Miracle-dz/UniFAR-FTUs huggingface dataset:
Microdevice Development and Artificial Organs.

Over the past several decades, there has been an explosion in the development of microfabricated medical sensors and actuators. From the earliest development of silicon based MicroElectroMechanical Systems or MEMS devices there has been an interest in developing MEMS technology to support the medical field (biomedical MEMS or BioMEMS) (1, 2). Many of these technologies have positively impacted the medical field in general and the Artificial Organs field in particular. These technologies have brought medical sensors into the clinic, operating rooms or even as implantable technologies (Figure 1). As the BioMEMS field has matured, devices are increasing being developed as an active interface between the artificial microdevice and patients. Microfabricated medical transducers have evolved from solid state physical transducers such as force, pressure and flow sensors for measuring respiration, blood pressure and flow rates, into microfabricated multielectrode intracortical stimulating and recording arrays (neural probes) (3, 4), neural prostheses (5, 6), and polymer based microfluidic devices (7, 8) to perform highly sensitive point of care diagnostic assays (9) or supporting microscale cell cultures or Organ on a Chip platforms (10, 11). At this time we are also beginning to see widespread commercialization of many of these diagnostic technologies (12). Such sensors are also part of the trend of creating sensorized or ‘smart’ products and creating the so-called ‘internet of things’ for wearable diagnostics or personalized healthcare monitors (9).
Dynamic platelet function is markedly different in patients with cancer compared to healthy donors

Abstract Despite a fivefold increased risk of thromboembolism in patients with cancer, the mechanism of arterial thromboembolism is poorly understood. To address this, we investigated platelet function in cancer patients and healthy controls using an assay that mimics the arterial vasculature. Blood samples from cancer patients (n = 36) and healthy controls (n = 22) were perfused through custom-made parallel-plate flow chambers coated with von Willebrand factor (VWF) under arterial shear (1,500 s−1). Multiparameter measurements of platelet interactions with the immobilized VWF surface were recorded by digital-image microscopy and analyzed using custom-designed platelet-tracking software. Six measured parameters that characterize in detail the surface motion and surface binding of several hundred platelets per blood sample differed significantly in those with cancer from the healthy donors. In particular, it was found that patients with cancer had decreased numbers of platelets interacting, translocating and adhering to VWF. There were also reductions in the speed and distances that platelets traveled on VWF in comparison to healthy controls. Platelet function differed between those with early-stage cancer compared to those with later stage cancer. Patients with advanced cancer had an increased number of platelets stably adhering to VWF and greater platelet surface coverage after a given time of interaction. To the best of our knowledge, our results demonstrate for the first time that dynamic platelet function is markedly different in patients with cancer compared to healthy donors.
Learning-based frequency response function estimation for nonlinear systems

ABSTRACT In this paper, we perform the nonlinear frequency response function (FRF) estimation for a class of nonlinear systems. Two non-parametric estimation techniques are considered: radial basis function neural network (RBF-NN)-based estimation and support vector machine (SVM)-based estimation. Based on the system's available observations, the proposed estimation models are used to predict its frequency response. Simulation results are provided to demonstrate the model implementation. Finally, a comparative study is carried out to evaluate the effectiveness of the RBF-NN and SVM schemes, which has demonstrated that the SVM outperformed RBF-NN in the FRF estimation.
Could Platelet Indices and Neutrophil to Lymphocyte Ratio Be New Biomarkers for Differentiation of Arteritic Anterior Ischemic Neuropathy from Non-Arteritic Type?

