bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of Anthocyanin Biosynthesis System Using Chalcone as a Substrate in Lactococcus lactis NZ9000
Authors: Tian Yujing , Liu Na , Zhao Xiaowen , Mei Xuefeng , Zhang Lei , Huang Jinhai , Hua Deping 
Published: July 2024

ABSTRACTAnthocyanins are high‐value natural compounds, but to date, their production still mainly relies on extraction from plants. A five‐step metabolic pathway was constructed in probiotic Lactococcus lactis NZ9000 for rapid, stable, and glycosylated anthocyanin biosynthesis using chalcone as a substrate. The genes were cloned from anthocyanin‐rich blueberry: chalcone isomerase (CHI), flavanone 3‐hydroxylase (F3H), dihydroflavonol 4‐reductase (DFR), anthocyanin synthase (ANS), and UDPG‐flavonoid 3‐O‐glycosyltransferase (3GT). Using HR, the polysaccharide pellicle (PSP) segment of the cell wall polysaccharide synthesis (cwps) gene cluster from L. lactis NZ9000 was cloned into vector p15A‐Cm‐repDE. Then, CHI and F3H were placed sequentially under the control of NZProm 3 of this gene cluster in the vector, which was transformed into L. lactis NZ9000 to obtain Strain A. Furthermore, Strain B was constructed by placing F3H‐DFR‐ANS and 3GT under NZProm 2 and 3, respectively. Using LC‐MS/MS analysis, several types of anthocyanins, including callistephin chloride, oenin chloride, malvidin O‐hexoside, malvidin 3,5‐diglucoside, and pelargonidin 3‐O‐malonyl‐malonylhexoside, increased in the supernatant of the co‐culture of Strains A and B compared to that of L. lactis NZ9000. This is the first time that a five‐step metabolic pathway has been developed for anthocyanin biosynthesis in probiotic L. lactis NZ9000. This work lays the groundwork for novel anthocyanin production by a process involving the placement of several biosynthesis genes under the control of a gene cluster.
A priori verification method for curl‐conforming basis functions in simplices
Authors: Amor‐Martin Adrian , Garcia‐Castillo Luis E. 
Published: July 2024

The construction of (hierarchical) curl‐conforming basis functions has been a hot topic in the last decades in the finite element community. Especially, functions applied to simplices have been quite popular after the work by Nédélec in 1980. Many mixed‐order and full‐order families have been provided in the last years, but sometimes, it is difficult to assess if they belong to the original space proposed by Nédélec (especially when orthogonalization procedures are applied). Here, a tool to determine if a family of basis functions belongs to the Nédélec space is provided. Since affine coordinates are the most frequent choice for simplices, particularities about its use with this kind of coordinates are detailed. A detailed survey of existing families is provided, and the practical application of the tool to a representative set of these families is discussed. The tool is also available for the community in a public repository.
A subset of image‐defined risk factors predict completeness of resection in children with high‐risk neuroblastoma: An international multicenter study
Authors: Espinoza Andres F. , Bagatell Rochelle , McHugh Kieran , Naranjo Arlene H. , Van Ryn Collin , Rojas Yesenia , Lyons Karen , Guillerman R. Paul , Kirby Chaim , Brock Penelope , Volchenboum Samuel , Simon Thorsten , States Lisa , Miller Alexandra , Krug Barbara , Sarnacki Sabine , Irtan Sabine , Brisse Herve J. , Valteau‐Couanet Dominique , von Schweinitz Dietrich , Kammer Birgit , Granata Claudio , Pio Luca , Park Julie R. , Nuchtern Jed G. 
Published: July 2024

