Miracle-dz/UniFAR-FTUs huggingface dataset:
Danish expanded newborn screening is a successful preventive public health programme.

INTRODUCTION Newborn screening is a public health programme for early diagnosis of treatable diseases. METHODS The subjects included were newborns born 2002-2019. Expanded newborn screening (eNBS) for metabolic diseases was introduced as a pilot project from 2002 to 2009, followed by routine screening with informed dissent. A total of 967,780 newborns were screened; 82,930 were unscreened. Furthermore, a historic cohort of clinically diagnosed children born in the 1992-2001 period was included. Children in the unscreened and historic cohorts were evaluated for the same diseases as were the screened children. Dried blood spot samples were collected locally and sent for screening analyses. We recorded newborns with true and false positive results as well as false negative results and their clinical signs at screening and at the last follow-up. RESULTS A total of 603 samples were screen positive: 354 false positives and 249 true positives (222 newborns and 27 mothers). The positive predictive value (PPV) was 41% for the entire screening period; 62% for 2018. The false positive rate (FPR) was 0.036% overall; 0.024% for 2018. The overall prevalence of diseases was 1:3,900; in the historic cohort, the prevalence of the same diseases was 1:8,300; 7.3% had symptoms at the time of screening. At follow-up, 93% of the children had no clinically significant sequelae. Among 82,930 unscreened newborns, 27 (1:3,000) had eNBS panel diseases, some with severe manifestations. CONCLUSIONS This update of eNBS in Denmark confirms that eNBS is a successful preventive public health programme. Early treatment in a latent phase of disease is effective and screening should be extended to other diseases not currently in the programme. FUNDING The work was supported by grants from The Ronald McDonald Børnefond, Danmarks Sundhedsfond, Direktør Ib Henriksens Fond, Ragnhild Ibsens Legat til Medicinsk Forskning, Gerda og Aage Haenschs Fond, Dronning Louises Børnehospitals Forskningsfond, Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis's Legat, Aase and Ejnar Danielsens Fond, Oda og Hans Svenningsens Fond, Fonden af 1870, Vanførefonden, Fonden til Lægevidenskabens Fremme and Danish Medical Research Council. TRIAL REGISTRATION not relevant.
A Simplified Sablik’s Approach to Model the Effect of Compaction Pressure on the Shape of Hysteresis Loops in Soft Magnetic Composite Cores

A novel approach to take into account the effect of compaction pressure on the shape of modeled hysteresis curves of self-developed soft magnetic composite cores is presented. The description relies on the introduction of an additional term in the so-called effective field, which is assumed proportional to the compaction pressure. The proposed model bears some resemblance to the Sablik’s extension of the Jiles–Atherton model, readily used in the studies of the magnetoelastic effect. Verification of the description is carried out using measurement data from self-developed iron-based composite cores.
Function Extension Based Real-Time Wavelet De-Noising Method for Projectile Attitude Measurement

The real-time measurement of the projectile attitude is the key to realize the whole process guidance of the projectile. Due to the high dynamic characteristics of the projectile motion, the attitude measurement is affected by the real-time and accuracy of the gyro signal de-noising. For the nonlinear discontinuity of the conventional extension method in real-time wavelet de-noising, a function extension real-time wavelet de-noising method is proposed in this paper. In this method, a prediction model of gyro signal is established based on the Roggla formula. According to the model, the signal is fitted in the sliding window, and the signal of the same length is predicted to realize the right boundary extension. The simulation and experiment results show that compared with the traditional extension method, the proposed method can in-crease the signal-to-noise ratio (SNR) and the smoothness, and can decrease the attitude mean absolute error (AMAE) and the attitude root mean square error (ARMSE). Moreover, the time delay caused by signal de-noising can be effectively solved. The real-time performance of the attitude measurement can be ensured.
Early Surgery Versus Biologic Therapy in Limited Nonstricturing Ileocecal Crohn's Disease-A Decision-making Analysis.

