bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triggering G‐Quadruplex Conformation Switching with [7]Helicenes
Authors: Lousen Bodil , Pedersen Stephan K. , Răsădean Dora M. , Pantoş G. Dan , Pittelkow Michael 
Published: December 2020

AbstractThe dynamic interplay between two types of chiral structures; fully conjugated racemic hetero[7]helicenes and DNA strands prone to fold into G‐quadruplex structures is described. Both the [7]helicenes and the G‐quadruplex DNA structures exist in more than one conformation in solution. We show that the structures interact with and stabilise each other, mutually amplifying and stabilising certain conformations at increased temperatures. The [7]helicene ligands L1 and L2 stabilise the parallel conformation of k‐ras significantly, whereas hybrid (K+) and antiparallel (Na+) h‐telo G‐quadruplexes are stabilised upon conformational switching into altered G‐quadruplex conformations. Both L1 and L2 induce parallel G‐quadruplexes from hybrid structures (K+) and L1 induces hybrid G‐quadruplexes from antiparallel conformations (Na+). Enantioselective binding of one helicene enantiomer is observed for helicene ligand L2, and VTCD melting experiments are used to estimate the racemisation barrier of the helicene.
Heparan sulfate fine‐tunes stromal‐epithelial communication in the prostate gland
Authors: Barbosa Guilherme O. , Biancardi Manoel F. , Carvalho Hernandes F. 
Published: December 2020

AbstractSeveral studies reported the concerted and mutual communication between the prostate epithelium and stroma, which determines the final organ architecture and function, but gets awry in cancer. Deciphering the mechanisms involved in this communication is crucial to find new therapeutic strategies. HS sequesters a number of secreted growth factors and cytokines, controlling their bioavailability to the target cells, suggesting that HS is an important regulator of the extracellular matrix (ECM) and a key player in the cell‐cell and cell‐microenvironment communication during prostate morphogenesis and physiology. We propose that by controlling HS biosynthesis and sulfation pattern, as well as the cleavage of the HS chain and/or the shedding of proteoglycans, epithelial and stromal cells are able to precisely tune the availability of signaling molecules and modulate ligand‐receptor interaction and intracellular signal transduction.
Retrotransposon‐based genetic diversity of Deschampsia antarctica Desv. from King George Island (Maritime Antarctic)
Authors: Androsiuk Piotr , Chwedorzewska Katarzyna J. , Dulska Justyna , Milarska Sylwia , Giełwanowska Irena 
Published: December 2020

AbstractDeschampsia antarctica Desv. can be found in diverse Antarctic habitats which may vary considerably in terms of environmental conditions and soil properties. As a result, the species is characterized by wide ecotypic variation in terms of both morphological and anatomical traits. The species is a unique example of an organism that can successfully colonize inhospitable regions due to its phenomenal ability to adapt to both the local mosaic of microhabitats and to general climatic fluctuations. For this reason, D. antarctica has been widely investigated in studies analyzing morphophysiological and biochemical responses to various abiotic stresses (frost, drought, salinity, increased UV radiation). However, there is little evidence to indicate whether the observed polymorphism is accompanied by the corresponding genetic variation. In the present study, retrotransposon‐based iPBS markers were used to trace the genetic variation of D. antarctica collected in nine sites of the Arctowski oasis on King George Island (Western Antarctic). The genotyping of 165 individuals from nine populations with seven iPBS primers revealed 125 amplification products, 15 of which (12%) were polymorphic, with an average of 5.6% polymorphic fragments per population. Only one of the polymorphic fragments, observed in population 6, was represented as a private band. The analyzed specimens were characterized by low genetic diversity (uHe = 0.021, I = 0.030) and high population differentiation (FST = 0.4874). An analysis of Fu's FS statistics and mismatch distribution in most populations (excluding population 2, 6 and 9) revealed demographic/spatial expansion, whereas significant traces of reduction in effective population size were found in three populations (1, 3 and 5). The iPBS markers revealed genetic polymorphism of D. antarctica, which could be attributed to the mobilization of random transposable elements, unique features of reproductive biology, and/or geographic location of the examined populations.
Naringenin suppresses Toll‐like receptor 2‐mediated inflammatory responses through inhibition of receptor clustering on lipid rafts
Authors: Kataoka Hideo , Saeki Ayumi , Hasebe Akira , Shibata Ken‐ichiro , Into Takeshi 
Published: December 2020