AbstractBackgroundImage‐defined risk factors (IDRFs) were promulgated for predicting the feasibility and safety of complete primary tumor resection in children with neuroblastoma (NB). There is limited understanding of the impact of individual IDRFs on resectability of the primary tumor or patient outcomes. A multicenter database of patients with high‐risk NB was interrogated to answer this question.Design/methodsPatients with high‐risk NB (age <20 years) were eligible if cross‐sectional imaging was performed at least twice prior to resection. IDRFs and primary tumor measurements were recorded for each imaging study. Extent of resection was determined from operative reports.ResultsThere were 211 of 229 patients with IDRFs at diagnosis, and 171 patients with IDRFs present pre‐surgery. A ≥90% resection was significantly more likely in the absence of tumor invading or encasing the porta hepatis, hepatoduodenal ligament, superior mesenteric artery (SMA), renal pedicles, abdominal aorta/inferior vena cava (IVC), iliac vessels, and/or diaphragm at diagnosis or an overlapping subset of IDRFs (except diaphragm) at pre‐surgery. There were no significant differences in event‐free survival (EFS) and overall survival (OS) when patients were stratified by the presence versus absence of any IDRF either at diagnosis or pre‐surgery.ConclusionTwo distinct but overlapping subsets of IDRFs present either at diagnosis or after induction chemotherapy significantly influence the probability of a complete resection in children with high‐risk NB. The presence of IDRFs was not associated with significant differences in OS or EFS in this cohort.
Evaluation of otorhinolaryngologic, audiologic, and genetic findings in children with cystic fibrosis: A tertiary care experience
Authors: Nayır Büyükşahin Halime , Yalcın Ebru , Gökırmak İlayda , Ertugrul Gorkem , Dayangaç Erden Didem , Sennaroglu Gonca , Ozer Serdar , Akkaplan Selvet , Yesil Ibrahım Emir , Guzelkas Ismail , Sunman Birce , Alboga Didem , Akgul Erdal Meltem , Demir İpek , Atan Raziye , Capraz Burcu , Emiralioglu Nagehan , Dogru Deniz , Ozcelik Ugur , Kiper Nural 
Published: July 2024

AbstractObjectivesTo evaluate otorhinolaryngologic findings and the relationship between aminoglycoside (AG) exposure and hearing loss in paediatric patients with cystic fibrosis (cwCF). We also aimed to investigate the genetic predisposition to AG ototoxicity by screening for m.1555A>G mutations.MethodsCwCF who underwent otorhinolaryngologic and audiologic examinations were retrospectively included. Clinical characteristics, ear‐nose‐throat related symptoms, and a history of ototoxic drug exposure were recorded. m.1555A>G mutations were retrospectively screened among patients with audiologic evaluations.ResultsTwo hundred thirty‐four cwCF were included in this study with a median age of 10.7 (range, 6.8–14.2) years. Nasal obstruction (14.1%) was the most common symptom. Fifty‐two (22.2%) patients had chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). There was a positive correlation between CRSwNP and the symptom of nasal obstruction (r:.234, p < .001), snoring (r:.179, p = .006), and sleeping with mouth open (r:.138, p = .034). One hundred forty‐nine (63.6%) patients had audiologic evaluations; 14 (9.4%) had hearing impairment. No statistical significance existed between ototoxicity and IV AG exposure (p = .90). Six (42.8%) of 14 patients did not receive ototoxic drugs. One hundred nineteen (50.8%) patients were screened for m.1555A>G mutations, and none were detected.ConclusionsAlmost a quarter of the study population had CRSwNP. Neither the relationship between AGs exposure and hearing loss nor the genetic predisposition to AG ototoxicity could be shown in cwCF.
Identification of severe acute pediatric asthma phenotypes using unsupervised machine learning
Authors: Rogerson Colin , Nelson Sanchez‐Pinto L. , Gaston Benjamin , Wiehe Sarah , Schleyer Titus , Tu Wanzhu , Mendonca Eneida 
Published: July 2024

