bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Quantitative Modeling and Simulation Framework to Support Candidate and Dose Selection of Anti‐SARS‐CoV‐2 Monoclonal Antibodies to Advance Bamlanivimab Into a First‐in‐Human Clinical Trial
Authors: Chigutsa Emmanuel , Jordie Eric , Riggs Matthew , Nirula Ajay , Elmokadem Ahmed , Knab Tim , Chien Jenny Y. 
Published: October 2021

Neutralizing monoclonal antibodies (mAb), novel therapeutics for the treatment of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2), have been urgently researched from the start of the pandemic. The selection of the optimal mAb candidate and therapeutic dose were expedited using open‐access in silico models. The maximally effective therapeutic mAb dose was determined through two approaches; both expanded on innovative, open‐science initiatives. A physiologically‐based pharmacokinetic (PBPK) model, incorporating physicochemical properties predictive of mAb clearance and tissue distribution, was used to estimate mAb exposure that maintained concentrations above 90% inhibitory concentration of in vitro neutralization in lung tissue for up to 4 weeks in 90% of patients. To achieve fastest viral clearance following onset of symptoms, a longitudinal SARS‐CoV‐2 viral dynamic model was applied to estimate viral clearance as a function of drug concentration and dose. The PBPK model‐based approach suggested that a clinical dose between 175 and 500 mg of bamlanivimab would maintain target mAb concentrations in the lung tissue over 28 days in 90% of patients. The viral dynamic model suggested a 700 mg dose would achieve maximum viral elimination. Taken together, the first‐in‐human trial (NCT04411628) conservatively proceeded with a starting therapeutic dose of 700 mg and escalated to higher doses to evaluate the upper limit of safety and tolerability. Availability of open‐access codes and application of novel in silico model‐based approaches supported the selection of bamlanivimab and identified the lowest dose evaluated in this study that was expected to result in the maximum therapeutic effect before the first‐in‐human clinical trial.
A clinical score to predict mortality in patients after acute heart failure from Japanese registry
Authors: Takabayashi Kensuke , Okada Yohei , Iwatsu Kotaro , Ikeda Tsutomu , Fujita Ryoko , Takenaka Hiroyuki , Kitamura Tetsuhisa , Kitaguchi Shouji , Nohara Ryuji 
Published: October 2021

AbstractAimsClinical scores that consider physical and social factors to predict long‐term observations in patients after acute heart failure are limited. This study aimed to develop and validate a prediction model for patients with acute heart failure at the time of discharge.Methods and resultsThis study was retrospective analysis of the Kitakawachi Clinical Background and Outcome of Heart Failure Registry database. The registry is a prospective, multicentre cohort of patients with acute heart failure between April 2015 and August 2017. The primary outcome to be predicted was the incidence of all‐cause mortality during the 3 years of follow‐up period. The development cohort derived from April 2015 to July 2016 was used to build the prediction model, and the test cohort from August 2016 to August 2017 was used to evaluate the prediction model. The following potential predictors were selected by the least absolute shrinkage and selection operator method: age, sex, body mass index, activities of daily living at discharge, social background, comorbidities, biomarkers, and echocardiographic findings; a risk scoring system was developed using a logistic model to predict the outcome using a simple integer based on each variable's β coefficient. Out of 1253 patients registered, 1117 were included in the analysis and divided into the development (n = 679) and test (n = 438) cohorts. The outcomes were 246 (36.2%) in the development cohort and 143 (32.6%) in the test cohort. Eleven variables including physical and social factors were set into the logistic regression model, and the risk scoring system was created. The patients were divided into three groups: low risk (score 0–5), moderate risk (score 6–11), and high risk (score ≥12). The observed and predicted mortality rates were described by the Kaplan–Meier curve divided by risk group and independently increased (P < 0.001). In the test cohort, the C statistic of the prediction model was 0.778 (95% confidence interval: 0.732–0.824), and the mean predicted probabilities in the groups were low, 6.9% (95% confidence interval: 3.8–10%); moderate, 30.1% (95% confidence interval: 25.4%–34.8%); and high, 79.2% (95% confidence interval: 72.6%–85.8%). The predicted probability was well calibrated to the observed outcomes in both cohorts.ConclusionsThe Kitakawachi Clinical Background and Outcome of Heart Failure score was helpful in predicting adverse events in patients with acute heart failure over a long‐term period. We should evaluate the physical and social functions of such patients before discharge to prevent adverse outcomes.
A Quasi‐Two‐Dimensional Copper Based Organic‐Inorganic Hybrid Perovskite with Reversible Thermochromism and Ferromagnetism
Authors: Fu Hanmei , Jiang Chunli , Luo Chunhua , Lin Hechun , Peng Hui 
Published: October 2021

