Miracle-dz/UniFAR-FTUs huggingface dataset:
On the impact of contaminants on the accuracy of genome skimming and the effectiveness of exclusion read filters

The ability to detect the identity of a sample obtained from its environment is a cornerstone of molecular ecological research. Thanks to the falling price of shotgun sequencing, genome skimming, the acquisition of short reads spread across the genome at low coverage, is emerging as an alternative to traditional barcoding. By obtaining far more data across the whole genome, skimming has the promise to increase the precision of sample identification beyond traditional barcoding while keeping the costs manageable. While methods for assembly-free sample identification based on genome skims are now available, little is known about how these methods react to the presence of DNA from organisms other than the target species. In this paper, we show that the accuracy of distances computed between a pair of genome skims based on k-mer similarity can degrade dramatically if the skims include contaminant reads; i.e., any reads originating from other organisms. We establish a theoretical model of the impact of contamination. We then suggest and evaluate a solution to the contamination problem: Query reads in a genome skim against an extensive database of possible contaminants (e.g., all microbial organisms) and filter out any read that matches. We evaluate the effectiveness of this strategy when implemented using Kraken-II, in detailed analyses. Our results show substantial improvements in accuracy as a result of filtering but also point to limitations, including a need for relatively close matches in the contaminant database.
Identification of CNS Injury-Related microRNAs as Novel Toll-Like Receptor 7/8 Signaling Activators by Small RNA Sequencing

Toll-like receptors (TLRs) belong to pattern recognition receptors, which respond to danger signals such as pathogen-associated molecular patterns or damage-associated molecular patterns. Upon TLR activation in microglia, the major immune cells in the brain, distinct signaling cascades trigger the production of inflammatory molecules, being a critical feature in neuroinflammation and neurodegenerative processes. Recently, individual microRNAs (miRNAs) were shown to act as endogenous TLR ligands. Here, we conducted systematic screening for miRNAs as potential TLR7/8 ligands by small RNA sequencing of apoptotic neurons and their corresponding supernatants. Several miRNA species were identified in both supernatants and injured neurons, and 83.3% of the media-enriched miRNAs activated murine and/or human TLR7/8 expressed in HEK293-derived TLR reporter cells. Among the detected extracellular miRNAs, distinct miRNAs such as miR-340-3p and miR-132-5p induced cytokine and chemokine release from microglia and triggered neurotoxicity in vitro. Taken together, our systematic study establishes miRNAs released from injured neurons as new TLR7/8 activators, which contribute to inflammatory and neurodegenerative responses in the central nervous system (CNS).
Sitravatinib Sensitizes ABCB1- and ABCG2-Overexpressing Multidrug-Resistant Cancer Cells to Chemotherapeutic Drugs

The development of multidrug resistance (MDR) in cancer patients driven by the overexpression of ATP-binding cassette (ABC) transporter ABCB1 or ABCG2 in cancer cells presents one of the most daunting therapeutic complications for clinical scientists to resolve. Despite many novel therapeutic strategies that have been tested over the years, there is still no approved treatment for multidrug-resistant cancers to date. We have recently adopted a drug repurposing approach to identify therapeutic agents that are clinically active and at the same time, capable of reversing multidrug resistance mediated by ABCB1 and ABCG2. In the present study, we investigated the effect of sitravatinib, a novel multitargeted receptor tyrosine kinase inhibitor, on human ABCB1 and ABCG2 in multidrug-resistant cancer cell lines. We discovered that at submicromolar concentrations, sitravatinib re-sensitizes ABCB1- and ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs. We found that sitravatinib blocks the drug efflux function of ABCB1 and ABCG2 in a concentration-dependent manner but does not significantly alter the protein expression of ABCB1 or ABCG2 in multidrug-resistant cancer cells. In conclusion, we reveal a potential drug repositioning treatment option for multidrug-resistant cancers by targeting ABCB1 and ABCG2 with sitravatinib and should be further investigated in future clinical trials.
The Effectiveness of Psychological Treatments in Women with Breast Cancer: A Systematic Review and Meta-Analysis

