Miracle-dz/UniFAR-FTUs huggingface dataset:
Interim positron emission tomography in diffuse large B-cell lymphoma.

Rationale: In diffuse large B-cell lymphoma, early assessment of treatment response by 18-fluorodeoxyglucose positron emission tomography (PET) may trigger treatment modification. Reliable identification of good and poor responders is important. We compared three competing methods of interim PET evaluation. Methods: Images from 449 patients participating in the 'Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas' trial were re-analyzed by applying the visual Deauville score and the standardized uptake value (SUV)-based qPET and ΔSUVmax scales to interim PET scans performed after two cycles of chemotherapy. qPET relates residual lymphoma 18-fluorodeoxyglucose uptake to physiological liver uptake, converting the ordinal Deauville scale into a continuous scale and permitting a direct comparison with the continuous ΔSUVmax scale, which is based on SUVmax changes between baseline and interim scans. Positive and negative predictive values were calculated for progression-free survival. Results: Using established thresholds to distinguish between good and poor responders (visual Deauville score 1-3 vs. 4-5; ΔSUVmax >66% vs. ΔSUVmax ≤66%), the positive predictive value was significantly lower with Deauville than ΔSUVmax (38.4% versus 56.6%; P = 0.03). qPET and ΔSUVmax were strongly correlated on the log scale (Pearson's r=0.75). When plotted along corresponding percentiles, the positive predictive value curves for qPET and ΔSUVmax were superimposable, with low values up to the 85th percentile and a steep rise thereafter. The recommended threshold of 66% SUVmax reduction for the identification of poor responders was equivalent to qPET=2.26 corresponding to score 5 on the visual Deauville scale. The negative predictive value curves were also superimposable, but remained flat between 80% and 70%. Conclusion: Continuous scales are better suited for interim PET-based outcome prediction than the ordinal Deauville scale. qPET and ΔSUVmax essentially carry the same information. The proportion of poor risk patients identified is less than 15%.
Synthesis of fragments of the capsular polysaccharide of Neisseria meningitidis (serogroup A) suitable for bioconjugation

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Interleukin 4 deficiency limits the development of a lupus‐like disease in mice triggered by phospholipids in a non‐bilayer arrangement

Non‐bilayer phospholipids arrangements (NPAs) are transient molecular associations different from lipid bilayers. When they become stable, they can trigger a disease in mice resembling human lupus, which is mainly characterized by the production of anti‐NPA IgG antibodies. NPAs are stabilized on liposomes or cell bilayers by the drugs procainamide or chlorpromazine, which produce drug‐induced lupus in humans. Here, we evaluated the participation of the TH2 response, through its hallmark cytokine IL‐4, on the development of the lupus‐like disease in mice. Wild‐type or IL‐4 knockout BALB/c mice received liposomes bearing drug‐induced NPAs, the drugs alone, or an anti‐NPA monoclonal antibody (H308) to induce the lupus‐like disease (the last two procedures stabilize NPAs on mice cells). IL‐4 KO mice showed minor disease manifestations, compared to wild‐type mice, with decreased production of anti‐NPA IgG antibodies, no anti‐cardiolipin, anti‐histones and anticoagulant antibodies, and no kidney or skin lesions. In these mice, H308 was the only inducer of anti‐NPA IgG antibodies. These findings indicate that IL‐4 has a central role in the development of the murine lupus‐like disease induced by NPA stabilization.
Colloidal properties of block copolymers based on 2-(acetoacetoxy)ethyl methacrylate: Organic-inorganic hybrid materials

Theodora Krasia and Helmut Schlaad. Colloid Chemistry, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, Golm, 14476, Germany This paper describes colloidal properties of a poly(n-butyl methacrylate)342-block-poly[2-(acetoacetoxy)ethyl methacrylate]39 (PBMA-b-PAEMA) copolymer in dilute cyclohexane solution. Spherical micelles of this block copolymer consist of a PAEMA core and a PBMA solvating corona (NMR and Light Scattering, DLS and SLS). The PAEMA core of the micelles could be loaded with metal ion salts (Fe3+, Co2+, Pd2+, etc.) (UV/visible spectroscopy and Analytical Ultracentrifugation, AUC) to yield stable organic-inorganic colloidal dispersions. These dispersions were used for the fabrication of ordered arrays of metal ions on a solid mica substrate (Atomic Force Microscopy, AFM).
Witnessing Parental Violence and Cyber IPV Perpetration in Hispanic Emerging Adults: The Mediating Role of Attitudes Toward IPV