AbstractToll‐like receptors (TLRs) are important innate immune receptors that sometimes cause excessive inflammatory responses and a perpetuated inflammatory loop that can be involved in inflammatory and autoimmune diseases. TLR2 recognizes bacterial lipoproteins in association with TLR1 or TLR6, and triggers inflammatory responses through activation of the transcription factor NF‐κB. Naringenin, a type of citrus flavonoid, has been shown to possess anti‐inflammatory properties, but its detailed action against TLR2 remains to be fully elucidated. The present study was designed to determine whether naringenin affects the inflammatory responses triggered by TLR2. Naringenin inhibited proinflammatory cytokine production and attenuated NF‐κB activation in cells stimulated with a synthetic triacylated‐type lipopeptide known as a TLR2/TLR1 ligand, as well as a synthetic diacylated‐type lipopeptide known as a TLR2/TLR6 ligand. Moreover, a similar inhibitory effect was observed in cells stimulated with a crude lipophilic fraction extracted from Staphylococcus aureus cell walls and in cells stimulated with S. aureus cells. Furthermore, we showed that such an effect is caused by inhibition of TLR2 clustering in lipid rafts on the cell membrane. These results suggest that naringenin suppresses the inflammatory responses induced by TLR2 signal transduction. Our findings indicate a novel anti‐inflammatory property of naringenin, mediated through the regulation of cell surface TLR2 functioning.
Mind‐mindedness versus mentalistic interpretations of behavior: Is mind‐mindedness a relational construct?
Authors: Larkin Fionnuala , Schacht Robin , Oostenbroek Janine , Hayward Emily , Fernyhough Charles , Muñoz Centifanti Luna C. , Meins Elizabeth 
Published: December 2020

ABSTRACTMind‐mindedness is a measure of the tendency to represent significant others in internal state terms and is central to supportive parent–infant relationships. The two studies reported here explored whether mind‐mindedness generalizes to representations of unknown individuals, using a novel task that assessed individual differences in adults’ tendency to interpret others’ behavior with reference to their internal states: the Unknown Mother–Infant Interaction Task (UMIIT). We compared UMIIT performance with measures of mind‐mindedness from (a) adults’ descriptions of close friends and partners (Study 1, N = 96) and (b) mothers’ appropriate versus nonattuned comments on their infants’ internal states (Study 2, N = 56). In line with the proposal that mind‐mindedness is a relational construct, UMIIT performance was unrelated to mind‐mindedness in both studies.
Vicenin‐2 inhibits the Helicobacterium pylori infection associated gastric carcinogenic events through modulation of PI3K/AKT and Nrf2 signaling in GES‐1 cells
Authors: Zhang Yifeng , Sun Jing , Dong Yu , Shen Xiaoran , Zhang Zhenyu 
Published: December 2020

AbstractHelicobacter pylori (H. pylori), a microbial carcinogen of Gram‐negative bacteria, has been recognized to be the highest risk factor for the growth of human gastric cancer (GC). Therefore, the inhibition of the growth rate of H. pylori has been considered an effective vital strategy to prevent GC development. This study highlights the inhibitory effect of vicenin‐2 against H. pylori‐induced gastric carcinogen signaling in human gastric epithelial cells (GES‐1). In vitro cytotoxicity studies reported that 40 µM of vicenin‐2 remarkably protects the gastric cells and this concentration shows 85% cell viability also does not produce toxicity. In addition, vicenin‐2 prevents H. pylori‐infected increased depletion of antioxidants mediated by reactive oxygen species generation, DNA damage, malondialdehyde, and nuclear fragmentation. Here, we noticed that vicenin‐2 remarkably suppressed the expression range of the phosphorylated form of phosphatidylinositol 3‐kinase/protein kinase B, phosphorylated p38 kinases, phosphorylated extracellular signal‐regulated kinase‐1, phosphorylated c‐Jun N‐terminal kinase, tumor necrosis factor‐α, interleukin‐6, cyclooxygenase‐2 in GES‐1 infected with H. pylori. Moreover, we observed that vicenin‐2 enhanced the antioxidants protein nuclear factor erythroid factor‐2 and phosphatase and tensin homolog expression in H. pylori‐infected cells. Thus, vicenin‐2 prevents the H. pylori‐associated infection, and its resistance might be a potential strategy in preventing GC induced by H. pylori.
Clinical effect and safety profile of pegzilarginase in patients with arginase 1 deficiency
Authors: Diaz George A. , Schulze Andreas , McNutt Markey C. , Leão‐Teles Elisa , Merritt J. Lawrence , Enns Gregory M. , Batzios Spyros , Bannick Allison , Zori Roberto T. , Sloan Leslie S. , Potts Susan L. , Bubb Gillian , Quinn Anthony G. 
Published: December 2020

