Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduced structural brain asymmetry during neonatal life is potentially related to autism spectrum disorders in children born extremely preterm

Disruption of the normal patterns of structural brain asymmetry, and in language‐related areas, has been reported in individuals with autism spectrum disorder (ASD). We tested the hypothesis that 16 children born extremely preterm (EPT), and diagnosed with ASD at 6.5 years of age (EPT‐ASD), would have different patterns of brain structural asymmetry, particularly in language‐related areas, to 21 EPT children without ASD and 15 term‐born children. They all underwent neonatal magnetic resonance imaging scans at 40 weeks of gestation. ASD diagnoses and the Weschler Intelligence Scale for Children—Fourth Edition, were performed in the EPT children, but not in the term group. Asymmetry indices (AIs) were assessed at three levels: global (hemispheres), lobar (brain lobes), and modular (primary sensorimotor, unimodal, and higher‐order association areas). AIs were also assessed in language‐related regions and correlational analyses were performed between these AIs and verbal scores. The EPT‐ASD group showed reduced structural asymmetry at the modular level, mainly involving the higher‐order association cortices and the language‐related areas. Predominant positive correlations between language functioning and leftward AIs in the inferior frontal gyrus (opercular) and supplementary cortices, and rightward asymmetry in the angular and supramarginal gyri, were identified in the EPT‐ASD group. The overall results suggest that reduced brain structural asymmetry identified during the neonatal period would be a risk factor for the development of ASD in EPT infants. This finding could identify EPT children at risk at an early stage, so that tailored interventions could be used to optimize their functions and quality of life. Autism Res 2019, 12: 1334–1343. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.
Hydrodynamics of Vortex Generation during Bell Contraction by the Hydromedusa Eutonina indicans (Romanes, 1876)

Swimming bell kinematics and hydrodynamic wake structures were documented during multiple pulsation cycles of a Eutonina indicans (Romanes, 1876) medusa swimming in a predominantly linear path. Bell contractions produced pairs of vortex rings with opposite rotational sense. Analyses of the momentum flux in these wake structures demonstrated that vortex dynamics related directly to variations in the medusa swimming speed. Furthermore, a bulk of the momentum flux in the wake was concentrated spatially at the interfaces between oppositely rotating vortices rings. Similar thrust-producing wake structures have been described in models of fish swimming, which posit vortex rings as vehicles for energy transport from locations of body bending to regions where interacting pairs of opposite-sign vortex rings accelerate the flow into linear propulsive jets. These findings support efforts toward soft robotic biomimetic propulsion.
Non‐equivalence in old‐ and new‐flagellum daughter cells of a proliferative division in Trypanosoma brucei

Differentiation of Trypanosoma brucei, a flagellated protozoan parasite, between life cycle stages typically occurs through an asymmetric cell division process, producing two morphologically distinct daughter cells. Conversely, proliferative cell divisions produce two daughter cells, which look similar but are not identical. To examine in detail differences between the daughter cells of a proliferative division of procyclic T. brucei we used the recently identified constituents of the flagella connector. These segregate asymmetrically during cytokinesis allowing the new‐flagellum and the old‐flagellum daughters to be distinguished. We discovered that there are distinct morphological differences between the two daughters, with the new‐flagellum daughter in particular re‐modelling rapidly and extensively in early G1. This re‐modelling process involves an increase in cell body, flagellum and flagellum attachment zone length and is accompanied by architectural changes to the anterior cell end. The old‐flagellum daughter undergoes a different G1 re‐modelling, however, despite this there was no difference in G1 duration of their respective cell cycles. This work demonstrates that the two daughters of a proliferative division of T. brucei are non‐equivalent and enables more refined morphological analysis of mutant phenotypes. We suggest all proliferative divisions in T. brucei and related organisms will involve non‐equivalence.
Lymphaticovenular anastomosis and venous arterialization in coexisting Raynaud's phenomenon and lymphedema: A case report

