julilili42/papers huggingface dataset:
New insights into the role ofCutibacterium acnes-derived extracellular vesicles in inflammatory skin disorders
2022-12-19

ABSTRACT Background Cutibacterium acnes ( C. acnes ) is one of the most prevalent bacteria that form the human skin microbiota and, depending on multifactorial conditions it can help to maintain the skin homeostasis. Actually, different phylotypes of C. acnes have been associated with different degrees of acne vulgaris development, while others, such as the H1 subtype, have been detected in patients with non-acneic skin. However, due to the physiology of the skin, the skin microbiota neither has direct access to the skin’s sebaceous glands nor to the main immune cells, as they are protected by a sebum layer. Therefore, the inter-kingdom communication relies on secreted factors and bacterial extracellular vesicles (EVs). In this context, the purpose of this project was to study the role of EVs secreted by three different phylotypes of C. acnes (A1 as pathogenic, H1 as beneficial and H2 as commensal). Results Main findings showed that the proteomic profile of the cargo embodied in the EVs reflects unique characteristics of the different C. acnes phylotypes in terms of lifestyle, survival and virulence. Moreover, in vitro skin models showed an extended pro-inflammatory modulation of A1 EVs, while H1 EVs displayed a high sebum-reducing potential. Conclusions This study has highlighted the role of C. acnes EVs as key modulators during skin alterations, specially H1 EVs as an alternative based-natural treatment to fight acne vulgaris symptomatology.
Off-label Use of an External Hand Fixator for Craniomaxillofacial Fractures – an Anatomical Feasibility Study
2022-12-19

Abstract Background The lack of resources limits the treatment of craniomaxillofacial fractures in low-income countries (LIC). Therefore, Barton bandage and/or interdental wiring are considered being gold standard in these regions. The fracture reduction is maintained by permanent occlusion for 6 weeks, which often leads to limited compliance and dissatisfying results. Furthermore, in these conditions the healing of nasopharyngeal fistula is difficult. During humanitarian missions CMF need to be treated by trauma surgeons. The aim of this cadaver-based study is to evaluate the feasibility of the use of an external face fixator (EFF) for the treatment of CMF, its biomechanical values and to define the optimal pin insertion points and angles. Material and methods A commercially available AO hand fixator was used. Craniomaxillofacial fractures type Le Fort 1-3 with split fracture of the hard palate were treated with EFF on 13 anatomical specimens. The fractures were created using a chisel. The pins were placed in specific anatomical regions. The maximal pull-out force [N] of the pins was analysed by a tensile force gauge. As a reference, Fmax of the mandibular pins was evaluated. Computer tomography (CT) scans were performed on the healthy, fractured and EFF-treated skulls. After reduction and EFF placement an adequate reposition was shown in the CT scans. Results The pull-out forces for the single pins were as follows: mandibular pins (n=15, median 488N), supraorbital pins (n=15, median 455.0N), zygomatic pins (n=14, median 269.1N), medial hard palate pins (n=12, median 208.4N) and lateral hard palate pins (n=8, median 49.6N). Conclusions The results of the presented study on the cadaver show, that the operation technique is feasible, and the stability of the EFF is sufficient for maintaining the reduction. In addition, the required pins can be safely inserted into the described areas and a good reduction result can be achieved. The technique of the EFF offers a feasible alternative to the non-surgical treatment of CMF in LIC. Thus, the gap between the open reduction and internal fixation techniques (mini-plates) used in High-income countries and the Barton bandage used in LIC can be closed. Trial registration: A vote of the local ethics committee was obtained (13.01.2022, Ethikkommission Land Salzburg, Austria). EK Nr: 1198/2021 Level of evidence: Level 2
Super-resolution STED imaging in the inner and outer whole-mount mouse retina
2022-12-19

