Miracle-dz/UniFAR-FTUs huggingface dataset:
Adding marrow R2∗ to proton density fat fraction improves the discrimination of osteopenia and osteoporosis in postmenopausal women assessed with 3D FACT sequence

Abstract Objective: To evaluate the role of three-dimensional Fat Analysis & Calculation Technique sequence in improving the diagnostic accuracy for the detection of osteopenia and osteoporosis by simultaneous quantification of proton density fat fraction (PDFF) and fat-corrected R2∗. Methods: Fat Analysis & Calculation Technique imaging of lumbar spine was obtained in 99 postmenopausal women including 52 normal bone mass, 29 osteopenia, and 18 osteoporosis. The diagnostic performance of PDFF and R2∗ in the differentiation of different bone-density groups was evaluated with the receiver operating characteristic curve. Results: The reproducibility of PDFF and R2∗ measures was satisfactory with the root mean square coefficient of variation, 2.16% and 2.70%, respectively. The intra- and interobserver agreements for the PDFF and R2∗ were excellent with the intraclass correlation coefficient > 0.9 for all. There were significant differences in PDFF and R2∗ among the three groups (P < 0.05). Bone density had a moderate inverse correlation with PDFF (r = −0.659) but a positive association with R2∗ (r = 0.508, P < 0.001). Adjusted for age, years since menopause and body mass index, odds ratios (95% confidence interval) for osteopenia and osteoporosis per standard deviation higher marrow PDFF and R2∗ were 2.9 (1.4-5.8) and 0.4 (0.2-0.8), respectively. The areas under the curve were 0.821 for PDFF, 0.784 for R2∗, and 0.922 for both combined for the detection of osteoporosis (P < 0.05). Similar results were obtained in distinguishing osteopenia from healthy controls. Conclusions: Simultaneous estimation of marrow R2∗ and PDFF improves the discrimination of osteopenia and osteoporosis in comparison with the PDFF or R2∗ alone.
Ocular toxicity assessment of nanoemulsion in-situ gel formulation of fluconazole

Purpose: Fluconazole is an effective anti-fungal drug. Due to the limitations of fluconazole, such as poor water solubility and consequently low ocular bioavailability, an optimized fluconazole nanoemulsion in-situ gel formulation (temperature-sensitive) was developed. Methods and Materials: To verify formulation’s safety for ophthalmic use, preparation was tested for potential ocular toxicity using a cell viability assay on retinal cells. The hen’s egg test-chorioallantoic membrane (HET-CAM), as a borderline test between in vivo and in vitro techniques, was chosen for investigating the irritation potential of the formulation. HET-CAM test was done by adding the formulation directly to the CAM surface and monitoring the vessels visually in terms of irritation reactions. Eye tolerance was determined using the modified Draize test. Results: Viability assay on retinal cells displayed that fluconazole nanoemulsion in-situ gel formulation was non-toxic and can be safely used in the eye at concentrations of 0.1% and 0.5%. HET-CAM and Draize tests revealed that optimized formulation of fluconazole did not result in any irritation and was considered non-irritant and well-tolerated for ocular use. Conclusion: Regarding to the findings of the three mentioned methods, fluconazole nanoemulsion in-situ gel formulation is harmless and as a proper and safe alternative, can be considered for ocular delivery of fluconazole in the future.
Effect of Impairment on the Prevalence and Comorbidities of Attention Deficit Hyperactivity Disorder in a National Survey: Nation-Wide Prevalence and Comorbidities of ADHD

Objective: This study aimed to determine the prevalence and comorbidities of attention-deficit hyperactivity disorder (ADHD) by evaluating a large-scale nation-wide sample of children. Method: The inclusion criterion was being enrolled as a 2nd, 3rd, or 4th-grade student. A semi-structured diagnostic interview (K-SADS-PL), DSM-IV-Based Screening Scale for Disruptive Behavior Disorders, and assessment of impairment (by both parents and teachers) were applied to 5,842 participants. Results: The prevalence of ADHD was 19.5% without impairment and 12.4% with impairment. Both ADHD with and without impairment groups had similar psychiatric comorbidity rates except for oppositional defiant disorder (ODD) and conduct disorder (CD) diagnoses. Impairment in the ADHD group resulted in significantly higher ODD and CD diagnoses. Conclusion: Even when impairment is not described, other psychiatric disorders accompany the diagnosis of ADHD and may cause impairment in the future. Impairment in the diagnosis of ADHD significantly increases the likelihood of ODD and CD.
Efficacy and tolerability of very low-volume bowel preparation in patients with inflammatory bowel diseases

