Miracle-dz/UniFAR-FTUs huggingface dataset:
A systematic review of low‐level light therapy for treatment of diabetic foot ulcer

Diabetes mellitus (DM) is a significant international health concern affecting more than 387 million individuals. A diabetic person has a 25% lifetime risk of developing a diabetic foot ulcer (DFU), leading to limb amputation in up to one in six DFU patients. Low‐level light therapy (LLLT) uses low‐power lasers or light‐emitting diodes to alter cellular function and molecular pathways, and may be a promising treatment for DFU. The goal of this systematic review is to examine whether the clinical use of LLLT is effective in the healing of DFU at 12 and 20 weeks in comparison with the standard of care, and to provide evidence‐based recommendation and future clinical guidelines for the treatment of DFU using LLLT. On September 30, 2015, we searched PubMed, EMBASE, CINAHL, and Web of Science databases using the following terms: “diabetic foot” AND “low level light therapy,” OR “light emitting diode,” OR “phototherapy,” OR “laser. ” The relevant articles that met the following criteria were selected for inclusion: randomized control trials (RCTs) that investigated the use of LLLT for treatment of DFU. Four RCTs involving 131 participants were suitable for inclusion based upon our criteria. The clinical trials used sham irriadiation, low dose, or nontherapeutic LLLT as placebo or control in comparison to LLLT. The endpoints included ulcer size and time to complete healing with follow‐up ranging from 2 to 16 weeks. Each article was assigned a level of evidence (LOE) and graded according to the Oxford Center for Evidence‐based Medicine Levels of Evidence Grades of Recommendation criteria. Limitations of reviewed RCTs include a small sample size (N < 100), unclear allocation concealment, lack of screening phase to exclude rapid healers, unclear inclusion/exclusion criteria, short (<30 days) follow‐up period, and unclear treatment settings (wavelength and treatment time). However, all reviewed RCTs demonstrated therapeutic outcomes with no adverse events using LLLT for treatment of DFU. This systematic review reports that LLLT has significant potential to become a portable, minimally invasive, easy‐to‐use, and cost effective modality for treatment of DFU. To enthusiastically recommend LLLT for treatment of DFU, additional studies with comparable laser parameters, screening period to exclude rapid healers, larger sample sizes and longer follow‐up periods are required. We envision future stringent RCTs may validate LLLT for treatment of DFU. Systematic review registration number: PROSPERO CRD42015029825.
Laceioside, a new cycloartane saponin from Astragalus tephrosioides Boiss. var. lacei (Ali) Kirchoff.

Abstract Phytochemical investigation of the aerial parts of Astragalus tephrosioides Boiss. var. lacei (Ali) Kirchoff. (Family Fabaceae) resulted in the isolation of a new cycloartane glycoside laceioside (1). The structure of the previously undescribed compound 1 was established as 16β-acetyloxy-3-O-β-d-glucopyranosyloxy-cycloartan-11α,24ξ, 25-triol. The structure elucidation of compound 1 was based primarily on 1D and 2D-NMR techniques including 1H and 13CNMR spectra, DEPT and by 2D COSY, HSQC and HMBC experiments.
Microbial Diseases of Bivalve Mollusks: Infections, Immunology and Antimicrobial Defense

