Miracle-dz/UniFAR-FTUs huggingface dataset:
Dysfunction of Caveolae‐Mediated Endocytic TβRI Degradation Results in Hypersensitivity of TGF‐β/Smad Signaling in Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a genetic disorder caused by mutations of type I collagen‐related genes, and excessive transforming growth factor‐beta (TGF‐β) signaling is a common mechanism. TGF‐β/Smad signaling has inhibitory effects on osteoblast differentiation and maturation and is mainly transduced and regulated by the internalization of a tetrameric receptor complex comprising types I and II TGF‐β receptors (TβRI and TβRII). During internalization, clathrin‐mediated endocytosis enhances TGF‐β/Smad signaling via Smad2/3 phosphorylation and receptors recycling, while caveolae‐mediated endocytosis turns off TGF‐β/Smad signaling by promoting receptor ubiquitination and degradation. In this study, using an animal model of OI (Colla2oim, osteogenesis imperfecta murine [oim]/oim mouse), we found that osteoblastic cells of oim/oim mice were more sensitive to the inhibitory effects of TGF‐β on osteoblast differentiation and maturation and had much higher cell membrane protein levels of TGF‐β receptors than those of wild‐type (wt)/wt mice. Further results showed that clathrin‐mediated endocytosis of TβRI was enhanced, whereas caveolae‐mediated TβRI endocytic degradation was reduced in oim/oim mice, combined with reduced caveolin‐1 (Cav‐1) phosphorylation. In addition, type I collagen downregulated TβRI via focal adhesion kinase (FAK) and Src activation‐dependent Cav‐1 phosphorylation. To further examine this mechanism, 4‐week‐old oim/oim and wt/wt mice were treated with either TβRI kinase inhibitor (SD‐208) or vehicle for 8 weeks. SD‐208 treatment significantly reduced the fracture incidence in oim/oim mice. Micro–computed tomography and biomechanical testing showed that femoral bone mass and strength were significantly improved with SD‐208 treatment in both genotypes. Additionally, SD‐208 significantly promoted osteoblast differentiation and bone formation and inhibited bone resorption. In conclusion, dysfunction of caveolae‐mediated endocytic TβRI degradation is a possible mechanism for the enhanced TGF‐β/Smad signaling in OI. Targeting this mechanism using a TβRI kinase inhibitor effectively reduced fractures and improved bone mass and strength in OI model and, thus, may offer a new strategy for the treatment of OI. © 2022 American Society for Bone and Mineral Research (ASBMR).
Added value of patient‐ and drug‐related factors to stratify drug‐drug interaction alerts for risk of QT prolongation: Development and validation of a risk prediction model

Many clinical decision support systems trigger warning alerts for drug‐drug interactions potentially leading to QT prolongation and torsades de pointes (QT‐DDIs). Unfortunately, there is overalerting and underalerting because stratification is only based on a fixed QT‐DDI severity level. We aimed to improve QT‐DDI alerting by developing and validating a risk prediction model considering patient‐ and drug‐related factors.
Diagnosis of Interproximal Caries Lesions in Bitewing Radiographs Using a Deep Convolutional Neural Network-Based Software

