bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing the Start Time of Biologics in Polyarticular Juvenile Idiopathic Arthritis: A Comparative Effectiveness Study of Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans
Authors: Kimura Yukiko , Schanberg Laura E. , Tomlinson George A. , Riordan Mary Ellen , Dennos Anne C. , Del Gaizo Vincent , Murphy Katherine L. , Weiss Pamela F. , Natter Marc D. , Feldman Brian M. , Ringold Sarah ,   the CARRA STOP‐JIA Investigators
Published: June 2021

ObjectiveThe optimal time to start biologics in polyarticular juvenile idiopathic arthritis (JIA) remains uncertain. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed 3 consensus treatment plans (CTPs) for untreated polyarticular JIA to compare strategies for starting biologics.MethodsStart Time Optimization of Biologics in Polyarticular JIA (STOP‐JIA) was a prospective, observational, CARRA Registry study comparing the effectiveness of 3 CTPs: 1) the step‐up plan (initial nonbiologic disease‐modifying antirheumatic drug [DMARD] monotherapy, adding a biologic if needed, 2) the early combination plan (DMARD and biologic started together), and 3) the biologic first plan (biologic monotherapy). The primary outcome measure was clinically inactive disease according to the provisional American College of Rheumatology (ACR) criteria, without glucocorticoids, at 12 months. Secondary outcome measures included Patient‐Reported Outcomes Measurement Information System (PROMIS) pain interference and mobility scores, inactive disease as defined by the clinical Juvenile Arthritis Disease Activity Score in 10 joints (JADAS‐10), and the ACR Pediatric 70 criteria (Pedi 70).ResultsOf 400 patients enrolled, 257 (64%) began the step‐up plan, 100 (25%) the early combination plan, and 43 (11%) the biologic first plan. After propensity score weighting and multiple imputation, clinically inactive disease according to the ACR criteria was achieved in 37% of those on the early combination plan, 32% on the step‐up plan, and 24% on the biologic first plan (P = 0.17). Inactive disease according to the clinical JADAS‐10 (score ≤2.5) was also achieved in more patients on the early combination plan than the step‐up plan (59% versus 43%; P = 0.03), as was ACR Pedi 70 (81% versus 62%; P = 0.008), but generalizability was limited by missing data. PROMIS measures improved in all groups, but without significant differences. Twenty serious adverse events were reported (mostly infections).ConclusionAchievement of clinically inactive disease without glucocorticoids did not significantly differ between groups at 12 months. While there was a significantly higher likelihood of early combination therapy achieving inactive disease according to the clinical JADAS‐10 and ACR Pedi 70, these results require further exploration.
Digital humanities as a cross‐disciplinary battleground: An examination of inscriptions in journal publications
Authors: Ma Rongqian , Li Kai 
Published: June 2021

AbstractInscriptionsare defined as traces of scientific research production that are embodied in material artifacts and media, which encompass a wide variety of nonverbal forms such as graphs, diagrams, and tables. Inscription serves as a fundamental rhetorical device in research outputs and practices. As many inscriptions are deeply rooted in a scientific research paradigm, they can be used to evaluate the level of scientificity of a scientific field. This is specifically helpful to understand the relationships between research traditions in digital humanities (DH), a highly cross‐disciplinary between various humanities and scientific traditions. This paper presents a quantitative, community‐focused examination of how inscriptions are used in English‐language research articles in DH journals. We randomly selected 252 articles published between 2011 and 2020 from a representative DH journal list, and manually classified the inscriptions and author domains in these publications. We found that inscriptions have been increasingly used during the past decade, and their uses are more intensive in publications led by STEM authors comparing to other domains. This study offers a timely survey of the disciplinary landscape of DH from the perspective of inscriptions and sheds light on how different research approaches collaborate and combat in the field of DH.
Keep it simple: Identification of basic versus complex emotions in spoken language in individuals with autism spectrum disorder without intellectual disability: A meta‐analysis study
Authors: Icht Michal , Zukerman Gil , Ben‐Itzchak Esther , Ben‐David Boaz M. 
Published: June 2021