AbstractHyperargininemia in patients with arginase 1 deficiency (ARG1‐D) is considered a key driver of disease manifestations, including spasticity, developmental delay, and seizures. Pegzilarginase (AEB1102) is an investigational enzyme therapy which is being developed as a novel arginine lowering approach. We report the safety and efficacy of intravenously (IV) administered pegzilarginase in pediatric and adult ARG1‐D patients (n = 16) from a Phase 1/2 study (101A) and the first 12 weeks of an open‐label extension study (102A). Substantial disease burden at baseline included lower‐limb spasticity, developmental delay, and previous hyperammonemic episodes in 75%, 56%, and 44% of patients, respectively. Baseline plasma arginine (pArg) was elevated (median 389 μM, range 238‐566) on standard disease management. Once weekly repeat dosing resulted in a median decrease of pArg of 277 μM after 20 cumulative doses (n = 14) with pArg in the normal range (40 to 115 μM) in 50% of patients at 168 hours post dose (mean pegzilarginase dose 0.10 mg/kg). Lowering pArg was accompanied by improvements in one or more key mobility assessments (6MWT, GMFM‐D & E) in 79% of patients. In 101A, seven hypersensitivity reactions occurred in four patients (out of 162 infusions administered). Other common treatment‐related adverse events (AEs) included vomiting, hyperammonemia, pruritus, and abdominal pain. Treatment‐related serious AEs that occurred in five patients were all observed in 101A. Pegzilarginase was effective in lowering pArg levels with an accompanying clinical response in patients with ARG1‐D. The improvements with pegzilarginase occurred in patients receiving standard treatment approaches, which suggests that pegzilarginase could offer benefit over existing disease management.
Follicular helper T cells and follicular regulatory T cells in the immunopathology of primary Sjögren’s syndrome
Authors: Chen Weiqian , Yang Fan , Xu Guanhua , Ma Jilin , Lin Jin 
Published: December 2020

Abstract
Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease, characterized by lymphocytic infiltration into exocrine glands, which causes dry eyes, dry mouth, and systemic damage. Although the precise etiology of pSS is not clear yet, highly activated B cells, abundant anti-SSA/Ro, and anti-SSB/La autoantibodies are the hallmarks of this disease. Follicular helper T cells (Tfh), a subset of CD4+T cells, with cell surface receptors PD-1 and CXCR5, express ICOS, transcription factor Bcl-6, and a cytokine IL-21. These cells help in the differentiation of B cells into plasma cells and stimulate the formation of germinal center (GC). Previous studies have demonstrated abundant Tfh cells in the peripheral blood and salivary glands (SGs) of the patients with pSS, correlated with extensive lymphocytic infiltration of the SGs and high disease activity scores. Patients with pSS who are treated with abatacept (CTLA-4 Ig) show fewer circulating Tfh cells, reduced expression of ICOS, and lower disease activity scores. Recently identified follicular regulatory T (Tfr) cells, a subset of regulatory T cells, control the function of Tfh cells and the GC reactions. Here, we summarize the observed alterations in Tfh and Tfr cell numbers, activation state, and circulating subset distribution in pSS. Our goal is to improve the understanding of the roles of Tfh and Tfr cells (surface marker expression, cytokine production, and transcription factors) in the pathogenesis of pSS, thus contributing to the identification of candidate therapeutic agents for this disease.
East–West differences in clinical manifestations of COVID‐19 patients: A systematic literature review and meta‐analysis
Authors: Liu Xiucheng , Li Xiang , Sun Teng , Qin Hao , Zhou Yeqing , Zou Chenghang , Cao Junli , Zhang Hao 
Published: December 2020

