Miracle-dz/UniFAR-FTUs huggingface dataset:
microRNAs: key triggers of neuronal cell fate

Development of the central nervous system (CNS) requires a precisely coordinated series of events. During embryonic development, different intra- and extracellular signals stimulate neural stem cells to become neural progenitors, which eventually irreversibly exit from the cell cycle to begin the first stage of neurogenesis. However, before this event occurs, the self-renewal and proliferative capacities of neural stem cells and neural progenitors must be tightly regulated. Accordingly, the participation of various evolutionary conserved microRNAs is key in distinct central nervous system (CNS) developmental processes of many organisms including human, mouse, chicken, frog, and zebrafish. microRNAs specifically recognize and regulate the expression of target mRNAs by sequence complementarity within the mRNAs 3′ untranslated region and importantly, a single microRNA can have several target mRNAs to regulate a process; likewise, a unique mRNA can be targeted by more than one microRNA. Thus, by regulating different target genes, microRNAs let-7, microRNA-124, and microRNA-9 have been shown to promote the differentiation of neural stem cells and neural progenitors into specific neural cell types while microRNA-134, microRNA-25 and microRNA-137 have been characterized as microRNAs that induce the proliferation of neural stem cells and neural progenitors. Here we review the mechanisms of action of these two sets of microRNAs and their functional implications during the transition from neural stem cells and neural progenitors to fully differentiated neurons. The genetic and epigenetic mechanisms that regulate the expression of these microRNAs as well as the role of the recently described natural RNA circles which act as natural microRNA sponges regulating post-transcriptional microRNA expression and function during the early stages of neurogenesis is also discussed.
Hormonal factors and risk of aneurysmal subarachnoid hemorrhage: an international population-based, case-control study.

BACKGROUND AND PURPOSE Subarachnoid hemorrhage (SAH) is more common in women than in men, but the role of hormonal factors in its etiology remains uncertain. The aim of this study was to examine the relationship between hormonal factors and risk of SAH in women. METHODS This was a prospective, multicenter, population-based, case-control study performed in 4 major urban centers in Australia and New Zealand. Two hundred sixty-eight female cases of first-ever aneurysmal SAH occurred during 1995-1998. Controls were 286 frequency-matched women from the general population of each center. Outcome measures included risk of SAH associated with use of oral contraceptive pills (OCPs), hormone replacement therapy (HRT), and various endogenous hormonal factors including menstrual patterns, parity, age at birth of first child, and breast-feeding practices. RESULTS Cases and controls did not differ with regard to menstrual and reproductive history except in age at birth of first child, where older age was associated with reduced risk of SAH (odds ratio [OR], 0.63; 95% CI, 0.43, 0.91). Relative to never use of HRT, the adjusted OR for ever use of HRT was 0.64 (95% CI, 0.41, 0.98), which did not alter significantly after further adjustment for possible confounding factors. Borderline evidence of an inverse association was detected for past use of HRT (adjusted OR, 0.59; 95% CI, 0.30, 1.13) and current use of HRT (adjusted OR, 0.67; 95% CI, 0.40, 1.13), but there was no evidence of an association for use of OCPs (adjusted OR, 0.97; 95% CI, 0.58, 1.60). CONCLUSIONS The risks of SAH are lower in women whose first pregnancy is at an older age and women who have ever used HRT but not OCPs. The findings suggest an independent etiologic role for hormonal factors in the pathogenesis of aneurysmal SAH and provide support for a protective role for HRT on risk of SAH in postmenopausal women.
Differences in cardiovascular disease risk factors associated with maximum and mean carotid intima-media thickness among hemodialysis patients.

