Miracle-dz/UniFAR-FTUs huggingface dataset:
Effectiveness of Mediterranean Diet’s Adherence in Children with Inflammatory Bowel Diseases

Background: Nutritional support is very important in the treatment of Paediatric Inflammatory Bowel Disease (IBD). The role of the Mediterranean Diet (MD) has been understudied in children with IBD. The aims of this study were to assess the dietary intakes of IBD children in comparison with healthy controls (HCs), their adherence to MD; and the relationship between inflammation and dietary behaviors. Methods: Paediatric IBD patients in clinical remission and HCs were enrolled. The nutritional status and adherence to the Mediterranean Diet was evaluated through a 3-day food diary and the Mediterranean Diet Quality Index for Children and Adolescents (KIDMED). Results: The analysis of food diaries showed a significantly higher kilocalorie intake in IBD patients compared to HCs (p = 0.012), an increase in carbohydrates (p = 0.015) and in protein intake (p = 0.024). Both IBD and HCs have an intermediate adherence to MD. The comparison between Crohn’s disease (CD) and Ulcerative colitis (UC) patients showed significant difference in protein intake in CD patients (p = 0.047), as well as for vitamin D (p = 0.044) and iron intake (p = 0.023). Interestingly; in IBD patients we found a significant association between adherence to MD and a low level of fecal calprotectin (p = 0.027). Conclusion: Children with IBD in remission have a sub-optimal food intake compared to HCs. MD seems to correlate to decreased intestinal inflammation.
Caffeine and caffeine-containing pharmaceuticals as promising inhibitors for 3-chymotrypsin-like protease of SARS-CoV-2

Abstract In December 2019, a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the outbreak of a pulmonary disease called COVID-19, which killed thousands of people worldwide. Therefore, the necessity to find out the potential therapeutic pharmaceuticals is imperious. This study investigates the inhibitory effect of SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) using caffeine and caffeine-containing pharmaceuticals (3CPs) based on molecular dynamics simulations and free energy calculations by means of molecular mechanics-Poisson–Boltzmann surface area (MMPBSA) and molecular mechanics-generalized-Born surface area (MMGBSA). Of these 3CPs, seven drugs approved by the US-Food and Drug Administration have shown a good binding affinity to the catalytic residues of 3CLpro of His41 and Cys145: caffeine, theophylline, dyphylline, pentoxifylline, linagliptin, bromotheophylline and istradefylline. Their binding affinity score ranged from –4.9 to –8.6 kcal/mol. The molecular dynamic simulation in an aqueous solution of docked complexes demonstrated that the 3CPs conformations bound to the active sites of 3CLpro during 200 ns molecular dynamics simulations. The free energy of binding also confirms the stability of the 3CPs–3CLpro complexes. To our knowledge, this in silico study shows for the first time very inexpensive drugs available in large quantities that can be potential inhibitors against 3CLpro. In particular, the repurposing of linagliptin, and caffeine are recommended for COVID-19 treatment after in vitro, in vivo and clinical trial validation. Communicated by Ramaswamy H. Sarma
Improved placental vascular repair in a rat preeclampsia model by implantation of endothelial progenitor cells treated with platelet microparticles

ABSTRACT Objective: To detect the role of endothelial progenitor cells (EPCs) treated with platelet microparticles (PMPs) in preeclampsia. Methods: EPCs treated with/without PMPs were labeled and injected to PE rats. The differentiation of EPCs, the change of endothelial nitric oxide synthase (eNOS), blood pressure and proteinuria were measured. The blood pressure and proteinuria increased in each of PE groups, and were improved by EPCs which was strengthened by PMPs. Transplantation of EPCs increased placental angiogenesis. The trend of change of NO was the same as blood pressure. Conclusion: Transplantation of EPCs treated with PMPs improved blood pressure and proteinuria more effectively.
AITC induces MRP1 expression by protecting against CS/CSE-mediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis

