Miracle-dz/UniFAR-FTUs huggingface dataset:
Cat eye syndrome chromosome breakpoint clustering: identification of two intervals also associated with 22q11 deletion syndrome breakpoints

The supernumerary cat eye syndrome (CES) chromosome is dicentric, containing two copies of 22pter→q11.2. We have found that the duplication breakpoints are clustered in two intervals. The more proximal, most common interval is the 450–650 kb region between D22S427 and D22S36, which corresponds to the proximal deletion breakpoint interval found in the 22q11 deletion syndrome (DiGeorge/velocardiofacial syndrome). The more distal duplication breakpoint interval falls between CRKL and D22S112, which overlaps with the common distal deletion interval of the 22q11 deletion syndrome. We have therefore classified CES chromosomes into two types based on the location of the two breakpoints required to generate them. The smaller type I CES chromosomes are symmetrical, with both breakpoints located within the proximal interval. The larger type II CES chromosomes are either asymmetrical, with one breakpoint located in each of the two intervals, or symmetrical, with both breakpoints located in the distal interval. The co-localization of the breakpoints of these different syndromes, plus the presence of low-copy repeats adjacent to each interval, suggests the existence of several specific regions of chromosomal instability in 22q11.2 which are involved in the production of both deletions and duplications. Since the phenotype associated with the larger duplication does not appear to be more severe than that of the smaller duplication, determination of the type of CES chromosome does not currently have prognostic value.
Restate the reference for EEG microstate analysis

Despite the decades of efforts, the choice of EEG reference is still a debated fundamental issue. Non-neutral reference can inevitably inject the uncontrolled temporal biases into all EEG recordings, which may influence the spatiotemporal analysis of brain activity. A method, termed microstates, identifying spatiotemporal EEG features as the quasi-stable topography states in milliseconds, suggests its potential as biomarkers of neurophysiological disease. As reference electrode standardization technique (REST) could reconstruct an infinity reference approximately, it is a question whether REST or the other references will be more reliable than average reference (AR) for the microstates analysis. In this study, we design the microstate-based EEG forward model, and apply different references for microstates analysis. The spatial similarity between the generated and assumed cluster maps is mainly investigated. Furthermore, the real EEG data by the parametric bootstrap method is used to validate the performance of the references. Finally, we find that REST is robust to recover more similar cluster maps to the assumption than AR in the simulation, and the cluster maps between REST and AR on the real EEG data are quite different. This study may indicate that REST contributes to identifying more objective microstates features than AR.
Physical Activity and Abdominal Fat Distribution in Greenland

Purpose We examined how total volume of physical activity and reallocation of time spent at various objectively measured intensities of physical activity (PA) were associated with overall and abdominal fat distribution in adult Inuit in Greenland. Methods Data were collected as part of a countrywide cross-sectional health survey in Greenland. A combined accelerometer and HR monitor measured total physical activity energy expenditure (PAEE) and intensities of PA (N = 1536). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were assessed by ultrasonography. Isotemporal substitution modeling was used to analyze the association between substitution of 1 h of sedentary time to light- or moderate-intensity PA and 1 h light-intensity PA to moderate- or vigorous-intensity PA in relation to body mass index (BMI), waist circumference (WC), SAT, and VAT. Results A negative linear association was found for total PAEE and BMI, WC, VAT, and SAT. Exchanging 1 h of sedentary time with light-intensity PA was associated with lower WC (−0.6 cm, P = 0.01), SAT (−0.08 cm, P < 0.001), and VAT (−0.04 cm, P = 0.359). Exchanging light-intensity PA with vigorous-intensity PA resulted in −6.1-cm lower WC (P < 0.001), −0.7-cm lower VAT (P = 0.018) and −0.7-cm lower SAT (P < 0.001). When further adjusting for BMI, the associations were attenuated; however, most of them remained significant, and the directions were mostly unchanged. All 1-, 5-, and 10-min bouts of MVPA were negatively associated with overall and abdominal fat distribution. Conclusion Physical activity energy expenditure is associated with lower BMI, WC, and abdominal fat among Greenland Inuit. The importance of promoting an upward shift of the whole PA intensity distribution and to spur even short bouts of MVPA to limit excessive accumulation of SAT and VAT is highlighted.
Mortality from Cancer of the Male Reproductive Tract and Environmental Exposure to the Anti-Androgen p,p′-Dichlorodiphenyldichloroethylene in the United States

