julilili42/papers huggingface dataset:
Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia
2023-06-01

Introductory Paragraph / Abstract The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope. The activity of the TcaA protein alters the sensitivity of the bacteria to cell wall attacking agents, including antimicrobial peptides, human defence fatty acids, and several antibiotics. This protein also affects the autolytic activity and lysostaphin sensitivity of the bacteria, suggesting that in addition to changing WTA abundance in the cell envelope, it also plays a role in peptidoglycan crosslinking. With TcaA rendering the bacteria more susceptible to serum killing, while simultaneously increasing the abundance of WTA in the cell envelope, it was unclear what effect this protein may have during infection. To explore this, we examined human data and performed murine experimental infections. Collectively, our data suggests that whilst mutations in tcaA are selected for during bacteraemia, this protein positively contributes to the virulence of S. aureus through its involvement in altering the cell wall architecture of the bacteria, a process that appears to play a key role in the development of bacteraemia.
Neurosurgical morbidity in pediatric supratentorial midline low-grade glioma: Results from the German LGG studies.
2023-06-01

10044 Background: Surgical resection is a mainstay of treatment for pediatric low-grade glioma (LGG) within all current therapy algorithms, yet associated morbidity is scarcely reported. As supratentorial midline (SML) interventions are particularly challenging, we investigated the frequency of neurosurgical complications/new impairments aiming to identify their risk factors. Methods: Records were retrospectively analyzed from 318 patients with SML-LGG from successive German multicenter LGG studies, undergoing surgery between May 1998 and June 2020. Results: 537 operations (230 resections, 167 biopsies, 140 non-tumor procedures) were performed in 318 patients (54% male, median age: 7.6 years at diagnosis, 9.5 years at operation, 11% NF1, 42.5% optic pathway glioma). Surgical mortality rate was 0.93%. Applying the Drake classification, postoperative surgical morbidity was observed in 254/537 (47.3%) and medical morbidity in 97/537 (18.1%) patients with a 40.1% 30-day persistence rate for newly developed neurological deficits (65/162). Neuroendocrine impairment affected 53/318 patients (16.7%), visual deterioration 34/318 (10.7%). Postsurgical morbidity was associated with patient age &lt;3 years at operation, tumor volume ≥80cm 3 , presence of hydrocephalus, complete resection, surgery in centers with less than median reported tumor-related procedures and during the earlier study period between 1998-2006, while the neurosurgical approach, tumor location, NF1 status or previous non-surgical treatment were not. Conclusions: Neurosurgery-associated morbidity was frequent in pediatric patients with SML-LGG undergoing surgery in the German LGG-studies. We identified patient- and institution-associated factors that may increase the risk for complications. We advocate that local multidisciplinary teams consider the planned extent of resection and surgical skills. [Table: see text]
MTHFR polymorphisms and neurotoxicity and overall survival after methotrexate-based therapy in primary CNS lymphoma.
2023-06-01

2079 Background: The folate-antagonist methotrexate (HD-MTX) is an integral to induction chemotherapy for primary CNS lymphoma (PCNSL); however, it can be associated with toxicities, including injury to cerebral white matter known as leukoencephalopathy. Methylenetetrahydrofolate Reductase (MTHFR) is involved in intracellular folate metabolism, and MTHFR polymorphisms may affect CNS-specific side effects of HD-MTX. Here, we evaluated the possible association of MTHFR polymorphisms an HD-MTX related CNS toxicity. Methods: We retrospectively searched our institutional database at the Massachusetts General Hospital for newly diagnosed PCNSL patients treated with HD-MTX (without use of radiotherapy or intrathecal chemotherapy). MTHFR polymorphisms were correlated with evolution of leukoencephalopathy over a time period of five years and patient outcomes. ROC curves were generated to estimate the diagnostic ability of specific MTHFR genotypes. Survival was calculated using Kaplan-Meier survival analysis and log-rank test. The significance level was set at p ≤ 0.05. Results: Among 68 PCNSL patients, MTHFR polymorphisms were found in 60 individuals (88.2%; 677C&gt;T: 29 patients, 1298A&gt;C: 18 patients, combined 677C&gt;T &amp; 1298A&gt;C: 13 patients). Neither MTX clearance nor disease response to HD-MTX was affected by specific genotypes, and complete response was achieved in 72.1% of patients by induction with HD-MTX-based therapy. However, the 1298A&gt;C genotype was associated with increased frequency and severity of leukoencephalopathy over time (χ 2 = 7.43). Such genotype predicted treatment-induced leukoencephalopathy with a sensitivity of 71.0%% and a specificity of 62.2% (ROC: p = 0.019). While progression-free survival did not differ in genotype-based subgroups, overall survival was significantly lower when the 1298A&gt;C genotype was present. Conclusions: The MTHFR 1298A&gt;C genotype may serve to identify PCNSL patients at elevated risk for HD-MTX-induced leukoencephalopathy. This was associated with reduced overall survival, potentially due to decreased functional status in patients less suitable for aggressive subsequent therapies.
From Charlotte Smith to Jane Austen: The Evolution of the English Novel
2023-06-01