AbstractRationaleMore targeted management of severe acute pediatric asthma could improve clinical outcomes.ObjectivesTo identify distinct clinical phenotypes of severe acute pediatric asthma using variables obtained in the first 12 h of hospitalization.MethodsWe conducted a retrospective cohort study in a quaternary care children's hospital from 2014 to 2022. Encounters for children ages 2–18 years admitted to the hospital for asthma were included. We used consensus k means clustering with patient demographics, vital signs, diagnostics, and laboratory data obtained in the first 12 h of hospitalization.Measurements and Main ResultsThe study population included 683 encounters divided into derivation (80%) and validation (20%) sets, and two distinct clusters were identified. Compared to Cluster 1 in the derivation set, Cluster 2 encounters (177 [32%]) were older (11 years [8; 14] vs. 5 years [3; 8]; p < .01) and more commonly males (63% vs. 53%; p = .03) of Black race (51% vs. 40%; p = .03) with non‐Hispanic ethnicity (96% vs. 84%; p < .01). Cluster 2 encounters had smaller improvements in vital signs at 12‐h including percent change in heart rate (−1.7 [−11.7; 12.7] vs. −7.8 [−18.5; 1.7]; p < .01), and respiratory rate (0.0 [−20.0; 22.2] vs. −11.4 [−27.3; 9.0]; p < .01). Encounters in Cluster 2 had lower percentages of neutrophils (70.0 [55.0; 83.0] vs. 85.0 [77.0; 90.0]; p < .01) and higher percentages of lymphocytes (17.0 [8.0; 32.0] vs. 9.0 [5.3; 14.0]; p < .01). Cluster 2 encounters had higher rates of invasive mechanical ventilation (23% vs. 5%; p < .01), longer hospital length of stay (4.5 [2.6; 8.8] vs. 2.9 [2.0; 4.3]; p < .01), and a higher mortality rate (7.3% vs. 0.0%; p < .01). The predicted cluster assignments in the validation set shared the same ratio (~2:1), and many of the same characteristics.ConclusionsWe identified two clinical phenotypes of severe acute pediatric asthma which exhibited distinct clinical features and outcomes.
Prospecting Specific Protein Patterns for High Body Mass Index (BMI), Metabolic Syndrome and Type 2 Diabetes in Saliva and Blood Plasma From a Brazilian Population
Authors: Ferreira da Silva Carlos Vinicius , da Silva Carlos José Ferreira , Bacila Sade Youssef , Naressi Scapin Sandra Mara , Thompson Fabiano L. , Thompson Cristiane , da Silva‐Boghossian Carina Maciel , de Oliveira Santos Eidy 
Published: July 2024

ABSTRACTPurposeObesity and its associated metabolic disorders, such as T2DM and MeS, are a growing public health problem worldwide. Our goal was the identification of protein patterns that are uniquely characteristic of higher BMI, MeS, and T2DM in a Brazilian population.Experimental DesignSaliva and plasma proteomes, clinical parameters were analyzed in a population from the state of Rio de Janeiro, Brazil, a mixed‐race population. Volunteers were sorted by their BMI into normal (n = 29), overweight (n = 25), and obese (n = 15) and were compared with individuals with MeS (n = 23) and T2DM (n = 11).ResultsThe Random Forest (RF) predictive model revealed that three clinical variables, BMI, HOMA‐IR, and fasting blood glucose, are most important for predicting MeS and T2DM. A total of six plasmatic proteins (ABCD4, LDB1, PDZ, podoplanin, lipirin‐alpha‐3, and WRS) and six salivary proteins (hemoglobin subunit beta, POTEE, T cell receptor alpha variable 9–2, lactotransferrin, cystatin‐S, carbonic anhydrase 6), are enhanced in T2DM and in MeS.Conclusions and Clinical RelevanceOur data revealed similar alterations in protein composition across individuals with abnormal weight gain, T2DM, and MeS. This finding confirms the close link between these conditions at the molecular level in the studied population, potentially enhancing our understanding of these diseases and paving the way for the development of novel diagnostic tools.
Use of protease substrate specificity screening in the rational design of selective protease inhibitors with unnatural amino acids: Application to HGFA, matriptase, and hepsin
Authors: Mahoney Matthew W. , Helander Jonathan , Kooner Anoopjit S. , Norman Mariah , Damalanka Vishnu C. , De Bona Paolo , Kasperkiewicz Paulina , Rut Wioletta , Poreba Marcin , Kashipathy Maithri M. , Battaile Kevin P. , Lovell Scott , O'Donoghue Anthony J. , Craik Charles S. , Drag Marcin , Janetka James W. 
Published: July 2024