Breast cancer is the most prevalent oncological disease among women, and it represents the second oncological cause of death. Many studies have considered the quality of life in people with breast cancer because this condition has high comorbidity with mental distress, anxiety, affective disorders and depression. Psychological interventions can reduce the stressful consequences of both the diagnosis and the medical treatments of breast cancer. However, different methods (e.g., group or individual therapy) and focus (e.g., improving personal skills or increasing emotional well-being) do not help to identify which type of psychological therapy can be more effective in improving quality of life in patients with breast cancer. This study was aimed to systematically review and compare, by means of a meta-analysis, the efficacy of cognitive behavioural, supportive-expressive or psycho-educational treatments in women with breast cancer, focusing on anxiety, depression, mood and quality of life as outcomes. The PRISMA statement was adopted. MEDLINE, PsycINFO, PUBMED and PsycArticles databases were used, and reference lists were examined for additional publications. In the selection of the articles were included studies considering women between 18 and 65 years who were diagnosed with breast cancer at any stage and under any treatment, and who underwent psychological group interventions. At the end of the systematic review, 45 studies met all inclusion criteria and were analysed in the meta-analysis. The overall effect size was medium, especially considering cognitive behavioural therapy and psycho-educational treatments. However, the studies are characterised by high methodological heterogeneity. Despite some limitations, this review and meta-analysis partially confirm the efficiency of cognitive-behavioural and psycho-educational therapies in the improvement of well-being in women with breast cancer.
Updates on spread through air spaces (STAS) in lung cancer

Air space invasion of tumours, particularly spread through air spaces (STAS), is a relatively recent concept that has been identified as a novel mechanism of invasion. It has predominantly been described in lung adenocarcinoma, although it may be seen in other primary lung malignancies as well. STAS in lung cancer has been reported to have numerous associations with poor survival. The objective of this article was to review the concept of air space invasion, update findings regarding its clinical impact, and discuss controversies in the field. With this aim, we performed a PubMed search of the English‐language literature. STAS has been introduced as a novel mechanism of invasion that is important for pathologists to recognise. There is a compelling body of evidence associating the presence of STAS with lower survival and suggesting that STAS is an independent prognostic factor, regardless of the stage of tumour. The standard of care for lung adenocarcinomas with STAS irrespective of size of tumour and nodal metastasis may be lobectomy rather than sublobar resection, owing to the risk of locoregional recurrence. Emerging data suggest that more work should be performed to improve consensus on and identification of STAS, including at frozen section.
The influence of ecological infrastructures adjacent to crops on their carabid assemblages in intensive agroecosystems

Background Conserving biodiversity and enhancing ecosystem services of interest in intensive agroecosystems is a major challenge. Perennial ecological infrastructures (EIs), such as hedges and grassy strips, and annual EI under Agri-Environment Schemes appear to be good candidates to promote both. Our study focused on carabids, an indicator group responding both at the species and functional trait level to disturbances and supporting pest control and weed seed consumption services. Methods We compared carabid assemblages at the species and functional traits levels, sampled via pitfall trapping, in three types of EIs (hedges, grassy strips and annual flower strips) and crops. We also tested via GLMs the effect of (1) the type of EI at the crops’ border and (2) the distance from the crops’ border (two meters or 30 meters) on carabid assemblages of crops. Tested variables comprised: activity-density, species richness, functional dispersion metrics (FDis) and proportions of carabids by functional categories (Diet: generalist predators/specialist predators/seed-eaters; Size: small/medium/large/very large; Breeding period: spring/autumn). Results and Discussion Carabid assemblages on the Principal Coordinate Analysis split in two groups: crops and EIs. Assemblages from all sampled EIs were dominated by mobile generalist predator species from open-land, reproducing in spring. Assemblages of hedges were poor in activity-density and species richness, contrarily to grassy and annual flower strips. Differences in carabid assemblages in crops were mainly driven by the presence of hedges. The presence of hedges diminished the Community Weighted Mean size of carabids in crops, due to an increased proportion of small (<5 mm) individuals, while distance from crops’ border favoured large (between 10–15 mm) carabids. Moreover, even if they were attracted by EIs, granivorous carabid species were rare in crops. Our results underlie the importance of local heterogeneity when adapting crops’ borders to enhance carabid diversity and question the relevance of hedge implantation in intensive agrolandscapes, disconnected from any coherent ecological network. Moreover, this study emphasizes the difficulty to modify functional assemblages of crops for purposes of ecosystem services development, especially for weed seed consumption, as well as the role of distance from the crops’ border in the shaping of crop carabid assemblages.
Developing a Novel Tactile P300 Brain-Computer Interface With a Cheeks-Stim Paradigm