A variety of bivalve mollusks (phylum Mollusca, class Bivalvia) constitute a prominent commodity in fisheries and aquacultures, but are also crucial in order to preserve our ecosystem’s complexity and function. Bivalve mollusks, such as clams, mussels, oysters and scallops, are relevant bred species, and their global farming maintains a high incremental annual growth rate, representing a considerable proportion of the overall fishery activities. Bivalve mollusks are filter feeders; therefore by filtering a great quantity of water, they may bioaccumulate in their tissues a high number of microorganisms that can be considered infectious for humans and higher vertebrates. Moreover, since some pathogens are also able to infect bivalve mollusks, they are a threat for the entire mollusk farming industry. In consideration of the leading role in aquaculture and the growing financial importance of bivalve farming, much interest has been recently devoted to investigate the pathogenesis of infectious diseases of these mollusks in order to be prepared for public health emergencies and to avoid dreadful income losses. Several bacterial and viral pathogens will be described herein. Despite the minor complexity of the organization of the immune system of bivalves, compared to mammalian immune systems, a precise description of the different mechanisms that induce its activation and functioning is still missing. In the present review, a substantial consideration will be devoted in outlining the immune responses of bivalves and their repertoire of immune cells. Finally, we will focus on the description of antimicrobial peptides that have been identified and characterized in bivalve mollusks. Their structural and antimicrobial features are also of great interest for the biotechnology sector as antimicrobial templates to combat the increasing antibiotic-resistance of different pathogenic bacteria that plague the human population all over the world.
Interactions between the Kynurenine and the Endocannabinoid System with Special Emphasis on Migraine

Both the kynurenine and the endocannabinoid systems are involved in several neurological disorders, such as migraine and there are increasing number of reports demonstrating that there are interactions of two systems. Although their cooperation has not yet been implicated in migraine, there are reports suggesting this possibility. Additionally, the individual role of the endocannabinoid and kynurenine system in migraine is reviewed here first, focusing on endocannabinoids, kynurenine metabolites, in particular kynurenic acid. Finally, the function of NMDA and cannabinoid receptors in the trigeminal system—which has a crucial role in the pathomechanisms of migraine—will also be discussed. The interaction of the endocannabinoid and kynurenine system has been demonstrated to be therapeutically relevant in a number of pathological conditions, such as cannabis addiction, psychosis, schizophrenia and epilepsy. Accordingly, the cross-talk of these two systems may imply potential mechanisms related to migraine, and may offer new approaches to manage the treatment of this neurological disorder.
On the permeation of large organic cations through the pore of ATP-gated P2X receptors

Significance Unlike many ion channels whose pore conductances remain relatively stable over time, it is thought that prolonged ATP applications to P2X receptors cause a striking increase over time in the permeability of large molecules, a process dubbed pore dilation. However, this mechanism remains poorly understood and highly controversial. Here, we use different methods spanning single-channel recordings, photochemistry, molecular biology, and computations to show that contrary to longstanding view, rapid activation by ATP allows the stable passage of large cations through the P2X pore. We further discover that spermidine, a large natural cation known to modulate other ion channels, is able to transit through many P2X receptors, including those thought to be nondilating. Our data thus reveal an unacknowledged P2X-mediated signaling. Pore dilation is thought to be a hallmark of purinergic P2X receptors. The most commonly held view of this unusual process posits that under prolonged ATP exposure the ion pore expands in a striking manner from an initial small-cation conductive state to a dilated state, which allows the passage of larger synthetic cations, such as N-methyl-d-glucamine (NMDG+). However, this mechanism is controversial, and the identity of the natural large permeating cations remains elusive. Here, we provide evidence that, contrary to the time-dependent pore dilation model, ATP binding opens an NMDG+-permeable channel within milliseconds, with a conductance that remains stable over time. We show that the time course of NMDG+ permeability superimposes that of Na+ and demonstrate that the molecular motions leading to the permeation of NMDG+ are very similar to those that drive Na+ flow. We found, however, that NMDG+ “percolates” 10 times slower than Na+ in the open state, likely due to a conformational and orientational selection of permeating molecules. We further uncover that several P2X receptors, including those able to desensitize, are permeable not only to NMDG+ but also to spermidine, a large natural cation involved in ion channel modulation, revealing a previously unrecognized P2X-mediated signaling. Altogether, our data do not support a time-dependent dilation of the pore on its own but rather reveal that the open pore of P2X receptors is wide enough to allow the permeation of large organic cations, including natural ones. This permeation mechanism has considerable physiological significance.
The Sound Quality of Cochlear Implants: Studies With Single-sided Deaf Patients.

