bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection
Authors: Wheatley Rachel , Diaz Caballero Julio , Kapel Natalia , de Winter Fien H. R. , Jangir Pramod , Quinn Angus , del Barrio-Tofiño Ester , López-Causapé Carla , Hedge Jessica , Torrens Gabriel , Van der Schalk Thomas , Xavier Basil Britto , Fernández-Cuenca Felipe , Arenzana Angel , Recanatini Claudia , Timbermont Leen , Sifakis Frangiscos , Ruzin Alexey , Ali Omar , Lammens Christine , Goossens Herman , Kluytmans Jan , Kumar-Singh Samir , Oliver Antonio , Malhotra-Kumar Surbhi , MacLean Craig 
Published: April 2021

AbstractIt is well established that antibiotic treatment selects for resistance, but the dynamics of this process during infections are poorly understood. Here we map the responses ofPseudomonas aeruginosato treatment in high definition during a lung infection of a single ICU patient. Host immunity and antibiotic therapy with meropenem suppressedP. aeruginosa, but a second wave of infection emerged due to the growth ofoprDandwbpMmeropenem resistant mutants that evolved in situ. Selection then led to a loss of resistance by decreasing the prevalence of low fitnessoprDmutants, increasing the frequency of high fitness mutants lacking the MexAB-OprM efflux pump, and decreasing the copy number of a multidrug resistance plasmid. Ultimately, host immunity suppressedwbpMmutants with high meropenem resistance and fitness. Our study highlights how natural selection and host immunity interact to drive both the rapid rise, and fall, of resistance during infection.
IP6-assisted CSN-COP1 competition regulates a CRL4-ETV5 proteolytic checkpoint to safeguard glucose-induced insulin secretion
Authors: Lin Hong , Yan Yuan , Luo Yifan , So Wing Yan , Wei Xiayun , Zhang Xiaozhe , Yang Xiaoli , Zhang Jun , Su Yang , Yang Xiuyan , Zhang Bobo , Zhang Kangjun , Jiang Nan , Chow Billy Kwok Chong , Han Weiping , Wang Fengchao , Rao Feng 
Published: April 2021

AbstractCOP1 and COP9 signalosome (CSN) are the substrate receptor and deneddylase of CRL4 E3 ligase, respectively. How they functionally interact remains unclear. Here, we uncover COP1–CSN antagonism during glucose-induced insulin secretion. Heterozygous Csn2WT/K70E mice with partially disrupted binding of IP6, a CSN cofactor, display congenital hyperinsulinism and insulin resistance. This is due to increased Cul4 neddylation, CRL4COP1 E3 assembly, and ubiquitylation of ETV5, an obesity-associated transcriptional suppressor of insulin secretion. Hyperglycemia reciprocally regulates CRL4-CSN versus CRL4COP1 assembly to promote ETV5 degradation. Excessive ETV5 degradation is a hallmark of Csn2WT/K70E, high-fat diet-treated, and ob/ob mice. The CRL neddylation inhibitor Pevonedistat/MLN4924 stabilizes ETV5 and remediates the hyperinsulinemia and obesity/diabetes phenotypes of these mice. These observations were extended to human islets and EndoC-βH1 cells. Thus, a CRL4COP1-ETV5 proteolytic checkpoint licensing GSIS is safeguarded by IP6-assisted CSN-COP1 competition. Deregulation of the IP6-CSN-CRL4COP1-ETV5 axis underlies hyperinsulinemia and can be intervened to reduce obesity and diabetic risk.
A survey of the kinome pharmacopeia reveals multiple scaffolds and targets for the development of novel anthelmintics
Authors: Knox Jessica , Joly Nicolas , Linossi Edmond M. , Carmona-Negrón José A. , Jura Natalia , Pintard Lionel , Zuercher William , Roy Peter J. 
Published: April 2021

