bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐quality genome‐scale metabolic model of Aurantiochytrium sp. T66
Authors: Simensen Vetle , Voigt André , Almaas Eivind 
Published: February 2021

AbstractThe long‐chain, ω‐3 polyunsaturated fatty acids (PUFAs) (e.g., eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]), are essential for humans and animals, including marine fish species. Presently, the primary source of these PUFAs is fish oils. As the global production of fish oils appears to be reaching its limits, alternative sources of high‐quality ω‐3 PUFAs is paramount to support the growing aquaculture industry. Thraustochytrids are a group of heterotrophic protists with the capability to synthesize and accrue large amounts of DHA. Thus, the thraustochytrids are prime candidates to solve the increasing demand for ω‐3 PUFAs using microbial cell factories. However, a systems‐level understanding of their metabolic shift from cellular growth into lipid accumulation is, to a large extent, unclear. Here, we reconstructed a high‐quality genome‐scale metabolic model of the thraustochytrid Aurantiochytrium sp. T66 termed iVS1191. Through iterative rounds of model refinement and extensive manual curation, we significantly enhanced the metabolic scope and coverage of the reconstruction from that of previously published models, making considerable improvements with stoichiometric consistency, metabolic connectivity, and model annotations. We show that iVS1191 is highly consistent with experimental growth data, reproducing in vivo growth phenotypes as well as specific growth rates on minimal carbon media. The availability of iVS1191 provides a solid framework for further developing our understanding of T66's metabolic properties, as well as exploring metabolic engineering and process‐optimization strategies in silico for increased ω‐3 PUFA production.
Cost‐effectiveness analysis of first‐line treatments for advanced epidermal growth factor receptor‐mutant non‐small cell lung cancer patients
Authors: Li Wen‐Qian , Li Ling‐Yu , Chai Jin , Cui Jiu‐Wei 
Published: February 2021

AbstractObjectivesRecent studies showed prolonged survival for advanced epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC) patients treated with both monotherapies and combined therapies. However, high costs limit clinical applications. Thus, we conducted this cost‐effectiveness analysis to explore an optimal first‐line treatment for advanced EGFR‐mutant NSCLC patients.Materials and MethodsSurvival data were extracted from six clinical trials, including ARCHER1050 (dacomitinib vs. gefitinib); FLAURA (osimertinib vs. gefitinib/erlotinib); JO25567 and NEJ026 (bevacizumab +erlotinib vs. erlotinib); NEJ009 (gefitinib +chemotherapy vs. gefitinib); and NCT02148380 (gefitinib +chemotherapy vs. gefitinib vs. chemotherapy) trials. Cost‐related data were obtained from hospitals and published literature. The effect parameter (quality‐adjusted life year [QALY]) was the reflection of both survival and utility. Incremental cost‐effectiveness ratio (ICER), average cost‐effectiveness ratio (ACER), and net benefit were calculated, and the willingness‐to‐pay (WTP) threshold was set at $30828/QALY from the perspective of the Chinese healthcare system. Sensitivity analysis was performed to explore the stability of results.ResultsWe compared treatment groups with control groups in each trial. ICERs were $1897750.74/QALY (ARCHER1050), $416560.02/QALY (FLAURA), ‐$477607.48/QALY (JO25567), ‐$464326.66/QALY (NEJ026), ‐$277121.22/QALY (NEJ009), ‐$399360.94/QALY (gefitinib as comparison, NCT02148380), and ‐$170733.05/QALY (chemotherapy as comparison, NCT02148380). Moreover, ACER and net benefit showed that the combination of EGFR‐TKI with chemotherapy and osimertinib was of more economic benefit following first‐generation EGFR‐TKIs. Sensitivity analyses showed that the impact of utilities and monotherapy could be cost‐effective with a 50% cost reduction.ConclusionFirst‐generation EGFR‐TKI therapy remained the most cost‐effective treatment option for advanced EGFR‐mutant NSCLC patients. Our results could serve as both a reference for both clinical practice and the formulation of medical insurance reimbursement.
Bladder cancer cell‐intrinsic PD‐L1 signals promote mTOR and autophagy activation that can be inhibited to improve cytotoxic chemotherapy
Authors: Zhang Deyi , Reyes Ryan M. , Osta Erica , Kari Suresh , Gupta Harshita B. , Padron Alvaro S. , Kornepati Anand V. R. , Kancharla Aravind , Sun Xiujie , Deng Yilun , Wu Bogang , Vadlamudi Ratna , Li Rong , Svatek Robert S. , Curiel Tyler J. 
Published: February 2021

