Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural insights into methylated DNA recognition by the C-terminal zinc fingers of the DNA reader protein ZBTB38

Methyl-CpG–binding proteins (MBPs) are selective readers of DNA methylation that play an essential role in mediating cellular transcription processes in both normal and diseased cells. This physiological function of MBPs has generated significant interest in understanding the mechanisms by which these proteins read and interpret DNA methylation signals. Zinc finger and BTB domain–containing 38 (ZBTB38) represents one member of the zinc finger (ZF) family of MBPs. We recently demonstrated that the C-terminal ZFs of ZBTB38 exhibit methyl-selective DNA binding within the ((A/G)TmCG(G/A)(mC/T)(G/A)) context both in vitro and within cells. Here we report the crystal structure of the first four C-terminal ZBTB38 ZFs (ZFs 6–9) in complex with the previously identified methylated consensus sequence at 1.75 Å resolution. From the structure, methyl-selective binding is preferentially localized at the 5′ mCpG site of the bound DNA, which is facilitated through a series of base-specific interactions from residues within the α-helices of ZF7 and ZF8. ZF6 and ZF9 primarily stabilize ZF7 and ZF8 to facilitate the core base–specific interactions. Further structural and biochemical analyses, including solution NMR spectroscopy and electrophoretic mobility gel shift assays, revealed that the C-terminal ZFs of ZBTB38 utilize an alternative mode of mCpG recognition from the ZF MBPs structurally evaluated to date. Combined, these findings provide insight into the mechanism by which this ZF domain of ZBTB38 selectively recognizes methylated CpG sites and expands our understanding of how ZF-containing proteins can interpret this essential epigenetic mark.
Effect of Hearing Aid Directionality and Remote Microphone on Speech Intelligibility in Complex Listening Situations

Remote microphones (RMs) have been developed to support hearing aid (HA) users in understanding distant talkers. In traditional clinical applications, a drawback of these systems is the deteriorated speech intelligibility in the near field. This study investigates advantages and disadvantages of clinical RM usage and the effects of different directionality settings of the HAs in complex listening situations in the laboratory. Speech intelligibility was investigated in 15 experienced severely hearing impaired participants in a noisy environment using a dual-task test paradigm where the tasks were presented from either a near field or a far field loudspeaker. Primary and secondary tasks were presented simultaneously so attention had to be shared on both tasks. In a second experiment, two speech intelligibility tests were presented from either the near field or the far field loudspeaker. The tests were interleaved to simulate a complex listening situation with shifting attention. Directional HA microphones yielded better performance than omnidirectional microphones (both combined with a RM) in near field when analyzing both tasks of the dual-task experiment separately. Furthermore, the integrated dual-task test results showed better performance with directional HA microphones compared with the omnidirectional setting (both cases in combination with a RM). These findings were confirmed by the results of the interleaved speech intelligibility test.
Semi-Automatic High-Accuracy Labelling Tool for Multi-Modal Long-Range Sensor Dataset

Many research works have contributed to achieve SAE levels 3 and 4 in some pre-defined areas under certain restrictions. A deeper scene understanding and precise predictions of drivers intentions are needed to continue improving autonomous driving capabilities to reach higher SAE levels. Deployment of accurate and detailed datasets could be considered as one of the most pressing needs to enhance autonomous driving capabilities. This work presents a novel data acquisition methodology for on-road vehicle trajectory collection. The proposed sensor setup improves the range and detection accuracy by using a high accuracy laser scanner covering 360° and two high-speed and high-resolution cameras. The sensor fusion increases the labelling resolution and extends the detection range sporting the best of each sensor. A Median Flow tracking algorithm and a Convolutional Neural Network enable a semi-automatic labelling process, which reduces the effort to create detailed annotated datasets. High accurate trajectories are reconstructed with few manual annotations up to 60m with a mean error below 2 cm. This methodology has been developed with a view to creating a dataset which enables the development of advanced vehicle trajectory prediction systems, and thus to contribute to human-like automated driving.
Validation of a non-invasive method for the early detection of metabolic syndrome: a diagnostic accuracy test in a working population

