bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trans‐limonenedioxide, a promisingbio‐basedepoxy monomer
Authors: Schutz Louis , Kazemi Forouzan , Mackenzie Elby , Bergeron Jean‐Yves , Gagnon Eric , Claverie Jerome P. 
Published: January 2021

AbstractVast quantities of the natural terpene (R)‐limonene can be collected from food waste. Epoxidation of its two double bonds provides limonene dioxide (LDO), a difunctional epoxy monomer. However, LDO is a mixture of four isomers, two of which (trans‐LDO) are actually difunctional while the others (cis‐LDO) have one epoxide group which is significantly less reactive, as revealed by Fourier transformed infrared spectroscopic analysis of formulations cross‐linked with polyethylene imine. These results are also confirmed when preparing epoxy formulations using respectivelycisortransisomers. From DFT calculations, the reactivity of each epoxide group of LDO has been assessed in model reactions with primary and secondary amines, in the presence of amine or alcohol hydrogen‐bond donors. The kinetics of cross‐linking has also been probed by differential scanning calorimetry. As measured by dynamic mechanical analysis, the resulting epoxy resins based ontransisomers have a storage modulus ofca1GPa at room temperature and a glass transition temperature (Tg) of 70°C. These results demonstrate thattransLDO is a promising bio‐based epoxy monomer, which could be used as an alternative to petroleum‐based epoxy monomers.
Longitudinal predictors of caregiver resilience outcomes at the end of childhood cancer treatment
Authors: Barakat Lamia P. , Madden Rebecca E. , Vega Gabriela , Askins Martha , Kazak Anne E. 
Published: January 2021

AbstractObjectiveCaregiver resilience in the context of childhood cancer treatment has been described using cross‐sectional and retrospective studies, but little is known about prospective predictors of resilience outcomes. We examined associations of demographics, cancer‐related variables, and intrapersonal and interpersonal factors at diagnosis (family psychosocial risk, perceived social support, and healthcare self‐efficacy) and psychosocial services provided during treatment with caregiver resilience outcomes at the end of treatment.MethodsFor a study validating a family psychosocial risk screener, 314 primary caregivers completed the measures at diagnosis of their child (aged 0–17 years) and when cancer treatment ended. Resilience outcomes were ratings of distress, posttraumatic stress, and posttraumatic growth. Multiple regression analyses evaluated the relative contribution of hypothesized predictors.ResultsCaregivers endorsed clinically significant distress, moderate posttraumatic growth, and low posttraumatic stress based on norms. Posttraumatic growth was not associated with posttraumatic stress or distress, which were significantly associated with each other. Over and above resilience at diagnosis, family psychosocial risk was associated with resilience at the end of treatment. Perceived social support, healthcare self‐efficacy, and psychosocial services provided demonstrated associations with resilience in univariate analyses, but demographics and cancer‐related variables did not.ConclusionsResilience and family psychosocial risk at diagnosis were the strongest predictors of caregiver resilience outcomes at the end of the treatment. Intrapersonal and interpersonal predictors were weaker and varied by resilience measure. Consistent with psychosocial standards of care, broad evaluation of caregiver risks, resources, and resilience processes and outcomes is recommended at diagnosis and through the treatment trajectory including the end of treatment.
Entering the era of highly effective modulator therapies
Authors: Dave Kavita , Dobra Rebecca , Scott Sandra , Saunders Clare , Matthews Jess , Simmonds Nicholas J. , Davies Jane C. 
Published: January 2021

