julilili42/papers huggingface dataset:
Thecaphora dahuangis , a new species causing leaf smut disease of the traditional medicinal plant dahuang ( Rheum palmatum ) in China
2021-04-10

Abstract Chinese rhubarb ( Rheum palmatum ) is an important crop that has been used in traditional Chinese medicine for over 2,000 years. The main cultivation areas are the Chinese provinces of Gansu, Qinhai, Tibet, and Sichuan. Various fungal diseases threaten Chinese rhubarb, the most common of which is leaf smut. In literature, the causal agent of this disease is described as Thecaphora schwarzmaniana . We present morphological data and molecular phylogenetic data of two rDNA loci (ITS1‐5.8S‐ITS2 and 28S D1‐D2) that justify the classification of the causal agent as a distinct species. Here we describe the new species Thecaphora dahuangis for the leaf smut pathogen of Chinese rhubarb.
Light-triggered and phosphorylation-dependent 14-3-3 association with NONPHOTOTROPIC HYPOCOTYL 3 is required for hypocotyl phototropism
2021-04-11

ABSTRACT N ON-PHOTOTROPIC HYPOCOTYL 3 (NPH3) is a key component of the phototropic response, acting downstream of the primary photoreceptor phototropin and upstream of auxin redistribution. Despite the obvious physiological significance of the blue light-induced differential growth process, the molecular mode of NPH3 action is poorly understood. Light-triggered dephosphorylation of NPH3, however, is thought to constitute a major signaling event. Here, we show that NPH3 directly binds to polyacidic phospholipids via a polybasic motif in its C-terminal domain, allowing for plasma membrane association in darkness. We further demonstrate that blue light induces phosphorylation of a C-terminal 14-3-3 binding motif in NPH3. Subsequent binding of 14-3-3 to the phosphorylated NPH3 in turn is required for light-triggered release of NPH3 from the plasma membrane. In the cytosol, NPH3 undergoes a dynamic transition from a dilute to a condensed state. Intriguingly, the dephosphorylated state of the 14-3-3 binding site as well as NPH3 plasma membrane association are recoverable in darkness. Given that NPH3 variants constitutively localizing either to the plasma membrane or to cytosolic condensates are non-functional, the phototropin-triggered and 14-3-3 mediated dynamic change in the subcellular localization of NPH3 seems to be crucial for its function. Taken together, our data demonstrate a fundamental role for 14-3-3 members in regulating NPH3 localization and auxin-dependent phototropic responses.
Treatment of Stress Urinary Incontinence with Muscle Stem Cells and Stem Cell Components: Chances, Challenges and Future Prospects
2021-04-12

Urinary incontinence (UI) is a major problem in health care and more than 400 million people worldwide suffer from involuntary loss of urine. With an increase in the aging population, UI is likely to become even more prominent over the next decades and the economic burden is substantial. Among the different subtypes of UI, stress urinary incontinence (SUI) is the most prevalent and focus of this review. The main underlying causes for SUI are pregnancy and childbirth, accidents with direct trauma to the pelvis or medical treatments that affect the pelvic floor, such as surgery or irradiation. Conservative approaches for the treatment of SUI are pelvic physiotherapy, behavioral and lifestyle changes, and the use of pessaries. Current surgical treatment options include slings, colposuspensions, bulking agents and artificial urinary sphincters. These treatments have limitations with effectiveness and bear the risk of long-term side effects. Furthermore, surgical options do not treat the underlying pathophysiological causes of SUI. Thus, there is an urgent need for alternative treatments, which are effective, minimally invasive and have only a limited risk for adverse effects. Regenerative medicine is an emerging field, focusing on the repair, replacement or regeneration of human tissues and organs using precursor cells and their components. This article critically reviews recent advances in the therapeutic strategies for the management of SUI and outlines future possibilities and challenges.
Intracellular persistence of Staphylococcus aureus in endothelial cells is promoted by the absence of phenol-soluble modulins
2021-04-12

