Miracle-dz/UniFAR-FTUs huggingface dataset:
Diversity of Internal Sensory Neuron Axon Projection Patterns Is Controlled by the POU-Domain Protein Pdm3 in Drosophila Larvae

Internal sensory neurons innervate body organs and provide information about internal state to the CNS to maintain physiological homeostasis. Despite their conservation across species, the anatomy, circuitry, and development of internal sensory systems are still relatively poorly understood. A largely unstudied population of larval Drosophila sensory neurons, termed tracheal dendrite (td) neurons, innervate internal respiratory organs and may serve as a model for understanding the sensing of internal states. Here, we characterize the peripheral anatomy, central axon projection, and diversity of td sensory neurons. We provide evidence for prominent expression of specific gustatory receptor genes in distinct populations of td neurons, suggesting novel chemosensory functions. We identify two anatomically distinct classes of td neurons. The axons of one class project to the subesophageal zone (SEZ) in the brain, whereas the other terminates in the ventral nerve cord (VNC). We identify expression and a developmental role of the POU-homeodomain transcription factor Pdm3 in regulating the axon extension and terminal targeting of SEZ-projecting td neurons. Remarkably, ectopic Pdm3 expression is alone sufficient to switch VNC-targeting axons to SEZ targets, and to induce the formation of putative synapses in these ectopic target zones. Our data thus define distinct classes of td neurons, and identify a molecular factor that contributes to diversification of axon targeting. These results introduce a tractable model to elucidate molecular and circuit mechanisms underlying sensory processing of internal body status and physiological homeostasis. SIGNIFICANCE STATEMENT How interoceptive sensory circuits develop, including how sensory neurons diversify and target distinct central regions, is still poorly understood, despite the importance of these sensory systems for maintaining physiological homeostasis. Here, we characterize classes of Drosophila internal sensory neurons (td neurons) and uncover diverse axonal projections and expression of chemosensory receptor genes. We categorize td neurons into two classes based on dichotomous axon target regions, and identify the expression and role of the transcription factor Pdm3 in mediating td axon targeting to one of these target regions. Our results provide an entry point into studying internal sensory circuit development and function, and establish Pdm3 as a regulator of interoceptive axon targeting.
Arvand: A Method to Integrate Multidimensional Data Sources Into Big Data Analytic Structures

OLAP (online analytic processing) systems provide valuable insights into organizations; thus, it becomes necessary to integrate legacy OLAP systems into scalable and distributable architectures. This project comprises two important tasks: the first is transferring OLAP cubes to share nothing architectures. The second task is integrating OLAP information with other OLAP systems over distributable and scalable architectures. The main problem is to convert conceptual model OLAP data sources to shared nothing architectures. An additional problem is query execution time on the shared nothing architectures because by default, complete data locality is not considered in these environments. In this paper, Arvand is proposed. This method can transfer multidimensional data sources into shared nothing architectures. Data are captured from multidimensional data sources and converted into a unified format. Through unification, multidimensional data sources can be easily distributed over homogeneous and heterogeneous nodes because the nodes will not need additional information from other nodes. As an added benefit, MapReduce methods can be used properly and with maximum performance for query retrieval. Arvand is implemented by adding some components to Hadoop. In this paper, architectures with different heterogeneous and homogenous nodes are proposed and evaluated using a TPC-DS benchmark.
Robust Linear Multiuser Receiver With Worst-Case Probability Guarantee

A novel robust linear receiver with worst-case probability guarantee is proposed in this correspondence. Based on multivariate Chebyshev inequality, deterministic expressions of the probabilistic constraints are derived, and then, an iterative second-order cone programming is developed to obtain the robust solutions. Compared to the existing receivers, our proposed receiver improves performance by allowing a small outage probability and a more general uncertainty model. Simulations illustrate the improvement of our proposed approach.
Significance of Endolymphatic Hydrops in Ears With Unilateral Sensorineural Hearing Loss.