The association of prostate cancer mortality and testicular cancer mortality with environmental exposure to the antiandrogen dichlorodiphenyltrichloroethane (DDT) derivative p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) in the USA was explored in the period 1971–1994 using multiple linear regression analysis. Environmental p,p′-DDE contamination by state was estimated by p,p′-DDE concentrations in the subcutaneous fat of population samples and by measurements of p,p′-DDE in tree bark. On average, African Americans had adipose p,p′-DDE levels 74% higher than Whites (8.49 vs. 4.88 µg/g; p < 0.001). Neither prostate cancer mortality nor testicular cancer mortality showed a positive association with either indicator of p,p′-DDE environmental contamination. On the contrary, the regression coefficient for prostate cancer was constantly inverse for adipose p,p′-DDE along the period of study, although it approached statistical significance only for African Americans in 1981–1985 (β = –0.755; 0.10 > p > 0.05). This ecologic study does not provide support to the hypothesis of a link between environmental exposure to DDT derivatives and cancer of the male reproductive tract.
CCR: A combined cleaning and resampling algorithm for imbalanced data classification

Abstract Imbalanced data classification is one of the most widespread challenges in contemporary pattern recognition. Varying levels of imbalance may be observed in most real datasets, affecting the performance of classification algorithms. Particularly, high levels of imbalance make serious difficulties, often requiring the use of specially designed methods. In such cases the most important issue is often to properly detect minority examples, but at the same time the performance on the majority class cannot be neglected. In this paper we describe a novel resampling technique focused on proper detection of minority examples in a two-class imbalanced data task. The proposed method combines cleaning the decision border around minority objects with guided synthetic oversampling. Results of the conducted experimental study indicate that the proposed algorithm usually outperforms the conventional oversampling approaches, especially when the detection of minority examples is considered.
Rapid response to changing environments during biological invasions: DNA methylation perspectives

Dissecting complex interactions between species and their environments has long been a research hot spot in the fields of ecology and evolutionary biology. The well‐recognized Darwinian evolution has well‐explained long‐term adaptation scenarios; however, “rapid” processes of biological responses to environmental changes remain largely unexplored, particularly molecular mechanisms such as DNA methylation that have recently been proposed to play crucial roles in rapid environmental adaptation. Invasive species, which have capacities to successfully survive rapidly changing environments during biological invasions, provide great opportunities to study molecular mechanisms of rapid environmental adaptation. Here, we used the methylation‐sensitive amplified polymorphism (MSAP) technique in an invasive model ascidian, Ciona savignyi, to investigate how species interact with rapidly changing environments at the whole‐genome level. We detected quite rapid DNA methylation response: significant changes of DNA methylation frequency and epigenetic differentiation between treatment and control groups occurred only after 1 hr of high‐temperature exposure or after 3 hr of low‐salinity challenge. In addition, we detected time‐dependent hemimethylation changes and increased intragroup epigenetic divergence induced by environmental stresses. Interestingly, we found evidence of DNA methylation resilience, as most stress‐induced DNA methylation variation maintained shortly (~48 hr) and quickly returned back to the control levels. Our findings clearly showed that invasive species could rapidly respond to acute environmental changes through DNA methylation modifications, and rapid environmental changes left significant epigenetic signatures at the whole‐genome level. All these results provide fundamental background to deeply investigate the contribution of DNA methylation mechanisms to rapid contemporary environmental adaptation.
Hyperleucocytosis in paediatric acute myeloid leukaemia – the challenge of white blood cell counts above 200 × 109/l. The NOPHO experience 1984–2014

