Miracle-dz/UniFAR-FTUs huggingface dataset:
MFN2 mutations in Charcot–Marie–Tooth disease alter mitochondria-associated ER membrane function but do not impair bioenergetics

Abstract Charcot–Marie–Tooth disease (CMT) type 2A is a form of peripheral neuropathy, due almost exclusively to dominant mutations in the nuclear gene encoding the mitochondrial protein mitofusin-2 (MFN2). However, there is no understanding of the relationship of clinical phenotype to genotype. MFN2 has two functions: it promotes inter-mitochondrial fusion and mediates endoplasmic reticulum (ER)–mitochondrial tethering at mitochondria-associated ER membranes (MAM). MAM regulates a number of key cellular functions, including lipid and calcium homeostasis, and mitochondrial behavior. To date, no studies have been performed to address whether mutations in MFN2 in CMT2A patient cells affect MAM function, which might provide insight into pathogenesis. Using fibroblasts from three CMT2AMFN2 patients with different mutations in MFN2, we found that some, but not all, examined aspects of ER–mitochondrial connectivity and of MAM function were indeed altered, and correlated with disease severity. Notably, however, respiratory chain function in those cells was unimpaired. Our results suggest that CMT2AMFN2 is a MAM-related disorder but is not a respiratory chain-deficiency disease. The alterations in MAM function described here could also provide insight into the pathogenesis of other forms of CMT.
painPREDICT: first interim data from the development of a new patient-reported pain questionnaire to predict treatment response using sensory symptom profiles

Abstract Objective: Sensory symptom patterns may be useful for predicting treatment response, and, thus, improve individual therapy in patients suffering from neuropathic pain (NeP). Existing screening questionnaires focus predominately on neuropathic mechanisms without consideration of nociceptive mechanisms or mixed pain states. This study aimed to develop a new questionnaire, painPREDICT, using a wide set of patient-reported descriptors potentially associated with neuropathic and nociceptive pain mechanisms, and to explore sensory symptom patterns. Methods: PainPREDICT was constructed based on exploratory (n = 27 patients) and cognitive debriefing interviews (n = 49 patients and nine physicians), across five NeP conditions. The pilot questionnaire was then administered in a non-interventional, cross-sectional, multi-center study to 840 pain patients across the US and Germany. The identification of a sensory symptom pattern was based on hybrid clustering resulting from items standardization followed by principal component analysis. Results: The final questionnaire included 20 items covering: pain intensity, location of pain, course of pain, and sensory symptoms. Most patients participating in the cross-sectional study suffered either from painful diabetic polyneuropathy (n = 330) or radiculopathy (n = 349), fewer from central pain (n = 61) or other types of NeP (n = 100). The hybrid clustering of the new questionnaire data identified three different characteristic sensory symptom profiles in patients with NeP: “Irritable nociceptors”, “deafferentation pain”, and “pain attacks with nociceptive component”. Although some differences in the distribution of the sensory profiles were found, all profiles were represented in all NeP etiology groups. Conclusions: This study set the ground of painPREDICT and showed promising results for its use to categorize patients according to sensory symptom patterns.
Propofol attenuates high glucose-induced P66shc expression in human umbilical vein endothelial cells through Sirt1