Objective: Tactile brain-computer interface (BCI) systems can provide new communication and control options for patients with impairments of eye movements or vision. One of the most common modalities used in these BCIs is the P300 potential. Until now, tactile P300 BCIs have been successfully constructed by situating tactile stimuli at various parts of the human body. This article proposed a novel tactile P300 BCI paradigm for further expanding the tactile stimulation methods. Methods: In our proposed paradigm, the spatial target vibrotactile stimuli were delivered to subject's left and right cheeks. To validate the feasibility of our proposed paradigm, a traditional tactile P300 BCI paradigm employing spatial target vibrotactile stimuli to subject's left and right wrists was used for comparison. Results: The experimental results of nine healthy subjects demonstrated that the proposed paradigm could obtain significantly higher classification accuracy and information transfer rate than the traditional paradigm (both for p < 0.05). Furthermore, the subjective feedback showed that our proposed paradigm was more favored by the subjects compared to the traditional paradigm, and most subjects reported that the new paradigm helped them easily distinguish between targets and non-targets. Conclusion: The proposed tactile P300 BCI paradigm is feasible, and can bring about superior performance and use-evaluation. Significance: The new paradigm might lead to many promising applications of such BCIs.
Reliability and Validity of a Short Form of the Korean Dementia Screening Questionnaire-Cognition

Background and Purpose We aimed to determine the reliability and validity of a short form of the Korean Dementia Screening Questionnaire-Cognition (KDSQ-C) as a screening tool for cognitive dysfunction. Methods This study recruited 420 patients older than 65 years and their informants from 11 hospitals, and categorized the patients into normal cognition, mild cognitive impairment, and dementia subgroups. The KDSQ-C was completed separately by the patients and their informants. We abstracted three components of the KDSQ-C and combined these components into the following four subscales: KDSQ-C-I (items 1–5, memory domain), KDSQ-C-II (items 1–5 & 11–15, memory domain+activities of daily living), KDSQ-C-III (items 1–5 & 6–10, memory domain+other cognitive domains), and KDSQ-C-IV (items 6–10 & 11–15, other cognitive domains+activities of daily living). The reliability and validity were compared between these four subscales. Results A receiver operating characteristic (ROC) analysis of questionnaire scores provided by the patients showed that the areas under the ROC curves (AUCs) for the KDSQ-C, KDSQC-I, and KDSQ-C-II for diagnosing dementia were 0.75, 0.72, and 0.76, respectively; the corresponding AUCs for informant-completed questionnaires were 0.92, 0.89, and 0.92, indicating good discriminability for dementia. Conclusions A short form of the patient- and informant-rated versions of the KDSQ-C (KDSQ-C-II) is as capable as the 15-item KDSQ-C in screening for dementia.
Design and Rationale of the ERA-CVD Consortium PREMED-CAD—Precision Medicine in Coronary Artery Disease

Cardiovascular diseases (CVDs) comprise 45% of all deaths in Europe and causes 3.9 million deaths annually. Coronary artery disease (CAD) which includes myocardial infarction (MI) represents the most common form of CVD. A relevant proportion of MI cases seems preventable since reports claim that up to two-thirds of these patients exhibit symptoms suggestive for MI within 12 months prior to the acute MI event. An early identification of these at-risk subjects is necessary to manage an early and efficient treatment during the ischemic phase. The aim of the PRecision MEDicine in Coronary Artery Disease (PREMED-CAD) consortium is to apply a system medicine approach towards studying and identifying an ischemia specific ‘biomarker signature’ that improves the identification of individuals ‘at-risk’ for acute MI. The consortium will take an interdisciplinary and translational approach integrating knowledge from CAD epidemiology, imaging, bioinformatics, statistics and molecular biology, as well as existing phenotypic, blood-based and clinical biomarker data of distinct CAD and subclinical MI phenotypes. This biomarker signature will be validated through atherosclerosis-prone mouse models and human cohorts. The validated signature will be translated in a real-world clinical setting using an ongoing clinical trial comprising patients with subclinical ischemia. The aim of the knowledge obtained from this project is to aid in early MI detection and reduce the mortality and morbidity rate in these at-risk MI individuals.
Leukotriene B4 Receptor Type 2 Accelerates the Healing of Intestinal Lesions by Promoting Epithelial Cell Proliferation