Abstract The article focuses on two female writers from the late eighteenth century and the first half of the nineteenth century: Charlotte Smith and Jane Austen. Based on Smith’s first novel Emmeline, the Orphan of the Castle (1788) and Austen’s Emma (1815), the novel’s evolutionary trajectory from prose fiction at the end of the eighteenth century to the full flowering of the realist novel will be traced in an exemplary fashion. Thereby, the analysis will argue that Emmeline represents a case of transition in which subjective modes of storytelling (literary conventions, character perspective) have not yet been synthetically combined with the objectifying framework of the narrative situation. Finally, this has been achieved with the realist novel as will be demonstrated with Emma .
Bracketing Ephemera: Robert Paltock’s The Life and Adventures of Peter Wilkins and Eighteenth-Century Book Culture
2023-06-01

Abstract The article seeks to conceive of Robert Paltock’s The Life and Adventures of Peter Wilkins (1750) as a hybrid text that employs certain (formal) elements of what was to become ‘the realist novel’ as integrative bracketing mechanisms for the text’s more ephemeral as well as fantastical and subversive aspects. To do so, the article builds on recent research on the realist novel which has dragged into the light the intricacies and interdependencies of the seemingly clear-cut categories of formal realism and ephemeral writing. Accordingly, texts such as Peter Wilkins can be treated as sites of exchange or integration between these modes of writing. The article moves from the emerging divide between ‘the novel’ and ephemera in the mid-eighteenth century to Paltock’s frame narrative and to paratextual devices as well as the metaphorical function of flight. By doing so, it will be shown that Paltock’s integrative approach in Peter Wilkins hinges on a deep awareness of the bias between realist and ephemeral/fantastical writing.
Sonographic and intraoperative image of a heterotopic pregnancy in 6+3 weeks of gestation
2023-06-01

A 32-year-old pregnant woman was referred due to moderate abdominal pain in the 6 + 3 week of gestation. The pregnancy resulted from an IVF-treatment. The actual level of HCG was 39.000 U/l. The medical history revealed a rightsided ectopic pregnancy right with salpingectomy. The transvaginal ultrasound demonstrated a vital intrauterine pregnancy and simultaneously an ectopic, intramural pregnancy on the right sight. The heterotopic pregnancy was treated by laparoscopic excision of the ectopic implantation. The further course of the intrauterine pregnancy was eventless. The patient delivered a healthy girl at 40+5 weeks of gestation.
OTHR-04. DEVELOPMENT OF A FUNCTIONAL PLATFORM FOR REAL-TIME PERSONALIZED DRUG SENSITIVITY PROFILING OF PATIENT-DERIVED 3D FRESH TUMOR TISSUE CULTURES IN THE PEDIATRIC PRECISION ONCOLOGY PROGRAM INFORM
2023-06-01

Abstract The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75-78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.
Levels of astrocyte‐derived glial fibrillary acidic protein (GFAP) and S100 calcium‐binding protein B (S100B) in the cerebrospinal fluid within the early stages of Alzheimer´s Disease
2023-06-01