OBJECTIVE The goal of the present study was to assess the sound quality of a cochlear implant for single-sided deaf (SSD) patients fit with a cochlear implant (CI). BACKGROUND One of the fundamental, unanswered questions in CI research is "what does an implant sound like? " Conventional CI patients must use the memory of a clean signal, often decades old, to judge the sound quality of their CIs. In contrast, SSD-CI patients can rate the similarity of a clean signal presented to the CI ear and candidate, CI-like signals presented to the ear with normal hearing. METHODS For Experiment 1 four types of stimuli were created for presentation to the normal hearing ear: noise vocoded signals, sine vocoded signals, frequency shifted, sine vocoded signals and band-pass filtered, natural speech signals. Listeners rated the similarity of these signals to unmodified signals sent to the CI on a scale of 0 to 10 with 10 being a complete match to the CI signal. For Experiment 2 multitrack signal mixing was used to create natural speech signals that varied along multiple dimensions. RESULTS In Experiment 1 for eight adult SSD-CI listeners, the best median similarity rating to the sound of the CI for noise vocoded signals was 1.9; for sine vocoded signals 2.9; for frequency upshifted signals, 1.9; and for band pass filtered signals, 5.5. In Experiment 2 for three young listeners, combinations of band pass filtering and spectral smearing lead to ratings of 10. CONCLUSION The sound quality of noise and sine vocoders does not generally correspond to the sound quality of cochlear implants fit to SSD patients. Our preliminary conclusion is that natural speech signals that have been muffled to one degree or another by band pass filtering and/or spectral smearing provide a close, but incomplete, match to CI sound quality for some patients.
Fitting Function for Flexural Strength of Cement Paste

There are many analytical expressions for compressive strength as functions of porosity of cement-based materials but only a few such expressions exist for flexural strength of these materials. In the present paper a new functional candidate for fitting the data of flexural strength of hydrated Portland cement paste has been tested. The functional candidate has been initially derived for porous polymeric materials on the basis of the percolation theory. The parameters of this function have been optimized for the cement paste by using the Levenberg-Marquardt iterative fitting procedure. The optimized function has been capable of accurate reproducing all the measured flexural data. This fact has been confirmed by a high value of the correlation coefficient and rather low values of statistical uncertainties. It has been shown that this modified fitting function is well applicable to the pastes of ordinary Portland cements and probably to other cementitious materials, too.
The Cryptococcus neoformans Alkaline Response Pathway: Identification of a Novel Rim Pathway Activator

The Rim101/PacC transcription factor acts in a fungal-specific signaling pathway responsible for sensing extracellular pH signals. First characterized in ascomycete fungi such as Aspergillus nidulans and Saccharomyces cerevisiae, the Rim/Pal pathway maintains conserved features among very distantly related fungi, where it coordinates cellular adaptation to alkaline pH signals and micronutrient deprivation. However, it also directs species-specific functions in fungal pathogens such as Cryptococcus neoformans, where it controls surface capsule expression. Moreover, disruption of the Rim pathway central transcription factor, Rim101, results in a strain that causes a hyper-inflammatory response in animal infection models. Using targeted gene deletions, we demonstrate that several genes encoding components of the classical Rim/Pal pathway are present in the C. neoformans genome. Many of these genes are in fact required for Rim101 activation, including members of the ESCRT complex (Vps23 and Snf7), ESCRT-interacting proteins (Rim20 and Rim23), and the predicted Rim13 protease. We demonstrate that in neutral/alkaline pH, Rim23 is recruited to punctate regions on the plasma membrane. This change in Rim23 localization requires upstream ESCRT complex components but does not require other Rim101 proteolysis components, such as Rim20 or Rim13. Using a forward genetics screen, we identified the RRA1 gene encoding a novel membrane protein that is also required for Rim101 protein activation and, like the ESCRT complex, is functionally upstream of Rim23-membrane localization. Homologs of RRA1 are present in other Cryptococcus species as well as other basidiomycetes, but closely related genes are not present in ascomycetes. These findings suggest that major branches of the fungal Kingdom developed different mechanisms to sense and respond to very elemental extracellular signals such as changing pH levels.
Functional Connectivity of the Pedunculopontine Nucleus and Surrounding Region in Parkinson's Disease

