Miracle-dz/UniFAR-FTUs huggingface dataset:
Obesity Impairs Embryonic Myogenesis by Enhancing BMP Signaling within the Dermomyotome

Obesity during pregnancy leads to adverse health outcomes in offspring. However, the initial effects of maternal obesity (MO) on embryonic organogenesis have yet to be thoroughly examined. Using unbiased single‐cell transcriptomic analyses (scRNA‐seq), the effects of MO on the myogenic process is investigated in embryonic day 9.5 (E9.5) mouse embryos. The results suggest that MO induces systematic hypoxia, which is correlated with enhanced BMP signaling and impairs skeletal muscle differentiation within the dermomyotome (DM). The Notch‐signaling effectors, HES1 and HEY1, which also act down‐stream of BMP signaling, suppress myogenic differentiation through transcriptionally repressing the important myogenic regulator MEF2C. Moreover, the major hypoxia effector, HIF1A, enhances expression of HES1 and HEY1 and blocks myogenic differentiation in vitro. In summary, this data demonstrate that MO induces hypoxia and impairs myogenic differentiation by up‐regulating BMP signaling within the DM, which may account for the disruptions of skeletal muscle development and function in progeny.
Overcoming GNA/RNA base-pairing limitations using isonucleotides improves the pharmacodynamic activity of ESC+ GalNAc-siRNAs

Abstract We recently reported that RNAi-mediated off-target effects are important drivers of the hepatotoxicity observed for a subset of GalNAc–siRNA conjugates in rodents, and that these findings could be mitigated by seed-pairing destabilization using a single GNA nucleotide placed within the seed region of the guide strand. Here, we report further investigation of the unique and poorly understood GNA/RNA cross-pairing behavior to better inform GNA-containing siRNA design. A reexamination of published GNA homoduplex crystal structures, along with a novel structure containing a single (S)-GNA-A residue in duplex RNA, indicated that GNA nucleotides universally adopt a rotated nucleobase orientation within all duplex contexts. Such an orientation strongly affects GNA-C and GNA-G but not GNA-A or GNA-T pairing in GNA/RNA heteroduplexes. Transposition of the hydrogen-bond donor/acceptor pairs using the novel (S)-GNA-isocytidine and -isoguanosine nucleotides could rescue productive base-pairing with the complementary G or C ribonucleotides, respectively. GalNAc-siRNAs containing these GNA isonucleotides showed an improved in vitro activity, a similar improvement in off-target profile, and maintained in vivo activity and guide strand liver levels more consistent with the parent siRNAs than those modified with isomeric GNA-C or -G, thereby expanding our toolbox for the design of siRNAs with minimized off-target activity.
The human olfactory bulb processes odor valence representation and cues motor avoidance behavior

Significance Whether an odor's perceived valence induces an approach response or triggers avoidance is critical for survival, and yet little is known about the neural mechanisms supporting this decision. Using electrophysiological measures from the human olfactory bulb (OB), the first processing stage of the olfactory system, and measures of full-body movement, we provide evidence that this process is initiated in the human OB. We demonstrate that odor valence is associated with both gamma and beta activity in the OB. Furthermore, we show that unpleasant odors have privileged temporal OB access, as indicated by early beta activity that is linked to a preparatory neural motor response in the motor cortex, which, in turn, is associated behaviorally with a fast full-body avoidance response. Determining the valence of an odor to guide rapid approach–avoidance behavior is thought to be one of the core tasks of the olfactory system, and yet little is known of the initial neural mechanisms supporting this process or of its subsequent behavioral manifestation in humans. In two experiments, we measured the functional processing of odor valence perception in the human olfactory bulb (OB)—the first processing stage of the olfactory system—using a noninvasive method as well as assessed the subsequent motor avoidance response. We demonstrate that odor valence perception is associated with both gamma and beta activity in the human OB. Moreover, we show that negative, but not positive, odors initiate an early beta response in the OB, a response that is linked to a preparatory neural motor response in the motor cortex. Finally, in a separate experiment, we show that negative odors trigger a full-body motor avoidance response, manifested as a rapid leaning away from the odor, within the time period predicted by the OB results. Taken together, these results demonstrate that the human OB processes odor valence in a sequential manner in both the gamma and beta frequency bands and suggest that rapid processing of unpleasant odors in the OB might underlie rapid approach–avoidance decisions.
Maternal iron deficiency alters trophoblast differentiation and placental development in rat pregnancy.

