Miracle-dz/UniFAR-FTUs huggingface dataset:
Audiological and Vestibular Findings in Subjects with MELAS Syndrome.

OBJECTIVES The mitochondrial DNA (mtDNA) point mutation m.3243A>G is known to express the following two syndromes among others: maternally inherited diabetes and deafness (MIDD) and mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Sensorineural hearing loss (SNHL) is the most frequent symptom in individuals harboring the m.3243A>G mutation. However, dysfunction of the vestibular organs has been scarcely examined. Therefore, the present study aimed to study the impact of the m.3243A>G mutation on the inner ear. MATERIALS AND METHODS A total of 8 subjects harboring the blood-verified m.3243A>G mutation underwent thorough audiological and vestibular examinations, including tone and speech audiometry, video head impulse test (vHIT), ocular and cervical vestibular-evoked myogenic potential (oVEMP and cVEMP), and full otoneurological examination. The subjects also answered a Dizziness Handicap Inventory (DHI) questionnaire. RESULTS SNHL was identified in all the 8 subjects, with a mean pure-tone average-4 (PTA-4) of 59 dB. Speech discrimination score (n=7) ranged from 24% to 100% (mean 74%), and vHIT (n=42) detected pathology in nine lateral semicircular canals (SCCs), five posterior SCCs, and one anterior SCC, whereas three measurements were inconclusive. All oVEMPs (n=14 ears) were absent, nine cVEMPs were absent, and two were inconclusive. Based on the DHI scores, 6 subjects reported none to mild dizziness, 1 reported moderate, and 1 reported severe dizziness. CONCLUSION Our study population had pathological findings from every audiological and vestibular end organs. The results indicated that the pathological findings originated from within the end organs themselves and not within the superior and inferior vestibular or cochlear nerve.
Three-Dimensional Leukemia Co-Culture System for In Vitro High-Content Metabolomics Screening

Metabolomics is increasingly applied to investigate different individuals and time-dependent responses to environmental stimuli. Rapid data acquisition and improved detection limits of direct infusion mass spectrometry (DIMS) are paving the way for applications of metabolomics in preclinical screening, opening new opportunities in drug discovery and personalized medicine. Three-dimensional (3D) cell culture systems, which mimic the in vivo cell microenvironment, are well recognized as tissue and organ substitutes. Here, we investigated cell viability and induction of reactive oxygen species (ROS) in stromal cells cultured in various 3D systems as well as the standard monolayer culture to evaluate which system provides the most favorable growing conditions. The selected 3D system was then tested for use in 3D co-culture of leukemia and stromal cells for DIMS-based high-throughput/high-content metabolic drug screens. The NanobioMatrix–poly(ε-caprolactone) (NBM–PCL) scaffold resulted in the lowest ROS production, supported rapid cell proliferation, and was suitable for the 96- and 384-well plate formats. Doxorubicin treatment in leukemia co-cultured with stromal cells induced some unique metabolic responses that drastically differed from those observed in leukemia cells alone. The DIMS results also showed that the drug-induced metabolic modulations in both normal and cancer cells were weakened by co-culturing even at high treatment doses, thereby demonstrating the value of the 3D co-culture high-content metabolic drug screen. In conclusion, we optimized a high sample throughput method for 3D co-culture with a DIMS-based high-content metabolic drug screen and drug development.
Corrigendum to "Cardiac rehabilitation improved oxygen uptake measured by cardiopulmonary exercise test in patients after aortic valve surgery" (Rev. Cardiovasc. Med. 2019, 20(1):47-52).

The support statement for Song F. et al., "Cardiac rehabilitation improved oxygen uptake measured by cardiopulmonary exercise test in patients after aortic valve surgery" Rev. Cardiovasc. Med. 2019 vol. 20(1), 47-52, was incorrectly attributed. This study was supported by the Medical Scientific Research Foundation of Guangdong Province, China (Grant No. A2017257) and the National Science Foundation for Young Scientists of China (Grant No. 81600255). The corrected article appears overleaf with its original pagination. This corrects the article DOI: 10.31083/j.rcm. 2019.01. 3183.
Innervation of internal female genital organs in the pig during prenatal development