AbstractInhibition of the proteolytic processing of hepatocyte growth factor (HGF) and macrophage stimulating protein (MSP) is an attractive approach for the drug discovery of novel anticancer therapeutics which prevent tumor progression and metastasis. Here, we utilized an improved and expanded version of positional scanning of substrate combinatorial libraries (PS‐SCL) technique called HyCoSuL to optimize peptidomimetic inhibitors of the HGF/MSP activating serine proteases, HGFA, matriptase, and hepsin. These inhibitors have an electrophilic ketone serine trapping warhead and thus form a reversible covalent bond to the protease. We demonstrate that by varying the P2, P3, and P4 positions of the inhibitor with unnatural amino acids based on the protease substrate preferences learned from HyCoSuL, we can predictably modify the potency and selectivity of the inhibitor. We identified the tetrapeptide JH‐1144 (8) as a single digit nM inhibitor of HGFA, matriptase and hepsin with excellent selectivity over Factor Xa and thrombin. These unnatural peptides have increased metabolic stability relative to natural peptides of similar structure. The tripeptide inhibitor PK‐1‐89 (2) has excellent pharmacokinetics in mice with good compound exposure out to 24 h. In addition, we obtained an X‐ray structure of the inhibitor MM1132 (15) bound to matriptase revealing an interesting binding conformation useful for future inhibitor design.
An open‐label study to explore the optimal design of CYP3A drug–drug interaction clinical trials in healthy Chinese people
Authors: Chen Jingcheng , Li Jiangshuo , Wu Jingxuan , Song Yuqin , Li Lijun , Zhang Jianxiong , Dong Ruihua 
Published: July 2024

AbstractA drug–drug interaction (DDI) trial of cytochrome P450 3A (CYP3A) is a necessary part of early‐phase trials of drugs mainly metabolized by this enzyme, but CYP3A DDI clinical trials do not have a standard design, especially for Chinese people. We aimed to offer specific recommendations for CYP3A DDI clinical trial design. This was an open, three‐cycle, self‐controlled study. Healthy subjects were given different administration strategies of CYP3A4 perpetrators. In each cycle, blood samples were collected before and within 24 h after the administration of midazolam, the CYP3A indicator substrate. The plasma concentrations of midazolam and 1‐hydroxymidazolam was obtained using liquid chromatography tandem mass spectrometry assay. For CYP3A inhibition, itraconazole exposure with a loading dose could increase the exposure of midazolam by 3.21‐fold based on maximum plasma concentration (Cmax), 8.37‐fold based on area under the curve Pharmacology Research & Perspectives for review only from zero to the time point (AUC0–t), and 11.22‐fold based on area under the curve from zero to infinity (AUC0–∞). The data were similar for itraconazole pretreatment without a loading dose. For CYP3A induction, the exposure of rifampin for 7 days decreased the plasma concentration of midazolam ~0.27‐fold based on Cmax, ~0.18‐fold based on AUC0–t, and ~0.18‐fold based on AUC0–∞. Midazolam exposure did not significantly change when the pretreatment of rifampin increased to 14 days. This study showed that itraconazole pretreatment for 3 days without a loading dose was enough for CYP3A inhibition, and pretreatment with rifampin for 7 days could induce near‐maximal CYP3A levels.
A rapid quarantine approach for the pathogenic and invasive Phytophthora species associated with imported fruits in China
Authors: Duan Jiaying , Ma Haiting , Wang Wenxin , Li Yaling , Shi Xiaoyu , Chen Xiaowei , Kageyama Koji , Yan Yaping , Li Mingzhu 
Published: July 2024