OBJECTIVE The purpose of this study was to investigate the existence of endolymphatic hydrops (EH) in affected and unaffected ears in patients with unilateral sensorineural hearing loss (SNHL) using contrast-enhanced magnetic resonance imaging (MRI), and to evaluate the significance of EH in various otological diseases. STUDY DESIGN Retrospective study. SETTING University hospital. METHODS One hundred eighty-two ears from 91 patients with unilateral SNHL were studied. The endolymphatic space was evaluated using 3-Tesla MRI with gadodiamide hydrate. Imaging data about the degree of EH in the cochlea and vestibule were analyzed and compared between ears with various otological diseases. RESULTS All affected ears with delayed endolymphatic hydrops had EH. In affected ears with definite Menière's disease, cochlear EH was observed in all ears and vestibular EH in 93% of ears, and these rates were significantly higher in the affected than in the unaffected ears. EH was also observed in the cochlea and vestibule in 66% and 41%, respectively, of the affected ears with idiopathic sudden SNHL; however, these percentages did not differ significantly from those in the unaffected ears (52% and 38%, respectively). CONCLUSION MRI showed that a high percentage of ears affected by Menière's disease or delayed endolymphatic hydrops had EH. Further studies should evaluate the implications of EH in ears, especially in those with sudden SNHL, in terms of secondary or pre-existing EH.
Actinic Prurigo in Singaporean Chinese: A Positive Association with HLA‐DRB1*03:01

Studies have reported the association of human leukocyte antigen (HLA) genes with susceptibility to develop actinic prurigo (AP) in Caucasians, but there were no studies in Asian populations, including the Chinese. Our study was performed to determine if AP is associated with susceptibility or protective HLA alleles or haplotypes in Singaporean Chinese. All Chinese patients diagnosed with AP at National Skin Center, Singapore, from January 2002 to April 2015 were invited to participate in the study. Clinical data and phototesting results were collated, and HLA typing was performed. Among 14 patients included, 11 were male and the mean age was 49.6 (37.9–61.3) years. All patients did not have a family history of AP and none had mucosal involvement, as such these clinical features differed from Caucasian AP patients. The frequency of DRB1*03:01 in AP patients was significantly higher compared to healthy controls (43% vs 16%, P = 0.022, odds ratio (OR) 3.89). Concurrently, the frequency of HLA‐B*58:01‐DRB1*03:01 haplotype was also significantly increased (25% vs 7%, P = 0.004, OR 4.23). In conclusion, HLA‐DRB1*03:01 was associated with AP in Singaporean Chinese patients. This novel allelic association may possibly be utilized as a biological marker to aid in the diagnosis of AP in Chinese patients.
Change in HbA1c associated with treatment intensification among patients with type 2 diabetes and poor glycemic control

Abstract Objective: We conducted a retrospective cohort study to investigate the HbA1c change associated with treatment intensification in a real-world population of patients with type 2 diabetes (T2D). Methods: Using a large US insurance claims database, patients aged ≥18 years with a T2D diagnosis and HbA1c ≥8.0% (64 mmol/mol) after ≥3 months of oral pharmacotherapy with metformin (± other oral antidiabetes agents) were identified (index date). Continuous enrollment was required for ≥12 months before (baseline) and after the index date with no baseline use of injectable antidiabetes drugs. We defined treatment intensification as prescriptions for injectable or additional oral antidiabetes drugs. Time to intensification was classified as timely (within 6 months) or not (≥6 months or not intensified). Linear regression models with propensity score 1:1 matching were performed to assess the effect of timely intensification on HbA1c. Results: Of the 11,525 patients meeting the inclusion criteria, only 37% had treatment intensified within 6 months. Mean age at index date was 57 years, 40% of the sample was female. The mean baseline A1C was 9.4% and 9.0%, while post-index A1C was 7.9% and 8.2% for timely intensified patients versus not, respectively. Patients with timely intensification had significantly greater HbA1c reduction compared with others (−0.33%, 95% CI: −0.41% to −0.25%) within 1 year of follow up. Conclusions: In this analysis of patients with T2D and treatment failure in a real-world setting, earlier treatment intensification was associated with better glycemic control as indicated by lower HbA1c values.
Population Pharmacokinetic Model-Based Evaluation of Standard Dosing Regimens for Cefuroxime Used in Coronary Artery Bypass Graft Surgery with Cardiopulmonary Bypass

