Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of an in vitro intervertebral disc innervation model to screen neuroinhibitory biomaterials

Pain originating from an intervertebral disc (discogenic pain) is a major source of chronic low back pain. Pathological innervation of the disc by pain‐sensing nerve fibers is thought to be a key component of discogenic pain, so treatment with biomaterials that have the ability to inhibit neurite growth will greatly benefit novel disc therapeutics. Currently, disc therapeutic biomaterials are rarely screened for their ability to modulate nerve growth, mainly due to a lack of models to screen neuromodulation. To address this deficit, our lab has engineered a three dimensional in vitro disc innervation model that mimics the interface between primary sensory nerves and the intervertebral disc. Further, herein we have demonstrated the utility of this model to screen the efficacy of chondroitin sulfate biomaterials to inhibit nerve fiber invasion into the model disc. Biomaterials containing chondroitin‐4‐sulfate (CS‐A) decrease neurite growth in a uniform gel and at an interface between a growth‐permissive and a growth‐inhibitory gel, while chondroitin‐6‐sulfate (CS‐C) is less neuroinhibitory. This in vitro model holds great potential for screening inhibitors of nerve fiber growth to further improve intervertebral disc replacements and therapeutics. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1016‐1026, 2020
Metacognitive Capacity Is Related to Self-Reported Social Functioning and May Moderate the Effects of Symptoms on Interpersonal Behavior

Abstract Impairments in metacognition or the ability to form integrated senses of self and others have been linked to deficits in laboratory-based measures of social functioning in schizophrenia. This study examined whether self-reported social functioning was related to metacognition in 88 adults in a nonacute phase of schizophrenia. Concurrent assessments were made of metacognition with the Metacognition Assessment Scale–Abbreviated, social functioning with the Social Functioning Scale, symptoms with the Positive and Negative Syndrome Scale, and neurocognition with the Wisconsin Card Sorting Task. Univariate correlations revealed that self-reported social functioning was related to metacognition. Symptom severity was linked to interpersonal relationships, and overall metacognition was found to significantly moderate that relationship such that the effects of symptoms on function grew less as metacognitive capacity was stronger, independent of the effects of neurocognition. This may suggest the potential of metacognitive interventions to titrate the negative effects of symptoms on social function.
Diffusion tensor imaging in neonatal encephalopathy: a systematic review

Background and objective Diffusion tensor imaging (DTI) during the first few days of life can be used to assess brain injury in neonates with neonatal encephalopathy (NE) for outcome prediction. The goal of this review was to identify specific white matter tracts of interest that can be quantified by DTI as being altered in neonates with this condition, and to investigate its potential prognostic ability. Methods Searches of Medline and the Cochrane Database of Systematic Reviews were conducted to identify studies with diffusion data collected in term-born neonates with NE. Results 19 studies were included which described restricted diffusion in encephalopathic neonates as compared with healthy controls, with the posterior limb of the internal capsule and the genu and splenium of the corpus callosum identified as particular regions of interest. Restricted diffusion was related to adverse outcomes in the studies that conducted a follow-up of these infants. Conclusions Obtaining diffusion measures in these key white matter tracts early in life before pseudonormalisation can occur can not only identify the extent of the damage but also can be used to examine the effectiveness of treatment and to predict neurodevelopmental outcome.
Inhibition of Dimethylarginine Dimethylaminohydrolase 1 Improves the Outcome of Sepsis in Pregnant Mice.