Recent studies indicate that the perpetration of intimate partner violence via cyberspaces (cyber IPV), namely, psychological aggression, sexual aggression, and cyberstalking is high among emerging adults. However, little is known of the risk factors that lead to cyber IPV and far lesser within Hispanic adults. Based on the intergenerational transmission of violence hypothesis, the present study examined the indirect effect of witnessing parental violence during childhood on the three types of cyber IPV through attitudes condoning IPV in Hispanic men and women, separately. Participants were 1,136 Hispanic emerging adults in the age range of 18–29 years (M = 20.53 years, SD = 2.42; 72.5% women, 88% Mexican descent). Over half of the participants (54.2%) witnessed at least one instance of parental violence during childhood. In contrast to women, men were more likely to hold attitudes accepting of IPV and perpetrate cyber sexual IPV, whereas women were more likely to report cyberstalking perpetration. Men and women with exposure to mother-to-father violence held attitudes justifying IPV that was associated with perpetrating the three cyber IPV types in adulthood (women: Brange = .016–.036; men: Brange = .016–.024). No significant gender differences were found in the associations of mother-to-father WPV and father-to-mother WPV on the three types of cyber IPV perpetration. These findings are discussed in the context of Hispanic culture, which has specific implications for cyber IPV intervention strategies.
Methoxyfenozide, a Molting Hormone Agonist, Affects Autogeny Capacity, Oviposition, Fecundity, and Fertility in Culex pipiens (Diptera: Culicidae)

Abstract The current study aimed to evaluate the effects of methoxyfenozide (RH-2485), an insect growth disrupter (IGD) belonging to molting hormone agonist class, against female adults of Culex pipiens L. under laboratory conditions. Lethal concentrations (LC50 = 24.54 µg/liter and LC90 = 70.79 µg/liter), previously determined against fourth instar larvae, were tested for adult female fertility, fecundity and oviposition after tarsal contact before mating and any bloodmeal. Methoxyfenozide was found to alter negatively their autogeny capacity and oviposition. A strong reduction of 56% and 72% (P < 0.001) in females' autogeny capacity was observed in both treated series, respectively. Alteration in oviposition were found to be higher with LC90 (OAI-LC90 = –0.62) than with the LC50 (OAI-LC50 = –0.42). Also fecundity and hatching rate (fertility) were significantly reduced in treated series as compared to controls. A significant reduction of 37.65 and 28.23% in fecundity and decrease of 56.85 and 71.87% in fertility were found, respectively in LC50 and LC90 treated series. Obtained data clearly demonstrated that methoxyfenozide have significant depressive effect on reproductive potential against medically important vector with minimizing ecotoxicological risks in mosquitoes management.
Functional properties of 4-PIOL at synaptic and extrasynaptic GABA-A receptors

