bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-associated macrophages in classical Hodgkin lymphoma: hormetic relationship to outcome
Authors: Werner Laura , Dreyer Johannes H. , Hartmann David , Barros Mário Henrique M. , Büttner-Herold Maike , Grittner Ulrike , Niedobitek Gerald 
Published: June 2020

AbstractCommonly attributed to the prevalence of M2 macrophages, tumor-associated macrophages (TAM) are linked to poor outcome in Hodgkin lymphoma (HL). MYC is supposed to control the expression of M2-specific genes in macrophages, and deficiency in MYC-positive macrophages inhibits tumor growth in mouse models. To verify this hypothesis for HL, seventy-six samples were subjected to immunohistochemical double staining using CD68 or CD163 macrophage-specific antibodies and a reagent detecting MYC. For each cell population, labelled cells were grouped according to low, intermediate and high numbers and related to disease-free survival (DFS) and overall survival (OS). MYC+ cells accounted for 21% and 18% of CD68+ and CD163+ cells, respectively. Numbers of MYC− macrophages were significantly higher in EBV+ cases while no differences were observed for MYC+ macrophages between EBV+ and EBV− cases. Cases with highest numbers of macrophages usually showed worst DFS and OS. In most scenarios, intermediate numbers of macrophages were associated with better outcome than very low or very high numbers. Our observations are reminiscent of the “hormesis hypothesis” and suggest that a relative lack of TAM may allow HL growth while macrophages display an inhibitory effect with increasing numbers. Above a certain threshold, TAM may again support tumor growth.
Low Intensity Vibrations Augment Mesenchymal Stem Cell Proliferation and Differentiation Capacity during in vitro Expansion
Authors: Bas Guniz , Loisate Stacie , Hudon Stephanie F. , Woods Kali , Hayden Eric J. , Pu Xinzhu , Beard Richard , Oxford Julia T. , Uzer Gunes 
Published: June 2020

AbstractA primary component of exercise, mechanical signals, when applied in the form of low intensity vibration (LIV), increases mesenchymal stem cell (MSC) osteogenesis and proliferation. While it is generally accepted that exercise effectively combats the deleterious effects of aging in the musculoskeletal system, how long-term exercise affects stem cell aging, which is typified by reduced proliferative and differentiative capacity, is not well explored. As a first step in understanding the effect of long-term application of mechanical signals on stem cell function, we investigated the effect of LIV during in vitro expansion of MSCs. Primary MSCs were subjected to either a control or to a twice-daily LIV regimen for up to sixty cell passages (P60) under in vitro cell expansion conditions. LIV effects were assessed at both early passage (EP) and late passage (LP). At the end of the experiment, P60 cultures exposed to LIV maintained a 28% increase of cell doubling and a 39% reduction in senescence-associated β-galactosidase activity (p < 0.01) but no changes in telomere lengths and p16INK4a levels were observed. Prolonged culture-associated decreases in osteogenic and adipogenic capacity were partially protected by LIV in both EP and LP groups (p < 0.05). Mass spectroscopy of late passage MSC indicated a synergistic decrease of actin and microtubule cytoskeleton-associated proteins in both control and LIV groups while LIV induced a recovery of proteins associated with oxidative reductase activity. In summary, our findings show that the application of long-term mechanical challenge (+LIV) during in vitro expansion of MSCs for sixty passages significantly alters MSC proliferation, differentiation and structure. This suggests LIV as a potential tool to investigate the role of physical activity during aging.
IHF stabilizes pathogenicity island I of uropathogenic Escherichia coli strain 536 by attenuating integrase I promoter activity
Authors: Chittò Marco , Berger Michael , Berger Petya , Klotz Luisa , Dröge Peter , Dobrindt Ulrich 
Published: June 2020