Sepsis is one of the most important causes of maternal mortality. In our previous work, we established a polymicrobial sepsis (caecal ligation and puncture, [CLP]) model in murine pregnancy and found that pregnant mice had a greater susceptibility to septic shock. In this model, mortality appeared to be associated with the development of early haemodynamic dysfunction and although circulating cytokine levels were similar, "off target" lung inflammatory cell numbers were greater in pregnant mice.Here, we have used the same CLP model to test the hypothesis that inhibiting the metabolism of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine would improve the outcome of sepsis in pregnancy. We used a dimethylarginine dimethylaminohydrolase 1-selective inhibitor (L-257), which reduces vascular nitric oxide synthesis without impairing immune cell function, in combination with a broad-spectrum antibiotic (Imipenem) and studied the outcome of septic shock in pregnant mice. Treatments were administered 3 hours after CLP and samples were taken 3 hours later. Both Imipenem and L-257 treatment alone slightly improved mortality rates from 13% (NaCl) to 20% (Imipenem) and 33% (L-257), while the combination of Imipenem and L-257, significantly improved survival to 50%. Imipenem and L-257 together prevented cardiovascular collapse and improved both organ function and bacterial killing but did not reduce lung inflammatory cell numbers and actually increased lung cytokine levels.These data suggest that conventional management in combination with selective inhibition of DDAH1 may have therapeutic potential in the management of sepsis in pregnancy.
An Efficient Algorithm for Moving Objects Segmentation

This paper presents a fast and accurate moving objects segmentation algorithm. Our algorithm consists of three components. The first one is the pixel level component which is based on assumption that the pixel value in the moving object’s position changes faster than those in the real background. It performs background updating only when the pixels value does not change much for a period of time. The second component is the connected components labeling which is used to reduce the misclassification regions. The third component is the region level component to refine the raw classification of the pixel level. Idea is that only foreground region that corresponds to an actual moving object will have high percent of pixels that belong to frame difference mask. In order to meet the real-time requirements, no computationally intensive operation is included in this method. The system is tested in typical outdoor traffic video sequence for handling automatic background modeling and object detection and test results are presented.
Omentin-1 in diabetes mellitus: A systematic review and meta-analysis

Objective Previous studies found inconsistent results on the relationship between diabetes mellitus and concentrations of omentin-1. This study performed a systematic review and meta-analysis to summarize previous findings on this relationship. Methods Studies related to this outcome were obtained using a systematic search in the electronic databases of Cochrane Library, PubMed, Embase, SCOPUS, Google Scholar, gray literature and Web of Science in September 2019. The random effects model was used to measure the strength of the association between diabetes mellitus and concentrations of omentin-1, using standardized mean difference. Results Forty-two eligible studies were included in the final meta-analysis. There was no significant difference in omentin-1 concentration between patients with type 1 diabetes mellitus and the controls. On the other hand, lower concentration levels of omentin-1 were observed in patients with gestational diabetes mellitus (standardized mean difference:-0.44, 95% confidence interval:-0.76; -0.12, p = 0.007), or type 2 diabetes mellitus (standardized mean difference: -1.74, 95% confidence interval: -2.31; -1.16, p< 0.001) than in the controls. Conclusion Decreased omentin-1 concentrations may be an important indicator for gestational diabetes mellitus and type 2 diabetes mellitus. More studies are needed to validate this hypothesis and evaluate the role of omentin-1 concentrations in type 1 diabetes mellitus.
Classification and Unified Modeling for Duplication–based Recovery

For fault detection often process/thread duplication is used. A fault is detected by comparing the process states and outputs after a processing round. When detected, several ways to handle that situation exist, depending on the allowed redundancy in space and time (e.g. [1], [2]). Based on our recent work, we found a clear and comprehensive classification scheme for duplication–based recovery. Furthermore, the way of modeling is inspired by this classification and treats different recovery schemes in a unified way. The model contains parameters that reflect a common hardware or software basis used for process duplication, e.g. a common operating system or a common processor with two simultaneous instruction streams [3].
Patient activation in psychotherapy interactions: Developing and validating the consultation interactions coding scheme.