BACKGROUND Surgery is the preferred option for patients with symptomatic localized fibrostenotic ileocecal Crohn's disease (CD) but not for those with predominantly active inflammation without obstruction. The benefit of early surgery in patients with a limited nonstricturing ileocecal CD over biologic treatment is still a debate. OBJECTIVE Our objective is to formulate a decision analysis model based on recently published data to explore whether early surgery in patients with limited nonstricturing CD is preferred over biologic treatment. METHODS We constructed a Markov model comparing 2 strategies of treatment: (1) early surgery vs (2) biologic treatment. To estimate the quality-adjusted life years (QALYs) and the costs in each strategy, we simulated 10,000 virtual patients with the Markov model using a Monte Carlo simulation 100 times. Sensitivity analyses were performed to evaluate the robustness of the model and address uncertainties in the estimation of model parameters. RESULTS The costs were $29,457 ± $407 and $50,382 ± $525 (mean ± SD) for early surgery strategy and biologic treatment strategy, respectively. The QALY was 6.24 ± 0.01 and 5.81 ± 0.01 for early surgery strategy and biologic treatment strategy, respectively. CONCLUSION The strategy of early surgery dominates (higher QALY value [efficacy] and less cost) compared with the strategy of biologic treatment in patients with limited ileocecal CD.
MGL1 Receptor Plays a Key Role in the Control of T. cruzi Infection by Increasing Macrophage Activation through Modulation of ERK1/2, c-Jun, NF-κB and NLRP3 Pathways

Macrophage galactose-C type lectin (MGL)1 receptor is involved in the recognition of Trypanosoma cruzi (T. cruzi) parasites and is important for the modulation of the innate and adaptive immune responses. However, the mechanism by which MGL1 promotes resistance to T. cruzi remains unclear. Here, we show that MGL1 knockout macrophages (MGL1−/− Mφ) infected in vitro with T. cruzi were heavily parasitized and showed decreased levels of reactive oxygen species (ROS), nitric oxide (NO), IL-12 and TNF-α compared to wild-type macrophages (WT Mφ). MGL1−/− Mφ stimulated in vitro with T. cruzi antigen (TcAg) showed low expression of TLR-2, TLR-4 and MHC-II, which resulted in deficient splenic cell activation compared with similar co-cultured WT Mφ. Importantly, the activation of p-ERK1/2, p-c-Jun and p-NF-κB p65 were significantly reduced in MGL1−/− Mφ exposed to TcAg. Similarly, procaspase 1, caspase 1 and NLRP3 inflammasome also displayed a reduced expression that was associated with low IL-β production. Our data reveal a previously unappreciated role for MGL1 in Mφ activation through the modulation of ERK1/2, c-Jun, NF-κB and NLRP3 signaling pathways, and to the development of protective innate immunity against experimental T. cruzi infection.
Deep Learning in Medical Imaging

The artificial neural network (ANN), one of the machine learning (ML) algorithms, inspired by the human brain system, was developed by connecting layers with artificial neurons. However, due to the low computing power and insufficient learnable data, ANN has suffered from overfitting and vanishing gradient problems for training deep networks. The advancement of computing power with graphics processing units and the availability of large data acquisition, deep neural network outperforms human or other ML capabilities in computer vision and speech recognition tasks. These potentials are recently applied to healthcare problems, including computer-aided detection/diagnosis, disease prediction, image segmentation, image generation, etc. In this review article, we will explain the history, development, and applications in medical imaging
The higher risk for sperm DNA damage in infertile men.

