julilili42/papers huggingface dataset:
What is the ‘normal life expectancy’ with ascending aorta disease?
2022-04-16

In their study, Skoglund Larsson et al. [1] addressed the long-term prognosis of patients after ascending aorta replacement and concluded that ‘patients undergoing surgery do not regain normal life expectancy’. This topic has not yet been extensively studied, and there are few 10-year data. This makes the study valuable despite its limited number of cases and its monocentric nature. Ascending aortic aneurysm is a remarkable condition: it is usually asymptomatic and, ironically, one can grow old and die in a subjectively healthy state. However, the potential complications, rupture and type A dissection (TAD) are problematic; the mortality is high, and despite emergency surgery, there is a high risk of subsequent morbidity and suffering. Most publications on the topic include heterogeneous pathologies (connective tissue disorders, dissections, etc.), procedures (root, arch, etc.) and proportions of emergency cases, which makes interpretation difficult; and this is equally true for the work of Skoglund Larsson. Table 1 shows an incomplete and arbitrary selection of literature with relatively homogeneous cohorts. Essentially, all authors achieve comparable short- and long-term postoperative results, but if surgery is performed in patients with acute TAD, then the early- and long-term results are poor. In patients with aneurysm and dissection, the prognosis differs considerably depending on pathoanatomy, accompanying diseases and necessary intervention, which complicates standardization in studies. In this context, we eagerly await the long-term data from multicentric registries, such as the German Registry for Acute Aortic Dissection Type A.
Shock Absorption Behavior of Elastic Polymers for Sports Mouthguards: An In Vitro Comparison of Thermoplastic Forming and Additive Manufacturing
2022-04-17

Background. There are several in vitro testing options to investigate the efficacy of sports mouthguards. None of these represent everyday situations, but the effects of simple laws of physics can be observed. This enables the comparison of conventional materials for mouthguards towards fabrications from additive manufacturing. Methods. A ball-drop experiment measured the maximum force and temporospatial distribution of a vertical impact on six material groups and a reference group (No-MG). Three conventional materials (ethylenvinylacetate) with 1, 2, and 3 layers were compared with additively manufactured (AM) specimens of comparable layering with a respective thickness of 4 mm, 5 mm, and 6.8 mm. Results. A maximum force of 8982.35 N ± 305.18 (No-MG) was maximum damped to 2470.60 N ± 87.00 (conventional 6.8 mm) compared with 5585.09 N ± 203.99 (AM 6.8 mm) Thereby, the ratio between shock absorption per millimeter was best for 4 mm thickness with means of 1722 N (conventional) and 624 N (AM). Conclusions. Polymer layers demonstrated a force reduction up to 71.68%. For now, additively processed resins of comparable hardness and layering are inferior to conventional fabrications.
Cysteine-Rich LIM-Only Protein 4 (CRP4) Promotes Atherogenesis in the ApoE−/− Mouse Model
2022-04-17

Vascular smooth muscle cells (VSMCs) can switch from their contractile state to a synthetic phenotype resulting in high migratory and proliferative capacity and driving atherosclerotic lesion formation. The cysteine-rich LIM-only protein 4 (CRP4) reportedly modulates VSM-like transcriptional signatures, which are perturbed in VSMCs undergoing phenotypic switching. Thus, we hypothesized that CRP4 contributes to adverse VSMC behaviours and thereby to atherogenesis in vivo. The atherogenic properties of CRP4 were investigated in plaque-prone apolipoprotein E (ApoE) and CRP4 double-knockout (dKO) as well as ApoE-deficient CRP4 wildtype mice. dKO mice exhibited lower plaque numbers and lesion areas as well as a reduced content of α-smooth muscle actin positive cells in the lesion area, while lesion-associated cell proliferation was elevated in vessels lacking CRP4. Reduced plaque volumes in dKO correlated with significantly less intra-plaque oxidized low-density lipoprotein (oxLDL), presumably due to upregulation of the antioxidant factor peroxiredoxin-4 (PRDX4). This study identifies CRP4 as a novel pro-atherogenic factor that facilitates plaque oxLDL deposition and identifies the invasion of atherosclerotic lesions by VSMCs as important determinants of plaque vulnerability. Thus, targeting of VSMC CRP4 should be considered in plaque-stabilizing pharmacological strategies.
Autophagy profiling in single cells with open source CellProfiler-based image analysis
2022-04-18