Perioperative hyperglycemia is a common metabolic disorder in clinic settings. Hyperglycemia leads to endothelial inflammation, endothelial cell apoptosis, and dysfunction, thus resulting in endothelial injury. Propofol (2,6-diisopropylphenol) is a widely used intravenous anesthetic in clinic settings. Our previous study indicated that propofol inhibits mitochondrial reactive oxygen species (ROS) production via down-regulation of phosphatase A2 (PP2A) expression, inhibition of Ser36-p66shc dephosphorylation and mitochondrial translocation, thus improving high glucose-induced endothelial injury. The expression of p66shc was inhibited by propofol in hyperglycemic human umbilical vein endothelial cells (HUVECs). However, the mechanism by which propofol inhibits p66shc expression in hyperglycemic HUVECs is still obscure. In the present study, we mainly examined how propofol inhibited high glucose-induced p66shc expression in HUVECs. Compared with 5 mM glucose treatment, high glucose increased p66shc expression and decreased sirt1 expression, which was inhibited by propofol treatment. Moreover, EX527 (a sirt1 inhibitor) reversed the effect of propofol against high glucose-induced p66shc expression. However, EX527 did not reverse the effects of propofol against high glucose-induced ROS accumulation, endothelial inflammation, and apoptosis. Furthermore, when cells were incubated with propofol, EX527, and FTY720 (a PP2A activator) simultaneously, the effects of propofol against high glucose-induced ROS accumulation, inflammation, and apoptosis were reversed. Our results suggested that propofol inhibited high glucose-induced p66shc expression via upregulation of sirt1 expression in hyperglycemic HUVECs. Moreover, propofol protects against high glucose-mediated ROS accumulation and endothelial injury via both inhibition of p66shc expression and dephosphorylation of Ser36-p66shc.
Transvaginal sonographic study of uterine changes in breast cancer patients treated with TAMOXIFEN

Poster: "2014 CSM / R-0012 / Transvaginal sonographic study of uterine changes in breast cancer patients treated with TAMOXIFEN" by: "M. H. Zahran, S. M. El Assal, A. M. El Nekeidy, V. G. Adly Ayad; ALEXANDRIA/EG"
Editorial: the role of vitamin D in autoimmune hepatitis

Cornelius Engelmann Stefan Schob Daniel Seehofer Thomas Berg Section Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany Institute for Liver and Digestive Health, University College London, London, UK Department for Neuroradiology, University Hospital Leipzig, Leipzig, Germany Department of Visceral, Vascular, Thoracic and Transplant Surgery, University Hospital Leipzig, Leipzig, Germany Email: c.engelmann@ucl.ac. uk REFERENCES
A reverse-transcription/RNase H based protocol for depletion of mosquito ribosomal RNA facilitates viral intrahost evolution analysis, transcriptomics and pathogen discovery

Studies aimed at identifying novel viral sequences or assessing intrahost viral variation require sufficient sequencing coverage to assemble contigs and make accurate variant calling at low frequencies. Many samples come from host tissues where ribosomal RNA represents more than 90% of total RNA preparations, making unbiased sequencing of viral samples inefficient and highly expensive, as many reads will be wasted on cellular RNAs. In the presence of this amount of ribosomal RNA, it is difficult to achieve sufficient sequencing depth to perform analyses such as variant calling, haplotype prediction, virus population analyses, virus discovery or transcriptomic profiling. Many methods for depleting unwanted RNA or enriching RNA of interest have been devised, including poly-A selection, RNase H based specific depletion, duplex-specific nuclease treatment and hybrid capture selection, among others. Although these methods can be efficient, they either cannot be used for some viruses (i.e. non-polyadenylated viruses), have been optimized for use in a single species, or have the potential to introduce bias. In this study, we describe a novel approach that uses an RNaseH possessing reverse transcriptase coupled with selective probes for ribosomal RNA designed to work broadly for three medically relevant mosquito genera; Aedes, Anopheles, and Culex. We demonstrate significant depletion of rRNA using multiple assessment techniques from a variety of sample types, including whole mosquitoes and mosquito midgut contents from FTA cards. To demonstrate the utility of our approach, we describe novel insect-specific virus genomes from numerous species of field collected mosquitoes that underwent rRNA depletion, thereby facilitating their detection. The protocol is straightforward, relatively low-cost and requires only common laboratory reagents and the design of several small oligonucleotides specific to the species of interest. This approach can be adapted for use with other organisms with relative ease, thus potentially aiding virus population genetics analyses, virus discovery and transcriptomic profiling in both laboratory and field samples.
Critical role of glutamatergic and GABAergic neurotransmission in the central mechanisms of theta‐burst stimulation