AbstractDaily functioning involves identifying emotions in spoken language, a fundamental aspect of social interactions. To date, there is inconsistent evidence in the literature on whether individuals with autism spectrum disorder without intellectual disability (ASD‐without‐ID) experience difficulties in identification of spoken emotions. We conducted a meta‐analysis (literature search following the PRISMA guidelines), with 26 data sets (taken from 23 peer‐reviewed journal articles) comparing individuals with ASD‐without‐ID (N = 614) and typically‐developed (TD) controls (N = 640), from nine countries and in seven languages (published until February 2020). In our analyses there was no sufficient evidence to suggest that individuals with HF‐ASD differ from matched controls in the identification of simple prosodic emotions (e.g., sadness, happiness). However, individuals with ASD‐without‐ID were found to perform significantly worse than controls in identification of complex prosodic emotions (e.g., envy and boredom). The level of the semantic content of the stimuli presented (e.g., sentences vs. strings of digits) was not found to have an impact on the results. In conclusion, the difference in findings between simple and complex emotions calls for a new‐look on emotion processing in ASD‐without‐ID. Intervention programs may rely on the intact abilities of individuals with ASD‐without‐ID to process simple emotions and target improved performance with complex emotions.Lay summaryIndividuals with autism spectrum disorder without intellectual disability (ASD‐without‐ID) do not differ from matched controls in the identification of simple prosodic emotions (e.g., sadness, happiness). However, they were found to perform significantly worse than controls in the identification of complex prosodic emotions (e.g., envy, boredom). This was found in a meta‐analysis of 26 data sets with 1254 participants from nine countries and in seven languages. Intervention programs may rely on the intact abilities of individuals with ASD‐without‐ID to process simple emotions.
Exposure to alirocumab during the first trimester of pregnancy: A case report
Authors: Vuignier Yann , Beaud Floriane , Kosinski Christophe , Panchaud Alice , Lebon Sébastien , Baud David , Kissling Sébastien , Collet Tinh‐Hai 
Published: June 2021

AbstractBackgroundFamilial hypercholesterolemia can be efficiently treated with combined lipid‐lowering drugs. Lipid‐lowering drugs are usually withdrawn for pregnancy and breastfeeding, ideally preconception, followed by lipid apheresis, however, careful plans can be precipitated due to unexpected pregnancy.CaseA 28‐year old woman with familial hypercholesterolemia due to heterozygous LDLR mutations had an LDL‐cholesterol level at 14.6 mmol/L and Lp(a) at 1150 mg/L. She required a three‐vessel coronary artery bypass graft, drug‐eluting stents, rosuvastatin, ezetimibe, and alirocumab at maximal dosage. Contraception was advised during the following 12 months, with a planned drug withdrawal to bridge with lipid apheresis, such as the direct adsorption of lipoproteins (DALI). However, an unplanned pregnancy required an abrupt stop of all oral medications at six gestational weeks, except for aspirin. Lipid apheresis controlled LDL‐cholesterol in the range of 4.9–7.9 mmol/L (before DALI session) to 1.2–3.2 mmol/L (after DALI session). Later, the regular pregnancy ultrasounds highlighted an isolated agenesis of the corpus callosum later confirmed by magnetic resonance imaging.ConclusionsA causal link between the early pregnancy exposure to PCSK9 inhibitors (or statins and ezetimibe taken concomitantly) and the observed complete agenesis of the corpus callosum seems unlikely in this case. Guidelines do not specifically recommend preconception measures to lower fetal and/or maternal risks of patients with severe FH considering pregnancy. We argue that lipid apheresis and other measures should be discussed with women with FH and maternity project on an individual basis, until pharmacoepidemiology studies assessing the safety of PCSK9 inhibitors in pregnancy are available.
Ribozyme‐processed guide RNA enhances virus‐mediated plant genome editing
Authors: Oh Youngbin , Kim Hyeonjin , Lee Hyo‐Jun , Kim Sang‐Gyu 
Published: June 2021

AbstractIn virus‐induced gene‐editing system, subgenomic promoters have been used to express guide RNAs (gRNAs). However, the transcription initiation site of the subgenomic promoters remains elusive. Here, we examined the sequence of gRNAs expressed by subgenomic promoters and found the variable length of overhangs at 5′‐end of gRNAs. The overhangs at 5′‐end of gRNA decrease the cleavage activity of SpCas9. To overcome this problem, we inserted hammerhead ribozyme between the subgenomic promoter and gRNA and confirmed that gRNAs with a precise 5′‐end increase the editing efficacy in wild tobacco. This system will be widely used for editing target genes in plants with high efficiency.
Comparative metabolomics and lipidomics study to evaluate the metabolic differences between first‐ and second‐generation mammalian or mechanistic target of rapamycin inhibitors
Authors: Rashid Md Mamunur , Lee Hyunbeom , Park Jinyoung , Jung Byung Hwa 
Published: June 2021

