. MATERIALS AND METHODS H9c2 cells were exposed to hypoxia (1% O2) to mimic the in vitro model of MI. The levels of lncRNA ILF3-AS1 and microRNA miR-212-3p were measured by real-time PCR (RT-PCR). Transfection was performed to upregulate the levels of ILF3-AS1 and miR-212-3p. Western blot assays were carried out to measure protein expression. The relationship between ILF3-AS1 and miR-212-3p was verified by Dual-Luciferase reporter assay. RESULTS We found that ILF3-AS1 was downregulated by hypoxia. Overexpression of ILF3-AS1 resulted in the relief of hypoxia-induced damage to H9c2 cells by rescuing cell viability, migration, and invasion and suppressing apoptosis, while downregulation of ILF3-AS1 had the opposite effects. Moreover, ILF3-AS1 could negatively regulate miR-212-3p expression, and upregulation of ILF3-AS1 could alleviate hypoxic injury via downregulation of miR-212-3p. Moreover, miR-212-3p negatively regulated SIRT1 expression. Further investigations revealed that ILF3-AS1 activated PI3K/Akt signaling and that application of the PI3K inhibitor LY294002 could abrogate the protective effects of ILF3-AS1 against hypoxia. CONCLUSIONS In summary, we concluded that ILF3-AS1 provides protection against hypoxia-induced injury via the PI3K/Akt pathway, which may provide clues for the treatment of patients with MI.
Genetic Variability of Ceraeochrysa cincta, Ceraeochrysa claveri, and Ceraeochrysa cubana (Neuroptera: Chrysopidae) Populations in Agroecosystems of Southeast Brazil

Abstract The species of the genus Ceraeochrysa, known as green lacewings or trash-carriers, are widely distributed along the Americas and its islands. In Brazil, 28 species are found, including Ceraeochrysa cincta (Schneider), Ceraeochrysa claveri (Navás), and Ceraeochrysa cubana (Hagen). These species are recorded on many crops, where they are often used for biological control. For this use, knowledge of the genetic features of the species is extremely important because they are associated to the species' ability to withstand different conditions in new environments, such as variations of temperature and presence of pathogens. However, little is known about the genetic features of Ceraeochrysa species. Here, we analyze and compare the distribution of the genetic variability of C. cincta, C. claveri, and C. cubana in agroecosystem populations of southeast Brazil. We found a high genetic diversity in each of the three species, and no strong genetic structure was detected, such that genetic diversity is broadly shared among the crops and localities analyzed. We can conclude that there was a high gene flow among the sampled Ceraeochrysa populations (natural or driven by anthropic action) since the exchange of seedlings among crops can lead to the distribution of the specimens.
Fine-grained statistical structure of speech

In spite of its acoustic diversity, the speech signal presents statistical regularities that can be exploited by biological or artificial systems for efficient coding. Independent Component Analysis (ICA) revealed that on small time scales (∼ 10 ms), the overall structure of speech is well captured by a time-frequency representation whose frequency selectivity follows the same power law in the high frequency range 1–8 kHz as cochlear frequency selectivity in mammals. Variations in the power-law exponent, i.e. different time-frequency trade-offs, have been shown to provide additional adaptation to phonetic categories. Here, we adopt a parametric approach to investigate the variations of the exponent at a finer level of speech. The estimation procedure is based on a measure that reflects the sparsity of decompositions in a set of Gabor dictionaries whose atoms are Gaussian-modulated sinusoids. We examine the variations of the exponent associated with the best decomposition, first at the level of phonemes, then at an intra-phonemic level. We show that this analysis offers a rich interpretation of the fine-grained statistical structure of speech, and that the exponent values can be related to key acoustic properties. Two main results are: i) for plosives, the exponent is lowered by the release bursts, concealing higher values during the opening phases; ii) for vowels, the exponent is bound to formant bandwidths and decreases with the degree of acoustic radiation at the lips. This work further suggests that an efficient coding strategy is to reduce frequency selectivity with sound intensity level, congruent with the nonlinear behavior of cochlear filtering.
Morphological variations of the human talus investigated using three‐dimensional geometric morphometrics

The shape of the talus determines the positional and kinematic features of the subtalar, talonavicular, and talocrural joints during walking. Thus, detailed knowledge of the pattern of sexual dimorphism of the human talus may be useful for revealing the pathogenetic mechanism of foot and knee disorders, which are more prevalent in females. The aim of this study was to characterize and visualize the three‐dimensional shape variations of the talus in relation to sex and age using geometric morphometrics.