Objectives An adequate bowel preparation is essential for a quality colonoscopy. Patients with inflammatory bowel disease (IBD) show low compliance with bowel preparation due to the large volume of lavage solution to be ingested, especially if active symptoms are present, and the frequency of having a colonoscopy. We evaluated the efficacy and tolerability of a very low-volume (VLV) polyethylene glycol (PEG)-based solution in patients with IBD. Methods A cohort of 103 consecutive patients, 56 with Crohn’s disease and 47 with ulcerative colitis, received a 1-L PEG-based bowel preparation divided into two 500-mL doses taken the evening before and the morning of the colonoscopy, each dose followed by at least another 500-mL of clear fluids. Colon cleansing was scored according to the Boston Bowel Preparation Scale (BBPS) and evaluated in relation to influencing variables. Results Bowel cleansing was adequate (BBPS ≥ 6) in 88 patients (85.4%). The time interval between the end of bowel preparation and the beginning of colonoscopy and the disease activity significantly affected colon cleansing. Most patients declared a complete intake of lavage solution (99%), the willingness to repeat the same bowel preparation in a future colonoscopy (86.4%), and a good taste assessment. Conclusion The VLV PEG-based bowel preparation is effective and well accepted by IBD patients. As minimizing the volume of lavage solution required, the VLV-bowel preparation here tested could be of choice in subjects who perform periodically colonoscopy or in those who do not tolerate a larger amount of liquids.
Potentiation of glutamatergic synaptic transmission onto lateral habenula neurons following early life stress and intravenous morphine self-administration in rats

Early life stress (ELS) presents an important risk factor for drug addiction and comorbid depression and anxiety through persistent effects on the mesolimbic dopamine (DA) pathways1. Using an ELS model for child neglect (a single 24 h episode of maternal deprivation, MD) in rats, recent published works from our lab show that MD induces dysfunction in ventral tegmental area (VTA) DA neurons 2–4 and its negative controller, the lateral habenula (LHb) 5–7. In regard to LHb, MD-induced potentiation of glutamatergic synaptic transmission onto LHb neurons shifts the coordination of excitation/inhibition (E/I) balance towards excitation, resulting in an increase in the overall spontaneous neuronal activity with elevation in bursting and tonic firing, and intrinsic excitability of LHb neurons in early adolescent male rats 5–7. Here, we explored how MD affects intravenous morphine self-administration (MSA) acquisition and sucrose preference as well as glutamatergic synaptic function in LHb neurons of adult male rats self-administering morphine. We found that MD-induced increases in LHb neuronal and glutamatergic synaptic activity and E/I ratio persisted into adulthood. Moreover, MD significantly reduced morphine intake, triggered anhedonia-like behavior in the sucrose preference test (SPT), and was associated with persistent glutamatergic potentiation 24h after the last MSA session. MSA also triggered postsynaptic glutamatergic potentiation in LHb neurons of control rats during this time period. Our data highlights that ELS-induced glutamatergic plasticity in LHb may dampen the positive reinforcing properties of natural rewards and opioids, and contribute to the development of anhedonic and dysphoric states associated with opioids.
Anti-interferon-gamma autoantibody related disseminated nontuberculous mycobacteriosis with pathological features of immunoglobulin G4-related disease