AbstractTumor cell‐intrinsic programmed death‐ligand 1 (PD‐L1) signals mediate immunopathologic effects in breast, colon, and ovarian cancers and in melanomas, but bladder cancer (BC) effects are unreported. We show here that BC cell‐intrinsic PD‐L1 signals in mouse MB49 and human RT4, UM‐UC3, and UM‐UC‐14 BC cells regulate important pathologic pathways and processes, including effects not reported in other cancers. α‐PD‐L1 antibodies reduced BC cell proliferation in vitro, demonstrating direct signaling effects. BC cell‐intrinsic PD‐L1 promoted mammalian target of rapamycin complex 1 (mTORC1) signals in vitro and augmented in vivo immune‐independent cell growth and metastatic cancer spread, similar to effects we reported in melanoma and ovarian cancer. BC cell‐intrinsic PD‐L1 signals also promoted basal and stress‐induced autophagy, whereas these signals inhibited autophagy in melanoma and ovarian cancer cells. BC cell‐intrinsic PD‐L1 also mediated chemotherapy resistance to the commonly used BC chemotherapy agents cis‐platinum and gemcitabine and to the mTORC1 inhibitor, rapamycin. Thus, BC cell‐intrinsic PD‐L1 signals regulate important virulence and treatment resistance pathways that suggest novel, actionable treatment targets meriting additional studies. As a proof‐of‐concept, we showed that the autophagy inhibitor chloroquine improved cis‐platinum treatment efficacy in vivo, with greater efficacy in PD‐L1 null versus PD‐L1‐replete BC.
MicroRNA‐340‐5p increases telomere length by targeting telomere protein POT1 to improve Alzheimer's disease in mice
Authors: Li Xin , Zhang Jiangkuan , Yang Yuhang , Wu Qi , Ning Hanbing 
Published: February 2021

AbstractAlzheimer′s disease (AD) is a chronic neurodegenerative disorder which is the primary cause of dementia in the elderly. Telomere attrition has been proposed as a hallmark of aging. Our study aimed to explore the mechanism of the protection of telomere 1 (POT1) in regulating telomere length and affecting cellular senescence in AD. The AD mouse model was established by d‐galactose and aluminum chloride, and the water maze test and dark avoidance test were used to detect the behaviors of mice and confirm the success of AD mouse model. AD cell model was established with HT22 cells induced by Aβ42 oligomers. POT1 expression in the AD model was detected by quantitative real‐time polymerase chain reaction. Cellular telomere length in hippocampal tissue was analyzed by telomere restriction fragment. Localization of intracellular POT1, telomerase, and telomeres was analyzed by immunofluorescence and fluorescence in situ hybridization. Dual‐luciferase assay was used to validate the targeted binding relationship between microRNA‐340‐5p (miR‐340‐5p) and POT1. After inhibiting POT1 expression, the symptoms of AD in mice were improved. Aβ1–42 deposition was reduced, whereas telomere length and telomerase activity was increased. Dual‐luciferase assay verified the binding relationship between miR‐340‐5p and POT1. An increase in miR‐340‐5p expression could alleviate cellular senescence and AD symptoms. miR‐340‐5p increased cellular telomere length and delayed cell senescence by inhibiting POT1 expression to improve AD symptoms. This study made a conclusion that miR‐340‐5p increased cellular telomere length and delayed cell senescence by inhibiting POT1 expression to improve AD symptoms in mice.
Mid‐ventricular obstruction is associated with non‐sustained ventricular tachycardia in patients with hypertrophic obstructive cardiomyopathy
Authors: Nie Changrong , Zhu Changsheng , Xiao Minghu , Yang Qiulan , Meng Yanhai , Wu Rong , Wang Shuiyun 
Published: February 2021

