bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Upadacitinib in Patients With Active Ankylosing Spondylitis and an Inadequate Response to Nonsteroidal Antiinflammatory Drug Therapy: One‐Year Results of a Double‐Blind, Placebo‐Controlled Study and Open‐Label Extension
Authors: Deodhar Atul , van der Heijde Désirée , Sieper Joachim , Van den Bosch Filip , Maksymowych Walter P. , Kim Tae‐Hwan , Kishimoto Mitsumasa , Ostor Andrew , Combe Bernard , Sui Yunxia , Chu Alvina D. , Song In‐Ho 
Published: July 2021

ObjectiveTo report the efficacy and safety of upadacitinib through 1 year in patients with ankylosing spondylitis (AS).MethodsIn the SELECT‐AXIS 1 study, adults with active AS and an inadequate response to nonsteroidal antiinflammatory drugs were randomized to receive upadacitinib 15 mg once daily or placebo. At week 14, patients who had been randomized to receive placebo were switched to upadacitinib, and all patients continued in the open‐label extension and received upadacitinib up to week 104; interim data up to week 64 are reported herein.ResultsOf 187 patients, 178 completed week 14 on study drug and entered the open‐label extension. Similar proportions of patients in either group (continuous upadacitinib or placebo‐to‐upadacitinib) achieved Assessment of SpondyloArthritis international Society 40% response (ASAS40) or Ankylosing Spondylitis Disease Activity Score (ASDAS) showing low disease activity at week 64: ≥70% of patients achieved these end points based on nonresponder imputation (NRI) and ≥81% based on as‐observed analyses. Furthermore, ≥34% (NRI) and ≥39% (as‐observed analysis) achieved ASDAS showing inactive disease or ASAS showing partial remission at week 64. Mean changes from baseline (week 0) to week 64 in pain, function, and inflammation showed consistent improvement or sustained maintenance through the study. Among 182 patients receiving upadacitinib (237.6 patient‐years), 618 adverse events (260.1 per 100 patient‐years) were reported. No serious infections, major adverse cardiovascular events, venous thromboembolic events, gastrointestinal perforation, or deaths were reported.ConclusionUpadacitinib 15 mg once daily showed sustained and consistent efficacy over 1 year. Patients who switched from placebo to upadacitinib at week 14 showed similar efficacy versus those who received continuous upadacitinib.
Using the Toxic Substance Control Act for Source Water Protection
Authors: Schlea Stephanie Hayes , Wilkes Wendi 
Published: July 2021

Key TakeawaysUS environmental laws should work in concert to mitigate risk from harmful chemical substances and mixtures. This can be done by considering potential risks from drinking water under the Toxic Substances Control Act's (TSCA's) evaluations and regulatory determinations.Drinking water associations are working with the US Environmental Protection Agency (USEPA) to ensure TSCA considers drinking water source protection in regulatory actions.Water systems interested in using TSCA to better protect drinking water sources should engage directly with USEPA through public comment opportunities or through their professional associations.
Integrating Supply Management With Finance and Asset Management
Authors: James Felicia , Baehr James M. 
Published: July 2021

Key TakeawaysEffective utility management focuses on implementing infrastructure management strategies, addressing financial viability, and optimizing operations.Allocating resources to renew critical infrastructure shifts them from optional budget items to mandatory expenditures.The well‐established management trio focused on budget–schedule–quality is evolving into a new paradigm of asset management–financial management–supply management.
Apprenticeships and Internships: Opportunities for Equity and Inclusion
Authors: Curtis Catherine , Jones Sherri 
Published: July 2021

Key TakeawaysOn‐the‐job training programs can help the water industry build and maintain a skilled and diverse workforce.The benefits are numerous for participants in apprenticeship and internship programs, with a well‐organized plan that offers training in specific skills, job assurance and potential for advancement, personal development, and financial stability.Where small or medium‐sized water utilities don't see the feasibility of developing their own formalized on‐the‐job training, a regional program is a possible solution.
Which has more complications?—Shockwave lithotripsy versus endoscopic treatment of renal calculi with 1‐year follow‐up in an Australian population
Authors: Farag Matthew , Jack Gregory S. , Papa Nathan , Wong Lih‐Ming , Bolton Damien M. , Lenaghan Daniel 
Published: July 2021