The present study aimed to examine the effect of allyl isothiocyanate (AITC) on chronic obstructive pulmonary disease and to investigate whether upregulation of multidrug resistance-associated protein 1 (MRP1) associated with the activation of the PARK7 (DJ-1)/nuclear factor erythroid 2-related factor 2 (Nrf2) axis. Lung function indexes and histopathological changes in mice were assessed by lung function detection and H&E staining. The expression levels of Nrf2, MRP1, heme oxygenase-1 (HO-1), and DJ-1 were determined by immunohistochemistry, Western blotting and reverse transcription-quantitative polymerase chain reaction. Next, the expression of DJ-1 in human bronchial epithelial (16HBE) cells was silenced by siRNA, and the effect of DJ-1 expression level on cigarette smoke extract (CSE)-stimulated protein degradation and AITC-induced protein expression was examined. The expression of DJ-1, Nrf2, HO-1, and MRP1 was significantly decreased in the wild type model group, while the expression of each protein was significantly increased after administration of AITC. Silencing the expression of DJ-1 in 16HBE cells accelerated CSE-induced protein degradation, and significantly attenuated the AITC-induced mRNA and protein expression of Nrf2 and MRP1. The present study describes a novel mechanism by which AITC induces MRP1 expression by protecting against CS/CSE-mediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis.
Breakfast Characteristics and Its Association with Daily Micronutrients Intake in Children and Adolescents–A Systematic Review and Meta-Analysis

Breakfast is an important source of key nutrients in the diet. For this reason, the aim of this review was to investigate the associations between breakfast consumption and daily micronutrients intake in both children and adolescents (aged 2–18 years). A peer-reviewed systematic search was conducted in three datasets (PubMed, Scopus and Cochrane Library) in February 2020 in English and Spanish. Two independent reviewers evaluated 3188 studies considering the AXIS critical appraisal and PRISMA methodologies. Meta-analysis was carried out comparing results according to type of breakfast consumed (Ready to eat cereals (RTEC) breakfast or other types of breakfast) and breakfast skipping. Thirty-three articles were included in the systematic review (SR) and 7 in the meta-analysis. In the SR, we observed that those children and adolescents who usually consume RTEC at breakfast had a higher consumption of B-vitamins than those not consuming RTEC at breakfast. Breakfast consumers had a higher mineral intake (iron, calcium, magnesium, potassium, zinc, and iodine) than breakfast skippers. In the Meta-Analysis, RTEC consumers had significantly higher vitamin C intake than breakfast skippers (Standard Mean Difference (SMD), −4.12; 95% confidence intervals (CI): −5.09, −3.16). Furthermore, those children who usually consume breakfast had significantly higher daily intake of calcium than breakfast skippers (SMD, −7.03; 95%CI: −9.02, −5.04). Our review proposes that breakfast consumption seems to be associated with higher daily micronutrients intake than breakfast skippers.
Pharmacologic Inhibition of FGFR Modulates the Metastatic Immune Microenvironment and Promotes Response to Immune Checkpoint Blockade

Immune checkpoint blockade (ICB) is limited in its effectiveness as a treatment for metastatic breast cancer. Sequential dosing of an FGFR inhibitor followed by ICB limits metastatic tumor growth and increases overall survival as compared to either monotherapy. The effectiveness of immunotherapy as a treatment for metastatic breast cancer is limited due to low numbers of infiltrating lymphocytes in metastatic lesions. Herein, we demonstrated that adjuvant therapy using FIIN4, a covalent inhibitor of fibroblast growth factor receptor (FGFR), dramatically delayed the growth of pulmonary metastases in syngeneic models of metastatic breast cancer. In addition, we demonstrated in a syngeneic model of systemic tumor dormancy that targeting of FGFR enhanced the immunogenicity of the pulmonary tumor microenvironment through increased infiltration of CD8+ lymphocytes and reduced presence of myeloid suppressor cells. Similar impacts on immune cell infiltration were observed upon genetic depletion of FGFR1 in tumor cells, which suggested a direct influence of FGFR signaling on lymphocyte trafficking. Suppression of CD8+ lymphocyte infiltration was consistent with FGFR-mediated inhibition of the T-cell chemoattractant CXCL16. Initial attempts to concomitantly administer FIIN4 with immune checkpoint blockade failed due to inhibition of immune-mediated tumor cell killing via blockade of T-cell receptor signaling by FIIN4. However, this was overcome by using a sequential dosing protocol that consisted of FIIN4 treatment followed by anti–PD-L1. These data illustrate the complexities of combining kinase inhibitors with immunotherapy and provide support for further assessment of FGFR targeting as an approach to enhance antitumor immunity and improve immunotherapy response rates in patients with metastatic breast cancer.
Microglia in Prion Diseases: Angels or Demons?

