Miracle-dz/UniFAR-FTUs huggingface dataset:
In Utero Exposure to Benzo[a]pyrene Induces Ovarian Mutations at Doses That Deplete Ovarian Follicles in Mice

Polycyclic aromatic hydrocarbons like benzo[a]pyrene (BaP) are ubiquitous environmental contaminants formed during incomplete combustion of organic materials. Our prior work showed that transplacental exposure to BaP depletes ovarian follicles and increases prevalence of epithelial ovarian tumors later in life. We used the MutaMouse transgenic rodent model to address the hypothesis that ovarian mutations play a role in tumorigenesis caused by prenatal exposure to BaP. Pregnant MutaMouse females were treated with 0, 10, 20, or 40 mg/(kg day) BaP orally on gestational days 7–16, covering critical windows of ovarian development. Female offspring were euthanized at 10 weeks of age; some ovaries with oviducts were processed for follicle counting; other ovaries/oviducts and bone marrow were processed for determination of lacZ mutant frequency (MF). Mutant plaques were pooled within dose groups and sequenced to determine the mutation spectrum. BaP exposure caused highly significant dose‐related decreases in ovarian follicles and increases in ovarian/oviductal and bone marrow mutant frequencies at all doses. Absence of follicles, cell packets, and epithelial tubular structures were observed with 20 and 40 mg/(kg day) BaP. Depletion of ovarian germ cells was inversely associated with ovarian MF. BaP induced primarily G > T and G > C transversions and deletions in ovaries/oviducts and bone marrow cells and produced a mutation signature highly consistent with that of tobacco smoking in human cancers. Overall, our results show that prenatal BaP exposure significantly depletes ovarian germ cells, causes histopathological abnormalities, and increases the burden of ovarian/oviductal mutations, which may be involved in pathogenesis of epithelial ovarian tumors. Environ. Mol. Mutagen. 60:410–420, 2019. © 2018 Her Majesty the Queen in Right of Canada
Long-Term Follow-Up of Cyclic Esotropia

ABSTRACT Background and Purpose: To describe the development and treatment of patients with cyclic esotropia. Patients and Methods: The clinical course of seven patients with cyclic esotropia were retrospectively reviewed and described. All patients underwent bilateral medial rectus recession based on the deviation manifested on the day they were esotropic. Additionally, one patient had previously undergone surgery for intermittent exotropia. Results: All patients developed excellent postoperative alignment. After strabismus surgery, normal eye alignment with some degree of binocularity was reached in five patients. Moreover, there was no recurrence of the cyclic deviation in any patient, and no patient experienced an overcorrection. Conclusions: Strabismus surgery aimed to correct the horizontal esotropic angle present on the day the esotropia is manifested provides a good outcome that is stable long-term, with minimal risk of overcorrection. Possible explanations for the origin of cyclic esotropia are discussed.
Complex regional pain syndrome and functional neurological disorders – time for reconciliation

There have been many articles highlighting differences and similarities between complex regional pain syndrome (CRPS) and functional neurological disorders (FND) but until now the discussions have often been adversarial with an erroneous focus on malingering and a view of FND as ‘all in the mind’. However, understanding of the nature, frequency and treatment of FND has changed dramatically in the last 10–15 years. FND is no longer assumed to be only the result of ‘conversion’ of psychological conflict but is understood as a complex interplay between physiological stimulus, expectation, learning and attention mediated through a Bayesian framework, with biopsychosocial predisposing, triggering and perpetuating inputs. Building on this new ‘whole brain’ perspective of FND, we reframe the debate about the ‘psychological versus physical’ basis of CRPS. We recognise how CRPS research may inform mechanistic understanding of FND and conversely, how advances in FND, especially treatment, have implications for improving understanding and management of CRPS.
Content Matters, a Qualitative Analysis of Verbal Hallucinations