Hyperleucocytosis in paediatric acute myeloid leukaemia (AML) is associated with increased morbidity and mortality. We studied hyperleucocytosis in 890 patients with AML aged 0–18 years registered in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) registry, with special focus on very high white blood cell counts (WBC >200 × 10/l). Eighty‐six patients (10%) had WBC 100–199 × 109/l and 57 (6%) had WBC ≥200 × 109/l. Patients with WBC ≥200 × 109/l had a high frequency of t(9;11) and a paucity of trisomy 8. Due to the high frequency of deaths within the first 2 weeks (30% vs. 1% for all others), overall survival in this group was inferior to patients with WBC <200 × 109/l (39% vs. 61%). Main cause of early death was intracranial haemorrhage and leucostasis. Twenty‐six per cent of these patients never started antileukaemic protocol therapy. Leukapheresis or exchange transfusion was used in 24% of patients with hyperleucocytosis without impact on survival. Patients with hyperleucocytosis surviving the first week had identical survival as patients with lower WBC. We conclude that death within the first days after diagnosis is the major challenge in patients with high WBC and advocate rapid initiation of intensive chemotherapy.
The relationship between theory of mind and insight in obsessive-compulsive disorder

Abstract Background: It is known that obsessive-compulsive disorder (OCD) patients with poor insight display more severe neuropsychological impairments than other patients with OCD. There are limited studies of OCD and theory of mind (ToM). Aim: To investigate ToM skills in patients with OCD and the relationship between insight and ToM skills by comparing OCD patients with good and poor insight. Methods: Eighty patients with OCD and 80 healthy controls completed the structured clinical interview for DSM-IV axis I disorders, the Yale Brown Obsessive-Compulsive Scale, the Beck Anxiety and Beck Depression Inventories, and the Brown Assessment of Beliefs Scale. To assess ToM skills, first- and second-order false-belief tests, a hinting test, a faux pas test, a reading the mind in the eyes test, and a double-bluff test were administered. Results: Patients with OCD had poorer ToM abilities than healthy controls. All ToM scores were significantly lower in the poor insight group than in the good insight group (p < .001). A significant negative correlation was found between the BABS-total scores and all the ToM test mean scores (p < .05). Conclusions: The finding of significantly lower ToM skills in OCD with poor insight than in OCD with good insight may contribute to the idea of OCD with poor insight being a subtype with different clinical and neuropsychological characteristics.
Correlated patterns of genetic diversity and differentiation across an avian family

Comparative studies of genomic differentiation among independent lineages can provide insights into aspects of the speciation process, such as the relative importance of selection and drift in shaping genomic landscapes, the role of genomic regions of high differentiation, and the prevalence of convergent molecular evolution. We investigated patterns of genetic diversity and divergence in stonechats (genus Saxicola), a widely distributed avian species complex with phenotypic variation in plumage, morphology, and migratory behavior, to ask whether similar genomic regions are important in the evolution of independent, but closely related, taxa. We used whole-genome pooled sequencing of 262 individuals from 5 taxa and found that patterns of genetic diversity and divergence are highly similar among different stonechat taxa. We then asked if these patterns remain correlated at deeper evolutionary scales and found that homologous genomic regions have become differentiated in stonechats and the closely related Ficedula flycatchers. Such correlation across a range of evolutionary divergence and among phylogenetically independent comparisons suggests that similar processes may be driving the differentiation of these independently evolving lineages, which in turn may be the result of intrinsic properties of particular genomic regions (e.g., areas of low recombination). Consequently, studies employing genome scans to search for areas important in reproductive isolation should account for corresponding regions of differentiation, as these regions may not necessarily represent speciation islands or facilitate local adaptation.
The 2016 revised World Health Organization definition of ‘myelodysplastic syndrome with isolated del(5q)’; prognostic implications of single versus double cytogenetic abnormalities

The definition of the myelodysplastic syndrome (MDS) subtype ‘MDS with isolated del(5q)’ was expanded to include cases with one additional non‐chromosome 7 based cytogenetic abnormality in the 2016 revised World Health Organization classification. This study applied the revised definition to a large primary MDS cohort, and evaluated the prognostic impact of the additional cytogenetic abnormality. Seventy‐two of 1067 patients (7%) met the ‘MDS with isolated del(5q)’ criteria, 11 (1%) of whom had an additional cytogenetic abnormality. There was no survival difference between patients in whom del(5q) occurred alone, compared to those with one additional cytogenetic abnormality (P = 0·52).
Advanced Prostate Cancer Is Associated with a Decrease in Serum Luteinizing Hormone