ABSTRACT The aim of this study was to assess the possible relationship between AAION (arteritic anterior ischemic optic neuropathy) and NAION (non-arteritic anterior ischemic optic neuropathy) with blood platelet parameters and NLR (neutrophil-to-lymphocyte ratio). The medical records of 12 patients with AAION, 33 patients with NAION, and 35 healthy subjects were examined. MPV, PDW, and PCT values showed marked elevation in AAION and NAION groups compared with control group. The mean NLR was statistically significantly higher only in AAION group compared to the NAION and control groups, suggesting that platelet function plays an important role in AIONs and NLR might be used to differentiate AAION from NAION.
Potentially functional genetic variants in the complement‐related immunity gene‐set are associated with non‐small cell lung cancer survival

The complement system plays an important role in the innate and adaptive immunity, complement components mediate tumor cytolysis of antibody‐based immunotherapy, and complement activation in the tumor microenvironment may promote tumor progression or inhibition, depending on the mechanism of action. In the present study, we conducted a two‐phase analysis of two independently published genome‐wide association studies (GWASs) for associations between genetic variants in a complement‐related immunity gene‐set and overall survival of non‐small cell lung cancer (NSCLC). The GWAS dataset from Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was used as the discovery, and multivariate Cox proportional hazards regression with false‐positive report probability for multiple test corrections were performed to evaluate associations between 14,699 single‐nucleotide polymorphisms (SNPs) in 111 genes and survival of 1,185 NSCLC patients. The identified significant SNPs in a single‐locus analysis were further validated with 984 NSCLC patients in the GWAS dataset from the Harvard Lung Cancer Susceptibility (HLCS) Study. The results showed that two independent, potentially functional SNPs in two genes (VWF rs73049469 and ITGB2 rs3788142) were significantly associated with NSCLC survival, with a combined hazards ratio (HR) of 1.22 [95% confidence interval (CI) = 1.07–1.40, P = 0.002] and 1.16 (1.07–1.27, 6.45 × 10−4), respectively. Finally, we performed expression quantitative trait loci (eQTL) analysis and found that survival‐associated genotypes of VWF rs73049469 were also significantly associated with mRNA expression levels of the gene. These results indicated that genetic variants of the complement‐related immunity genes might be predictors of NSCLC survival, particularly for the short‐term survival, possibly by modulating the expression of genes involved in the host immunity.
Insulin Resistance and Vulnerability to Cardiac Ischemia

Hepatic and myocardial ectopic lipid deposition has been associated with insulin resistance (IR) and cardiovascular risk. Lipid overload promotes increased hepatic oxidative capacity, oxidative stress, and impaired mitochondrial efficiency, driving the progression of nonalcoholic fatty liver disease (NAFLD). We hypothesized that higher lipid availability promotes ischemia-induced cardiac dysfunction and decreases myocardial mitochondrial efficiency. Mice with adipose tissue–specific overexpression of sterol element–binding protein 1c as model of lipid overload with combined NAFLD-IR and controls underwent reperfused acute myocardial infarcts (AMIs). Whereas indexes of left ventricle (LV) contraction were similar in both groups at baseline, NAFLD-IR showed severe myocardial dysfunction post-AMI, with prominent LV reshaping and increased end-diastolic and end-systolic volumes. Hearts of NAFLD-IR displayed hypertrophy, steatosis, and IR due to 18:1/18:1-diacylglycerol–mediated protein kinase Cε (PKCε) activation. Myocardial fatty acid–linked respiration and oxidative stress were increased, whereas mitochondrial efficiency was decreased. In humans, decreased myocardial mitochondrial efficiency of ventricle biopsies related to IR and troponin levels, a marker of impaired myocardial integrity. Taken together, increased lipid availability and IR favor susceptibility to ischemia-induced cardiac dysfunction. The diacylglycerol-PKCε pathway and reduced mitochondrial efficiency both caused by myocardial lipotoxicity may contribute to the impaired LV compensation of the noninfarcted region of the myocardium.
Rediscovering Deep Neural Networks in Finite-State Distributions

