bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of rare coding variants in 200,000 exome‐sequenced subjects reveals novel genetic risk factors for type 2 diabetes
Authors: Curtis David 
Published: July 2021

AbstractAimsThe study aimed to elucidate the effects of rare genetic variants on the risk of type 2 diabetes (T2D).Materials and methodsWeighted burden analysis of rare variants was applied to a sample of 200,000 exome‐sequenced participants in the UK Biobank project, of whom over 13,000 were identified as having T2D. Variant weights were allocated based on allele frequency and predicted effect, as informed by a previous analysis of hyperlipidaemia.ResultsThere was an exome‐wide significant increased burden of rare, functional variants in three genes, GCK, HNF4A and GIGYF1. GIGYF1 has not previously been identified as a diabetes risk gene and its product appears to be involved in the modification of insulin signalling. A number of other genes did not attain exome‐wide significance but were highly ranked and potentially of interest, including ALAD, PPARG, GYG1 and GHRL. Loss of function (LOF) variants were associated with T2D in GCK and GIGYF1 whereas nonsynonymous variants annotated as probably damaging were associated in GCK and HNF4A. Overall, fewer than 1% of T2D cases carried one of these variants. In HNF1A and HNF1B there was an excess of LOF variants among cases but the small numbers of these fell short of statistical significance.ConclusionsRare genetic variants make an identifiable contribution to T2D in a small number of cases but these may provide valuable insights into disease mechanisms. As larger samples become available it is likely that additional genetic factors will be identified.
Circular RNA_0001946 is insufficiently expressed in tumor tissues, while its higher expression correlates with less lymph node metastasis, lower TNM stage, and improved prognosis in NSCLC patients
Authors: Zhang Minghua , Wen Fangjing , Zhao Ke 
Published: July 2021

AbstractObjectiveCircular RNA_0001946 (circ_0001946) inhibits tumor progression but promotes chemosensitivity in non‐small‐cell lung cancer (NSCLC); however, its correlation with tumor features and prognosis in NSCLC patients is still unclear; therefore, this study aimed to investigate these issues.MethodsA total of 284 NSCLC patients were retrospectively analyzed. Circ_0001946 expression in tumor (n = 284) and adjacent (n = 125) tissues was detected by the reverse transcription‐quantitative polymerase chain reaction. Meanwhile, patients’ clinical characteristics, recurrence, and survival data were extracted from the electrical database.ResultsCirc_0001946 expression in adjacent tissues was over 3‐folds as that in tumor tissues (P < .001). Meanwhile, higher tumor circ_0001946 expression was correlated with less lymph node metastasis (P < .001) and decreased TNM stage (P = .001), but did not correlate with other clinicopathological features. Moreover, higher tumor circ_0001946 expression was associated with prolonged disease‐free survival (DFS) (P < .001) and overall survival (OS) (P < .001), respectively. Subgroup analyses revealed that higher tumor circ_0001946 was correlated with improved DFS in patients with TNM stage I, II, or III, respectively (all P < .05), while only correlated with prolonged OS in patients with TNM stage III (P = .037), but not in patients with TNM stage I or II. Further multivariate Cox's proportional hazard regression analyses suggested that higher tumor circ_0001946 expression could independently predict improved DFS (P < .001, hazard ratio (HR) = 0.719) and OS (P < .001, HR = 0.746), respectively.ConclusionCirc_0001946 is insufficiently expressed in tumor tissues, whereas its higher expression correlates with less lymph node metastasis, reduced TNM stage, and improved prognosis in NSCLC patients.
L‐proline modified inactivated lipase and its immobilization on cellulose‐based material: stability and enantioselectivity
Authors: Ozyilmaz Elif , Caglar Ozge , Yilmaz Mustafa 
Published: July 2021