Objective: Depletion of serum LH by LHRH agonists is used as a therapeutic treatment in hormone–sensitive prostate cancer (PCa). However, little information on serum LH in different patient groups is available.Methods: Patients with biopsy–proven PCa, men with BPH (biopsy–proven absence of PCa), two subgroups (serum PSA <4 ng/ml; PCa and BPH), and a PCa cohort before and after radical prostatectomy were analyzed for serum LH, testosterone (T), dihydrotestosterone (DHT), total and free PSA by immunological procedures.Results: PCa patients with cancer volumes >10 cm3, or with advanced Gleason scores, had significantly lower LH values than men in a cancer–free control group (PSA <4 ng/ml). Eight weeks after radical prostatectomy, LH levels had returned to the level of the control group (p<0.0001). These alterations were not accompanied by corresponding changes of serum androgens. Introduction of a PSA/LH ratio appeared to increase the differences between BPH and PCA groups ranked according to Gleason scores, versus PSA or LH alone. However, the calculation of ROC curves indicated that PSA/LH ratios may not improve the discrimination of malignant and benign forms of the disease, compared to presently used parameters.Conclusions: A significant reduction of circulating LH is observed in the most advanced forms of PCa. The effect does not come about by T– or DHT–mediated feedback inhibition. Since LH values after prostatectomy returned to practically the same levels as seen in the control group (BPH with <4 ng/ml PSA), it appears that the healthy prostate has no marked influence on serum LH while advanced PCa induces a decrease in serum LH.
Peri‐operative management of patients with type‐2 diabetes mellitus undergoing non‐cardiac surgery using liraglutide, glucose–insulin–potassium infusion or intravenous insulin bolus regimens: a randomised controlled trial

In this open‐label multicentre randomised controlled trial, we investigated three peri‐operative treatment strategies to lower glucose and reduce the need for rescue insulin in patients aged 18–75 years with type‐2 diabetes mellitus undergoing non‐cardiac surgery. Patients were randomly allocated using a web‐based randomisation program to premedication with liraglutide (liraglutide group), glucose–insulin–potassium infusion (insulin infusion group) or insulin bolus regimen (insulin bolus group), targeting a glucose < 8.0 mmol.l−1. The primary outcome was the between group difference in median glucose levels 1 h after surgery. We analysed 150 patients (liraglutide group n = 44, insulin infusion group n = 53, insulin bolus group n = 53) according to the intention‐to‐treat principle. Median (IQR [range]) plasma glucose 1 h postoperatively was lower in the liraglutide group compared with the insulin infusion and insulin bolus groups (6.6 (5.6–7.7 [4.2–13.5]) mmol.l−1 vs. 7.5 (6.4–8.3 [3.9–16.6]) mmol.l−1 (p = 0.026) and 7.6 (6.4–8.9 [4.7–13.2]) mmol.l−1) p = 0.006, respectively). The incidence of hypoglycaemia and postoperative complications did not differ between the groups. Six patients had pre‐operative nausea in the liraglutide group, of which two had severe nausea, compared with no patients in the insulin infusion and insulin bolus groups (p = 0.007). The pre‐operative administration of liraglutide stabilised peri‐operative plasma glucose levels and reduced peri‐operative insulin requirements, at the expense of increased pre‐operative nausea rates.
CKS1 expression in melanocytic nevi and melanoma