We propose a new way of thinking about deep neural networks, in which the linear and non-linear components of the network are naturally derived and justified in terms of principles in probability theory. In particular, the models constructed in our framework assign probabilities to uncertain realizations, leading to Kullback-Leibler Divergence (KLD) as the linear layer. In our model construction, we also arrive at a structure similar to ReLU activation supported with Bayes' theorem. The non-linearities in our framework are normalization layers with ReLU and Sigmoid as element-wise approximations. Additionally, the pooling function is derived as a marginalization of spatial random variables according to the mechanics of the framework. As such, Max Pooling is an approximation to the aforementioned marginalization process. Since our models are comprised of finite state distributions (FSD) as variables and parameters, exact computation of information-theoretic quantities such as entropy and KLD is possible, thereby providing more objective measures to analyze networks. Unlike existing designs that rely on heuristics, the proposed framework restricts subjective interpretations of CNNs and sheds light on the functionality of neural networks from a completely new perspective.
A strong spatial association between e‐waste burn sites and childhood lymphoma in the West Bank, Palestine

A paper in the International Journal of Cancer analyzed Palestinian cancer registry data in the West Bank from 1998 to 2007, showing a cluster of elevated cancer incidence in rural villages in south‐west Hebron, with a 4.10 risk ratio for childhood lymphoma (p = 0.0023). The paper called for investigation of the environmental or genetic etiologies of this cluster in an otherwise unremarkable rural area.1 Our research in these same villages shows them to be the center of an extensive informal electronic and electrical waste (e‐waste) dismantling industry in Palestine, operating for almost two decades. This entails extensive open‐burning of e‐waste components to extract valuable metals or dispose of nonvaluable waste, releasing high concentrations of hazardous contaminants, which may be an important factor in the elevated cancer incidence. We offer a first step in assessing this link. We applied a novel multitemporal object‐based method to map the prevalence and intensity of e‐waste burn sites in the entire Hebron Governorate (1,060 km2) between 1999 and 2007. A weighted standard deviation ellipse of cumulative burn activity covers a smaller area (247 km2) very closely matching the childhood lymphoma cluster: it contains 85% of the core cluster area (RR of 4.1), and falls almost entirely (95%) within the broader area of elevated risk (RR of 2.8). Extensive international evidence linking informal e‐waste processing to elevated cancer incidence and this strong spatial association of e‐waste burning activity with a distinct unexplained cancer cluster in the Palestinian context signals the urgent need for investigation and intervention.
Drug-susceptible tuberculosis treatment success and associated factors in Ethiopia from 2005 to 2017: a systematic review and meta-analysis

Objectives The main aim of this study was to assess the overall tuberculosis (TB) treatment success in Ethiopia and to identify potential factors for poor TB treatment outcome. Design A systematic review and meta-analysis of published literature was conducted. Original studies were identified through a computerised systematic search using PubMed, Google Scholar and Science Direct databases. Heterogeneity across studies was assessed using Cochran’s Q test and I2 statistic. Pooled estimates of treatment success were computed using the random-effects model with 95% CI using Stata V.14 software. Results A total of 230 articles were identified in the systematic search. Of these 34 observational studies were eligible for systematic review and meta-analysis. It was found that 117 750 patients reported treatment outcomes. Treatment outcomes were assessed by World Health Organization (WHO) standard definitions of TB treatment outcome. The overall pooled TB treatment success rate in Ethiopia was 86% (with 95% CI 83%_88%). TB treatment success rate for each region showed that, Addis Ababa (93%), Oromia (84%), Amhara (86%), Southern Nations (83%), Tigray (85%) and Afar (86%). Mainly old age, HIV co-infection, retreatment cases and rural residence were the most frequently identified factors associated with poor TB treatment outcome. Conclusion The result of this study revealed that the overall TB treatment success rate in Ethiopia was below the threshold suggested by WHO (90%). There was also a discrepancy in TB treatment success rate among different regions of Ethiopia. In addition to these, HIV co-infection, older age, retreatment cases and rural residence were associated with poor treatment outcome. In order to further improve the treatment success rate, it is strategic to give special consideration for regions which had low TB treatment success and patients with TB with HIV co-infection, older age, rural residence and retreatment cases.
Fluctuating Asymmetry as a Bioindicator of Environmental Stress Caused by Pollution in a Pioneer Plant Species