OBJECTIVES Supplementary assays are needed for determination of relationships between sperm biomarkers and fertility potential. Therefore, our research was designed to determine the extent of sperm DNA fragmentation (SDF) and establish a discriminating threshold of SDF for fertility potential. MATERIAL AND METHODS Semen characteristics were evaluated according to World Health Organization recommendations, and SDF was assessed by sperm chromatin dispersion test on ejaculated spermatozoa from infertile and healthy normozoospermic men. RESULTS A higher proportion of SDF was noted in infertile men (median 23.00%) than normozoospermic (median 14.00%). Significantly less subjects (17.03%) with low SDF level (≤ 15%) and more (35.17%) with high SDF level ( > 30%) were found for the infertile group vs the normooospermic (57.90% and 5.26%, respectively). Infertile group had significantly lower odds ratio (OR) for having a low SDF level (OR: 0.1493) and higher OR for having a high SDF level (OR: 9.7627). Receiver operating characteristic analysis [area under curve (AUC) = 0.785] revealed that 20% SDF is predictive value for discriminating between infertile and normozoospermic subjects. SDF was negatively correlated with the sperm number, morphology, progressive motility and vitality but positively with the teratozoospermia index. CONCLUSIONS Our study demonstrates: (1) a significant difference in the extent of SDF and in the risk for having damaged sperm DNA between infertile and normozoospermic men, (2) > 20% SDF has negative predictive value for fertility potential, (3) coexistence of abnormal standard sperm parameters with sperm chromatin damages. Therefore, SDF should be considered as a highly valuable indicator of male fertility potential.
Astragaloside IV protects ATDC5 cells from lipopolysaccharide-caused damage through regulating miR-203/MyD88

Abstract Context Osteoarthritis (OA) is a degenerative arthrosis sickness. Astragaloside IV (AS-IV) functions by relieving inflammatory damage. Objective We aimed to investigate the mechanism by which AS-IV protects ATD cells from lipopolysaccharide (LPS)-induced damage. Materials and methods ATDC5 cells were transfected with miR-203 inhibitor and NC inhibitor (150 nM) or pEX-MyD88 and sh-MyD88 (50 nM) for 48 h, pre-treated by 15 μg/mL AS-IV for 24 h, then treated by 5 μg/mL LPS for 12 h. Dual-luciferase activity testing was used to determine whether miR-203 could bind to MyD88. CCK-8 and flow cytometry were used to detect cell activity and apoptosis, respectively, and qRT-PCR, western blots, and ELISA were performed to detect expression levels of miR-203 and inflammatory cytokines. Results Based on the 50% inhibiting concentration (IC50), there was no significant difference of AS-IV (0 to 15 μg/mL) on cell viability. Fifteen μg/mL was the optimal concentration of AS-IV in treating LPS-induced inflammatory damage in subsequent experiments since this was a semi-lethal concentration. AS-IV significantly reduces LPS-induced viability, apoptosis and the release of TNF-α, IL-6 and iNOS mainly through up-regulating miR-203. Further, MyD88 was a target gene of miR-203 and negatively regulated by miR-203. Knockdown of MyD88 inhibited LPS-induced inflammatory damage by inhibiting the NF-κB signal pathway. Discussion and conclusions AS-IV protects ATDC5 cells against LPS-induced damage mainly via regulating miR-203/MyD88. Our results support a theoretical basis for in-depth study of the function of AS-IV and the clinical cure of OA.
The protective effort of GPCR kinase 2–interacting protein‐1 in neurons via promoting Beclin1‐Parkin induced mitophagy at the early stage of spinal cord ischemia‐reperfusion injury

In spinal cord ischemia‐reperfusion (I/R) injury, large amounts of reactive oxygen species can cause mitochondrial damage. Therefore, mitophagy acts as the main mechanism for removing damaged mitochondria and protects nerve cells. This study aimed to illustrate the important role of GPCR kinase 2–interacting protein‐1 (GIT1) in mitophagy in vivo and in vitro. The level of mitophagy in the neurons of Git1 knockout mice was significantly reduced after ischemia‐reperfusion. However, the overexpression of adeno‐associated virus with Git1 promoted mitophagy and inhibited the apoptosis of neurons. GIT1 regulated the phosphorylation of Beclin‐1 in Thr119, which could promote the translocation of Parkin to the mitochondrial outer membrane. This process was independent of PTEN‐induced kinase 1 (PINK1), but it could not rescue the role in the absence of PINK1. Overall, GIT1 enhanced mitophagy and protected neurons against ischemia‐reperfusion injury and, hence, might serve as a new research site for the protection of ischemia‐reperfusion injury.
Resveratrol and the Interaction between Gut Microbiota and Arterial Remodelling