AbstractBackgroundMid‐ventricular obstruction (MVO) is a rare subtype of hypertrophic cardiomyopathy (HCM) but it is associated with ventricular arrhythmia. The relationship between MVO and non‐sustained ventricular tachycardia (NSVT) in HCM patients is unknown.HypothesisThe severity of MVO increases the incidence of NSVT in patients with hypertrophic obstructive cardiomyopathy (HOCM).MethodsFive hundred and seventy‐two consecutive patients diagnosed with HOCM in Fuwai Hospital between January 2015 and December 2017 were enrolled in this study. Holter electrocardiographic and clinical parameters were compared between HOCM patients with and without MVO.ResultsSeventy‐six (13.3%) of 572 patients were diagnosed with MVO. Compared to patients without MVO, those with MVO were much younger, and had a higher incidence of syncope, greater left ventricular (LV) posterior wall thickness, a higher percentage of LV late gadolinium enhancement, and higher prevalence of NSVT. Furthermore, the prevalence of NSVT increased with the severity of MVO (without, mild, moderate or severe: 11.1%, 18.2%, 25.6%, respectively, p for trend < .01). Similarly, the prevalence of NSVT differed among patients with isolated LV outflow tract (LVOTO), both MVO and LVOTO, and isolated MVO (11.1%, 21.3%, 26.6%, respectively, p for trend = .018). In addition to age, diabetes, left atrial diameter, and maximal wall thickness, multivariate analysis revealed the presence of MVO as an independent risk factor for NSVT (Odds ratio 2.69; 95% confidence interval 1.41 to 5.13, p = .003).ConclusionsThe presence and severity of MVO was associated with higher incidence of NSVT in HOCM patients.
Columnar Mesomorphism of Board‐Shaped Perylene, Diketopyrrolopyrrole, Isoindigo, Indigo, and Quinoxalino‐Phenanthrophenazine Dyes
Authors: Eichhorn S. Holger , El‐Ballouli A. O. , Cassar Adam , Kaafarani Bilal R. 
Published: February 2021

AbstractThe properties of organic dyes depend as much on their intermolecular interactions as on their molecular structure. While it is generally predictable what supramolecular structure would be ideal for a specific application, the generation of specific supramolecular structures by molecular design and suitable processing methods remains to be a challenge. A versatile approach to different supramolecular structures has been the application of mesomorphism in conjunction with alignment techniques and self‐assembly at interfaces. Reviewed here is the columnar mesomorphism of board‐shaped dyes perylene, indigo, isoindigo, diketopyrrolopyrrole, and quinoxalinophenanthrophenazine. They generate a larger number of different supramolecular structures than conventional disc‐shaped (discotic) mesogens because of their non‐circular shape and directional intermolecular interactions. The mesomorphism of all but the perylene derivatives is systematically and comprehensively covered for the first time.
Impact of Multiple Prescriptions With Anticholinergic Properties on Adverse Clinical Outcomes in the Elderly: A Longitudinal Cohort Study in Taiwan
Authors: Hsu Wen‐Han , Huang Shih‐Tsung , Lu Wan‐Hsuan , Wen Yu‐Wen , Chen Liang‐Kung , Hsiao Fei‐Yuan 
Published: February 2021

The cumulative effect of multiple pharmaceutics with anticholinergic properties (i.e., anticholinergic burden), can serve as an indicator of suboptimal prescribing in the elderly. Yet, no research is available concerning the effect of different compositions of score on adverse outcomes under the same anticholinergic burden. This population‐based cohort study investigated whether different combinations of medications with anticholinergic properties have different impacts on adverse outcomes in the elderly using the Anticholinergic Risk Scale (ARS) and Anticholinergic Cognitive Burden Scale (ACB) scores. We included 116,043 people aged 65 years and older from Taiwan’s Longitudinal Health Insurance Database and measured their monthly anticholinergic burden over a 10‐year follow‐up period (from January 1, 2002, to December 31, 2011). We analyzed the association between different anticholinergic score compositions and adverse outcomes (emergency department visits, all‐cause hospitalizations, fracture‐specific hospitalizations, and incident dementia) via generalized estimating equations. Cumulative effects of multiple medications with low anticholinergic activity were associated with a greater risk for emergency department visits and all‐cause hospitalizations (emergency department visits for 65–74 year olds (y/o): ACB 1 + 1 + 1, adjusted odds ratio (aOR) 2.05 (1.99–2.12); ACB 1 + 2, aOR 2.04 (1.91–2.17); and ACB 3, aOR 1.62 (1.57–1.66)). In contrast, using medications with greater potency had a greater impact on central adverse outcomes (incident dementia for 65–74 y/o: ACB 1 + 1 + 1, aOR 3.30 (2.84–3.84); ACB 1 + 2, aOR 5.84 (4.59–7.41); and ACB 3, aOR 9.15 (8.38–9.99)). The quantity of anticholinergics (even with low score) an older person used matters in risk of emergency department visit and all‐cause hospitalization but the potency of anticholinergics (i.e., those with high score) matters in risk of fracture‐specific hospitalization and incident dementia.
Evaluation of children's pain expression and behavior using audio visual distraction
Authors: Delgado Alicia , Ok Soo‐Min , Ho Donald , Lynd Tyler , Cheon Kyounga 
Published: February 2021