Iron deficiency occurs when iron demands chronically exceed intake, and is prevalent in pregnant women. Iron deficiency during pregnancy poses major risks for the baby, including fetal growth restriction and long-term health complications. The placenta serves as the interface between a pregnant mother and her baby, and ensures adequate nutrient provisions for the fetus. Thus, maternal iron deficiency may impact fetal growth and development by altering placental function. We used a rat model of diet-induced iron deficiency to investigate changes in placental growth and development. Pregnant Sprague-Dawley rats were fed either a low-iron or iron-replete diet starting two weeks before mating. Compared to controls, both maternal and fetal hemoglobin were reduced in dams fed low-iron diets. Iron deficiency decreased fetal liver and body weight, but not brain, heart or kidney weight. Placental weight was increased in iron deficiency, due primarily to expansion of the placental junctional zone. The stimulatory effect of iron deficiency on junctional zone development was recapitulated in vitro, as exposure of rat trophoblast stem cells to the iron chelator deferoxamine increased differentiation toward junctional zone trophoblast subtypes. Gene expression analysis revealed 464 transcripts changed at least 1.5-fold (P<0.05) in placentas from iron-deficient dams, including altered expression of genes associated with oxygen transport and lipoprotein metabolism. Expression of genes associated with iron homeostasis was unchanged despite differences in levels of their encoded proteins. Our findings reveal robust changes in placentation during maternal iron deficiency, which could contribute to the increased risk of fetal distress in these pregnancies.
Using copulas to enable causal inference from nonexperimental data: Tutorial and simulation studies.

Causal inference in psychological research is typically hampered by unobserved confounding. A copula-based method can be used to statistically control for this problem without the need for instruments or covariates, given relatively lenient distributional assumptions on independent variables and error terms. The current study aims to: (a) provide a user-friendly introduction to the copula method for psychology researchers, and (b) examine the degree of non-normality in the independent variables required for satisfactory performance. A Monte Carlo simulation study was used to assess the behavior of the copula method under various combinations of conditions (sample size, skewness of independent variables, effect size, and magnitude of confounding). In addition, an applied example from research on the effects of parental rearing on adult personality and life satisfaction was used to illustrate the method. Simulations revealed that the copula method performed better at higher levels of skewness in the independent variables, and that the impacts of lower skewness can be offset to some extent by larger sample size. When skewness and/or sample size is too small, the copula method is biased toward the uncorrected model. In the applied example, parental rejection/punishment predicted less adaptive personality and life satisfaction, with no evidence of confounding. For parental control/overprotection, there was evidence that confounding attenuated the estimated relationship with personality/life satisfaction. Copula adjustment is a promising method for handling unobserved confounding. The discussion focuses on how to proceed when assumptions are not quite met, and outlines potential avenues for future research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
TCF4 trinucleotide repeat expansion in Swedish cases with Fuchs' endothelial corneal dystrophy

Fuchs' endothelial corneal dystrophy (FECD) has been considered a genetically heterogeneous disease but is increasingly associated with the transcription factor 4 (TCF4) gene. This study investigates the prevalence of the cytosine‐thymine‐guanine (CTG)n repeat expansion in TCF4 among FECD patients in northern Sweden coupled to the phenotype.
Interpretation of a 12-Lead Electrocardiogram by Medical Students: Quantitative Eye-Tracking Approach