Single cell-based analysis of macroautophagy/autophagy is largely achieved through the use of fluorescence microscopy to detect autophagy-related proteins that associate with autophagic membranes and therefore can be quantified as fluorescent puncta. In this context, an automated analysis of the number and size of recognized puncta is preferable to a manual count, because more reliable results can be generated in a short time. Here we present a method for open source CellProfiler software-based analysis for quantitative autophagy assessments using GFP-tagged WIPI1 (WD repeat domain, phosphoinositide interacting 1) images acquired with Airyscan or confocal laser-scanning microscopy. The CellProfiler protocol is provided as a ready-to-use software pipeline, and the creation of this pipeline is detailed in both text and video formats. In addition, we provide CellProfiler pipelines for endogenous SQSTM1/p62 (sequestosome 1) or intracellular lipid droplet (LD) analysis, suitable to assess forms of selective autophagy. All protocols and software pipelines can be quickly and easily adapted for the use of alternative autophagy markers or cell types, and can also be used for high-throughput purposes.<b>Abbreviations:</b> AF Alexa Fluor ATG autophagy related BafA1 bafilomycin A1 BSA bovine serum albumin DAPI 4,6-diamidino-2-phenylindole DMEM Dulbecco's modified Eagle's medium DMSO dimethyl sulfoxide EDTA ethylenediaminetetraacetic acid EBSS Earle's balanced salt solution FBS fetal bovine serum GFP green fluorescent protein LD lipid droplet LSM laser scanning microscope MAP1LC3B microtubule associated protein 1 light chain 3 beta MTOR mechanistic target of rapamycin kinase PBS phosphate-buffered saline PIK3C3/VPS34 phosphatidylinositol 3-kinase catalytic subunit type 3 SQSTM1 sequestosome 1 TIFF tagged image file format U2OS U-2 OS cell line WIPI WD repeat domain, phosphoinositide interacting.
Occurrence of a novel cleavage site for cathepsin G adjacent to the polybasic sequence within the proteolytically sensitive activation loop of the SARS-CoV-2 Omicron variant: The amino acid substitution N679K and P681H of the spike protein
2022-04-18

The serine proteases neutrophil elastase (NE), proteinase 3 (PR3), cathepsin G (CatG), and neutrophil serine protease 4 (NSP4) are secreted by activated neutrophils as a part of the innate immune response against invading pathogens. However, these serine proteases might be adopted by viruses to mediate viral surface protein priming resulting in host cell entrance and productive infection. Indeed, NE and PR3 hydrolyze the scissile peptide bond within the proteolytically sensitive polybasic sequence of the activation loop of SARS-CoV-2 located at the S1/S2 interface of the Spike (S) protein; an amino acid motif which differs from SARS-CoV-1. The occurrence of novel SARS-CoV-2 variants and substitution of distinct amino acids at the polybasic sequence prompts serious concerns regarding increased transmissibility. We propose that a novel cleavage site by CatG of the Omicron variant and the increased substrate turnover of the Delta variant by furin within the polybasic sequence should be considered for increased transmission of SARS-CoV-2 variants.
Global Transcriptomic Analysis of Bacteriophage-Host Interactions between a Kayvirus Therapeutic Phage and Staphylococcus aureus
2022-04-18

Bacterium Staphylococcus aureus is a common human and veterinary pathogen that causes mild to life-threatening infections. As strains of S. aureus are becoming increasingly resistant to multiple antibiotics, the need to search for new therapeutics is urgent.
Cell Type-Specific Anti-Adhesion Properties of Peritoneal Cell Treatment with Plasma-Activated Media (PAM)
2022-04-18