AbstractBACKGROUNDChemical modification is a simple, low cost, very fast and easy production that has no limits as to the nature of the groups introduced into the enzymes. Chemical modification may be directed to improve enzyme stability, as well as selectivity, specificity, and activity.RESULTSCandida rugosa lipase (CRL) was immobilized onto a cellulose‐based support. The native, inactivated, and immobilized lipases were modified by the reaction of L‐proline (Prl) in the presence of coupling reagent (EDC). The catalytic properties of the modified lipases were evaluated by hydrolysis of p‐nitrophenylpalmitate and the enantioselective hydrolysis of racemic naproxen methyl ester. It was observed that by chemical modification with proline, the hydrolytic activities of native, inactivated, and immobilized lipases increased 2.4, 11.0, and 2.2‐fold, respectively. The immobilized lipase retained 64% of its activity after 120 min at 60 °C, while immobilized L‐proline modified lipase was found to retain 72%. It was also found that the immobilized inactivated lipase kept 44% of its activity at 60 °C for 2 h, while the immobilized L‐proline modified inactivated lipase retained their activity at 65%. In addition, the attained results of the best enantioselectivity of CRL‐Prl exhibited a 2.2‐fold improvement compared to the native enzyme.CONCLUSIONThe method is simple, cost‐effective, very fast, and it can obtain stronger biocatalysts. It was understood that a lipase lost its activity and could be reused after being simply modified with L‐proline. This study predicts that such facile chemical modifications will open new avenues to develop industrially important biocatalyst with superior catalytic properties. © 2021 Society of Chemical Industry (SCI).
Optimization of calcium pectinate gel production from high methoxyl pectin
Authors: Duan Hanying , Wang Xiaoyun , Azarakhsh Nima , Wang Chao , Li Meng , Fu Guiming , Huang Xuesong 
Published: July 2021

AbstractBACKGROUNDCalcium pectinate (CaP) gel is traditionally prepared by de‐esterifying high methoxyl pectin (HMP) to low methoxyl pectin (LMP), followed by gelation with calcium. To save both time and cost in the production of CaP gel, an alternative method was developed by the addition of CaCl2 to HMP at alkaline pH. To optimize the production, response surface methodology (RSM) was used to investigate the effects of temperature (30–50 °C), time (20–40 min) and pH (8–10) on yield, calcium content of the CaP gel and the degree of esterification (DE) of pectin following decalcification of CaP (DC‐pectin).RESULTSThe linear term for pH had a significant effect (P < 0.01) on all three responses, whereas interaction effects were not significant (P > 0.01), except on the calcium content (P < 0.01). The optimized process conditions (temperature, time and pH) to obtain maximum CaP‐HMP gel yield (88.83%) were 50 °C, 40 min and pH 9.6, and for the highest calcium content (97.23 mg g–1) they were 40 °C, 30 min and pH 9.7. DC‐pectin was a typical LMP with DE varying from 26.92% to 50.33%. The DE of DC‐pectin could be predicted by a model that proved significant (R2 = 0.9888).CONCLUSIONThe optimum conditions were established to produce CaP gels from HMP with high yield and calcium content. Also, LMP with predictable DE can be produced following a significant model. This study provides new insights into the production and application of CaP gel. © 2021 Society of Chemical Industry.
Characteristics of the Dual Board‐Certified Sleep Otolaryngology Workforce
Authors: Yu Phoebe K. , Gadkaree Shekhar K. , Li Joanna , McCarty Justin C. , Huyett Phillip , Bergmark Regan W. 
Published: July 2021

ObjectiveSleep medicine is a multidisciplinary field that includes otolaryngology. After 2011, sleep medicine board eligibility required completion of a dedicated sleep medicine fellowship. The objective of our study is to describe the characteristics and geographic distribution of the dual board‐certified sleep otolaryngology workforce and to assess the impact of the 2011 change.MethodsA cross‐sectional analysis of sleep‐certified otolaryngologists registered with the American Board of Otolaryngology‐Head and Neck Surgery in 2019 was performed to characterize the sleep otolaryngology workforce. County and regional analysis of provider density was conducted by comparing provider characteristics with county‐level data from the United States Census Bureau.ResultsThere were 275 active dual board‐certified sleep otolaryngologists, or approximately 1 for every 1.12 million Americans. 77.8% were in private practice and 2.9% had American Society of Pediatric Otolaryngology membership. Eighty‐eight percent were male, with females more likely than males to be in an academic setting (36.4% for females compared to 20.2% for males; P = .045). The South Atlantic and South Central regions had the highest number of sleep board‐certified otolaryngologists per capita. Before 2011, an average of 75.7 otolaryngologists took the sleep board exam per 2‐year cycle, compared to 14.3 otolaryngologists after 2011 (P = .029).ConclusionThere are few dual board‐certified sleep otolaryngologists across the country, which may affect care for patients with sleep‐disordered breathing. Increased resident exposure and otolaryngology training in sleep medicine can strengthen the otolaryngology contribution to the multidisciplinary care of these patients.Level of Evidence4 Laryngoscope, 131:E2712–E2717, 2021
Prenatal cerebellar growth is altered in congenital diaphragmatic hernia on ultrasound
Authors: Van der Veeken Lennart , Russo Francesca M. , Litwinska Ewelina , Gomez Olga , Emam Doaa , Lewi Liesbeth , Basurto David , Van der Veeken Stephan , De Catte Luc , Gratacos Eduard , Eixarch Elisenda , Nicolaides Kypros , Deprest Jan 
Published: July 2021

