bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of spray-dried Gac aril extract and estimated shelf life of β-carotene and lycopene
Authors: Thumthanaruk Benjawan , Laohakunjit Natta , Chism Grady W.
Published: March 2021

Background

Fresh Gac (Momordica cochinchinensis) fruit is rich in carotenoids, mainly β-carotene and lycopene, but these compounds are sensitive to degradation. Spray drying is used to encapsulate the sensitive β-carotene and lycopene with different materials. Only a few reports of using highly branched cyclodextrin (HBCD) have been published. Additionally, studies of β-carotene and lycopene losses in Gac powders during storage are limited. Therefore, the encapsulation of β-carotene and lycopene of Gac aril with HBCD by spray drying at different inlet temperatures were compared. The shelf life of β-carotene and lycopene during storage was also calculated.

Methods

The fresh Gac aril was separated and kept frozen before the experiment. Gac aril and water (1:5 w/v) were centrifuged at 8,000 g at 20 °C for 15 min using a high-speed centrifuge (Sorval; Dupont, Wilmington, DE, USA). The supernatant was filtered twice and concentrated until 15° Brix using a rotary evaporator (R-200; Buchi, Flawil, Switzerland). The mixture of concentrated aril extract and highly branched cyclodextrin at 5% (w/v) was dried at three inlet temperatures by a spray dryer (B-290; Buchi, Flawil, Switzerland) with drying air flow rate, compressor air pressure, and feed rate set at 473 L/h, 40 m3/h, and 3 mL/min, respectively . The physicochemical qualities, particle image morphology, and estimated storage time of β-carotene and lycopene were determined.

Results

Increased inlet temperatures of spray drying decreased the bulk density, β-carotene, and lycopene content of spray-dried powders significantly. The color values of dried powders had significant differences in yellowness (b*) and chroma, but not lightness (L*), redness (a*), and hue when the inlet temperature increased from 160 °C to 180 °C. The maximum reduction of β-carotene and lycopene observed during storage at 55 °C was 90.88% and 91.11% for 33 and 18 days. For β-carotene, the estimated shelf-life (retention of 50% of β-carotene) was 9.9, 48.4, and 91.6 days at 25 °C, 10 °C, and 4 °C. The shelf-life of lycopene was 26, 176, and 357 days at 25 °C, 10 °C, and 4 °C, respectively. HBCD could be potentially used as an encapsulating agent in spray-dried Gac aril, but the shelf-life of β-carotene and lycopene needs to be improved to be useful as a food ingredient.
Grimontia
Authors: Pujalte María J. , Macián M. Carmen , Lucena Teresa , Arahal David R.
Published: March 2021

Gri.mon'ti.a. N.L. gen. n.
Grimontia
of Grimont, after the French microbiologist P. A. D. Grimont.

Proteobacteria / Gammaproteobacteria / Vibrionales / Vibrionaceae / Grimontia

The genus
Grimontia
pertains to the family
Vibrionaceae
and accommodates three species validly published:
Grimontia hollisae
,
Grimontia marina
, and
Grimontia celer
. “
Grimontia indica
,” isolated from seawater collected from Palk Bay in India, was effectively but not validly published.

Cells are Gram‐negative curved rods or short spirals, 1.8–2.8 μm in length and 0.5–0.7 μm in width, and highly motile by a polar flagellum. Spores are not formed. Chemoheterotrophic, mesophilic, and moderately halophilic. Oxidase‐ and catalase‐positive. Facultative anaerobe, fermenting
d
‐glucose without gas production. Strains are negative for Voges–Proskauer reaction, lysine, and ornithine decarboxylase, but nitrate reduction is positive. Indole production and arginine dihydrolase are variable with species. Colonies on Marine Agar are cream colored, round, and convex and have regular borders after 48 h at 26°C. The main cellular fatty acids are summed feature 3 (C
16:1
ω6
c
and/or C
16:1
ω7
c
), summed feature 8 (C
18:1
ω6
c
and/or C
18:1
ω7
c
), and C
16:0
. The major respiratory quinone is Q‐8. The major polar lipids include diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine. The known habitats are seawater, marine animals, and, in the case of
G. hollisae
, also patients suffering diarrhea.