AbstractMammalian or mechanistic target of rapamycin (mTOR) drives its fundamental cellular functions through two distinct catalytic subunits, mTORC1 and mTORC2, and is frequently dysregulated in most cancers. To treat cancers, developed mTOR inhibitors have been classified into first and second generations based on their ability to inhibit single (first‐generation) and dual (second‐generation) mTOR subunits. However, the underlying metabolic differences due to the effects of first‐ and second‐generation mTOR inhibitors have not been clearly evaluated. In this study, rapamycin (sirolimus) and AZD8055 and PP242 were selected as first‐ and second‐generation mTOR inhibitors, respectively, to evaluate the metabolic differences due to these two generations of mTOR inhibitors after a single oral dose using untargeted metabolomics and lipidomics approaches. The metabolic differences at each time point were compared using multivariate analysis. The multivariate and data analyses showed that metabolic disparity was more prominent within 8 h after drug administration and a broad class of metabolites were affected by the administration of both generations of mTOR inhibitors. Among the metabolite classes, changes in the pattern of fatty acids and glycerophospholipids were opposite, specifically at 4 and 8 h between the two generations of mTOR inhibitors. We speculate that the inhibition of the mTORC2 subunit by the second‐generation mTOR inhibitor may have resulted in a distinct metabolic pattern between the first‐ and second‐generation inhibitors. Finally, the findings of this study could assist in a more detailed understanding of the key metabolic differences caused by first‐ and second‐generation mTOR inhibitors.
Characterizing online crowdfunding campaigns for patients with kidney cancer
Authors: Thomas Hannah S. , Lee Austin W. , Nabavizadeh Behnam , Namiri Nikan K. , Hakam Nizar , Martin‐Tuite Patrick , Rios Natalie , Enriquez Anthony , Mmonu Nnenaya A. , Cohen Andrew J. , Breyer Benjamin N. 
Published: June 2021

AbstractBackgroundCancer patients incur high care costs; however, there is a paucity of literature characterizing unmet financial obligations for patients with urologic cancers. Kidney cancer patients are particularly burdened by costs associated with novel systemic treatments. This study aimed to ascertain the characteristics of GoFundMe® crowdfunding campaigns for patients with kidney cancer, in order to better understand the financial needs of this population.MethodsWe performed a cross‐sectional, quantitative, and qualitative analysis of all kidney cancer GoFundMe® campaigns since 2010. Fundraising metrics such as goal funds and amount raised, were extracted. Eight independent investigators collected patient, disease and campaign‐level variables from campaign stories (κ = 0.72). In addition, we performed a content analysis of campaign narratives spotlighting the primary appeal of the patient's life story.ResultsA total of 486 GoFundMe® kidney cancer campaigns were reviewed. The median goal funds were 10,000USD [IQR = 5000, 20,000] and the median amount raised was 1450USD [IQR = 578, 4050]. Most campaigns were for adult males (53%) and 62% of adults had children. A minority were for pediatric patients (17%). Thirty‐seven percent of adult patients were primary wage earners and 43% reported losing their job or substantially reducing hours due to illness. Twenty‐nine percent reported no insurance or insufficient coverage. Campaigns most frequently sought funds for medical bills (60%), nonmedical bills (27%), and medical travel (23%). Qualitative campaign narratives mostly emphasized patients’ hardship (46.3%) or high moral character (35.2%). Only 8% of campaigns achieved their target funds.ConclusionsDespite fundraising efforts, patients with kidney cancer face persistent financial barriers, incurring both medical and nonmedical cost burdens. This may be compounded by limited or no insurance. Cancer care providers should be aware of financial constraints placed on kidney cancer patients, and consider how these may impact treatment regimens.
Approaches to Introduce Helical Structure in Cysteine‐Containing Peptides with a Bimane Group
Authors: Horsfall Aimee J. , McDougal Daniel P. , Scanlon Denis B. , Bruning John B. , Abell Andrew D. 
Published: June 2021