AbstractObjectiveChildren with congenital diaphragmatic hernia (CDH) are at risk for neurodevelopmental delay. Herein we report on prenatal changes in biometry and brain perfusion in fetuses with isolated CDH.Study DesignThis retrospective study evaluated fetuses with isolated, left‐sided CDH in three European referral centers. Abdominal circumference (AC), femur length (FL), head circumference (HC), transcerebellar diameter (TCD), middle cerebral artery (MCA) Doppler, and ventricular width (VW) were assessed during four gestational periods (<24 weeks, 25–28 weeks, 29–32 weeks, >33 weeks). Z‐scores were calculated, and growth curves were created based on longitudinal data.ResultsIn 367 fetuses, HC, AC and FL were within normal ranges throughout gestation. The TCD diminished with advancing gestational age to fall below the fifth percentile after 32 weeks. A less pronounced but similar trend was seen in VW. The peak systolic velocity of the MCA was consistently approximately 10% lower than normal. Disease severity was correlated to TCD (p = 0.002) and MCA doppler values (p = 0.002). There were no differences between fetuses treated with FETO and those managed expectantly.ConclusionFetuses with isolated left‐sided CDH have a small cerebellum and reduced MCA peak systolic velocity. Follow up studies are necessary to determine the impact of these changes on neurodevelopment.
Association between methylphenidate and risk of myocardial infarction: A multinational self‐controlled case series study
Authors: Jeong Han Eol , Lee Hyesung , Lai Edward Chia‐Cheng , Liao Tzu‐Chi , Man Kenneth K. C. , Wong Ian C. K. , Coghill David , Chi Mei‐Hung , Hsieh Cheng‐Yang , Shin Ju‐Young 
Published: July 2021

AbstractPurposeTo investigate the association between use of methylphenidate and risk of myocardial infarction among Asians.MethodsWe conducted a multinational self‐controlled case series study using nationwide healthcare databases of South Korea (2002–2018), Taiwan (2004–2015), and Hong Kong (2001–2016). Of patients with myocardial infarction who were also prescribed methylphenidate within the observation period, methylphenidate use was classified into four mutually exclusive periods by each person‐day: exposed (exposed to methylphenidate), pre‐exposure (prior to the first methylphenidate prescription), washout (after the end of methylphenidate treatment), and baseline (unexposed to methylphenidate). Risk of myocardial infarction among the three periods of methylphenidate use was compared to the baseline period using conditional Poisson regression analysis to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CIs).ResultsWe identified 2104, 484, and 30 patients from South Korea, Taiwan, and Hong Kong, respectively. Risk of myocardial infarction was the highest during the pre‐exposure period in all three populations: South Korea, pre‐exposure (IRR 3.17, 95% CI 3.04–3.32), exposed (1.05, 1.00–1.11), washout (1.92, 1.80–2.04); Taiwan, pre‐exposure (1.97, 1.78–2.17), exposed (0.72, 0.65–0.80), washout (0.56, 0.46–0.68); Hong Kong, pre‐exposure (18.09, 8.19–39.96), exposed (9.32, 3.44–25.28), washout (7.69, 1.72–34.41). Following stratification for age and sex, the trends remained analogous to the main findings across all three populations.ConclusionsAlthough a positive association between initiating methylphenidate and the onset of myocardial infarction was observed, the risk was the highest in the period before its initiation. Thus, this multinational study suggests there was no causal relationship between methylphenidate and myocardial infarction among Asians.
Fabrication and Characterization of Saffron Stamen Aqueous Extract Controlled Release System as Potential Topical Treatment of Thermal Burn Wounds
Authors: Burak Ozdemir MsC. , Burcin Piskin Mehmet , Bahar Gok MsC. , Demir Neslihan , Budama‐Kilinc Yasemin 
Published: July 2021