AbstractTwo‐dimensional (2D) organic‐inorganic hybrid perovskites (OHPs) have been gaining more and more attention for their unique optical, electrical and magnetic behaviors. Herein, we report a multifunctional quasi‐2D hybrid perovskite, 1, 6‐hexanediammonium tetrachlorocuprate ((1, 6‐HDA)CuCl4), which exhibit reversible thermochromic behavior, temperature‐dependent conductivity and ferromagnetism. Changing temperature results in the reversible color change of (1, 6‐HDA)CuCl4 between yellow and brown. A screen‐printing ink is prepared by using (1, 6‐HDA)CuCl4 and used to print thermochromic patterns. The reversible thermochromism originates from the CuCl6 octahedron distortions and lattice expansion in the crystal structure. The conductivity varies more than two orders of magnitude upon temperature change. (1, 6‐HDA)CuCl4 also shows ferromagnetic property with Curie temperatures around 12 K.
Iodine‐Mediated Cross‐Dehydrogenative Coupling of Heterocyclic Thiols with Amines: An Easy and Practical Formation of S−N Bond
Authors: Wu Yue‐Xiao , Peng Kang , Hu Zhi‐Chao , Fan Yong‐Hao , Shi Zhen , Hao Er‐Jun , Dong Zhi‐Bing 
Published: October 2021

AbstractAn efficient iodine‐mediated construction of S−N bond was developed. Such a cross‐dehydrogenative coupling of heterocyclic thiols with amines proceeded smoothly under metal‐free and base‐free conditions, and afforded a series of sulfenamides in good to excellent yields. The easily available substrates and convenient synthetic procedure illustrate potential synthetic value of this protocol for the preparation of sulfenamide related biologically or pharmaceutically active compounds.
A conjoint multi metal‐ion iminodiacetic acid monolith microfluidic chip for structural‐based protein pre‐fractionation
Authors: Khaparde Ashish , Lokesh Kumar S. , Vijayalakshmi M. A. , Tetala Kishore K. R. 
Published: October 2021

AbstractPDMS‐based multichannel microfluidic chip was designed and fabricated in a simple approach using readily available tools. UV‐initiated in situ polymerization of poly(2‐hydroxy ethyl methacrylate‐co‐di(ethylene glycol) diacrylate‐co‐N,Nʹ‐diallyl l‐tartardiamide) in an Eppendorf tube was achieved within 40 min. This polymerization process was successfully translated to a microfluidic chip format without any further modifications. Iminodiacetic acid was successfully immobilized on aldehyde functional monoliths via Schiff base reaction and confirmed by FT‐IR spectroscopy. Four transition metal ions (Co (II), Zn (II), Ni (II), and Cu (II)) were chelated individually on four IDA‐monolith microfluidic chips. The conjoint metal‐ion monolith microfluidic chip has displayed high permeability (9.40 × 10–13 m2) and a porosity of 32.8%. This affinity microfluidic chip has pre‐fractioned four human plasma proteins (fibrinogen, immunoglobulin, transferrin, and human serum albumin) based on their surface‐exposed histidine surface topography. A protein recovery of approximately 95% (Bradford assay data) was achieved. The multimonolith microchip can be reusable even after three protein adsorption‐desorption cycles.
A machine learning‐based method for automatic diagnosis of ankle fracture using X‐ray images
Authors: Wu Mengkun , Sun Hao , Sun Zhenhui , Guo Xin , Duan Lunhui , Tan Yinglun , Cui Rui 
Published: October 2021