Abstract Since its invention in 1994, super-resolution microscopy has become a popular tool for advanced imaging of biological structures, allowing visualisation of subcellular structures at a spatial scale below the diffraction limit. Thus, it is not surprising that recently, different super-resolution techniques are being applied in neuroscience, e.g. to resolve the clustering of neurotransmitter receptors and protein complex composition in presynaptic terminals. Still, the vast majority of these experiments were carried out either in cell cultures or very thin tissue sections, while there are only a few examples of super-resolution imaging in thick (&gt; ~50 μm) biological samples. In that context, the mammalian whole-mount retina has rarely been studied with super-resolution microscopy. Here, we aimed at establishing a stimulated-emission-depletion (STED) microscopy protocol for imaging whole-mount retina. To this end, we developed sample preparation including horizontal slicing of retinal tissue, an immunolabeling protocol with STED-compatible fluorophores and optimised the STED microscope’s settings. We labelled subcellular structures in somata, dendrites, and axons of retinal ganglion cells in the inner mouse retina. Under optimal conditions, we achieved a mean lateral spatial resolution of ~120 nm (using the full width of half-maximum as a proxy) for the thinnest filamentous structures in our preparation and a resolution enhancement of two or higher compared to conventional confocal images. When combined with horizontal slicing of the retina, these settings allowed us visualisation of putative GABAergic horizontal cell synapses in the outer retina with a similar resolution. Taken together, we successfully established a STED protocol for reliable super-resolution imaging in the whole-mount mouse retina, which enables investigating, for instance, protein complex composition and cytoskeletal ultrastructure at retinal synapses in health and disease.
THE MOLECULAR INTERACTION PATTERN OF LENVATINIB ENABLES INHIBITION OF WILD-TYPE OR KINASE-MUTATED FGFR2-DRIVEN CHOLANGIOCARCINOMA
2022-12-19

&amp;lt;p&amp;gt;Enclosed are the molecular dynamics simulations of drug&amp;ndash;FGFR2 systems and the MM-GBSA raw data. The zip archives include the molecular dynamics trajectory files in Desmond Maestro format (*_trj;&amp;nbsp;*-out.cms), the naming of zip archives is as following: Drug_Studied FGFR2 mutant.&amp;lt;/p&amp;gt;\\n\\n&amp;lt;p&amp;gt;MM-GBSA raw data is attached in the csv format.&amp;lt;/p&amp;gt;\\n\\n&amp;lt;p&amp;gt;&amp;nbsp;&amp;lt;/p&amp;gt;
PrImary decompressive Craniectomy in AneurySmal Subarachnoid hemOrrhage (PICASSO) trial: study protocol for a randomized controlled trial
2022-12-20

Abstract Background Poor-grade aneurysmal subarachnoid hemorrhage (SAH) is associated with poor neurological outcome and high mortality. A major factor influencing morbidity and mortality is brain swelling in the acute phase. Decompressive craniectomy (DC) is currently used as an option in order to reduce intractably elevated intracranial pressure (ICP). However, execution and optimal timing of DC remain unclear. Methods PICASSO resembles a multicentric, prospective, 1:1 randomized standard treatment-controlled trial which analyzes whether primary DC (pDC) performed within 24 h combined with the best medical treatment in patients with poor-grade SAH reduces mortality and severe disability in comparison to best medical treatment alone and secondary craniectomy as ultima ratio therapy for elevated ICP. Consecutive patients presenting with poor-grade SAH, defined as grade 4–5 according to the World Federation of Neurosurgical Societies (WFNS), will be screened for eligibility. Two hundred sixteen patients will be randomized to receive either pDC additional to best medical treatment or best medical treatment alone. The primary outcome is the clinical outcome according to the modified Rankin Scale (mRS) at 12 months, which is dichotomized to favorable (mRS 0–4) and unfavorable (mRS 5–6). Secondary outcomes include morbidity and mortality, time to death, length of intensive care unit (ICU) stay and hospital stay, quality of life, rate of secondary DC due to intractably elevated ICP, effect of size of DC on outcome, use of duraplasty, and complications of DC. Discussion This multicenter trial aims to generate the first confirmatory data in a controlled randomized fashion that pDC improves the outcome in a clinically relevant endpoint in poor-grade SAH patients. Trial registration DRKS DRKS00017650. Registered on 09 June 2019.
Estimating areal effects in typology: a case study of African phoneme inventories
2022-12-20