DNA G + C content (mol%)
:
48.2–49.6 (genome).

Type species
:
Grimontia hollisae
Thompson et al. 2003
VP
.
Planctomycetes
Authors: Ward Naomi L. , Dedysh Svetlana N.
Published: March 2021

Planc.to.my.ce'tes. N.L. pl. n.
Planctomycetia
the type class of the phylum; ‐
etes
ending to denote a phylum; N.L. fem. pl. n.
Planctomycetes
the phylum of
Planctomycetia
.

The phylum
Planctomycetes
was circumscribed on the basis of the phylogenetic analysis of 16S rRNA gene sequences. This phylum accommodates Gram‐stain‐negative bacteria, which divide either by budding or by binary fission and colonize a wide spectrum of aquatic and terrestrial habitats. The phylum contains two classes with validly published names, that is,
Planctomycetia
and
Phycisphaerae
, which accommodate aerobic and anaerobic chemoorganotrophs. Chemolithoautotrophic “anammox” planctomycetes, which are capable of anaerobic ammonium oxidation, comprise the class
Candidatus
Brocadiae.

Type class
:
Planctomycetia
Ward 2011b, VL194.
Metal Catalyst to Construct Carbon Nanotubes Networks on Metal Oxide Microparticles towards Designing High‐Performance Electrode for High‐Voltage Lithium‐Ion Batteries
Authors: Sun Qujiang , Cao Zhen , Zhang Junli , Cheng Haoran , Zhang Jiao , Li Qian , Ming Hai , Liu Gang , Ming Jun
Published: March 2021

Designing carbon nanotubes (CNTs)‐based materials are attracting great attention due to their fantastic properties and greater performance. Herein, a new CNTs network triggered by metal catalysts (e.g., Co, Ni, or Cu) is constructed on metal oxide (e.g., MnO) microparticles, giving rise to a high‐performance Co‐MnO@C‐CNTs anode in lithium‐ion batteries (LIBs). An extremely high capacity of 1050 mAh g−1, extraordinary rate capacities over 10 A g−1, and a long lifespan over 500 cycles are demonstrated. The great features of Co‐MnO@C‐CNTs anode are further confirmed in LIBs when the nickel‐rich cathode (e.g., LiNi0.8Co0.1Mn0.1O2) is used and charged at a high voltage over 4.5 V. A high‐capacity retention of 71.5% can be maintained at 1 C over 150 cycles. The superior performance relates to the CNTs network, which not only acts as an “expressway network” for fast ion/electron transportation but also buffers structural variation. Moreover, the metal nanoparticles can also enhance the electrical conductivity and catalyze the (de‐)lithiation of metal oxide, resulting in higher reversibility and long‐term cyclability. This study opens a new avenue to prepare CNTs‐based functional materials and also explores the potential applications of metal oxide‐based anode for high‐performance batteries.
Deconvoluting Energy Transport Mechanisms in Metal Halide Perovskites Using CsPbBr3 Nanowires as a Model System
Authors: Oksenberg Eitan , Fai Calvin , Scheblykin Ivan G. , Joselevich Ernesto , Unger Eva L. , Unold Thomas , Hages Charles , Merdasa Aboma
Published: March 2021

Understanding energy transport in metal halide perovskites is essential to effectively guide further optimization of materials and device designs. However, difficulties to disentangle charge carrier diffusion, photon recycling, and photon transport have led to contradicting reports and uncertainty regarding which mechanism dominates. In this study, monocrystalline CsPbBr3 nanowires serve as 1D model systems to help unravel the respective contribution of energy transport processes in metal‐halide perovskites. Spatially, temporally, and spectrally resolved photoluminescence (PL) microscopy reveals characteristic signatures of each transport mechanism from which a robust model describing the PL signal accounting for carrier diffusion, photon propagation, and photon recycling is developed. For the investigated CsPbBr3 nanowires, an ambipolar carrier mobility of μ = 35 cm2 V−1 s−1 is determined, and is found that charge carrier diffusion dominates the energy transport process over photon recycling. Moreover, the general applicability of the developed model is demonstrated on different perovskite compounds by applying it to data provided in previous related reports, from which clarity is gained as to why conflicting reports exist. These findings, therefore, serve as a useful tool to assist future studies aimed at characterizing energy transport mechanisms in semiconductor nanowires using PL.
Diverse Metal–Organic Framework Architectures for Electromagnetic Absorbers and Shielding
Authors: Shu Jin‐Cheng , Cao Wen‐Qiang , Cao Mao‐Sheng
Published: March 2021