Leukotriene B4 receptor type 2 (BLT2) is a low-affinity leukotriene B4 receptor that is highly expressed in intestinal epithelial cells. Previous studies demonstrated the protective role of BLT2 in experimentally induced colitis. However, its role in intestinal lesion repair is not fully understood. We investigated the role of BLT2 in the healing of indomethacin-induced intestinal lesions in mice. There was no significant different between wild-type (WT) and BLT2-deficient (BLT2KO) mice in terms of the development of indomethacin-induced intestinal lesions. However, healing of these lesions was significantly impaired in BLT2KO mice compared with WT mice. In contrast, transgenic mice with intestinal epithelium–specific BLT2 overexpression presented with superior ileal lesion healing relative to WT mice. An immunohistochemical study showed that the number of Ki-67–proliferative cells was markedly increased during the healing of intestinal lesions in WT mice but significantly attenuated in BLT2KO mice. Exposure of cultured mouse intestinal epithelial cells to CAY10583, a BLT2 agonist, promoted wound healing and cell proliferation in a concentration-dependent manner. Nevertheless, these responses were abolished under serum-free conditions. The CAY10583-induced proliferative effect was also negated by Go6983, a protein kinase C (PKC) inhibitor, U-73122, a phospholipase C (PLC) inhibitor, LY255283, a BLT2 antagonist, and pertussis toxin that inhibits G protein–coupled receptor signaling via Gi/o proteins. Thus, BLT2 plays an important role in intestinal wound repair. Moreover, this effect is mediated by the promotion of epithelial cell proliferation via the Gi/o protein–dependent and PLC/PKC signaling pathways. The BLT2 agonists are potential therapeutic agents for the treatment of intestinal lesions. SIGNIFICANCE STATEMENT The healing of indomethacin-induced Crohn’s disease–like intestinal lesions was impaired in mice deficient in low-affinity leukotriene B4 receptor type 2 (BLT2). They presented with reduced epithelial cell proliferation during the healing. In contrast, healing was promoted in mice overexpressing intestinal epithelial BLT2. In cultured intestinal epithelial cells, the BLT2 agonist CAY10583 substantially accelerated wound repair by enhancing cell proliferation rather than migration. Thus, BLT2 plays an important role in the intestinal lesions via acceleration of epithelial cell proliferation.
TNFα Selectively Activates the IRE1α/XBP1 Endoplasmic Reticulum Stress Pathway in Human Airway Smooth Muscle Cells.

Airway inflammation is a key aspect of diseases such as asthma. Pro-inflammatory cytokines such as TNFα mediate the inflammatory response. In various diseases,inflammation leads to endoplasmic reticulum (ER) stress, the accumulation of unfolded proteins, which triggers homeostatic responses to restore normal cellular function. We hypothesized that TNFα triggers ER stress through an increase in ROS generation in human airway smooth muscle (hASM) with downstream effect on mitofusin 2 (Mfn2). In hASM cells isolated from lung specimens incidental to patient surgery, dose and time dependent effects of TNFα exposure were assessed. Exposure of hASM to tunicamycin was used as a positive control. Tempol (500 μM) was used as superoxide scavenger. Activation of three ER stress pathways were evaluated by Western blot: 1) autophosphorylation of IRE1α leading to splicing of XBP1; 2) autophosphorylation PERK leading to phosphorylation of eIF2α; and 3) translocation and cleavage of ATF6. We found that exposure of hASM cells to tunicamycin activated all three ER stress pathways. In contrast, TNFα selectively activated the IRE1α/XBP1 pathway in a dose and time dependent fashion. Our results indicate that TNFα does not activate the PERK and ATF6 pathways. Exposure of hASM cells to TNFα also decreased Mfn2 protein expression. Concurrent exposure to TNFα and Tempol reversed the effect of TNFα on IRE1α phosphorylation and Mfn2 protein expression. Selective activation of the IRE1α/XBP1 pathway in hASM cells after exposure to TNFα may reflect a unique homeostatic role of this pathway in the inflammatory response of hASM cells.
Formins specify membrane patterns generated by propagating actin waves