AbstractAn i−i+4 or i−i+3 bimane‐containing linker was introduced into a peptide known to target Estrogen Receptor alpha (ERα), in order to stabilise an α‐helical geometry. These macrocycles were studied by CD and NMR to reveal the i−i+4 constrained peptide adopts a 310‐helical structure in solution, and an α‐helical conformation on interaction with the ERα coactivator recruitment surface in silico. An acyclic bimane‐modified peptide is also helical, when it includes a tryptophan or tyrosine residue; but is significantly less helical with a phenylalanine or alanine residue, which indicates such a bimane modification influences peptide structure in a sequence dependent manner. The fluorescence intensity of the bimane appears influenced by peptide conformation, where helical peptides displayed a fluorescence increase when TFE was added to phosphate buffer, compared to a decrease for less helical peptides. This study presents the bimane as a useful modification to influence peptide structure as an acyclic peptide modification, or as a side‐chain constraint to give a macrocycle.
Screen‐printed Nickel‐Cerium Hydroxide Sensor for Acetaminophen Determination in Body Fluids
Authors: Azeredo Nathália F. B. , Gonçalves Josué M. , Lima Irlan S. , Araki Koiti , Wang Joseph , Angnes Lúcio 
Published: June 2021

AbstractThe possibility of fast, reliable, and sensitive (μmol L−1) quantification of acetaminophen (AAP) directly in saliva and sweat was demonstrated in the pH range of 4 to 7 using a new user‐friendly and cost‐effective graphite screen‐printed electrode (SPE) modified with 2–3 nm diameter alpha‐nickel‐cerium hydroxide nanoparticles. The nanoparticles (NPs) were fully characterized by transmission electron microscopy (TEM, HRTEM and STEM), XRD, and the electrochemical conditions for AAP analysis optimized, pushing down the limit of detection with good selectivity. The possibility of real‐time measurements of AAP was demonstrated by carrying out experiments directly in biofluids, without significant interference from species such as lactate, glucose, ascorbic and uric acid usually present in this kind of samples. This is the first report combining the catalytic properties and easy incorporation of alpha‐nickel‐cerium hydroxide nanoparticles into graphite ink to prepare an SPE for AAP electrochemical detection in secreting body fluids. The α‐Ni0.9Ce0.1(OH)2 SPE features good accuracy and selectivity, fast response, good accuracy and selectivity, as well as low reagent consumption for determination of AAP in real saliva and sweat samples.
Practical Enzymatic Production of Carbocycles
Authors: Wang Weijin , Taber Douglass F. , Renata Hans 
Published: June 2021

AbstractThe Pd‐catalyzed carbon‐carbon bond formation pioneered by Heck in 1969 has dominated medicinal chemistry development for the ensuing fifty years. As the demand for more complex three‐dimensional active pharmaceuticals continues to increase, preparative enzyme‐mediated assembly, by virtue of its exquisite selectivity and sustainable nature, is poised to provide a practical and affordable alternative for accessing such compounds. In this minireview, we summarize recent state‐of‐the‐art developments in practical enzyme‐mediated assembly of carbocycles. When appropriate, background information on the enzymatic transformation is provided and challenges and/or limitations are also highlighted.
Tracking the Electrocatalytic Activity of a Single Palladium Nanoparticle for the Hydrogen Evolution Reaction
Authors: Chen Mengjie , Lu Si‐Min , Peng Yue‐Yi , Ding Zhifeng , Long Yi‐Tao 
Published: June 2021

AbstractThe nanoparticle‐based electrocatalysts’ performance is directly related to their working conditions. In general, a number of nanoparticles are uncontrollably fixed on a millimetre‐sized electrode for electrochemical measurements. However, it is hard to reveal the maximum electrocatalytic activity owing to the aggregation and detachment of nanoparticles on the electrode surface. To solve this problem, here, we take the hydrogen evolution reaction (HER) catalyzed by palladium nanoparticles (Pd NPs) as a model system to track the electrocatalytic activity of single Pd NPs by stochastic collision electrochemistry and ensemble electrochemistry, respectively. Compared with the nanoparticle fixed working condition, Pd NPs in the nanoparticle diffused working condition results in a 2–5 orders magnitude enhancement of electrocatalytic activity for HER at various bias potential. Stochastic collision electrochemistry with high temporal resolution gives further insights into the accurate study of NPs’ electrocatalytic performance, enabling to dramatically enhance electrocatalytic efficiency.
Trapping of Terminal Platinapolyynes by Copper(I) Catalyzed Click Cycloadditions; Probes of Labile Intermediates in Syntheses of Complexes with Extended sp Carbon Chains, and Crystallographic Studies
Authors: Amini Hashem , Weisbach Nancy , Gauthier Sébastien , Kuhn Helene , Bhuvanesh Nattamai , Hampel Frank , Reibenspies Joseph H. , Gladysz John A. 
Published: June 2021