AbstractIn our study, we aimed the preparation of Saffron stamen aqueous extract (SSAE) loaded chitosan nanoparticles (CNPs) to be used topically for thermal burns. First, biological activity tests such as DNA binding, DNA cleavage and antibacterial activity were performed to determine the effectiveness of SSAE to be encapsulated. Additionally, a genotoxicity test was performed for the reliability of SSAE. Ionic gelation method was used for encapsulation, and SSAE‐loaded CNPs were obtained. Average particle size, zeta potential, polydispersity index (PdI), morphology, and releasing kinetics of the SSAE‐loaded CNPs and blank CNPs were determined. DNA binding showed that SSAE interacted with DNA electrostatically. It was determined that all doses of SSAE used in hydrolytic and oxidative DNA cleavage experiments cleave DNA. As a result of the Ames / Salmonella test, it was found that 1,25 mg SSAE was not genotoxic. Then, this concentration was used in nanoparticle synthesis. As a result of DLS analysis, it was determined that SSAE‐loaded CNPs have an average size of 57.61±1.234 nm, 0.175±0.008 PdI, and +14±0.755 mV zeta potential. Encapsulation efficiency and loading capacity of SSAE‐loaded CNPs calculated as 71.76 % and 2,64 % respectively. As a result of releasing kinetics, it was determined that 79.54 % of SSAE was released after 168 hours. Antibacterial results revealed that SSAE loaded CNPs were more effective against bacteria than blank SSAE.
Synthesis, In Vitro Antiprotozoal Activity and Cytotoxicity of New Thymol Carbonate Derivatives
Authors: Clemente Camila M. , Ravetti Soledad , Allemandi Daniel A. , Hergert Lisandro Y. , Pineda Tatiana , Robledo Sara M. 
Published: July 2021

AbstractConsidering the biological properties of thymol and its derivatives and the urgency of effective drugs for neglected tropical diseases, we report the synthesis of a novel series of carbonates of thymol, using N,N‐carbonyldiimidazole and several aliphatic alcohols. The in vitro leishmanicidal, trypanocidal, antiplasmodial and cytotoxic activities of thymol and derivatives were also studied together with the in silico physicochemical and pharmacokinetic properties of synthesized compounds. Both, thymol and carbonate derivatives although were cytotoxic to mammal U‐937 cells, they were also highly active against Plasmodium falciparum and Trypanosoma cruzi parasites. When relating the cytotoxicity with antiparasitic activity all compounds, except 1 g and 1 i were more selective against parasites than against the mammal cells. Computational analysis indicates good oral bioavailability for all compounds. Results suggest that thymol and their carbonate derivatives have promising therapeutic potential as antiplasmodial, trypanocidal and leishmanicidal agents; nonetheless further studies are needed to validate their efficacy as antiparasitic drugs in in vivo assays.
Ultrasensitive and Selective Protein Recognition with Nanobody‐Functionalized Synthetic Nanopores
Authors: Duznovic Ivana , Gräwe Alexander , Weber Wadim , Müller Lena K. , Ali Mubarak , Ensinger Wolfgang , Tietze Alesia , Stein Viktor 
Published: July 2021

AbstractThe development of flexible and reconfigurable sensors that can be readily tailored toward different molecular analytes constitutes a key goal and formidable challenge in biosensing. In this regard, synthetic nanopores have emerged as potent physical transducers to convert molecular interactions into electrical signals. Yet, systematic strategies to functionalize their surfaces with receptor proteins for the selective detection of molecular analytes remain scarce. Addressing these limitations, a general strategy is presented to immobilize nanobodies in a directional fashion onto the surface of track‐etched nanopores exploiting copper‐free click reactions and site‐specific protein conjugation systems. The functional immobilization of three different nanobodies is demonstrated in ligand binding experiments with green fluorescent protein, mCherry, and α‐amylase (α‐Amy) serving as molecular analytes. Ligand binding is resolved using a combination of optical and electrical recordings displaying quantitative dose–response curves. Furthermore, a change in surface charge density is identified as the predominant molecular factor that underlies quantitative dose–responses for the three different protein analytes in nanoconfined geometries. The devised strategy should pave the way for the systematic functionalization of nanopore surfaces with biological receptors and their ability to detect a variety of analytes for diagnostic purposes.
Nanoparticle‐Mediated Blocking of Excessive Inflammation for Prevention of Heart Failure Following Myocardial Infarction
Authors: Kwon Sung Pil , Hwang Byung‐Hee , Park Eun‐Hye , Kim Han Young , Lee Ju‐Ro , Kang Mikyung , Song Seuk Young , Jung Mungyo , Sohn Hee Su , Kim Eunmin , Kim Chan Woo , Lee Kwan Yong , Oh Gyu Chul , Choo Eunho , Lim Songhyun , Chung Yeonseok , Chang Kiyuk , Kim Byung‐Soo 
Published: July 2021