Background Accurate interpretation of a 12-lead electrocardiogram (ECG) demands high levels of skill and expertise. Early training in medical school plays an important role in building the ECG interpretation skill. Thus, understanding how medical students perform the task of interpretation is important for improving this skill. Objective We aimed to use eye tracking as a tool to research how eye fixation can be used to gain a deeper understanding of how medical students interpret ECGs. Methods In total, 16 medical students were recruited to interpret 10 different ECGs each. Their eye movements were recorded using an eye tracker. Fixation heatmaps of where the students looked were generated from the collected data set. Statistical analysis was conducted on the fixation count and duration using the Mann-Whitney U test and the Kruskal-Wallis test. Results The average percentage of correct interpretations was 55.63%, with an SD of 4.63%. After analyzing the average fixation duration, we found that medical students study the three lower leads (rhythm strips) the most using a top-down approach: lead II (mean=2727 ms, SD=456), followed by leads V1 (mean=1476 ms, SD=320) and V5 (mean=1301 ms, SD=236). We also found that medical students develop a personal system of interpretation that adapts to the nature and complexity of the diagnosis. In addition, we found that medical students consider some leads as their guiding point toward finding a hint leading to the correct interpretation. Conclusions The use of eye tracking successfully provides a quantitative explanation of how medical students learn to interpret a 12-lead ECG.
Complete Genome Sequences of Six Salmonella enterica Strains (S. enterica subsp. arizonae, S. enterica subsp. diarizonae, and S. enterica subsp. salamae) Isolated from Poultry Houses

Non-enterica subspecies of Salmonella enterica are associated with cold-blood animals. We report the complete genomes of six S. enterica strains (one S. enterica subsp. arizonae strain, four S. enterica subsp. salamae strains, and one S. enterica subsp. diarizonae strain) isolated from Spanish poultry houses. This will increase our knowledge of these non-enterica subspecies. ABSTRACT Non-enterica subspecies of Salmonella enterica are associated with cold-blood animals. We report the complete genomes of six S. enterica strains (one S. enterica subsp. arizonae strain, four S. enterica subsp. salamae strains, and one S. enterica subsp. diarizonae strain) isolated from Spanish poultry houses. This will increase our knowledge of these non-enterica subspecies.
Long-term effects of the mean hemoglobin A1c levels after percutaneous coronary intervention in patients with diabetes

Background/Aims The clinical benefit of strict blood glucose-lowering therapy for patients with coronary artery disease (CAD) is still debated. We aimed to evaluate the long-term outcomes of patients with diabetes who underwent percutaneous coronary intervention (PCI), according to the mean hemoglobin A1c (HbA1c) level after PCI. Methods We evaluated 675 diabetes patients with CAD treated with PCI. We categorized the study population into three groups based on the mean observed HbA1c levels during the follow-up duration, as follows: aggressive control (AC) group (HbA1c level < 6.5%, n = 148), moderate control (MC) group (HbA1c level ≥ 6.5% and < 7.0%, n = 138), and uncontrolled (UC) group (HbA1c level ≥ 7.0%, n = 389). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as cardiac death, myocardial infarction, repeat target vessel revascularization, and stroke. Results The mean HbA1c level of the AC group was significantly lower than that of the MC and UC groups (6.04% ± 0.36% vs. 6.74% ± 0.14% vs. 8.39% ± 1.20%, p < 0.001). The incidence of MACCEs was significantly lower in the AC group than in the MC and UC groups (16.0% vs. 24.3% vs. 26.3%, p = 0.010), mostly driven by the incidence of stroke (4.4% vs. 14.0% vs. 11.4%, p = 0.013). Multivariate Cox regression analysis showed that only the AC group was associated with a reduced rate of MACCEs (hazard ratio, 0.499; 95% confidence interval, 0.316 to 0.786; p = 0.004) compared with the UC group. Conclusions Our study showed that intensive glycemic control (HbA1c level < 6.5%) is associated with improved clinical outcomes after PCI in patients with diabetes.
Expanding the Burkholderia pseudomallei Complex with the Addition of Two Novel Species: Burkholderia mayonis sp. nov. and Burkholderia savannae sp. nov.