Objectives A non-invasive method for the early detection of metabolic syndrome (NIM-MetS) using only waist-to-height ratio (WHtR) and blood pressure (BP) has recently been published, with fixed cut-off values for gender and age. The aim of this study was to validate this method in a large sample of Spanish workers. Design A diagnostic test accuracy to assess the validity of the method was performed. Setting Occupational health services. Participants The studies were conducted in 2012–2016 on a sample of 60 799 workers from the Balearic Islands (Spain). Interventions The NCEP-ATP III criteria were used as the gold standard. NIM-MetS has been devised using classification trees (the χ2 automatic interaction detection method). Main outcome measures Anthropometric and biochemical variables to diagnose MetS. Sensitivity, specificity, validity index and Youden Index were determined to analyse the accuracy of the diagnostic test (NIM-MetS). Results With regard to the validation of the method, sensitivity was 54.7%, specificity 94.9% and the Validity Index 91.2%. The cut-off value for WHtR was 0.54, ranging from 0.51 (lower age group) to 0.56 (higher age group). Variables more closely associated with MetS were WHtR (area under the curve (AUC)=0.85; 95% CI 0.84 to 0.86) and systolic BP (AUC=0.79; 95% CI 0.78 to 0.80)). The final cut-off values for the non-invasive method were WHtR ≥0.56 and BP ≥128/80 mm Hg, which includes four levels of MetS risk (very low, low, moderate and high). Conclusions The analysed method has shown a high validity index (higher than 91%) for the early detection of MetS. It is a non-invasive method that is easy to apply and interpret in any healthcare setting. This method provides a scale of MetS risk which allows more accurate detection and more effective intervention.
Identification of Primary Medication Concerns Regarding Thyroid Hormone Replacement Therapy From Online Patient Medication Reviews: Text Mining of Social Network Data

Background Patients with hypothyroidism report poor health-related quality of life despite having undergone thyroid hormone replacement therapy (THRT). Understanding patient concerns regarding levothyroxine can help improve the treatment outcomes of THRT. Objective This study aimed to (1) identify the distinctive themes in patient concerns regarding THRT, (2) determine whether patients have unique primary medication concerns specific to their demographics, and (3) determine the predictability of primary medication concerns on patient treatment satisfaction. Methods We collected patient reviews from WebMD in the United States (1037 reviews about generic levothyroxine and 1075 reviews about the brand version) posted between September 1, 2007, and January 30, 2017. We used natural language processing to identify the themes of medication concerns. Multiple regression analyses were conducted in order to examine the predictability of the primary medication concerns on patient treatment satisfaction. Results Natural language processing of the patient reviews of levothyroxine posted on a social networking site produced 6 distinctive themes of patient medication concerns related to levothyroxine treatment: how to take the drug, treatment initiation, dose adjustment, symptoms of pain, generic substitutability, and appearance. Patients had different primary medication concerns unique to their gender, age, and treatment duration. Furthermore, treatment satisfaction on levothyroxine depended on what primary medication concerns the patient had. Conclusions Natural language processing of text content available on social media could identify different themes of patient medication concerns that can be validated in future studies to inform the design of tailored medication counseling for improved patient treatment satisfaction.
Estrogen Signaling in Bystander Foxp3neg CD4+ T Cells Suppresses Cognate Th17 Differentiation in Trans and Protects from Central Nervous System Autoimmunity