Postoperative abdominal adhesions are responsible for serious clinical disorders. Administration of plasma-activated media (PAM) to cell type-specific modulated proliferation and protein biosynthesis is a promising therapeutic strategy to prevent pathological cell responses in the context of wound healing disorders. We analyzed PAM as a therapeutic option based on cell type-specific anti-adhesive responses. Primary human peritoneal fibroblasts and mesothelial cells were isolated, characterized and exposed to different PAM dosages. Cell type-specific PAM effects on different cell components were identified by contact- and marker-independent Raman imaging, followed by thorough validation by specific molecular biological methods. The investigation revealed cell type-specific molecular responses after PAM treatment, including significant cell growth retardation in peritoneal fibroblasts due to transient DNA damage, cell cycle arrest and apoptosis. We identified a therapeutic dose window wherein specifically pro-adhesive peritoneal fibroblasts were targeted, whereas peritoneal mesothelial cells retained their anti-adhesive potential of epithelial wound closure. Finally, we demonstrate that PAM treatment of peritoneal fibroblasts reduced the expression and secretion of pro-adhesive cytokines and extracellular matrix proteins. Altogether, we provide insights into biochemical PAM mechanisms which lead to cell type-specific pro-therapeutic cell responses. This may open the door for the prevention of pro-adhesive clinical disorders.
Proof of Concept for Operando Infrared Spectroscopy Investigation of Light-Excited Metal Oxide-Based Gas Sensors
2022-04-18

Light-excitation of semiconducting metal-oxide (SMOX)-based gas sensors is a promising means to lower their operation temperature, thereby reducing power consumption, which would allow for their broader application. Despite increased research interest in light-excited gas sensors, progress has been slow because of a lack of mechanistic understanding. Notably, significant differences between light-excitation and, the better understood, thermal-excitation mechanisms have been identified. Insights from operando spectroscopic studies have been key to understanding the surface chemistry that determines the performance of thermally activated SMOX, but they have not yet been performed on illuminated sensors. Here, for the first time, we demonstrate that it is possible to perform operando diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy measurements on sensors under illumination. We demonstrate the benefits of the approach and show that under light illumination the splitting of water on the WO<sub>3</sub> surface is responsible for the increased resistance of the sensor during exposure to high humidity.
Interaction of Bartonella henselae with Fibronectin Represents the Molecular Basis for Adhesion to Host Cells
2022-04-18

Deciphering the mechanisms of bacterial host cell adhesion is a clue for preventing infections. We describe the underestimated role that the extracellular matrix protein fibronectin plays in the adhesion of human-pathogenic Bartonella henselae to host cells.
To Trust or Not to Trust? COVID-19 Facemasks in China–Europe Relations: Lessons from France and the United Kingdom
2022-04-18

At the crossroads of sociology and international relations, this interdisciplinary and comparative research article explores how the COVID-19 outbreak has impacted China–Europe relations. Unfolding the critical moments of the COVID-19 outbreak, this article characterizes the evolution of China–Europe relations with regard to the facemask. This simple object of self-protection against the coronavirus strikingly became a source of contention between peoples and states. In the face of this situation, we argue that the facemask is the prism through which to illustrate (1) the transnational links between China and its overseas population, (2) the changing social perceptions of China and Chinese-looking people in European societies, and (3) the advent of China’s health diplomacy and its reception in Europe. Comparing two European settings—France and the United Kingdom (UK)—the common denominator appears to be the reduced trust, if not outright distrust, between individuals and communities in the French and British contexts, and in Sino–French and Sino–British relations at the transnational level. Combining critical juncture theory and (dis)trust in international relations as our analytical framework, this article examines how the facemask became a politicized object, both between states and between Mainland China and its overseas population, as the epidemic unfolded throughout Europe. Adopting a qualitative approach, our dataset comprises the analysis of official speeches and statements; press releases; traditional and social media content (especially through hashtags such as #JeNeSuisPasUnVirus, #IAmNotAVirus, #CoronaRacism, etc.); and interviews with Chinese, French, and British community members.
Reduction of impulsivity after an impulsivity-focused group intervention in patients with binge eating disorder in a long-term follow-up of the randomized controlled IMPULS trial
2022-04-18

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Comprehensive validation of fasting- and oral glucose tolerance test-based indices of insulin secretion against gold-standard measures
2022-04-18