Prion diseases are rare transmissible neurodegenerative disorders caused by the accumulation of a misfolded isoform (PrPSc) of the cellular prion protein (PrPC) in the central nervous system (CNS). Neuropathological hallmarks of prion diseases are neuronal loss, astrogliosis, and enhanced microglial proliferation and activation. As immune cells of the CNS, microglia participate both in the maintenance of the normal brain physiology and in driving the neuroinflammatory response to acute or chronic (e.g., neurodegenerative disorders) insults. Microglia involvement in prion diseases, however, is far from being clearly understood. During this review, we summarize and discuss controversial findings, both in patient and animal models, suggesting a neuroprotective role of microglia in prion disease pathogenesis and progression, or—conversely—a microglia-mediated exacerbation of neurotoxicity in later stages of disease. We also will consider the active participation of PrPC in microglial functions, by discussing previous reports, but also by presenting unpublished results that support a role for PrPC in cytokine secretion by activated primary microglia.
Performance Improvement Based on Modified Lossless Quantization (MLQ) for Secret Key Generation Extracted from Received Signal Strength

In symmetric cryptography systems have problems in the distribution of secret keys. The two users who will communicate require sharing keys through the public channel. The proposed solution to overcome these problems is to utilize information from the physical layer (e.g. RSS). Received Signal Strength (RSS) is an indicator for measuring the power received by wireless devices. The advantage of secret key extraction using physical layer information from a wireless channel is that it allows both devices within the transmission range to extract the secret key together. In this paper, we propose a secret key generation scheme adopted from an existing scheme with modifications to improve performance. Our proposed system is applied to static and dynamic conditions to test performance. The proposed algorithm is able to obtain a reduction in KDR (Key Disagreement Rate) up to 48.42% and an increase in the KGR (Key Generation Rate) up to 23.35% when compared to the existing scheme. Our proposed system also successfully passed the randomness using the NIST test with the approximate value of entropy generated 0.80 in static conditions and 0.81 in dynamic conditions.
Meta-analysis of the association between adiponectin SNP 45, SNP 276, and type 2 diabetes mellitus

Objective The present study aimed to determine whether the polymorphisms at rs2241766 and rs1501299 on the ADIPOQ gene were related to the susceptibility of type 2 diabetes mellitus (T2DM). Methods Eight databases, PubMed, GWAS, Embase, Lochrane, Ebsco, CNKI (Chinese National Knowledge Infrastructure), VIP (Viper Database) and ChinaInfo were searched, and a meta-analysis of susceptibility was conducted between SNP45, SNP276 polymorphisms and T2DM. Furthermore, HWE test was conducted to assess the genetic balance of the study, evaluate the quality of Newcastle–Ottawa quality assessment scale (NOS), and establishing allelic, dominant, recessive, heterozygous, and homozygous gene models. Results This meta-analysis included 53 articles, encompassing 9285 cases with rs2241766 and 14156 controls and 7747 cases with rs1501299 and 10607 controls. For the rs2241766 locus, a significant correlation was found in the three models by the subgroup analysis. Western Asians: dominant gene model (TT + TG vs. GG, P = 0.01); heterozygous gene model (TG vs. GG, P = 0.02); homozygous gene model (TT vs. GG, P = 0.01). South Asians: dominant gene model (TT + TG vs. GG, P = 0.004); heterozygous gene model (TG vs. GG, P = 0.009); homozygous gene model (TT vs. GG, P = 0.005). However, no statistically significant correlation was established among the five genetic models for rs1501299 locus. Conclusion The findings of the present study indicated that the T allele of rs2241766 polymorphism is the susceptibility locus of T2DM in the West Asian population, but has a protective effect in the South Asian population, albeit further studies are needed in other populations. Also, no association was found between the ADIPOQ rs1501299 polymorphism and T2DM.
Phylogenetic position of the freshwater ciliate Euplotes daidaleos within the family of Euplotidae, obtained from small subunit rDNA gene sequence

The Culture Collection of Algae and Protozoa (CCAP) (http://www.ccap.ac.uk) is the largest and most genotypically diverse microbial Biological Resource Centre (BRC) in Europe. The collection includes a wide variety of ciliates including ten Euplotes cultures, four of which are in the public collection. This study focuses on the freshwater ciliate E. daidaleos DILLER & KOUNARIS, 1966, the only species of Euplotes that lives in endosymbiosis with ‘Chlorella’ like green algae. We sequenced the small subunit of the nuclear ribosomal operon (SSU rDNA) and compared this sequence with others of 40 taxa of different Euplotes species. In our phylogenetic analyses we determined six, well-supported clades and two single taxa (E. rariseta and E. euryhalinus). Euplotes daidaleos belongs to a clade containing dominantly freshwater species of Euplotes of which E. octocarinatus is its closest relative.
Forced Expiratory Time: A Composite of Airway Narrowing and Airway Closure.