AbstractPathogenicity islands (PAIs) represent horizontally acquired chromosomal regions and encode their cognate integrase, which mediates chromosomal integration and excision of the island. These site-specific recombination reactions have to be tightly controlled to maintain genomic stability, and their directionality depends on accessory proteins. The integration host factor (IHF) and the factor for inversion stimulation (Fis) are often involved in recombinogenic complex formation and controlling the directionality of the recombination reaction. We investigated the role of the accessory host factors IHF and Fis in controlling the stability of six PAIs in uropathogenic Escherichia coli strain 536. By comparing the loss of individual PAIs in the presence or absence of IHF or Fis, we showed that IHF specifically stabilized PAI I536 and that in particular the IHFB subunit seems to be important for this function. We employed complex genetic studies to address the role of IHF in PAI I536-encoded integrase (IntI) expression. Based on different YFP-reporter constructs and electrophoretic mobility shift assays we demonstrated that IntI acts a strong repressor of its own synthesis, and that IHF binding to the intI promoter region reduces the probability of intI promoter activation. Our results extend the current knowledge of the role of IHF in controlling directionality of site specific recombination reactions and thus PAI stability.
Long-term outcome of posterior fossa medulloblastoma in patients surviving more than 20 years following primary treatment in childhood
Authors: Frič Radek , Due-Tønnessen Bernt Johan , Lundar Tryggve , Egge Arild , Kronen Krossnes Bård , Due-Tønnessen Paulina , Stensvold Einar , Brandal Petter 
Published: June 2020

AbstractThe aim of the study was to analyze the long-term outcome (>20 years) after treatment of posterior fossa medulloblastoma (MB) in childhood. We analyzed data from patients treated for posterior fossa MB between 1974 (introduction of the first international treatment protocol in Norway) and 1987 (when use of radiotherapy was abandoned in children under 4 years of age). Out of 47 children, 24 survived >20 years. At the time of analysis, 16 patients (median age 41 years, range 32–52) were alive (median follow-up 34 years, range 30–42), while 8 patients died 22–41 years (median 31 years) after primary treatment: one late death (after 22 years) was due to tumor recurrence whilst other 7 deaths (after 23 to 41 years) were related to the detrimental effects of the treatment (secondary tumors, stroke, severe epilepsy and depression). Observed 20- and 30-year survival rates were 51% and 44%, respectively. Despite successful treatment of MB in childhood and satisfactory tumor control during the first 20 years following primary treatment, our data indicates that even long-term survivors may die from tumor recurrence. However, the main factors causing late mortality and morbidity in long-term survivors seem to be the complications related to radiotherapy given in childhood.
Transcriptional control of the gonococcal ompA gene by the MisR/MisS two-component regulatory system
Authors: Holley Concerta L. , Ayala Julio C. , Shafer William M. 
Published: June 2020

AbstractNeisseria gonorrhoeae, the causative agent of gonorrhea, is an exclusive human pathogen whose growing antibiotic resistance is causing worldwide concern. The increasing rise of antibiotic resistance expressed by gonococci highlights the need to find alternative approaches to current gonorrhea treatment such as vaccine development or novel therapeutics. The gonococcal OmpA protein was previously identified as a potential vaccine candidate due to its conservation and stable expression amongst strains of Neisseria gonorrhoeae. However, factors that might modulate levels of OmpA and therefore potential vaccine efficacy are unknown. Earlier work indicated that ompA is part of the MisR/MisS regulon and suggested that it was a MisR-activated gene. Herein, we confirmed MisR/MisS regulation of ompA and report that the MisR response regulator can bind upstream of the ompA translational start codon. Further, we describe the contribution of a DNA sequence upstream of the ompA promoter that is critical for MisR activation of ompA transcription. Our results provide a framework for understanding the transcription of gonococcal ompA through a regulatory system known to be important for survival of gonococci during experimental infection.
Imaging characteristics of intravascular spherical contrast agents for grating-based x-ray dark-field imaging – effects of concentrations, spherical sizes and applied voltage
Authors: Notohamiprodjo Susan , Treitl Karla Maria , Hauke Christian , Sutter Sven-Martin , Auweter Sigrid , Pfeiffer Franz , Reiser Maximilian Ferdinand , Hellbach Katharina 
Published: June 2020