Theta‐burst stimulation (TBS) is a varied form of repetitive transcranial magnetic stimulation (rTMS) and has more rapid and powerful effects than rTMS. Experiments on the human motor cortex have demonstrated that intermittent TBS has facilitatory effects, whereas continuous TBS has inhibitory effects. Huang's simplified model provides a solid basis for elucidating such after‐effects. However, evidence increasingly indicates that not all after‐effects of TBS are as expected, and high variability among individuals has been observed. Studies have suggested that the GABAergic and glutamatergic neurotransmission play a vital role in the aforementioned after‐effects, which might explain the interindividual differences in these after‐effects. Herein, we reviewed the latest findings on TBS from animal and human experiments on glutamatergic and GABAergic neurotransmissions in response to TBS. Furthermore, an updated theoretical model integrating glutamatergic and GABAergic neurotransmissions is proposed.
Perspective: Mitochondria-ER Contacts in Metabolic Cellular Stress Assessed by Microscopy

The interplay of mitochondria with the endoplasmic reticulum and their connections, called mitochondria-ER contacts (MERCs) or mitochondria-associated ER membranes (MAMs), are crucial hubs in cellular stress. These sites are essential for the passage of calcium ions, reactive oxygen species delivery, the sorting of lipids in whole-body metabolism. In this perspective article, we focus on microscopic evidences of the pivotal role of MERCs/MAMs and their changes in metabolic diseases, like obesity, diabetes, and neurodegeneration.
Evaluating the novel added value of neurophysiological pain sensitivity within the fear‐avoidance model of pain

The fear‐avoidance model (FAM) is a leading theoretical paradigm for explaining persistent pain following musculoskeletal injury. The model suggests that as injuries heal, pain‐related outcomes are increasingly determined by psychological, rather than physiological factors. Increasing literature, however, suggests that neurophysiological processes related to pain sensitivity also play an important role in chronicity. To date, there has been limited research that has specifically explored the role of pain sensitivity within the FAM. This study addresses this gap by evaluating whether clinical measures of pain sensitivity help explain FAM‐related outcomes, beyond model‐relevant psychological predictors.
Electrical, Structural, Optical, and Adhesive Characteristics of Aluminum-Doped Tin Oxide Thin Films for Transparent Flexible Thin-Film Transistor Applications

The properties of Al-doped SnOx films deposited via reactive co-sputtering were examined in terms of their potential applications for the fabrication of transparent and flexible electronic devices. Al 2.2-atom %-doped SnOx thin-film transistors (TFTs) exhibit improved semiconductor characteristics compared to non-doped films, with a lower sub-threshold swing of ~0.68 Vdec−1, increased on/off current ratio of ~8 × 107, threshold voltage (Vth) near 0 V, and markedly reduced (by 81%) Vth instability in air, attributable to the decrease in oxygen vacancy defects induced by the strong oxidizing potential of Al. Al-doped SnOx films maintain amorphous crystallinity, an optical transmittance of ~97%, and an adhesive strength (to a plastic substrate) of over 0.7 kgf/mm; such films are thus promising semiconductor candidates for fabrication of transparent flexible TFTs.
EL SECTOR PESQUERO DE SANTA ELENA: ANÁLISIS DE LAS ESTRATEGIAS DE COMERCIALIZACIÓN. SANTA ELENA FISHING SECTOR. ANALYSIS OF MARKETING STRATEGIES.