AbstractOver one billion people are currently infected with a parasitic nematode. Symptoms can include anemia, malnutrition, developmental delay, and in severe cases, death. Resistance is emerging to the anthelmintics currently used to treat nematode infection, prompting the need to develop new anthelmintics. Towards this end, we identified a set of kinases that may be targeted in a nematode-selective manner. We first screened 2040 inhibitors of vertebrate kinases for those that impair the model nematode Caenorhabditis elegans. By determining whether the terminal phenotype induced by each kinase inhibitor matched that of the predicted target mutant in C. elegans, we identified 17 druggable nematode kinase targets. Of these, we found that nematode EGFR, MEK1, and PLK1 kinases have diverged from vertebrates within their drug-binding pocket. For each of these targets, we identified small molecule scaffolds that may be further modified to develop nematode-selective inhibitors. Nematode EGFR, MEK1, and PLK1 therefore represent key targets for the development of new anthelmintic medicines.
Extracellular vesicles derived from ascitic fluid enhance growth and migration of ovarian cancer cells
Authors: Mitra Aparna , Yoshida-Court Kyoko , Solley Travis N. , Mikkelson Megan , Yeung Chi Lam Au , Nick Alpa , Lu Karen , Klopp Ann H. 
Published: April 2021

AbstractOvarian cancer is associated with a high mortality rate due to diagnosis at advanced stages. Dissemination often occurs intraperitoneally within the ascites fluid. The microenvironment can support dissemination through several mechanisms. One potential ascites factor which may mediate dissemination are EVs or extracellular vesicles that can carry information in the form of miRNAs, proteins, lipids, and act as mediators of cellular communication. We present our observations on EVs isolated from ascitic supernatants from patients diagnosed with high grade serous ovarian carcinoma in augmenting motility, growth, and migration towards omental fat. MicroRNA profiling of EVs from malignant ascitic supernatant demonstrates high expression of miR 200c-3p, miR18a-5p, miR1246, and miR1290 and low expression of miR 100- 5p as compared to EVs isolated from benign ascitic supernatant. The migration of ovarian cancer spheroids towards omental fat is enhanced in the presence of malignant ascitic EVs. Gene expression of these cells showed increased expression of ZBED2, ZBTB20, ABCC3, UHMK1, and low expression of Transgelin and MARCKS. We present evidence that ovarian ascitic EVs increase the growth of ovarian cancer spheroids through miRNAs.
Stress-induced differential gene expression in cardiac tissue
Authors: de Carvalho Ana Elisa T. S. , Cordeiro Marco A. , Rodrigues Luana S. , Ortolani Daniela , Spadari Regina C. 
Published: April 2021

AbstractThe stress response is adaptive and aims to guarantee survival. However, the persistence of a stressor can culminate in pathology. Catecholamines released as part of the stress response over activate beta adrenoceptors (β-AR) in the heart. Whether and how stress affects the expression of components of the intracellular environment in the heart is still, however, unknown. This paper used microarray to analyze the gene expression in the left ventricle wall of rats submitted to foot shock stress, treated or not treated with the selective β2-AR antagonist ICI118,551 (ICI), compared to those of non-stressed rats also treated or not with ICI, respectively. The main findings were that stress induces changes in gene expression in the heart and that β2-AR plays a role in this process. The vast majority of genes disregulated by stress were exclusive for only one of the comparisons, indicating that, in the same stressful situation, the profile of gene expression in the heart is substantially different when the β2-AR is active or when it is blocked. Stress induced alterations in the expression of such a large number of genes seems to be part of stress-induced adaptive mechanism.
Real-world outcomes of first-line pembrolizumab plus pemetrexed-carboplatin for metastatic nonsquamous NSCLC at US oncology practices
Authors: Velcheti Vamsidhar , Hu Xiaohan , Piperdi Bilal , Burke Thomas 
Published: April 2021