The aim of this study was to evaluate the diagnostic reliability of a web-based artificial intelligence program for the detection of interproximal caries in bitewing radiographs. Three hundred bitewing radiographs of patients were subjected to the evaluation of a convolutional neural network. First, the images were visually evaluated by a previously trained and calibrated operator with radiodiagnosis experience. Then, ground truth was established and was clinically validated. For enamel caries, clinical assessment included a combination of clinical-visual and radiography evaluations. For dentin caries, clinical validation was performed by instrumentally accessing the cavity. Second, the images were uploaded and analyzed by the web-based software. Four different models were established to analyze its evaluations according to the confidence threshold (0–100%) offered by the program: model 1 (values >0% were considered positive and values of 0% were considered negative), model 2 (values ≥25% were considered positive and values <25% were considered negative), model 3 (values ≥50% were considered positive and values <50% were considered negative), and model 4 (values ≥75% were considered positive and values <75% were considered negative). The accuracy rate (A), sensitivity (S), specificity (E), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and areas under receiver operating characteristic curves (AUC) were calculated for the four models of agreement with the software. Models showed the following results respectively: A = 70.8%, 82%, 85.6%, 86.1%; S = 87%, 69.8%, 57%, 41.6%; E = 66.3%, 85.4%, 93.7%, 98.5%; PPV = 42%, 57.2%, 71.6%, 88.6%; NPV = 94.8%, 91%, 88.6%, 85.8%; PLR = 2.58, 4.78, 9.05, 27.73; NLR = 0.2, 0.35, 0.46, 0.59; AUC = 0.767, 0.777, 0.753, 0.701. Findings in the present study suggest that the artificial intelligence web-based software provides a good diagnostic reliability on the detection of dental caries. Our study highlighted model 2 for showing the best results to differentiate between healthy teeth and decayed teeth.
Tracking Daily Concentrations of PM2.5 Chemical Composition in China since 2000

PM2.5 chemical components play significant roles in the climate, air quality, and public health, and the roles vary due to their different physicochemical properties. Obtaining accurate and timely updated information on China’s PM2.5 chemical composition is the basis for research and environmental management. Here, we developed a full-coverage near-real-time PM2.5 chemical composition data set at 10 km spatial resolution since 2000, combining the Weather Research and Forecasting–Community Multiscale Air Quality modeling system, ground observations, a machine learning algorithm, and multisource-fusion PM2.5 data. PM2.5 chemical components in our data set are in good agreement with the available observations (correlation coefficients range from 0.64 to 0.75 at a monthly scale from 2000 to 2020 and from 0.67 to 0.80 at a daily scale from 2013 to 2020; most normalized mean biases within ±20%). Our data set reveals the long-term trends in PM2.5 chemical composition in China, especially the rapid decreases after 2013 for sulfate, nitrate, ammonium, organic matter, and black carbon, at the rate of −9.0, −7.2, −8.1, −8.4, and −9.2% per year, respectively. The day-to-day variability is also well captured, including evolutions in spatial distribution and shares of PM2.5 components. As part of Tracking Air Pollution in China (http://tapdata.org.cn), this daily-updated data set provides large opportunities for health and climate research as well as policy-making in China.
R-spondin 3 deletion induces Erk phosphorylation to enhance Wnt signaling and promote bone formation in the appendicular skeleton

Activation of Wnt signaling leads to high bone density. The R-spondin family of four secreted glycoproteins (Rspo1-4) amplifies Wnt signaling. In humans, RSPO3 variants are strongly associated with bone density. Here, we investigated the role of Rspo3 in skeletal homeostasis in mice. Using a comprehensive set of mouse genetic and mechanistic studies, we show that in the appendicular skeleton, Rspo3 haplo-insufficiency and Rspo3 targeted deletion in Runx2+ osteoprogenitors lead to an increase in trabecular bone mass, with increased number of osteoblasts and bone formation. In contrast and highlighting the complexity of Wnt signaling in the regulation of skeletal homeostasis, we show that Rspo3 deletion in osteoprogenitors results in the opposite phenotype in the axial skeleton, i.e., low vertebral trabecular bone mass. Mechanistically, Rspo3 deficiency impairs the inhibitory effect of Dkk1 on Wnt signaling activation and bone mass. We demonstrate that Rspo3 deficiency leads to activation of Erk signaling which in turn, stabilizes β-catenin and Wnt signaling activation. Our data demonstrate that Rspo3 haplo-insufficiency/deficiency boosts canonical Wnt signaling by activating Erk signaling, to favor osteoblastogenesis, bone formation, and bone mass.
Cor triatriatum sinister: Long‐term surgical outcomes in children and a proposal for a new classification

Cor Triatriatum Sinister (CTS) is a rare congenital anomaly with an estimated incidence of 0.4%, resulting from abnormal left atrial septation. It may present in isolation or in association with other heart defects. High percentage of patients require surgery with low mortality and recurrence rates. CTS has been classified in the past however we aim to describe a case series with more comprehensive and inclusive classification.
The effect of the severity of neurocognitive disorders on emotional and motor responses to music