Cyclin-dependent kinase subunit 1 (Cks1) regulates the degradation of p27, an important G1-S inhibitor, which is up regulated by MAPK pathway activation. In this study, we sought to determine whether Cks1 expression is increased in melanocytic tumors and correlates with outcome and/or other clinicopathologic prognostic markers. Cks1 expression was assessed by immunohistochemistry in 298 melanocytic lesions. The frequency and intensity of cytoplasmic and nuclear expression was scored as a labeling index and correlated with clinico-pathological data. Nuclear Cks1 protein was found in 63% of melanocytic nevi, 89% primary and 90% metastatic melanomas with mean labeling index of 7 ± 16, 19 ± 20, and 30 ± 29, respectively. While cytoplasmic Cks1 was found in 41% of melanocytic nevi, 84% primary and 95% metastatic melanomas with mean labeling index of 18 ± 34, 35 ± 34, and 52 ± 34, accordingly. Histologic stepwise model of tumor progression, defined as progression from benign nevi to primary melanomas, to melanoma metastases, revealed a significant increase in nuclear and cytoplasmic Cks1 expression with tumor progression. Nuclear and cytoplasmic Cks1 expression correlated with the presence of ulceration, increased mitotic rate, Breslow depth, Clark level, tumor infiltrating lymphocytes and gender. However, other well-known prognostic factors (age, anatomic site, and regression) did not correlate with any type of Cks1 expression. Similarly, increasing nuclear expression of Cks1 significantly correlated with worse overall survival. Thus, Cks1 expression appears to play a role in the progression of melanoma, where high levels of expression are associated with poor outcome. Cytoplasmic expression of Cks1 might represent high turnover of protein via the ubiquination/proteosome pathway.
Imaging the Met Receptor Tyrosine Kinase (Met) and Assessing Tumor Responses to a Met Tyrosine Kinase Inhibitor in Human Xenograft Mouse Models with a [99mTc] (AH-113018) or CY 5** (AH-112543) Labeled Peptide

Developing an imaging agent targeting the hepatocyte growth factor receptor protein (Met) status of cancerous lesions would aid in the diagnosis and monitoring of Met-targeted tyrosine kinase inhibitors (TKIS). A peptide targeting Met labeled with [99mTc] had high affinity in vitro (Kd = 3.3 nM) and detected relative changes in Met in human cancer cell lines. In vivo [99mTc]-Met peptide (AH-113018) was retained in Met-expressing tumors, and high-expressing Met tumors (MKN-45) were easily visualized and quantitated using singlephoton emission computed tomography or optical imaging. In further studies, MKN-45 mouse xenografts treated with PHA 665752 (Met TKI) or vehicle were monitored weekly for tumor responses by [99mTc]-Met peptide imaging and measurement of tumor volumes. Tumor uptake of [“mTc]-Met peptide was significantly decreased as early as 1 week after PHA 665752 treatment, corresponding to decreases in tumor volumes. These results were comparable to Cy5**-Met peptide (AH-112543) fluorescence imaging using the same treatment model. [99mTc] or Cy5**-Met peptide tumor uptake was further validated by histologic (necrosis, apoptosis) and immunoassay (total Met, p Met, and plasma shed Met) assessments in imaged and nonimaged cohorts. These data suggest that [99mTc] or Cy5**-Met peptide imaging may have clinical diagnostic, prognostic, and therapeutic monitoring applications.
Reovirus transcriptase activation in vitro: further studies on the facilitation phenomenon.

Activation of the transcriptase in purified reovirus by chymotrypsin requires facilitating conditions in the digestion mix. In the presence of facilitation the virions are uncoated to cores. Without facilitation, uncoating is blocked at an intermediate stage, with transcriptase latent. Two independent types of facilitation have been discovered. The first type is mediated by K+, Rb+ or Cs+ ions. A second type, described here, is mediated by suitably high concentrations of virus in the digestion mix and requires collisions between intermediate subviral particles for its occurrence. The virus-concentration-mediated process is reversibly inhibited by high levels of active chymotrypsin.
Drug drug interaction extraction from the literature using a recursive neural network

Detecting drug-drug interactions (DDI) is important because information on DDIs can help prevent adverse effects from drug combinations. Since there are many new DDI-related papers published in the biomedical domain, manually extracting DDI information from the literature is a laborious task. However, text mining can be used to find DDIs in the biomedical literature. Among the recently developed neural networks, we use a Recursive Neural Network to improve the performance of DDI extraction. Our recursive neural network model uses a position feature, a subtree containment feature, and an ensemble method to improve the performance of DDI extraction. Compared with the state-of-the-art models, the DDI detection and type classifiers of our model performed 4.4% and 2.8% better, respectively, on the DDIExtraction Challenge’13 test data. We also validated our model on the PK DDI corpus that consists of two types of DDIs data: in vivo DDI and in vitro DDI. Compared with the existing model, our detection classifier performed 2.3% and 6.7% better on in vivo and in vitro data respectively. The results of our validation demonstrate that our model can automatically extract DDIs better than existing models.