Raynaud's phenomenon is highly prevalent in the general population. The optimal medical management for patients with severe Raynaud's phenomenon remains unclear. Venous arterialization (VA) may be considered as a salvage procedure when no distal vessels are available for vascular reconstruction. Surgical treatments for lymphedema, including lymphovenous anastomosis (LVA), are becoming popular alternatives to conservative therapy. Here, we report on a patient with comorbid primary Raynaud's phenomenon and lymphedema in whom both VA and LVA were performed. The patient was a 60‐year‐old woman with an edematous right upper limb and pain and cold sensitivity in the middle, ring, and small fingers that was refractory to medication. Indocyanine green lymphography and computed tomography angiography suggested coexistence of lymphedema and primary Raynaud's phenomenon. VA and LVA were performed to reduce the risks of cellulitis and amputation. Computed tomography angiography was performed regularly after surgery to examine the arterialized venous system and Doppler echography to search for developing branches. Five months later, three branches of the arterialized veins that flowed proximally at the level of the hand and wrist were ligated. By around 1 year after surgery, the lymphedema index in the affected upper limb had improved from 116 to 103 and the patient's numerical rating scale score for intractable pain and cold sensitivity had improved from 6–7 to 1–2. We believe that the combination of VA and LVA in the early stages of primary Raynaud's phenomenon and lymphedema was effective in this case.
Boosting the apoptotic response of high‐grade serous ovarian cancers with CCNE1 amplification to paclitaxel in vitro by targeting APC/C and the pro‐survival protein MCL‐1

Ovarian cancer exhibits the highest mortality rate among gynecological malignancies. Antimitotic agents, such as paclitaxel, are frontline drugs for the treatment of ovarian cancer. They inhibit microtubule dynamics and their efficiency relies on a prolonged mitotic arrest and the strong activation of the spindle assembly checkpoint (SAC). Although ovarian cancers respond well to paclitaxel, the clinical efficacy is limited due to an early onset of drug resistance, which may rely on a compromised mitosis exit associated with weakend intrinsic apoptosis. Accordingly, we aimed at overcoming SAC silencing that occurs rapidly during paclitaxel‐induced mitotic arrest. To do this, we used a specific anaphase‐promoting complex/cyclosome (APC/C) inhibitor to prevent a premature mitotic exit upon paclitaxel treatment. Furthermore, we investigated the role of the antiapoptotic BCL‐2 family member MCL‐1 in determining the fate of ovarian cancer cells lines with CCNE1 amplification that are challenged with clinically relevant dose of paclitaxel. Using time‐laps microscopy, we demonstrated that APC/C and MCL‐1 inhibition under paclitaxel prevents mitotic slippage in ovarian cancer cell lines and restores death in mitosis. Consistent with this, the combinatorial treatment reduced the survival of ovarian cancer cells in 2D and 3D cell models. Since a therapeutic ceiling has been reached with taxanes, it is of utmost importance to develop alternative strategies to improve the patient's survival. Thus, our study provides not only elements to understand the causes of taxane resistance in CCNE1‐amplified ovarian cancers but also suggests a new combinatorial strategy that may improve paclitaxel‐based efficacy in this highly lethal gynecological disease.
Improved SH0 Guided Wave Transducers Based on Piezoelectric Fiber Patches †

A piezoelectric fiber patch (PFP) is a transducer type that is suitable for guided-wave-based structural health monitoring (SHM) due to its light, thin, and flexible characteristics. In our previous work, a PFP-based transducer design for selective excitation of the zero-order shear horizontal wave mode (SH0) was introduced (shear horizontal PFP (SHPFP)). In this work, two modified SH0 wave PFP transducer designs are proposed: the rounded corner design and the dual design. The degree of improvement is determined by a numerical simulation and the dual design—the design with the most promise—is experimentally realized. Laser Vibrometry measured the generated wave field, confirming the results from the simulation. The new designs can generate an almost pure SH0 wave. The dual design has a very strong directivity that is useful for several guided-wave-based SHM applications. The conclusions on the design’s properties as a transmitter are also valid for its properties as a sensor due to the reciprocity of piezoelectric transducers.
Correlates between Five‐Factor Model traits and the Revised Diagnostic Interview for Borderlines dimensions in an adolescent clinical sample