Abstract Deep brain stimulation of the pedunculopontine nucleus and surrounding region (PPNR) is a novel treatment strategy for gait freezing in Parkinson's disease (PD). However, clinical results have been variable, in part because of the paucity of functional information that might help guide selection of the optimal surgical target. In this study, we use simultaneous magnetoencephalography and local field recordings from the PPNR in seven PD patients, to characterize functional connectivity with distant brain areas at rest. The PPNR was preferentially coupled to brainstem and cingulate regions in the alpha frequency (8‐12 Hz) band and to the medial motor strip and neighboring areas in the beta (18‐33 Hz) band. The distribution of coupling also depended on the vertical distance of the electrode from the pontomesencephalic line: most effects being greatest in the middle PPNR, which may correspond to the caudal pars dissipata of the pedunculopontine nucleus. These observations confirm the crucial position of the PPNR as a functional node between cortical areas such as the cingulate/ medial motor strip and other brainstem nuclei, particularly in the dorsal pons. In particular they suggest a special role for the middle PPNR as this has the greatest functional connectivity with other brain regions.
Glioma tumor suppressor candidate region gene 1 (GLTSCR1) and its paralog GLTSCR1-like form SWI/SNF chromatin remodeling subcomplexes

The mammalian SWI/SNF chromatin remodeling complex is a heterogeneous collection of related protein complexes required for gene regulation and genome integrity. It contains a central ATPase (BRM or BRG1) and various combinations of 10–14 accessory subunits (BAFs for BRM/BRG1 Associated Factors). Two distinct complexes differing in size, BAF and the slightly larger polybromo-BAF (PBAF), share many of the same core subunits but are differentiated primarily by having either AT-rich interaction domain 1A/B (ARID1A/B in BAF) or ARID2 (in PBAF). Using density gradient centrifugation and immunoprecipitation, we have identified and characterized a third and smaller SWI/SNF subcomplex. We termed this complex GBAF because it incorporates two mutually exclusive paralogs, GLTSCR1 (glioma tumor suppressor candidate region gene 1) or GLTSCR1L (GLTSCR1-like), instead of an ARID protein. In addition to GLTSCR1 or GLTSCR1L, the GBAF complex contains BRD9 (bromodomain-containing 9) and the BAF subunits BAF155, BAF60, SS18, BAF53a, and BRG1/BRM. We observed that GBAF does not contain the core BAF subunits BAF45, BAF47, or BAF57. Even without these subunits, GBAF displayed in vitro ATPase activity and bulk chromatin affinity comparable to those of BAF. GBAF associated with BRD4, but, unlike BRD4, the GBAF component GLTSCR1 was not required for the viability of the LNCaP prostate cancer cell line. In contrast, GLTSCR1 or GLTSCR1L knockouts in the metastatic prostate cancer cell line PC3 resulted in a loss in proliferation and colony-forming ability. Taken together, our results provide evidence for a compositionally novel SWI/SNF subcomplex with cell type–specific functions.
Fronto-parietal organization for response times in inhibition of return: The FORTIOR model