Auditory verbal hallucinations have traditionally especially been researched from a form-based approach, with content getting much less attention. In this article, we argue for the importance of looking at content to get a fuller understanding of the hallucinatory experience. Guided by Lacanian psychoanalysis, we conducted a thematic and a narrative analysis on interviews with 10 schizophrenic patients about their hallucinations. We discerned five themes in the data, which were based on Lacanian theory and had to do with existential questions: parenthood and authority, sexuality and relationships, gender identity, life in the light of death, and what does the other want? Furthermore, we added a theme for unclassified content. Narratively, we found that participants constructed a story of four steps about their hallucinatory experiences. These steps were disturbing events in the past posing an existential question, triggering event, period of confusion, and hearing voices that allude to existential themes. Participants succeed in different degrees in integrating their hallucinatory experiences in their own life history. These stories can be situated on a continuum by making use of three prototypical narrating styles: the meta-delusional, delusional, and chaotic narrative type. Overall, our analysis shows that hallucinations can both be thematically and narratively organized, by making use of a theoretical framework like Lacanian psychoanalysis. Our research demonstrates that hallucinatory contents are not random but are about existential issues imbedded in a life narrative. Future research would benefit of integrating content and form-based approaches.
The Diagnostic Value of Irisin in Pediatric Patients with Acute Abdominal Pain

Objectives Diagnosis of pediatric patients presenting to the Emergency Department with acute abdominal pain is not always easy. The purpose of this study was to investigate the effectiveness of irisin, a peptide hormone with reactivity shown in the appendix and neutrophils, in the differential diagnosis of pediatric patients with acute abdominal pain. Methods 162 subjects consenting to participate, including 112 patients presenting to the Pediatric Emergency and Pediatric Surgery clinics with acute abdominal pain and 50 controls, were enrolled in the study. Blood was collected from all patients following initial examination for irisin, WBC, and CRP investigation. Results Mean irisin levels in cases of acute appendicitis (AA) and perforated appendicitis (PA) were statistically significantly higher compared to nonspecific abdominal pains and the control group. No statistically significant difference was observed in irisin levels between AA and PA cases. WBC and CRP levels were also significantly higher in cases of AA and PA compared to nonspecific abdominal pains. Conclusions Differential diagnosis of acute abdominal pains in children and deciding on surgery are a difficult and complex process. Our study shows that irisin can be a useful biomarker in differentiating AA and PA from other acute abdominal pains in children.
CRISPR/Cas9-mediated homology-directed repair by ssODNs in zebrafish induces complex mutational patterns resulting from genomic integration of repair-template fragments

ABSTRACT Targeted genome editing by CRISPR/Cas9 is extremely well fitted to generate gene disruptions, although precise sequence replacement by CRISPR/Cas9-mediated homology-directed repair (HDR) suffers from low efficiency, impeding its use for high-throughput knock-in disease modeling. In this study, we used next-generation sequencing (NGS) analysis to determine the efficiency and reliability of CRISPR/Cas9-mediated HDR using several types of single-stranded oligodeoxynucleotide (ssODN) repair templates for the introduction of disease-relevant point mutations in the zebrafish genome. Our results suggest that HDR rates are strongly determined by repair-template composition, with the most influential factor being homology-arm length. However, we found that repair using ssODNs does not only lead to precise sequence replacement but also induces integration of repair-template fragments at the Cas9 cut site. We observed that error-free repair occurs at a relatively constant rate of 1-4% when using different repair templates, which was sufficient for transmission of point mutations to the F1 generation. On the other hand, erroneous repair mainly accounts for the variability in repair rate between the different repair templates. To further improve error-free HDR rates, elucidating the mechanism behind this erroneous repair is essential. We show that the error-prone nature of ssODN-mediated repair, believed to act via synthesis-dependent strand annealing (SDSA), is most likely due to DNA synthesis errors. In conclusion, caution is warranted when using ssODNs for the generation of knock-in models or for therapeutic applications. We recommend the application of in-depth NGS analysis to examine both the efficiency and error-free nature of HDR events. This article has an associated First Person interview with the first author of the paper. Summary: NGS-based analysis reveals that CRISPR/Cas9-induced double-strand-break repair using single-stranded repair templates is error prone in zebrafish, resulting in complex patterns of integrated repair-template fragments.
The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome

Post-exertional malaise, or a variation of this term, is a key symptom of myalgic encephalomyelitis and chronic fatigue syndrome, as this symptom is mentioned in almost all myalgic encephalomyelitis and chronic fatigue syndrome case definitions. Until now there has not been a comprehensive questionnaire to assess post-exertional malaise. To rectify this situation, in this article we describe the development of a new questionnaire, called the DePaul Post-Exertional Malaise Questionnaire, which was based on input from hundreds of patients. Preliminary validation was provided by the findings of significant and predictable relationships between different domains of this post-exertional malaise questionnaire and physical functioning.
Ascending flight and decelerating vertical glides in Anna's hummingbirds