Abstract A 72-year-old man who was diagnosed as pulmonary mycobacterium avium complex (MAC) disease had suffered from antibiotics resistant fever with left renal enlargement surrounded by inflammatory change and multiple osteolytic lesions on computed tomography (CT). The renal biopsied samples pathologically showed immunoglobulin G4 (IgG4) positive plasma cell infiltration and many acid-fast bacilli without granuloma formation. Nucleic acid identification test for MAC from the samples of vertebral osteolytic lesion was positive. In the autopsy samples from left kidney, epithelioid cell granuloma and Langhans giant cell with many acid-fast bacilli were shown pathologically. In addition to osteolytic lesions on CT study, these pathological findings were not consistent with IgG4-related disease (IgG4-RD). The diagnosis of disseminated nontuberculous mycobacteriosis was made, and plasma anti-interferon-gamma (IFN-γ) autoantibody was found as the cause of underlying immunodeficiency. Disturbed function of IFN-γ resulted in impaired ability of phagocytic cells against pathogens and leading to spread of infection. T-helper type 2 dominant immune response was induced by prolonged antigenic stimulation of mycobacteria, which might have contributed to form the pathological features of IgG4-RD.
CD40L/CD40 Regulates Adipokines and Cytokines by H3K4me3 Modification in Epicardial Adipocytes

Abstract: Epicardial adipose tissue (EAT) dysfunction mediates chronic inflammation by regulating inflammation-related adipokines and cytokines, and it further promotes coronary artery disease (CAD) development. CD40L/CD40 is involved in multiple inflammatory pathways that contribute to various pathophysiological processes. However, the function of CD40L/CD40 in the expression and production of adipokines and cytokines in epicardial adipocytes remains unclear. The purpose of the present study was to explore the role and underlying mechanisms of CD40L/CD40 in adipokine and cytokine expression and production. We isolated adipocytes from EAT tissues of CAD and non-CAD patients. We noticed that CD40 was dramatically increased in EAT tissues of CAD patients. Loss-of-function and gain-of-function studies were performed. The results showed that CD40 silencing reduced recombinant CD40 ligand (rCD40L)–induced upregulation of plasminogen activator inhibitor-1, leptin, interleukin-6, and monocyte chemotactic protein-1 messenger RNA levels and secretion. Overexpression of CD40 displayed the opposite results. In addition, rCD40L triggered mixed lineage leukemia protein-1 (MLL1) expression both in messenger RNA and protein levels. CD40 depletion apparently blocked MLL1 expression, whereas gain of function of CD40 resulted in augmentation of MLL1 levels. Interestingly, chromatin immunoprecipitation-quantitative real-time polymerase chain reaction analysis revealed that CD40 elimination dampened histone H3 lysine 4 trimethylation enrichment at plasminogen activator inhibitor-1, leptin, interleukin-6, and monocyte chemotactic protein-1 promoter regions in the presence of rCD40L. The reverse pattern was observed upon ectopic expression of CD40. Most important, MLL1 silencing effectively reversed the promotive effects of CD40 on adipokine and cytokine secretion. Taken together, our findings suggest that CD40L/CD40 regulates adipokine and cytokine expression by H3 lysine 4 trimethylation modification in adipocytes.
Enhancement of Near-Infrared-to-Visible Upconversion Luminescence Using Engineered Plasmonic Gold Surfaces

An engineered plasmonic gold surface, specifically designed to couple with 980 nm radiation, is shown to enhance near-infrared-to-visible upconversion luminescence from a monolayer of β-NaYF4: 17%Yb, 3%Er nanocrystals in poly(methyl methacrylate) on that gold surface. Confocal imaging of upconversion luminescence from the surface is used to characterize the nature of the enhancement. It is shown that the luminescence data were acquired below the so-called “high power limit” for excitation, but some saturation was evident, as the observed power dependence was less than quadratic. Over the range of excitation power densities used, the intrinsic enhancement factor for upconversion from the patterned surface was greater than a factor of 3 but decreased slowly with increasing excitation power. The red and green upconversion were enhanced by similar factors, which would support the intensification of the excitation field by the plasmonic surface as being the mechanism of enhancement. In the absence of other enh.
Socio-economic functioning in patients with bipolar disorder and their unaffected siblings – results from a nation-wide population-based longitudinal study

