Miracle-dz/UniFAR-FTUs huggingface dataset:
Fluorescence in‐situ hybridisation for TP63 rearrangements in T cell lymphomas: single‐site experience of 470 patients and implications for clinical testing

The aims of this study were to review our 5‐year experience with clinical FISH testing for TP63 rearrangements using both TP63 break‐apart (BAP) and TBL1XR1/TP63 dual‐fusion (D‐FISH) probes to evaluate the frequency of TP63 rearrangements and the distribution of TBL1XR1 vs. alternate partner loci, and to assess whether both probe sets are necessary in all cases undergoing FISH testing.
Mesoporous Silica Nanoparticles Trigger Liver and Kidney Injury and Fibrosis Via Altering TLR4/NF-κB, JAK2/STAT3 and Nrf2/HO-1 Signaling in Rats

Mesoporous silica nanoparticles (MSNs) represent a promising inorganic platform for multiple biomedical applications. Previous studies have reported MSNs-induced hepatic and renal toxicity; however, the toxic mechanism remains unclear. This study aimed to investigate MSNs-induced hepatic and nephrotoxicity and test the hypothesis that altered TLR4/MyD88/NF-κB, JAK2/STAT3, and Nrf2/ARE/HO-1 signaling pathways mediate oxidative stress, inflammation, and fibrosis induced by MSNs. Rats were administered 25, 50, 100, and 200 mg/kg MSNs for 30 days, and samples were collected for analyses. MSNs induced functional and histologic alterations, increased the levels of reactive oxygen species (ROS), lipid peroxidation and nitric oxide, suppressed antioxidants, and Nrf2/HO-1 signaling in the liver and kidney of rats. MSNs up-regulated the expression of liver and kidney TLR4, MyD88, NF-κB p65, and caspase-3 and increased serum pro-inflammatory cytokines. In addition, MSNs activated the JAK2/STAT3 signaling pathway, down-regulated peroxisome proliferator activated receptor gamma (PPARγ), and promoted fibrosis evidenced by the increased collagen expression and deposition. In conclusion, this study conferred novel information on the role of ROS and deregulated TLR4/MyD88/NF-κB, JAK2/STAT3, PPARγ, and Nrf2/ARE/HO-1 signaling pathways in MSNs hepatic and nephrotoxicity. These findings provide experimental evidence for further studies employing genetic and pharmacological strategies to evaluate the safety of MSNs for their use in nanomedicine.
Agreement between the Danish Cancer Registry and the Danish Colorectal Cancer Group Database

Abstract Background: The Danish Cancer Registry (DCR) and the Danish Colorectal Cancer Group (DCCG) database are population-based registries collecting information on Danish patients with colorectal cancer (CRC). DCR registers all patients with incident CRC whereas DCCG records patients with first time CRC. The registries use different inclusion criteria. The consequencenses of this are unknown and not previously evaluated. The aim of this study was to examine the agreement between patients registered in DCR and DCCG and to evaluate its influence on estimated survival and mortality. Material and methods: Patients registered in DCR and DCCG with CRC in 2014–2015 were included. Because of different inclusion criteria, DCCG’s inclusion criteria were applied to DCR. Descriptive statistics were used for comparisons. One-year relative survival (1-year RS) was calculated, and the Cox proportional hazard model used for calculating 1-year mortality rate ratios (1-year MRR). Results: In 2014–2015, DCR registered 9678 Danish residents with CRC that fulfilled DCCG’s inclusion criteria, while DCCG registered 10,312 Danish residents with CRC. Allowing ±180 days between dates of diagnosis, 10,688 patients were registered with CRC in the merger of the two registries. Of these, 86% were included in both registers, 4% only in DCR, and 10% only in DCCG. No difference was found in 1-year RS between patients in DCR 86% (95% CI: 85–87) and DCCG 85% (95% CI: 84–86). However, patients registered in DCCG had a 1-year MRR of 1.09 (95% CI: 1.01–1.17) compared to DCR. Conclusion: An agreement of 86% of patients was found between the two registries. The discrepancy did not influence 1-year RS. DCCG registered more patients than DCR, and 1-year MRR of patients in DCCG was increased compared to patients in DCR. Regular linkage of the registries is recommended to improve data quality of both registries.
Time series analysis of delta neutrophil index as the predictor of sepsis in patients with acute poisoning