AbstractThis study investigates the x-ray scattering characteristics of microsphere particles in x-ray-grating-based interferometric imaging at different concentrations, bubble sizes and tube voltages (kV). Attenuation (ATI), dark-field (DFI) and phase-contrast (PCI) images were acquired. Signal-to-noise (SNR) and contrast-to-noise ratios with water (CNRw) and air as reference (CNRa) were determined. In all modalities, a linear relationship between SNR and microbubbles concentration, respectively, microsphere size was found. A significant gain of SNR was found when varying kV. SNR was significantly higher in DFI and PCI than ATI. The highest gain of SNR was shown at 60 kV for all media in ATI and DFI, at 80 kV for PCI. SNR for all media was significantly higher compared to air and was slightly lower compared to water. A linear relationship was found between CNRa, CNRw, concentration and size. With increasing concentration and decreasing size, CNRa and CNRw increased in DFI, but decreased in PCI. Best CNRa and CNRw was found at specific combination of kV and concentration/size. Highest average CNRa and CNRw was found for microspheres in ATI and PCI, for microbubbles in DFI. Microspheres are a promising contrast-media for grating-based-interferometry, if kV, microsphere size and concentration are appropriately combined.
Male neotenic reproductives accelerate additional differentiation of female reproductives by lowering JH titer in termites
Authors: Oguchi Kohei , Sugime Yasuhiro , Shimoji Hiroyuki , Hayashi Yoshinobu , Miura Toru 
Published: June 2020

AbstractEusocial insects exhibit reproductive division of labor, in which only a fraction of colony members differentiate into reproductives. In termites, reproductives of both sexes are present in a colony and constantly engaged in reproduction. It has been suggested that the sex ratio of reproductives is maintained by social interactions. The presence of reproductives is known to inhibit the additional differentiation of same-sex reproductives, while it promotes the differentiation of opposite-sex reproductives. In this study, using the damp-wood termite Hodotermopsis sjostedti, physiological effects of male/female reproductives on the differentiation of supplementary reproductives (neotenics) were examined. The results showed that the only male-neotenic condition, i.e., the presence of male neotenics in the absence of female neotenics, accelerated the neotenic differentiation from female workers (i.e., pseudergates). Under this condition, the rise of juvenile hormone (JH) titer was repressed in females, and the application of a JH analog inhibited the female neotenic differentiation, indicating that the low JH titer leads to rapid differentiation. Thus, the only male-neotenic condition that actively promotes reproductive differentiation by manipulating physiological condition of females is suggested to be a mechanism underlying sexual asymmetry in reproductive function, which may lead the female-biased sex allocation of reproductives.
A small-molecule inhibitor of lectin-like oxidized LDL receptor-1 acts by stabilizing an inactive receptor tetramer state
Authors: Schnapp Gisela , Neubauer Heike , Büttner Frank H. , Handschuh Sandra , Lingard Iain , Heilker Ralf , Klinder Klaus , Prestle Jürgen , Walter Rainer , Wolff Michael , Zeeb Markus , Debaene Francois , Nar Herbert , Fiegen Dennis 
Published: June 2020

AbstractThe C-type lectin family member lectin-like oxidized LDL receptor-1 (LOX-1) has been object of intensive research. Its modulation may offer a broad spectrum of therapeutic interventions ranging from cardiovascular diseases to cancer. LOX-1 mediates uptake of oxLDL by vascular cells and plays an important role in the initiation of endothelial dysfunction and its progression to atherosclerosis. So far only a few compounds targeting oxLDL-LOX-1 interaction are reported with a limited level of characterization. Here we describe the identification and characterization of BI-0115, a selective small molecule inhibitor of LOX-1 that blocks cellular uptake of oxLDL. Identified by a high throughput screening campaign, biophysical analysis shows that BI-0115 binding triggers receptor inhibition by formation of dimers of the homodimeric ligand binding domain. The structure of LOX-1 bound to BI-0115 shows that inter-ligand interactions at the receptor interfaces are key to the formation of the receptor tetramer thereby blocking oxLDL binding.
Diverse reactivity of isatin-based N,N′-cyclic azomethine imine dipoles with arynes: synthesis of 1′-methyl-2′-oxospiro [indene-1,3′-indolines] and 3-aryl-3-pyrazol-2-oxindoles
Authors: Meerakrishna Ramakrishnan Suseela , Smile Suresh Snoxma , Athira Mohanakumaran , Choutipalli Venkata Surya Kumar , Shanmugam Ponnusamy 
Published: June 2020

Reaction of aryne with isatin based N,N′-cyclic AMI 1,3-dipole afforded 3,3-disubstituted oxindole while methyl substitution on the pyrrolidine ring of 1,3-dipole directed [3+2] cycloaddition products.
KRT8 and KRT19, associated with EMT, are hypomethylated and overexpressed in lung adenocarcinoma and link to unfavorable prognosis
Authors: Wang Wenlong , He Junhong , Lu Hongda , Kong Qingzhi , Lin Shengyou 
Published: June 2020