Arterial remodelling refers to the alteration in the structure of blood vessel that contributes to the progression of hypertension and other cardiovascular complications. Arterial remodelling is orchestrated by the crosstalk between the endothelium and vascular smooth muscle cells (VSMC). Vascular inflammation participates in arterial remodelling. Resveratrol is a natural polyphenol that possesses anti-oxidant and anti-inflammatory properties and has beneficial effects in both the endothelium and VSMC. Resveratrol has been studied for the protective effects in arterial remodelling and gut microbiota, respectively. Gut microbiota plays a critical role in the immune system and inflammatory processes. Gut microbiota may also regulate vascular remodelling in cardiovascular complications via affecting endothelium function and VSMC proliferation. Currently, there is new evidence showing that gut microbiota regulate the proliferation of VSMC and the formation of neointimal hyperplasia in response to injury. The change in population of the gut microbiota, as well as their metabolites (e.g., short-chain fatty acids) could critically contribute to VSMC proliferation, cell cycle progression, and migration. Recent studies have provided strong evidence that correlate the effects of resveratrol in arterial remodelling and gut microbiota. This review aims to summarize recent findings on the resveratrol effects on cardiovascular complications focusing on arterial remodelling and discuss the possible interactions of resveratrol and the gut microbiota that modulate arterial remodelling.
Tocopherol Allergic Dermatitis Masquerading as Lifelong Atopic Dermatitis.

1. Matthews MR, VanderVelde JC, Caruso DM, et al. Lemons in the Arizona sunshine: the effects of furocoumarins leading to phytophotodermatitis and burn-like injuries. Wounds 2017;29(12):E118–E124. 2. Wang L, Sterling B, Don P. Berloque dermatitis induced by “Florida water”. Cutis 2002;70(1):29–30. 3. Pongpairoj K, Morar N, McFadden JP. ‘Seborrhoeic dermatitis’ of the head and neck without scalp involvement—remember nail varnish allergy. Contact Dermatitis 2016;74(5):306–307. 4. Hamann D, Zirwas M. Successful patch testing of a patient receiving antiinterleukin-17 therapy with secukinumab: a case report. Contact Dermatitis 2017;376(6):378–379.
The P. gingivalis Autocitrullinome Is Not a Target for ACPA in Early Rheumatoid Arthritis

Rheumatoid arthritis (RA), a chronic inflammatory disease affecting primarily the joints, is frequently characterized by the presence of autoimmune anticitrullinated protein antibodies (ACPA) during preclinical stages of disease and accumulation of hypercitrullinated proteins in arthritic joints. A strong association has been reported between RA and periodontal disease, and Porphyromonas gingivalis, a known driver of periodontitis, has been proposed as the microbial link underlying this association. We recently demonstrated P. gingivalis–mediated gut barrier breakdown and exacerbation of joint inflammation during inflammatory arthritis. In the present study, we investigated another potential role for P. gingivalis in RA etiopathogenesis, based on the generation of ACPA through the activity of a unique P. gingivalis peptidylarginine deiminase (PPAD) produced by this bacterium, which is capable of protein citrullination. Using a novel P. gingivalis W50 PPAD mutant strain, incapable of protein citrullination, and serum from disease-modifying antirheumatic drug–naïve early arthritis patients, we assessed whether autocitrullinated proteins in the P. gingivalis proteome serve as cross-activation targets in the initiation of ACPA production. We found no evidence for patient antibody activity specific to autocitrullinated P. gingivalis proteins. Moreover, deletion of PPAD did not prevent P. gingivalis–mediated intestinal barrier breakdown and exacerbation of disease during inflammatory arthritis in a murine model. Together, these findings suggest that the enzymatic activity of PPAD is not a major virulence mechanism during early stages of inflammatory arthritis.
Prevalence of Workplace Physical Violence against Health Care Professionals by Patients and Visitors: A Systematic Review and Meta-Analysis