AbstractIntroduction and objectivesRenal calculi are a common medical problem with incidence rates calculated to be approximately 6%‐9% in men & 3%‐4% in women worldwide. Incidence appears to be increasing. This study compares emergency presentations and unplanned readmissions between extracorporeal shock wave lithotripsy (SWL) and pyeloscopic stone treatment in the population of Victoria, Australia after 1‐year follow‐up.MethodsThis is a population study comparing all patients with renal calculi electively treated with SWL to those initially treated with flexible ureteroscopy (URS) in Victoria, Australia. We used data linkage across the state of Victoria to follow patients treated with either modality in a 12 months period (with no urological surgery in the prior 12 months). Each patient's emergency presentations and subsequent re‐admissions were followed up for 1 year after their index treatment to assess for stone complications. We assessed for selection bias between the two patient groups by comparing age, gender, insurance status, geographical location, and comorbidity scores.ResultsWe report stone‐related complications for 739 flexible URS and 1317 SWL procedures undertaken across public and private hospitals in Victoria over 12 months. Unplanned emergency presentations within 60‐days of surgery were (22/739) 2.98% for flexible URS patients and (83/1317) 6.30% for SWL patients (P = .001); however, at 12 months, this became 16.23% (120/739) for flexible URS patients and 12.83% (169/1317) for SWL patients (P = .034). Flexible URS patients were more likely than SWL patients to be admitted with 71.76% of flexible URS versus 53.97% of SWL patients requiring an admission at any given emergency presentation (P ≤ .001) within 12 months. On multivariate analysis, both flexible URS ([OR] 1.67, CI 1.23‐2.26, P = .001) and being a public patient ([OR] 3.06, CI 2.24‐4.18, P < .001) significantly increased the likelihood that patients required an unplanned re‐admission within 12 months.ConclusionsThere is work needed to reduce emergency presentations and unplanned re‐admissions after both SWL and flexible URS. At 12‐months follow‐up, unplanned emergency visits and re‐admission rates were significantly more after flexible URS. Symptoms at emergency presentation indicate that better education regarding stent management is needed, especially in the public health care system.
Application of peptide nucleic acid in electrochemical nucleic acid biosensors
Authors: Sun Haobo , Kong Jinming , Zhang Xueji 
Published: July 2021

AbstractThe early diagnosis of major diseases, such as malignant tumors, has always been an important field of research. Through screening, early detection of such diseases, and timely and effective treatment can significantly improve the survival rate of patients and reduce medical costs. Therefore, the development of a simple detection method with high sensitivity and strong specificity, and that is low cost is of great significance for the diagnosis and prognosis of the disease. Electrochemical DNA biosensing analysis is a technology based on Watson Crick base complementary pairing, which uses the capture probe of a known sequence to specifically recognize the target DNA and detect its concentration. Because of its advantages of low cost, simple operation, portability, and easy miniaturization, it has been widely researched and has become a cutting‐edge topic in the field of biochemical analysis and precision medicine. However, the existing methods for electrochemical DNA biosensing analysis have some shortcomings, such as poor stability and specificity of capture probes, insufficient detection sensitivity, and long detection cycles. In this review, we focus on improving the sensitivity and practicability of electrochemical DNA biosensing analysis methods and summarize a series of research work carried out by using electrically neutral peptide nucleic acid as an immobilized capture probe.
Candidate l‐methionine target piRNA regulatory networks analysis response to cocaine‐conditioned place preference in mice
Authors: Zhang Kunlin , Ji Guanyu , Zhao Mei , Wang Yan 
Published: July 2021

AbstractBackgroundMethionine has been proven to inhibit addictive behaviors of cocaine dependence. However, the mechanism of methionine response to cocaine CPP is unknown. Recent evidence highlights piRNAs to regulate genes via a miRNA‐like mechanism. Here, next‐generation sequencing is used to study mechanism on methionine response to drug‐induced behaviors though piRNA.Methodsl‐methionine treatment cocaine CPP animal model was used to do non‐coding RNA sequencing. There were four groups to sequence: saline+saline (SS), MET+saline (MS), MET+cocaine (MC), and cocaine+saline. Combining mRNA sequencing data, the network and regulation of piRNA were analyzed with their corresponding mRNA and miRNA.ResultsAnalysis of the piRNAome reveals that piRNAs inversely regulated their target mRNA genes. KEGG analysis of DE‐piRNA target mRNA genes were enriched in Morphine addiction, GABAergic synapse and Cholinergic synapse pathway. Furthermore, four significantly differential expressed genes Cacna2d3, Epha6, Nedd4l, and Vav2 were identified and regulated by piRNAs in the process of l‐methionine inhibits cocaine CPP. Thereinto, Vav2 was regulated by multiple DE piRNAs by sharing the common sequence: GTCTCTCCAGCCACCTT. Meanwhile, it was found that piRNA positively regulates miRNA and three genes Bcl3, Il20ra, and Insrr were identified and regulated by piRNA through miRNA.ConclusionThe results showed that piRNA negatively regulated target mRNA genes and positively regulated target miRNA genes. Genes located in substance dependence, signal transduction and also nervous functions pathways were identified. When taken together, these data may explain the roles of l‐methionine in counteracting the effects of cocaine CPP via piRNAs.
GDP Induces PANC‐1 Human Pancreatic Cancer Cell Death Preferentially under Nutrient Starvation by Inhibiting PI3K/Akt/mTOR/Autophagy Signaling Pathway
Authors: Sun Sijia , Kim Min Jo , Omar Ashraf M. , Duy Phan Nguyen , Aoike Mio , Awale Suresh 
Published: July 2021