The successful design of musical interventions for dementia patients requires knowledge of how rhythmic abilities change with disease severity. In this study, we tested the impact of the severity of the neurocognitive disorders (NCD) on the socioemotional and motor responses to music in three groups of patients with Major NCD, Mild NCD, or No NCD. Patients were asked to tap to a metronomic or musical rhythm while facing a live musician or through a video. We recorded their emotional facial reactions and their sensorimotor synchronization (SMS) abilities. Patients with No NCD or Mild NCD expressed positive socioemotional reactions to music, but patients with Major NCD did not, indicating a decrease in the positive emotional impact of music at this stage of the disease. SMS to a metronome was less regular and less precise in patients with a Major NCD than in patients with No NCD or Mild NCD, which was not the case when tapping with music, particularly in the presence of a live musician, suggesting the relevance of live performance for patients with Major NCD. These findings suggest that the socioemotional and motor reactions to music are negatively affected by the progression of the NCD.
Influence of magnetic field on plasma parameters and thin film deposition along axial and radial distances in DC magnetron

Magnetic field (B) distribution of the magnetron was measured and discussed its effect on plasma parameters and deposition rate. Plasma parameters such as electron temperature (Te), electron number density (ne) were estimated using electron flux (EF) and electron energy distribution function (EEDF) methods as function of axial, radial distances from the cathode. Te and ne decreased with increasing of axial, radial distances from the cathode. Dr was obtained for the same positions where the above plasma parameters were measured, and found that similar profile with Te and ne. Magnetron configuration was simulated using COMSOL Multiphysics software and compared with the experimentally measured profile. Further, density distribution was simulated using measured B through particle in cell - Monte Carlo collision and found simulation results are well supported to the experimental results.
Long‐term efficacy of complete trigonal electrofulguration for women with recurrent urinary tract infections

Recurrent urinary tract infections (R‐UTIs) have a negative impact on quality of life and contribute to antimicrobial resistance. Long‐term antibiotic therapy is the main treatment alternative but, in some cases, this approach may not be accepted by the patient, is ineffective or poorly tolerated. In selected women, electrofulguration (EF) of trigonal lesions has been shown to reduce urinary tract infection (UTI) episodes.
Psychiatric Disorder Incidence Among Adolescents and Young Adults Aged 15-39 With Cancer: Population-Based Cohort

Abstract Background Adolescent and young adult (AYA) cancer survivors face physical and psychological sequelae related to having cancer decades after treatment completion. It is unclear if AYA cancer survivors are at increased risk for late psychiatric disorders. Methods We used the Alberta AYA Cancer Survivor Study that includes 5-year survivors of cancer diagnosed at age 15-39 years during 1991 to 2013. The primary outcome was incidence of psychiatric disorder (composite outcome) including anxiety, depressive, trauma- and stressor-related, psychotic, and substance use disorders that were identified using coding algorithms for administrative health databases. A validated coding algorithm identified people who experienced a suicide attempt or event of self-harm. Secondary outcomes were incidences of diagnoses by type of psychiatric disorder. Results Among 12 116 AYA 5-year cancer survivors (n = 4634 [38%] males; n = 7482 [62%] females), 7426 (61%; n = 2406 [32%] males; n = 5020 [68%] females) were diagnosed with at least 1 of 5 psychiatric disorders occurring at least 3 years after cancer diagnosis. Survivors of all cancer types were most often diagnosed with anxiety (males: 39.0%, 95% confidence interval [CI] = 37.6% to 40.4%; females: 54.5%, 95% CI = 53.3% to 55.6%), depressive (males: 32.7%, 95% CI = 31.3% to 34.0%; females: 47.0%, 95% CI = 45.8% to 48.1%), and trauma- and stressor-related disorders (males: 13.5%, 95% CI =12.5% to 14.5%; females: 22.5%, 95% CI = 21.6% to 23.5%). Conclusions Anxiety, depressive, and trauma- and stressor-related disorders are common among 5-year survivors of AYA cancer. Primary, secondary, or tertiary preventive strategies for AYAs diagnosed with cancer, particularly at an early age, are needed to mitigate risk of potentially severe outcomes because of psychiatric disorders.
Impaired driving and other risky drug use and sex behaviors: a cross-sectional examination of high-risk rural women incarcerated in jail