Abstract Objective Extensive evidence supports the association between Five‐Factor Model (FFM) traits involving high neuroticism, low agreeableness and low conscientiousness and borderline personality disorder (BPD) characteristics, particularly among adults in community samples. However, studies supporting this link in adolescent samples are relatively limited, and few studies have examined the links between FFM traits and specific dimensions of BPD, such as those distinguished by the Revised Diagnostic Interview for Borderlines (DIB‐R). In this study, we examined associations between FFM traits and BPD characteristics in a group of clinical and non‐clinical adolescents. Method We evaluated the correlations between the FFM personality traits, as measured by the NEO‐Five‐Factor Inventory and BPD characteristics as measured by the DIB‐R in a sample of adolescents (N = 162). Results Consistent with previous research, BPD dimensions were highly associated with high neuroticism, low conscientiousness, low agreeableness and to a somewhat lesser extent with low extraversion. Specificity of associations between FFM traits and DIB‐R section scores was limited, in part because of strong intercorrelations among DIB‐R scores. Discussion These results imply that evidence about trait–BPD associations in adult samples generalizes well to adolescents. Clinical implications of these findings are discussed.
Amyotrophic lateral sclerosis as a multi-step process: an Australia population study

Abstract Objective: This study sought to investigate whether a multistep process was also evident in an Australian amyotrophic lateral sclerosis (ALS) population. Methods: Mortality rates for ALS patients (years 2007–2016) were obtained from the Australian Institute of Health and Welfare (AIHW). The log incidence of ALS, as reflected by crude mortality rates, was regressed against log of age disease onset. Results: From a total population of 24 million, 6524 cases of ALS were identified. A linear relation between the log incidence and log age was identified, with r2 value of 0.99, indicating that ALS is a multistep process. The linear slope estimate was 5.0, suggesting that six steps were required for development of ALS. Conclusions: This study established a linear relationship between log incidence and log age onset in an Australia ALS population, consistent with a multistep process. Identification of these steps will likely be of therapeutic benefit in ALS.
Neoadjuvant Three-Dimensional Conformal Radiotherapy for Resectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Randomized, Open-Label, Multicenter Controlled Study

PURPOSE To compare the survival outcomes of neoadjuvant three-dimensional conformal radiotherapy (RT) followed by hepatectomy with hepatectomy alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). PATIENTS AND METHODS A randomized, multicenter controlled study was conducted from January 2016 to December 2017 in patients with resectable HCC and PVTT. Patients were randomly assigned to receive neoadjuvant RT followed by hepatectomy (n = 82) or hepatectomy alone (n = 82). The modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines were used to evaluate the therapeutic effects of RT. The primary end point was overall survival. The expression of interleukin-6 (IL-6) in patients’ serum before RT and in surgical specimens was correlated with response to RT. RESULTS In the neoadjuvant RT group, 17 patients (20.7%) had partial remission. The overall survival rates for the neoadjuvant RT group at 6, 12, 18, and 24 months were 89.0%, 75.2%, 43.9%, and 27.4%, respectively, compared with 81.7%, 43.1%, 16.7%, and 9.4% in the surgery-alone group (P < .001). The corresponding disease-free survival rates were 56.9%, 33.0%, 20.3%, and 13.3% versus 42.1%, 14.9%, 5.0%, and 3.3% (P < .001). On multivariable Cox regression analyses, neoadjuvant RT significantly reduced HCC-related mortality and HCC recurrence rates compared with surgery alone (hazard ratios, 0.35 [95% CI, 0.23 to 0.54; P < .001] and 0.45 [95% CI, 0.31 to 0.64; P < .001]). Increased expressions of IL-6 in pre-RT serum and tumor tissues were significantly associated with resistance to RT. CONCLUSION For patients with resectable HCC and PVTT, neoadjuvant RT provided significantly better postoperative survival outcomes than surgery alone. IL-6 may predict response to RT in these patients.
C‐reactive protein for risk prediction of post‐operative delirium and post‐operative neurocognitive disorder