OBJECTIVE We describe the development of an instrument aiming to offer interaction-level feedback based on "patient activation": client confidence and perceived ability to manage their health. METHOD Twenty-two session-transcripts from cognitive behavioral therapy with high-users of healthcare were analyzed thematically, producing themes describing in-session interactions. Themes were subcategorized using patient activation theory into high and low activation presentations. Two coders new to the process were trained to use this consultation interactions coding scheme (CICS). Inter-rater reliability (IRR), convergent validity, and clinical utility were assessed and illustrated with extreme cases. RESULTS Good-to-excellent IRR was achieved. The CICS, therapeutic alliance, and therapist competence were correlated. Client engagement in session-structuring interactions correlated with outcome. The highest CICS scorer showed multiple outcome-improvements, the lowest scorer reported deteriorations. CONCLUSIONS This study presents the CICS's psychometric properties and indicates the value of client engagement in session-structuring.
Desensitization of NMDA channels requires ligand binding to both GluN1 and GluN2 subunits to constrict the pore beside the activation gate

N‐methyl‐D‐aspartate (NMDA) receptor channels are activated by glutamate (or NMDA) and glycine. The channels also undergo desensitization, which denotes decreased channel availability, after prolonged exposure to the activating ligands. Glycine apparently has a paradoxical negative effect on desensitization, as the increase in ambient glycine in concentrations required for channel activation would increase sustained NMDA receptor currents. We hypothesized that this classical “glycine‐dependent desensitization” could be glycine‐dependent activation in essence. By performing electrophysiological recordings and biophysical analyses with rat brain NMDA receptors heterogeneously expressed in Xenopus laevis oocytes, we characterized that the channel opened by “only” NMDA (in nominally glycine‐free condition probably with the inevitable nanomolar glycine) would undergo a novel form of deactivation rather than desensitization, and is thus fully available for subsequent activation. Moreover, external tetrapentylammonium ions (TPentA), tetrabutylammonium ions, and tetrapropylammonium ions (TPA, in higher concentrations) block the pore and prohibit channel desensitization with a simple “foot‐in‐the‐door” hindrance effect. TpentA and TPA have the same voltage dependence but show different flow dependence in binding affinity, revealing a common binding site at an electrical distance of ~0.7 from the outside yet differential involvement of the flux‐coupling region in the external pore mouth. The smaller tetraethylammonium ion and the larger tetrahexylammonium and tetraheptylammonium ions may block the channel but could not affect desensitization. We conclude that NMDA receptor desensitization requires concomitant binding of both glycine and glutamate, and thus movement of both GluN1 and GluN2 subunits. Desensitization gate itself embodies a highly restricted pore reduction with a physical distance of ~4 Å from the charged nitrogen atom of bound tetraalkylammonium ions, and is located very close to the activation gate in the bundle‐crossing region in the external pore vestibule.
Letter to the editor in response to ‘Molecular detection of rabies virus strain with N-gene that clustered with China lineage 2 co-circulating with Africa lineages in Monrovia, Liberia: first reported case in Africa’

© The Author(s) 2019. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. Letter to the editor in response to ‘Molecular detection of rabies virus strain with N-gene that clustered with China lineage 2 co-circulating with Africa lineages in Monrovia, Liberia: first reported case in Africa’
Phylogeny of the Neotropical tribe Jacarandeae (Bignoniaceae).

PREMISE The tribe Jacarandeae includes Jacaranda (49 species) and Digomphia (3 species), two genera of trees and woody shrubs with Neotropical distribution. Jacarandeae is sister to the rest of the Bignoniaceae, but not much is known about interspecific and intergeneric relationships within this group. METHODS We reconstructed the phylogeny of Jacarandeae using chloroplast (ndhF, rpl32-trnL, trnL-F) and nuclear (ETS, PPR62) markers. Evolutionary relationships within Jacarandeae were inferred using Bayesian, Maximum Likelihood, and species tree approaches. The resulting phylogenetic framework was used as the basis to interpret the evolution of key morphological character states (i.e., stamen and calyx traits) and revise the infra-generic classification of the group. RESULTS Jacaranda and Digomphia belong to a well-supported clade, with Digomphia nested within Jacaranda. We propose the necessary taxonomic changes to recognize monophyletic taxa, including a broadly circumscribed Jacaranda divided into four sections: (1) Jacaranda sect. Nematopogon, species previously included in Digomphia and united by divided staminode apices and spathaceous calyces; (2) Jacaranda sect. Copaia, species with monothecal anthers and cupular calyces; (3) Jacaranda sect. Jacaranda, species with monothecal anthers and campanulate calyces; and (4) Jacaranda sect. Dilobos, species with dithecal anthers and cupular calyces, and including more than half of the species of the genus, all restricted to Brazil. CONCLUSIONS As circumscribed here, Jacarandeae includes only a broadly defined Jacaranda divided into four sections. Each section is defined by a unique combination of anther and calyx morphologies.
Liposomal delivery of vascular endothelial growth factor/receptors and their inhibitors