Abstract In this paper, we combine several statistical techniques (multivariate probit models, Gaussian processes, and phylogenetic regression) into a new approach for exploring the areal patterns associated with the presence and absence of typological features. This model allows us to estimate and control for areal and genetic effects, the correlations between features, and their expected frequency of occurrence in the data. We use this model to explore the distribution of consonants in African languages, inferring several linguistic areas which have been proposed in the literature. Our results suggest that the combination of these methods is a promising new way of approaching language contact.
E. coli Toxin YjjJ (HipH) Is a Ser/Thr Protein Kinase That Impacts Cell Division, Carbon Metabolism, and Ribosome Assembly
2022-12-20

Adaptation to growth condition is the key for bacterial survival, and protein phosphorylation is one of the strategies adopted to transduce extracellular signal in physiological response. In a previous work, we identified YjjJ, a putative kinase, as target of the persistence-related HipA kinase.
The Cyanobacterial “Nutraceutical” Phycocyanobilin Inhibits Cysteine Protease Legumain
2022-12-20

Abstract The blue biliprotein phycocyanin, produced by photo‐autotrophic cyanobacteria including spirulina ( Arthrospira ) and marketed as a natural food supplement or “nutraceutical,” is reported to have anti‐inflammatory, antioxidant, immunomodulatory, and anticancer activity. These diverse biological activities have been specifically attributed to the phycocyanin chromophore, phycocyanobilin (PCB). However, the mechanism of action of PCB and the molecular targets responsible for the beneficial properties of PCB are not well understood. We have developed a procedure to rapidly cleave the PCB pigment from phycocyanin by ethanolysis and then characterized it as an electrophilic natural product that interacts covalently with thiol nucleophiles but lacks any appreciable cytotoxicity or antibacterial activity against common pathogens and gut microbes. We then designed alkyne‐bearing PCB probes for use in chemical proteomics target deconvolution studies. Target identification and validation revealed the cysteine protease legumain (also known as asparaginyl endopeptidase, AEP) to be a target of PCB. Inhibition of this target may account for PCB's diverse reported biological activities.
MR-spectroscopy in metachromatic leukodystrophy: A model free approach and clinical correlation
2022-12-20

The applied model and fitting free interval integration approach to analyse MRS data of a semi-LASER sequence at 3T suits well to detect and quantify pathological changes in MLD patients through the different courses of the disease and correlates well with clinical symptoms while showing smaller dimensions of variation compared to the more sophisticated single metabolite analysis using LCModel. NAA seems the most clinically meaningful biomarker to use in this context. Its correlation with urine measurements further underlines its potential as a clinically and biologically useful parameter of disease progression in MLD.
Linear Stochastic Analysis of the Partial Reversibility of Ensemble and Effective Dispersion in Heterogeneous Porous Media
2022-12-20

Abstract Macrodispersion in heterogeneous formations is caused by spatial variability of the velocity field, making different parts of a plume experience different advective displacements. Differential advection interacts with diffusion, which hardly affects longitudinal ensemble dispersion (i.e., the spread of the ensemble‐averaged concentration) but determines effective dispersion, that is, the expected spread of individual plumes for point injections. The latter has been suggested as metric of solute mixing. Pure advection is fully reversible, whereas diffusion is completely irreversible. We quantify the partial reversibility of macrodispersion by analyzing the second central ensemble and effective spatial moments for advective‐diffusive transport in heterogeneous domains with flow reversal, applying linear stochastic theory to approximate the corresponding moments and comparing them to particle‐tracking random‐walk simulations in periodic media. Diffusion causes solute particles to deviate from their forward trajectories when flow is reversed. As long as advective memory dominates, both types of second central moments decrease during backward motion, then reach a minimum, and increase again. The reversibility is considerably bigger for ensemble than effective dispersion but the latter also shows partial reversibility, challenging its use as metric of mixing. The stronger diffusion is in comparison to advection, the less reversible dispersion becomes. After equally long times of forward and backward motion, the two types of second central moments differ, but to a much smaller extent than in pure forward motion. In realistic settings, the advective memory affects dispersion so strongly that the asymptotic regime is not reached before the plume center has returned to its origin.
TGF-beta Modulates the Integrity of the Blood Brain Barrier in Vitro, and is Associated with Metabolic Alterations in Pericytes
2022-12-20