Inhibition of Return (IOR) refers to a slowing of response times (RTs) for visual stimuli repeated at the same spatial location, as compared to stimuli occurring at novel locations. The functional mechanisms and the neural bases of this phenomenon remain debated. Here we present FORTIOR, a model of the cortical control of visual IOR in the human brain. The model is based on known facts about the anatomical and functional organization of fronto-parietal attention networks, and accounts for a broad range of behavioral findings in healthy participants and brain-damaged patients. FORTIOR does that by combining four principles of asymmetry: Asymmetry in the networks topography, whereby the temporoparietal junction (TPJ) and ventrolateral prefrontal cortex (vlPFC) nodes are lateralized to the right hemisphere, causing higher activation levels in the right intraparietal sulcus (IPS) and frontal eye field (FEF) nodes. Asymmetry in inter-hemispheric connectivity, in which inter-hemispheric connections from left hemisphere IPS to right hemisphere IPS and from left hemisphere FEF to right hemisphere FEF are weaker than in the opposite direction. Asymmetry of visual inputs, stipulating that the FEF receives direct visual input coming from the ipsilateral visual cortex, while the right TPJ and vlPFC and IPS nodes receive input from both the contralateral and the ipsilateral visual fields. Asymmetry in the response modality, with a higher response threshold for the manual response system than that required to trigger a saccadic response. This asymmetry results in saccadic IOR being more robust to interference than manual IOR. FORTIOR accounts for spatial asymmetries in the occurrence of IOR after brain damage and after non-invasive transcranial magnetic stimulation on parietal and frontal regions. It also provides a framework to understand dissociations between manual and saccadic IOR, and makes testable predictions for future experiments to assess its validity. Research highlights FORTIOR is a model of cortical control of visual IOR in the human brain FORTIOR is based on the architecture of fronto-parietal networks FORTIOR presents asymmetries favoring the right hemisphere FORTIOR explains complex patterns of IOR-related results FORTIOR provides testable predictions
Accuracy of three-dimensional dental resin models created by fused deposition modeling, stereolithography, and Polyjet prototype technologies: A comparative study.

OBJECTIVES The aim of this study was to assess the dimensional accuracy of fused deposition modeling (FDM)-, Polyjet-, and stereolithography (SLA)-produced models by comparing them to traditional plaster casts. MATERIALS AND METHODS A total of 12 maxillary and mandibular posttreatment orthodontic plaster casts were selected from the archives of the Orthodontic Department at the Indiana University School of Dentistry. Plaster models were scanned, saved as stereolithography files, and printed as physical models using three different three-dimensional (3D) printers: Makerbot Replicator (FDM), 3D Systems SLA 6000 (SLA), and Objet Eden500V (Polyjet). A digital caliper was used to obtain measurements on the original plaster models as well as on the printed resin models. RESULTS Comparison between the 3D printed models and the plaster casts showed no statistically significant differences in most of the parameters. However, FDM was significantly higher on average than were plaster casts in maxillary left mixed plane (MxL-MP) and mandibular intermolar width (Md-IMW). Polyjet was significantly higher on average than were plaster casts in maxillary intercanine width (Mx-ICW), mandibular intercanine width (Md-ICW), and mandibular left mixed plane (MdL-MP). Polyjet was significantly lower on average than were plaster casts in maxillary right vertical plane (MxR-vertical), maxillary left vertical plane (MxL-vertical), mandibular right anteroposterior plane (MdR-AP), mandibular right vertical plane (MdR-vertical), and mandibular left vertical plane (MdL-vertical). SLA was significantly higher on average than were plaster casts in MxL-MP, Md-ICW, and overbite. SLA was significantly lower on average than were plaster casts in MdR-vertical and MdL-vertical. CONCLUSIONS Dental models reconstructed by FDM technology had the fewest dimensional measurement differences compared to plaster models.
Assisted reproductive technologies in the common marmoset: an integral species for developing nonhuman primate models of human diseases†

Abstract Generation of nonhuman primate models of human disease conditions will foster the development of novel therapeutic strategies. Callithrix jacchus, or the common marmoset, is a New World, nonhuman primate species that exhibits great reproductive fitness in captivity with an ovarian cycle that can be easily managed with pharmacological agents. This characteristic, among others, provides an opportunity to employ assisted reproductive technologies to generate embryos that can be genetically manipulated to create a variety of nonhuman primate models for human disease. Here, we review methods to synchronize the marmoset ovarian cycle and stimulate oocyte donors, and compare various protocols for in vitro production of embryos. In light of advances in genomic editing, recent approaches used to generate transgenic or genetically edited embryos in the marmoset and also future perspective are reviewed. Summary Sentence This review presents a summary of assisted reproductive technologies utilized to generate in vitro produced embryos in the common marmoset and describes prospects for genomic editing and transgenesis to create nonhuman primate models of human disease.