AbstractEvidence from real-world clinical settings is lacking with regard to first-line immunotherapy plus chemotherapy for the treatment of non-small cell lung cancer (NSCLC). Our aim was to describe outcomes for patients treated with first-line pembrolizumab-combination therapy for metastatic nonsquamous NSCLC in US oncology practices. Using an anonymized, nationwide electronic health record-derived database, we identified patients who initiated pembrolizumab plus pemetrexed-carboplatin in the first-line setting (May 2017 to August 2018) after diagnosis of metastatic nonsquamous NSCLC that tested negative for EGFR and ALK genomic aberrations. Eligible patients had ECOG performance status of 0–1. An enhanced manual chart review was used to collect outcome information. Time-to-event analyses were performed using the Kaplan–Meier method. Of 283 eligible patients, 168 (59%) were male; median age was 66 years (range 33–84); and the proportions of patients with PD-L1 tumor proportion score (TPS) of ≥ 50%, 1–49%, < 1%, and unknown were 28%, 27%, 28%, and 17%, respectively. At data cutoff on August 31, 2019, median patient follow-up was 20.3 months (range 12–28 months), and median real-world times on treatment (rwToT) with pembrolizumab and pemetrexed were 5.6 (95% CI 4.5–6.4) and 2.8 months (95% CI 2.2–3.5), respectively. Median overall survival (OS) was 16.5 months (95% CI 13.2–20.6); estimated 12-month survival was 59.5% (95% CI 53.3–65.0); rwProgression-free survival was 6.4 months (95% CI 5.4–7.8); and rwTumor response rate (complete or partial response) was 56.5% (95% CI 50.5–62.4). Median OS was 20.6, 16.3, 13.2, and 13.7 months for patient cohorts with PD-L1 TPS ≥ 50%, 1–49%, < 1%, and unknown, respectively. These findings demonstrate the effectiveness of pembrolizumab plus pemetrexed-carboplatin by describing clinical outcomes among patients with metastatic nonsquamous NSCLC who were treated at US oncology practices.
Central administration of afzelin extracted from Ribes fasciculatum improves cognitive and memory function in a mouse model of dementia
Authors: Oh So-Young , Jang Min Jun , Choi Yun-Hyeok , Hwang Hongik , Rhim Hyewhon , Lee Bonggi , Choi Chun Whan , Kim Min Soo 
Published: April 2021

AbstractNeurodegenerative disorders are characterized by the decline of cognitive function and the progressive loss of memory. The dysfunctions of the cognitive and memory system are closely related to the decreases in brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) signalings. Ribes fasciculatum, a medicinal plant grown in diverse countries, has been reported to pharmacological effects for autoimmune diseases and aging recently. Here we found that afzelin is a major compound in Ribes fasciculatum. To further examine its neuroprotective effect, the afzelin (100 ng/µl, three times a week) was administered into the third ventricle of the hypothalamus of C57BL/6 mice for one month and scopolamine was injected (i.p.) to these mice to impair cognition and memory before each behavior experiment. The electrophysiology to measure long-term potentiation and behavior tests for cognitive and memory functions were performed followed by investigating related molecular signaling pathways. Chronic administration of afzelin into the brain ameliorated synaptic plasticity and cognitive/memory behaviors in mice given scopolamine. Studies of mice’s hippocampi revealed that the response of afzelin was accountable for the restoration of the cholinergic systems and molecular signal transduction via CREB-BDNF pathways. In conclusion, the central administration of afzelin leads to improved neurocognitive and neuroprotective effects on synaptic plasticity and behaviors partly through the increase in CREB-BDNF signaling.
An analytic solution of full-sky spherical geometry for satellite relative motions
Authors: Lee Soung Sub , Hall Christopher D. 
Published: April 2021