The blood-brain barrier (BBB) is a selectively permeable boundary that separates the circulating blood from the extracellular fluid of the brain and is an essential component for brain homeostasis. In glioblastoma (GBM), the BBB of peritumoral vessels is often disrupted. Pericytes, being important to maintain the BBB integrity, can be functionally modified by GBM cells by inducing proliferation and cell motility via the TGF-&amp;beta;-mediated induction of central epithelial to mesenchymal transition (EMT) factors., We demonstrate that pericytes strengthen the integrity of the BBB in primary endothelial cell/pericyte co-cultures as in vitro BBB model, using TEER measurement of the barrier integrity. In contrast, this effect was abrogated by TGF-&amp;beta; or conditioned medium from TGF-&amp;beta; secreting GBM cells, finally leading to the disruption of a so far intact and tight BBB. TGF-&amp;beta; dramatically changed the metabolic behavior of pericytes, such as shutting down the TCA cycle, driving energy generation from oxidative phosphorylation towards glycolysis, and by shifting the cells towards the activation of pathways that are necessary to produce molecules used for proliferation and cell division. Furthermore, combined metabolomics and RNASeq analyses indicated that the observed functional changes of TGF-&amp;beta;-treated pericytes are closely connected with their behavior.
Body-dissatisfaction directs avatar perception: Embodiment and selective visual attention in body-mass modified self-avatars
2022-12-20

Human agents immersed in metaverse technologies such as virtual reality (VR) are routinely disconnected from their actual physical appearance and embodied in another virtual body, referred to as self-avatar. Such body transformations can have implications for patients with eating disorders, or persons with extreme body dissatisfaction (BD). Changes in BD, weight anxiety, or body image are theoretically linked to visual selective attention, which can be measured with eye-tracking. In the present study, 43 women with high or low BD were immersed in animated body-weight manipulated self-avatars in VR. Prior to a brief mirror exposure with their self-avatars, they experienced synchronous visuo-motor and visuo-tactile contingencies in VR to increase embodiment, delivered through small movement exercises with real-time animation from first-person-perspective and passive haptics. In a cross-over study design, self-avatar weight was manipulated (normal weight vs. overweight) in both groups (low BD vs. high BD) and subjective experience was assessed before and after exposure. In contrast to our hypotheses, BD was not affected by the self-avatar condition. Embodiment decreased during mirror exposure, possibly due to the avatars wearing head-mounted displays. Interestingly, disembodiment was stronger in women with low BD. Further, eye-tracking showed that participants with high BD looked longer at weight-related body-parts when immersed in the overweight self-avatar, whereas participants with low BD looked longer at weight-related body-parts when immersed in the normal-weight self-avatar. Overall, results support body-specific visual attention and suggest that particularly participants with low BD show stronger disembodiment during self-avatar mirror exposure, possibly alleviating momentary body experience.
Generalization and Personalization of Mobile Sensing-Based Mood Inference Models
2022-12-21

Mood inference with mobile sensing data has been studied in ubicomp literature over the last decade. This inference enables context-aware and personalized user experiences in general mobile apps and valuable feedback and interventions in mobile health apps. However, even though model generalization issues have been highlighted in many studies, the focus has always been on improving the accuracies of models using different sensing modalities and machine learning techniques, with datasets collected in homogeneous populations. In contrast, less attention has been given to studying the performance of mood inference models to assess whether models generalize to new countries. In this study, we collected a mobile sensing dataset with 329K self-reports from 678 participants in eight countries (China, Denmark, India, Italy, Mexico, Mongolia, Paraguay, UK) to assess the effect of geographical diversity on mood inference models. We define and evaluate country-specific (trained and tested within a country), continent-specific (trained and tested within a continent), country-agnostic (tested on a country not seen on training data), and multi-country (trained and tested with multiple countries) approaches trained on sensor data for two mood inference tasks with population-level (non-personalized) and hybrid (partially personalized) models. We show that partially personalized country-specific models perform the best yielding area under the receiver operating characteristic curve (AUROC) scores of the range 0.78--0.98 for two-class (negative vs. positive valence) and 0.76--0.94 for three-class (negative vs. neutral vs. positive valence) inference. Further, with the country-agnostic approach, we show that models do not perform well compared to country-specific settings, even when models are partially personalized. We also show that continent-specific models outperform multi-country models in the case of Europe. Overall, we uncover generalization issues of mood inference models to new countries and how the geographical similarity of countries might impact mood inference.
Environmental changes affect the microbial release of hydrogen sulfide and methane from sediments at Boknis Eck (SW Baltic Sea)
2022-12-21