ABSTRACT The purpose of this study was to investigate the population pharmacokinetics (PK) of cefuroxime in patients undergoing coronary artery bypass graft (CABG) surgery. In this observational pharmacokinetic study, multiple blood samples were collected over a 48-h interval of intravenous cefuroxime administration. The samples were analyzed by using a validated high-performance liquid chromatography (HPLC) method. Population pharmacokinetic models were developed using Monolix (version 4.4) software. Pharmacokinetic-pharmacodynamic (PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. A total of 468 blood samples from 78 patients were analyzed. The PK for cefuroxime were best described by a two-compartment model with between-subject variability on clearance, the volume of distribution of the central compartment, and the volume of distribution of the peripheral compartment. The clearance of cefuroxime was related to creatinine clearance (CLCR). Dosing simulations showed that standard dosing regimens of 1.5 g could achieve the PK-PD target of the percentage of the time that the free concentration is maintained above the MIC during a dosing interval (fTMIC) of 65% for an MIC of 8 mg/liter in patients with a CLCR of 30, 60, or 90 ml/min, whereas this dosing regimen failed to achieve the PK-PD target in patients with a CLCR of ≥125 ml/min. In conclusion, administration of standard doses of 1.5 g three times daily provided adequate antibiotic prophylaxis in patients undergoing CABG surgery. Lower doses failed to achieve the PK-PD target. Patients with high CLCR values required either higher doses or shorter intervals of cefuroxime dosing. On the other hand, lower doses (1 g three times daily) produced adequate target attainment for patients with low CLCR values (≤30 ml/min).
COPI mediates recycling of an exocytic SNARE by recognition of a ubiquitin sorting signal

The COPI coat forms transport vesicles from the Golgi complex and plays a poorly defined role in endocytic trafficking. Here we show that COPI binds K63-linked polyubiquitin and this interaction is crucial for trafficking of a ubiquitinated yeast SNARE (Snc1). Snc1 is a v-SNARE that drives fusion of exocytic vesicles with the plasma membrane, and then recycles through the endocytic pathway to the Golgi for reuse in exocytosis. Removal of ubiquitin from Snc1, or deletion of a β'-COP subunit propeller domain that binds K63-linked polyubiquitin, disrupts Snc1 recycling causing aberrant accumulation in internal compartments. Moreover, replacement of the β'-COP propeller domain with unrelated ubiquitin-binding domains restores Snc1 recycling. These results indicate that ubiquitination, a modification well known to target membrane proteins to the lysosome or vacuole for degradation, can also function as recycling signal to sort a SNARE into COPI vesicles in a non-degradative pathway.
The effect of task modality and stimulus frequency in paced serial addition tests on functional brain activity

Introduction The paced serial addition test (PSAT) is regularly used to assess cognitive deficits in various neuropsychiatric conditions. Being a complex test, it reflects the status of multiple cognitive domains such as working memory, information processing speed and executive functioning. Two versions of the PSAT exist. One uses auditory stimuli through spoken numbers and is known as the PASAT, while the other one presents patients with visual stimuli and is called PVSAT. The PASAT is considered more frustrating by patients, and hence the visual version is usually preferred. Research has suggested that an interference might exist between patients’ verbal answers and the auditory presentation of stimuli. We therefore removed the verbal response in this study, and aimed to investigate differences in functional brain activity through functional magnetic resonance imaging. Methods Fifteen healthy controls performed the two test versions inside an MRI scanner—switching between stimulus modality (auditory vs. visual) as well as inter-stimulus frequency (3s vs. 2s). We extracted 11 independent components from the data: attentional, visual, auditory, sensorimotor and default mode networks. We then performed statistical analyses of mean network activity within each component, as well as inter-network connectivity of each component pair during the different task types. Results Unsurprisingly, we noted an effect of modality on activity in the visual and auditory components. However, we also describe bilateral frontoparietal, anterior cingulate and insular attentional network activity. An effect of frequency was noted only in the sensorimotor network. Effects were found on edges linking visual and auditory regions. Task modality influenced an attentional-sensorimotor connection, while stimulus frequency had an influence on sensorimotor-default mode connections. Conclusions Scanner noise during functional MRI may interfere with brain activation—especially during tasks involving auditory pathways. The question whether to use PVSAT or PASAT for an fMRI study is, therefore, an important one. Specific effects of both modalities should be known to study designers. We conclude that both tests should not be considered interchangeable, as significant changes were brought to light during test performance in different modalities.
The Draft Genome of the Invasive Walking Stick, Medauroidea extradendata, Reveals Extensive Lineage-Specific Gene Family Expansions of Cell Wall Degrading Enzymes in Phasmatodea