Metal–organic frameworks (MOFs) and their derivatives, featuring unique 3D microstructures and enhanced electromagnetic properties, are illuminating infinite possibilities for electromagnetic functional materials and devices, receiving significant attention from domestic and foreign researchers. Herein, the design strategy of the MOF monomer is investigated, and the electromagnetic response mechanism is systematically analyzed. Research is emphatically introduced regarding MOF‐based materials in microwave absorption and electromagnetic interference shielding. Finally, a clear insight on the quickly growing field is given, and the current challenges and future research directions are summarized and predicted.
Weighted Mobility Ratio Engineering for High‐Performance Bi–Te‐Based Thermoelectric Materials via Suppression of Minority Carrier Transport
Authors: Kim Minyoung , Kim Sang‐il , Kim Sung Wng , Kim Hyun‐Sik , Lee Kyu Hyoung
Published: March 2021

Thermoelectrics, which can generate electricity from a temperature difference, or vice versa, is a key technology for solid‐state cooling and energy harvesting; however, its applications are constrained owing to low efficiency. Since the conversion efficiency of thermoelectric devices is directly obtained via a figure of merit of materials, zT, which is related to the electronic and thermal transport characteristics, the aim here is to elucidate physical parameters that should be considered to understand transport phenomena in semiconducting materials. It is found that the weighted mobility ratio of the majority and minority carrier bands is an important parameter that determines zT. For nanograined Bi–Sb–Te alloy, the unremarked role of this parameter on temperature‐dependent electronic transport properties is demonstrated. This analysis shows that the control of the weighted mobility ratio is a promising way to enhance zT of narrow bandgap thermoelectric materials.
Active Targeting Nanoparticle Self‐Assembled from Cisplatin‐Palbociclib Amphiphiles Ensures Optimal Drug Ratio for Combinatorial Chemotherapy
Authors: Xiang Yucheng , Liu Chendong , Chen Liqiang , Li Lian , Huang Yuan
Published: March 2021

Triple negative breast cancer (TNBC) not only exhibits aggressive progression and metastasis, but also responds to neither hormone therapy nor checkpoint blockade therapy. Thus, combinatorial chemotherapy is indispensable for TNBC treatment. However, due to the different pharmacokinetics of individual drugs and weak synergistic effects caused by random drug molar ratio in tumor, direct coadministration is far from satisfactory. Constructing a nanoscale drug delivery system with fixed drug molar ratios and maximum drug content is an urgent problem. Herein, an active targeting nanoparticle self‐assembled from cisplatin‐palbociclib amphiphiles with optimal drug ratio is reported. The combination of cisplatin and palbociclib at a molar ratio of 1:2 is found to have the best synergistic effect and is selected for follow‐up studies. After conjugating two palbociclib molecules to one cisplatin molecule, a fixed cisplatin/palbociclib (1:2) molar ratio is enabled and this amphiphilic conjugate can self‐assemble into nanoparticles. A small amount of iRGD coupled 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐polyethylene glycol‐2000 (DSPE‐PEG‐iRGD) that further stabilizes the nanoparticle is introduced to fabricate the desired nanoparticle (iRGD‐PCN) and endow active tumor‐targeting ability. On an orthotopic TNBC mouse model, iRGD‐PCN efficiently accumulates in tumors and inhibits tumor growth. Additionally, the formation of lung metastasis nodes is also significantly suppressed. In general, the active targeting nanoparticles self‐assembled from cisplatin‐palbociclib amphiphiles provide options for combinatorial chemotherapy.
Recent Progress on Wear‐Resistant Materials: Designs, Properties, and Applications
Authors: Zhai Wenzheng , Bai Lichun , Zhou Runhua , Fan Xueling , Kang Guozheng , Liu Yong , Zhou Kun
Published: March 2021