Abstract Background The quantitative analysis of biomarker proteins in the cerebrospinal fluid (CSF) substantiates the clinical diagnosis of Alzheimer ́s disease (AD). A substantial problem in the early diagnosis of AD is that clinical symptoms as measured by neuropsychological tests appear only after massive cell loss has already occurred in the brain. However, when the disease manifests, abeta‐ and tau‐protein levels have already become static. In this study, we asked whether concentrations of the astrocyte‐derived proteins glial fibrillary acidic protein (GFAP) and S100 calcium‐binding protein B (S100B) in CSF might serve as markers of pathophysiological events and astrocyte reactivation in the course of AD. Although, there are some previously studies reporting high GFAP levels in cerebrospinal fluid of AD group, the CSF levels of GFAP and S100B in the early course of the AD have not been reported. Methods We measured the levels of GFAP and S100B in the CSF of healthy control subjects (n = 90), first degree relatives of AD (parent or sibling, n = 46), subjective memory decline (SCD) (n = 211), mild cognitive impairment (MCI) (n = 114) and AD (n = 65) patients in a well‐structured cohort (DELCODE Cohort), which has a larger sample size than previous studies. Results After comparing the CSF levels of GFAP in the study groups, we found that healthy controls had significantly lower GFAP levels than AD patients (p = 0.001, Figure 1) and the MCI patients (p = 0,004, Figure 1). It might prove to be a very important evidence of the role of astrogliosis in early stages. Furthermore, no significantly differences were found in levels of S100B, although S100B mean values show also gradual increasing from SCD to AD (Figure 2). As a note to the reader, we also found that there was low correlation between the levels of glial markers (GFAP und S100B) and markers of classical biomarkers (Aβ‐42, Ratio Aβ‐42/Aβ‐40, Total‐τ, Phospho‐τ‐181) of neurodegeneration in the disease course. Conclusion This result may prove the role of early reactive astrocytes in early stages of disease. And this finding could lead to develop another treatment concepts targeting the early reactive astrocytes.
White matter hyperintensities in the corpus callosum are associated with beta‐amyloid, neurodegeneration and cognitive performance
2023-06-01

Abstract Background WMH in the corpus callosum (CC), as previously related to AD pathology (1) and lower cognition in AD patients (2) , are suggested to play an important role in AD. The Aim of this study was to substantiate the associations between WMH location, biomarkers of AD pathophysiology, and cognitive performance in the DELCODE study. Method 429 participants were included (HC: 126, SCD: 165, MCI: 87, AD: 51). WMH volumes were segmented from FLAIR images. WMH volumes were adjusted for total intracranial volume and log‐transformed. Beta‐Amyloid and total Tau (Aß42 and tTau, measured in CSF) and neurodegeneration (ND, measured by hippocampal volume) were log‐transformed and used as surrogate markers for AD pathophysiology. Cognitive performance was assessed by a global cognitive composite. Path modelling, adjusted for age, sex and education, was performed to estimate direct and indirect associations between regional WMH volumes (in the CC splenium, body, genu and the frontal lobe as possible control region), AD biomarkers and cognition. Results The correlation matrix (Figure 1) showed the highest correlation of Aß42 and tTau with WMH volume the splenium CC. Greater WMH volume in the splenium CC was directly associated with lower global cognition (Figure 2a, ß = ‐0.10, p = 0.01) and indirectly through Aß42 (ß = ‐0.10, p = 0.001) and ND (Figure 2b, ß = ‐0.05, p = 0.001). The same indirect association was statistically significant regarding tTau (ß = ‐0.03, p &lt; 0.001). Model outcomes were similar for the body and genu of the CC. For frontal WMH volume, the direct association with global cognition was not statistically significant (ß = ‐0.002, p = 0.96), only through indirect associations with Aß42 (ß = ‐0.05, p = 0.003) and ND (ß = ‐0.02, p = 0.05). Conclusion WMH in the CC are associated with lower cognitive performance through direct and indirect associations with Aß42 and neurodegeneration. Similar associations were seen for frontal WMH. However, a direct association between frontal WMH volume and cognition was not noticed, when considering AD biomarkers. Our study substantiates the clinical relevance and impact of WMH in the CC, in particular the splenium, in AD. 1) Gaubert et al.,2021 2) Garnier‐Crussard et al.,2021
Ukraine as the Hub of Postimperial Formalism. Ukrainness, Revolutionary Populism, and the Theory of Poetical Language ‘in’ Russia and ‘in’ Poland
2023-06-01

