bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unsatisfactory quality of E. coli asparaginase biogenerics in India: Implications for clinical outcomes in acute lymphoblastic leukaemia
Authors: Sidhu Jasmeet , Gogoi Manash Pratim , Agarwal Praveen , Mukherjee Tathagata , Saha Debparna , Bose Priyanka , Roy Prakriti , Phadke Yogesh , Sonawane Bhatu , Paul Pritha , Saha Vaskar , Krishnan Shekhar 
Published: May 2021

AbstractBackgroundThe biotherapeutic asparaginase is a cornerstone of therapy in acute lymphoblastic leukaemia (ALL). With limited access to the original native Escherichia coli‐derived asparaginase (EcASNase), a variety of EcASNase biogenerics are used in low‐middle‐income countries (LMICs). The variable quality of these biogenerics potentially influences clinical outcomes.ProcedureSeven biogeneric EcASNases (P1–P7) marketed widely in India were evaluated, with P2 as an exemplar for in vivo monitoring. Therapeutic activity of P2 (10,000 IU/m2/dose, intramuscular, every 72 hours) was monitored during induction therapy, and drug‐related toxicities recorded. Molecular identity, purity and in vitro drug activity of seven biogenerics were characterised using multimodal analyses, and findings compared with reference EcASNase (R).ResultsIn patients (N = 62) receiving P2, subtherapeutic asparaginase activity (<100 U/L) was observed in 66% (46/70) of trough timepoints (72 hours postdose) during induction. Twelve patients (19%), 11 with high‐risk ALL, developed hypersensitivity. Isoforms of EcASNase were identified in all seven biogenerics. All generic products contained impurities with batch‐to‐batch variability. These included high levels of protein aggregates and host cell protein contamination. In vitro assays of EcASNase activity and leukaemia cell line cytotoxicity were not discriminatory.ConclusionsOur findings confirm widespread concerns over the unsatisfactory quality and therapeutic activity of native EcASNase biogenerics marketed in LMICs. Appropriate use of these products requires monitored studies to identify clinical suitability and determine appropriate dosing and schedule. For large parts of the world, assured access to high‐quality asparaginases remains an unmet therapeutic need.
High‐temperature creep resistant ternary blends based on polyethylene and polypropylene for thermoplastic power cable insulation
Authors: Ouyang Yingwei , Pourrahimi Amir Masoud , Lund Anja , Xu Xiangdong , Gkourmpis Thomas , Hagstrand Per‐Ola , Müller Christian 
Published: May 2021

AbstractThe impact of a small amount of polystyrene‐b‐poly(ethylene‐co‐butylene)‐b‐polystyrene (SEBS) on the thermomechanical and electrical properties of blends comprising low‐density polyethylene (LDPE) and isotactic polypropylene (PP) is investigated. SEBS is found to assemble at the PP:LDPE interface as well as within isolated PP domains. The addition of 10 wt% SEBS significantly increases the storage modulus between the melting temperatures of the two polyolefins, 110 and 160°C, and results in improved resistance to creep during both tensile deformation as well as compression. Furthermore, the ternary blends display a very low direct‐current (DC) conductivity as low as 3.4 × 10−15 S m−1 at 70°C and 30 kV mm−1, which is considerably lower than values measured for neat LDPE. The here presented type of ternary blend shows potential as an insulation material for high‐voltage direct current power cables.
Nutritional status, swallowing disorders, and respiratory prognosis in adult Duchenne muscular dystrophy patients
Authors: Fayssoil Abdallah , Chaffaut Cendrine , Prigent Helene , Laforet Pascal , Clair Bernard , Orlikowski David , Ogna Adam , Chevret Sylvie , Meng Paris , Annane Djillali , Lofaso Frederic , Crenn Pascal 
Published: May 2021