AbstractHerein, an exact and efficient analytic solution for an unperturbed satellite relative motion was developed using a direct geometrical approach. The derivation of the relative motion geometrically interpreted the projected Keplerian orbits of the satellites on a sphere (Earth and celestial spheres) using the solutions of full-sky spherical triangles. The results were basic and computationally faster than the vector and plane geometry solutions owing to the advantages of the full-sky spherical geometry. Accordingly, the validity of the proposed solution was evaluated by comparing it with other analytic relative motion theories in terms of modeling accuracy and efficiency. The modeling accuracy showed an equivalent performance with Vadali’s nonlinear unit sphere approach, which is essentially equal to the Yan–Alfriend nonlinear theory. Moreover, the efficiency was demonstrated by the lowest computational cost compared with other models. In conclusion, the proposed modeling approach illustrates a compact and efficient closed-form solution for satellite relative motion dynamics.
Saccharomyces boulardii modulates oxidative stress and renin angiotensin system attenuating diabetes-induced liver injury in mice
Authors: Barssotti Leticia , Abreu Isabel C. M. E. , Brandão Ana Beatriz P. , Albuquerque Raquel C. M. F. , Ferreira Fabiana G. , Salgado Miguel A. C. , Dias Danielle D. S. , De Angelis Kátia , Yokota Rodrigo , Casarini Dulce E. , Souza Lívia B. , Taddei Carla R. , Cunha Tatiana S. 
Published: April 2021

AbstractType 1 diabetes (T1DM) is a chronic disease characterized by hyperglycemia due to a deficiency in endogenous insulin production, resulting from pancreatic beta cell death. Persistent hyperglycemia leads to enhanced oxidative stress and liver injury. Several studies have evaluated the anti-diabetic and protective effects of probiotic strains in animal models. In the present study, we investigated, through histopathological and biochemical analyses, the effects of eight weeks of administration of Saccharomyces boulardii (S. boulardii) yeast on the liver of streptozotocin (STZ) induced diabetic C57BL/6 mice. Our results demonstrated that S. boulardii attenuates hepatocytes hydropic degeneration and hepatic vessels congestion in STZ-induced diabetic mice. The treatment attenuated the oxidative stress in diabetic mice leading to a reduction of carbonylated protein concentration and increased activity of antioxidant enzymes superoxide dismutase and glutathione peroxidase, compared to untreated diabetic animals. The results also show the beneficial influence of S. boulardii in regulating the hepatic concentration of renin angiotensin system (RAS) peptides. Therefore, our results demonstrated that S. boulardii administration to STZ-induced diabetic mice reduces oxidative stress and normalizes the concentration of RAS peptides, supporting the hypothesis that this yeast may have a role as a potential adjunctive therapy to attenuate diabetes-induced liver injury.
Microanchored borehole fiber optics allows strain profiling of the shallow subsurface
Authors: Zhang Cheng-Cheng , Shi Bin , Zhang Song , Gu Kai , Liu Su-Ping , Gong Xu-Long , Wei Guang-Qing 
Published: April 2021

AbstractVertical deformation profiles of subterranean geological formations are conventionally measured by borehole extensometry. Distributed strain sensing (DSS) paired with fiber-optic cables installed in the ground opens up possibilities for acquiring high-resolution static and quasistatic strain profiles of deforming strata, but it is currently limited by reduced data quality due to complicated patterns of interaction between the buried cables and their surroundings, especially in upper soil layers under low confining pressures. Extending recent DSS studies, we present an improved approach using microanchored fiber-optic cables—designed to optimize ground-to-cable coupling at the near surface—for strain determination along entire lengths of vertical boreholes. We proposed a novel criterion for soil–cable coupling evaluation based on the geotechnical bearing capacity theory. We applied this enhanced methodology to monitor groundwater-related vertical motions in both laboratory and field experiments. Corroborating extensometer recordings, acquired simultaneously, validated fiber optically determined displacements, suggesting microanchored DSS as an improved means for detecting and monitoring shallow subsurface strain profiles.
Strayfield calculation for micromagnetic simulations using true periodic boundary conditions
Authors: Bruckner Florian , Ducevic Amil , Heistracher Paul , Abert Claas , Suess Dieter 
Published: April 2021