Forced expiratory time (FET) is a spirometrically-derived variable thought to reflect lung function, but its physiologic basis remains poorly understood. We developed a mathematical theory of FET assuming a linear forced expiratory flow-volume profile that terminates when expiratory flow falls below a defined detection threshold. FET is predicted to correlate negatively with both FEV1 and FVC if variations in the rate of lung emptying (relative to normal) among individuals in a population exceed variations in the amount of lung emptying. We retrospectively determined FET pre- and post-methacholine challenge in 1241 patients (818 had normal lung function, 137 were obstructed, and 229 were restricted) and examined its relationships to spirometric and demographic variables in both hyperresponsive and normoresponsive individuals. Mean FET was 9.6 ± 2.2 s in the normal group, 12.3 ± 3.0 s in those with obstruction, and 8.8 ± 1.9 s in those with restriction. FET was inversely related to FEV1/FVC in all groups, negatively related to FEV1 in the obstructed patients, and positively related to FVC in both the normal and restricted patients. There was no relationship with methacholine responsiveness. Overall, our theory of the relationship between FET to the spirometric indices is supported by these findings, and in addition potentially explains how FET is affected by gender, age, smoking status, and possibly body mass index.
Relapse risk after in-ward electroconvulsive therapy for acute polymorphic psychotic disorder

Abstract Purpose Acute polymorphic psychotic disorder (APPD) without symptoms of schizophrenia is a serious psychiatric condition. APPD can be effectively treated with electroconvulsive therapy (ECT), but little is known about relapse prevention after ECT for APPD. Materials and methods This was a retrospective register-based study conducted with 97 patients with APPD (ICD-10 diagnosis F23.0). We estimated the rates of readmission and suicide, and the prognostic factors of these outcomes after ECT. We combined data from several national Swedish registers and used Cox’s regression analysis to identify demographic factors, disease characteristics, and relapse preventive treatments that predicted time to readmission or suicide (relapse). Data registered between 2011 and 2016 were used in the study. Results Twenty percent of cases relapsed within a year. Thereafter, relapse rate was low. Two cases died during follow-up, whereof one by suicide. Anxiolytic treatment, lamotrigine treatment, and having more than four previous psychiatric hospital admissions were associated with shorter time to relapse. The most robust of these associations was between anxiolytics and relapse risk. Conclusions The first year after discharge from APPD is the period associated with the highest risk of relapse. Having many previous admissions was associated to relapse risk after ECT for APPD. The associations between anxiolytics, lamotrigine, and relapse are uncertain and might be influenced by indication bias.
Herpes simplex virus type 1 infection leads to neurodevelopmental disorder-associated neuropathological changes

Neonatal herpes simplex virus type 1 (HSV-1) infections contribute to various neurodevelopmental disabilities and the subsequent long-term neurological sequelae into the adulthood. However, further understanding of fetal brain development and the potential neuropathological effects of the HSV-1 infection are hampered by the limitations of existing neurodevelopmental models due to the dramatic differences between humans and other mammalians. Here we generated in vitro neurodevelopmental disorder models including human induced pluripotent stem cell (hiPSC)-based monolayer neuronal differentiation, three-dimensional (3D) neuroepithelial bud, and 3D cerebral organoid to study fetal brain development and the potential neuropathological effects induced by the HSV-1 infections. Our results revealed that the HSV-1-infected neural stem cells (NSCs) exhibited impaired neural differentiation. HSV-1 infection led to dysregulated neurogenesis in the fetal neurodevelopment. The HSV-1-infected brain organoids modelled the pathological features of the neurodevelopmental disorders in the human fetal brain, including the impaired neuronal differentiation, and the dysregulated cortical layer and brain regionalization. Furthermore, the 3D cerebral organoid model showed that HSV-1 infection promoted the abnormal microglial activation, accompanied by the induction of inflammatory factors, such as TNF-α, IL-6, IL-10, and IL-4. Overall, our in vitro neurodevelopmental disorder models reconstituted the neuropathological features associated with HSV-1 infection in human fetal brain development, providing the causal relationships that link HSV biology with the neurodevelopmental disorder pathogen hypothesis.
Prognostic value of anti‐HBc quantification in hepatitis B virus related acute‐on‐chronic liver failure