El sector pesquero de Santa Elena ha llegado a ocupar un rubro importante de la economia local y fuente primordial del ingreso familiar. Sin embargo, sus estrategias de comercializacion siguen basandose en mecanismos tradicionales y poco sustentables en economias vulnerables ante el mercado externo como es el caso de Ecuador en la provincia de Santa Elena, en el cual, el precio del producto es el eje fundamental de equilibrio para los artesanos en la toma de decisiones. En tal sentido, la idea central de este trabajo es analizar las estrategias utilizadas por el sector pesquero a partir de un estudio interno y externo de las mismas y de su entorno, considerando que por diversas causas el precio ha dejado de ser el unico factor de competencia como via para asegurar la rentabilidad del sector. El trabajo propone una lectura de la percepcion que tiene el pescador respecto de su empresa y el entorno. Palabras clave: precio, ingresos familiares, participacion. Abstract The fisheries sector in Santa Elena Peninsula has become an important aspect of the local economy and a primary source of family income. However, commercialization strategies are still based on mechanisms that are traditional and not so-sustainable in economies vulnerable to the external market as is the case of Ecuador in the Santa Elena province, where the price of the product is the key balancing point in decision making for artisans. Therefore, the central idea of this paper is to analyze the strategies used by the fishing industry from an internal and external study of them and their environment, considering that for various reasons price is no longer the only competition factor to ensure profitability of the sector. The paper proposes a reading of the fisherman’s perception of his business and the environment. Keywords: Price, family income, participation. Recibido: septiembre de 2014 Aprobado: noviembre de 2014
Evolutionary constraints on disparity of ericaceous pollen grains.

BACKGROUND AND AIMS Flowering plants show a high diversity of pollen morphology, assumed to reflect not only variations in the underlying design, but also stress imposed by ecological conditions related to pollen survival and germination. Both components are expected to constrain the accumulation of pollen disparity. However, this assumption has rarely been tested using empirical data. METHODS This study is designed to test this hypothesis by inferring the accumulation of pollen disparity in Ericaceae, a large eudicot family with recent, ongoing radiations, with focus on three functionally significant pollen characters using a dated phylogeny. KEY RESULTS Multiple lines of evidence supported the hypothesis that pollen disparity in Ericaceae did not evolve steadily but rather pulsed over time, clearly decoupling from the relative constant rate pattern of species diversification inferred. In a 3-D pollen morphospace, most major clades appear to occupy distinct neighbouring regions, whereas the subfamily Epacridoideae overlaps extensively with other subfamilies. No evidence for correlations was found between dimension of pollen disparity and species diversity at either the subfamily or generic level. Furthermore, the distribution of species in present pollen morphospace showed a strong central tendency, with the core compartment containing a large number of species from species-rich genera. CONCLUSIONS The recovered evidence fits well with the expectations of limitations on available pollen morphological disparity, and suggests that innovation of pollen germination traits may have little effect on species diversification.
Content-Aware Focal Plane Selection and Proposals for Object Tracking on Plenoptic Image Sequences

Object tracking is a fundamental problem in computer vision since it is required in many practical applications including video-based surveillance and autonomous vehicles. One of the most challenging scenarios in the problem is when the target object is partially or even fully occluded by other objects. In such cases, most of existing trackers can fail in their task while the object is invisible. Recently, a few techniques have been proposed to tackle the occlusion problem by performing the tracking on plenoptic image sequences. Although they have shown promising results based on the refocusing capability of plenoptic images, there is still room for improvement. In this paper, we propose a novel focus index selection algorithm to identify an optimal focal plane where the tracking should be performed. To determine an optimal focus index, we use a focus measure to find maximally focused plane and a visual similarity to capture the plane where the target object is visible, and its appearance is distinguishably clear. We further use the selected focus index to generate proposals. Since the optimal focus index allows us to estimate the distance between the camera and the target object, we can more accurately guess the scale changes of the object in the image plane. Our proposal algorithm also takes the trajectory of the target object into account. We extensively evaluate our proposed techniques on three plenoptic image sequences by comparing them against the prior tracking methods specialized to the plenoptic image sequences. In experiments, our method provides higher accuracy and robustness over the prior art, and those results confirm that the merits of our proposed algorithms.
How to Avoid Death by Meeting