A large proportion of clinical <i>S. aureus</i> isolates that carry an inactive Agr system are associated with persistent infection that is difficult to treat. Once <i>S. aureus</i> is inside the bloodstream, it can cross the endothelial barrier and invade almost every organ in the human body. Endothelial cells can either be lysed by this pathogen or they serve as a niche for its intracellular long-term survival. Following phagocytosis, several vesicles such as phagosomes and autophagosomes, target intracellular <i>S. aureus</i> for elimination. <i>S. aureus</i> can escape from these vesicles into the host cytoplasm through the activation of phenol-soluble modulins (PSMs) αβ. Thereafter, it replicates and lyses the host cell to disseminate to adjacent tissues. Herein we demonstrate that staphylococcal strains which lack the expression of PSMs employ an alternative pathway to better persist within endothelial cells. The intracellular survival of <i>S. aureus</i> is associated with the co-localization of the autophagy marker LC3. In cell culture infection models, we found that the absence of <i>psmαβ</i> decreased the host cell lysis and increased staphylococcal long-term survival. This study explains the positive selection of <i>agr</i>-negative strains that lack the expression of <i>psmαβ</i> in chronic infection due to their advantage in surviving and evading the clearance system of the host.
Tetrahydroquinoline/4,5‐Dihydroisoxazole Molecular Hybrids as Inhibitors of Breast Cancer Resistance Protein (BCRP/ABCG2)
2021-04-12

Abstract Multidrug resistance (MDR) is one of the major factors in the failure of many chemotherapy approaches. In cancer cells, MDR is mainly associated with the expression of ABC transporters such as P‐glycoprotein, MRP1 and ABCG2. Despite major efforts to develop new selective and potent inhibitors of ABC drug transporters, no ABCG2‐specific inhibitors for clinical use are yet available. Here, we report the evaluation of sixteen tetrahydroquinoline/4,5‐dihydroisoxazole derivatives as a new class of ABCG2 inhibitors. The affinity of the five best inhibitors was further investigated by the vanadate‐sensitive ATPase assay. Molecular modelling data, proposing a potential binding mode, suggest that they can inhibit the ABCG2 activity by binding on site S1, previously reported as inhibitors binding region, as well targeting site S2, a selective region for substrates, and by specifically interacting with residues Asn436, Gln398, and Leu555. Altogether, this study provided new insights into THQ/4,5‐dihydroisoxazole molecular hybrids, generating great potential for the development of novel most potent ABCG2 inhibitors.
Formalin Fixation as Tissue Preprocessing for Multimodal Optical Spectroscopy Using the Example of Human Brain Tumour Cross Sections
2021-04-12

Characterization of brain tumours requires neuropathological expertise and is generally performed by histological evaluation and molecular analysis. One emerging technique to assist pathologists in future tumour diagnostics is multimodal optical spectroscopy. In the current clinical routine, tissue preprocessing with formalin is widely established and suitable for spectroscopic investigations since degradation processes impede the measurement of native tissue. However, formalin fixation results in alterations of the tissue chemistry and morphology for example by protein cross-linking. As optical spectroscopy is sensitive to these variations, we evaluate the effects of formalin fixation on multimodal brain tumour data in this proof-of-concept study. Nonfixed and formalin-fixed cross sections of different common human brain tumours were subjected to analysis of chemical variations using ultraviolet and Fourier-transform infrared microspectroscopy. Morphological changes were assessed by elastic light scattering microspectroscopy in the visible wavelength range. Data were analysed with multivariate data analysis and compared with histopathology. Tissue type classifications deduced by optical spectroscopy are highly comparable and independent from the preparation and the fixation protocol. However, formalin fixation leads to slightly better classification models due to improved stability of the tissue. As a consequence, spectroscopic methods represent an appropriate additional contrast for chemical and morphological information in neuropathological diagnosis and should be investigated to a greater extent. Furthermore, they can be included in the clinical workflow even after formalin fixation.
Expression patterns of the immune checkpoint ligand CD276 in urothelial carcinoma
2021-04-12