Abstract Background: Despite women accounting for an increasing proportion of impaired drivers and higher rates of impaired driving and road fatalities in rural areas, little is known about rural women who drive impaired and their other risky behavior. Objective: The present study assessed the association between impaired driving history, risky substance use, and other drug- and sex-related risk behaviors in a sample of high-risk rural women incarcerated in jail. Methods: Four hundred women from three rural jails provided information about their impaired driving, drug use, injection drug use practices, and sex risk behaviors. Groups were stratified on whether they self-reported impaired driving in the year prior to incarceration. Impaired drivers (n = 260, M = 31.90 years old) were compared to women who did not drive impaired (n = 131, M = 34.42 years old) using MANCOVA and logistic regression analyses. Results: Impaired drivers had significantly (p < .05) higher substance use severity scores for cannabis, sedatives, and prescription opioids. Furthermore, impaired drivers were significantly (p < .05) more likely to have been the passenger of an impaired driver (78.08% vs. 53.44%), been an injection drug user (69.62% vs. 41.98%), had a casual sex partner (47.31% vs. 25.95%), and traded sex for drugs or money (31.15% vs. 15.27%) in the year prior to incarceration. Conclusions: This study found a consistent association between past year impaired driving and a range of drug- and sex-related risk behaviors in a sample of high-risk rural women incarcerated in jail. These findings highlight an opportunity to intervene in criminal justice settings to reduce multiple health risk behaviors.
Anatomy of Ursa Majoris

A nearby friable cloud in Ursa Majoris contains 270 galaxies with radial velocities 500 < VLG < 1500 km s^-1 inside the area of RA= [11h; 13h] and DEC= [+40deg; +60deg]. At present, 97 galaxies of them have individual distance estimates. We use these data to clarify the structure and kinematics of the UMa complex. According to Makarov & Karachentsev (2011), most of the UMa galaxies belong to seven bound groups, which have the following median parameters: velocity dispersion of 58 km s^-1, harmonic projected radius of 300 kpc, virial mass of 2.10^12 Msol, and virial- mass-to-K-band-luminosity of 27Msol/Lsol. Almost a half of the UMa cloud population are gas-rich dwarfs (Ir, Im, BCD) with active star formation seen in the GALEX UV-survey. The UMa groups reside within 15-19 Mpc from us, being just at the same distance as Virgo cluster. The total virial mass of the UMa groups is 4.10^13 Msol, yielding the average density of dark matter in the UMa cloud to be Omega_m = 0.08, i.e. a factor three lower than the cosmic average. This is despite the fact that the UMa cloud resides in a region of the Universe that is an apparent overdensity. A possible explanation for this is that most mass in the Universe lies in the empty space between clusters. Herewith, the mean distances and velocities of the UMa groups follow nearly undisturbed Hubble flow without a sign of the 'Z-wave" effect caused by infall toward a massive attractor. This constrains the total amount of dark matter between the UMa groups within the cloud volume.
ALMA Observations of the Archetypal “Hot Core” That Is Not: Orion-KL

We present sensitive high angular resolution (∼0.″1–0.″3) continuum Atacama Large Millimeter/Submillimeter Array (ALMA) observations of the archetypal hot core located in the Orion Kleinmann-Low (KL) region. The observations were made in five different spectral bands (bands 3, 6, 7, 8, and 9) covering a very broad range of frequencies (149–658 GHz). Apart from the well-known millimeter emitting objects located in this region (Orion Source I and BN), we report the first submillimeter detection of three compact continuum sources (ALMA1–3) in the vicinities of the Orion-KL hot molecular core. These three continuum objects have spectral indices between 1.47 and 1.56, and brightness temperatures between 100 and 200 K at 658 GHz, suggesting that we are seeing moderate, optically thick dust emission with possible grain growth. However, as these objects are not associated with warm molecular gas, and some of them are farther out from the molecular core, we thus conclude that they cannot heat the molecular core. This result favors the hypothesis that the hot molecular core in Orion-KL core is heated externally.
Understanding and Addressing Older Adults’ Loneliness: The Social Relationship Expectations Framework