GABAA receptors are the major inhibitory ligand-gated ion channels in the mammalian CNS. They mediate their physiological effects via two temporally and spatially distinct forms of signalling, denoted as phasic and tonic inhibition. These two forms of inhibition are mediated by distinct GABAA receptor subtypes, with phasic inhibition relying on the activation of synaptically-located γ2 subunit-containing receptors, and tonic inhibition requiring the activation of extrasynaptic receptors, predominantly thought to contain δ-subunits. The importance of tonic inhibition in regulating cell and network excitability has become increasingly apparent. Moreover, elevated tonic currents accompany neurological disorders such as stroke and absence epilepsy, suggesting that selectively reducing tonic inhibition might be therapeutically useful. Due to a lack of δ-selective antagonists, the theoretically predominant antagonist profile of the weak partial agonist, 4-PIOL, was studied as a potential mechanism for selectively reducing tonic inhibition. The functional effects of 4-PIOL were investigated firstly on whole-cell GABA-activated currents of several recombinant γ2- and δ-containing receptors expressed in HEK293 cells. As expected for a partial agonist, 4-PIOL exhibited both agonist- (at γ2-subunit GABAA receptors) and antagonist-type (at δ-subunit receptors) behaviours, depending on the GABA concentration. 4-PIOL was then assessed on tonic and phasic currents of cerebellar granule cells (CGCs), hippocampal pyramidal neurons and thalamic relay-neurons. In CGCs, 4-PIOL inhibited tonic currents, without affecting spontaneous inhibitory postsynaptic currents (sIPSCs); whereas in hippocampal and thalamic relay neurons, 4-PIOL enhanced, or reduced, tonic currents depending on the extrasynaptic GABA concentration, consistent with an action at extrasynaptic γ2-containing receptors. Moreover, 4-PIOL antagonised sIPSCs in these two brain regions, in accord with targeting presynaptic and postsynaptic GABAA receptors. In conclusion, the therapeutic potential of GABAA receptor partial agonists, such as 4-PIOL will be critically dependent on not only the ambient GABA concentration, but also on the relative expression of different GABAA receptor subtypes.
Quantitative interactions between Candida albicans and the mutans streptococci in patients with Down Syndrome

Background Oral microorganisms produce damage through the transfer to bloodstream, colonizing other tissues or direct damage in the oral cavity. Aim to study the quantitative interactions between C. albicans and the mutans streptococci and ms serotypes in the saliva of the oral cavity of patients with Down syndrome (DS). Material and Methods Included 120 patients of both genders, 60 patients with Down syndrome (DS) and 60 patients as a control group (CG). Samples of saliva were taken, and bacteria and fungi were grown on TYCSB and Saboureaud agar. Microbiological, serological and quantitative analyses were performed to determine the kind of isolated of microorganisms corresponding to the ms c, e, f and k for species S. mutans and d and g for S. sobrinus and C. albicans. Electronic scanning microscopy was employed to visualize and confirm the colonies under study. Statistics analysis included t-test proofs for matched data test, Scheffé and ANOVA. Results Forming units (CFU) per mL of saliva of C. albicans a significant difference was observed among DS>CG groups. A correlation of the C. albicans quantity and the ms count was found by age intervals however, tendencies were different in SD and CG. Also, the CFU of C. albicans was different among the serotypes of ms (c, e, f, k <d, g, h, <notyped). Conclusions These results show a significant non-random association between these two commensal microorganisms in different patient groups. Key words:Down Syndrome, Candida albicans, microorganism interactions, mutans streptococci and oral cavity.
Effects of behavioural parent training for children with attention-deficit/hyperactivity disorder on parenting behaviour: a protocol for an individual participant data meta-analysis

Introduction Behavioural parent training (BPT) is a well-established treatment for children with attention-deficit/hyperactivity disorder (ADHD). BPT is based on the hypothesis that improvements in parenting are mediators of improvements in children’s behaviours. However, meta-analyses show considerate heterogeneity in effects of BPT on child outcomes, and meta-analyses on parenting outcomes are scarce. Also, few studies have investigated parenting factors as mediators of child outcomes. This study aims to examine the effects and moderators of BPT on parenting outcomes and whether improvements in parenting mediate amelioration of behaviour and impairment in children with ADHD. Methods and analyses We will conduct an individual participant data meta-analysis (IPDMA), making use of individual data of existing trials, and giving the opportunity for highly powered moderator analyses. This IPDMA will be performed by the Psychosocial ADHD INTervention (PAINT) collaboration. We will include randomised controlled trials of BPT, for individuals with ADHD below 18 years old. Systematic searches have been performed to locate relevant papers. Authors are currently contacted to share their data with the PAINT-IPDMA project. We will examine effects of BPT on parenting outcomes (eg, positive and negative parenting, management of affect, perceived parenting competence, parenting stress), moderators of these effects (eg, parental depression, parenting stress, severity of the child’s ADHD symptoms) and subsequently perform mediation analyses where parenting outcomes are modelled as mediators of child outcomes (eg, symptoms and severity of ADHD, comorbid psychopathology and impairment). Ethics and dissemination We will include data from randomised control trials for which ethical approval has been received and consent forms have been signed. Deidentified data will be provided by the original investigators. We aim to disseminate our findings through peer-reviewed scientific journals, presentations at (inter)national scientific meetings, newsletters, the website of our project and the Dutch academic workspace ADHD. PROSPERO registration number CRD42017069877.
Karnofsky Performance Scale and Neurological Assessment of Neuro-Oncology Scale as Early Predictor in Glioma