ABSTRACT Hummingbirds are observationally well known for their capacity to vertically ascend whilst hovering, but the underlying mechanics and possible energetic limits to ascent rates are unclear. Decelerations during vertical ascent to a fixed target may also be associated with specific visual responses to regulate the body's trajectory. Here, we studied climbing flight and subsequent deceleration in male Anna's hummingbirds (Calypte anna) over an approximately 2 m vertical distance. Birds reached vertical speeds and accelerations up to ∼4 m s−1 and 10 m s−2, respectively, through the use of flapping frequencies as high as 56 Hz and stroke amplitudes slightly greater than 180 deg. Total mass-specific power at maximal ascent speed was up to 92 W kg−1 body mass. Near the end of the ascending trajectory, all individuals decelerated ballistically via cessation of flapping and folding of wings over the body without losing control, a behavior termed here a vertical glide. Visual modulation of the deceleration trajectory during ascent was indicated by a constant value (∼0.75) for the first derivative of the time-to-contact to target. Our results indicate that hummingbirds in rapid vertical ascent expended near-maximal power output during flight, but also tightly controlled their subsequent deceleration during the vertical glide. Summary: During rapid ascending flights, Anna's hummingbirds exert near-maximal power expenditure, and then decelerate by folding their wings over the body to adopt a ballistic posture.
Endovascular Thrombectomy for Mild Strokes: How Low Should We Go? A Multicenter Cohort Study

Background and Purpose— Endovascular thrombectomy (EVT) is effective for acute ischemic stroke with large vessel occlusion and National Institutes of Health Stroke Scale (NIHSS) ≥6. However, EVT benefit for mild deficits large vessel occlusions (NIHSS, <6) is uncertain. We evaluated EVT efficacy and safety in mild strokes with large vessel occlusion. Methods— A retrospective cohort of patients with anterior circulation large vessel occlusion and NIHSS <6 presenting within 24 hours from last seen normal were pooled. Patients were divided into 2 groups: EVT or medical management. Ninety-day mRS of 0 to 1 was the primary outcome, mRS of 0 to 2 was the secondary. Symptomatic intracerebral hemorrhage was the safety outcome. Clinical outcomes were compared through a multivariable logistic regression after adjusting for age, presentation NIHSS, time last seen normal to presentation, center, IV alteplase, Alberta Stroke Program early computed tomographic score, and thrombus location. We then performed propensity score matching as a sensitivity analysis. Results were also stratified by thrombus location. Results— Two hundred fourteen patients (EVT, 124; medical management, 90) were included from 8 US and Spain centers between January 2012 and March 2017. The groups were similar in age, Alberta Stroke Program early computed tomographic score, IV alteplase rate and time last seen normal to presentation. There was no difference in mRS of 0 to 1 between EVT and medical management (55.7% versus 54.4%, respectively; adjusted odds ratio, 1.3; 95% CI, 0.64–2.64; P=0.47). Similar results were seen for mRS of 0 to 2 (63.3% EVT versus 67.8% medical management; adjusted odds ratio, 0.9; 95% CI, 0.43–1.88; P=0.77). In a propensity matching analysis, there was no treatment effect in 62 matched pairs (53.5% EVT, 48.4% medical management; odds ratio, 1.17; 95% CI, 0.54–2.52; P=0.69). There was no statistically significant difference when stratified by any thrombus location; M1 approached significance (P=0.07). Symptomatic intracerebral hemorrhage rates were higher with thrombectomy (5.8% EVT versus 0% medical management; P=0.02). Conclusions— Our retrospective multicenter cohort study showed no improvement in excellent and independent functional outcomes in mild strokes (NIHSS, <6) receiving thrombectomy irrespective of thrombus location, with increased symptomatic intracerebral hemorrhage rates, consistent with the guidelines recommending the treatment for NIHSS ≥6. There was a signal toward benefit with EVT only in M1 occlusions; however, this needs to be further evaluated in future randomized control trials.
Environmental, behavioural and multicomponent interventions to reduce adults' sitting time: a systematic review and meta-analysis