There has been tremendous interest in the development of different innovative wear‐resistant materials, which can help to reduce energy losses resulted from friction and wear by ≈40% over the next 10–15 years. This paper provides a comprehensive review of the recent progress on designs, properties, and applications of wear‐resistant materials, starting with an introduction of various advanced technologies for the fabrication of wear‐resistant materials and anti‐wear structures with their wear mechanisms. Typical strategies of surface engineering and matrix strengthening for the development of wear‐resistant materials are then analyzed, focusing on the development of coatings, surface texturing, surface hardening, architecture, and the exploration of matrix compositions, microstructures, and reinforcements. Afterward, the relationship between the wear resistance of a material and its intrinsic properties including hardness, stiffness, strength, and cyclic plasticity is discussed with underlying mechanisms, such as the lattice distortion effect, bonding strength effect, grain size effect, precipitation effect, grain boundary effect, dislocation or twinning effect. A wide range of fundamental applications, specifically in aerospace components, automobile parts, wind turbines, micro‐/nano‐electromechanical systems, atomic force microscopes, and biomedical devices are highlighted. This review is concluded with prospects on challenges and future directions in this critical field.
Magnetic State Generation using Hamiltonian Guided Variational Autoencoder with Spin Structure Stabilization
Authors: Kwon Hee Young , Yoon Han Gyu , Park Sung Min , Lee Doo Bong , Choi Jun Woo , Won Changyeon
Published: March 2021

Numerical generation of physical states is essential to all scientific research fields. The role of a numerical generator is not limited to understanding experimental results; it can also be employed to predict or investigate characteristics of uncharted systems. A variational autoencoder model is devised and applied to a magnetic system to generate energetically stable magnetic states with low local deformation. The spin structure stabilization is made possible by taking the explicit magnetic Hamiltonian into account to minimize energy in the training process. A significant advantage of the model is that the generator can create a long‐range ordered ground state of spin configuration by increasing the role of stabilization even if the ground states are not necessarily included in the training process. It is expected that the proposed Hamiltonian‐guided generative model can bring about great advances in numerical approaches used in various scientific research fields.
Metal‐Organic Fragments with Adhesive Excipient and Their Utilization to Stabilize Multimetallic Electrocatalysts for High Activity and Robust Durability in Oxygen Evolution Reaction
Authors: Choi Won Ho , Kim Keon‐Han , Lee Heebin , Choi Jae Won , Park Dong Gyu , Kim Gi Hwan , Choi Kyung Min , Kang Jeung Ku
Published: March 2021

Multimetallic electrocatalysts have shown great potential to improve electrocatalytic performance, but their deteriorations in activity and durability are yet to be overcome. Here, metal‐organic fragments with adhesive excipient to realize high activity with good durability in oxygen evolution reaction (OER) are developed. First, a leaf‐like zeolitic–imidazolate framework (ZIF‐L) is synthesized. Then, ionized species in hydrogen plasma attack preferentially the organic linkers of ZIF‐L to derive cobalt–imidazole fragments (CIFs) as adhesive excipient, while they are designed to retain the coordinated cobalt nodes. Moreover, the vacant coordination sites at cobalt nodes and the unbound nitrogen at organic linkers induce high porosity and conductivity. The CIFs serve to stably impregnate trimetallic FeNiMo electrocatalysts (CIF:FeNiMo), and CIF:FeNiMo containing Fe contents of 22% and hexavalent Mo contents show to enable high activity with low overpotentials (203 mV at 10 mA cm−2 and 238 mV at 100 mA cm−2) in OER. The near O K‐edge extended X‐ray absorption fine structure proves further that high activity for OER originates from the partially filled eg orbitals. Additionally, CIF:FeNiMo exhibit good durability, as demonstrated by high activity retention during at least 45 days in OER.
Hematopoietic expression of a chimeric murine‐human CALR oncoprotein allows the assessment of anti‐CALR antibody immunotherapies in vivo
Authors: Achyutuni Sarada , Nivarthi Harini , Majoros Andrea , Hug Eva , Schueller Christina , Jia Ruochen , Varga Cecilia , Schuster Michael , Senekowitsch Martin , Tsiantoulas Dimitris , Kavirayani Anoop , Binder Christoph J , Bock Christoph , Zagrijtschuk Oleh , Kralovics Robert
Published: March 2021