Delta neutrophil index (DNI), which reflects the fraction of immature granulocytes, is used to detect infection and sepsis from noninfectious conditions, but few studies have evaluated in the early stage of acute poisoning. This retrospective observational study was performed on acute poisoning patients who visited to the emergency department (ED) and were consecutively admitted in intensive care units over 18-month period. The serial DNI, conventional inflammatory biomarkers, and culture results were obtained in the ED and after admission. The outcomes were the identification of sepsis, bacteremia, and 30-day mortality. Of 166 patients (mean age, 56.0 years) in this cohort, 59 (35.5%) had sepsis and 29 (17.5%) had bacteremia. Initial and peak DNI fractions 24 h after ED admission were strong independent predictors of sepsis development. Analysis of the area under the curve according to multiple receiver operating characteristics showed that DNI had a higher capability to predict sepsis than other parameters (0.815 for DNI, 0.700 for procalcitonin, 0.681 for C-reactive protein, and 0.741 for white blood cell). Using multivariable logistic regression analysis, it was found that DNI was an independent predictor of sepsis (95% confidence interval (CI) of odds: 1.03–1.18) and bacteremia (95% CI: 1.01–1.14). Therefore, initial and serial measurement of DNI may serve as useful risk predictor for development of sepsis or bacteremia in acute poisoning.
Carotid Artery Tortuosity Is Associated with Connective Tissue Diseases

BACKGROUND AND PURPOSE: There is a general assumption in the cerebrovascular literature that there is an association between carotid artery tortuosity and connective tissues disease; however, this has not been firmly established. The purpose of this study was to determine the prevalence of carotid artery tortuosity in patients with connective tissue diseases relative to matched controls. MATERIALS AND METHODS: Patients with previous CTA or MRA and a diagnosis of connective tissue diseases were identified and compared with a cohort of age-matched controls. Radiologists blinded to the diagnosis reviewed the images and evaluated the presence of carotid artery tortuosity (including loops, kinks, or coils). Continuous variables were compared using the Student t test, and categoric variables with χ2 tests. RESULTS: One hundred forty-three patients with connective tissue disease and 143 controls were included in this study. Specific diagnoses included Marfan (n = 33), nonvascular Ehlers-Danlos (n = 36), Ehlers-Danlos vascular-type (n = 32), neurofibromatosis type 1 (n = 26), and Loeys-Dietz (n = 16) syndromes. The presence of carotid tortuosity was 44% in connective tissue disease and 16% in controls (P < .001). Of tortuosity manifestations, coils were most prevalent (23% versus 3%; P < .001). Among the various connective tissue diseases, the rates of any carotid tortuosity were 88% for Marfan syndrome, 63% for Loeys-Dietz syndrome, 42% for neurofibromatosis type 1, and 19% for both vascular- and nonvascular-type Ehlers-Danlos syndrome. The positive predictive value of the combination of aortic aneurysm and carotid tortuosity being associated with connective tissue disease was 95.4%. The specificity was 98.6%. CONCLUSIONS: Carotid artery tortuosity is highly associated with connective tissue diseases, particularly Marfan syndrome, Loeys-Dietz syndrome, and neurofibromatosis type 1. Such findings are relevant in risk assessment for vascular complications in connective tissue disease, endovascular treatment planning, and in understanding the pathomechanisms of vascular tortuosity in general.
Automatic detection of microsleep episodes with feature-based machine learning.