AbstractSince the discovery of the gene responsible for cystic fibrosis (CF) in 1989, hopes have been pinned on a future with novel therapies tackling the basis of the disease rather than its symptoms. These have become a reality over the last decade with the development through to the clinic of CF transmembrane conductance regulator (CFTR) modulators. These are oral drugs which improve CFTR protein function through either increasing the time the channel pore is open (potentiators) or facilitating its trafficking through the cell to its location on the cell membrane (correctors). The first potentiator, ivacaftor, is now licensed and available clinically in many parts of the world. It is highly effective with impressive clinical impact in the lungs and gastrointestinal tract; longer‐term data from patient registries show fewer exacerbations, a slower rate of lung function loss and reduced need for transplantation in patients receiving ivacaftor. However, as a single drug, it is suitable for only a small minority of patients. The commonest CFTR mutation, F508del, requires both correction and potentiation for clinical efficacy. Two dual‐agent drugs (lumacaftor/ivacaftor and tezacaftor/ivacaftor) have progressed through to licensing, although their short term impact is more modest than that of ivacaftor; this is likely due to only partial correction of protein misfolding and trafficking. Most recently, triple compounds have been developed: two different corrector molecules (elexacaftor and tezacaftor) which, by addressing different regions in the misfolded F508del protein, more effectively improve trafficking. In addition to large improvements in clinical outcomes in people with two copies of F508del, the combination is sufficiently effective that it works in patients with only one copy of F508del and a second, nonmodulator responsive mutation. For the first time, we thus have a drug suitable for around 85% of people with CF. Even more gains are likely to be possible when these drugs can be used in younger children, although more sensitive outcome measures are needed for this age group. Special consideration is needed for people with very rare mutations; those with nonmodulatable mutation combinations will likely require gene or messenger RNA‐based therapeutic approaches, many of which are being explored. Although this progress is hugely to be celebrated, we still have more work to do. The international collaboration between trials networks, pharma, patient organizations, registries, and people with CF is something we are all rightly proud of, but innovative trial design and implementation will be needed if we are to continue to build on this progress and further develop drugs for people with CF.
Tracheal anomalies associated with Down syndrome: A systematic review
Authors: Fockens M. Matthijs , Hölscher Michiel , Limpens Jacqueline , Dikkers Frederik G. 
Published: January 2021

AbstractIntroductionAirway anomalies are accountable for a substantial part of morbidity and mortality in children with Down syndrome (DS). Although tracheal anomalies occur more often in DS children, a structured overview on the topic is lacking. We systematically reviewed the characteristics of tracheal anomalies in DS children.MethodsA MEDLINE and EMBASE search for DS and tracheal anomalies was performed. Tracheal anomalies included tracheal stenosis, complete tracheal ring deformity (CTRD), tracheal bronchus, tracheomalacia, tracheal web, tracheal agenesis or atresia, laryngotracheoesophageal cleft type 3 or 4, trachea sleeve, and absent tracheal rings.ResultsFifty‐nine articles were included. The trachea of DS children is significantly smaller than non‐DS children. Tracheomalacia and tracheal bronchus are seen significantly more often in DS children. Furthermore, tracheal stenosis, CTRD, and tracheal compression by vascular structures are seen regularly in children with DS. These findings are reflected by the significantly higher frequency of tracheostomy and tracheoplasty performed in DS children.ConclusionIn children with DS, tracheal anomalies occur more frequently and tracheal surgery is performed more frequently than in non‐DS children. When complaints indicative of tracheal airway obstruction like biphasic stridor, dyspnea, or wheezing are present in children with DS, diagnostic rigid laryngotracheobronchoscopy with special attention to the trachea is indicated. Furthermore, imaging studies (computed tomography, magnetic resonance imaging, and ultrasound) play an important role in the workup of DS children with airway symptoms. Management depends on the type, number, and extent of tracheal anomalies. Surgical treatment seems to be the mainstay in severe cases.
Heart failure is not a determinant of central sleep apnea in the pediatric population
Authors: Wheeler Jonathan A. , Tutrow Kaylee D. , Ebenroth Eric S. , Gaston Benjamin , Bandyopadhyay Anuja 
Published: January 2021