Burkholderia species can be important sources of novel natural products, and new species are of interest to diverse scientific disciplines. Although many Burkholderia species are saprophytic, Burkholderia pseudomallei is the causative agent of the disease melioidosis. ABSTRACT Distinct Burkholderia strains were isolated from soil samples collected in tropical northern Australia (Northern Territory and the Torres Strait Islands, Queensland). Phylogenetic analysis of 16S rRNA and whole genome sequences revealed these strains were distinct from previously described Burkholderia species and assigned them to two novel clades within the B. pseudomallei complex (Bpc). Because average nucleotide identity and digital DNA-DNA hybridization calculations are consistent with these clades representing distinct species, we propose the names Burkholderia mayonis sp. nov. and Burkholderia savannae sp. nov. Strains assigned to B. mayonis sp. nov. include type strain BDU6T (=TSD-80; LMG 29941; ASM152374v2) and BDU8. Strains assigned to B. savannae sp. nov. include type strain MSMB266T (=TSD-82; LMG 29940; ASM152444v2), MSMB852, BDU18, and BDU19. Comparative genomics revealed unique coding regions for both putative species, including clusters of orthologous genes associated with phage. Type strains of both B. mayonis sp. nov. and B. savannae sp. nov. yielded biochemical profiles distinct from each other and from other species in the Bpc, and profiles also varied among strains within B. mayonis sp. nov. and B. savannae sp. nov. Matrix-assisted laser desorption ionization time-of-flight (MLST) analysis revealed a B. savannae sp. nov. cluster separate from other species, whereas B. mayonis sp. nov. strains did not form a distinct cluster. Neither B. mayonis sp. nov. nor B. savannae sp. nov. caused mortality in mice when delivered via the subcutaneous route. The addition of B. mayonis sp. nov. and B. savannae sp. nov. results in a total of eight species currently within the Bpc. IMPORTANCE Burkholderia species can be important sources of novel natural products, and new species are of interest to diverse scientific disciplines. Although many Burkholderia species are saprophytic, Burkholderia pseudomallei is the causative agent of the disease melioidosis. Understanding the genomics and virulence of the closest relatives to B. pseudomallei, i.e., the other species within the B. pseudomallei complex (Bpc), is important for identifying robust diagnostic targets specific to B. pseudomallei and for understanding the evolution of virulence in B. pseudomallei. Two proposed novel species, B. mayonis sp. nov. and B. savannae sp. nov., were isolated from soil samples collected from multiple locations in northern Australia. The two proposed species belong to the Bpc but are phylogenetically distinct from all other members of this complex. The addition of B. mayonis sp. nov. and B. savannae sp. nov. results in a total of eight species within this significant complex of bacteria that are available for future studies.
Patient and practitioner views on cancer risk discussions in primary care: a qualitative study

Background It is estimated that nearly 600 000 cancer cases in the UK could have been avoided in the past 5 years if people had healthier lifestyles, with the principle modifiable risk factors being smoking, obesity, alcohol consumption, and inactivity. There is growing interest in the use of cancer risk information in general practice to encourage lifestyle modification. Aim To explore the views and experiences of patients and practitioners in relation to cancer prevention and cancer risk discussions in general practice. Design & setting Qualitative study among patients and practitioners in general practices in Glasgow, UK. Method Semi-structured interviews were conducted with nine practitioners (five GPs and four practice nurses, recruited purposively from practices based on list size and deprivation status), and 13 patients (aged 30–60 years, with two or more specified comorbidities). Results Currently, cancer risk discussions focus on smoking and cancer, with links between alcohol and/or obesity and cancer rarely made. There was support for the use of the personalised cancer risk tool as an additional resource in primary care. Practitioners felt practice nurses were best placed to use it. Use in planned appointments (for example, chronic disease reviews) was preferred over opportunistic use. Concerns were expressed, however, about generating anxiety, time constraints, and widening inequalities. Conclusion Health behaviour change is complex and the provision of information alone is unlikely to have significant effects. Personalised risk tools may have a role, but important concerns about their use remain, particularly in areas of socioeconomic disadvantage.
An electrically light-transmittance-controllable film with a low-driving voltage from a coexistent system of polymer-dispersed and polymer-stabilised cholesteric liquid crystals

ABSTRACT Polymer-dispersed liquid crystal (PDLC) films have been successfully applied in the field of smart windows, building partitions and projection screens. However, the high-driving voltage of the state-of-the-art PDLC films not only results in serious security problems but also leads to huge energy consumptions. Although studied for decades, however, no tangible improvements of reducing the driving voltage have been achieved due to the movements liquid crystals (LCs) are greatly confined by the porous polymer structures of PDLCs. In this paper, an electrically light-transmittance-controllable film with an unprecedented low-driving voltage (more than 50% lower than that of the typical PDLC films) was prepared from a new polymer dispersed and stabilised cholesteric LC system. Also, the effects of the amounts of chiral dopants on the electro-optical properties were studied. Graphical Abstract
Complete Genome Sequence of Salmonella enterica Serovar Typhi Strain ISP2825