This study investigated the innervation of internal genital organs in 5‐, 7‐ and 10‐week‐old female pig foetuses using single and double‐labelling immunofluorescence methods. The structure and topography of the organs was examined using a scanning electron microscope (SEM). The investigations revealed differences in the innervation between the three developmental periods. Immunostaining for protein gene product 9.5 (PGP; general neural marker) disclosed solitary nerve fibres in the external part of the gonadal ridge and just outside of the mesenchyme surrounding mesonephric ducts in 5‐week‐old foetuses. Double‐labelling immunohistochemistry revealed that nerve fibres associated with the ridge expressed dopamine β‐hydroxylase (DβH; adrenergic marker) or vesicular acetylcholine transporter (VAChT; cholinergic marker). In 7‐week‐old foetuses, the PGP‐positive nerve terminals were absent from the gonad but some of them ran outside and along, and sometimes penetrated into the mesenchyme surrounding the tubal and uterine segments of the paramesonephric ducts and uterovaginal canal. Few axons penetrated into the mesenchyme. DβH‐positive fibres were found in single nerve strands or bundles distributed at the edge of the mesenchyme. VAChT‐positive nerve terminals formed delicate bundles located at the edge of the mesenchyme, and the single nerves penetrated into the mesenchyme. DβH was also expressed by neurons which formed cell clusters comprising also DβH‐ or VAChT‐positive nerve fibres. In 10‐week‐old foetuses, PGP‐positive nerve fibres were still absent from the ovary but some were distributed in the mesenchyme associated with the uterovaginal canal and uterine and a tubal segment of the paramesonephric ducts, respectively. DβH‐ or VAChT‐positive nerve fibres were distributed at the periphery of the mesenchyme associated with the uterovaginal canal. Some DβH‐ and many VAChT‐positive nerve fibres were evenly distributed throughout the mesenchyme. The clusters of nerve cells comprised DβH‐positive perikarya and DβH‐ or VAChT‐positive nerve fibres. The investigations revealed no DβH/VAChT‐positive nerve fibres or neurons as well as no nerve structures stained for calcitonin gene‐related peptide and/or substance P (sensory markers) associated with the genital organs in the studied prenatal periods.
A Systematic Analysis and Exploration of the Regression Testing Techniques

: Software system undergoes various evolutions from its initial development to practical use. There are various kinds of corrections, modifications and additions at each module in the software. Sometimes, software is shifted from one platform to another platform which can adversely affect the software system. To ensure the system from bugs, faults & errors, the system undergoes the regression testing. Regression testing ensures the quality of the software with testing all the required phases. It is easy to perform regression testing to ensure the proper working of software in case small software or software having limited programming code lines but it becomes difficult after the addition of phases and new modules to software. It also becomes costlier to perform regression testing for the large projects having large number of test cases. To resolve this problem, there are various techniques of regression testing like test suite minimization, prioritization of test cases and test case selection. Researchers are working on these techniques to handle large projects by using different methods on mentioned regression testing techniques. In this paper, we have explored the regression testing techniques and analyzed new methods and trends in the field of regression testing. The presented analysis indicates the continuous growth of the concept in wider research applications.
Association between red cell distribution width-to-platelet ratio and hepatic fibrosis in nonalcoholic fatty liver disease

Abstract Background: We aimed to assess the association between red cell distribution width-to-platelet ratio (RPR) and hepatic fibrosis in nonalcoholic fatty liver disease. Methods: The 388 subjects fulfilling the diagnostic criteria of Nonalcoholic fatty liver disease (NAFLD) were enrolled in this cross-sectional study. Red cell distribution, platelet, and other clinical and laboratory parameters were measured. Results: NAFLD patients with advanced fibrosis had significantly higher RPR than those without fibrosis (P < .001). Spearman correlation analysis showed that RPR were significantly correlated with age, sex, creatinine, hemoglobin, white blood cell, and advanced fibrosis (all with P < .05). Multivariate logistic regression analysis showed that RPR was an independent factor predicting advanced fibrosis (fibrosis-4 calculator ≥1.3) in NAFLD patients (OR: 5.718, 95%CI: 3.326–9.830, P < .001). Conclusions: Our findings suggested that RPR were significantly associated with advanced fibrosis in nonalcoholic fatty liver disease patients.
16S rRNA Gene Amplicon Profiling of Anaerobic Bulking-Associated Prokaryotic Microbiota in a Mesophilic Expanded Granular Sludge Bed Reactor for Beverage Wastewater Treatment