AbstractPancreatic tumors are hypovascular, which leads to a poor nutrient supply to support the aggressively proliferating tumor cells. However, human pancreatic cancer cells have extreme resistance to nutrition starvation, which enables them to survive under severe metabolic stress conditions within the tumor microenvironment, a phenomenon known as “austerity” in cancer biology. Discovering agents which can preferentially inhibit the cancer cells’ ability to tolerate starvation conditions represents a new generation of anticancer agents. In this study, geranyl 2,4‐dihydroxy‐6‐phenethylbenzoate (GDP), isolated from Boesenbergia pandurata rhizomes, exhibited potent preferential cytotoxicity against PANC‐1 human pancreatic cancer cells under nutrition starvation conditions. GDP also possessed PANC‐1 cell migration and colony formation inhibitory activities under normal nutrient‐rich conditions. Mechanistically, GDP inhibited PI3K/Akt/mTOR/autophagy survival signaling pathway, leading to selective PANC‐1 cancer cell death under the nutrition starvation condition. Therefore, GDP is a promising anti‐austerity agent for drug development against pancreatic cancer.
Effect of extrusion on physical and chemical properties and storage stability of corn germ
Authors: Xiao Zhigang , Wang Kexin , Li Fanshu , Cao Huiying , Duan Qingsong , Zhu Minpeng , Wang Peng , Gao Yuzhe , Duan Yumin 
Published: July 2021

AbstractBackground and objectivesCorn germ is a by‐product of corn starch processing, which is rich in nutrients but easy to rancidity. In order to improve the storage stability of corn germ and prevent the metamorphism, raw germ was treated with twin‐screw extruder. Lipase (LA) and lipoxygenase (LOX) activities, free fatty acid (FFA), nutrient composition, microbiology, and microstructure of germ were investigated and the shelf lives were calculated.FindingsExtruding doubled the content of SDF, LA activity reduced to 19.42% and LOX activity reduced to 0% at 120°C and 25 Hz. The total bacteria count and mold count of raw germ decreased significantly. FFA of extruded germ increased slower than that of raw germ during storage and the shelf lives were predicted by a mathematical model experiment and it was 13.5 times as raw corn germ while extruded in 25 Hz and 120°C.ConclusionsExtrusion stabilization technology did not only keep the nutrients of corn germ, but improve the quality and prolonged the shelf life.Significance and noveltyThis study could provide an important reference for further research and industrial production of corn germ.
Impervious synthetic layered silicates coating to restrict the swelling of clay‐rich shales
Authors: Patel Hasmukh A. , Santra Ashok 
Published: July 2021