AbstractDue to the complex mechanism of ankle injury, the clinical diagnosis of ankle fracture is extremely difficult. In order to simplify the fracture diagnosis process, this study proposes an automatic diagnosis model of ankle fractures. Firstly, an ankle fracture classification method suitable for machine learning was developed. By dividing six fracture regions, multiple types of fractures were clarified, and a corresponding dataset was created accordingly. Secondly, the random forest model was used to preprocess the X‐ray images and segment the fracture foreground part of the X‐ray images. Finally, the bag of visual words (BoVW) was used for feature extraction, and classifiers were constructed in different regions for classification. The area under the curve (AUC) of XGBoost was 0.92 ± 0.06. The performance of the XGBoost has proved to be better compared with the SVM when training on a small dataset in each region.
High D‐index during mobilization predicts poor mobilization ofCD34+ cells after anti‐lymphoma salvage chemotherapy
Authors: Ebisawa Kazutoshi , Honda Akira , Chiba Akira , Masamoto Yosuke , Okazaki Hitoshi , Kurokawa Mineo 
Published: October 2021

AbstractBackgroundPerforming stem cell collection after mobilization chemotherapy was a well‐balanced strategy between anti‐tumor effect and efficient collection of CD34+ cells, but deep and prolonged nadir exposed patients to risk of febrile neutropenia. Febrile neutropenia was known to be associated with lower yields of CD34+ cells, but quantitative data referring to association between yields of CD34+ cells and severity of neutropenia was lacking. We hypothesized that D‐index, which was developed for quantitative evaluation of severity of neutropenia especially in the field of hematologic malignancies, could predict yields of CD34+ cells.MethodsWe performed a single center, retrospective analysis of patients with relapsed or refractory aggressive lymphoma who were mobilized with ESHAP or modified ESHAP. We evaluated the association between yields of CD34+ cells at first apheresis and D‐index.ResultsThirty‐six patients were included, and we demonstrated that yields of CD34+ cells from patients with higher D‐index were significantly lower than those from patients with lower D‐index. Multivariate linear regression analysis and logistic regression analysis also demonstrated the significant predictive power of D‐index. Further, D‐index was significantly correlated to platelet count before starting mobilization chemotherapy. Platelet count was known to predict yields of CD34+ cells, and combination of platelet count and D‐index could identify patients with lowest CD34+ yields.ConclusionD‐index could predict yields of CD34+ cells and it seemed that its predictive power was not less than that of platelet count. Prospective studies including more heterogeneous patients were needed to validate our study.
Integrated care to address child and adolescent health in the 21st century: A clinical review
Authors: Fazel Mina , Townsend Alice , Stewart Harriet , Pao Maryland , Paz Isabel , Walker Jane , Sawyer Susan M. , Sharpe Michael 
Published: October 2021

AbstractBackgroundIncreasing specialisation and technical sophistication of medical tools across the 21st century have contributed to dramatic improvements in the life‐expectancy of children and adolescents with complex physical health problems. Concurrently, there is growing appreciation within the community of the extent that children and adolescents experience mental disorders, which are more prevalent in those with complex chronic, serious or life‐limiting health conditions. In this context, there are compelling reasons for paediatric services to move to a model of care that promotes greater integration of child psychiatry within the medical, somatic teams that care for children and adolescents in children’s hospitals.AimsIn this article, we discuss the range of medical disorders managed by contemporary paediatrics.Materials and MethodsWe conducted a broad review of the literature and existing services, and use individual accounts to illustrate adolescents’ healthcare preferences in the context of the challenges they experience around their mental health.ResultsRelevant disorders include life‐limiting disorders, such as cancer; disorders involving the brain, such as epilepsy; common chronic disorders, such as asthma and diabetes; psychiatric emergencies, such as deliberate self‐harm; and conditions that most commonly present to paediatric services, but where psychiatric input is required, such as severe eating disorders, somatic symptom disorders and gender dysphoria. The persisting legacy of the historical separation of physical and mental health services is described. Yet there are many models of service integration that can promote more collaborative care between psychiatrists and medical specialists, including some which have been taken to scale.DiscussionIn essence, clinical teams in children’s hospitals require more collaborative approaches that facilitate early recognition and treatment of the psychological aspects of illness as an integral part of patient‐centred, family‐focussed paediatric care, rather than as something that is bolted on when things go wrong.ConclusionWhilst trust and goodwill between services and providers will be required for novel models of care to be implemented, evaluation of these new models and incorporation of young people’s healthcare preferences is needed.
Franz Joseph Gall on God and religion: “Dieu et Cerveau, rien que Dieu et cerveau!”
Authors: Eling Paul , Finger Stanley 
Published: October 2021