Information regarding prokaryotic microbiota associated with anaerobic bulking is limited. Here, we provide 16S rRNA gene-based prokaryotic diversity profiles for anaerobic bulking and healthy granular sludge in a mesophilic expanded granular sludge bed (EGSB) reactor. These data were tabulated at the phylum level based on high-quality reads. ABSTRACT Information regarding prokaryotic microbiota associated with anaerobic bulking is limited. Here, we provide 16S rRNA gene-based prokaryotic diversity profiles for anaerobic bulking and healthy granular sludge in a mesophilic expanded granular sludge bed (EGSB) reactor. These data were tabulated at the phylum level based on high-quality reads.
Functional analysis of novel RUNX2 mutations identified in patients with cleidocranial dysplasia

RUNX2 (Runt‐related transcription factor 2) is a master regulator of osteoblast differentiation, cartilage and bone development. Pathogenic variants in RUNX2 have been linked to the Cleidocranial dysplasia (CCD), which is characterized by hypoplasia or aplasia of clavicles, delayed fontanelle closure, and dental anomalies. Here, we report 11 unrelated Polish patients with CCD caused by pathogenic alterations located in the Runt domain of RUNX2. In total, we identified eight different intragenic variants, including seven missense and one splicing mutation. Three of them are novel: c.407T>A p.(Leu136Gln), c.480C>G p.(Asn160Lys), c.659C>G p.(Thr220Arg), additional three were not functionally tested: c.391C>T p.(Arg131Cys), c.580+1G>T p.(Lys195_Arg229del), c.652A>G p.(Lys218Glu), and the remaining two: c.568C>T p.(Arg190Trp), c.673C>T p.(Arg225Trp) were previously reported and characterized. The performed transactivation and localization studies provide evidence of decreased transcriptional activity of RUNX2 due to mutations targeting the Runt domain and prove that impairment of nuclear localization signal (NLS) affects the subcellular localization of the protein. Presented data show that pathogenic variants discovered in our patients have a detrimental effect on RUNX2, triggering the CCD phenotype.
Draft Whole-Genome Sequences of Haemophilus influenzae Biogroup aegyptius Strains Isolated from Five Brazilian Purpuric Fever Cases and One Conjunctivitis Case

Brazilian purpuric fever is a febrile hemorrhagic pediatric disease caused by Haemophilus influenzae biogroup aegyptius, a bacterium which was formerly associated with only self-limited purulent conjunctivitis. Here, we present draft genomes of strains from five Brazilian purpuric fever cases and one conjunctivitis case. ABSTRACT Brazilian purpuric fever is a febrile hemorrhagic pediatric disease caused by Haemophilus influenzae biogroup aegyptius, a bacterium which was formerly associated with only self-limited purulent conjunctivitis. Here, we present draft genomes of strains from five Brazilian purpuric fever cases and one conjunctivitis case.
Simulation of Exascale Nodes through Runtime Hardware Monitoring

The node-level architecture of exascale systems may look significantly different than current designs. Heterogeneous cores [13] will be severely powerand heat-constrained [6]. They may have large amounts of 2.5D [11] or 3D [17] stacked DRAM and may have even larger non-volatile storage [5]. Simulating the large design space of these systems is important in order to find the best candidates for further study. Current simulation techniques offer good visibility into low-level details but are too slow and memory intensive for such explorations.
Beet the cold: Beetroot juice improves peripheral blood flow, endothelial function and anti-inflammatory status in individuals with Raynaud's phenomenon.