Plant cell wall components are the most abundant macromolecules on Earth. The study of the breakdown of these molecules is thus a central question in biology. Surprisingly, plant cell wall breakdown by herbivores is relatively poorly understood, as nearly all early work focused on the mechanisms used by symbiotic microbes to breakdown plant cell walls in insects such as termites. Recently, however, it has been shown that many organisms make endogenous cellulases. Insects, and other arthropods, in particular have been shown to express a variety of plant cell wall degrading enzymes in many gene families with the ability to break down all the major components of the plant cell wall. Here we report the genome of a walking stick, Medauroidea extradentata, an obligate herbivore that makes uses of endogenously produced plant cell wall degrading enzymes. We present a draft of the 3.3Gbp genome along with an official gene set that contains a diversity of plant cell wall degrading enzymes. We show that at least one of the major families of plant cell wall degrading enzymes, the pectinases, have undergone a striking lineage-specific gene family expansion in the Phasmatodea. This genome will be a useful resource for comparative evolutionary studies with herbivores in many other clades and will help elucidate the mechanisms by which metazoans breakdown plant cell wall components.
Application and comparison of the FADES, MADIT, and SHFM-D risk models for risk stratification of prophylactic implantable cardioverter-defibrillator treatment

Aims Implantable cardioverter-defibrillator (ICD) treatment is beneficial in selected patients. However, it remains difficult to accurately predict which patients benefit most from ICD implantation. For this purpose, different risk models have been developed. The aim was to validate and compare the FADES, MADIT, and SHFM-D models. Methods and results All patients receiving a prophylactic ICD at the Leiden University Medical Center were evaluated. Individual model performance was evaluated by C-statistics. Model performances were compared using net reclassification improvement (NRI) and integrated differentiation improvement (IDI). The primary endpoint was non-benefit of ICD treatment, defined as mortality without prior ventricular arrhythmias requiring ICD intervention. A total of 1969 patients were included (age 63 ± 11 years; 79% male). During a median follow-up of 4.5 ± 3.9 years, 318 (16%) patients died without prior ICD intervention. All three risk models were predictive for event-free mortality (all: P < 0.001). The C-statistics were 0.66, 0.69, and 0.75, respectively, for FADES, MADIT, and SHFM-D (all: P < 0.001). Application of the SHFM-D resulted in an improved IDI of 4% and NRI of 26% compared with MADIT; IDI improved 11% with the use of SHFM-D instead of FADES (all: P < 0.001), but NRI remained unchanged (P = 0.71). Patients in the highest-risk category of the MADIT and SHFM-D models had 1.7 times higher risk to experience ICD non-benefit than receive appropriate ICD interventions [MADIT: mean difference (MD) 20% (95% CI: 7–33%), P = 0.001; SHFM-D: MD 16% (95% CI: 5–27%), P = 0.005]. Patients in the highest-risk category of FADES were as likely to experience ICD intervention as ICD non-benefit [MD 3% (95% CI: –8 to 14%), P = 0.60]. Conclusion The predictive and discriminatory value of SHFM-D to predict non-benefit of ICD treatment is superior to FADES and MADIT in patients receiving prophylactic ICD treatment.
Frequency response characteristics of sympathetically mediated vasomotor waves in humans.