Abstract The development of nanocarrier delivery systems opened new opportunities in the nano-technology field. Liposomes, possessing useful characteristics including their biocompatibility, stability in colloidal solutions and biodegradability are appropriate candidates for drug delivery applications. Vascular endothelial growth factors (VEGF) and their receptors (VEGFR) play a key role in the development of angiogenesis in physiological and pathological conditions such as wound healing and cancer, respectively. To overcome the delivery problems (e.g. drug half-life, cellular uptake, rate of release and efficacy) of VEGF/VEGFRs and their inhibitors, many studies focussed on the use of liposomes as nanocarrier drug delivery system. In this review we aim to describe the state-of-the-art targeting of VEGF/VEGFR and delivery of its inhibitors with liposomal nanocarriers. The lessons from this technology of liposomal nanocarriers should be instructive for scientists developing nano-encapsulation and delivery systems and those focussing on tissue engineering and innovative cancer therapy applications.
Early experience with the ATTUNE Total Knee Replacement System

Background: Modern TKA implants promise to improve functional outcomes, stability, patient satisfaction and operating room efficiency. The purpose of this retrospective study is to evaluate our short-term clinical and radiological results and survival using the ATTUNE Total Knee Replacement System. Methods: The authors reviewed 228 primary cemented TKAs using ATTUNE Total Knee Replacement System which were implanted between 2014 and 2018 concerning short-term clinical and radiographical outcomes and survival. Clinical evaluation was performed using the Knee injury Osteoarthritis Outcome Score (KOOS), the Oxford Score and a Numeric Rating Scale (NRS) for pain. Radiographic analysis was performed using the Modern Knee Society Score Evaluation System. Results: The means of the clinical results as measured with KOOS score were Pain 82,7, Symptoms 79, ADL 78,3, Sport & recreation 51,8 and QOL 78,6. The mean Oxford score was 35 and NRS 2. The mean ROM was 113,4 (SD 9,4 range 90-130). Radiographically mean mechanical axis was 1,97° of Varus and radiolucent lines were detected in 43 knees (22,4%). The survival rate is 98.4% at 2 years and 97.4% at 5 years.Conclusion: At short-term follow-up the ATTUNE Knee Replacement System provide excellent clinical and radiographical outcomes and good results regarding revision rate. Due to high incidence of radiolucent lines, those patients should be closely monitored even though they show no clinical evidence for loosening. (www.actabiomedica.it)
An improved molecular tool for screening bacterial colonies using GFP expression enhanced by a Dictyostelium sequence

During molecular cloning, screening of bacterial transformants is a time-consuming and labor-intensive process. However, tractable tools that can be applied to various vectors for visual confirmation of desired colonies are limited. Recently, we reported that TED (translational enhancement by a Dictyostelium gene sequence) boosted protein expression even without an expression inducer in Escherichia coli. Here, we demonstrate a generally applicable molecular tool using the expression of green fluorescent protein (GFP) enhanced by TED. By inserting a module related to TED into the cloning site in advance, we effectively screened E. coli colonies harboring the desired plasmid functions in a prokaryote (Magnetospirillum gryphiswaldense) or eukaryote (Dictyostelium discoideum). Thus, our system represents a user-friendly technique for cloning.
High CD206 levels in Hodgkin lymphoma‐educated macrophages are linked to matrix‐remodeling and lymphoma dissemination