STUDY OBJECTIVES Microsleep episodes (MSEs) are brief episodes of sleep, mostly defined to be shorter than 15 s. In the electroencephalogram (EEG), MSEs are mainly characterized by a slowing in frequency. The identification of early signs of sleepiness and sleep (e.g. MSEs) is of considerable clinical and practical relevance. Under laboratory conditions, the maintenance of wakefulness test (MWT) is often used for assessing vigilance. METHODS We analyzed MWT recordings of 76 patients referred to the Sleep-Wake-Epilepsy-Center. MSEs were scored by experts defined by the occurrence of theta dominance on ≥1 occipital derivation lasting 1-15 s, while the eyes were at least 80% closed. We calculated spectrograms using an autoregressive model of order 16 of 1-s epochs moved in 200-ms steps in order to visualize oscillatory activity and derived seven features per derivation: power in delta, theta, alpha and beta bands, ratio theta/(alpha+beta), quantified eye movements, and median frequency. Three algorithms were used for MSE classification: support vector machine (SVM), random forest (RF), and an artificial neural network (long short-term memory [LSTM] network). Data of 53 patients were used for the training of the classifiers, and 23 for testing. RESULTS MSEs were identified with a high performance (sensitivity, specificity, precision, accuracy, and Cohen's kappa coefficient). Training revealed that delta power and the ratio theta/(alpha+beta) were most relevant features for the RF classifier and eye movements for the LSTM network. CONCLUSIONS The automatic detection of MSEs was successful for our EEG-based definition of MSEs, with good performance of all algorithms applied.
Recent developments and highlights in drug hypersensitivity

Drug hypersensitivity reactions (DHRs) are nowadays the third cause of allergy after rhinitis and asthma with a significant increase in prevalence in both adults and paediatric population with new drugs included as culprit. For this, DHRs represent not only a health problem but also a significant financial burden for affected individuals and health systems. Mislabelling DHRs is showing to be a relevant problem for both, false label of drug allergic and false label of nonallergic. All this reinforces the need to improve accurate diagnostic approaches that allow an appropriate management. Moreover, there is a need for training both, nonallergist stakeholders and patients to improve the reaction identification and therefore decrease the mislabelling. The use of allergy cards has shown to be relevant to avoid the induction of DHRs due to the prescription of wrong medication.
Compilation, Revision and Updating of the Global VAR (GVAR) Database, 1979Q2-2019Q4

This is the latest version of the Global VAR (GVAR) dataset. The GVAR is a global modelling framework for analyzing the international macroeconomic transmission of shocks, taking into account drivers of economic activity, interlinkages and spillovers between different countries, and the effects of unobserved or observed common factors. This dataset includes quarterly macroeconomic variables for 33 economies (log real GDP, yit, the rate of inflation, dpit, short-term interest rate, rit, long-term interest rate, lrit, the log deflated exchange rate, epit, and log real equity prices, eqit), as well as quarterly data on commodity prices (oil prices, poilt, agricultural raw material, pmatt, and metals prices, pmetalt), over the 1979Q2 to 2019Q4 period. These 33 countries cover more than 90% of world GDP. You can download the data, as well as a description of the compilation, revision and updating of the GVAR Database, from the GVAR database website. It would be appreciated if use of the updated dataset could be acknowledged as: “Mohaddes and Raissi (2020). Compilation, Revision and Updating of the Global VAR (GVAR) Database, 1979Q2-2019Q4. University of Cambridge: Judge Business School (mimeo)”. ∗We are grateful to Paul Cashin, Alexander Chudik, M. Hashem Pesaran, and Vanessa Smith for their helpful comments and suggestions. The views expressed in this document are those of the authors and do not necessarily represent those of the International Monetary Fund or IMF policy. †Corresponding author. Email address: km418@cam.ac. uk.
Using Statistical Phylogenetics for Investigation of Enterovirus 71 Genotype A Reintroduction into Circulation

Neurovirulent enterovirus 71 (EV-A71) caused a massive epidemic in China in 2008–2011. While subgenotype C4 was the major causative agent, a few isolates were almost identical to the prototype EV-A71 strain and belonged to genotype A. This variant was allegedly extinct since 1970, and its identification in this epidemic suggests reintroduction of the archive virus. Regression analysis of genetic distances (TempEst software) was of moderate utility due to the low resolution of classical phylogenetic methods. Bayesian phylogenetic analysis (BEAST software) suggested artificial introduction event based on highly aberrant phylogenetic tree branch rates that differed by over three standard deviations from the mean substitution rate for EV71. Manual nucleotide-level analysis was used to further explore the virus spread pattern after introduction into circulation. Upon reintroduction, the virus accumulated up to seven substitutions in VP1, most of them non-synonymous and located within the capsid’s canyon or at its rims, compatible with readaptation of a lab strain to natural circulation.
Physicochemical Characterization and Antioxidant Activity Evaluation of Idebenone/Hydroxypropyl-β-Cyclodextrin Inclusion Complex †