Salmonella enterica serovar Typhi ISP2825, isolated in 1983 from a Chilean patient, is one of the major S. Typhi strains used for research, along with strains Ty2, CT18, and H58. The complete genome sequence of ISP2825, consisting of a 4,774,014-bp circular chromosome, will help us understand typhoid pathogenesis and evolution. ABSTRACT Salmonella enterica serovar Typhi ISP2825, isolated in 1983 from a Chilean patient, is one of the major S. Typhi strains used for research, along with strains Ty2, CT18, and H58. The complete genome sequence of ISP2825, consisting of a 4,774,014-bp circular chromosome, will help us understand typhoid pathogenesis and evolution.
Cytokines profile in patients with acute and chronic hepatitis B infection

Hepatitis B virus (HBV) is one of the leading causes of acute and chronic hepatitis and represents a serious public health threat. Cytokines are important chemical mediators that regulate the differentiation, proliferation, and function of immune cells, with accumulating evidence indicating that the inadequate immune responses are responsible for the elimination or persistence of HBV. This study aimed to determine the cytokine profiles (IFN‐γ, TNF‐α, IL‐2, IL‐4, IL‐6, IL‐10, and IL‐17A) during HBV infection and investigate their association with genotypes. A total of 66 plasma samples, 19 from patients with acute and 47 with chronic hepatitis B infection, were subjected to biochemical tests, nested‐PCR, and real‐time PCR, with cytokines evaluated using a commercial BD Cytometric Bead Array Human Th1/Th2/Th17 Cytokine Kit. Healthy controls (10 individuals) were selected from blood donors with no history of liver diseases. No correlation was found between genotypes, viral load, and cytokines analyzed. All cytokines showed higher levels of production among infected individuals when compared with the control group. A positive correlation classified as moderate to strong was found between cytokines IFN‐γ, TNF, IL‐10, IL‐6, IL‐4, and IL‐2 through the Spearman correlation coefficient. TNF (P = 0.009), IL‐10 (P < 0.001), and IL‐6 (P < 0.001) levels were higher in acute individuals compared with chronic and control groups. Theses cytokines could be involved in the elimination of virus and protection against chronicity.
High-Performance Acceleration of 2-D and 3-D CNNs on FPGAs Using Static Block Floating Point

Over the past few years, 2-D convolutional neural networks (CNNs) have demonstrated their great success in a wide range of 2-D computer vision applications, such as image classification and object detection. At the same time, 3-D CNNs, as a variant of 2-D CNNs, have shown their excellent ability to analyze 3-D data, such as video and geometric data. However, the heavy algorithmic complexity of 2-D and 3-D CNNs imposes a substantial overhead over the speed of these networks, which limits their deployment in real-life applications. Although various domain-specific accelerators have been proposed to address this challenge, most of them only focus on accelerating 2-D CNNs, without considering their computational efficiency on 3-D CNNs. In this article, we propose a unified hardware architecture to accelerate both 2-D and 3-D CNNs with high hardware efficiency. Our experiments demonstrate that the proposed accelerator can achieve up to 92.4% and 85.2% multiply-accumulate efficiency on 2-D and 3-D CNNs, respectively. To improve the hardware performance, we propose a hardware-friendly quantization approach called static block floating point (BFP), which eliminates the frequent representation conversions required in traditional dynamic BFP arithmetic. Comparing with the integer linear quantization using zero-point, the static BFP quantization can decrease the logic resource consumption of the convolutional kernel design by nearly 50% on a field-programmable gate array (FPGA). Without time-consuming retraining, the proposed static BFP quantization is able to quantize the precision to 8-bit mantissa with negligible accuracy loss. As different CNNs on our reconfigurable system require different hardware and software parameters to achieve optimal hardware performance and accuracy, we also propose an automatic tool for parameter optimization. Based on our hardware design and optimization, we demonstrate that the proposed accelerator can achieve 3.8–5.6 times higher energy efficiency than graphics processing unit (GPU) implementation. Comparing with the state-of-the-art FPGA-based accelerators, our design achieves higher generality and up to 1.4–2.2 times higher resource efficiency on both 2-D and 3-D CNNs.