Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutation Analysis and Disease Features at Presentation in a Multi-Center Cohort of Children With Monogenic Cholestasis

Supplemental Digital Content is available in the text ABSTRACT Objectives: To advance our understanding of monogenic forms of intrahepatic cholestasis. Methods: Analyses included participants with pathogenic biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 11 (ABCB11) (bile salt export pump; BSEP) or adenosine triphosphatase (ATPase) phospholipid transporting 8B1 (ATP8B1) (familial intrahepatic cholestasis; FIC1), or those with monoallelic or biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 4 (ABCB4) (multidrug resistance; MDR3), prospectively enrolled in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC; NCT00571272) between November 2007 and December 2013. Summary statistics were calculated to describe baseline demographics, history, anthropometrics, laboratory values, and mutation data. Results: Ninety-eight participants with FIC1 (n = 26), BSEP (n = 53, including 8 with biallelic truncating mutations [severe] and 10 with p.E297G or p.D482G [mild]), or MDR3 (n = 19, including four monoallelic) deficiency were analyzed. Thirty-five had a surgical interruption of the enterohepatic circulation (sEHC), including 10 who underwent liver transplant (LT) after sEHC. Onset of symptoms occurred by age 2 years in most with FIC1 and BSEP deficiency, but was later and more variable for MDR3. Pruritus was nearly universal in FIC1 and BSEP deficiency. In participants with native liver, failure to thrive was common in FIC1 deficiency, high ALT was common in BSEP deficiency, and thrombocytopenia was common in MDR3 deficiency. sEHC was successful after more than 1 year in 7 of 19 participants with FIC1 and BSEP deficiency. History of LT was most common in BSEP deficiency. Of 102 mutations identified, 43 were not previously reported. Conclusions: In this cohort, BSEP deficiency appears to be correlated with a more severe disease course. Genotype–phenotype correlations in these diseases are not straightforward and will require the study of larger cohorts.
ASCL1 represses a SOX9+ neural crest stem-like state in small cell lung cancer

In this study, Olsen et al. show that alterations in Rb1/Trp53/Myc in the mouse lung induce an ASCL1+ state of small cell lung cancer (SCLC) in multiple cells of origin. Their findings show that in a MYC-driven SCLC model, ASCL1 promotes neuroendocrine fate and represses the emergence of a SOX9+ nonendodermal stem-like fate that resembles neural crest.
Kinetic Analysis of CO2 Gasification of Petroleum Coke at High Pressures

Determining the intrinsic gasification rates at high pressures is essential for designing and modeling high-pressure technologies. In this study, the intrinsic kinetics of CO2 gasification of petroleum coke was investigated. The kinetic experiments were performed in a high-pressure thermogravimetric analysis unit at different temperatures (1173–1248 K) and pressures (0.1–2.4 MPa). Grain, volume, and random-pore models were applied to the experimental results to determine the kinetic parameters. The random-pore model provided the best fit to the data and was used to determine the kinetic parameters such that the activation energies and reaction orders could be determined. The reaction rates were described by a power law model that was half-order (0.49 ± 0.02) in CO2 pressure. Similar activation energies, 260 ± 24 and 254 ± 12 kJ/mol, were determined for pressures of 0.1 and 1.4 MPa, respectively, indicating similar reaction mechanisms for these pressures.
Psychosocial Adjustment in Emerging Adults With and Without Spina Bifida: A 14-Year Follow-up Study

ABSTRACT: Objective: A 14-year follow-up of youth with spina bifida (SB), as compared to a matched comparison sample without a chronic health condition, focused on psychosocial adjustment during emerging adulthood (ages 22–23). Methods: The initial cohort at time 1 consisted of 68 families with an 8-year-old or 9-year-old child with SB and a matched comparison sample of 68 typically developing children and their families. At the final assessment (time 7), participants included 56 emerging adults with SB (82% of those who participated at time 1) and 62 comparison youth (91% of those who participated at time 1) who completed a set of self-report measures. Results: Emerging adults with SB continue to lag behind across several important developmental milestones, including decision-making responsibility, involvement in social and romantic relationships, sexual intimacy, educational and vocational achievement, financial independence, and engagement in health-related behaviors. However, from a resilience perspective, these individuals also exhibited a number of strengths across the following areas: identity development, quality of social supports, and fewer problem behaviors (e.g., alcohol and other substance use). Most findings were still significant after controlling for a verbal intelligence quotient proxy. Conclusion: This study highlighted vulnerabilities and strengths of individuals with SB as they enter emerging adulthood, with considerable continuity across childhood, adolescence, and emerging adulthood.
Psycholinguistic Markers of COVID-19 Conspiracy Tweets and Predictors of Tweet Dissemination