Post‐operative delirium (POD) and post‐operative neurocognitive disorder (NCD) are frequently seen in the elderly. Development of biomarkers for pre‐operative risk prediction is of major relevance. As inflammation present before surgery might predispose to POD and post‐operative NCD development, we aim to determine associations between pre‐operative C‐reactive protein (CRP) and the incidence of POD and post‐operative NCD.
Self-exercise programs and occlusal splints in the treatment of TMD-related myalgia - evidence based medicine?

BACKGROUND The low cost, and reversible treatments concerning disorders of the masticatory muscles represent a vast array of regimens. Common treatments include information, stretching exercises, manual therapy, acrylic splints and cognitive behavioural therapy. OBJECTIVE The aim of this study was to evaluate the evidence behind the use of self-exercising programs and occlusal splints in the treatment of myofascial pain. METHODS We conducted a thorough search of five databases, using four cardinal search terms in combination with twelve supporting terms. We also assessed the evidence quality, using GRADEpro software. RESULTS The search resulted in 4967 individual studies. 18 studies met the inclusion criteria, and were re-evaluated. CONCLUSION The selected studies were in favour of a self-care or an occlusal splint treatment of myalgia. However, a GRADE assessment showed that 14 of the 18 selected studies had low or very low evidence quality. Studies also showed weaknesses with regard to nomenclature and reproducibility. Hence it is our professional opinion that the evidence level for prescribing self-exercises and occlusal splints in the treatment of myalgia is low. This article is protected by copyright. All rights reserved.
Comparative in Vitro Cytotoxicity of Realistic Doses of Benchmark Multi-Walled Carbon Nanotubes towards Macrophages and Airway Epithelial Cells

Multi-walled carbon nanotubes (MWCNT) have many outstanding physical and chemical properties that make them useful in many applications in nanotechnology. However, these properties are reported to be potentially harmful for the human body. The effects of low and realistic doses of three well-characterized preparations of MWCNT, obtained from the Joint Research Centre (JRC) (NM-400, NM-401, and NM-402), were assessed in two murine macrophage lines, Raw264.7, of peritoneal origin, and MH-S, derived from alveolar macrophages. Macrophage viability, evaluated with two distinct methods, was significantly lowered by NM-401 (needle-like, average length 4 μm, diameter 67 nm) with IC50 values of 10 μg/cm2, whereas NM-400 and NM-402 (tangled, average lengths 846–1372 nm, diameter 11 nm) had much smaller effects. In contrast, at 10 μg/cm2, NM-400 and NM-402 induced the M1 marker Nos2 and, consistently, a sizable accumulation of nitrites in the medium, whereas NM-401 had no significant effect. None of the MWCNT preparations induced the M2 marker Arg1. Phagocytic activity, assessed in Raw264.7 macrophages, was significantly reduced in cells exposed to NM-401, but not to NM-400 or NM-402. When tested on Calu-3 bronchial epithelial cell monolayers, the three MWCNT preparations did not affect cell viability, but decreased the trans-epithelial electrical resistance at the maximal dose tested (80 μg/cm2), with the most evident effect detected for NM-401, even at 10 μg/cm2. In conclusion, among the possible structural determinants of the toxic effects exerted by MWCNT towards macrophages and airway epithelial cells, shape and length appear the most relevant at low, realistic doses.
Effectiveness, Feasibility, and Acceptability of Dynamic Elastomeric Fabric Orthoses (DEFO) for Managing Pain, Functional Capacity, and Quality of Life during Prenatal and Postnatal Care: A Systematic Review