Macrophages (Mφ) are abundantly present in the tumor microenvironment and may predict outcome in solid tumors and defined lymphoma subtypes. Mφ heterogeneity, the mechanisms of their recruitment, and their differentiation into lymphoma‐promoting, alternatively activated M2‐like phenotypes are still not fully understood. Therefore, further functional studies are required to understand biological mechanisms associated with human tumor‐associated Mφ (TAM). Here, we show that the global mRNA expression and protein abundance of human Mφ differentiated in Hodgkin lymphoma (HL)‐conditioned medium (CM) differ from those of Mφ educated by conditioned media from diffuse large B‐cell lymphoma (DLBCL) cells or, classically, by macrophage colony‐stimulating factor (M‐CSF). Conditioned media from HL cells support TAM differentiation through upregulation of surface antigens such as CD40, CD163, CD206, and PD‐L1. In particular, RNA and cell surface protein expression of mannose receptor 1 (MRC1)/CD206 significantly exceed the levels induced by classical M‐CSF stimulation in M2‐like Mφ; this is regulated by interleukin 13 to a large extent. Functionally, high CD206 enhances mannose‐dependent endocytosis and uptake of type I collagen. Together with high matrix metalloprotease9 secretion, HL‐TAMs appear to be active modulators of the tumor matrix. Preclinical in ovo models show that co‐cultures of HL cells with monocytes or Mφ support dissemination of lymphoma cells via lymphatic vessels, while tumor size and vessel destruction are decreased in comparison with lymphoma‐only tumors. Immunohistology of human HL tissues reveals a fraction of cases feature large numbers of CD206‐positive cells, with high MRC1 expression being characteristic of HL‐stage IV. In summary, the lymphoma‐TAM interaction contributes to matrix‐remodeling and lymphoma cell dissemination.
Design choices for observational studies of the effect of exposure on disease incidence

The purpose of this paper is to help readers choose an appropriate observational study design for measuring an association between an exposure and disease incidence. We discuss cohort studies, sub-samples from cohorts (case-cohort and nested case-control designs), and population-based or hospital-based case-control studies. Appropriate study design is the foundation of a scientifically valid observational study. Mistakes in design are often irremediable. Key steps are understanding the scientific aims of the study and what is required to achieve them. Some designs will not yield the information required to realise the aims. The choice of design also depends on the availability of source populations and resources. Choosing an appropriate design requires balancing the pros and cons of various designs in view of study aims and practical constraints. We compare various cohort and case-control designs to estimate the effect of an exposure on disease incidence and mention how certain design features can reduce threats to study validity.
Changes in neurocognitive function and central nervous system structure in childhood acute lymphoblastic leukaemia survivors after treatment: a meta‐analysis

Acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Although the survival rate has increased dramatically over the last decades, patients struggle with the adverse side effects of treatment. Treatment for ALL includes chemotherapy and irradiation ‐ both of which are linked to cognitive impairments and alterations in central nervous system (CNS) structure and function detected by neuroimaging and in neurocognitive studies. The present article is a meta‐analysis of the existing evidence for the mechanisms underlying changes in the CNS and neurocognitive function in ALL survivors after treatment. We found that compared with controls, ALL survivors develop: (i) cognitive sequelae in intelligence, academics, attention, memory, processing speed and executive function domains; (ii) decreased grey and white matter volume in cortical and several subcortical brain regions, with functional changes particularly in frontal regions and the hippocampus; (iii) neurocognitive impairments related to CNS changes; and (iv) reduction, but not resolution, of late neurocognitive sequelae in patients in whom prophylactic irradiation was replaced by systemic/intrathecal chemotherapy. Continued work with advanced functional magnetic resonance imaging techniques will hopefully allow the detection of early CNS changes as biomarkers to help guide early diagnosis and intervention for neurocognitive defects in patients with childhood ALL.