AbstractBackground/ObjectivesAdults with heart failure (HF) have high prevalence of central sleep apnea (CSA). While this has been repeatedly investigated in adults, there is a deficiency of similar research in pediatric populations. The goal of this study was to compare prevalence of CSA in children with and without HF and correlate central apneic events with heart function.MethodsRetrospective analysis of data from children with and without HF was conducted. Eligible children were less than 18 years old with echocardiogram and polysomnogram within 6 months of each other. Children were separated into groups with and without HF based on left ventricular ejection fraction (LVEF). Defining CSA as central apnea‐hypopnea index (CAHI) more than 1/hour, the cohort was also classified into children with and without CSA for comparative study.ResultsA total of 120 children (+HF: 19, −HF: 101) were included. The +HF group was younger, with higher prevalence of trisomy 21, muscular dystrophy, oromotor incoordination, and structural heart disease. The +HF group had lower apnea‐hypopnea index (median: 3/hour vs. 8.6/hour) and lower central apnea index (CAI) (median: 0.2/hour vs. 0.55/hour). Prevalence of CSA was similar in both groups (p = .195). LogCAHI was inversely correlated to age (Pearson correlation coefficient: −0.245, p = .022). Children with CSA were younger and had higher prevalence of prematurity (40% vs. 5.3%). There was no significant difference in LVEF between children with and without CSA. After excluding children with prematurity, relationship between CAHI and age was no longer sustained.ConclusionsIn contrast to adults, there is no difference in prevalence of CSA in children with and without HF. Unlike in adults, LVEF does not correlate with CAI in children. Overall, it appears that central apneic events may be more a function of age and prematurity rather than of heart function.
Necrotizing pneumonia among Italian children in the pneumococcal conjugate vaccine era
Authors: Carloni Ines , Ricci Silvia , Rubino Chiara , Cobellis Giovanni , Rinaldelli Giampaolo , Azzari Chiara , de Benedictis Fernando M. 
Published: January 2021

AbstractBackgroundNecrotizing pneumonia (NP) is a severe complication of community‐acquired pneumonia. The impact of 13‐valent pneumococcal conjugate vaccine (PCV13) on the epidemiology of NP in children has not been assessed.Patients and methodsMedical records of children less than 18 years admitted with NP to two pediatric hospitals in Italy between 2005 and 2019 were reviewed. The following four periods were defined: 2005–2010 (pre‐PCV13), 2011–2013 (early post‐PCV13), 2014–2016 (intermediate post‐PCV13), and 2017–2019 (late post‐PCV13).ResultsForty‐three children (median age, 44 months) were included. Most of them (93%) were previously healthy. No differences in age, sex, season of admission, comorbidity, clinical presentation, or hospital course were identified between pre‐PCV13 and post‐PCV13 periods. A significant decrease in the rate of NP‐associated hospitalizations was found between the early (1.5/1000 admissions/year) and the intermediate (0.35/1000 admissions/year) post‐PCV13 period (p = .001). An increased trend in admissions was found thereafter. Streptococcus pneumoniae was the most common agent detected in both periods (pre‐PCV13: 11/18, 61%; post‐PCV13: 13/25, 52%). Serotype 3 was the most common strain in both periods (pre‐PCV13: 3/11, 27%; post‐PCV13; 4/13, 31%). There were no changes in the etiology over time, but most patients with Streptococcus pyogenes or Staphylococcus aureus infection were admitted during the post‐PCV13 period.ConclusionsThe hospitalization rate for NP in children decreased a few years after the implementation of PCV13 immunization in Italy. However, an increased trend in admissions was found thereafter. S. pneumoniae was the most frequent causal agent in both pre‐ and post‐PCV13 periods. Pneumococcal serotypes were mainly represented by Strain 3.
Human SARS CoV‐2 spike protein mutations
Authors: Guruprasad Lalitha 
Published: January 2021

AbstractThe human spike protein sequences from Asia, Africa, Europe, North America, South America, and Oceania were analyzed by comparing with the reference severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) protein sequence from Wuhan‐Hu‐1, China. Out of 10333 spike protein sequences analyzed, 8155 proteins comprised one or more mutations. A total of 9654 mutations were observed that correspond to 400 distinct mutation sites. The receptor binding domain (RBD) which is involved in the interactions with human angiotensin‐converting enzyme‐2 (ACE‐2) receptor and causes infection leading to the COVID‐19 disease comprised 44 mutations that included residues within 3.2 Å interacting distance from the ACE‐2 receptor. The mutations observed in the spike proteins are discussed in the context of their distribution according to the geographical locations, mutation sites, mutation types, distribution of the number of mutations at the mutation sites and mutations at the glycosylation sites. The density of mutations in different regions of the spike protein sequence and location of the mutations in protein three‐dimensional structure corresponding to the RBD are discussed. The mutations identified in the present work are important considerations for antibody, vaccine, and drug development.
Mycobacterium tuberculosis puromycin hydrolase displays a prolyl oligopeptidase fold and an acyl aminopeptidase activity
Authors: Zhao YuanHao , Feng Qiaoli , Zhou Xiao , Zhang Yan , Lukman Maxwell , Jiang Jie , Ruiz‐Carrillo David 
Published: January 2021