AbstractWe present methods for calculating the strayfield in finite element and finite difference micromagnetic simulations using true periodic boundary conditions. In contrast to pseudo periodic boundary conditions, which are widely used in micromagnetic codes, the presented methods eliminate the shape anisotropy originating from the outer boundary. This is a crucial feature when studying the influence of the microstructure on the performance of composite materials, which is demonstrated by hysteresis calculations of soft magnetic structures that are operated in a closed magnetic loop configuration. The applied differential formulation is perfectly suited for the application of true periodic boundary conditions. The finite difference equations can be solved by a highly efficient Fast Fourier Transform method.
Antenatal diagnosis of placenta accreta spectrum after in vitro fertilization-embryo transfer: a systematic review and meta-analysis
Authors: Matsuzaki Shinya , Nagase Yoshikazu , Takiuchi Tsuyoshi , Kakigano Aiko , Mimura Kazuya , Lee Misooja , Matsuzaki Satoko , Ueda Yutaka , Tomimatsu Takuji , Endo Masayuki , Kimura Tadashi 
Published: April 2021

AbstractIncreasing evidence suggests a relationship between in vitro fertilization-embryo transfer (IVF-ET) and placenta accreta spectrum (PAS). Some studies have reported a lower rate of antenatal diagnosis of PAS after IVF-ET compared to PAS with spontaneous conception. This study aimed to review the diagnostic accuracy of PAS after IVF-ET and to explore the relationship between IVF-ET pregnancy and PAS. According to the PRISMA guidelines, a comprehensive systematic review of the literature was conducted through August 31, 2020 to determine the effects of IVF-ET on PAS. In addition, a meta-analysis was conducted to explore the relationship between IVF-ET pregnancy and PAS. Twelve original studies (2011–2020) met the inclusion criteria. Among these, 190,139 IVF-ET pregnancies and 248,534 spontaneous conceptions met the inclusion criteria. In the comparator analysis between PAS after IVF-ET and PAS with spontaneous conception (n = 2), the antenatal diagnosis of PAS after IVF-ET was significantly lower than that of PAS with spontaneous conception (22.2% versus 94.7%, P < 0.01; < 12.9% versus 46.9%, P < 0.01). The risk of PAS was significantly higher in women who conceived with IVF-ET than in those with spontaneous conception (odds ratio [OR]: 5.03, 95% confidence interval [CI]: 3.34–7.56, P < 0.01). In the sensitivity analysis accounting for the type of IVF-ET, frozen ET was associated with an increased risk of PAS (OR: 4.60, 95%CI: 3.42–6.18, P < 0.01) compared to fresh ET. Notably, frozen ET with hormone replacement cycle was significantly associated with the prevalence of PAS compared to frozen ET with normal ovulatory cycle (OR: 5.76, 95%CI 3.12–10.64, P < 0.01). IVF-ET is associated with PAS, and PAS after IVF-ET was associated with a lower rate of antenatal diagnosis. Therefore, clinicians can pay more attention to the presence of PAS during antenatal evaluation in women with IVF-ET, especially in frozen ET with hormone replacement cycle.
Body weight variability and the risk of cardiovascular outcomes in patients with nonalcoholic fatty liver disease
Authors: Kim Mi Na , Han Kyungdo , Yoo Juhwan , Ha Yeonjung , Chon Young Eun , Lee Ju Ho , Simon Tracey G. , Chan Andrew T. , Hwang Seong Gyu 
Published: April 2021