ABSTRACT Meetings can be great opportunities to create the synergy that leads to better productivity and a more satisfying work experience. Leaders can create a “POP-Purpose, Outcome, and Plan” to uncover specific goals and identify the best methods to achieve them. Agendas should be carefully formatted with the desirable result in mind. Adding time specifications, assigning names to topics, and providing a layout conducive to resulting action assists both leaders and meeting participants. Facilitation techniques assure active participation by everyone and help move the discussion toward a productive outcome.
Neutrophil elastase plays a non‐redundant role in remodeling the venular basement membrane and neutrophil diapedesis post‐ischemia/reperfusion injury

Ischemia/reperfusion (I/R) injury is a severe inflammatory insult associated with numerous pathologies, such as myocardial infarction, stroke and acute kidney injury. I/R injury is characterized by a rapid influx of activated neutrophils secreting toxic free radical species and degrading enzymes that can irreversibly damage the tissue, thus impairing organ functions. Significant efforts have been invested in identifying therapeutic targets to suppress neutrophil recruitment and activation post‐I/R injury. In this context, pharmacological targeting of neutrophil elastase (NE) has shown promising anti‐inflammatory efficacy in a number of experimental and clinical settings of I/R injury and is considered a plausible clinical strategy for organ care. However, the mechanisms of action of NE, and hence its inhibitors, in this process are not fully understood. Here we conducted a comprehensive analysis of the impact of NE genetic deletion on neutrophil infiltration in four murine models of I/R injury as induced in the heart, kidneys, intestine and cremaster muscle. In all models, neutrophil migration into ischemic regions was significantly suppressed in NE−/− mice as compared with wild‐type controls. Analysis of inflamed cremaster muscle and mesenteric microvessels by intravital and confocal microscopy revealed a selective entrapment of neutrophils within venular walls, most notably at the level of the venular basement membrane (BM) following NE deletion/pharmacological blockade. This effect was associated with the suppression of NE‐mediated remodeling of the low matrix protein expressing regions within the venular BM used by transmigrating neutrophils as exit portals. Furthermore, whilst NE deficiency led to reduced neutrophil activation and vascular leakage, levels of monocytes and prohealing M2 macrophages were reduced in tissues of NE−/− mice subjected to I/R. Collectively our results identify a vital and non‐redundant role for NE in supporting neutrophil breaching of the venular BM post‐I/R injury but also suggest a protective role for NE in promoting tissue repair. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Exploring Validity, Reliability, and Factor Analysis of the Quebec User Evaluation of Satisfaction with Assistive Technology in an Italian Population: A Cross-Sectional Study

Abstract This study explores validity, reliability, and factor analysis of the Quebec User Evaluation of Satisfaction with Assistive Technology (IT-QUEST) for users of assistive technology devices in an Italian population. It was administered to 75 people to determine which of the 24 original items were relevant to the Italian context using exploratory and confirmatory factor analyses (EFAs and CFAs) were conducted with internal consistency and test-retest reproducibility also evaluated. The EFA and CFA showed that the 24-item survey may have limited relevance to the Italian context. We individuated 12 significative items, divided into two subscales, as well as the original validation. The test-retest showed high values of the Intraclass Correlation Coefficient (ICC) (0.7–0.9), with a 0.812 ICC for the total scale providing support and evidence for Italian professionals to evaluate user satisfaction with assistive technology devices. This research also lays the foundation for developing a validation study of the IT-QUEST 2.0 that is relevant to the Italian culture. Further research may investigate psychometric properties involving more participants and different users of assistive technology devices.
New and emerging AAC technology supports for children with complex communication needs and their communication partners: State of the science and future research directions

Abstract This paper discusses recent research and development with a specific focus on selected new and emerging research-based augmentative and alternative communication (AAC) technologies that are developmentally appropriate and responsive to the individual interests, needs, and skills of children with developmental disabilities, their families, peers, and other communication partners. Specifically, this paper reviews the state of the science and future directions related to recent research and development of AAC technologies as supports to (a) enhance language learning, (b) facilitate social interaction, (c) improve literacy skills, (d) increase participation in society, and (e) teach interaction strategies to communication partners.