17β-Estradiol (E2) suppresses the development of experimental autoimmune encephalomyelitis (EAE) through estrogen receptor (ER) α, yet the cellular targets remain elusive. We have used an adoptive transfer model of myelin oligodendrocyte glycoprotein–specific CD4+ T cells from 2D2 TCR transgenic mice. We show that in the recipient mice, ERα expression in bystander CD4+ T cells, rather than in cognate 2D2 T cells, is required for the inhibition of Th17 cell differentiation by E2. Coadministration of estrogen-primed WT, but not ERα-deficient CD4+ T cells, with naive 2D2 T cells lacking ERα inhibited the development of Th17 cell–mediated EAE. Suppression of Th17 cells and protection from EAE were maintained when ERα was deleted in Foxp3+ regulatory T cells. We showed that in vivo PD-L1 blockade alleviated the anti-inflammatory action of E2 and that PD-1 expression on cognate but not bystander T cells was required for the E2-dependent inhibition of Th17 differentiation. In cotransfer experiments, we found that only WT but not PD-1KO 2D2 T cells were amenable to E2-dependent inhibition of Th17 differentiation. These results support the conclusion that the restriction of Th17 cell development by E2-primed bystander CD4+ T cells requires cell-intrinsic PD-1 signaling within cognate T cells rather than induction of regulatory 2D2 T cells through PD-1 engagement. Altogether, our results indicate that pregnancy-level concentrations of estrogen signal in conventional Foxp3neg CD4+ T cells to limit the differentiation of cognate Th17 cells through a trans-acting mechanism of suppression that requires a functional PD-1/PD-L1 regulatory axis.
Molecular detection and phylogenetic properties of isolated infectious bronchitis viruses from broilers in Ahvaz, southwest Iran, based on partial sequences of spike gene

Infectious bronchitis (IB) is a highly contagious disease involving mostly upper respiratory tract in chickens, leading to significant economic losses in the poultry industry worldwide. One of the major concerns regarding to IB is the emergence of new types of infectious bronchitis viruses (IBVs). The purpose of this study was to identify the IBVs isolated from Iranian broiler chickens with respiratory symptoms. Twenty-five broiler flocks around Ahwaz (southwest of Iran) were examined for IBV. The specimens including trachea, lung, liver, kidney, and ceacal tonsil, were collected from diseased birds and inoculated into chicken embryonated eggs. Harvested allantoic fluids were subjected to reverse transcription polymerase chain reaction (RT-PCR) using primers in order to amplify spike 1 (S1) gene of IBV. The RT-PCR products of four IBV isolates were sequenced. The results showed that from 25 examined flocks with respiratory disease, 12 flocks (48.00%) were positive for IBV. In phylogenetic analysis, our isolates were closely related to the QX-like viruses such as PCRLab/06/2012 (Iran), QX, HC9, HC10, CK/CH/GX/NN11-1, CK/CH/JS/YC11-1, CK/CH/JS/2010/13, CK/CH/JS/2011/2 (China), QX/SGK-21, QX/SGK-11 (Iraq) with nucleotide homology up to 99.00%. This study indicates the role of IBVs in the respiratory disorders of broiler flocks located in southwest Iran, and also the existence of a variant of IBV, which is distinguishable from the other Iranian variants.
Screen Printed Tactile Sensing Arrays for Prosthetic Applications

The lack of tactile sensation in current upper limb prostheses is the key limitation to enable more intuitive use of the prosthesis and restore the functionality of the natural limb. Electronic skin in the form of tactile sensing arrays can be integrated onto the upper limb prosthetic device to record information about touch, given back to the amputee as a sensory feedback. This contribution focusses on the development of tactile sensing arrays based on PVDF-TrFE piezoelectric polymers. Both piezoelectric polymer sensors and metal contacts have been screen-printed on a transparent plastic foil. The geometric layout and size of the 4×4 array is suitable for prosthesis fingertips. Preliminary experimental validation of the skin patches is reported in this paper.
Data Collection and Processing Methods for the Evaluation of Vehicle Road Departure Detection Systems