INTRODUCTION Carotid intima-media thickness (CIMT) could be used as a surrogate marker of atherosclerosis in hemodialysis patients. Since different mechanisms are involved in the atheroma formation and arterial wall thickness, we assessed the relationship between the maximum and the mean CIMT with different cardiovascular risk factors in dialysis patients. MATERIALS AND METHODS The mean and the maximum CIMT were measured using a B-mode ultrasonography in 75 hemodialysis patients, and the correlation between CIMT and cardiovascular risk factors were assessed. RESULTS The mean and maximum CIMT measurements were 0.5 mm (range, 0.2 mm to 1 mm) and 3.4 mm (1.4 mm to 5.6 mm), respectively. Among all the studied variables, age (P = .04, r = 0.238), HS-CRP (P = .01, r = 0.284), mean arterial blood pressure (P = .003, r = 0.343), and DM (P = .02) had significant correlations with the mean CIMT, while only age (P = .02, r = 0.473) and serum creatinine levels (P = .02, r = -0.493) were significantly associated with the maximum CIMT. A positive nonsignificant correlation was observed between the mean and maximum CIMT values (P = .08, R2 linear = 0.214). CONCLUSIONS These findings suggest that in dialysis patients, effects of cardiovascular risk factors on the mean and maximum CIMT might be different. Further studies are recommended to evaluate the prediction impact of each risk factor in end-stage renal disease patients compared with otherwise healthy individuals.
Potential Role of Biofilm Formation in the Development of Digestive Tract Cancer With Special Reference to Helicobacter pylori Infection

Bacteria are highly social organisms that communicate via signaling molecules and can assume a multicellular lifestyle to build biofilm communities. Until recently, complications from biofilm-associated infection have been primarily ascribed to increased bacterial resistance to antibiotics and host immune evasion, leading to persistent infection. In this theory and hypothesis article we present a relatively new argument that biofilm formation has potential etiological role in the development of digestive tract cancer. First, we summarize recent new findings suggesting the potential link between bacterial biofilm and various types of cancer to build the foundation of our hypothesis. To date, evidence has been particularly convincing for colorectal cancer and its precursor, i.e., polyps, pointing to several key individual bacterial species, such as Bacteroides fragilis, Fusobacterium nucleatum, and Streptococcus gallolyticus subsp. Gallolyticus. Then, we further extend this hypothesis to one of the most common bacterial infection in humans, Helicobacter pylori (Hp), which is considered a major cause of gastric cancer. Thus far, there has been no direct evidence linking in vivo Hp gastric biofilm formation to gastric carcinogenesis. Yet, we synthesize the information to support an argument that biofilm associated-Hp is potentially more carcinogenic, summarizing biological characteristics of biofilm-associated bacteria. We also discuss mechanistic pathways as to how Hp or other biofilm-associated bacteria control biofilm formation and highlight recent findings on Hp genes that influence biofilm formation, which may lead to strain variability in biofilm formation. This knowledge may open a possibility of developing targeted intervention. We conclude, however, that this field is still in its infancy. To test the hypothesis rigorously and to link it ultimately to gastric pathologies (e.g., premalignant lesions and cancer), studies are needed to learn more about Hp biofilms, such as compositions and biological properties of extracellular polymeric substance (EPS), presence of non-Hp microbiome and geographical distribution of biofilms in relation to gastric gland types and structures. Identification of specific Hp strains with enhanced biofilm formation would be helpful not only for screening patients at high risk for sequelae from Hp infection, but also for development of new antibiotics to avoid resistance, regardless of its association with gastric cancer.
Generalized chromatic numbers and additive hereditary properties of graphs

An additive hereditary property of graphs is a class of simple graphs which is closed under unions, subgraphs and isomorphisms. Let P and Q be additive hereditary properties of graphs. The generalized chromatic number χQ(P) is defined as follows: χQ(P) = n iff P ⊆ Qn but P 6⊆ Qn−1. We investigate the generalized chromatic numbers of the well-known properties of graphs Ik, Ok, Wk, Sk and Dk.
Changes in functional connectivity correlate with behavioral gains in stroke patients after therapy using a brain-computer interface device