Myeloproliferative neoplasms (MPNs) are characterized by a pathologic expansion of myeloid lineages. Mutations in JAK2, CALR and MPL genes are known to be three prominent MPN disease drivers. Mutant CALR (mutCALR) is an oncoprotein that interacts with and activates the thrombopoietin receptor (MPL) and represents an attractive target for targeted therapy of CALR mutated MPN. We generated a transgenic murine model with conditional expression of the human mutant exon 9 (del52) from the murine endogenous Calr locus. These mice develop essential thrombocythemia like phenotype with marked thrombocytosis and megakaryocytosis. The disease exacerbates with age showing prominent signs of splenomegaly and anemia. The disease is transplantable and mutCALR stem cells show proliferative advantage when compared to wild type stem cells. Transcriptome profiling of hematopoietic stem cells revealed oncogenic and inflammatory gene expression signatures. To demonstrate the applicability of the transgenic animals for immunotherapy, we treated mice with monoclonal antibody raised against the human mutCALR. The antibody treatment lowered platelet and stem cell counts in mutant mice. Secretion of mutCALR did not constitute a significant antibody sink. This animal model not only recapitulates human MPN but also serves as a relevant model for testing immunotherapeutic strategies targeting epitopes of the human mutCALR.
A rare case of postnatal mosaic trisomy 12 with severe congenital heart disease and literature review
Authors: Hu Xiaolin , Ayala Sofia Saenz , Dyer Lisa , Guan Qiaoning , Pena Loren
Published: March 2021

Trisomy 12 is a rare autosomal aneuploidy. All postnatally diagnosed individuals with trisomy 12 have been mosaic for this chromosome abnormality. We herein report an infant girl presented at 2 weeks of age with severe congenital heart defect, tracheobronchomalacia, and dysmorphic features. All of the dysmorphic features of this patient fit into the known phenotype spectrum of mosaic trisomy 12, although this patient uniquely presented with macrocephaly. Tracheo‐bronchomalacia has been described once previously but had a significant impact on this patient's clinical course. The patient passed away at 2‐month‐old due to cardiac and respiratory complications. Chromosomal single nucleotide polymorphism (SNP) microarray analysis on a peripheral blood sample from the patient revealed trisomy 12 in approximately 50% of cells. Concurrent fluorescence in situ hybridization analysis of uncultured blood cells detected a comparable level of trisomy 12 mosaicism. Compared to conventional cytogenetics, SNP microarray examines all nucleated cells without sampling bias, has an increased power to estimate mosaicism level, and can provide a quick assessment of the underlying mechanism. Here we demonstrate the utilization of SNP microarray in the clinical diagnosis of those once considered rare disorders but might have been missed by conventional cytogenetic techniques.
The mystery of monozygotic twinning I: What can Amyoplasia tell us about monozygotic twinning and the possible role of twin–twin transfusion?
Authors: Hall Judith G.
Published: March 2021

Amyoplasia is a very specific, nongenetic clinically recognizable form of arthrogryposis, representing about one‐third of individuals with arthrogryposis surviving the newborn period. There is a markedly increased number of individuals with Amyoplasia who are one of monozygotic (MZ) twins, with the other twin being normal. Thus, it would appear that Amyoplasia is definitely associated with and may be caused by an MZ twinning event. The twin–twin transfusion seen in MZ twins could play an etiologic role in producing Amyoplasia. In this article, Amyoplasia twinning is compared to twinning in other forms of arthrogryposis. The accompanying paper examines various types of MZ twinning (Hall, 2021). Amyoplasia is primarily associated with spontaneous MZ twinning.
Natural history study of adults with Wolf–Hirschhorn syndrome 1: Case series of personally observed 35 individuals
Authors: Battaglia Agatino , Lortz Amanda , Carey John C.
Published: March 2021