In a recent study, we demonstrated that transmission from peripheral sympathetic nerves to vascular smooth muscles is strongest in the frequency band from 0.2 to 0.5 Hz in conscious rats. In contrast, sympathetic modulation of vasomotor tone in humans is suggested to be reflected in the power spectrum of arterial blood pressure in a frequency range centered around ∼0.1 Hz. Therefore, we addressed whether frequency response characteristics of sympathetic transmission from peripheral sympathetic nerves to vascular smooth muscles in humans differ from those in rats. In 12 male subjects, skin-sympathetic fibers of the left median nerve were electrically stimulated via microneurography needles with stimulation frequencies ranging from 0.01 to 0.5 Hz. Simultaneously, blood flow in the innervated skin area at the palm of the ipsilateral hand was recorded by a laser-Doppler device. The skin blood flow in the same area of the contralateral hand was recorded as a control. Median nerve stimulation produced transient decreases in skin blood flow in the ipsilateral hand. At frequencies ranging from 0.025 to 0.10 Hz, median nerve stimulation evoked high-power peaks at the same frequencies in the skin blood flow power spectra of the ipsilateral but not of the contralateral hand. The greatest responses were found in the frequency range from 0.075 to 0.10 Hz. Therefore, these data indicate that the transmission from peripheral sympathetic nerves to cutaneous vascular smooth muscles in humans is slower than in rats. In addition, the frequency range believed to be most important in sympathetic modulation of vasomotor activity in humans corresponds to the frequency band of the greatest response of cutaneous vascular smooth muscle contraction to sympathetic nerve stimulation.
The everyday lives of energy transitions: Contested sociotechnical imaginaries in the American West

This article brings together two growing literatures – on sociotechnical imaginaries in science and technology studies and on resource materialities in anthropology – to explore how two energy-producing communities in the American West understand the moral salience of energy systems and the place of labor within them. Studies of energy sociotechnical imaginaries overwhelmingly focus on the role that state and transnational actors play in shaping perceptions of the ‘good society’, rather than how these imaginaries inform and are transformed in the lived experience of everyday people. We illuminate the contested dimension of sociotechnical imaginaries and their positioning within structures of power that inform visions of moral behavior and social order. Whereas the role of energy in national imaginaries is grounded almost entirely in the consumption it enables, examining the everyday ethics of people who live and work in Colorado’s uranium-rich Western Slope and Wyoming’s coal-rich Powder River Basin reveals an insistence that ‘good’ energy systems also provide opportunities for dignified and well-paid blue-collar work. This imaginary, we argue, remains ‘bounded’ at a local scale rather than circulating more widely to gain national or international traction. Theorizing this boundedness illustrates not only the contested nature of sociotechnical imaginaries, but also the constraints that material assemblages and sediments of the past place on imagined futures.
Learning and Visualizing Localized Geometric Features Using 3D-CNN: An Application to Manufacturability Analysis of Drilled Holes

3D Convolutional Neural Networks (3D-CNN) have been used for object recognition based on the voxelized shape of an object. However, interpreting the decision making process of these 3D-CNNs is still an infeasible task. In this paper, we present a unique 3D-CNN based Gradient-weighted Class Activation Mapping method (3D-GradCAM) for visual explanations of the distinct local geometric features of interest within an object. To enable efficient learning of 3D geometries, we augment the voxel data with surface normals of the object boundary. We then train a 3D-CNN with this augmented data and identify the local features critical for decision-making using 3D GradCAM. An application of this feature identification framework is to recognize difficult-to-manufacture drilled hole features in a complex CAD geometry. The framework can be extended to identify difficult-to-manufacture features at multiple spatial scales leading to a real-time design for manufacturability decision support system.
Cross-language MeSH Indexing using Morpho-Semantic Normalization

We consider three alternative procedures for the automatic indexing of medical documents using MeSH thesaurus identifiers as target units (document descriptors). Rather than considering complete words as the starting point of the indexing procedure, we here propose morphologically plausible subwords as basic units from which MeSH terms are derived. We describe the morphological segmentation and normalization procedures, as well as the mappings from subwords to MeSH terms, and discuss results from an evaluation carried out on a German-language corpus.