AbstractFranz Joseph Gall's (1758–1828) doctrine of many faculties of mind with corresponding cortical organs led him to be accused of materialism, fatalism, and even atheism. Yet little has been written about the specific charges he felt forced to respond to in Vienna, while visiting the German States, or in Paris, where he published his books. This article examines these accusations and Gall's responses. It also looks at what Gall wrote about a cortical faculty for God and religion and seeing intelligent design in the functional organization of the brain. Additionally, it presents what can be gleaned about his private thoughts on God and organized religion. We conclude that Gall was sincere in his admiration for and belief in God the Creator, but that as an enlightened scientist was recognizing the need to separate metaphysics from the laws of nature when presenting his new science of man.
New chronology and extended palaeoenvironmental data to the 1975 loess profile of Madaras brickyard, South Hungary
Authors: Sümegi Pál , Gulyás Sándor , Molnár Dávid , Bozsó Gábor , Fekete István , Makó László , Cseh Péter , Molnár Mihály , Sümegi Balázs P. , Almond Peter , Zeeden Christian , Törőcsik Tünde , Nett Janina J. , Markó András , Lehmkuhl Frank 
Published: October 2021

ABSTRACTThe 10 m thick Madaras loess–palaeosol profile is one of the Hungarian outcrops that yielded Upper Palaeolithic artefacts in 1966. To clarify the nature of the deposits and establish a reliable litho‐ and chronostratigraphy, a profile was opened and sampled at 25 cm intervals on the northern side of the brickyard in 1975. Analyses focused on grain size, carbonate content and the mollusc fauna. The chronology was based on the mollusc composition and a single date from the archaeological layer at the depth of ca 7 m below the surface. The 1975 profile was destroyed by mining but the reposited samples allowed an extended analysis of this important Marine Isotope Stage 2 record to which archaeological features were directly assigned. A new absolute chronology was built based on 11 14C dates. Environmental magnetic, geochemical and palaeoecological investigations allowed a refined view of site evolution with reliable chronology for the Last Glacial Maximum. Our results corroborated those of previous investigations done on other coeval loess–palaeosol sequences of the Southern Carpathian Basin. This also allowed for a temporal correlation to another local record with the published high‐resolution chronology of the same brickyard and enabled modelling of local‐scale heterogeneity of the environment in the long run.
Effects of low‐temperature microwave treatment of wheat germ
Authors: Meriles Silvina P , Steffolani Maria E , Penci Maria C , Curet Sebastien , Boillereaux Lionel , Ribotta Pablo D 
Published: October 2021

AbstractBACKGROUNDWheat germ has a great potential byproduct in food formulations for its outstanding nutritional value. To allow valorization, there is a need to inactivate endogenous enzymes such as lipases to avoid lipid oxidation. In the present study, the effects of microwaves on enzyme activity, as well as on functional and physical properties of wheat germ, were evaluated. Microwave treatments were performed at 50, 60 and 70 °C for 5–20 min.RESULTSLipase activity was severely affected at 60 and 70 °C in contrast to lipoxygenase. Microwave treatment did not cause changes in germ moisture content or color parameters. No significant changes were observed in equilibrium moisture content when comparing the adsorption and desorption processes of raw and microwave‐treated wheat germ. The best model to describe sorption process was the Guggenheim–Anderson–De Boer equation. According to the dielectric properties of raw wheat germ, it could be considered as transparent to energy (ε′ < 1.87 and ε′′ < 0.35). Thermal analysis of proteins showed a low denaturation degree (below 35% to raw material). In addition, some functional properties were enhanced such as oil retention capacity. Conformational changes as a result of microwave treatment were associated with the slight decline observed on the monolayer moisture content.CONCLUSIONMicrowave treatments of wheat germ at 60 and 70 °C were effective for lipase inactivation. Physical properties did not change drastically after the treatments. Microwave‐treated wheat germ could be a good source of high‐protein ingredient in food product development. © 2021 Society of Chemical Industry.
Effects of fermentation time and pH on quality of black carrot juice fermented by kefir culture during storage
Authors: Alagöz Kabakcı Sümeyye , Türkyılmaz Meltem , Özkan Mehmet 
Published: October 2021