AbstractPuromycin‐hydrolizing peptidases have been described as members of the prolyl oligopeptidase peptidase family. These enzymes are present across all domains of life but still little is known of the homologs found in the pathogenic bacterium Mycobacterium tuberculosis. The crystal structure of a M. tuberculosis puromycin hydrolase peptidase has been determined at 3 Angstrom resolution, revealing a conserved prolyl oligopeptidase fold, defined by α/β‐hydrolase and β‐propeller domains with two distinctive loops that occlude access of large substrates to the active site. The enzyme displayed amino peptidase activity with a substrate specificity preference for hydrophobic residues in the decreasing order of phenylalanine, leucine, alanine and proline. The enzyme's active site is lined by residues Glu564 for the coordination of the substrates amino terminal moiety and His561, Val608, Tyr78, Trp306, Phe563 and Ty567 for the accommodation of hydrophobic substrates. The availability of a crystal structure for puromycin hydrolase of M. tuberculosis shall facilitate the development of inhibitors with therapeutic applications.
The photocatalytic antibacterial molecular mechanisms towards Pseudomonas syringae pv. tabaci by g‐C3N4 nanosheets: insights from the cytomembrane, biofilm and motility disruption
Authors: Cai Lin , Jia Huanyu , He Lanying , Wei Xuefeng , Feng Hui , Fan Guangjin , Ma Xiaozhou , Ma Guanhua , Sun Xianchao 
Published: January 2021

AbstractBACKGROUNDAntibacterial photocatalytic therapy has been employed as a promising strategy to combat antibiotic‐resistant bacteria in the water disinfection field, especially some non‐metal inorganic nanomaterials. However, their antibacterial activities on plant phytopathogens are poorly understood. Here, the photocatalytic antibacterial mechanism of the urea‐synthesized graphitic carbon nitride nanosheets (g‐C3N4 nanosheets) against Pseudomonas syringae pv. tabaci was systematically investigated in vitro and in vivo.RESULTSThe g‐C3N4 nanosheets exhibited remarkable concentration‐dependent and irradiation‐time‐dependent antibacterial properties, and the 0.5 mg mL−1 concentration ameliorated tobacco wildfire disease in host plants. Specifically, under visible irradiation, g‐C3N4 nanosheets produced numerous reactive oxygen species (ROS), supplementing the plentiful extracellular and intracellular ROS in bacteria. After exposing light‐induced g‐C3N4 nanosheets for 1 h, 500 genes were differentially expressed, according to transcriptome analyses. Notably, the expression of genes related ‘antioxidant activity’ and ‘membrane transport’ was sharply upregulated, and those related to ‘bacterial chemotaxis’, ‘biofilm formation’, ‘energy metabolism’ and ‘cell motility’ were downregulated. After exposure for over 2 h, the longer‐time pressure on the target bacteria cause the decreased biofilm formation and flagellum motility, further injuring the cell membranes leading to cytoplasm leakage and damaged DNA, eventually resulting in the bacterial death. Concomitantly, the attachment of g‐C3N4 nanosheets was a synergistic physical antibacterial pathway. The infection capacity assessment also supported the earlier supposition.CONCLUSIONThese results provide novel insights into the photocatalytic antibacterial mechanisms of g‐C3N4 nanosheets at the transcriptome level, which are expected to be useful for dissecting the response pathways in antibacterial activities and for improving g‐C3N4‐based photocatalysts practices in plant disease control. © 2021 Society of Chemical Industry
Yacon as an alternative host plant for Encarsia formosa mass‐rearing: validating a multinomial theorem for bootstrap technique in life table research
Authors: Zhao Yue , Zhao Chun‐Li , Yang Xiangbing , Chi Hsin , Dai Peng , Desneux Nicolas , Benelli Giovanni , Zang Lian‐Sheng 
Published: January 2021