Objective: Glioma is one of the most frequent and disabling primary brain tumour. Patients are not only dealing with survival, but also quality of life, which remains another major concern. Karnofsky Performance Scale (KPS) is one of the most commonly used scale to assess patients’ quality of life. A recent scale, known as Neurological Assessment of Neuro-Oncology Scale, has surfaced to examine neurological disability caused by brain tumour. Previous study showed this scale to be superior to KPS in predicting survival. However, these scales have never been used to foresee functional scale improvement during disease progression. We sought to determine whether initial KPS and NANO Scale can predict functional scale improvement 2 months after surgery. Methods: Patients with glioma grade II-IV were included in the study. IDH mutation and MGMT methylation were tested. KPS and NANO scale were examined before surgery and 2 months after surgery. Favorable outcome (FO) was defined as improvement in functional scale 2 months after surgery. Patients initial functional scales were analyzed towards favorable outcome. Results: Glioma WHO grade II, III and IV was found in 17 patients (36.2%), 3 patients (6.4%) and 27 patients (57.4%) respectively. Median KPS before and 2 months after surgery were 50 (30-80) and 60 (0-100), whereas median NANO scale before and 2 months after surgery were 5 (0-12) and 3 (0-12). Favorable outcome was found in 63.8% (KPS) and 78.7% (NANO Scale). Patients initial functional scales were significantly related to FO. Conclusion: Good initial functional scales are 4 to 5 times likely of having a favorable outcome 2 months after surgery.
End of Induction Patient Reported Outcomes Predict Clinical Remission but not Endoscopic Remission in Crohn's Disease.

BACKGROUND AND AIMS It is unclear however whether early symptom improvement in Crohn's disease (CD) provides any prognostic information for patients long-term. This paper aims to investigate the relationship between early patient reported outcomes (PROs) after completion of induction of infliximab and their relationship with long-term clinical remission (CR) and endoscopic remission (ER). METHODS This post-hoc analysis (Clinicaltrials.gov: NCT02096861) used data from 220 CD patients to evaluate the relationship of week 6 and 14 PRO variables and week 54 clinical remission (CR) (CDAI < 150), PRO2 remission (mean score abdominal pain (AP) ≤ 1 and stool frequency (SF) ≤ 1.5), and endoscopic remission (SES-CD < 3). Multivariable logistic regression models adjusted for confounders were used to assess the relationships between post-induction PROs and outcomes of interest. RESULTS Patients with moderate or severe AP after induction had reduced odds of achieving one-year CR and PRO2 remission compared to those with mild AP (aOR for CR 0.31, 95% CI 0.17-0.57, p=0.0002). Similarly, patients with moderate to severely elevated SF after induction had reduced odds of one-year CR and PRO2 remission compared to patients with less SF (aOR for CR 0.31, 95% CI 0.16-0.58, p=0.0003). No significant differences were found when comparing higher week 6 or 14 PRO scores of AP and/or SF to lower PRO scores in the odds of achieving one-year ER. CONCLUSIONS Post-induction PROs of AP and SF strongly predict likelihood of one-year CR but are not associated with one-year ER. Clinical symptoms alone should not be relied upon when assessing response to therapies for CD.
A New Catalog of Structural Variants in 1,301 A. thaliana Lines from Africa, Eurasia, and North America Reveals a Signature of Balancing Selection at Defense Response Genes