Circular actin waves separate two distinct areas on the substrate-attached cell surface from each other: an external area from an inner territory that is circumscribed by the wave. These areas differ in composition of actin-associated proteins and of phosphoinositides in the membrane. At the propagating wave, one area is converted into the other. By photo-conversion of Eos-actin and analysis of actin network structures we show that both in the inner territory and the external area the actin network is subject to continuous turnover. To address the question of whether areas in the wave pattern are specified by particular actin polymerizing machines, we locate five members of the formin family to specific regions of the wave landscape using TIRF microscopy and constitutively active formin constructs tagged with fluorescent protein. Formin ForB favors the actin wave and ForG the inner territory, whereas ForA, ForE, and ForH are more strongly recruited to the external area. Fluctuations of membrane binding peculiar to ForB indicate transient states in the specification of membrane domains before differentiation into ForB decorated and depleted ones. Annihilation of the patterns by 1 µM of the formin inhibitor SMIFH2 supports the implication of formins in their generation.
Alcohol Consumption, Drinking Patterns, and Cognitive Performance in Young Adults: A Cross-Sectional and Longitudinal Analysis

Long-term alcohol abuse is associated with poorer cognitive performance. However, the associations between light and moderate drinking and cognitive performance are less clear. We assessed this association via cross-sectional and longitudinal analyses in a sample of 702 Dutch students. At baseline, alcohol consumption was assessed using questionnaires and ecological momentary assessment (EMA) across four weeks (‘Wave 1’). Subsequently, cognitive performance, including memory, planning, and reasoning, was assessed at home using six standard cognition tests presented through an online platform. A year later, 436 students completed the four weeks of EMA and online cognitive testing (‘Wave 2’). In both waves, there was no association between alcohol consumption and cognitive performance. Further, alcohol consumption during Wave 1 was not related to cognitive performance at Wave 2. In addition, EMA-data-based drinking patterns, which varied widely between persons but were relatively consistent over time within persons, were also not associated with cognitive performance. Post-hoc analyses of cognitive performance revealed higher within-person variance scores (from Wave 1 to Wave 2) than between-person variance scores (both Wave 1 and Wave 2). In conclusion, no association was observed between alcohol consumption and cognitive performance in a large Dutch student sample. However, the online cognitive tests performed at home may not have been sensitive enough to pick up differences in cognitive performance associated with alcohol consumption.
Radiomics signature for prediction of lateral lymph node metastasis in conventional papillary thyroid carcinoma

Purpose Preoperative neck ultrasound (US) for lateral cervical lymph nodes is recommended for all patients undergoing thyroidectomy for thyroid malignancy, but it is operator dependent. We aimed to develop a radiomics signature using US images of the primary tumor to preoperatively predict lateral lymph node metastasis (LNM) in patients with conventional papillary thyroid carcinoma (cPTC). Methods Four hundred consecutive cPTC patients from January 2004 to February 2006 were enrolled as the training cohort, and 368 consecutive cPTC patients from March 2006 to February 2007 served as the validation cohort. A radiomics signature, which consisted of 14 selected features, was generated by the least absolute shrinkage and selection operator (LASSO) regression model in the training cohort. The discriminating performance of the radiomics signature was assessed in the validation cohort with the area under the receiver operating characteristic curve (AUC). Results The radiomics signature was significantly associated with lateral cervical lymph node status (p < 0.001). The AUC of its performance in discriminating metastatic and non-metastatic lateral cervical lymph nodes was 0.710 (95% CI: 0.649–0.770) in the training cohort and was 0.621 (95% CI: 0.560–0.682) in the validation cohort. Conclusions The present study showed that US radiomic features of the primary tumor were associated with lateral cervical lymph node status. Although their discriminatory performance was slightly lower in the validation cohort, our study shows that US radiomic features of the primary tumor alone have the potential to predict lateral LNM.