AbstractBACKGROUNDYacon (Smallanthus sonchifolius) is a broadleaf host plant suitable for rearing the greenhouse whitefly, Trialeurodes vaporariorum (Westwood). Here, the possibility of using yacon as an alternative host plant for production of the parasitoid, Encarsia formosa Gahan, one of the most important natural enemies of whiteflies, was explored. Data on the demographic characteristics, parasitism rate, and host‐feeding rate were collected and analyzed using the TWOSEX‐MSChart, CONSUME‐MSChart, and TIMING‐MSChart computer programs, and then contrasted with comparable data from the more commonly utilized host plant, tobacco.RESULTSHigher fecundity (F) (190.13 eggs/female) and more oviposition days (Od) (16.60 days) were observed in E. formosa when yacon was used as the host plant for rearing T. vaporariorum, compared with when tobacco was used (F = 150.13 eggs/female, Od = 15.27 days). The intrinsic rate of increase (r), finite rate of increase (λ), and net reproduction rate (R0) were significantly higher in E. formosa parasitizing T. vaporariorum reared on yacon compared with those parasitizing tobacco‐reared T. vaporariorum. Furthermore, the net host‐feeding rate (C0 = 40.87 prey/parasitoid), net killing rate (Z0 = 239.73 prey/parasitoid), and finite killing rate ( = 0.2560/day) for E. formosa on yacon‐reared whiteflies were significantly higher than those from tobacco‐reared whiteflies.CONCLUSIONOur results showed that yacon is more suitable than tobacco as a host plant for mass‐rearing E. formosa for biological control programs to manage whiteflies. An innovative application of the multinomial theorem for calculating the exact probability of bootstrap samples in life table research was also introduced. © 2021 Society of Chemical Industry
Field validation of biocontrol strategies to control brown rot on stone fruit in several European countries
Authors: Casals Carla , Guijarro Belén , De Cal Antonieta , Torres Rosario , Usall Josep , Perdrix Víctor , Hilscher Ulrike , Ladurner Edith , Smets Tom , Teixidó Neus 
Published: January 2021

AbstractBACKGROUNDBrown rot caused by Monilinia spp. is the most significant disease of stone fruit. New approaches to fruit production have necessitated the development of control strategies that are more eco‐ and consumer‐friendly. An efficient field strategy to control brown rot was previously designed based on the application of two biocontrol agents (BCAs), Bacillus amyloliquefaciens CPA‐8 (CPA‐8) or Penicillium frequentans 909 (Pf909), with calendar‐based treatment. In the present study, the strategy was validated on different stone fruit hosts in four producing countries over two seasons.RESULTSThe results obtained were reported according to three different scenarios: Scenario 1, in which there was no presence of disease in the field; Scenario 2, in which high disease pressure occurred in the field and treatments (biologicals or chemicals) were not effective; and Scenario 3, with low or medium to high disease presence. The results were successful because, in general, BCA strategies were shown to control brown rot to a similar extent as chemicals strategies. We found that most of the trials conducted in this study were classed under Scenario 3 (62.5%), with only 12.5% and 25% of the trials classed under Scenarios 1 and 2, respectively.CONCLUSIONThese novel findings allowed the formulation of CPA‐8 and Pf909 as valuable tools for farmers to produce stone fruits more competitively and meet consumer demand for safer and more environmentally friendly products. © 2021 Society of Chemical Industry
A weighted log‐rank test and associated effect estimator for cancer trials with delayed treatment effect
Authors: Yu Chang , Huang Xiang , Nian Hui , He Philip 
Published: January 2021

AbstractThe standard log‐rank test has been extended by adopting various weight functions. Cancer vaccine or immunotherapy trials have shown a delayed onset of effect for the experimental therapy. This is manifested as a delayed separation of the survival curves. This work proposes new weighted log‐rank tests to account for such delay. The weight function is motivated by the time‐varying hazard ratio between the experimental and the control therapies. We implement a numerical evaluation of the Schoenfeld approximation (NESA) for the mean of the test statistic. The NESA enables us to assess the power and to calculate the sample size for detecting such delayed treatment effect and also for a more general specification of the non‐proportional hazards in a trial. We further show a connection between our proposed test and the weighted Cox regression. Then the average hazard ratio using the same weight is obtained as an estimand of the treatment effect. Extensive simulation studies are conducted to compare the performance of the proposed tests with the standard log‐rank test and to assess their robustness to model mis‐specifications. Our tests outperform theGρ,γclass in general and have performance close to the optimal test. We demonstrate our methods on two cancer immunotherapy trials.