AbstractMalnutrition and swallowing disorders are common in Duchenne muscular dystrophy (DMD) patients. We assessed, in adult DMD with home mechanical ventilation (HMV) and cough assist device, its prevalence and the relationships with respiratory muscle strength and long‐term respiratory prognosis. We reviewed the patients (n = 117, age 18–39 years [median 24]), followed in a reference center, from 2006 to 2015, to obtain clinical baseline, nutritional status, vital capacity (VC), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP). The median body mass index (BMI) was low (15.6 kg/m²). Included patients had severe restrictive respiratory function with a median VC of 10.5% [7–17] of the predicted value. All patients were on HMV. Prevalence of malnutrition, swallowing disorders, and gastrostomy were respectively 62%, 34%, and 11%. BMI and serum albumin level were significantly associated with MIP, MEP, and VC. The 1‐year/5‐years cumulative incidences of respiratory events (pulmonary sepsis and acute respiratory distress) were, respectively, 20.7%/44.5%. Using univariate analysis, predictive factors for respiratory events were swallowing disorders (p = .001), transthyretinemia (p = .034), MIP (p = .039), and MEP (p = .03) but not BMI or albuminemia. Using multivariate analysis, only swallowing disorders remained significantly associated with respiratory events (OR = 4.2, IC 95% 1.31–12.2, p = .01). In conclusion, this study highlights the interrelationships between nutritional intake, swallowing function, airway clearance, and respiratory function in adult DMD. A multidisciplinary approach focusing on these previous factors is essential to optimize DMD patient health.
DNA‐binding domain as the minimal region driving RNA‐dependent liquid–liquid phase separation of androgen receptor
Authors: Ahmed Junaid , Meszaros Attila , Lazar Tamas , Tompa Peter 
Published: May 2021

AbstractAndrogen receptor (AR) is a nuclear hormone receptor that regulates the transcription of genes involved in the development of testis, prostate and the nervous system. Misregulation of AR is a major driver of prostate cancer (PC). The primary agonist of full‐length AR is testosterone, whereas its splice variants, for example, AR‐v7 implicated in cancer may lack a ligand‐binding domain and are thus devoid of proper hormonal control. Recently, it was demonstrated that full‐length AR, but not AR‐v7, can undergo liquid–liquid phase separation (LLPS) in a cellular model of PC. In a detailed bioinformatics and deletion analysis, we have analyzed which AR region is responsible for LLPS. We found that its DNA‐binding domain (DBD) can bind RNA and can undergo RNA‐dependent LLPS. RNA regulates its LLPS in a reentrant manner, that is, it has an inhibitory effect at higher concentrations. As RNA binds DBD more weakly than DNA, while both RNA and DNA localizes into AR droplets, its LLPS depends on the relative concentration of the two nucleic acids. The region immediately preceding DBD has no effect on the LLPS propensity of AR, whereas the functional part of its long N‐terminal disordered transactivation domain termed activation function 1 (AF1) inhibits AR‐v7 phase separation. We suggest that the resulting diminished LLPS tendency of AR‐v7 may contribute to the misregulation of the transcription function of AR in prostate cancer.
Repeated exposure of house dust mite induces progressive airway inflammation in mice: Differential roles of CCL17 and IL‐13
Authors: Malaviya Ravi , Zhou Zhao , Raymond Holly , Wertheimer Josh , Jones Brian , Bunting Rachel , Wilkinson Patrick , Madireddy Lohith , Hall LeRoy , Ryan Mary , Rao Tadimeti S. 
Published: April 2021

AbstractWe conducted a systematic evaluation of lung inflammation indued by repeated intranasal exposure (for 10 consecutive days) to a human aeroallergen, house dust mite (HDM) in BALB/c mice. Peak influx of neutrophils, monocytes/lymphocytes, and eosinophils was observed in bronchoalveolar lavage (BAL) on days 1, 7 and 11, respectively, and normalized to baseline by day 21. Peak elevations of Th2, myeloid‐derived cytokines/chemokines and serum IgE were seen both in BAL and lung tissue homogenates between days 7 and 11, and declined thereafter; however, IL‐33 levels remained elevated from day 7 to day 21. Airway hyperreactivity to inhaled methacholine was significantly increased by day 11 and decreased to baseline by day 21. The lung tissue showed perivascular and peribronchial cuffing, epithelial hypertrophy and hyperplasia and goblet cell formation in airways by day 11, and resolution by day 21. Levels of soluble collagen and tissue inhibitors of metalloproteinases (TIMP) also increased reflecting tissue remodeling in the lung. Microarray analysis demonstrated a significant time‐dependent up‐regulation of several genes including IL‐33, CLCA3, CCL17, CD4, CD10, CD27, IL‐13, Foxa3, IL‐4, IL‐10, and CD19, in BAL cells as well as the lung. Pre‐treatment of HDM challenged mice with CCL17 and IL‐13 antibodies reduced BAL cellularity, airway hyper‐responsiveness (AHR), and histopathological changes. Notably, anti‐IL‐13, but not anti‐CCL17 monoclonal antibodies (mAbs) reduced BAL neutrophilia while both mAbs attenuated eosinophilia. These results suggest that CCL17 has an overlapping, yet distinct profile versus IL‐13 in the HDM model of pulmonary inflammation and potential for CCL17‐based therapeutics in treating Th2 inflammation.
Beyond the single average tumor: Understanding IO combinations using a clinical QSP model that incorporates heterogeneity in patient response
Authors: Kumar Rukmini , Thiagarajan Kannan , Jagannathan Lakshmanan , Liu Liming , Mayawala Kapil , de Alwis Dinesh , Topp Brian 
Published: May 2021