Abstract Fluctuating asymmetry (FA) is a widely used tool to detect developmental instability and plants under stressful conditions are expected to exhibit increased values of asymmetry, as well as higher levels of herbivory. This study evaluated whether dust from roads can cause major deviations in the axis of symmetry of leaves of the pioneer plant species Cecropia pachystachya Trécul (Urticaceae). It was also investigated whether plants exposed to dust have greater nitrogen content and higher levels of herbivory levels. Ten leaves of 20 individuals of C. pachystachya were collected on two roads with different levels of dust deposition and a control area. FA was calculated as the size-scaled difference between the right (RW) and left (LW) leaf widths and leaf area removed was determined by the ratio between leaf area removed and total leaf area. C. pachystachya plants in areas under strong influence of dust pollution exhibited the highest FA values (0.279 cm), whereas plants in the control area exhibited the lowest. A positive relationship between levels of leaf area removed by insects and a gradient of dust pollution was also observed. Differences in foliar nitrogen concentration among sampling areas indicated differences in leaf quality and influenced herbivory levels of Cecropia. This study indicated that FA can be used as an indicator of developmental instability of plants and those individuals under the impact of road dust and pollution might be more susceptible to insect attack.
Fronto-Temporal Circuits in Musical Hallucinations: A PET-MR Case Study

The aim of the study is to investigate morphofunctional circuits underlying musical hallucinations (MH) in a 72-years old female that underwent a simultaneous 18fluoredeoxyglucose positron emission tomography (PET) and advanced magnetic resonance (MR) exam. This represents a particular case of MH occurred in an healthy subject, not displaying neurological or psychopathological disorders, and studied simultaneously with a multimodal approach. For the resting-state fMRI analysis a seed to seed approach was chosen. For the task-based fMRI, 4 different auditory stimuli were presented. Imaging findings were compared with data obtained by ten healthy controls matched for age and sex. Neuropsychological evaluation and questionnaires investigating depression and anxiety were also administered. PET findings showed hypermetabolism of: superior temporal gyri, anterior cingulate, left orbital frontal, and medial temporal cortices. Structural MRI did not show macroscopical lesions except for gliotic spots along the uncinate fascicle pathways with an increased cortical thickness for the right orbitofrontal cortex (p = 0.003). DTI showed increased fractional anisotropy values in the left uncinate fascicle, when compared to controls (p = 0.04). Resting-state fMRI showed increased functional connectivity between the left inferior frontal gyrus and the left temporal fusiform cortex (p = 0.01). Task-based fMRI confirmed PET findings showing an increased activation of the superior temporal gyrus in all the auditory tasks except for the monotone stimulus, with a significant activation of the left orbital frontal cortex only during the song in foreign language, object of MH. Results on cognitive test did not show cognitive impairment, excepting for the performance on Frontal Assessment Battery where the patient fails in the cognitive domains of conceptualization, sensitive to interference, and inhibitory control. The subject did not show depressive or anxiety symptoms. Summarizing, multimodal imaging analyses in the MH case showed a microstructural alteration of the left uncinate fascicle paralleled by an increased metabolism and functional connectivity of cortical regions that receive left uncinate projections (orbital frontal cortex, and medial temporal cortex). This alteration of fronto-hyppocampal circuits could be responsible of retrieval of known songs even in the absence of real stimuli.
Expression Profile and Functional Characterization Suggesting the Involvement of Three Chemosensory Proteins in Perception of Host Plant Volatiles in Chilo suppressalis (Lepidoptera: Pyralidae)