AbstractObjectivesDental anxiety distresses children and their families with consequent poor oral health and costly pediatric dental services. Children's behaviors could be modified using a distraction technique for improved dental treatment. The study evaluates the effects of an audio‐visual distraction on children's behaviors and pain expressions during dental treatment.Material and MethodsOne hundred healthy children, between 4 and 6 years of age, were randomly assigned to one of two groups: audio visual distraction (AVD, N = 61) group and control (CTR, N = 39) group. The pre and post pain expression was collected using a faces pain rating scale from the participated children. Children's behavior was evaluated using the Frankl behavior rating scale by the assigned dentist. Data was analyzed using chi‐squared tests and analysis of variance.ResultsThe AVD group demonstrated more “definitely positive” behavior (91.8%) compared to the CTR group (35.9%) based on the Frankl scale evaluation from pre‐ and post‐treatment (p < 0.0001). The pain rating scale did not demonstrate a significant difference in post‐treatment pain scales (p = 0.2073) or changes in pain (p = 0.1532) between the AVD group and CTR group.ConclusionsThe AVD is an effective distraction tool for young children during dental treatment regardless of child's subjective pain expression.
Preliminary evaluation of wild bean (Phaseolus spp.) germplasm for resistance to Fusarium cuneirostrum and Fusarium oxysporum
Authors: Haus Miranda J. , Pierz Logan D. , Jacobs Janette L. , Wiersma Andrew T. , Awale Halima E. , Chilvers Martin I. , Buell C. Robin , Cichy Karen E. 
Published: February 2021

AbstractFusarium root rot (Fusarium cuneirostrum; FRR) and Fusarium wilt (Fusarium oxysporum; FW) are major constraints on common bean (Phaseolus vulgaris L.) production worldwide because limited genetic resistance is available in current cultivars. Wild accessions have greater genetic diversity than cultivated germplasm and could provide novel sources of resistance for these diseases. We screened 248 wild bean accessions in a greenhouse setting for responses to both FRR and FW and recorded disease severity; resistance was observed in 21 and 16 accessions, respectively. Accession PI417775 was the most resistant to FRR, exhibiting very few symptoms, whereas accessions PI661845 and PI535441 were the most resistant to FW. Only accessions MX‐GT‐1 and PI535445 were resistant to both FRR and FW. Overall, accessions collected from Andean regions had greater disease symptoms (5.4 ± 1.28 for FRR; 5.8 ± 1.12 for FW) than accessions collected from Middle America (4.7 ± 1.33 for FRR; 4.42 ± 1.04 for FW), though the highest and lowest disease scores for FRR were both found in the Middle American accessions. Introgression of Fusarium resistance from wild bean accessions into cultivated lines provides an avenue to improve disease resistance in elite cultivars.
Multiple applications of mepiquat chloride enhanced development of plant‐wide fruits from square initiation to boll opening in cotton
Authors: Liao Baopeng , Ren Xiaoming , Du Mingwei , Eneji A. Egrinya , Tian Xiaoli , Li Zhaohu 
Published: February 2021

AbstractMepiquat chloride (MC) has been widely used for the field management of cotton (Gossypium hirsutum L.) and could enhance yield and quality. However, it is not completely clear how MC influences cotton development. A field study was conducted during 2011∼2012 cotton growing seasons to determine the effects of multiple MC applications (from the late seedling stage to near cutout) on the development of each fruit by calendar days and thermal time. Two cotton cultivars (GX3 and XK4) were used for the study. The MC application significantly hastened the appearance of squares across fruiting positions by 0.4–2.9 d in 2011; and those on upper (from the 11th) fruiting branches and on inner (first two) fruiting nodes of middle (5th‐10th) fruiting branches under MC treatment formed 1.8–3.8 d earlier in 2012 compared with control. Also, MC decreased the duration from squaring to flowering by 0.1–0.3 d, and that from bloom to boll opening by 0.9–2.1 d. The MC application reduced the growing degree days (GDD) of most fruiting positions from planting to squaring owing to the early onset of squares. However, it increased the GDD of cotton bolls on the upper fruiting branches during maturation period, presumably due to their early set which exposed them to the higher temperatures during development. These results have improved our understanding of MC‐induced earliness in cotton and could help growers to optimize earliness management.
A Peanut‐Like Sb‐Embedded Polyoxoniobate Cage for Hydrolytic Decomposition of Chemical Warfare Agent
Authors: Wu Yan‐Lan , Zhong Zhuo‐Hao , Wu Ping‐Xin , Sun Yan‐Qiong , Li Xin‐Xiong , Zheng Shou‐Tian 
Published: February 2021