AbstractA quantitative systems pharmacology model for metastatic melanoma was developed for immuno‐oncology with the goal of predicting efficacy of combination checkpoint therapy with pembrolizumab and ipilimumab. This literature‐based model is developed at multiple scales: (i) tumor and immune cell interactions at a lesion level; (ii) multiple heterogeneous target lesions, nontarget lesion growth, and appearance of new metastatic lesion at a patient level; and (iii) interpatient differences at a population level. The model was calibrated to pembrolizumab and ipilimumab monotherapy in patients with melanoma from Robert et al., specifically, waterfall plot showing target lesion response and overall response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), which additionally considers nontarget lesion growth and appearance of new metastatic lesions. We then used the model to predict waterfall and RECIST version 1.1 for combination treatment reported in Long et al. A key insight from this work was that nontarget lesions growth and appearance of new metastatic lesion contributed significantly to disease progression, despite reduction in target lesions. Further, the lesion level simulations of combination therapy show substantial efficacy in warm lesions (intermediary immunogenicity) but limited advantage of combination in both cold and hot lesions (low and high immunogenicity). Because many patients with metastatic disease are expected to have a mixture of these lesions, disease progression in such patients may be driven by a subset of cold lesions that are unresponsive to checkpoint inhibitors. These patients may benefit more from the combinations which include therapies to target cold lesions than double checkpoint inhibitors.
Failure mode and effects analysis using function–motion–action decomposition method and integrated risk priority number for mechatronic products
Authors: Wang Zhichao , Ran Yan , Yu Hui , Jin Chuanxi , Zhang Genbao 
Published: April 2021

AbstractFailure mode and effects analysis is a widely applied risk assessment method in various engineering and management domains. However, the identification of failure modes is difficult and uncountable. Therefore, a function–motion–action (FMA) decomposition method is developed to identify failure modes from the perspective of motion and extraordinarily suitable for mechatronic products. In the typical risk assessment, the ranking orders of failure modes are determined by risk priority number (RPN), which has been criticized for several drawbacks and improved by some alternative RPNs, but some drawbacks still exist, such as duplicate values, narrow admissible value range, and missing failure modes’ and risk factors’ weights. This study formulates several alternative weighted RPNs to overcome the above drawbacks, and the final ranking orders of failure modes are garnered through the integrated RPN (IRPN). First, failure modes are identified via the proposed FMA decomposition method and evaluated with crisp values, whose weights are aggregated from the basic failure modes’ weights. Second, the weights of the basic failure modes, risk factors and different RPN methods are derived from analytic hierarchy process. Third, the conditional weights of risk factors are determined by incorporating risk factors’ weights and failure modes’ conditional weights deduced from Shannon entropy. Next, several alternative weighted RPNs and IRPN are formulated to rank failure modes’ risk levels. Finally, an illustrative example about computer numerical control machine center is presented to demonstrate the application and effectiveness of the proposed method.
Pathways of interest and participation: How STEM‐interested youth navigate a learning ecosystem
Authors: Shaby Neta , Staus Nancy , Dierking Lynn D. , Falk John H. 
Published: May 2021

AbstractDespite considerable efforts in recent years to encourage Science, Technology, Engineering and Mathematics (STEM) interest and participation among youth, STEM interest during adolescence continues to decline. Recently, researchers, educators, and policymakers have used a learning ecology perspective to better understand the development and persistence of youth interest in STEM topics or activities. This study examined the dynamics of the STEM interest and participation pathways of three youth in an under‐resourced, urban community. These three cases offer insights into how youth with a strong interest in a STEM topic or activity perceived the resources that were available to them in a STEM learning ecosystem and highlight the affordances and constraints each faced in pursuit of their interests. We interviewed each youth 4–5 times during their middle school and high school years (ages 11–14). The analysis reinforces the unique nature of youth interest pathways, but also common factors that contributed to each of these pathways. The ability of youth to navigate the ecosystem depended on the availability and accessibility of both in‐ and out‐of‐school learning resources related to their interest, and the support they received from significant adults in their lives in terms of both social, cultural, and financial capital. This study offers important insights into how STEM learning ecosystems might best be structured to enable more youth to develop strong, enduring interests in STEM.
Alleviating debt distress and advancing the sustainable development goals
Authors: Haughton Howard , Keane Jodie 
Published: May 2021