Workplace physical violence against health care professionals perpetrated by patients and visitors has been a persistent problem worldwide. Prevalence estimates varied vastly across studies and there was a lack of quantitative syntheses of prevalence studies. This review aimed to quantify pooled one-year prevalence estimates at the global and regional levels. A systematic literature search was performed in the databases of PubMed, PsycINFO, Web of Science, and Embase between 1 January 2000 and 8 October 2018. Studies providing information about one-year prevalence of self-reported workplace physical violence against health care professionals perpetrated by patients or visitors were included. Heterogeneity between studies was evaluated using Cochran’s chi-squared test (Cochran’s Q) and I2 values. Subgroup analysis and meta-regression were used to explore heterogeneity. A total of 65 eligible studies reported one-year prevalence estimates for 61,800 health care professionals from 30 countries. The pooled one-year prevalence of workplace physical violence against health care professionals perpetrated by patients or visitors was 19.33% (95% confidence interval (CI): 16.49–22.53%) and the overall heterogeneity was high across studies. We noted geographic and staff categories variations for prevalence estimates through subgroup analysis. The meta-regression showed that sample size, type of health care setting, and quality score were significant moderators for heterogeneity. One in five health care professionals experienced workplace physical violence perpetrated by patients or visitors worldwide annually. Practical intervention was needed to ensure safety of health care professionals.
Effects of Stripe Rust Infection on the Levels of Redox Balance and Photosynthetic Capacities in Wheat

Wheat stripe rust (Puccinia striiformis f. sp. tritici, Pst) is the most destructive wheat disease and a major problem for the productivity of wheat in the world. To obtain a better understanding about different effects of redox homeostasis and photosystem (PS) to Pst infection in wheat, we investigated the differences in photosynthesis and the antioxidant defense system in wheat cultivar Chuanmai42 (CM42) in response to two Chinese Pst races known as CYR32 and V26. The results showed that V26-infected wheat accumulated a higher reactive oxygen species (ROS), cell death, and energy dissipation than CYR32-infected wheat when compared with the control. Furthermore, we found that the activities of three antioxidant enzymes (APX, GR, and GPX) and four resistance-related enzymes in CYR32-infected wheat were significantly higher than that in V26-infected wheat. In addition, quantitative RT-PCR indicated that the expression levels of two genes associated with resistant stripe rust in CYR32-infected wheat were clearly higher than that in V26-infected wheat. Compared with CYR32-infected wheat, lower photochemical efficiencies were observed in V26-infected wheat at the adult stage. Meanwhile, only a marked decline in D1 protein was observed in V26-infected wheat. We therefore deduced that wheat with stripe rust resistance could maintain high resistance and photosynthetic capacity by regulating the antioxidant system, disease-resistant related enzymes and genes, and the levels of PSII reaction center proteins.
Fe-Loaded MOF-545(Fe): Peroxidase-Like Activity for Dye Degradation Dyes and High Adsorption for the Removal of Dyes from Wastewater

Methods to remove dye pollutants with natural enzyme, like horseradish peroxidase (HRP), are still limited due to high costs and low stability levels. The development of such a method with similar enzymatic activity is important and could be helpful in wastewater disposal. A metal organic framework material, Fe-loaded MOF-545 (Fe), was synthesized in our study as a new way to remove dyes due to its peroxidase-like activity. The structural characterizations of Fe-loaded MOF-545(Fe) was investigated using scanning electron microscopy (SEM), UV-Vis absorption spectra, and X-ray diffraction (XRD). The peroxidase-like (POD-like) activity of Fe-loaded MOF-545(Fe) was investigated under different pH and temperature conditions. Because of the Fe added into the MOF-545 structure, the absorption of Fe-loaded MOF-545(Fe) for acid (anionic) dyes (methyl orange (MO)) was better than for basic (cationic) dyes (methylene blue (MB)). The Fe-loaded MOF-545(Fe) could give a significant color fading for MO and MB over a short time (about two hours) with peroxidase-like activity. The remarkable capacity of Fe-loaded MOF-545(Fe) to remove the MO or MB is due to not only physical adsorption, but also degradation of the MO and MB with POD-like activity. Therefore, Fe-loaded MOF-545(Fe) has significant potential regarding dye removal from wastewater.