AbstractWe investigated the association between body weight variability and the risks of cardiovascular disease and mortality in patients with nonalcoholic fatty liver disease (NAFLD) using large-scale, nationwide cohort data. We included 726,736 individuals with NAFLD who underwent a health examination between 2009 and 2010. NAFLD was defined as a fatty liver index ≥ 60, after excluding significant alcohol intake, viral hepatitis, and liver cirrhosis. Body weight variability was assessed using four indices, including variability independent of the mean (VIM). During a median 8.1-year follow-up, we documented 11,358, 14,714, and 22,164 cases of myocardial infarction (MI), stroke, and all-cause mortality, respectively. Body weight variability was associated with an increased risk of MI, stroke, and mortality after adjusting for confounding variables. The hazard ratios (HRs) (95% confidence intervals) for the highest quartile, compared with the lowest quartile, of VIM for body weight were 1.15 (1.10–1.20), 1.22 (1.18–1.26), and 1.56 (1.53–1.62) for MI, stroke, and all-cause mortality, respectively. Body weight variability was associated with increased risks of MI, stroke, and all-cause mortality in NAFLD patients. Appropriate interventions to maintain a stable weight could positively affect health outcomes in NAFLD patients.
Log-linear relationship between endogenous insulin secretion and glycemic variability in patients with type 2 diabetes on continuous glucose monitoring
Authors: Miya Aika , Nakamura Akinobu , Handa Takahisa , Nomoto Hiroshi , Kameda Hiraku , Cho Kyu Yong , Nagai So , Ito Yoichi M. , Miyoshi Hideaki , Atsumi Tatsuya 
Published: April 2021

AbstractThe contribution of endogenous insulin secretion to glycemic variability (GV) may differ between patients with impaired insulin secretion and those with preserved secretion. Our objective was to determine the linearity of the relationship between fasting C-peptide (CPR) as a marker of endogenous insulin secretion and GV in type 2 diabetes (T2DM), regardless of the type of antidiabetic treatment. We conducted a prospective observational study using continuous glucose monitoring obtained from 284 Japanese outpatients with T2DM with various HbA1c values and antidiabetic treatment. We constructed a prediction curve of base-line CPR versus coefficient of variation (CV) and identified the clinical factors associated with CV using multiple regression analysis. Fasting CPR showed a significant negative log-linear relationship with CV (P < 0.0001), and the latter being strikingly high in the low-CPR group. The multiple regression analysis showed that low CPR was an independent predictor of high CV (P < 0.0001). The significant correlations were sustained in both patients with/without insulin treatment. The contribution of endogenous insulin secretion to GV depends on the extent of insulin secretion impairment. Fasting CPR may represent a useful indicator of GV instability in T2DM.
Normative Nasalance Values in Vietnamese With Southern Dialect: Vowel and Tone Effects
Authors: Nguyen Duc Minh , Lee Sue Ann S. , Hayakawa Toko , Yamamoto Masahiko , Natsume Nagato 
Published: April 2021

PurposeThe purpose of the current study was to examine normative nasalance values in Vietnamese adult speakers with Southern dialect and to investigate the effects of vowels and tones on nasalance. Previous studies examining nasalance have been mainly conducted with Indo-European languages. Limited information on nasalance is available in tone languages other than Chinese. Furthermore, tone and vowel effects on nasalance scores in tone languages have not been fully examined.MethodNasalance scores of various speech stimuli including passages, syllables, and prolonged vowels were obtained from Vietnamese-speaking adults with Southern dialect (Mage= 23 years) using a nasometer (KayPENTAX 6450).ResultsThe average nasalance scores of Southern Vietnamese adult speakers were 24.16%, 38.17%, and 70.03% for the oral, oral–nasal, and nasal passages, respectively. Southern Vietnamese speakers produced the highest nasalance scores on the vowel /a/, followed by /i/ and /u/. Nasalance scores of stimuli produced with the falling and restricted tone were significantly lower than those produced with the other tones.ConclusionsThe normative nasalance values of the current study will contribute as a reference index for the Vietnamese language. The effects of vowels and tones can also provide insight into the development of nasalance testing stimuli and for characterizing nasalance values across languages.