Abstract The notion of ‘postimperial formalism’ accounts of the interconnectedness of Russian, Ukrainian, and Polish variants of formalism, whose distinctive character is contingent on the dialectics of liberation and subjugation (or autonomy and heteronomy) operating in the multinational entity of the Russian empire. Specifically, the theory of poetic language – the pars pro toto of early literary theory – carries with itself the survivals of the conditions of the multinational empire. This is most eloquently expressed in the writings of Polish and Jewish-Ukrainian populist activists turned ethnographic researchers, who prepared a theory of poetic language to which the formalists could have recourse. I first map the dimensions of the Ukrainian investment into the formulation of the theory of poetic language. Secondly, I describe the role of the constructed Ukrainness – under the guise of the so-called Ukrainian school of Polish romanticism – in the emergence of Polish formalism.
HER2CLIMB-05: Phase 3 study of tucatinib or placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer (trial in progress)
2023-06-01

Objective Despite advances in 1L SOC (trastuzumab+pertuzumab+taxane) for patients, most HER2+ metastatic breast cancer (MBC) progresses during maintenance therapy (trastuzumab+pertuzumab). Tucatinib is a TKI approved in combination with trastuzumab and capecitabine for adults with HER2+ MBC with/without brain metastases (BMs). In HER2CLIMB, tucatinib, trastuzumab, and capecitabine significantly prolonged PFS and OS in patients with HER2+ MBC and was well tolerated. The risk of disease progression or death in patients with untreated and/or active BMs was also reduced. HER2CLIMB-05 investigates whether adding tucatinib to 1L SOC as maintenance therapy will extend PFS while maintaining quality of life (QOL).
Analysis of the complete plastomes of Bidens pilosa L. 1753 (Asteraceae, Coreopsideae) from Beijing, China reveals high genetic diversity and possible misidentifications
2023-06-01

<i>Bidens pilosa</i> L. 1753 is a perennial herbaceous flowering plant, traditionally used in foods and medicines. In this study, we sequenced, assembled, and characterized the complete plastome of <i>B. pilosa</i> from Beijing, China. The plastome (MN385242) is circularized with a conservative quadripartite structure. Its length is 150,524 bp, including a large single-copy region (83,535 bp), a small single-copy region (17,627 bp), and a pair of inverted repeat regions (each 24,681 bp). The plastome consists of 128 genes, including 78 unique protein-coding, 28 unique tRNA, and 4 unique rRNA genes. Phylogenetic analyses showed all five <i>B. pilosa</i> plants couldn’t form a monophyletic clade and were separated into three clades. The results of K2P distance and molecular markers were all consistent with those of phylogenetic analysis, revealing high genetic diversity and even possible misidentifications of the <i>B. pilosa</i>. Our results highlighted the importance of correct species identification of materials in medicinal products.
The association between screen use and central obesity among children and adolescents: a systematic review and meta-analysis
2023-06-02

Abstract Currently, there is no summative study evaluating the association between central obesity and screen time. This systematic review and meta-analysis aimed to summarize the results of studies evaluating the association between screen time and central obesity among children and adolescents. To this end, we performed a systematic search in three electronic databases, including Scopus, PubMed, and Embase to retrieve the related studies up to March 2021. Nine studies were eligible to be included in the meta-analysis. There was no association between odds of central obesity and screen time [odds ratio (OR) 1.136; 95% CI 0.965–1.337; P = 0.125]; however, waist circumference (WC) was 1.23 cm higher in those with highest screen time versus those in the lowest screen time category [weighted mean difference (WMD) = 1.23; 95% 95% CI 0.342–2.112; P = 0.007; Fig. 3]. Moreover, the possible sources of heterogeneity in the included studies were continent and sample size. No evidence of publication bias was reported. For the first time, the current systematic review and meta-analysis revealed that those with the highest screen time had higher WC compared with those with the lowest screen time. Although, there was no association between odds of central obesity and screen time. Due to the observational design of the included studies, it is impossible to infer the cause-effect relationship. Therefore, further interventional and longitudinal studies are warranted to better elucidate the causality of these associations.
Identification of a damage‐associated molecular pattern (DAMP) receptor and its cognate peptide ligand in sweet potato (Ipomoea batatas)
2023-06-02