AbstractExternal debt levels will be unprecedented in 2021—in this last decade of action to secure the sustainable development goals (SDGs)—and mostly in distress for low‐income‐developing countries (LIDC) and least developed countries (LDCs). However, increased levels of debt distress were on the horizon even before the dire economic effects of COVID‐19. These high levels of external debt and a decreasing inability to access international capital were already expected to impede the advancement of the SDGs; the situation has become far graver because of the Great Lockdown and efforts to stymie transmission of COVID‐19. The international community faces perhaps its greatest challenge: it must alleviate poor countries debt burdens exacerbated by COVID‐19 to effectively combat its spread, but there is no consensus as to how to achieve this. Though there is no historical parallel to the current debt crisis, the heavily indebted poor country initiative (HIPC) suggests debt relief alone will be insufficient to keep the SDGs on track. While the challenges that arise with regards to the scaling up of debt swap initiatives—learned from previous efforts—are formidable, this article provides critical reflection as to their effective operationalization within the current context: responding to the economic and social devastation wrought by COVID‐19 and keeping the SDGs on track. It shows how debt swaps can be effectively deployed as part of a revitalized global partnership for development, for the advancement of the SDGs and broader debt sustainability.
Efficacy and Safety of Secukinumab for the Treatment of Severe ABCA12 Deficiency-Related Ichthyosis in a Child
Authors: Yogarajah J. , Gouveia C. , Iype J. , Häfliger S. , Schaller A. , Nuoffer J.M. , Fux M. , Gautschi M. 
Published: May 2021

Summary

Background
Patients with severe autosomal recessive congenital ichthyosis (ARCI) show a T helper 17/interleukin 17 (Th17/IL17) skewing in their skin and serum, resembling the inflammatory profile of psoriatic patients. Secukinumab, an IL-17A inhibitor, has shown clinical efficacy in patients with moderate-to-severe plaque psoriasis.

Aims
To test the clinical efficacy and safety of secukinumab in a paediatric patient with ATP-binding cassette subfamily A member 12 deficiency-related severe erythrodermic ARCI.

Materials & Methods
6-months therapeutic trial. During the first 4-weeks induction period, the patient received weekly subcutaneous injections of 150 mg secukinumab (five injections in total). During the following 20-weeks maintenance period, the patient was given a subcutaneous injection of 150 mg secukinumab every 4 weeks.

Result & Discussion
After the 6-months therapy period, there was a 48% reduction from the baseline Ichthyosis-Area-Severity-Index (-Erythema/-Scaling) score. The treatment was well tolerated. Moreover, cytokine analysis revealed a reduction of keratinocyte-derived proinflammatory cytokines and an abrogation of Th17-skewing during therapy.

Conclusion
Further studies are needed to evaluate the effects of the use of IL-17A inhibition in ARCI patients.
Copper (II) and Palladium (II) Schiff‐Base Complexes as Homogeneous and Heterogeneous Catalyst for Efficient α‐Methyl Oxidation Reaction: Experimental and DFT Approaches
Authors: Lashanizadegan Maryam , Ghiasi Mina , Mirzazadeh Hoda , Ferizhandi Azam N. 
Published: April 2021

AbstractNew homogenous catalysts of Schiff base/M(II), (M(II)=Cu, Pd), and new heterogeneous catalysts [graphene oxide (GO)/3‐chlorotrimethoxisilane (CPS) /Schiff base/M(II)] has been successfully synthesized. The heterogenous catalysts were synthesized using 3‐chlorotrimethoxisilane (CPS) via covalent bonding on graphene oxide and were characterized using fourier transform infrared spectroscopy (FTIR), x‐ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive x‐ray spectroscopy(EDS) techniques. Schiff base/M(II) and GO/CPS/Schiff base/M(II) were used as homogenous and heterogeneous catalysts in the oxidation of alkens. Catalytic results showed all the prepared samples were active in the oxidation of α‐methyl styrene. Over as‐prepared heterogeneous catalysts, more than 99 % conversion and selectivity for acetophenone could be achieved using (tert‐butyl hydroproxide (TBHP) : 22.5 mmol, Acetonitrile as solvent after 6 h).The recyclability experiment results indicated that heterogenous catalysts are excellent for α‐methyl styrene conversion and acetophenone selectivity even after being used for four cycles. Moreover, the electronic structures and net atomic charges are interpreted by density functional theory (DFT) calculations. Running title: Copper (II) and palladium (II) Schiff base complexes for experimental and theory study
Ag@AgCl Photocatalyst Loaded on the 3D Graphene/PANI Hydrogel for the Enhanced Adsorption‐Photocatalytic Degradation and In Situ SERS Monitoring Properties
Authors: Chen Fenghua , Liang Weiwei , Qin Xiaoyun , Jiang Liying , Zhang Yonghui , Fang Shaoming , Luo Dan 
Published: April 2021