Abstract Background CD276 is an immune checkpoint molecule. Elevated CD276 expression by urothelial carcinoma is associated with poor prognosis, but little is known about its expression across different tumor stages. We therefore investigated CD276 expression in bladder cancer (BC) cells and in tissue samples of BC stages from pT2 to pT4. Methods CD276 expression was explored in 4 urothelial cancer cell lines and 4 primary normal urothelial cell populations by quantitative RT-PCR, Western blot and flow cytometry. CD276 was investigated in bladder tumors from 98 patients by immunohistochemistry using a score (0–300) incorporating both, staining intensity and area of CD276 staining. Normal appearing urothelium in the bladder of the same patients served as controls. Results The urothelial carcinoma cell lines expressed significantly higher levels of CD276 on transcript ( p &lt; 0.006), total protein levels ( p &lt; 0.005), and on the cell surface ( p &lt; 0.02) when compared to normal urothelial cells. In pT2–T4 tumor tissue samples, CD276 was overexpressed (median score 185) when compared to corresponding healthy tissues from the same patients (median score 50; p &lt; 0.001). No significant differences in CD276 expression were recorded in late, locally advanced ≥ pT3a tumors (median score 185) versus organ-confined &lt; pT3a tumors (median score 190), but it was significantly lower in the normal urothelial tissue associated with ≥ pT3a tumors (median score 40) versus &lt; pT3a tumors (median score 80; p &lt; 0.05). Conclusion CD276 expression is significantly elevated in urothelial carcinoma cells in all stages but varies between individuals considerably. Reduced CD276 expression in normal urothelial cells may imply that these cells would be protected from CD276-mediated immuno therapies.
The Long-Term Public Health Impact of a Community-Based Participatory Research Project for Health Promotion Among Socially Disadvantaged Women—A Case Study Protocol
2021-04-12

Introduction: Community-based participatory research (CBPR) is considered to be of high potential for health promotion among socially disadvantaged groups. However, the long-term implementation and transfer of these approaches remain challenging, and the public health impact they achieve is difficult to study. This also pertains to the potential health effects and cost-effectiveness of CBPR. This study protocol describes the follow-up case study (NU-BIG) after 15 years of the BIG project (“movement as investment in health”), a project to promote physical activity among socially disadvantaged women. Through a participatory approach, BIG empowers the addressed women to plan and implement low-threshold physical activity offers. Since the project started in 2005, it was transferred to 17 communities in Germany. Materials and Analysis: NU-BIG intends to examine the long-term effects, including economic aspects, of the BIG project on individual and structural levels at all project sites, as well as its long-term implementation and transfer. NU-BIG is a cross-sectional and longitudinal study using a mixed method approach. For the longitudinal section, we re-analyze existing data from former BIG evaluations. For cross-sectional data collection, we use questionnaires and conduct qualitative interviews and focus groups. Women who take part in BIG program offers are part of the research team and will use the photo-voice approach to report on the effects of BIG. The study population consists of about 800 women who participate in BIG project offers and 50 persons involved in the implementation of the BIG project at local sites. Discussion: The expected results from NU-BIG are highly relevant for studying the long-term public health impact of CBPR. In particular, this project intends to answer questions on how the transfer of such projects can succeed and which factors determine if a CBPR project can be sustained at the community level. Eventually, these results can contribute to the further development of participatory approaches to provide effective health promotion among socially disadvantaged groups. Conclusion: Although CBPR is seen of having the potential to reduce health disparities, there is still a lack of research on its long-term effects and public health impact. NU-BIG aims at generating knowledge about the economic effects, reach, efficacy, adoption, implementation, and maintenance of a CBPR project. The expected results could be of high interest for BIG and other CBPR-projects.
Synthesis of an Addition-Crosslinkable, Silicon-Modified Polyolefin via Reactive Extrusion Monitored by In-Line Raman Spectroscopy
2021-04-12