Road departure detection systems (RDDSs) for avoiding/mitigating road departure crashes have been developed and included on some production vehicles in recent years. In order to support and provide a standardized and objective performance evaluation of RDDSs, this paper describes the development of the data acquisition and data post-processing systems for testing RDDSs. Seven parameters are used to describe road departure test scenarios. The overall structure and specific components of data collection system and data post-processing system for evaluating vehicle RDDSs is devised and presented. Experimental results showed sensing system and data post-processing system could capture all needed signals and display vehicle motion profile from the testing vehicle accurately. Test track testing under different scenarios demonstrates the effective operations of the proposed data collection system.
Incidence of mental health hospitalizations, treated self‐harm, and emergency room visits following new anxiety disorder diagnoses in privately insured U.S. children

Anxiety disorders are one of the most common mental illnesses in children and associated with high healthcare utilization. We aimed to estimate 2‐year cumulative incidence of mental health–related hospitalizations, treated self‐harm, and emergency room (ER) visits in children newly diagnosed with anxiety disorders and, for context, in children without anxiety disorders.
Cerebral Cortical Microinfarcts on Magnetic Resonance Imaging and Their Association With Cognition in Cerebral Amyloid Angiopathy

Background and Purpose— We aimed to explore the association between presence of cerebral cortical microinfarcts (CMIs) on magnetic resonance imaging and other small-vessel disease neuroimaging biomarkers in cerebral amyloid angiopathy (CAA) and to analyze the role of CMIs on individual cognitive domains and dementia conversion. Methods— Participants were recruited from an ongoing longitudinal research cohort of eligible CAA patients between March 2006 and October 2016. A total of 102 cases were included in the analysis that assessed the relationship of cortical CMIs to CAA neuroimaging markers. Ninety-five subjects had neuropsychological tests conducted within 1 month of magnetic resonance imaging scanning. Seventy-five nondemented CAA patients had cognitive evaluation data available during follow-up. Results— Among 102 patients enrolled, 40 patients had CMIs (39%) on magnetic resonance imaging. CMIs were uniformly distributed throughout the cortex without regional predilection (P=0.971). The presence of CMIs was associated with lower total brain volume (odds ratio, 0.85; 95% CI, 0.74–0.98; P=0.025) and presence of cortical superficial siderosis (odds ratio, 2.66; 95% CI, 1.10–6.39; P=0.029). In 95 subjects with neuropsychological tests, presence of CMIs was associated with impaired executive function (&bgr;, −0.23; 95% CI, −0.44 to −0.02; P=0.036) and processing speed (&bgr;, −0.24; 95% CI, −0.45 to −0.04; P=0.020). Patients with CMIs had a higher cumulative dementia incidence compared with patients without CMIs (P=0.043), whereas only baseline total brain volume (hazard ratio, 0.76; 95% CI, 0.62–0.92; P=0.006) independently predicted dementia conversion. Conclusions— Magnetic resonance imaging–detected CMIs in CAA correlated with greater overall disease burden. The presence of CMIs was associated with worse cognitive performance, whereas only total brain atrophy independently predicted dementia conversion.
Optimal PSF Estimation for Simple Optical System Using a Wide-Band Sensor Based on PSF Measurement

Simple optical system imaging is a method to simplify optical systems by removing aberrations using image deconvolution. The point spread function (PSF) used in deconvolution is an important factor that affects the image quality. However, it is difficult to obtain optimal PSFs. The blind estimation of PSFs relies heavily on the information in the image. Measured PSFs are often misused because real sensors are wide-band. We present an optimal PSF estimation method based on PSF measurements. Narrow-band PSF measurements at a single depth are used to calibrate the optical system; these enable the simulation of real lenses. Then, we simulate PSFs in the wavelength pass range of each color channel all over the field. The optimal PSFs are computed according to these simulated PSFs. The results indicated that the use of the optimal PSFs significantly reduces the artifacts caused by misuse of PSFs, and enhances the image quality.
A Compact Map Representation for Large-scale Environments and Localization Method based on Similarity Measure