AbstractHere, 3D GH/PANI/Ag@AgCl composites were successfully synthesized by binding Ag+ ions with the Cl− ions of HCl‐doped PANI in 3D GH/PANI and the subsequent photo‐assisted reduction. Compared with 3D GH/PANI, Ag@AgCl and GO/PANI/Ag@AgCl catalysts, the synergistic effects of porous GH network structure, conductive 1D PANI, and the localized surface plasmon resonance of Ag@AgCl, enabled 3D GH/PANI/Ag@AgCl superior adsorption‐photocatalytic degradation performance of RhB under visible‐light irradiation. PL spectra and a serious of photoelectrochemical measurements were employed to investigate the reasons for such enhanced photocatalytic activity. Combined with the active species trapping experiments, the possible improved photocatalytic degradation mechanism was proposed. With the prepared 3D GH/PANI/Ag@AgCl photocatalyst itself as the substrate, real‐time SERS detection of the presence of RhB and its degradation process can also be achieved. Besides these important results, easy separation and good regeneration property of 3D GH/PANI/Ag@AgCl further make it a promising application in water purification.
Copper‐Based Metal‐Organic Framework for Selective CO2 Adsoprtion and Catalysis Fixation of CO2 into Cyclic Carbonates
Authors: Nguyen Phuong T. K. , Tran Y B. N. 
Published: April 2021

AbstractGiven the capture and utilization of carbon dioxide (CO2) emission, the CO2 separation and catalysis fixation of CO2 and epoxides have been of intense interest. In this respect, a microporous copper‐based metal‐organic framework (MOF) Cu2(ABTC) (ABTC=3,3’,5,5’‐azobenzenetetra‐carboxylic acid) was synthesized. The Cu–MOF endowed with open Cu sites, accessible pore cages and hexagonal channel (9.6 & 11 Å) exhibits permanent porosity (BET surface area of 2200 m2 g−1), good low‐pressure CO2 uptake (93 cm3 g−1, at 298 K), and moderate CO2 selectivity over N2 and CH4. In light of catalysis fixation of CO2 and epoxides, Cu2(ABTC) exhibited outstanding performance with high conversion of styrene oxide (96 %), and yield towards the formation of styrene carbonate (90 %) under mild conditions (1 atm of CO2, 60 °C, 8 h). Notably, the catalytic activity of Cu2(ABTC) outperformed that of other Cu‐MOFs, and the recovered Cu2(ABTC) can be reused up to six times without considerable reduction in catalytic activity.
Free‐enzymatic Indirect Detection of Malathion by SiC@CuO‐NPs Composite Nanomaterial Modified Glassy Carbon Electrode
Authors: Bakytkarim Yrysgul , Tursynbolat Satar , Huang Jianzhi , Wang Lishi 
Published: April 2021

AbstractWe prepared a highly sensitive electrochemical sensor for the free‐enzymatic indirect detection of malathion. The electrochemical sensor was based silicon carbide and copper oxide nanocomposite material. The structural and morphological properties of the SiC@CuO‐NPs nanocomposite was characterized by scanning electron microscopy (SEM) and X‐ray diffraction (XRD). SiC‐NPs has the function of malathion pre‐concentration and SiC@CuO‐NPs nanocomposite was noted to possess high affinity towards malathion, thus the redox reaction of CuO could be hindered. This feature was utilized to design as a simple strategy for electrochemical detection of malathion. Electrochemical detection of malathion was investigated via cyclic voltammetry (CV), differential pulse voltammetry (DPV), respectively. Under the optimized experimental conditions, the inhibition rate displays a good linear relationship with the concentration of malathion, the linear range is 0.03 nM∼3.0 nM, and the detection limit is 0.01 nM (S/N=3). In addition, the sensor exhibits good selectivity, stability and reproducibility, and has been successfully used in the detection of malathion in actual water samples with recoveries between 99.33 % and 106.6 %, which is satisfactory experimental results.