We present the modification of ethylene-propylene rubber (EPM) with vinyltetra-methydisiloxane (VTMDS) via reactive extrusion to create a new silicone-based material with the potential for high-performance applications in the automotive, industrial and biomedical sectors. The radical-initiated modification is achieved with a peroxide catalyst starting the grafting reaction. The preparation process of the VTMDS-grafted EPM was systematically investigated using process analytical technology (in-line Raman spectroscopy) and the statistical design of experiments (DoE). By applying an orthogonal factorial array based on a face-centered central composite experimental design, the identification, quantification and mathematical modeling of the effects of the process factors on the grafting result were undertaken. Based on response surface models, process windows were defined that yield high grafting degrees and good grafting efficiency in terms of grafting agent utilization. To control the grafting process in terms of grafting degree and grafting efficiency, the chemical changes taking place during the modification procedure in the extruder were observed in real-time using a spectroscopic in-line Raman probe which was directly inserted into the extruder. Successful grafting of the EPM was validated in the final product by 1H-NMR and FTIR spectroscopy.
The TIR-NBS-LRR protein CSA1 is required for autoimmune cell death in Arabidopsis pattern recognition co-receptorbak1andbir3mutants
2021-04-12

Abstract The BRI1-associated kinase BAK1/SERK3 is a positive regulator of multiple leucine rich receptor kinase-mediated signaling pathways including pattern triggered immunity (PTI). Absence or overexpression of BAK1 leads to spontaneous cell death formation. BAK1-interacting receptors (BIR) constitutively interact with BAK1, and plants lacking or overexpressing BIR proteins phenocopy the cell death symptoms observed in bak1 knock outs or overexpressors. In the interactome of BIR3, the TIR-NBS-LRR protein CONSTITUTIVE SHADE-AVOIDANCE 1 (CSA1) was identified by mass spectrometry. CSA1 physically interacts with BIR proteins and can be detected in complexes with BAK1. Direct interaction was shown only for CSA1 with BIR proteins but not BAK1. Double mutant bak1 bir3 genotypes develop strong dwarfism and cell death symptoms that are dependent on EDS1 and salicylic acid. Loss of CSA1 blocks bak1 and bak1 bir3 -mediated cell death formation thus demonstrating that CSA1 is causal for this type of cell death. We propose that CSA1 guards BIR proteins and initiates autoimmune cell death that is observed when BAK1 BIR complexes are impaired. Our findings reveal how cell death in the absence of BAK1 and BIR3 is executed and links BAK1, a common co-receptor of many pattern recognition receptors, to NLR proteins typically implicated in effector-triggered immunity.
Repetitive Transcranial Magnetic Stimulation for Tinnitus Treatment in Vestibular Schwannoma: A Pilot Study
2021-04-12

Background: Vestibular schwannomas (VS) are brain tumors affecting the vestibulocochlear nerve. Thus, VS patients suffer from tinnitus (TN). While the pathophysiology is mainly unclear, there is an increasing interest in repetitive transcranial magnetic stimulation (rTMS) for TN treatment. However, the results have been divergent. In addition to the methodological aspects, the heterogeneity of the patients might affect the outcome. Yet, there is no study evaluating rTMS exclusively in VS-associated tinnitus. Thus, the present pilot study evaluates low-frequency rTMS to the right dorsolateral pre-frontal cortex (DLPFC) in a VS-associated tinnitus. Methods: This prospective pilot study enrolled nine patients with a monoaural VS-associated tinnitus ipsilateral to the tumor. Patients were treated with a 10-day rTMS regime (1 Hz, 100% RMT, 1,200 pulses, right DLPFC). The primary endpoint of the study was the reduction of TN distress (according to the Tinnitus Handicap Inventory, THI). The secondary endpoint was a reduction of TN intensity (according to the Tinnitus Matching Test, TMT) and the evaluation of factors predicting tinnitus outcome (i.e., hearing impairment, TN duration, type of tinnitus). Results: No complications or side effects occurred. There was one drop-out due to a non-responsiveness of the complaint. There was a significant acute effect of rTMS on the THI and TMT. However, there was no significant long-term effect after 4 weeks. While the THI failed to detect any clinically relevant acute effect of rTMS in 56% of the patients, TMT revealed a reduction of TN intensity for more than 20 in 89% and for more than 50 in 56% of the patients. Notably, the acute effect of rTMS was influenced by the TN type and duration. In general, patients with a tonal TN and shorter TN duration showed a better response to the rTMS therapy. Conclusion: The present pilot study is the first one to exclusively evaluate the effect of low-frequency rTMS to the right DLPFC in a VS-associated tinnitus. Our results prove the feasibility and the efficacy of rTMS in this patient cohort. There is a significant acute but a limited long-term effect. In addition, there is evidence that patients with a tonal tinnitus and shorter tinnitus duration might have the strongest benefit. A larger, randomized controlled study is necessary to prove these initial findings.
Perinatal hypoxia and the risk of severe Molar-Incisor Hypomineralisation (MIH): a retrospective analysis of the pH value of umbilical arterial blood after birth
2021-04-12