ABSTRACT The adoption of conspiracy theories about COVID-19 has been fairly widespread among the general public and associated with the rejection of self-protective behaviors. Despite their significance, however, a gap remains in our understanding of the underlying characteristics of messages used to disseminate COVID-19 conspiracies. We used the construct of resonance as a framework to examine a sample of more than 1.8 million posts to Twitter about COVID-19 made between April and June 2020. Our analyses focused on the psycholinguistic properties that distinguish conspiracy theory tweets from other COVID-19 topics and predict their spread. COVID-19 conspiracy tweets were distinct and most likely to resonate when they provided explanations and expressed negative emotions. The results highlight the sensemaking functions served by conspiracy tweets in response to the profound upheaval caused by the pandemic.
The Brazilian Cerrado is becoming hotter and drier

The Brazilian Cerrado is a global biodiversity hotspot with notoriously high rates of native vegetation suppression and wildfires over the past three decades. As a result, climate change can already be detected at both local and regional scales. In this study, we used three different approaches based on independent datasets to investigate possible changes in the daytime and nighttime temperature and air humidity between the peak of the dry season and the beginning of the rainy season in the Brazilian Cerrado. Additionally, we evaluated the tendency of dew point depression, considering it as a proxy to assess impacts on biodiversity. Monthly increases of 2.2−4.0℃ in the maximum temperatures and 2.4−2.8℃ in the minimum temperatures between 1961 and 2019 were recorded, supported by all analyzed datasets which included direct observations, remote sensing, and modeling data. The warming raised the vapor pressure deficit, and although we recorded an upward trend in absolute humidity, relative humidity has reduced by ~15%. If these tendencies are maintained, gradual air warming will make nightly cooling insufficient to reach the dew point in the early hours of the night. Therefore, it will progressively reduce both the amount and duration of nocturnal dewfall, which is the main source of water for numerous plants and animal species of the Brazilian Cerrado during the dry season. Through several examples, we hypothesize that these climate changes can have a high impact on biodiversity and potentially cause ecosystems to collapse. We emphasize that the effects of temperature and humidity on Cerrado ecosystems cannot be neglected and should be further explored from a land use perspective.
Association of single‐nucleotide polymorphisms in tumour necrosis factor and human leukocyte antigens genes with type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disease characterized by progressive destruction of insulin‐producing pancreatic beta cells. This multifactorial disease has a strong genetic component associated with the human leukocyte antigens (HLA) and non‐HLA regions. In this study, we compared frequencies of HLA‐DRB1 alleles and single‐nucleotide polymorphisms (SNPs) associated the genes coding for: toll‐like receptors (TLRs), tumour necrosis factor (TNF), interleukin‐1 (IL‐1), interleukin‐1 receptor type 1 (IL‐1R1), interleukin‐1 receptor antagonist (IL‐1RN), interleukin‐2 (IL‐2) and interleukin‐12B (IL‐12B), between T1D patients and healthy controls. The aim was to identify frequency differences and linkage between these genetic markers in T1D patients and healthy controls. Twelve SNPs were investigated as follows: rs16944 (IL‐1B), rs1143634 (IL‐1B), rs1800587 (IL‐1A), rs2069762 (IL‐2), rs3212227 (IL‐12B), rs2234650 (IL‐1R1), rs315952 (IL‐1RN), rs3804099 (TLR2), rs4986790 (TLR4), rs4986791 (TLR4), rs1800629 (TNF) and rs361525 (TNF). TaqMan genotype assay method was used for SNPs genotyping. HLA‐DRB1* genes were typed by Sequence Specific Oligonucleotide Probe (SSOP). SPSS and SNPStats programs were used for the statistical analysis. Significant differences between T1D and control groups were found for the dominant model of rs361525 and rs1800629A:rs361525G genotypes for TNF. Increased frequencies of DRB1*03 and DRB1*04 and decreased frequencies of DRB1*07, DRB1*11 and DRB1*13 and DRB1*15 were observed in T1D patients compared with controls. However, the genotype, DRB1*07 with rs1800629A/G was associated with T1D. We have confirmed that DRB1*03 and DRB1*04 are associated with increased risk and DRB1*07, DRB1*11 and DRB1*13 and DRB1*15 with decreased risk of T1D. Also, the dominant model of rs361525A, and the rs1800629G:361525A genotype were associated with increased risk. The simultaneous presence of DRB1*07 and rs1800629A/G genotypes in 23 out of 27 DRB1*07 positive T1D patients implied that islet cell peptide processing may have been biased towards autoimmunity by upregulation of TNF associated intronic SNPs.
Evaluation of 15 years of modeled atmospheric oxidized nitrogen compounds across the contiguous United States