Anthropogenic activities are modifying the oceanic environment rapidly and are causing ocean warming and deoxygenation, affecting biodiversity, productivity, and biogeochemical cycling. In coastal sediments, anaerobic organic matter degradation essentially fuels the production of hydrogen sulfide and methane. The release of these compounds from sediments is detrimental for the (local) environment and entails socio-economic consequences. Therefore, it is vital to understand which microbes catalyze the re-oxidation of these compounds under environmental dynamics, thereby mitigating their release to the water column. Here we use the seasonally dynamic Boknis Eck study site (SW Baltic Sea), where bottom waters annually fall hypoxic or anoxic after the summer months, to extrapolate how the microbial community and its activity reflects rising temperatures and deoxygenation. During October 2018, hallmarked by warmer bottom water and following a hypoxic event, modeled sulfide and methane production and consumption rates are higher than in March at lower temperatures and under fully oxic bottom water conditions. The microbial populations catalyzing sulfide and methane metabolisms are found in shallower sediment zones in October 2018 than in March 2019. DNA-and RNA profiling of sediments indicate a shift from primarily organotrophic to (autotrophic) sulfide oxidizing Bacteria, respectively. Previous studies using data collected over decades demonstrate rising temperatures, decreasing eutrophication, lower primary production and thus less fresh organic matter transported to the Boknis Eck sediments. Elevated temperatures are known to stimulate methanogenesis, anaerobic oxidation of methane, sulfate reduction and essentially microbial sulfide consumption, likely explaining the shift to a phylogenetically more diverse sulfide oxidizing community based on RNA.
Postoperative complications and oncologic outcomes after multimodal therapy of localized high risk soft tissue sarcoma
2022-12-21

Abstract Background Standard therapy for localized high-risk soft tissue sarcoma includes surgical resection and neoadjuvant or adjuvant radiation therapy (± chemotherapy and locoregional hyperthermia). No difference in oncologic outcomes for patients treated with neoadjuvant and adjuvant radiation therapy was reported, whereas side effect profiles differ. The aim of this analysis was to analyse oncologic outcomes and postoperative complications in patients treated with multimodal treatment. Methods Oncologic outcomes and major wound complications (MWC, subclassified as wound healing disorder, infection, abscess, fistula, seroma and hematoma) were evaluated in 74 patients with localized high-risk soft tissue sarcoma of extremities and trunk undergoing multimodal treatment, and also separately for the subgroup of lower extremity tumors. Clinical factors and treatment modalities (especially neoadjuvant vs. adjuvant radiotherapy) were evaluated regarding their prognostic value and impact on postoperative wound complications. Results Oncologic outcomes were dependent on number of high risk features (tumor size, depth to superficial fascia and grading), but not on therapy sequencing (however with higher risk patients in the neoadjuvant group). Different risk factors influenced different subclasses of wound healing complications. Slightly higher MWC-rates were observed in patients treated with neoadjuvant therapy, compared to adjuvant radiotherapy, although only with a trend to statistical significance (31.8% vs. 13.3%, p = 0.059). However, except for wound infections, no significant difference for other subclasses of postoperative complications was observed between neoadjuvant and adjuvant therapy. Diabetes was confirmed as a major risk factor for immune-related wound complications. Conclusion Rates of major wound complications in this cohort are comparable to published data, higher rates of wound infections were observed after neoadjuvant radiotherapy. Tumor localization, patient age and diabetes seem to be major risk factors. The number of risk factors for high risk soft tissue sarcoma seem to influence DMFS. Neoadjuvant treatment increases the risk only for wound infection treated with oral or intravenous antibiotic therapy and appears to be a safe option at an experienced tertiary center in absence of other risk factors.