AbstractBackground: Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer. To date, the prognosis of patients with LUAD remains dismal. Methods: Three datasets were downloaded from the GEO database. Differentially expressed genes (DEGs) were obtained. FunRich was used to perform pathway enrichment analysis. Protein–protein interaction (PPI) networks were established and hub genes were obtained by Cytoscape software. GEPIA was utilized to conduct correlation and survival analysis. Upstream miRNAs of DEGs were predicted via miRNet database, and methylation status of promoters of DEGs was determined through UALCAN database. Results: A total of 375 DEGs, including 105 and 270 up-regulated and down-regulated genes in LUAD, were commonly appeared in three datasets. These DEGs were significantly enriched in mesenchymal-to-epithelial transition (MET) and epithelial-to-mesenchymal transition (EMT). About 8 up-regulated and 5 down-regulated DEGs were commonly appeared in EMT/MET-related gene set and the top 50 hub gene set. Among the 13 genes, increased expression of KRT8 and KRT19 indicated unfavorable prognosis whereas high expression of DCN and CXCL12 suggested favorable prognosis in LUAD. Correlation analysis showed that KRT8 (DCN) expression was linked to KRT19 (CXCL12) expression. Further analysis displayed that KRT8 and KRT19 could jointly forecast poor prognosis in LUAD. About 42 and 2 potential miRNAs were predicted to target KRT8 and KRT19, respectively. Moreover, methylation level analysis demonstrated that KRT8 and KRT19 were significantly hypomethylated in LUAD compared with normal controls. Conclusions: All these findings suggest that KRT8 and KRT19 are hypomethylated and overexpressed in LUAD and associated with unfavorable prognosis.
Occupation of a thermoresistant-scaffold (αRep) at SP1-NC cleavage site disturbs the function of HIV-1 protease
Authors: Hadpech Sudarat , Peerakam Nichakan , Chupradit Koollawat , Tayapiwatana Chatchai 
Published: June 2020

Abstract
HIV-1 nucleocapsid (NC) becomes an attractive target for the development of novel anti-HIV-1 agents. Discovering of non-antibody scaffolds that disrupt the function of NC will be a potential aspect for disturbing viral maturation process. Correspondingly, we explored the specific binding site of the thermoresistant-scaffold protein, αRep9A8 which formerly demonstrated the inhibitory effect on HIV-1 replication. The portion of Gag, CA21-SP1-NC has been used as a template for designing nine overlapping peptides (P4–P12). The P9 peptide showed the strongest binding activity followed by P8 and P12 respectively. The amino acid sequences on those peptides resemble the N-terminal domain of the NC proximity to the SP1-NC initial cleavage site and across the conserved CCHC zinc finger 1 (ZF1) of NC. The interaction KD between αRep9A8 with its target was 224.9 ± 57.4 nM. Consequently, αRep9A8 demonstrated the interference of the HIV-1 protease function by hindering a protease cleavage site. The released NC product from CA21-SP1-NC was diminished. The present study provided an additional information of αRep9A8 function in interfering of viral maturation processes resulting in the decremental efficiency of viral infectivity.
Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis
Authors: Su Xinhuan , Zhao Ying , Li Yang , Ma Shizhan , Wang Zhe 
Published: June 2020