It has been reported that serum quantification of anti‐HBc (qAnti‐HBc) could predict antiviral response in chronic hepatitis B (CHB) patients, while its role in hepatitis B virus‐related acute‐on‐chronic liver failure (HBV‐ACLF) remains unclear. Its implication in HBV‐ACLF was evaluated in this study.
A Novel Dissection Gesture Classification to Characterize Robotic Dissection Technique for Renal Hilar Dissection.

PURPOSE Deconstruction of robotic surgical gestures into semantic vocabulary yields an effective tool for surgical education. In this study we disassembled tissue dissection into basic gestures, created a classification system, and showed its ability to distinguish between experts and novices. MATERIALS AND METHODS Videos of renal hilum preparation during robotic assisted partial nephrectomies were manually reviewed to identify all discrete surgical movements. Identified dissection movements were classified into distinct gestures based on the consensus of 6 expert surgeons. This classification system was then employed to compare expert and novice dissection patterns during the renal hilum preparation. RESULTS A total of 40 robotic renal hilum preparation videos were reviewed, representing 16 from 6 expert surgeons (100 or more robotic cases) and 24 from 13 novice surgeons (fewer than 100 robotic cases). Overall 9,819 surgical movements were identified, including 5,667 dissection movements and 4,152 supporting movements. Nine distinct dissection gestures were identified and classified into the 3 categories of single blunt dissection (spread, peel/push, hook), single sharp dissection (cold cut, hot cut and burn dissect) and combination gestures (pedicalize, 2-hand spread, and coagulate then cut). Experts completed 5 of 9 dissection gestures more efficiently than novices (p ≤0.033). In consideration of specific anatomical locations, experts used more peel/push and less hot cut while dissecting the renal vein (p <0.001), and used more pedicalize while dissecting the renal artery (p <0.001). CONCLUSIONS Using this novel dissection gesture classification system, key differences in dissection patterns can be found between experts/novices. This comprehensive classification of dissection gestures may be broadly applied to streamline surgical education.
The Emerging Role of Drug-Induced Sleep Endoscopy in the Management of Obstructive Sleep Apnea

Obstructive sleep apnea is a prevalent sleep disorder characterized by partial or complete obstruction of the upper airway. Continuous positive airway pressure is the first-line therapy for most patients, but adherence is often poor. Alternative treatment options such as mandibular advancement devices, positional therapy, and surgical interventions including upper airway stimulation target different levels and patterns of obstruction with varying degrees of success. Drug-induced sleep endoscopy enables the visualization of upper airway obstruction under conditions mimicking sleep. In the era of precision medicine, this additional information may facilitate better decision-making when prescribing alternative treatment modalities, with the hope of achieving better adherence and/or success rates. This review discusses the current knowledge and evidence on the role of drug-induced sleep endoscopy in the non-positive airway pressure management of obstructive sleep apnea.
Genome streamlining in a minute herbivore that manipulates its host plant

The tomato russet mite, Aculops lycopersici, is among the smallest animals on earth. It is a worldwide pest on tomato and can potently suppress the host’s natural resistance. We sequenced its genome, the first of an eriophyoid, and explored whether there are genomic features associated with the mite’s minute size and lifestyle. At only 32.5 Mb, the genome is the smallest yet reported for any arthropod and, reminiscent of microbial eukaryotes, exceptionally streamlined. It has few transposable elements, tiny intergenic regions, and is remarkably intron-poor, as more than 80% of coding genes are intronless. Furthermore, in accordance with ecological specialization theory, this defense-suppressing herbivore has extremely reduced environmental response gene families such as those involved in chemoreception and detoxification. Other losses associate with this species’ highly derived body plan. Our findings accelerate the understanding of evolutionary forces underpinning metazoan life at the limits of small physical and genome size.