AbstractA Sb‐embedded polyoxoniobate has been originally synthesized under hydrothermal conditions. Particularly, the peanut‐like [Sb2Nb24O72]18− cluster cage in 1 with C2h symmetry is composed of two 9‐nuclear {SbNb9O33} motifs and one {Nb6O24} crown‐shaped ring. The compound 1 present the novel structure of Sb‐substituted sandwich‐type polyoxoniobate with antimoniobate cluster cage. Decomposition catalytic studies indicate that compound 1 exhibits good hydrolytic activity and stability on the degradation of nerve agent simulant dimethylphosphonate (DMMP).
Synthesis of Polycyclic Chromene Cores through Gold (I)‐Catalyzed Intramolecular Hydroarylation Reaction (IMHA)
Authors: Arcadi Antonio , Fabrizi Giancarlo , Fochetti Andrea , Franzini Roberta , Ghirga Francesca , Goggiamani Antonella , Iazzetti Antonia , Marrone Federico , Serraiocco Andrea 
Published: February 2021

AbstractA regioselective gold (I)‐catalyzed approach for the construction of polycyclic chromene cores has been developed. The reaction proceeds in good to excellent yields under mild condition with a broad range of substrates providing a simple and efficient tool for the synthesis of pyranochromene derivatives. Moreover, the regiochemical control of the annulation of unsymmetrically substituted propargylic ethers has been investigated focusing on electronic/steric effects of the ligands of gold complexes as well as on the electronic effects of the groups on the aromatic rings.
Critical stable sectional area of downstream surge tank of hydropower plant with sloping ceiling tailrace tunnel
Authors: Guo Wencheng , Zhu Daoyi 
Published: February 2021

AbstractThis paper investigates the critical stable sectional area (CSSA) of downstream surge tank (DST) of hydropower plant with sloping ceiling tailrace tunnel (SCTT). Firstly, two types of nonlinear mathematical model of hydropower plant with SCTT during transient process are established. Then, the criterion of operation stability of hydropower plant is obtained based on nonlinear stability theory. Formulae for CSSAs of DST under two types of mathematical model are derived. Finally, the similarities, differences, and relationships of different CSSAs are clarified. The effect mechanisms of the assumption of steady power output of hydro‐turbine and the SCTT on CSSA of DST are revealed. The recommended use conditions of different CSSAs are explained. The results indicate that, under the assumption of steady power output of hydro‐turbine, the formula for CSSA of DST of hydropower plant with SCTT is analytical and has a simple expression. Under the complete model, the formula for CSSA of DST of hydropower plant with SCTT is not analytical and has a complicated expression. The former formula is suggested to be given the priority of use because of good precision and concise expression. SCTT can improve the stability of hydropower plant and decrease the CSSA of DST.
Vulnerability of Aquatic Insect Species to Insecticides, Depending on Their Flight Period and Adult Life Span
Authors: Kjær Christian , Sørensen Peter Borgen , Wiberg-Larsen Peter , Bak Jesper , Bruus Marianne , Strandberg Beate , Larsen Søren Erik , Rasmussen Jes Jessen , Strandberg Morten 
Published: February 2021

Abstract
Effects of insecticides on terrestrial adult life stages of otherwise aquatic insects, such as mayflies (Ephemeroptera), stoneflies (Plecoptera), and caddisflies (Trichoptera), are largely unknown. In the present study, a risk model was used to pinpoint the species most likely to experience effects due to spray drift exposure during the adult life stage. Using data from an earlier case study with lambda-cyhalothrin, 6 species with different life cycle traits were used to explore how life cycle characteristics may influence vulnerability. In addition, we performed a generic calculation of the potential effect on the terrestrial life stages of 53 species (including 47 species with unknown sensitivity). Our approach incorporated temporal and spatial distribution of both the insect and the insecticide, creating different exposure conditions among species due to variation in the relative proportion of the populations present at the time of insecticide spraying. The Ephemeroptera species represented were least vulnerable due to their extremely short adult life span and relatively short flight period. Based on their life cycle characteristics, Plecoptera and Trichoptera species were more vulnerable. These vulnerable species segregated into 2 distinct groups; one with a long adult life span to emergent period ratio and another with a high overlap between emergent period and spraying season. We therefore recommend that future ecotoxicological tests be done on species with these life cycle characteristics. Environ Toxicol Chem 2021;40:1778–1787. © 2021 SETAC