Brain-computer interface (BCI) technology is being incorporated into new stroke rehabilitation devices, but little is known about brain changes associated with its use. We collected anatomical and functional MRI of nine stroke patients with persistent upper extremity motor impairment before, during, and after therapy using a BCI system. Subjects were asked to perform finger tapping of the impaired hand during fMRI. Action Research Arm Test (ARAT), 9-Hole Peg Test (9-HPT), and Stroke Impact Scale (SIS) domains of Hand Function (HF) and Activities of Daily Living (ADL) were also assessed. Group-level analyses examined changes in whole-brain task-based functional connectivity (FC) to seed regions in the motor network observed during and after BCI therapy. Whole-brain FC analyses seeded in each thalamus showed FC increases from baseline at mid-therapy and post-therapy (p < 0.05). Changes in FC between seeds at both the network and the connection levels were examined for correlations with changes in behavioral measures. Average motor network FC was increased post-therapy, and changes in average network FC correlated (p < 0.05) with changes in performance on ARAT (R2 = 0.21), 9-HPT (R2 = 0.41), SIS HF (R2 = 0.27), and SIS ADL (R2 = 0.40). Multiple individual connections within the motor network were found to correlate in change from baseline with changes in behavioral measures. Many of these connections involved the thalamus, with change in each of four behavioral measures significantly correlating with change from baseline FC of at least one thalamic connection. These preliminary results show changes in FC that occur with the administration of rehabilitative therapy using a BCI system. The correlations noted between changes in FC measures and changes in behavioral outcomes indicate that both adaptive and maladaptive changes in FC may develop with this therapy and also suggest a brain-behavior relationship that may be stimulated by the neuromodulatory component of BCI therapy.
BioCreative V track 4: a shared task for the extraction of causal network information using the Biological Expression Language

Automatic extraction of biological network information is one of the most desired and most complex tasks in biological and medical text mining. Track 4 at BioCreative V attempts to approach this complexity using fragments of large-scale manually curated biological networks, represented in Biological Expression Language (BEL), as training and test data. BEL is an advanced knowledge representation format which has been designed to be both human readable and machine processable. The specific goal of track 4 was to evaluate text mining systems capable of automatically constructing BEL statements from given evidence text, and of retrieving evidence text for given BEL statements. Given the complexity of the task, we designed an evaluation methodology which gives credit to partially correct statements. We identified various levels of information expressed by BEL statements, such as entities, functions, relations, and introduced an evaluation framework which rewards systems capable of delivering useful BEL fragments at each of these levels. The aim of this evaluation method is to help identify the characteristics of the systems which, if combined, would be most useful for achieving the overall goal of automatically constructing causal biological networks from text.
Disentangling taste and toxicity in aposematic prey

Many predators quickly learn to avoid attacking aposematic prey. If the prey vary in toxicity, the predators may alternatively learn to capture and taste-sample prey carefully before ingesting or rejecting them (go-slow behaviour). An increase in prey toxicity is generally thought to decrease predation on prey populations. However, while prey with a higher toxin load are more harmful to ingest, they may also be easier to recognize and reject owing to greater distastefulness, which can facilitate a taste-sampling foraging strategy. Here, the classic diet model is used to study the separate effects of taste and toxicity on predator preferences. The taste-sampling process is modelled using signal detection theory. The model is applicable to automimicry and Batesian mimicry. It shows that when the defensive toxin is sufficiently distasteful, a mimicry complex may be less profitable to the predator and better protected against predation if the models are moderately toxic than if they are highly toxic. Moreover, taste mimicry can reduce the profitability of the mimicry complex and increase protection against predation. The results are discussed in relation to the selection pressures acting on prey defences and the evolution of mimicry.
Verification of alternative splicing variants based on domain integrity, truncation length and intrinsic protein disorder