AbstractThe coronavirus disease 2019 (COVID‐19) pandemic is currently not under control. We aimed to assess whether there are differences in clinical manifestations between COVID‐19 patients from the East (East and South‐East Asian countries including China, South Korea, and Thailand) and the West (North American, European, and Middle East countries, including the United States, Italy, France, and Iran). For this meta‐analysis, we searched for eligible studies about COVID‐19 in three databases: PubMed, EMBASE, and the Cochrane Library. Studies were divided into two cohorts for analysis: the East and the West. Stata 13.1 software was used for the meta‐analysis. Of the 1527 studies initially identified by the literature search, 169 full‐text articles were retrieved and screened for eligibility. Fifty‐seven of these, describing 19,353 patients, were deemed eligible for inclusion. Of these, 45 studies with 8416 patients were from the East while 12 studies with 10,937 patients were from the West. The results indicated that the incidences of cough, headache, dizziness, nasal congestion, and digestive symptoms in COVID‐19 patients from the East were lower than those in the West. The laboratory data showed that there were no significant differences in the levels of lymphocytes, leukocytes, C‐reactive protein, and platelet counts between the two groups. In addition, our results also showed that the incidence of cardiac and kidney injury, as well as increased levels of creatinine, alanine transaminase, and aspartate transaminase, were significantly higher in patients from the West than from the East. Our meta‐analysis indicated that there are differences in the clinical manifestations of COVID‐19 in patients from the East and the West. COVID‐19 patients from the West appear to suffer more severe liver, kidney, and heart damage due to SARS‐CoV‐2.
Controversy over smoking in COVID‐19—A real world experience in New York city
Authors: Ho Kam Sing , Narasimhan Bharat , Sheehan Jacqueline , Wu LingLing , Fung Jennifer Y. 
Published: December 2020

AbstractData are conflicting regarding the impact of tobacco smoking in people with pneumonia due to SARS‐CoV‐2 infection (COVID‐19). We performed a retrospective multicentre cohort study of 9991 consecutive patients hospitalized in a major New York academic center between March 7th and June 5th, 2020 with laboratory‐confirmed COVID‐19. The clinical outcomes assessed included risk of hospitalization, in‐hospital mortality, risk of intensive care unit (ICU) admission, and need for mechanical ventilation among smokers (current and former). Multivariable logistic regression and propensity score models were built to adjust for potential confounders. Among 9991 consecutive patients diagnosed with COVID‐19, 2212 (22.1%) patients were self‐reported smokers (406 current and 1806 former). Current smoking was not associated with an increased risk of hospitalization (propensity score [PS]‐adjusted OR 0.91; p = .46), in‐hospital mortality (PS‐OR 0.77; p = .12), ICU admission (PS‐OR 1.18; p = .37), or intubation (PS‐OR 1.04; p = .85). Similarly, former smoking was not associated with an increased risk of hospitalization (PS‐OR 0.88; p = .11), in‐hospital mortality (PS‐OR 1.03; p = .78), ICU admission (PS‐OR 1.03; p = .95), or intubation (PS‐OR 0.93; p = .57). Furthermore, smoking (current or former) was not associated with an increased risk of hospitalization (PS‐OR 0.85; p = .05), in‐hospital mortality (PS‐OR 0.94; p = .49), ICU admission (PS‐OR 0.86; p = .17), or intubation (PS‐OR 0.79; p = .06). Smoking is a well‐known risk factor associated with greater susceptibility and subsequent increased severity of respiratory infections. In the current COVID‐19 pandemic, smokers may have increased risk and severe pneumonia. In the current COVID‐19 pandemic, smokers are believed to have an increased risk of mortality as well as severe pneumonia. However, in our analysis of real‐world clinical data, smoking was not associated with increased in‐patient mortality in COVID‐19 pneumonia, in accordance with prior reports.
Meniscus cell regional phenotypes: Dedifferentiation and reversal by biomaterial embedding
Authors: Andress Benjamin , Kim Jason H. , Cutcliffe Hattie C. , Amendola Annunziato , Goode Adam P. , Varghese Shyni , DeFrate Louis E. , McNulty Amy L. 
Published: December 2020