Atmospheric nitrogen oxide and nitrogen dioxide (NO + NO2, together termed as NOX) estimates from annual photochemical simulations for years 2002–2016 are compared to surface network measurements of NOX and total gas-phase-oxidized reactive nitrogen (NOY) to evaluate the Community Multiscale Air Quality (CMAQ) modeling system performance by U.S. region, season, and time of day. In addition, aircraft measurements from 2011 Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality are used to evaluate how emissions, chemical mechanism, and measurement uncertainty each contribute to the overall model performance. We show distinct seasonal and time-of-day patterns in NOX performance. Summertime NOX is overpredicted with bimodal peaks in bias during early morning and evening hours and persisting overnight. The summertime morning NOX bias dropped from between 28% and 57% for earlier years (2002–2012) to between −2% and 7% for later years (2013–2016). Summer daytime NOX tends to be unbiased or underpredicted. In winter, the evening NOX overpredictions remain, but NOX is unbiased or underpredicted overnight, in the morning, and during the day. NOX overpredictions are most pronounced in the Midwestern and Southern United States with Western regions having more of a tendency toward model underpredictions of NOX. Modeled NOX performance has improved substantially over time, reflecting updates to the emission inputs and the CMAQ air quality model. Model performance improvements are largest for years simulated with CMAQv5.1 or later and for emission inventory years 2014 and later, coinciding with reduced onroad NOX emissions from vehicles with newer emission control technologies and improved treatment of chemistry, deposition, and vertical mixing in CMAQ. Our findings suggest that emissions temporalization of specific mobile source sectors have a small impact on model performance, while chemistry updates improve predictions of NOY but do not improve summertime NOX bias in the Baltimore/DC area. Sensitivity runs performed for different locations across the country suggest that the improvement in summer NOX performance can be attributed to updates in vertical mixing incorporated in CMAQv5.1.
Assessing the role of rare genetic variants in drug‐resistant, non‐lesional focal epilepsy

Resistance to antiseizure medications (ASMs) is one of the major concerns in the treatment of epilepsy. Despite the increasing number of ASMs available, the proportion of individuals with drug‐resistant epilepsy remains unchanged. In this study, we aimed to investigate the role of rare genetic variants in ASM resistance.
Increased connectivity and depth improve the effectiveness of marine reserves