According to current estimations ∼95% of multi-exonic human protein-coding genes undergo alternative splicing (AS). However, for 4000 human proteins in PDB, only 14 human proteins have structures of at least two alternative isoforms. Surveying these structural isoforms revealed that the maximum insertion accommodated by an isoform of a fully ordered protein domain was 5 amino acids, other instances of domain changes involved intrinsic structural disorder. After collecting 505 minor isoforms of human proteins with evidence for their existence we analyzed their length, protein disorder and exposed hydrophobic surface. We found that strict rules govern the selection of alternative splice variants aimed to preserve the integrity of globular domains: alternative splice sites (i) tend to avoid globular domains or (ii) affect them only marginally or (iii) tend to coincide with a location where the exposed hydrophobic surface is minimal or (iv) the protein is disordered. We also observed an inverse correlation between the domain fraction lost and the full length of the minor isoform containing the domain, possibly indicating a buffering effect for the isoform protein counteracting the domain truncation effect. These observations provide the basis for a prediction method (currently under development) to predict the viability of splice variants.
Serum APE1 Autoantibodies: A Novel Potential Tumor Marker and Predictor of Chemotherapeutic Efficacy in Non-Small Cell Lung Cancer

Apurinic/apyrimidinic endonuclease 1 (APE1), which has the dual functions of both DNA repair and redox activity, has been reported to be highly expressed in non-small cell lung cancer (NSCLC), and this appears to be a characteristic related to chemotherapy resistance. In this study, we identified serum APE1 autoantibodies (APE1-AAbs) in NSCLC patients and healthy controls by immunoblotting and investigated the expression of APE1-AAbs by indirect ELISA from the serum of 292 NSCLC patients and 300 healthy controls. In addition, serum APE1-AAbs level alterations of 91 patients were monitored before and after chemotherapy. Our results showed that serum APE1-AAbs can be detected in both NSCLC patients and healthy controls. Serum APE1-AAbs were significantly higher than those of healthy controls and closely related to APE1 antigen levels both in tumor tissues and the peripheral blood. Moreover, the change in levels of serum APE1-AAbs in NSCLC is closely associated with the response to chemotherapy. These results suggest that APE1-AAbs is a potential tumor marker and predictor of therapeutic efficacy in NSCLC.
Identification of CELF splicing activation and repression domains in vivo

CUG-BP and ETR-3 like factor (CELF) proteins are regulators of pre-mRNA alternative splicing. We created a series of truncation mutants to identify the regions of CELF proteins that are required to activate and to repress alternative splicing of different exons. This analysis was performed in parallel on two CELF proteins, ETR-3 (CUG-BP2, NAPOR, BRUNOL3) and CELF4 (BRUNOL4). We identified a 20-residue region of CELF4 required for repression or activation, in contrast to ETR-3, for which the required residues are more disperse. For both ETR-3 and CELF4, distinct regions were required to activate splicing of two different alternative exons, while regions required for repression of an additional third exon overlapped with regions required for activation. Our results suggest that activation of different splicing events by individual CELF proteins requires separable regions, implying the nature of the protein–protein interactions required for activation are target-dependent. The finding that residues required for activation and repression overlap suggests either that the same region interacts with different proteins to mediate different effects or that interactions with the same proteins can have different effects on splicing due to yet-to-be defined downstream events. These results provide a foundation for identifying CELF-interacting proteins involved in activated and/or repressed splicing.
Throughput Analysis of CSMA With Imperfect Collision Detection in Full Duplex-Enabled WLAN

As an alternative to carrier sense multiple access (CSMA) with collision avoidance in half-duplex wireless local area network (WLAN) that incurs heavy control overhead, full-duplex WLANs enabling wireless collision detection (WCD) by simultaneous carrier sensing and data transmission are gathering tremendous research interest. Although CSMA with perfect WCD leads to large throughput enhancements, actual performances will highly depend on the wireless environment, user distributions, and resulting collision patterns. Hence, we derive the achievable system throughput accounting for imperfect WCD, and evaluate the throughput gains that can be expected from CSMA with imperfect WCD over conventional random access protocols.
Comprehensive Coach Education Reduces Head Impact Exposure in American Youth Football