AbstractSevere cardiac damage following myocardial infarction (MI) causes excessive inflammation, which sustains tissue damage and often induces adverse cardiac remodeling toward cardiac function impairment and heart failure. Timely resolution of post‐MI inflammation may prevent cardiac remodeling and development of heart failure. Cell therapy approaches for MI are time‐consuming and costly, and have shown marginal efficacy in clinical trials. Here, nanoparticles targeting the immune system to attenuate excessive inflammation in infarcted myocardium are presented. Liposomal nanoparticles loaded with MI antigens and rapamycin (L‐Ag/R) enable effective induction of tolerogenic dendritic cells presenting the antigens and subsequent induction of antigen‐specific regulatory T cells (Tregs). Impressively, intradermal injection of L‐Ag/R into acute MI mice attenuates inflammation in the myocardium by inducing Tregs and an inflammatory‐to‐reparative macrophage polarization, inhibits adverse cardiac remodeling, and improves cardiac function. Nanoparticle‐mediated blocking of excessive inflammation in infarcted myocardium may be an effective intervention to prevent the development of post‐MI heart failure.
Maximizing Magnesiation Capacity of Nanowire Cluster Oxides by Conductive Macromolecule Pillaring and Multication Intercalation
Authors: Yao Zhenguo , Yu Yifan , Wu Qingping , Cui Mengnan , Zhou Xuejun , Liu Jianjun , Li Chilin 
Published: July 2021

AbstractMagnesium metal batteries (MMBs) have obtained the reputation owing to the high volumetric capacity, low reduction potential, and dendrite‐free deposition behavior of the Mg metal anode. However, the bivalent nature of the Mg2+ causes its strong coulombic interaction with the cathode host, which limits the reaction kinetics and reversibility of MMBs, especially based on oxide cathodes. Herein, a synergetic modulation of host pillaring and electrolyte formulation is proposed to activate the layered V2O5 cathode with expanded interlayers via sequential intercalations of poly(3,4‐ethylenedioxythiophene) (PEDOT) and cetyltrimethylammonium bromide (CTAB). The preservation of bundled nanowire texture, copillaring behavior of PEDOT and CTA+, dual‐insertion mode of Mg2+ and MgCl+ at cathode side enable the better charge transfers in both the bulk and interface paths as well as the interaction mitigation effect between Mg‐species cations and host lattices. The introduction of CTA+ as electrolyte additive can also lower the interface resistance and smoothen the Mg anode morphology. These modifications endow the full cells coupled with metallic Mg anode with the maximized reversible capacity (288.7 mAh g‐1) and superior cyclability (over 500 cycles at 500 mA g‐1), superior to most already reported Mg‐ion shuttle batteries even based on passivation‐resistant non‐Mg anodes or operated at higher temperatures.
Assessment of existing reinforced‐concrete bridges under road‐traffic loads according to the new Italian guidelines
Authors: Cosenza Edoardo , Losanno Daniele 
Published: July 2021

AbstractThe Italian “Guidelines for risk classification, safety assessment and structural health monitoring of existing bridges” were recently approved to define the technical principles for the management of the national network of existing bridges. This is a powerful tool to establish a common framework for risk mitigation and safety assessment of reinforced concrete (R.C.) bridges that represent most of the existing stock. The guidelines are code‐based and allow practitioners to deal with the concepts behind the modern design in terms of target reliability and partial safety factors as well as properly developed traffic‐load models. This paper illustrates a novel methodology for safety assessment and performance class definition of existing R.C. bridges according to the guidelines. A prestressed R.C. bridge is finally presented as a case study to show the completeness of the procedure.
Monte Carlo simulation of proton- and neutron-induced radiation damage in a tantalum target irradiated by 70 MeV protons
Authors: Ophoven Niklas , Mauerhofer Eric , Li Jingjing , Rücker Ulrich , Zakalek Paul , Baggemann Johannes , Gutberlet Thomas , Brückel Thomas , Langer Christoph 
Published: July 2021

AbstractBeams of free neutrons are an important probe to analyze the structure and dynamics of condensed matter and are produced at neutron research reactors, neutron spallation sources or compact accelerator-based neutron sources (CANS). An efficient construction of CANS with a maximized neutron yield and brilliance requires reliable knowledge of the consequences of radiation-induced material damage, the predominating bottleneck of a target’s lifetime. In the framework of the Jülich High-Brilliance neutron Source project, the impact of proton- and neutron-induced material damage of a tantalum target was investigated. The Monte Carlo codes FLUKA and SRIM were utilized to extract the number of displacements per atom resulting from atomic rearrangements. The simulations performed distinctly identify the rear of the neutron target as the most vulnerable area, with the protons as main damage contributors. The minor contribution of neutrons is a material-specific phenomenon due to their high mean free path length in tantalum. Numerical results of the simulations served to calculate average and peak damage rates $${R}_{\mathrm{d}}$$

R
d

(dpa/s), both in turn scaled to annual displacement doses for continuous operation in a full power year (dpa/fpy). Supplemented by the literature, a minimum target lifetime $$\tau _{\min }$$

τ
min

of 2.6 years (33 Ah) is concluded.