Abstract Background and aims With prediabetes and diabetes increasingly recognized as heterogenous conditions, assessment of beta-cell function is gaining clinical importance to identify disease subphenotypes. Our study aims to comprehensively validate all types of surrogate indices based on OGTT- and fasting-measurements in comparison with gold standard methods. Materials and methods The hyperglycaemic clamp extended with GLP-1 infusion and IVGTT, as well as OGTT, was performed in two well-phenotyped cohorts. The gold-standard-derived indices were compared with surrogate insulin secretion markers, derived from fasting state and OGTT, using both Pearson’s and Spearman’s correlation coefficients. The insulin- and C-peptide-based indices were analysed separately in different groups of glucose tolerance and the entire cohorts. Results The highest correlation coefficients were found for AUC (I 0-30 )/AUC (G 0-30 ), first-phase Stumvoll and Kadowaki model. These indices have high correlation coefficients with measures obtained from both insulin and C-peptide levels from IVGTT and hyperglycaemic clamp. AUC (I 0-30 )/AUC (G 0-30 ), first-phase Stumvoll, AUC (I 0-120 )/AUC (G 0-120 ) and BIGTT-AIR 0-60-120 demonstrated the strongest association with incretin-stimulated insulin response. Conclusion We have identified glucose- and GLP-1-stimulated insulin secretion indices, derived from OGTT and fasting state, that have the strongest correlation with gold-standard measures and could be potentially used in future researches and clinical practice.
α-Gal present on both glycolipids and glycoproteins contributes to immune response in meat-allergic patients
2022-04-19

Both α-Gal-carrying glycoproteins and glycolipids are able to strongly activate patient basophils. In PK and beef, α-Gal epitopes seem to be less abundant on glycolipids than on glycoproteins, suggesting a major role of glycoproteins in delayed anaphylaxis upon consumption of these food sources.
Signature of Alzheimer’s Disease in Intestinal Microbiome: Results From the AlzBiom Study
2022-04-19

Background Changes in intestinal microbiome composition have been described in animal models of Alzheimer’s disease (AD) and AD patients. Here we investigated how well taxonomic and functional intestinal microbiome data and their combination with clinical data can be used to discriminate between amyloid-positive AD patients and cognitively healthy elderly controls. Methods In the present study we investigated intestinal microbiome in 75 amyloid-positive AD patients and 100 cognitively healthy controls participating in the AlzBiom study. We randomly split the data into a training and a validation set. Intestinal microbiome was measured using shotgun metagenomics. Receiver operating characteristic (ROC) curve analysis was performed to examine the discriminatory ability of intestinal microbiome among diagnostic groups. Results The best model for discrimination of amyloid-positive AD patients from healthy controls with taxonomic data was obtained analyzing 18 genera features, and yielded an area under the receiver operating characteristic curve (AUROC) of 0.76 in the training set and 0.61 in the validation set. The best models with functional data were obtained analyzing 17 GO (Gene Ontology) features with an AUROC of 0.81 in the training set and 0.75 in the validation set and 26 KO [Kyoto Encyclopedia of Genes and Genomes (KEGG) ortholog] features with an AUROC of 0.83 and 0.77, respectively. Using ensemble learning for these three models including a clinical model with the 4 parameters age, gender, BMI and ApoE yielded an AUROC of 0.92 in the training set and 0.80 in the validation set. Discussion In conclusion, we identified a specific Alzheimer signature in intestinal microbiome that can be used to discriminate amyloid-positive AD patients from healthy controls. The diagnostic accuracy increases from taxonomic to functional data and is even better when combining taxonomic, functional and clinical models. Intestinal microbiome represents an innovative diagnostic supplement and a promising area for developing novel interventions against AD.
Long‐term results from the multicentric European randomized phase 3 trial CWS/RMS‐96 for localized high‐risk soft tissue sarcoma in children, adolescents, and young adults
2022-04-19