Idebenone (IDE) is an antioxidant drug active at the level of the central nervous system (CNS), whose poor water solubility limits its clinical application. An IDE/2-hydroxypropyl-β-cyclodextrin (IDE/HP-β-CD) inclusion complex was investigated by combining experimental methods and theoretical approaches. Furthermore, biological in vitro/ex vivo assays were performed. Phase solubility studies showed an AL type diagram, suggesting the presence of a 1:1 complex with high solubility. Scanning electron microscopy (SEM) allowed us to detect the morphological changes upon complexation. The intermolecular interactions stabilizing the inclusion complex were experimentally characterized by exploring the complementarity of Fourier-transform infrared spectroscopy in attenuated total reflectance geometry (FTIR-ATR) with mid-infrared light, Fourier-transform near-infrared (FT-NIR) spectroscopy, and Raman spectroscopy. From the temperature evolution of the O–H stretching band of the complex, the average enthalpy ΔHHB of the hydrogen bond scheme upon inclusion was obtained. Two-dimensional (2D) rotating frame Overhauser effect spectroscopy (ROESY) analysis and computational studies involving molecular modeling and molecular dynamics (MD) simulation demonstrated the inclusion of the quinone ring of IDE inside the CD ring. In vitro/ex vivo studies evidenced that complexation produces a protective effect of IDE against the H2O2-induced damage on human glioblastoma astrocytoma (U373) cells and increases IDE permeation through the excised bovine nasal mucosa.
Does the New Rural Pension System Promote Farmland Transfer in the Context of Aging in Rural China: Evidence from the CHARLS

The lack or instability of the pension system for the elderly in rural China has become a paramount obstacle for sustainable land transfer, namely land use right transfer among farmers, in the context of aging. The New Rural Pension System (NRPS), a pilot project that provided basic security for the elderly, was implemented in 10% of counties in 2009 and rapidly promoted nationwide in China. This study evaluates the impact of NRPS on farmland transfer by developing econometric models by employing the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2015. The participation rate in NRPS increased from 25.87% in 2011 to 80.85% in 2015, and the participation rate in farmland transfer rose from 11.56% to 24.04%. Everything else being held equal, the probability of farmers who transferred out their land increased by approximately 13% and the land area has been transferred increased by 11.2% due to participation in NRPS, indicating that the NRPS improved the operation efficiency of land rental market. Furthermore, the heterogeneity analysis showed that the probability and area mentioned above had a significant upward trend with the increase of the time and insured amount of participation in NRPS, which reduced dependence on farmland for the elderly and promoted the sustainability of land transfer. The government should further encourage farmers to increase the coverage and insured amount of pension system in the context of aging. Meanwhile, a platform to promote land transfer should be established to provide information about land supply and demand and reduce the transaction cost of land rental market.
High dose intravenous methylprednisolone pulse therapy causes transient increase of serum calcium and phosphate levels.

High and very high doses of intravenous methylprednisolone (IVMP) administered in pulses are the first-line treatment for active, moderateto- severe, as well as sight-threatening Graves' orbitopathy (GO). However, glucocorticoid therapy is associated with side effects, among others, it affects bone metabolism. AIM The aim of study was to assess the acute effects of high and very high doses of IVMP on calcium (Ca) and phosphate (P) balance in euthyroid patients with moderate-to-severe GO and sight-threatening GO due to dysthyroid optic neuropathy (DON). MATERIALS AND METHODS Thirty-six patients with active, moderate-tosevere GO were treated with twelve once-weekly pulses (with cumulative dose of 4.5 g IVMP) and 11 patients with DON received 3 intravenous pulses of 1.0 g IVMP on three consecutive days. We measured serum levels of Ca and P at baseline and on the following days after the beginning of the IVMP therapy. RESULTS We observed a significant increase in serum Ca level on the next day after the 1st IVMP pulse both in patients with moderate-tosevere GO and with DON. Then, on the day 3, the decrease of serum Ca was noticed. In patients with moderate-to-severe GO, on the day 2 serum P showed a significant increase and then, it returned to basal level on the day 3. CONCLUSIONS We observed a significant increase in serum Ca level on the next day after the 1st IVMP pulse both in patients with moderate-tosevere GO and with DON. Then, on the day 3, the decrease of serum Ca was noticed. In patients with moderate-to-severe GO, on the day 2 serum P showed a significant increase and then, it returned to basal level on the day 3.
Rebuilding the Retina: Prospects for Müller Glial-mediated Self-repair