Raynaud's phenomenon (RP) is characterised by recurrent transient peripheral vasospasm and lower nitric oxide (NO) bioavailability in the cold. We investigated the effect of nitrate-rich beetroot juice (BJ) supplementation on i) NO-mediated vasodilation, ii) cutaneous vascular conductance (CVC) and skin temperature (Tsk) following local cooling and iii) systemic anti-inflammatory status. Following baseline testing, twenty-three individuals with RP attended four times, in a double-blind, randomized crossover design, following acute and chronic (14 days) BJ and nitrate-depleted beetroot juice (NDBJ) supplementation. Peripheral Tsk and CVC were measured during and after mild hand and foot cooling, and during transdermal delivery of acetylcholine and sodium nitroprusside. Markers of anti-inflammatory status were also measured. Plasma [nitrite] was increased in the BJ conditions (P < 0.001). Compared to the baseline visit, thumb CVC was greater following chronic-BJ (Δ2.0 flux·mmHg-1, P = 0.02) and chronic-NDBJ (Δ1.45 flux·mmHg-1, P = 0.01) supplementation; however, no changes in Tsk were observed (P > 0.05). Plasma [interleukin-10] was greater, pan endothelin and systolic and diastolic blood pressure (BP) were reduced, and forearm endothelial function was improved ,by both BR and NDBJ supplementation (P < 0.05). Acute and chronic BJ and NDBJ supplementation improved anti-inflammatory status, endothelial function and BP. CVC following cooling increased post chronic-BJ and chronic-NDBJ supplementation, but no effect on Tsk was observed.
Surgical nuances to avoid blind areas in endoscopic surgery: A new surgical technique

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‐NonCommercial‐ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‐commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. How to cite this article: Sowmini PR, Vijayashankar P, Gobinathan S. Multiple symmetric lipomatosis: A clinical marker of mitochondrial cytopathy. Neurol India 2019;67:920‐3. © 2019 Neurology India, Neurological Society of India | Published by Wolters Kluwer ‐ Medknow Access this article online
Integrated Design Approaches for 3D Printed Tissue Scaffolds: Review and Outlook

Emerging 3D printing technologies are enabling the fabrication of complex scaffold structures for diverse medical applications. 3D printing allows controlled material placement for configuring porous tissue scaffolds with tailored properties for desired mechanical stiffness, nutrient transport, and biological growth. However, tuning tissue scaffold functionality requires navigation of a complex design space with numerous trade-offs that require multidisciplinary assessment. Integrated design approaches that encourage iteration and consideration of diverse processes including design configuration, material selection, and simulation models provide a basis for improving design performance. In this review, recent advances in design, fabrication, and assessment of 3D printed tissue scaffolds are investigated with a focus on bone tissue engineering. Bone healing and fusion are examples that demonstrate the needs of integrated design approaches in leveraging new materials and 3D printing processes for specified clinical applications. Current challenges for integrated design are outlined and emphasize directions where new research may lead to significant improvements in personalized medicine and emerging areas in healthcare.
Strategies and Tools for Public Health Workforce Training Needs Assessments in Diverse and Changing Population Health Contexts.

CONTEXT A key component of the improvement of public health infrastructure in the United States revolves around public health workforce development and training. Workforce challenges faced by the public health system have long been recognized, but there are additional challenges facing any region-wide or cross-jurisdictional effort to accurately assess priority workforce training needs and develop training resources to address those needs. These challenges include structural variability of public health organizations; diverse population health contexts; capturing both topic-specific skill sets and foundational competencies among public health workers; and reaching/representing the target population despite suspicion, disinterest, and/or assessment "fatigue" among employees asked to participate in workforce development surveys. OBJECTIVE The purpose of this article is to describe the challenges, strategies to meet those challenges, and lessons learned conducting public health workforce training needs assessments by academic and practice partners of the Region 2 Public Health Training Center (R2/PHTC). SETTING AND PARTICIPANTS The R2/PHTC is hosted by the Mailman School of Public Health at Columbia University and serves New York, New Jersey, Puerto Rico, and the US Virgin Islands within its jurisdiction. RESULTS Strategies for responding to diverse organizational structures and population health contexts across the region; defining training priorities that address both foundational competencies for public health professionals and content-specific training to address local public health needs; reaching/representing target populations of public health workers; and analysis and report writing to encourage rapid response to identified needs and comprehensive workforce development planning are discussed. Lessons learned are likely instructive to other workforce training needs assessments in complex and ever-changing public health environments.
Portable, Low-Cost, Solid-State Luminescence-Based O2 Sensor