AbstractThe silylated hexatriynyl complex trans‐(C6F5)(p‐tol3P)2Pt(C≡C)3SiEt3 (PtC6TES) is converted in situ to PtC6H (wet n‐Bu4N+ F−, THF) and cross coupled with the diyne H(C≡C)2SiEt3 (HC4TES; CuCl/TMEDA, O2) to give PtC10TES (71 %). This sequence is repeated twice to afford PtC14TES (65 %) and then PtC18TES (27 %). An analogous series of reactions starting with PtC8TES gives PtC12TES (60 %), then PtC16TES (43 %), and then PtC20TES (17 %). Similar cross couplings with H(C≡C)2Si(i‐Pr)3 (HC4TIPS) give PtC12TIPS (68 %), PtC14TIPS (68 %), and PtC16TIPS (34 %). The trialkylsilyl species (up to PtC18TES) are converted to 3+2 “click” cycloadducts or 1,4‐disubstituted 1,2,3‐triazoles trans‐(C6F5)(p‐tol3P)2Pt(C≡C)n‐1C=CHN(CH2C6H5)N=N (29–92 % after workups). The most general procedure involves generating the terminal polyynes PtCxH (wet n‐Bu4N+ F−, THF) in the presence of benzyl azide in DMF and aqueous CuSO4/ascorbic acid. All of the preceding complexes are crystallographically characterized and the structural and spectroscopic properties analyzed as a function of chain length. Two pseudopolymorphs of PtC20TES are obtained, both of which feature molecules with parallel sp carbon chains in a pairwise head/tail packing motif with extensive sp/sp van der Waals contacts.
Flexible Energy from Biogas: Use of Secondary Digesters for Heat Storage—Results of Fermentation Tests
Authors: Seick Ingolf , Vergara‐Araya Mónica , Wiese Jürgen 
Published: June 2021

AbstractA process for a more efficient and flexible use of the produced heat in biogas plants is tested under real operational conditions. The process uses a mesophilic digester and a thermophilic secondary digester, and the heat demand of the plant is covered by using the heat stored in the secondary digester. The efficient heat use is achieved by a controlled variation of temperature in combination with a suitable process monitoring, without affecting the biogas production or disturbing the biological process. The concept was previously tested in ideal laboratory conditions. Here, the validation tests, in preparation for a planned large‐scale trial, comprising one‐year semicontinuous fermentation tests in the laboratory (close to real operational conditions) are presented. These real conditions are characterized by a high organic load of the reactors as well as by a more manifold substrate mix. During the experimental phase, it is determined that the maximum temperature, at high variation rates between −4 and +2 K per day, reaches 54 °C, allowing a stable process. These experiments confirm that the adaptability to temperature changes depends on the boundary conditions of the fermentation and case‐specific experiments are required before significant changes are made to the temperature management of anaerobic digestion systems.
Randomized trial on acute toxicities of weekly vs three‐weekly cisplatin‐based chemoradiation in head and neck cancer
Authors: Ameri Ahmad , Norouzi Shokoufe , Sourati Ainaz , Azghandi Samira , Novin Kambiz , Taghizadeh‐Hesary Farzad 
Published: June 2021

AbstractBackgroundThe current first‐line treatment of locally advanced head and neck carcinoma (LAHNC) is concurrent chemoradiation with three‐weekly cisplatin 100 mg/m2. However, prescribing cisplatin at this dose increases the treatment toxicity, which may compromise the treatment results. An alternative schedule is weekly 40 mg/m2 cisplatin.AimTo compare the acute hematologic and renal toxicities of these two regimens.MethodsThis randomized clinical trial included 77 LAHNC patients who were allocated to a high dose (100 mg/m2 every 3 weeks) or low dose (40 mg/m2 weekly) cisplatin group concurrent with radiotherapy. Hematologic and renal indices were measured weekly during chemoradiation.ResultsThe average age of patients was 55.3 years. Overall, 71.4% of patients were treated in a definitive setting. The incidence of severe hematologic events was not significantly different. However, the average estimated glomerular filtration rate (eGFR) was significantly greater in the three‐weekly group (67.85 vs. 58.57% mL/min per 1.73 m2; P‐value = .02). Cumulative cisplatin dose of ≥240 mg/m2 was significantly greater in the weekly group. Totally, treatment breaks occurred in 40.3% of patients due to treatment toxicity. Treatment interruption was primarily due to neutropenia in the three‐weekly and renal dysfunction and thrombocytopenia in the weekly group.ConclusionsSevere acute hematologic toxicities were comparable for three‐weekly and weekly groups. The decrease in eGFR through treatment was more significant with weekly cisplatin. Further follow‐up, however, is needed to confirm its impact on delayed renal function.