Targeted at autonomous driving, compact map representation for localization is needed to deal with limited disk space or communication bandwidth. State-of-the-art compact map representations distinguish partial-objects such as lane markings from whole-object data. However, they require that objects are correctly detected in both map generation and localization. Therefore, the localization may fail if either of these conditions is violated due to occlusion, poor road texture, or other complications. In this paper, we propose a novel map generation and localization method that uses whole-object data without object detection. The novel map so produced has compactness comparable to state-of-the-art methods involving object detection because it is described as blocks of quantized representation in a voxel grid. In the localization step, we formulate localization as a similarity search between the map data and differently sampled sensor data. The proposed localization method performs the search at a sub-voxel level while alleviating voxel discretization error. This enables accurate localization even with low-resolution voxels. Experiments show the proposed method achieves sufficient localization accuracy and real-time processing with a map having a data size of 32 kB per km. The storage efficiency is at least 161 times greater than state-of-the-art maps covering the same area.
Sustained Results in Long-Term Follow-Up of Autologous Chondrocyte Implantation (ACI) for Distal Femur Juvenile Osteochondritis Dissecans (JOCD)

Introduction Concern regarding ability of autologous chondrocyte implantation (ACI) to correct for the bone and cartilage pathology of knee juvenile osteochondritis dissecans (JOCD) exists. The purpose of this study was to determine long-term, patient-based outcomes of ACI treatment of JOCD in young patients. Authors hypothesized long-term outcomes are comparable to reported mid-term outcomes. Methods A single institution, longitudinal cohort study design combining medical record review and outcome surveys was used. Inclusion criteria included isolated JOCD diagnosis, failed primary healing of operatively treated JOCD, ACI surgery > 5 years ago, and ≤20 years of age at time of ACI. Results 10/26 eligible patients (38.5%) participated (M: F = 5:5, age at ACI: 18.3 ± 2.5 y, current age: 30.8 ± 5.1 y, and current BMI: 24.6 ± 2.1). Follow-up was 12.0 ± 4.5 y. Lesion size at ACI was 9.1 ± 1.9 cm2. Femoral condyle location was medial = 6 and lateral = 4. All required treatment at some point for knee symptoms after ACI. During the past one year, four patients required treatment. Patient reported outcome scores at 12 years following ACI were IKDC score: 73.0 ± 3.6, KOOS scores including pain [88.7 ± 2.3], symptoms [78.2 ± 4.6], activity of daily living [94.7 ± 1.9], function, sports, and recreational activities [73.0 ± 5.3], and quality of life [57.5 ± 5.8], and Modified Cincinnati Knee Rating score was 77.9 ± 4.1. A moderate to good relationship was found between KOOS symptoms and BMI and lesion size. Function, sports, and recreational activities of the KOOS were greater in participants who had ≤1 lesion prior to ACI procedures (p = 0.044). Conclusion This study of ACI treatment of knee JOCD patients confirms sustained, long-term results. Number of lesions prior to ACI procedure influenced status of function, sports, and recreational activities.
Web-based Volume Rendering using Progressive Importance-based Data Transfer

WebGL 2.0 makes it possible to implement efﬁcient volume rendering that runs in browsers using 3D textures and complex fragment shaders. However, a typical bottleneck for web-based volume rendering is the size of the volumetric data sets. Transferring these data to the client for rendering can take a substantial amount of time, depending on the network speed. This can introduce latency that can in turn affect interactive rendering at the client. We address this challenge by introducing a multi-resolution bricked volume rendering, where data is transferred progressively. Similar to MIP-Mapping, the volume data is divided into multiple levels of detail. Each level of detail is broken down into bricks. The client requests the data brick by brick starting with the lowest resolution and renders each brick immediately as it is received. The 3D volume texture is updated as bricks with higher resolution are received asynchronously from the server. The advantages of this algorithm are that it reduces latency, the user can see at least a reduced-detail version of the data almost immediately, and the application always stays responsive while the data is updated. We also implemented a prioritization scheme for the bricks, where each brick can be assigned an importance value. Using this information, the client can request more important bricks ﬁrst. Furthermore, we investigated the inﬂuence of data compression on the transfer and processing times.