Abstract Genomic variation in the model plant Arabidopsis thaliana has been extensively used to understand evolutionary processes in natural populations, mainly focusing on single-nucleotide polymorphisms. Conversely, structural variation has been largely ignored in spite of its potential to dramatically affect phenotype. Here, we identify 155,440 indels and structural variants ranging in size from 1 bp to 10 kb, including presence/absence variants (PAVs), inversions, and tandem duplications in 1,301 A. thaliana natural accessions from Morocco, Madeira, Europe, Asia, and North America. We show evidence for strong purifying selection on PAVs in genes, in particular for housekeeping genes and homeobox genes, and we find that PAVs are concentrated in defense-related genes (R-genes, secondary metabolites) and F-box genes. This implies the presence of a “core” genome underlying basic cellular processes and a “flexible” genome that includes genes that may be important in spatially or temporally varying selection. Further, we find an excess of intermediate frequency PAVs in defense response genes in nearly all populations studied, consistent with a history of balancing selection on this class of genes. Finally, we find that PAVs in genes involved in the cold requirement for flowering (vernalization) and drought response are strongly associated with temperature at the sites of origin.
Measurement of Serum EGFR mRNA Expression is a Reliable Predictor of Treatment Response and Survival Outcomes in Non- Small Cell Lung Cancer

Background: EGFR over-expression plays a key role in the development and progression of lung cancer. However, its status as a prognostic biomarker for survival outcomes is unclear. Objectives: To evaluate the prognostic utility of serum EGFR mRNA expression in Non-Small cell lung cancer (NSCLC) for treatment response and survival. Methods: EGFR mRNA levels were determined in serum using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Based on ROC curve, a cut off value of 16.0-fold increase was selected to categorize patients into low EGFR (≤ 16.0) and high EGFR (> 16.0) groups. Results: A total of 350 subjects were included (78.3% males), with mean (± SD) age of 57.1 (± 11.2) years, and including 247 (70.6%) adenocarcinoma (ADC). Majority (73.1%) had metastatic (stage IV) disease. Patients had higher pre-treatment serum EGFR mRNA levels than controls [median fold-increase (min, max), 16.2 (1.9, 66.7). Serum EGFR mRNA levels significantly reduced in those who achieved objective response and disease control. Significantly longer OS and PFS was observed in subjects having baseline EGFR mRNA expression ≤ 16.0 fold- increase compared to those with > 16.0 fold- increase [median (95% CI) OS: 25.0 (14.9, NR) versus 7.7 (6.3, 8.9) months; HR (95% CI) 2.9 (2.3, 4.0), p< 0.001; and PFS: 9.9 (7.1, 11.5) versus 6.0 (4.1, 7.5) months; HR (95% CI) 1.8 (1.3, 2.4), p< 0.001]. Conclusion: Serum EGFR mRNA expression is a useful parameter for predicting treatment response and survival outcomes in NSCLC.
Severe fever with thrombocytopenia syndrome virus: a highly lethal bunyavirus

Abstract Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel bunyavirus. Since 2007, SFTS disease has been reported in China with high fatality rate up to 30%, which drew high attention from Centre for Disease Control and Prevention and government. SFTSV is endemic in the centra l and eastern China, Korea and Japan. There also have been similar cases reported in Vietnam. The number of SFTSV infection cases has a steady growth in these years. As SFTSV could transmitted from person to person, it will expose the public to infectious risk. In 2018 annual review of the Blueprint list of priority diseases, World Health Organisation has listed SFTSV infection as prioritised diseases for research and development in emergency contexts. However, the pathogenesis of SFTSV remains largely unclear. Currently, there are no specific therapeutics or vaccines to combat infections of SFTSV. This review discusses recent findings of epidemiology, transmission pathway, pathogenesis and treatments of SFTS disease.
Canal transportation using Mani GPR or HyFlex NT during the retreatment of curved root canals: A micro-computed tomographic study.

This study assessed the apical transportation using Mani GPR or HyFlex NT during the retreatment of curved root canals. Thirty-eight roots were analysed using micro-CT for the comparison of apical transportation produced by two retreatment systems. Longitudinal transportation, horizontal transportation, variation in the canal angle of curvature and variation in the canal/root width ratio were analysed. Longitudinal transportation was frequently observed, regardless of the system used. The canals retreated with Mani GPR showed a significantly higher horizontal transportation at 1 mm from the root apex (P < 0.01) and greater variation of the canal curvature angle (P < 0.01). The canal/root width ratio was similar between groups (P > 0.05). In conclusion, longitudinal transportation occurred more frequently in the mesial canal walls. Mani GPR showed greater horizontal transportation at 1 mm short of the apex, and higher variation of the canal curvature angle compared with HyFlex NT.