Objective To examine the overall effectiveness of interventions for reducing adult sedentary behaviour and to directly compare environmental, behavioural and multicomponent interventions. Design Intervention systematic review with meta-analysis. Data sources Ovid PsycINFO, Ovid MEDLINE, EBSCOHost CINAHL, EBSCOHost SPORTDiscus and PubMed were searched from inception to 26 July 2017. Eligibility criteria Trials including randomised controlled trials, quasi-randomised, cluster-randomised, parallel group, prepost, factorial and crossover trials where the primary aim was to change the sedentary behaviour of healthy adults assessed by self-report (eg, questionnaires, logs) or objective measures (eg, accelerometry). Results Thirty-eight trials of 5983 participants published between 2003 and 2017 were included in the qualitative synthesis; 35 studies were included in the quantitative analysis (meta-analysis). The pooled effect was a significant reduction in daily sitting time of −30.37 min/day (95% CI −40.86 to −19.89) favouring the intervention group. Reductions in sitting time were similar between workplace (−29.96 min/day; 95% CI −44.05 to –15.87) and other settings (−30.47 min/day; 95% CI −44.68 to –16.26), which included community, domestic and recreational environments. Environmental interventions had the largest reduction in daily sitting time (−40.59 min/day; 95% CI −61.65 to –19.53), followed by multicomponent (−35.53 min/day; 95% CI −57.27 to –13.79) and behavioural (−23.87 min/day; 95% CI −37.24 to –10.49) interventions. Conclusion Interventions targeting adult sedentary behaviour reduced daily sitting time by an average of 30 min/day, which was likely clinically meaningful.
Associations Between Characteristics of Obstructive Sleep Apnea and Nocturnal Blood Pressure Surge

Research suggests that oxygen desaturation and sleep stage during obstructive sleep apnea (OSA) are related to the magnitude of high blood pressure (BP) in a laboratory setting. However, in a clinical setting, these associations have not been well studied. We used a noninvasive oscillometric BP measurement device to investigate the association between oxygen-triggered BP levels at the end of each OSA episode and the characteristics of the preceding OSA episode. In 42 newly diagnosed OSA patients (average age, 63.5±12.5 years; average apnea-hypopnea index, 32.6±18.2 per hour), 258 BP measurements were obtained at the end of OSA episodes. Hypoxia-peak systolic BP (SBP), defined as the maximum oxygen-triggered SBP value, was significantly higher in rapid eye movement sleep (144.9±19.9 mm Hg) than in non–rapid eye movement stage 1 sleep (129.5±15.1 mm Hg; P<0.001) and non–rapid eye movement stage 2 sleep (129.4±14.7 mm Hg; P<0.001). In a multivariate-linear mixed model, the lowest oxygen saturation percentage during each OSA episode was associated with increased hypoxia-peak SBP (−0.501 mm Hg; P<0.001), nocturnal SBP surge (−0.395 mm Hg; P<0.001), defined as the difference between the hypoxia-peak SBP and the mean nocturnal SBP, and maximum value of SBP surge (−0.468 mm Hg; P<0.001), defined as the difference between the hypoxia-peak SBP and the minimum nocturnal SBP independent of sleep stage. These values were not associated with the duration of each OSA episode. The contribution of rapid eye movement sleep and severe oxygen desaturation to OSA-related BP elevation measured with a noninvasive oscillometric method was determined in a clinical setting.
Breast cancer risk among women under 55 years of age by joint effects of usage of oral contraceptives and hormone replacement therapy