Background: Despite little evidence that defines a threshold of head impact exposure or that participation in youth sports leads to long-term cognitive impairments, it is prudent to identify methods of reducing the frequency of head impacts. Purpose: To compare the mean number of head impacts between youth football players in practice and games between leagues that implemented the Heads Up Football (HUF) educational program and those that did not (NHUF). Study Design: Cohort study; Level of evidence, 2. Methods: During the 2014 season, head impact exposure was measured using xPatch accelerometers from 70 youth football players aged 8 to 15 years from 5 leagues. Data were collected during both games and practices. The NHUF group comprised 32 players from 8 teams within 3 leagues. The HUF group comprised 38 players from 7 teams within 2 leagues. Independent-sample t tests evaluated differences in head impact exposure across groups (ie, HUF and NHUF). Results: Players (mean ± SD: age, 11.7 ± 1.4 years; height, 152.2 ± 10.5 cm; weight, 51.6 ± 9.6 kg) experienced a total of 7478 impacts over 10g, of which 4250 (56.8%) and 3228 (43.2%) occurred in practices and games, respectively. The majority of impacts occurred within the NHUF group (62.0%), followed by the HUF group (38.0%). With a 10g impact threshold, the mean number of impacts during practice per individual event was lower in the HUF group (mean ± SD, 5.6 ± 2.9) than in the NHUF group (mean ± SD, 8.9 ± 3.1; difference, 3.4; 95% CI, 2.9-3.9). This difference was attenuated when the threshold was changed to 20g but remained significant (difference, 1.0; 95% CI, 0.7-1.3). At both the 10g and 20g impact thresholds, no differences were found in games. Conclusion: Players who participated in HUF leagues accumulated fewer head impacts per practice at both the 10g and 20g thresholds. Youth football leagues should consider the HUF educational program, while exploring additional interventions, to help reduce the number of head impacts in players.
MUC1 as a target antigen for cancer immunotherapy

The cancer-associated antigen MUC1 is overexpressed and modified by tumor cells in over half of all cancer cases. Despite various complexities associated with this antigen, it is well worth pursuing as a vaccine for the immunotherapy of cancer. In this review, the authors describe the discovery of MUC1 and its association with cancer, recent observations showing that the immunology of MUC1 is complicated, animal data showing that it can be a target for immune-mediated tumor rejection, and finally, preliminary clinical results to show that vaccine-based immunotherapy with MUC1 does have an impact on the therapy of cancer.
Convolutional neural networks for histopathology image classification: Training vs. Using pre-trained networks

We explore the problem of classification within a medical image data-set based on a feature vector extracted from the deepest layer of pre-trained Convolution Neural Networks. We have used feature vectors from several pre-trained structures, including networks with/without transfer learning to evaluate the performance of pre-trained deep features versus CNNs which have been trained by that specific dataset as well as the impact of transfer learning with a small number of samples. All experiments are done on Kimia Path24 dataset which consists of 27,055 histopathology training patches in 24 tissue texture classes along with 1,325 test patches for evaluation. The result shows that pre-trained networks are quite competitive against training from scratch. As well, fine-tuning does not seem to add any tangible improvement for VGG16 to justify additional training while we observed considerable improvement in retrieval and classification accuracy when we fine-tuned the Inception structure.
Body Mass Index and Mortality: A Twelve-Year Prospective Study in Korea

The relation between body mass index (kg/m2) and noncoronary mortality is not well established. To study this relation, a population with low coronary mortality may be especially useful. We conducted a 12-year follow-up study of 235,398 Korean men 40–64 years of age. Study subjects had undergone health examinations in 1986 (baseline) and 1990. We excluded subjects with substantial weight loss during this period. There were 13,387 deaths, including 600 deaths from coronary events, between 1990 and 1998. We estimated the relation of body mass index to the risk of death after adjusting for common risk factors. There was a positive relation between body mass index and coronary mortality, but this relation was attenuated after serum total cholesterol, blood pressure, and fasting serum glucose were taken into account. A J-shaped relation with cerebrovascular mortality was also attenuated after adjustment. Even after this adjustment and exclusion of early deaths between 1990 and 1994, the relation of body mass index to all-cause (U-shaped), cancer (J-shaped), and noncancer noncoronary noncerebrovascular (inverse J-shaped) mortality remained. Both high and low body mass index were related to increased mortality among these Korean men.