AbstractBACKGROUNDThe effects of fermentation time (17–48 h) and pH (3.37–4.50) on qualities of fermented beverages (FBs) produced from black carrot juice (BCJ) were monitored during storage at 4 °C for 20 weeks.RESULTSFermentation and adjusting the pH level provided significant increases (up to 22%) in anthocyanin content and the absorbance value at λmax (Amax). Moreover, the stability of anthocyanins, color density, and Amax in FBs was somewhat higher than those in BCJ. Lactic acid showed a co‐pigmentation effect on cyanidin‐3‐galactoside‐xyloside‐glucoside‐sinapic acid and cyanidin‐3‐galactoside‐xyloside‐glucoside‐ferulic acid. Sucrose was degraded much faster at pH 4.50 (17 h) and 4.35 (48 h) than at lower pH levels. During storage, pH 4.35 caused a balanced distribution between counts of lactic acid bacteria (LAB) and yeasts, and antioxidant activity of all FBs increased. Fermented beverages at 4.35 and 3.90 were found to be more palatable by panelists.CONCLUSIONWe recommend FB production at pH 4.35 after 48 h fermentation due to the balanced distribution of probiotics, high color enhancement, and consumer preference. © 2021 Society of Chemical Industry.
Soil chemical quality assessment and spatial distribution of pomelo orchards in acidic red soil hilly regions of China
Authors: Guo Jiuxin , Luo Ziwei , Tao Jingxia , Zhang Jun , Gan Zengguang , Lin Feng , Luo Lijuan , Liao Wenqiang , Chen Li‐Song , Li Yan 
Published: October 2021

AbstractBACKGROUNDSoil quality assessment is a critical strategy for determining optimum fertilization in intensive pomelo production. In this study, we evaluated the soil quality status and mapped the spatial distribution of 347 soil samples collected from pomelo orchards in Pinghe County, southern China. We analyzed nine chemical parameters and an altitude indicator.RESULTSThe mean soil quality index (SQI) was 0.355 in the total data set (TDS) and 0.292 in the minimum data set (MDS). Available Ca (Avail‐Ca), pH value, organic matter and altitude were selected as indicators of soil quality in the MDS. The SQI in mature orchards (>10 years) was higher than that in young orchards (<10 years), while no differences between soil types and altitude gradients were identified. We detected a significant positive correlation between the SQI based on TDS (SQITDS) and the SQI based on MDS (SQIMDS), and the spatial distribution of soil properties and SQITDS showed a uniform pattern, except for Avail‐N, Avail‐B and SQIMDS. Overall, unfavorable soil quality indicators, including rich in Avail‐P, deficient in Avail‐Ca, ‐Mg and ‐B, soil acidification and high altitude, were considered to be limiting factors for pomelo production.CONCLUSIONThe soil chemical quality in pomelo orchards is generally low, indicating that integrated management by controlling acidification, reducing planting altitude, regulating fertilization and monitoring soil properties is required for sustainable pomelo production. © 2021 Society of Chemical Industry.
Determination of sulfonamides in milk and egg samples by HPLC with mesoporous polymelamine‐formaldehyde as magnetic solid‐phase extraction adsorbent
Authors: Liao Wanliang , Ning Yuhan , Zhang Ying , Wang Weiping , Wang Ai‐jun 
Published: October 2021

AbstractIn this work, magnetic mesoporous polymelamine‐formaldehyde composites were synthesized via a facile Schiff base reaction. The magnetic mesoporous polymelamine‐formaldehyde composites combined both the properties of mesoporous polymelamine‐formaldehyde and the magnetism of NH2‐SiO2@Fe3O4 nanoparticles, possessing high specific surface area (150.66 m2 g–1) and good magnetism (24.50 emu g–1). The magnetic mesoporous polymelamine‐formaldehyde composites were employed as magnetic adsorbent for the extraction of sulfonamides. Under optimal conditions, good linearities with correlation coefficients higher than 0.9984 were obtained between peak area and sulfonamides concentration (2–200 μg L–1) with limits of detection in the range of 0.33–0.58 μg L–1. The established method was successfully applied for the determination of sulfonamides in egg and milk samples. The adsorption mechanisms demonstrated that the adsorption of magnetic mesoporous polymelamine‐formaldehyde composites toward sulfonamides was a multilayer process, and adsorption kinetics followed the pseudo‐second‐order model.