Marine reserves are a key tool for the conservation of marine biodiversity, yet only ~2.5% of the world's oceans are protected. The integration of marine reserves into connected networks representing all habitats has been encouraged by international agreements, yet the benefits of this design has not been tested empirically. Australia has one of the largest systems of marine reserves, providing a rare opportunity to assess how connectivity influences conservation success. An Australia‐wide dataset was collected using baited remote underwater video systems deployed across a depth range from 0 to 100 m to assess the effectiveness of marine reserves for protecting teleosts subject to commercial and recreational fishing. A meta‐analytical comparison of 73 fished species within 91 marine reserves found that, on average, marine reserves had 28% greater abundance and 53% greater biomass of fished species compared to adjacent areas open to fishing. However, benefits of protection were not observed across all reserves (heterogeneity), so full subsets generalized additive modelling was used to consider factors that influence marine reserve effectiveness, including distance‐based and ecological metrics of connectivity among reserves. Our results suggest that increased connectivity and depth improve the aforementioned marine reserve benefits and that these factors should be considered to optimize such benefits over time. We provide important guidance on factors to consider when implementing marine reserves for the purpose of increasing the abundance and size of fished species, given the expected increase in coverage globally. We show that marine reserves that are highly protected (no‐take) and designed to optimize connectivity, size and depth range can provide an effective conservation strategy for fished species in temperate and tropical waters within an overarching marine biodiversity conservation framework.
High-Pass Sigma–Delta Modulator With Techniques of Operational Amplifier Sharing and Programmable Feedforward Coefficients for ECG Signal Acquisition

A high-pass sigma–delta modulator (HPSDM) is proposed for electrocardiography (ECG) signal acquisition system. The HPSDM is implemented using operational amplifier (op-amp) sharing and programmable feedforward coefficients. The op-amp sharing is adopted to reduce the quantity of amplifiers because they dominate the power consumption of the HPSDM. In addition, given that the magnitude of the ECG is dependent on different persons, programmable feedforward coefficients are utilized to extend the dynamic range of the HPSDM to fit the actual application. The proposed HPSDM is fabricated in a 0.18-μm standard CMOS process. Measurement results reveal that the proposed HPSDM has a signal-to-noise and distortion ratio (SNDR) of 54.5 dB and a power consumption of 2.25 μW under a 1.2 V supply voltage and achieves a figure of merit (FoM) of 12.96 pJ/conv. Moreover, the proposed HPSDM has an SNDR of 64.8 dB and a power consumption of 5.2 μW under a 1.8 V supply voltage and achieves a FoM of 9.15 pJ/conv due to the op-amp sharing technique. Under the 1.2 V and 1.8 V supply voltages, the dynamic range of the HPSDM is extended to approximately 12 dB due to the technique of programmable feedforward coefficients.
Exploring the relationships between resilience, mindfulness, and experiential avoidance after the use of a mindfulness- and acceptance-based mobile app for posttraumatic stress disorder.

PURPOSE This study used a mindfulness- and acceptance-based mobile app to examine the relationships between resilience, mindfulness, experiential avoidance, and posttraumatic stress disorder (PTSD) symptoms. DESIGN AND METHODS A quasi-experimental pre-posttest, single-group study design was used. A total of 23 college student veterans used the app for 4 weeks. Outcomes of resilience, mindfulness, experiential avoidance, and PTSD were measured at three time-points (baseline, end of Week 2, and end of Week 4). FINDINGS All outcomes significantly improved at postintervention. Improvements in resilience and PTSD significantly correlated with improvement in mindfulness. PRACTICE IMPLICATIONS Mindfulness- and acceptance-based mobile apps can be safely used by individuals with PTSD as a complementary approach to enhance resilient coping with PTSD.
Facilitators and barriers of 2-1-1 HIV pre-exposure prophylaxis