ABSTRACT Retinal degeneration is a leading cause of untreatable blindness in the industrialised world. It is typically irreversible and there are few curative treatments available. The use of stem cells to generate new retinal neurons for transplantation purposes has received significant interest in recent years and is beginning to move towards clinical trials. However, such approaches are likely to be most effective for relatively focal areas of repair. An intriguing complementary approach is endogenous self-repair. Retinal cells from the ciliary marginal zone (CMZ), retinal pigment epithelium (RPE) and Müller glial cells (MG) have all been shown to play a role in retinal repair, typically in lower vertebrates. Among them, MG have received renewed interest, due to their distribution throughout (centre to periphery) the neural retina and their potential to re-acquire a progenitor-like state following retinal injury with the ability to proliferate and generate new neurons. Triggering these innate self-repair mechanisms represents an exciting therapeutic option in treating retinal degeneration. However, these cells behave differently in mammalian and non-mammalian species, with a considerably restricted potential in mammals. In this short review, we look at some of the recent progress made in our understanding of the signalling pathways that underlie MG-mediated regeneration in lower vertebrates, and some of the challenges that have been revealed in our attempts to reactivate this process in the mammalian retina.
How do women and health care professionals view hormonal long-acting reversible contraception? Results from an international survey

Abstract Purpose: Evidence from real-world settings is important to provide an accurate picture of health care delivery. We investigated use of long-acting reversible contraception (LARC) in women aged 15–49 years. Materials and methods: Two surveys, one of women and one of health care professionals (HCPs), were conducted in parallel across seven countries. Participating women completed an online survey to assess contraceptive awareness, current method of contraception, age, and experience with current contraceptive method. HCPs participated in an online survey to provide practice-level information and three anonymous charts of hormonal LARC users. Results: Of 6903 women who completed the survey, 3225 provided information about their current primary contraception method. Overall, 16% used LARC methods, while 52% used oral contraceptives (OCs). Of hormonal intrauterine system users, 72% described their experience as ‘very favourable’, compared with only 53% of women using OCs. Anonymous patient records (n = 1605) were provided by 550 HCPs who completed the online survey. Most women (64%) had used short-acting reversible contraception before switching to LARC. Physicians perceived 56–84% of LARC users to be highly satisfied with their current form of contraception. Conclusions: Although usage of LARC was low, most women using LARC were highly satisfied with their method of contraception.
Type 1 Diabetes Accelerates Progression of Coronary Artery Calcium Over the Menopausal Transition: The CACTI Study

OBJECTIVE Type 1 diabetes is associated with a higher risk of cardiovascular disease (CVD) in women. Although menopause increases risk of CVD, it is uncertain how menopause affects risk of CVD in women with type 1 diabetes. We examined whether risk of CVD changes differentially in women with and those without type 1 diabetes over the transition through menopause. RESEARCH DESIGN AND METHODS Premenopausal women with type 1 diabetes (n = 311) and premenopausal women without diabetes (n = 325) enrolled in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study and attended up to four study visits over 18 years. Coronary artery calcium (CAC) volume was measured from computed tomography scans obtained at each visit. Longitudinal repeated-measures modeling estimated the effect of diabetes on CAC volume over time and the effect of menopause on the diabetes-CAC relationship. RESULTS CAC volume was higher at baseline and increased more over time in women with type 1 diabetes than in women without diabetes. A significant diabetes-by-menopause interaction was found (P < 0.0001): postmenopausal women with type 1 diabetes had significantly higher CAC volumes than premenopausal women (5.14 ± 0.30 vs. 2.91 ± 0.18 mm3), while there was no difference in women without diabetes (1.78 ± 0.26 vs. 1.78 ± 0.17 mm3). This interaction remained significant after adjusting for CVD risk factors. CONCLUSIONS Type 1 diabetes was associated with higher CAC volume and accelerated progression of CAC over time. Menopause increased CAC progression more in women with diabetes than in women without diabetes independent of age and other CVD risk factors known to worsen with menopause.