Objective: To assess effects on breast cancer risk of exposure to both oral contraceptives and menopausal hormones, an increasingly common exposure. Design: A case-control study of breast cancer among women under the age of 55 years in Atlanta, GA involving 1,031 cases and 919 population controls was conducted. Results: Ever use of oral contraceptives was associated with a relative risk of 1.1 (95% 0.9-1.4), whereas the relative risk for hormone replacement therapy was 0.9 (95% CI 0.7-1.2). Seventeen percent of the cases versus 19% of the population controls reported exposure to both agents, resulting in a relative risk of 1.0 (95% CI 0.7-1.4) relative to those unexposed to either preparation. Although there was little variation in risk associated with joint effects by either age or race, there were statistically nonsignificant elevations in risk for this exposure among women who had experienced a natural menopause (relative risk = 2.0, 95% CI 0.7-5.6), were relatively thin (relative risk = 1.5, 0.8-3.0), or who had a first degree relative with breast cancer (relative risk = 2.0, 0.6-7.0). When joint effects of longer term use of both agents were considered, subjects who reported use of oral contraceptives for 10 or more years and hormone replacement for 3 or more years had a relative risk of 3.2 (95% CI 1.4-7.4) compared with nonusers of either preparation. Conclusions: Although our results must be cautiously interpreted given small numbers within subgroups, they raise concern and emphasize the need for further evaluation on breast cancer risk of the increasingly common exposure to both oral contraceptives and hormone replacement therapy.
An update on adaptive deep brain stimulation in Parkinson's disease

Advancing conventional open‐loop DBS as a therapy for PD is crucial for overcoming important issues such as the delicate balance between beneficial and adverse effects and limited battery longevity that are currently associated with treatment. Closed‐loop or adaptive DBS aims to overcome these limitations by real‐time adjustment of stimulation parameters based on continuous feedback input signals that are representative of the patient's clinical state. The focus of this update is to discuss the most recent developments regarding potential input signals and possible stimulation parameter modulation for adaptive DBS in PD. Potential input signals for adaptive DBS include basal ganglia local field potentials, cortical recordings (electrocorticography), wearable sensors, and eHealth and mHealth devices. Furthermore, adaptive DBS can be applied with different approaches of stimulation parameter modulation, the feasibility of which can be adapted depending on specific PD phenotypes. Implementation of technological developments like machine learning show potential in the design of such approaches; however, energy consumption deserves further attention. Furthermore, we discuss future considerations regarding the clinical implementation of adaptive DBS in PD. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Positive expression of chemokine (C-C Motif) ligand 18 and prognosis in cancer: A meta-analysis.

PURPOSE Chemokine (C-C Motif) Ligand 18 (CCL18) is a chemotactic cytokine involved in the pathogenesis and progression of various cancers by activating downstream signaling pathways and affecting cellular behaviors. We conducted a meta-analysis to evaluate the CCL18 as a prognostic marker for cancer and determine the relationship between CCL18 and clinicopathological features of cancer. METHODS We searched the PubMed, Cochrane, Embase, Web of Science and SinoMed databases for publications to investigate the association between CCL18 expression and survival outcome in cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) of overall survival (OS) were pooled. Odds ratios (ORs) of clinicopathological features were computed. Meta-analysis was performed using STATA 12.0 software. RESULTS Our meta-analysis identified a total of 17 studies including 2829 cases. Meta-analysis revealed that the expression of CCL18 in various cancer tissues was significantly higher than that in the normal group (OR=16.694, 95% CI=14.117-27.476, p<0.01, random effects). The abnormal expression of CCL18 was associated with lymph node metastasis (OR=4.409, 95% CI=2.129-9.128, p<0.01, random effects) and TNM stage (breast cancer subgroup: III+IV vs I+II OR=13.187, 95% CI=8.417-20.660, p<0.01; gastric cancer subgroup: III+IV vs I+II OR=0.034, 95% CI=0.008-0.137, p<0.01) but is was not related to gender (male vs. female: OR=0.88, 95% CI=0.667-1.162, p=0.368) and age (>60 vs. ≤60 years: OR=1.118, 95% CI=0.795-1.571, p-0.522). CCL18 overexpression was associated with poor overall prognosis of breast cancer (Hazard Ratio/HR=2.969, 95% CI=1.361- 6.478, p<0.01, random effects). CONCLUSIONS CCL18 is highly expressed in cancer tissues and is closely related to tumor metastasis and prognosis, and its role in tumor development is worth of further study.
A Gaussian Process perspective on Convolutional Neural Networks

In this paper we cast the well-known convolutional neural network in a Gaussian process perspective. In this way we hope to gain additional insights into the performance of convolutional networks, in particular understand under what circumstances they tend to perform well and what assumptions are implicitly made in the network. While for fully-connected networks the properties of convergence to Gaussian processes have been studied extensively, little is known about situations in which the output from a convolutional network approaches a multivariate normal distribution.