Abstract Background Few studies have reported real-life data on socio-economic functioning in patients with bipolar disorder and their unaffected first-degree relatives. Methods We used Danish nation-wide population-based longitudinal register linkage to investigate socio-economic functioning in 19 955 patients with bipolar disorder, their 13 923 siblings and 20 sex, age and calendar-matched control individuals from the general population. Follow-up was from 1995 to 2017. Results Patients with a diagnosis of bipolar disorder had lower odds of having achieved the highest educational level [OR 0.75 (95% confidence interval (CI) 0.73–0.77)], being employed [OR 0.16 (95% CI 0.159–0.168)], having achieved the 80% highest quartile of income [OR 0.33 (95% CI 0.32–0.35)], cohabitating [OR 0.44 (95% CI 0.43–0.46)] and being married [OR 0.54 (95% CI 0.52–0.55)] at first contact to hospital psychiatry as inpatient or outpatient compared with control individuals from the general population. Similarly, siblings to patients with bipolar disorder had a lower functioning within all five socio-economic areas than control individuals. Furthermore, patients and partly siblings showed substantially decreased ability to enhance their socio-economic functioning during the 23 years follow-up compared to controls. Conclusions Socio-economic functioning is substantially decreased in patients with bipolar disorder and their siblings and does not improve during long-term follow-up after the initial hospital contact, highlighting a severe and overlooked treatment gap.
The prevalence and risk factors of acute kidney injury in patients undergoing hip fracture surgery: a meta-analysis

ABSTRACT Acute kidney injury (AKI) was a frequent complication following hip fracture surgery, but recent studies reported inconsistent findings. Our study was aimed at clarifying the prevalence and risk factors of AKI after hip fracture surgery. Pubmed, Embase, and Web of Science were systematically searched from the inception to March 2020 to identify observational studies investigating the prevalence and risk factors of AKI in patients undergoing hip fracture surgery. Pooled prevalence and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using a random-effects model. Publication bias was evaluated with a funnel plot and statistical test. All the statistical analyses were performed using Stata version 12.0. A total of 11 studies with 16,421 patients was included in the current meta-analysis. The pooled prevalence of AKI in patients undergoing hip fracture surgery was 17% (95%CI, 14%-21%) with substantial heterogeneity (I2 = 95%). Postoperative serum albumin (OR 1.80; 95%CI, 1.38–2.36) was a significant predictor for AKI. Age (OR 1.01; 95%CI, 0.95–1.07) and ACE inhibitors (OR 1.38; 95%CI, 0.92–2.07) were associated with increased the risk of AKI, but the results were not statistically significant. No significant publication bias was identified through statistical tests (Egger’s test, p = 0.258 and Begg’s test, p = 0.087). In conclusion, our findings indicated that the pooled AKI following hip fracture surgery was approximately 17%. Postoperative serum albumin was a potential significant risk factor for AKI. GRAPHICAL ABSTRACT
Non‐transplantable cord blood units as a source for adoptive immunotherapy of leukaemia and a paradigm of circular economy in medicine

Advances in immunotherapy with T cells armed with chimeric antigen receptors (CAR‐Ts), opened up new horizons for the treatment of B‐cell lymphoid malignancies. However, the lack of appropriate targetable antigens on the malignant myeloid cell deprives patients with refractory acute myeloid leukaemia of effective CAR‐T therapies. Although non‐engineered T cells targeting multiple leukaemia‐associated antigens [i.e. leukaemia‐specific T cells (Leuk‐STs)] represent an alternative approach, the prerequisite challenge to obtain high numbers of dendritic cells (DCs) for large‐scale Leuk‐ST generation, limits their clinical implementation. We explored the feasibility of generating bivalent‐Leuk‐STs directed against Wilms tumour 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) from umbilical cord blood units (UCBUs) disqualified for allogeneic haematopoietic stem cell transplantation. By repurposing non‐transplantable UCBUs and optimising culture conditions, we consistently produced at clinical scale, both cluster of differentiation (CD)34+ cell‐derived myeloid DCs and subsequently polyclonal bivalent‐Leuk‐STs. Those bivalent‐Leuk‐STs contained CD8+ and CD4+ T cell subsets predominantly of effector memory phenotype and presented high specificity and cytotoxicity against both WT1 and PRAME. In the present study, we provide a paradigm of circular economy by repurposing unusable UCBUs and a platform for future banking of Leuk‐STs, as a ‘third‐party’, ‘off‐the‐shelf’ T‐cell product for the treatment of acute leukaemias.
Daylight Saving Time preferences in Norway: Do individual chronotype and home address’ latitude and longitude matter?