An alternative strategy for men who have sex with men (MSM) experiencing challenges with daily HIV pre-exposure prophylaxis (PrEP) includes 2-1-1 dosing. Understanding 2-1-1 PrEP facilitators and barriers, especially during the SARS-CoV-2 pandemic, may guide researchers and healthcare providers in future studies and clinical preparedness. We conducted a national cross-sectional study of MSM in the US who had taken 2-1-1 PrEP to examine facilitators and barriers of this on-demand PrEP dosing option. With the shelter-in-place orders in March 2020, this study was adapted to include questions on how the SARS-CoV-2 pandemic affected participants’ PrEP use. A total of 140 individuals participated in the survey, 106 of which completed questions pertaining to the SARS-CoV-2 pandemic. The most common reasons for switching from once-daily to 2-1-1 PrEP included having sex less frequently (63.6%) and wanting to take fewer pills (46.4%). Participants reported high medication adherence based on each component of 2-1-1 PrEP dosing (>84%). The most common barriers with 2-1-1 PrEP dosing included unplanned sexual encounters resulting in missing the double-dose pre-sex (43.6%) and trouble remembering doses post-sex (29.3%). Facilitators of the 2-1-1 PrEP dosing strategy included reductions in sexual encounters (63.6%), preference to take fewer pills (46.4%), need to reduce cost (22.1%), and desire to reduce side effects (19.3%). Challenges to receiving PrEP services during the pandemic included obtaining laboratory testing (25.5%) and PrEP refills (either receipt of a refill authorization from a healthcare provider or processing of a refill from the pharmacy) (18.9%). 2-1-1 PrEP is an effective HIV prevention method; therefore, understanding facilitators and barriers of this dosing strategy can result in continuous provision of HIV prevention efforts, particularly during a pandemic.
Age‐related telomere attrition causes aberrant gene expression in sub‐telomeric regions

Telomere attrition has been proposed as a biomarker and causal factor in aging. In addition to causing cellular senescence and apoptosis, telomere shortening has been found to affect gene expression in subtelomeric regions. Here, we analyzed the distribution of age‐related differentially expressed genes from the GTEx RNA sequencing database of 54 tissue types from 979 human subjects and found significantly more upregulated than downregulated genes in subtelomeric regions as compared to the genome‐wide average. Our data demonstrate spatial relationships between telomeres and gene expression in aging.
Solid State Electrochromic Devices of Plasma Modified WO3 Hybrids

Electrochromic (EC) properties of tungsten trioxide (WO3) was improved with preparing hybrids of tungsten trioxide–titanium dioxide (WO3–TiO2) and tungsten trioxide–poly(3,4-ethylenedioxythiophene) (WO3–PEDOT) by a rotating capacitively coupled radio frequency (rf 13.56 MHz) plasma reactor. Energy-dispersive X-ray spectroscopy mapping results indicated that TiO2 and PEDOT were coated homogeneously onto the surface of the WO3 powders. Thin films of hybrid powders have been prepared by the physical vapor deposition method of the electron beam evaporation technique. Redox potentials, optical contrast at 700 nm, and durability during 2000 cycles of EC devices were investigated, comparatively. Hybrids of WO3 indicated excellent coloration efficiency (cm2 C–1) and switching speed values compared with untreated WO3. The coloration efficiency values were found to be 85.88 and 41.61 cm2 C–1 of WO3–TiO2 and WO3–PEDOT, respectively. The switching speed of WO3 (13.3 s, from bleached state to colored state) increased .
Composition and Dynamic Changes of Sugars and Acids in Chinese Dwarf Cherry(Cerasus humilis Bunge) during Fruit Development

The contents of sugars and organic acids during fruit development were investigated and the dynamic changes of sugars and organic acids were analyzed in the fruit of Chinese dwarf cherry cultivars ‘Nongda 3’,'Nongda 4' and 'Nongda 5'. The results showed that:(1)The content differences of total sugars,total acids and sugar acid ratio in three cultivars were obvious. (2)The content of fructose was at higher level,glucose and sucrose were at lower level,and only a little sorbitol was found in the ripening stage of three cultivars.The malic acid was the main acid in the the ripening stage of three cultivars,compared to the low content of citric acid. (3)The contents of fructose,surcose,glucose and sorbitol were increasing in the whole fruit development period in three cultivars.Fructose was the major sugar in the fruit.The content of fructose increased quickly in the mid-period of fruit development in ‘Nongda 3’,and was obviously higher than that in other two cultivars.The changing trends of sucrose were similar during the different cultivars,which was increasing slowly in the early-period and mid-period and was increasing quickly(above 70 percent of total sugars) in the late-period of fruit development. (4)The changing trends of acids were similar in three cultivars.The contents of malic acid and citric acid was lower in the early-period and mid-period of fruit development,and increasing rapidly in the late-period,but reducing dramatically when the fruit was close to mature.To sum up,the contents and the dynamic changes of frutose and malic acid were main factors which affect the sugar acid ratio and determine the fruit flavor.