Loneliness is an experience resulting from a perceived discrepancy between expected and actual social relationships. Although this discrepancy is widely considered the “core mechanism” of loneliness, previous research and interventions have not sufficiently addressed what older adults specifically expect from their social relationships. To address this gap and to help situate research on older adults’ loneliness within broader life span developmental theories, we propose a theoretical framework that outlines six key social relationship expectations of older adults based on research from psychology, gerontology, and anthropology: availability of social contacts, receiving care and support, intimacy and understanding, enjoyment and shared interests, generativity and contribution, and being respected and valued. We further argue that a complete understanding of loneliness across the life span requires attention to the powerful impacts of contextual factors (e.g., culture, functional limitations, social network changes) on the expression and fulfillment of older adults’ universal and age-specific relationship expectations. The proposed Social Relationship Expectations Framework may fruitfully inform future loneliness research and interventions for a heterogeneous aging population.
PREVALENCE AND PARASITE INTENSITY OF HAEMOGREGARINES IN AFRICAN BELL HINGE-BACK (KINIXYS BELLIANA) AND AFRICAN HOME'S HINGE-BACK (KINIXYS HOMEANA) TORTOISES IN IBADAN, NIGERIA

Abstract: Haemogregarines are a group of intracellular blood parasites reported in reptiles, other vertebrate taxa including mammals and fish, and haematophagous invertebrates. Information on prevalence, biodiversity, and host-specificity of haemogregarines of tortoises in Nigeria are scarce. A total of 120 African hinge-back tortoises (Kinixys belliana, n=70, and K. homeana, n=50) were bought from the Wildlife and Herbal Market in Ibadan, Nigeria. Blood was withdrawn via the subcarapacial sinuses of each tortoise. The prevalence and parasite intensity of haemogregarine infection was determined using a light microscope, and parasite species were determined by PCR using HepF300 and HepR900 primers. A sequence of 654 base pairs (bp; Hepatozoon cf. fitzsimonsi) from the study aligned with published 18SrRNA and closely related with a similarity of 97.38% to Hepatozoon fitzsimonsi sequenced from Kinixys zobensis in South Africa. Overall prevalence of haemogregarines was 53.33% from light microcopy and 75.83% from PCR, which is considered very high. Higher prevalence and mean±SD parasite intensity were recorded for K. belliana (82.89%, 0.29%) than for K. homeana (66.00%, 0.26%). Prevalence rates and parasite intensities of haemogregarines were significantly higher in wet than in dry seasons. The differences in prevalence and intensity between and within species may be due to habitat characteristics, feeding habits of vectors and hosts, seasons, and vector abundance.
Chronic pain: Evidence from the national child development study

Using data from all those born in a single week in 1958 in Britain we track associations between short pain and chronic pain in mid-life (age 44) and subsequent health, wellbeing and labor market outcomes in later life. We focus on data taken at age 50 in 2008, when the Great Recession hit and then five years later at age 55 in 2013 and again at age 62 in 2021 during the Covid pandemic. We find those suffering both short-term and chronic pain at age 44 continue to report pain and poor general health in their 50s and 60s. However, the associations are much stronger for those with chronic pain. Furthermore, chronic pain at age 44 is associated with a range of poor mental health outcomes, pessimism about the future and joblessness at age 55 whereas short-duration pain at age 44 is not. Pain has strong predictive power for pain later in life: pain in childhood predicts pain in mid-life, even when one controls for pain in early adulthood. Pain appears to reflect other vulnerabilities as we find that chronic pain at age 44 predicts whether or not a respondent has Covid nearly twenty years later.