AbstractAn incremental demand towards the use of water‐based fluids for drilling oil and gas wells has generated numerous challenges in the field of shale inhibition characteristics. One of the major problems associated with the use of water‐based drilling fluids is the interaction of water with clay‐rich shales that leads to hydration and swelling of reactive clays. We have developed functionalized nanoplatelets composed of amine functionalities anchored on the nanometre‐thick magnesium silicates (LMS‐NH2). A facile synthetic approach was employed to synthesize lab‐scale quantity of LMS‐NH2 through combination of sol–gel and precipitation techniques. The structural characterization was conducted using powder X‐ray diffraction, Fourier transform infrared spectroscopy, and thermogravimetric analysis to evaluate generation of anticipated LMS‐NH2. Shale stabilization characteristics of LMS‐NH2 were tested and compared with other commercial shale inhibitors. Clay swelling and clay dispersion tests were performed to demonstrate the effectiveness of the impermeable coating of nano‐platelets on to the clay‐rich shales. The LMS‐NH2 demonstrated 87% recovery of swellable shales after dispersion tests. The microscopic study conducted on shales revealed the formation of inorganic film, which provide impervious coating to protect the water‐susceptible clays. The linear swelling measurements were also performed to understand the effectiveness of LMS‐NH2 over 72 h. LMS‐NH2 demonstrated linear swelling of 31.7% when compared with drilling fluid without shale inhibitor. The newly developed inhibitor in the current study has outperformed conventional shale inhibitors (a 18.7% reduction in linear swelling), wherein the presence of inorganic constituents aids stronger film formation compared to solely organic inhibitors.
Gold Segregation Improves Electrocatalytic Activity of Icosahedron Au@Pt Nanocluster: Insights from Machine Learning†
Authors: Chen Dingming , Lai Zhuangzhuang , Zhang Jiawei , Chen Jianfu , Hu Peijun , Wang Haifeng 
Published: July 2021

Main observation and conclusionAs a common electrocatalytic system, Au‐Pt alloy particles are often prepared as Au‐core‐Pt‐shell (Au@Pt) to make full use of platinum. However, Au has a strong tendency to segregate to the outer surface, leading to the redistribution of the active sites. Unfortunately, the mechanism of such reconstruction and its effect on the electrocatalytic activity have not been thoroughly discussed, largely owing to the complexity of in‐situ characterization and computational modeling. Herein, by taking the 55‐atom Au13Pt42 core‐shell nanocluster as an example, we utilized the neural network potential at density functional theory (DFT) level and the genetic algorithm to search the complex global configurational space. It turns out that it is thermodynamically favorable when all gold atoms are segregated to the surface and the shape of the cluster tends to change from icosahedron to a distorted amorphous structure (at a reduced core, DRC) with a unique gold distribution. Towards understanding the dynamic activity variation of oxygen reduction reaction (ORR) on this bimetallic Au@Pt system, oxygen adsorption energy calculations show that this reconstruction could not only increase the number of adsorption sites but also dramatically improve the ORR catalytic activity of each site, thus enhance the overall ORR reactivity.
Cu/Picolinamides‐Catalyzed Coupling of (Hetero)aryl Halides with Secondary Phosphine Oxides and Phosphite†
Authors: Fang Chao , Wei Bangguo , Ma Dawei 
Published: July 2021

Main observation and conclusionSome 4‐hydroxy‐picolinic acid derived amides were revealed as more efficient ligands for Cu‐catalyzed coupling of (hetero)aryl halides with secondary phosphine oxides and phosphites. Only 3—5 mol% CuI and ligands were required to ensure coupling with a number of (hetero)aryl bromides and iodides to complete at 120 oC in 10—20 h.
Patients, caregivers, and clinicians differ in performance status ratings: Implications for pediatric cancer clinical trials
Authors: Maurer Scott H. , Hinds Pamela S. , Reeve Bryce B. , Mack Jennifer W. , McFatrich Molly , Lin Li , Withycombe Janice S. , Jacobs Shana S. , Baker Justin N. , Castellino Sharon M. , Freyer David R. 
Published: July 2021