Abstract
Background Previous studies have shown that the gut microbiome is associated with thyroid diseases, including Graves’ disease, Hashimoto's disease, thyroid nodules, and thyroid cancer. However, the association between intestinal flora and primary hypothyroidism remains elusive. We aimed to characterize gut microbiome in primary hypothyroidism patients.
Methods Fifty-two primary hypothyroidism patients and 40 healthy controls were recruited. The differences in gut microbiota between the two groups were analyzed by 16S rRNA sequencing technology. Fecal microbiota transplantation (FMT) was performed in mice using flora from both groups; changes in thyroid function were then assessed in the mice.
Results There were significant differences in α and β diversities of gut microbiota between primary hypothyroidism patients and healthy individuals. The random forest analysis indicated that four intestinal bacteria (Veillonella, Paraprevotella, Neisseria, and Rheinheimera) could distinguish untreated primary hypothyroidism patients from healthy individuals with the highest accuracy; this was confirmed by receiver operator characteristic curve analysis. The short chain fatty acid producing ability of the primary hypothyroidism patients’ gut was significantly decreased, which resulted in the increased serum lipopolysaccharide (LPS) levels. The FMT showed that mice receiving the transplant from primary hypothyroidism patients displayed decreased total thyroxine levels.
Conclusions Our study suggests that primary hypothyroidism causes changes in gut microbiome. In turn, an altered flora can affect thyroid function in mice. These findings could help understand the development of primary hypothyroidism and might be further used to develop potential probiotics to facilitate the adjuvant treatment of this disease.
Impact of coronavirus pandemic crisis in endoscopic clinical practice: Results from a national survey in Brazil
Authors: Arantes Vitor Nunes , Martins Bruno Costa , Seqatto Raphael , Milhomen-Cardoso Daniela Medeiros , Franzini Tomazo Prince , Zuccaro Anna Maria , Alves Jairo Silva , Maluf-Filho Fauze 
Published: June 2020

Abstract
Background and study aims In March 2020, the World Health Organization declared coronavirus disease of 2019 (COVID-19) as a pandemic, mobilizing all countries to contain the disease spread. Activity in endoscopy centers globally was severely affected. We conducted a national survey aiming to assess the impact of the COVID-19 outbreak on endoscopic clinical practice in Brazil.
Methods In April 2020, 3,719 associate members of SOBED (Brazilian Society of Digestive Endoscopy) were invited to respond to an electronic survey. An Internet link was established to provide access to the online questionnaire with 40 questions regarding personal profile, endoscopy unit logistics and schedule, availability and use of personal protective equipment (PPE), financial impact, and exposure to COVID-19.
Results A total of 2,131 individuals (67 %) accessed the questionnaire and 1155 responses were received. After review, 980 responses were considered valid. According to almost 90 % of respondents, endoscopy activity was restricted to urgent procedures, in both public and private hospitals. All respondents increased PPE use after the outbreak, however, institutions provided adequate PPE to only 278 responders (28.7 %). Significant income loss was universally reported. A total of 10 practitioners (1 %) reported COVID-19 infection and attributed the contamination to endoscopic procedures.
Conclusions Based on this nationwide survey with almost 1,000 respondents, the COVID-19 pandemic substantially reduced the activity of endoscopy units in private and public settings. The pandemic increased awareness of PPE use, but its availability was not universal and 1 % of the respondents became infected with COVID-19, allegedly due to exposure during endoscopic procedures.
Riechstörungen bei COVID-19 – aktueller Wissensstand
Authors: Otte Martin Sylvester , Klußmann Jens Peter , Luers Jan Christoffer 
Published: June 2020

ZusammenfassungNachdem anfängliche Berichte über die SARS-CoV-2-Infektion Riech- und Schmeckstörungen kaum erwähnten, haben mittlerweile mehrere Studien, insbesondere aus Europa und den USA, diese Symptome als Merkmal von COVID-19 bestätigt. Gut 2 Drittel der Erkrankten scheinen im Verlauf der Erkrankung eine Riech- und Schmeckminderung zu erleiden, wobei die meisten der bislang veröffentlichten Studien auf Fragebögen und anamnestischen Daten basieren. Validierte Riechtests wurden bislang nur in wenigen Studien eingesetzt. Eine Unterscheidung zwischen Schmeck- und Geschmacksstörungen, also eine Abgrenzung des retronasalen Aromaschmeckens über das olfaktorische System von der Dysfunktion von Geschmackspapillen und der weiterführenden Hirnnerven, erfolgte in den bisher verfügbaren Studien zumeist nicht. Einige Berichte assoziieren die Riechstörungen mit einem milderen klinischen Krankheitsverlauf. Gleichzeitig stellt das Riechsystem über den Bulbus olfactorius eine Eintrittspforte in das zentrale Nervensystem dar, und eine Riechstörung könnte ein prädisponierender Faktor für zentral-neurologische Symptome sein. Die klinische Bedeutung von Riech- und Schmeckstörungen bei COVID-19-Patienten ist aktuell noch unklar. Weitere offene Fragen betreffen die genaue Prävalenz und die Prognose, sodass insgesamt höherwertige Studien mit validierten Riechtests und größeren Patientenzahlen zu fordern sind.