Abstract Sweet potato ( Ipomoea batatas ) is an important tuber crop, but also target of numerous insect pests. Intriguingly, the abundant storage protein in tubers, sporamin, has intrinsic trypsin protease inhibitory activity. In leaves, sporamin is induced by wounding or a volatile homoterpene and enhances insect resistance. While the signalling pathway leading to sporamin synthesis is partially established, the initial event, perception of a stress‐related signal is still unknown. Here, we identified an Ib LRR‐RK1 that is induced upon wounding and herbivory, and related to peptide‐elicitor receptors (PEPRs) from tomato and Arabidopsis. We also identified a gene encoding a precursor protein comprising a peptide ligand ( Ib Pep1) for Ib LRR‐RK1. Ib Pep1 represents a distinct signal in sweet potato, which might work in a complementary and/or parallel pathway to the previously described hydroxyproline‐rich systemin (HypSys) peptides to strengthen insect resistance. Notably, an interfamily compatibility in the Pep/PEPR system from Convolvulaceae and Solanaceae was identified.
Reactions of 1,2-Azaborinine, a BN-Benzyne, with Organic π Systems
2023-06-02

Ortho-benzyne and 1,2-azaborinine are related by the formal exchange of the CC triple bond by the isoelectronic BN unit. The (2 + 2) and (2 + 4) cycloaddition reactions of 1,2-azaborinine with the different organic π systems (ethene, ethyne, 1,3-butadiene, 1,3-cyclopentadiene, furan, benzene) were examined computationally using density functional, second-order perturbation, and coupled-cluster methods. All reactions of 1,2-azaborinine with the studied substrates are highly exothermic and involve the formation of Lewis acid-base complexes of 1,2-azaborinine and respective π systems. The interaction between the π bond of the substrates and the empty p orbital of the boron atom in these complexes is remarkably strong, resulting in two-step mechanisms for the (2 + 2) and (2 + 4) cycloaddition reactions. Cycloaddition reactions have lower barriers than CH insertion reactions, and (2 + 4) reactions are favored over (2 + 2) cycloadditions.
RETRACTED: Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach
2023-06-02

Background: Cancer-associated fibroblasts (CAFs) of ovarian cancer (OvC) are the most prevalent element of the tumor microenvironment (TM). By promoting angiogenesis, immunological suppression, and invasion, CAFs speed up the growth of tumors by changing the extracellular matrix’s structure and composition and/or initiating the epithelial cells (EPT). IL-33/ST2 signaling has drawn a lot of attention since it acts as a pro-tumor alarmin and encourages spread by altering TM. Methods: Differentially expressed genes (DEGs) of the OvC tumor microenvironment were found in the GEO database, qRT-PCR, western blotting, and immunohistochemistry, and their presence and changes in healthy and tumor tissue content were examined. Primary cultures of healthy fibroblasts and CAFs obtained from healthy and tumor tissues retrieved from OvC samples were used for in vitro and in vivo investigations. Cultured primary human CAFs were utilized to investigate the regulation and the IL-33/ST2 axis role in the inflammation reactions. Results: Although ST2 and IL-33 expression was detected in both epithelial (EPT) and fibroblast cells of ovarian cancer, they are more abundant in CAFs. Lipopolysaccharides, serum amyloid A1, and IL-1β, the inflammatory mediators, could all induce IL-33 expression through NF-κB activation in human CAFs. In turn, via the ST2 receptor, IL-33 affected the production of IL-6, IL-1β, and PTGS2 in human CAFs via the MAPKs-NF-κB pathway. Conclusion: Our findings suggest that IL-33/ST2 is affected by the interaction of CAFs and epithelial cells inside the tumor microenvironment. Activation of this axis leads to increased expression of inflammatory factors in tumor CAFs and EPT cells. Therefore, targeting the IL-33/ST2 axis could have potential value in the prevention of OvC progression.