Abstract Background : CWS/RMS‐96 was an international multicenter trial with randomization between two therapy arms of the standard four‐drug therapy (vincristine, ifosfamide, adriamycin, dactinomycin [VAIA]) versus an intensified six‐drug regimen (carboplatin, epirubicin, vincristine, dactinomycin, ifosfamide, and etoposide [CEVAIE]) for high‐risk rhabdomyosarcoma (RMS), extraskeletal Ewing sarcoma (EES), and undifferentiated sarcoma (UDS) in children, adolescents, and young adults aiming to improve their survival. Intensified chemotherapy with CEVAIE did not improve outcome. Methods : Patients younger than 21 years with a previously untreated localized HR‐RMS, EES, and UDS were enrolled from Cooperative Weichteilsarkom Studiengruppe (CWS) centers in Germany, Austria, Poland, Switzerland, and from Italian Soft Tissue Sarcoma Committee (STSC) centers. Randomization (1:1) to receive either 9 × 21 days cycles of VAIA or CEVAIE was performed separately in CWS and STSC. Hyperfractionated accelerated radiotherapy (32–44.8 Gy) was added at week 9–12 according to histology and response to chemotherapy. A secondary microscopically complete nonmutilating resection was performed if possible. Primary endpoints were response to chemotherapy, event‐free (EFS) and overall survival (OS). Results : Five hundred fifty‐seven patients (HR‐RMS: n = 416, EES and UDS: n = 141) underwent randomization: VAIA ( n = 273) or CEVAIE ( n = 284). Radiotherapy was given to 70% of patients in both groups. A secondary resection was performed in 47% and 48% patients, respectively. The 5‐year EFS and OS for the VAIA and CEVAIE treatment arms were 59.8% and 60.8% ( p = .89), and 74.2% and 68.3% ( p = .16), respectively. No differences in response, toxicity, or second malignancies emerged in the two groups. Conclusion : The use of an intensified regimen failed to show a significant improvement in tumor response and outcome of patients with localized HR‐RMS, EES, and UDS.
Nx4 Modulated Resting-State Functional Connectivity Between Amygdala and Prefrontal Cortex in a Placebo-Controlled, Crossover Trial
2022-04-19

<b><i>Background:</i></b> The basic functional organization of the resting brain, assessed as resting-state functional connectivity (rsFC), can be affected by previous stress experience and it represents the basis on which subsequent stress experience develops. Notably, the rsFC between the amygdala and the cortical regions associated with emotion regulation and anxiety are affected during stress. The multicomponent drug Neurexan<sup>®</sup> (Nx4) has previously demonstrated a reduction in amygdala activation in an emotional face matching task and it ameliorated stress-related symptoms. We, thus, investigated the effect of Nx4 on rsFC of the amygdala before stress induction compared with baseline in mildly to moderately stressed participants. <b><i>Methods:</i></b> In a randomized, placebo-controlled, double-blind, crossover trial 39 participants received a single dose of placebo or Nx4. Resting-state functional magnetic resonance imaging scans were performed pre-dose and 40 to 60 min post-dose, before any stress induction. First, highly connected functional hubs were identified by global functional connectivity density (gFCD) analysis. Second, by using a seed-based approach, rsFC maps of the left centromedial amygdala (CeMA) were created. The effect of Nx4 on both was evaluated. <b><i>Results:</i></b> The medial prefrontal cortex was identified as a relevant functional hub affected by Nx4 in an explorative whole brain gFCD analysis. Using the seed-based approach, we then demonstrated that Nx4 significantly enhanced the negative connectivity between the left CeMA and two cortical regions: the dorsolateral and medial prefrontal cortices. <b><i>Conclusions:</i></b> In a resting-state condition, Nx4 reduced the prefrontal cortex gFCD and strengthened the functional coupling between the amygdala and the prefrontal cortex that is relevant for emotion regulation and the stress response. Further studies should elaborate whether this mechanism represents enhanced regulatory control of the amygdala at rest and, consequently, to a diminished susceptibility to stress. ClinicalTrials.gov ID: NCT02602275.
Ictal Electroencephalographic Characteristics of Nodding Syndrome: A Comparative Case‐Series from South Sudan, Tanzania, and Uganda
2022-04-19

Nodding syndrome (NS) is a poorly understood form of childhood‐onset epilepsy that is characterized by the pathognomonic ictal phenomenon of repetitive vertical head drops. To evaluate the underlying ictal neurophysiology, ictal EEG features were evaluated in nine participants with confirmed NS from South Sudan, Tanzania, and Uganda and ictal presence of high frequency gamma oscillations on scalp EEG were assessed. Ictal EEG during the head nodding episode predominantly showed generalized slow waves or sharp‐and‐slow wave complexes followed by electrodecrement. Augmentation of gamma activity (30–70 Hz) was seen during the head nodding episode in all the participants. We confirm that head nodding episodes in persons with NS from the three geographically distinct regions in sub‐Saharan Africa share the common features of slow waves with electrodecrement and superimposed gamma activity. ANN NEUROL 2022;92:75–80