AbstractBACKGROUNDPhytophthora spp. represent a pivotal genus of plant pathogens with a global distribution, exerting significant deleterious effects on food safety and forestry ecosystems. Numerous pathogenic and invasive Phytophthora species, introduced through imported fruits, have been frequently detected at Chinese ports. With the rise in global trade activities, the plant quarantine of imported fruits is becoming increasingly important but challenging. Fast, simple, and labor‐saving techniques are necessary and anticipated.RESUITSA polymerase chain reaction restriction fragment length polymorphism capillary electrophoresis (PCR‐RFLP‐CE) technology‐based quarantine approach was developed for 16 Phytophthora species associated with the imported fruits in China. The Ypt1 gene, exhibiting abundant interspecific variations, was selected as the marker gene for PCR. The restriction endonuclease AluI was proven to be capable and compatible in simultaneously separating different Phytophthora species during CE. By combining with a fast and efficient DNA extraction kit, the developed PCR‐RFLP‐CE technique was successfully applied to identify Phytophthora species in artificially infested fruits.CONCLUSIONWe provide a quick, practical, and high‐throughput detection approach for hazardous and invasive Phytophthora species associated with imported fruits in China. This strategy can give good convenience and technological support for carrying out massive quarantine activities at Chinese ports. © 2024 Society of Chemical Industry.
The cultivable gut bacteria Enterococcus mundtii promotes early‐instar larval growth of Conogethes punctiferalis via enhancing digestive enzyme activity
Authors: Li Jiayu , Ni Boqing , Wu Yanan , Yang Yueyue , Mu Dongli , Wu KaiNing , Zhang Aihuan , Du Yanli , Li Qian 
Published: July 2024

AbstractBACKGROUNDGut bacteria are crucial in influencing insect development and even phenotypic plasticity. The yellow peach moth Conogethes punctiferalis, as a significant borer pest, has been the subject of limited reports regarding the structural and diversification changes in its gut microbiota during feeding, and their potential impacts on the growth and development of the host insects.RESULTSThis study, employing 16S rRNA sequencing, demonstrates distinct shifts in the larvae gut microbiome of C. punctiferalis between different feeding stages, highlighting a pronounced diversity in the early‐instar with Enterococcus as a predominant genus in laboratory populations. Through in vitro cultivation and sequencing, three bacterial strains – Micrococcus sp., Brevibacterium sp. and Enterococcus mundtii – were isolated and characterized. Bioassays revealed that E. mundtii‐infused corn significantly boosts early‐instar larval growth, enhancing both body length and weight. Quantitative PCR and spectrophotometry confirmed a higher abundance of E. mundtii in younger larvae, correlating with increased digestive enzyme activity and total protein levels.CONCLUSIONThis study reveals the heightened gut microbiota diversity in early instars of C. punctiferalis larvae, highlighting that Enterococcus represent a predominant bacteria in laboratory populations. In vitro cultivation and bioassays unequivocally demonstrate the significant role of the cultivable gut bacteria E. mundtii in promoting the growth of early‐instar larva. These findings provide a solid theoretical foundation for advancing the comprehension of the intricate interactions between gut microbiota and insect hosts, as well as for the development of eco‐friendly pest control technologies based on targeted manipulation of insect gut microbial communities. © 2024 Society of Chemical Industry.
Comparative Study of the Mechanical, Electronic Structure, and Optical Properties of Cubic Lithium‐Based Perovskite LiMgX3 (X = Cl, Br, I) under Pressure Effects: First‐Principles Calculations
Authors: Luo Wei , Song Shiyi , Du Yaxin , Hu Siying 
Published: July 2024