Conservative interventions for addressing prenatal and postnatal ailments have been described in the research literature. Research results indicated that maternity support belts assist with reducing pain and other symptoms in these phases; however, compliance in wearing maternity support belts is poor. To combat poor compliance, commercial manufacturers designed dynamic elastomeric fabric orthoses (DEFO)/compression garments that target prenatal and postnatal ailments. This systematic review aimed to identify, critically appraise, and synthesize key findings on the effectiveness, the feasibility, and the acceptability of using DEFO to manage ailments during pre-natal and postnatal phases of care. Electronic databases were systematically searched to identify relevant studies, resulting in 17 studies that met the eligibility criteria. There were variations in DEFO descriptors, including hosiery, support belts, abdominal binders and more, making it difficult to compare findings from the research articles regarding value of DEFO during prenatal and/or postnatal phases. A meta-synthesis of empirical research findings suggests wearing DEFOs during pregnancy has a significant desirable effect for managing pain and improving functional capacity. Further research is required to investigate the use of DEFOs for managing pain in the postnatal period and improving quality life during prenatal and postnatal care.
Interferon-Stimulated Genes: What Do They All Do?

In the absence of an intact interferon (IFN) response, mammals may be susceptible to lethal viral infection. IFNs are secreted cytokines that activate a signal transduction cascade leading to the induction of hundreds of interferon-stimulated genes (ISGs). Remarkably, approximately 10% of the genes in the human genome have the potential to be regulated by IFNs. What do all of these genes do? It is a complex question without a simple answer. From decades of research, we know that many of the protein products encoded by these ISGs work alone or in concert to achieve one or more cellular outcomes, including cell intrinsic antiviral defense, antiproliferative activities, and stimulation of adaptive immunity. The focus of this review is the antiviral activities of the IFN/ISG system. This includes general paradigms of ISG function, supported by specific examples in the literature, as well as methodologies to identify and characterize ISG function. Expected final online publication date for the Annual Review of Virology Volume 6 is September 30, 2019. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Caffeine, type of coffee and risk of ovarian cancer: a dose-response meta-analysis of prospective studies.

CONTEXT Prospective studies on caffeine and different types of coffee intake in relation to the risk of ovarian cancer have shown conflicting results. OBJECTIVE The aim of this study was to perform a dose-response meta-analysis of cohort studies on the association between dietary caffeine intake, different types of coffee consumption and risk of ovarian cancer. DATA SOURCES PubMed/Medline, ISI Web of Science, Scopus and EMBASE were searched to identify relevant articles published until October 2018. STUDY SELECTION Prospective cohort studies that considered caffeine and different types of coffee as the exposure variable and ovarian cancer as the main outcome variable or as one of the outcome variables were included in this systematic review and meta-analysis. Two authors independently screened 9344 publications. A total of 14 cohort studies were included in the meta-analysis. DATA EXTRACTION Two authors independently extracted the data. Any disagreements were resolved in consultation with the principal investigator. RESULTS In total, 940359 participants, including 4434 subjects with ovarian cancer, aged >20 years were included in this systematic review and meta-analysis. Combining 13 effect sizes, we found no significant association between coffee consumption and risk of ovarian cancer (RR: 1.08; 95% CI: 0.89, 1.33). Also, one additional cup per day of coffee consumption was marginally significantly associated with increased risk of ovarian cancer (RR: 1.02; 95% CI: 0.99, 1.05; P=0.21; I2=0.0%; Pheterogeneity=0.68). No significant association was observed between caffeine intake, caffeinated or decaffeinated coffee consumption and risk of ovarian cancer. CONCLUSIONS We found no significant association between caffeine, different types of coffee and risk of ovarian cancer.
The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation

The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of proinflammatory cytokines IL-1β/IL-18 in response to microbial infection and cellular damage. However, the aberrant activation of the NLRP3 inflammasome has been linked with several inflammatory disorders, which include cryopyrin-associated periodic syndromes, Alzheimer’s disease, diabetes, and atherosclerosis. The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage have been shown to trigger its activation. How NLRP3 responds to those signaling events and initiates the assembly of the NLRP3 inflammasome is not fully understood. In this review, we summarize our current understanding of the mechanisms of NLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3.