AbstractMeniscus injuries are common and a major cause of long‐term joint degeneration and disability. Current treatment options are limited, so novel regenerative therapies or tissue engineering strategies are urgently needed. The development of new therapies is hindered by a lack of knowledge regarding the cellular biology of the meniscus and a lack of well‐established methods for studying meniscus cells in vitro. The goals of this study were to (1) establish baseline expression profiles and dedifferentiation patterns of inner and outer zone primary meniscus cells, and (2) evaluate the utility of poly(ethylene glycol) diacrylate (PEGDA) and gelatin methacrylate (GelMA) polymer hydrogels to reverse dedifferentiation trends for long‐term meniscus cell culture. Using reverse transcription‐quantitative polymerase chain reaction, we measured expression levels of putative meniscus phenotype marker genes in freshly isolated meniscus tissue, tissue explant culture, and monolayer culture of inner and outer zone meniscus cells from porcine knees to establish baseline dedifferentiation characteristics, and then compared these expression levels to PEGDA/GelMA embedded passaged meniscus cells.COL1A1showed robust upregulation, whileCHAD, CILP, andCOMPshowed downregulation with monolayer culture. Expression levels ofCOL2A1, ACAN, andSOX9were surprisingly similar between inner and outer zone tissue and were found to be less sensitive as markers of dedifferentiation. When embedded in PEGDA/GelMA hydrogels, expression levels of meniscus cell phenotype genes were significantly modulated by varying the ratio of polymer components, allowing these materials to be tuned for phenotype restoration, meniscus cell culture, and tissue engineering applications.
The limitations of mono‐ and combination antibiotic therapies on immature biofilms in a murine model of implant‐associated osteomyelitis
Authors: Tomizawa Takuya , Nishitani Kohei , Ito Hiromu , Okae Yu , Morita Yugo , Doi Kohei , Saito Motoo , Ishie Shinichiro , Yoshida Shigeo , Murata Koichi , Yoshitomi Hiroyuki , Kuroda Yutaka , Matsuda Shuichi 
Published: December 2020

AbstractTreatment of implant‐associated orthopedic infections remains challenging, partly because antimicrobial treatment is ineffective after a mature biofilm covers the implant surface. Currently, the relative efficacy of systemic mono‐ and combination standard‐of‐care (SOC) antibiotic therapies over the course of mature biofilm formation is unknown. Thus, we assessed the effects of cefazoline (CEZ), gentamicin (GM), and vancomycin, with or without rifampin (RFP), on Staphylococcus aureus biofilm formation during the establishment of implant‐associated osteomyelitis in a murine tibia model. Quantitative scanning electron microscopy of the implants harvested on Days 0, 3, and 7 revealed that all treatments except CEZ monotherapy significantly reduced biofilm formation when antibiotics started at Day 0 (0.46‐ to 0.25‐fold; p < 0.05). When antibiotics commenced 3 days after the infection, only GM monotherapy significantly inhibited biofilm growth (0.63‐fold; p < 0.05), while all antibiotics inhibited biofilm formation in combination with RFP (0.56‐ to 0.44‐fold; p < 0.05). However, no treatment was effective when antibiotics commenced on Day 7. To confirm these findings, we assessed bacterial load via colony‐forming unit and histology. The results showed that GM monotherapy and all combination therapies reduced the colony‐forming unit in the implant (0.41‐ to 0.23‐fold; p < 0.05); all treatments except CEZ monotherapy reduced the colony‐forming unit and staphylococcus abscess communities in the tibiae (0.40‐ to 0.10‐fold; p < 0.05). Collectively, these findings demonstrate that systemic SOC antibiotics can inhibit biofilm formation within 3 days but not after 7 days of infection. The efficacy of SOC monotherapies, CEZ particularly, is very limited. Thus, combination treatment with RFP may be necessary to inhibit implant‐associated osteomyelitis.