ABSTRACT Daylight Saving Time is highly debated and associated with several health risks. Health experts recommend terminating adjusting the clock time, and to keep permanent standard (winter) time year around. The aims of the study were to investigate preferences for keeping or terminating this biannual adjustment of clock times and for permanent standard or summer time, in the general Norwegian population. Furthermore, we aimed to investigate whether such preferences depended on individual chronotype and home address’ latitude/longitude. The online survey included 47,194 participants. Chronotype was measured with the Composite Scale of Morningness (morning types, intermediate types, evening types). Results showed that 78.2% preferred to terminate adjusting the clock time. Summer time year around was preferred by 61.5% whereas 29.1% preferred standard time year around, and 9.4% did not have any preference. Preferences for terminating adjustment of clock times and summer time year around were found in all chronotypes and regardless of living south (latitude 58–59°N), north (latitude 69–71°N), west (longitude 5–6°E) or east (longitude 19–31°E). However, a relatively larger proportion of evening chronotypes preferred to terminate adjusting the clock time compared to morning chronotypes, and relatively more people living north or east preferred termination than people living south or west, respectively. Permanent standard time was more strongly preferred by extreme morning types in comparison with the other chronotypes. In conclusion, nearly four out of five participants reported to prefer to terminate adjusting the clock time, in line with recommendations. However, in contrast to advice from health experts, permanent summer time was preferred by twice as many as permanent standard time. Both chronotype and home address’ latitude and longitude mattered in regard to such preferences, but only to a small degree.
Evidence suggesting that deletion of expression of N‐glycolylneuraminic acid (Neu5Gc) in the organ‐source pig is associated with increased antibody‐mediated rejection of kidney transplants in baboons

Pigs deficient in three glycosyltransferase enzymes (triple‐knockout [TKO] pigs) and expressing “protective” human transgenes are likely sources of organs for transplantation into human recipients. Testing of human sera against red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) from TKO pigs has revealed minimal evidence of natural antibody binding. However, unlike humans, baboons exhibit natural antibody binding to TKO pig cells. The xenoantigen specificities of these natural antibodies are postulated to be one or more carbohydrate moieties exposed when N‐glycolylneuraminic acid (Neu5Gc) is deleted. The aim of this study was to compare the survival of renal grafts in baboons from pigs that either expressed Neu5Gc (GTKO pigs; Group1, n = 5) or did not express Neu5Gc (GTKO/CMAHKO [DKO] or TKO pigs; Group2, n = 5). An anti‐CD40mAb‐based immunosuppressive regimen was administered in both groups. Group1 kidneys functioned for 90‐260 days (median 237, mean 196 days), with histopathological features of antibody‐mediated rejection in two kidneys. Group2 kidneys functioned for 0‐183 days (median 35, mean 57), with all of the grafts exhibiting histologic features of antibody‐mediated rejection. These findings suggest that the absence of expression of Neu5Gc on pig kidneys impacts graft survival in baboon recipients.
Single-mode characteristic of a supermode microcavity Raman laser

Significance Microlasers in near-degenerate supermodes play a pivotal role for studies of non-Hermitian physics, novel light sources, and advanced sensors. However, the widely observed beating phenomena and the single-mode nature of the stimulated scattering have been generating the lasing characteristic dilemma. In this article, we experimentally elucidate the lasing spectral paradox by investigating the lasing dynamics of supermode Raman microlasers. The single-mode lasing behavior is confirmed, and the beating signal has been recognized as the transient interference during the lasing switching between the supermodes with the help of the self-injection technique. This work provides an insightful guidance for microlaser-based precision measurements and paves the way to reconfigurable light sources. Microlasers in near-degenerate supermodes lay the cornerstone for studies of non-Hermitian physics, novel light sources, and advanced sensors. Recent experiments of the stimulated scattering in supermode microcavities reported beating phenomena, interpreted as dual-mode lasing, which, however, contradicts their single-mode nature due to the clamped pump field. Here, we investigate the supermode Raman laser in a whispering-gallery microcavity and demonstrate experimentally its single-mode lasing behavior with a side-mode suppression ratio (SMSR) up to 37 dB, despite the emergence of near-degenerate supermodes by the backscattering between counterpropagating waves. Moreover, the beating signal is recognized as the transient interference during the switching process between the two supermode lasers. Self-injection is exploited to manipulate the lasing supermodes, where the SMSR is further improved by 15 dB and the laser linewidth is below 100 Hz.