BackgroundThe Lansky Play‐Performance Scale (LPPS) is often used to determine a child's performance status for cancer clinical trial eligibility. Differences between clinician and caregiver LPPS ratings and their associations with child‐reported functioning have not been evaluated.MethodsChildren aged 7 to 18 years who were receiving cancer treatment and their caregivers were recruited from 9 pediatric cancer centers. Caregivers and clinicians reported LPPS scores, and children completed Patient‐Reported Outcomes Measurement Information System (PROMIS) pediatric functioning and symptom measures before treatment (time 1 [T1]) and after treatment (time 2 [T2]). t tests and mixed‐linear models were used to assess differences in caregiver and clinician LPPS scores; polyserial correlations quantified associations between PROMIS and LPPS scores.ResultsOf 482 children, 281 had matched caregiver‐ and clinician‐reported LPPS T1/T2 scores. Caregivers rated children significantly worse on the LPPS than clinicians at both T1 (mean, 73.3 vs 87.4; P < .01) and T2 (mean, 67.9 vs 83.1; P < .01). These differences were not related to a child's age (P = .89), diagnosis (P = .17), or sex (P = .64) or to the time point (P = .45). Small to moderate associations existed between caregiver‐ and clinician‐reported LPPS ratings and child‐reported PROMIS scores for mobility (caregiver T1/T2 r = 0.51/0.45; P < .01; clinician T1/T2 r = 0.40/0.35; P < .01), fatigue (caregiver T1/T2 r = –0.46/–0.37; P < .01; clinician T1/T2 r = –0.26/–0.27; P < .01), and pain interference (caregiver T1/T2 r = –0.32/–0.30; P < .01; clinician T1/T2 r = –0.17/–0.31; P < .01). Caregivers and clinicians assigned significantly lower LPPS scores at T2 (caregiver Δ = –5.37; P < .01; clinician Δ = –4.20; P < .01), whereas child‐reported PROMIS scores were clinically stable.ConclusionsSignificant differences between clinician and caregiver LPPS ratings of child performance were sustained over time; their associations with child reports were predominantly small to moderate. These data suggest that clinician‐reported LPPS ratings by themselves are inadequate for determining clinical trial eligibility and should be supplemented by appropriate measures of a child's functional status reflecting the child and caregiver perspectives.
Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations
Authors: Fediuk Daryl J. , Sahasrabudhe Vaishali , Dawra Vikas Kumar , Zhou Susan , Sweeney Kevin 
Published: July 2021

AbstractErtugliflozin, a sodium‐glucose cotransporter 2 inhibitor, is approved for treatment of type 2 diabetes. Two population pharmacokinetic (PK) analyses were conducted, using data from up to 17 phase 1 to 3 studies, to characterize ertugliflozin PK parameters in select ethnic subgroups: (1) East/Southeast (E/SE) Asian vs non‐E/SE Asian subjects; (2) Asian subjects from mainland China vs Asian subjects from the rest of the world and non‐Asian subjects. A 2‐compartment model with first‐order absorption, lag time, and first‐order elimination was fitted to the observed data. For the E/SE Asian vs non‐E/SE Asian analysis (13 692 PK observations from 2276 subjects), E/SE Asian subjects exhibited a 17% increase in apparent clearance (CL/F) and 148% increase in apparent central volume of distribution (Vc/F) vs non‐E/SE Asian subjects. However, individual post hoc CL/F values were similar between groups when body weight differences were considered. For the second analysis (16 018 PK observations from 2620 subjects), compared with non‐Asian subjects, CL/F was similar while Vc/F increased by 44% in Asian subjects from mainland China and both CL/F and Vc/F increased in Asian subjects from the rest of the world (8% and 115%, respectively) vs non‐Asian subjects. Increases in Vc/F would decrease the ertugliflozin maximum concentration but would not impact area under the concentration‐time curve. Therefore, the differences in CL/F (area under the concentration‐time curve) and Vc/F were not considered clinically relevant or likely to result in meaningful ethnic differences in the PK of ertugliflozin.
Enhanced Photovoltaic Performance of BiSCl Solar Cells Through Nanorod Array
Authors: Li Sen , Xu Linfeng , Kong Xingang , Kusunose Takafumi , Tsurumach Noriaki , Feng Qi 
Published: July 2021

AbstractBiSCl single‐crystalline nanofibers were synthesized by a facile one‐pot solvothermal approach for the first time. BiSCl possesses a double chain type structure and grows readily along the c‐axis, resulting the fibrous morphology. UV/Vis absorption spectroscopy revealed that BiSCl nanofibers exhibit a strong light absorption in a wavelength range from UV to visible light, corresponding to a bandgap of 1.96 eV. Ultraviolet photoelectron spectroscopy and density functional theory calculations revealed that BiSCl is a direct n‐type semiconductor with valence band maximum and conduction band minimum located at 6.04 and 4.08 eV below the vacuum level, respectively. To investigate the photovoltaic performance, the homogeneous thin film of BiSCl‐nanorod array was fabricated on a TiO2 porous film by a modified solvothermal process, where the nanorod array is oriented vertically to the surface of the TiO2 porous film. A proper band alignment of BiSCl‐based solar cells with an architecture of fluorine‐doped tin oxide (FTO)/TiO2/BiSCl/(I3−/I−)/Pt gave a PCE of 1.36 % and a relatively large short‐circuit photocurrent density of 9.87 mA cm−2 for the first time. The preliminary photovoltaic study result revealed a potential possibility of BiSCl‐nanorod array as a light absorber for solar cells that can be fabricated by the low‐cost solution process.