Abstract Purpose Molar-Incisor Hypomineralisation (MIH) remains a widespread developmental disorder of the teeth with a still largely unknown etiology. Perinatal events were blamed in previous studies for the development of MIH. The aim of the present study was to evaluate the influence of perinatal hypoxia—determined by the pH value of the umbilical cord blood—and to investigate its correlation with severe MIH retrospectively. In addition, cesarean section was recorded as differentiation variable. Methods A total number of 138 children (mean age 8.0 years ± 1.7), who were treated for severe MIH in a dental office in Berlin between the years 2008 and 2019, were included in the study. The control group was comprised of patients with the same date of birth (44 children, mean age 7.7 years ± 1.7). Information on the pH value of the arterial blood from the umbilical cord taken immediately after birth, whose recording is mandatory in Germany, was received from the parents by letter survey requesting the entries from the German Child Health Booklet. Results In the group of the male children born without cesarean section, the pH value of the control group was significantly lower (7.19 ± 0.09) than the pH value of the MIH group (7.27 ± 0.07, p = 0.0008). In female children born with or without cesarean section as well as in male children born by cesarean section there were no significant differences between the MIH and control group. Conclusions No significant association between MIH and the pH value of the umbilical cord blood or birth by cesarean section could be found in the examined patient population.
Ethical, Legal and Social Implications of Symptom Checker Applications in Primary Health Care (CHECK.APP): Study Protocol of an Interdisciplinary Mixed-Methods Study
2021-04-12

<title>Abstract</title> <underline>Background:</underline> Symptom checker applications (SCA) are accessible tools that provide early symptom assessment for users. Ethical, legal, and social implications of SCA, their impact on the patient-physician relationship, the health care providers and the health care system have sparsely been examined. This study protocol describes an approach to investigate possible impacts and implications of SCA on different levels of health care provision. It considers the perspectives of users, non-users, general practitioners and (international) health care experts. We aim to assess a comprehensive overview of the use of SCA and reveal problematic issues.<underline>Methods</underline>: The primary outcomes of this study are empirically informed, multi-perspective recommendations for different stakeholders on ethical, legal, and social implications of SCA. Quantitative and qualitative methods will be used in several consecutive and interconnected parts: Study part 1 comprises a survey that will be analyzed with a logistic regression. It aims to assess the user degree of SCA in Germany as well as predictors for SCA usage. Study part 2 will comprise self-observational diary and user-interviews, which will be analyzed as integrated cases to assess the user perspectives, usage pattern and arising problems. Study part 3 will comprise GP interviews to assess their experiences, perspectives, self-image, and concepts and will be analyzed with the basic procedure by Kruse. Moreover, interviews with health care experts will be conducted in study part 3 and will be analyzed by using the reflexive thematical analysis by Braun and Clark. <underline>Discussion</underline>: Possible ethical, social and legal implications of a widespread use of SCA affect stakeholders and stakeholder groups on different levels of health care. The proposed methodological approach provides a multi-faceted and diverse empirical basis for a broad discussion on these implications.<underline>Trial registration:</underline> The study is registered in the German Clinical Trials Register (DRKS) with the ID: DRKS00022465 since the 7<sup>th</sup> of August 2020.
Editorial
2021-04-12

aDr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart bDepartment of Clinical Pharmacology, University Hospital Tuebingen, Tuebingen, Germany Received 15 February 2021 Accepted 15 February 2021 Correspondence to Matthias Schwab, MD, Dr Margargarete Fischer-Bosch-Institute of Clinical Pharmacology, Auerbacshtr. 112, 70376 Stuttgart, Germany, Tel: +49 711 8101 3700; e-mail: [email protected]