The mechanical, electronic structure, and optical properties of lithium‐based perovskite LiMgX3 (X = Cl, Br, I) are investigated for the first time at 0–20 GPa using density‐functional theory. The Born stability criteria reveal that the phase transition points of LiMgCl3, LiMgBr3, and LiMgI3 are 20.7, 20.9, and 23.4 GPa, respectively. At 0 GPa, studies on the electronic properties using the Heyd‐Scuseria‐Ernzerhof (HSE06) functional show that LiMgCl3 and LiMgBr3 are indirect bandgap insulators with values of 5.336 and 4.113 eV, whereas LiMgI3 is an indirect bandgap semiconductor with a value of 2.055 eV. In addition, the bandgap calculated using both the PBEsol and HSE06 functionals decreases with increasing pressure, and the bandgap trends with pressure are consistent. Both functionals are also used to study the optical properties of LiMgX3 compounds, which show that they have potential for use in vacuum ultraviolet and photovoltaic applications. The mechanical and optical characteristics of the materials are significantly enhanced under pressure.
Selexipag in patients with pulmonary arterial hypertension associated with connective tissue disease (PAH‐CTD): Real‐world experience from EXPOSURE
Authors: Gaine Sean , Escribano‐Subias Pilar , Muller Audrey , Fernandes Catarina C. , Fontana Martina , Remenova Tatiana , Söderberg Stefan , Lange Tobias J. 
Published: July 2024

AbstractSelexipag is indicated for the treatment of pulmonary arterial hypertension (PAH), including PAH associated with connective tissue disease (CTD), and further insights into the management of selexipag‐treated PAH‐CTD patients in clinical settings are needed. These analyses of the ongoing, multicenter, prospective EXPOSURE (EUPAS19085) study describe characteristics, treatment patterns, tolerability, and outcomes of PAH‐CTD patients initiating selexipag in Europe/Canada. All analyses were descriptive, with idiopathic PAH patients who typically display better prognosis included for context. Six hundred ninety‐eight selexipag‐treated patients had follow‐up information; 178 (26%) had PAH‐CTD. The median age was 68 years, patients were predominantly female (88%), and with WHO functional class III symptoms (63%); the median time since diagnosis was 1.7 years. There were 5% patients at low, 25% intermediate‐low, 40% intermediate‐high, and 30% high risk of 1‐year mortality, according to the ESC/ERS 4‐strata risk score. Most (80%) initiated selexipag as a triple oral therapy, and most of these (62%) remained on triple therapy 6 months post‐baseline. Over a median (Q1−Q3) selexipag exposure period of 8.6 (2.5−17.2) months, 79 (44%) patients discontinued selexipag; 36 (20%) due to tolerability/adverse events. Sixty (34%) patients were hospitalized at least once; 120 hospitalizations occurred, with 49 (48%) deemed PAH‐related. Survival at 1 year was 85%, and at 2 years was 71%; 29 (16%) patients died. These results describe the use of combination therapy with selexipag for patients with PAH‐CTD. These findings suggest an opportunity to optimize the benefits of selexipag among patients with PAH‐CTD by moving from escalating after years in response to clinical deterioration to escalating sooner to prevent clinical deterioration.
A weakest link theory‐based probabilistic fatigue life prediction method for the turbine disc considering the influence of the number of critical sections
Authors: Wang Tianxing , Li Yan‐Feng , Huang Hong‐Zhong , Bai Song 
Published: July 2024

AbstractThis study utilizes the rank correlation coefficient to examine the multi‐site failure correlation of turbine discs. Drawing from the stress‐strength interference model, reliability models both with and without factoring in the multi‐site failure correlation are constructed. Furthermore, the weakest link theory (WLT) within the context of the Weibull distribution function is invoked to develop a model for predicting the fatigue life of turbine discs, taking into account the quantity of critical sections. The variability in the low cycle fatigue (LCF) of turbine discs is scrutinized, leading to the formulation of a probabilistic fatigue life prediction method for these discs. When comparing theoretical values with experimental ones, it becomes evident that factoring in the multi‐site failure correlation significantly enhances the accuracy of turbine disc life predictions.