A novel sensor for quantifying molecular O2 based entirely on solid-state electronics is presented. The sensor is based on the luminescence quenching of tris(4,7-diphenyl-1, 10-phenanthroline)ruthenium(II) ([Ru(dpp)3]2+) by molecular O2. The sensor involves immobilizing the ruthenium complex within a porous sol-gel-processed glass film and casting this film directly onto the surface of a blue quantum-well light-emitting diode (LED). The ruthenium complex is excited by the LED, the [Ru(dpp)3]2+ emission is filtered from the excitation with a low-cost acrylic color filter, and the emission is detected with an inexpensive silicon photodiode. The sensor response to gaseous O2 and dissolved O2 in water is presented. The sensor exhibits fast response times and good reversibility, and detection limits are 0.5%, 0.02%, and 110 ppb, respectively, for O2 in the gaseous (linear Stern–Vobner and multi-site Stern–Volmer analysis) and aqueous phase. This sensor provides a cost-effective alternative to traditional electrochemical-based O2 sensing and also provides a platform for other optically based sensors.
Acquisition and consolidation of hierarchical representations of space

Navigation – the ability to reach targets which are no visible from the current position depends on the correct recall of the desired target and the environment between one's current position and this target. The content of these representations are subject to influences from different modalities, e.g. vision, and language. A place can be recognized through different cues, e.g. due to a salient object, but also because of the angles of the routes at an intersection, or a name. The location of places as well as the routes connecting them can be integrated and memorized in an allocentric, survey-like representation. Depending on the amount of detail, the granularity level of a representation can be coarser or finer; the different levels are organized hierarchically. Characteristics of a superordinate category, like a region, can affect the perception of its constituting elements, the places; an inheritance of qualities from region to place levels is possible. The formation of superordinate categories depends both on environmental factors as well as individual ones: what is recognized, what is remembered, and which predictions are drawn from this representation? In this dissertation I examine the acquisition of representations of space, in order to identify features that are well suited for being remembered and auxiliary for navigation. I have two research foci: First, I examine the impact of language by using different hierarchically structured naming schemes as place names. Wiener & Mallot (2003) found that characterizing places only with landmarks belonging to different semantic categories influenced route choice as well as the representations of space. I compare these findings to the impact of different naming schemes. I show that there are naming schemes that may influence behavior in a similar way as a landmark does, but that seeing something and reading its name is by far the same thing. The second part focuses on the content of representations established during navigation. With three different navigation experiments, I examine the content of the concepts of space that are acquired during navigation. What is remembered the location of places, the routes, or the hierarchical structure of the experimental environment? Are there features that are more likely to be consolidated during sleep, e.g., the transfer of concrete knowledge about places and routes into an abstract, survey-like representation? I show that there are improvements in one wayfinding task correlated to sleep. In the other experiments, learning effects were found for both groups. I also address the question of suitable parameters for measuring survey knowledge.
Dephosphorylation of clustered phosphoserine residues in human Grb14 by protein phosphatase 1 and its effect on insulin receptor complex formation

The physical interaction of the human growth factor receptor‐bound protein 14 (hGrb14) and the insulin receptor (IR) represses insulin signaling. With respect to the recruiting mechanism of hGrb14 to IR respond to insulin stimulus, our previous reports have suggested that phosphorylation of Ser358, Ser362, and Ser366 in hGrb14 by glycogen synthase kinase‐3 repressed hGrb14–IR complex formation. In this study, we investigated phosphatase‐mediated dephosphorylation of the hGrb14 phosphoserine residues. An in vitro phosphatase assay with hGrb14‐derived synthetic phosphopeptides suggested that protein phosphatase 1 (PP1) is involved in the dephosphorylation of Ser358 and Ser362. Furthermore, coimmunoprecipitation experiments suggested that insulin‐induced hGrb14–IR complex formation was repressed by the substitution of Ser358 or Ser362 with glutamic acid. These findings suggested that phosphate groups on Ser358 and Ser362 in hGrb14 are dephosphorylated by PP1, and the dephosphorylation facilitates hGrb14–IR complex formation.