Abstract The high sensitivity of the olfactory system is essential for feeding and oviposition in moth insects, and some chemosensory proteins (CSPs) are thought to play roles in this system by binding and carrying hydrophobic odorants across the aqueous sensillar lymph. In this study, to identify the olfactory CSPs from a repertoire of 21 CSP members in the notorious rice pest Chilo suppressalis (Walker) (Lepidoptera: Pyralidae), tissue expression patterns were firstly examined by quantitative real-time polymerase chain reaction (qPCR). It showed that CSP2 was antennae specific and seven more CSPs (CSP1, 3, 4, 6, 15, 16, and 17) were antennae biased in expression, suggesting their olfactory roles; while other CSPs were multiple-tissue expressed and non-antennae biased, suggesting other functions for these genes. To further determine the ligand binding specificity, three putative olfactory genes (CSP1–3) were expressed in Escherichia coli cells, and binding affinity of these three recombinant CSP proteins were measured for 35 plant volatiles by the ligand binding assays. CSP1 and CSP2 exhibited high binding affinities (Ki ≤ 10.00 µM) for four (2-tridecanone, benzaldehyde, laurinaldehyde and 2-pentadecanone) and two (2-heptanol and (+)-cedrol) host plant volatiles, respectively; the three CSPs also showed moderate binding affinity (Ki = 10.01–20.00 µM) for 16 plant volatiles. Our study suggests that the three CSPs play essential roles in the perception of host plant volatiles, providing bases for the elucidation of olfactory mechanisms in this important pyralid pest.
Alterations in intrinsic fronto‐thalamo‐parietal connectivity are associated with cognitive control deficits in psychotic disorders

Despite a growing number of reports about alterations in intrinsic/resting brain activity observed in patients with psychotic disorders, their relevance to well‐established cognitive control deficits in this patient group is not well understood. Totally 88 clinically stabilized patients with a psychotic disorder and 50 healthy controls participated in a resting‐state magnetic resonance imaging study (rs‐MRI) and performed an antisaccade task in the laboratory to assess voluntary inhibitory control ability. Deficits on this task are a well‐established biomarker across psychotic disorders as we found in the present patient sample. First, regional cerebral function was evaluated by measuring the amplitude of low frequency fluctuations (ALFF) in rs‐MRI BOLD signals. We found reduced ALFF in patients in regions known to be relevant to antisaccade task performance including bilateral frontal eye fields (FEF), supplementary eye fields (SEF) and thalamus. Second, areas with ALFF alterations were used as seed areas in whole‐brain functional connectivity (FC) analysis. Altered FC was observed in a fronto‐thalamo‐parietal network that was associated with inhibition error rate in patients but not in controls. In contrast, faster time to generate a correct antisaccade was associated with FC in FEF and SEF in controls but this effect was not seen in patients. These findings establish a behavioral relevance of resting‐state fMRI findings in psychotic disorders, and extend previous reports of alterations in fronto‐thalamo‐parietal network activation during antisaccade performance seen in task‐based fMRI studies.
Role of transcription complexes in the formation of the basal methylation pattern in early development

Significance This paper reveals the molecular logic for generating the basal methylation pattern in each individual following erasure of the gametic profile in the preimplantation embryo. The results show that transcription factors and the RNA polymerase complex play a major role in protecting recognized regions from de novo methylation by recruiting the H3K4 methylation machinery. Because methylation is stably maintained through development, this mechanism serves to perpetuate the activity state present in the early embryo. This model may also help explain how transient factors from the gametes may influence methylation patterns in the offspring and, thereby, contribute to intergenerational epigenetic inheritance. Following erasure in the blastocyst, the entire genome undergoes de novo methylation at the time of implantation, with CpG islands being protected from this process. This bimodal pattern is then preserved throughout development and the lifetime of the organism. Using mouse embryonic stem cells as a model system, we demonstrate that the binding of an RNA polymerase complex on DNA before de novo methylation is predictive of it being protected from this modification, and tethering experiments demonstrate that the presence of this complex is, in fact, sufficient to prevent methylation at these sites. This protection is most likely mediated by the recruitment of enzyme complexes that methylate histone H3K4 over a local region and, in this way, prevent access to the de novo methylation complex. The topological pattern of H3K4me3 that is formed while the DNA is as yet unmethylated provides a strikingly accurate template for modeling the genome-wide basal methylation pattern of the organism. These results have far-reaching consequences for understanding the relationship between RNA transcription and DNA methylation.