Wolf–Hirschhorn syndrome (WHS) is a contiguous gene disorder, clinically delineated by prenatal and postnatal growth deficiency, distinctive craniofacial features, intellectual disability, and seizures. The disorder is caused by partial loss of material from the distal portion of the short arm of chromosome 4 (4p16.3). Although more than 300 persons with WHS have been reported in the literature, there is sparse, if any, long‐term follow‐up of these individuals and thus little knowledge about course and potential further complications and health risks during adulthood and advanced age. This study attempted to assess medical conditions and function of adult individuals with WHS. It was one component of a two‐part investigation on adults with WHS. The other part of the study is the patient‐reported outcomes study reported elsewhere. About 35 individuals with WHS (26 females; nine males), aged between 19 and 55 years were recruited. About 25 individuals were personally observed at the IRCCS Stella Maris Foundation by A.B. and followed up between 5 and 20 years; and 10 were recruited from the 4p‐Support Group, The United States. Of note, 23/35 (66%) are close to total care. About 11 out of 35 (31%) were partly self‐independent, requiring supervision on certain daily routines, and 1 out of 35 (3%) was fully independent. However, a positive perspective is given by the overall good health enjoyed by the 66% of our cohort of individuals. Overall, quality of life and level of function into adulthood appear to be less critical than anticipated from previous studies.
Design and synthesis of benzenesulfonamide‐linked imidazo[2,1‐b][1,3,4]thiadiazole derivatives as carbonic anhydrase I and II inhibitors
Authors: Swain Baijayantimala , Aashritha Kamtam , Singh Priti , Angeli Andrea , Kothari Abhay , Sigalapalli Dilep K. , Yaddanapudi Venkata M. , Supuran Claudiu T. , Arifuddin Mohammed
Published: March 2021

A novel series of imidazothiadiazole‐linked benzenesulfonamide derivatives (5a–t) was synthesized and subjected for screening against the four physiologically and pharmacologically relevant human carbonic anhydrase (hCA) isoforms: hCA I, II, VA, and IX. The compounds selectively inhibited hCA I and II over hCA VA and IX. Furthermore, among the two cytosolic isoforms, hCA II was more effectively inhibited as compared with hCA I. The most active compounds were 5o with K
i = 0.246 µM and 5p with K
i = 0.376 µM against hCA II, whereas compound 5f showed good inhibition against both hCA I and II with K
i = 0.493 and 0.4 µM, respectively. This class of underexplored sulfonamides may be used to design isoform‐selective CA inhibitors targeting enzymes of medicinal chemistry interest.
Integrated geophysical study in the cemetery of Marquis of Haihun
Authors: Li Man , Zhang Zhiyong , Yang Jun , Xie Shangping
Published: March 2021

A group of Han dynasty tombs were found in a small town in central eastern China. It is difficult to infer the underground structures of the cemetery based on surface information. Geophysical methods are nonintrusive technology that can be used in archaeological excavations to provide important underground information. Multiple geophysical methods including total magnetic field (TMF), self‐potential (SP), direct‐current resistivity (DCR) and ground‐penetrating radar (GPR) were used to investigate the structure of ancient tombs. Total magnetic anomaly (TMA) and SP data can be used to obtain the projections of anomalous bodies on earth surface. DCR and GPR data can be used to gauge and further determine the spatial locations and depths of the anomalies. The results of the integrated geophysical interpretation were used to optimize the excavation plans and were verified by the subsequent works, such as coffin chambers, dromoi, ancient building foundations and funeral pit. Integrated geophysical survey can effectively reduce the uncertainly of a single method and obtain the targets more accurately.
Ethical considerations for remote sensing and open data in relation to the endangered archaeology in the Middle East and North Africa project
Authors: Fisher Michael , Fradley Michael , Flohr Pascal , Rouhani Bijan , Simi Francesca
Published: March 2021

The UK‐based Endangered Archaeology in the Middle East and North Africa (EAMENA) project uses remote sensing techniques to rapidly record and evaluate the status of archaeological and cultural heritage sites in the MENA region. Applying remote sensing methods to the archaeological landscapes of 20 countries, EAMENA is one of the largest documentation projects of its kind. Such a scope raises important ethical questions fundamental to the practice of remote‐sensed archaeology, and this paper contributes to this discussion by reflecting on EAMENA's unique role in this subfield. We present ethical issues and possible solutions related to remote sensing and archaeology, drawing on models developed within the humanitarian aid sector and postcolonial archaeology. In addition, we consider issues of national sovereignty and their relationship to the engagement of local communities. Finally, this paper examines the roles of data openness and open access policies as ethical factors and how EAMENA has addressed these so far.
Serum Metabolomics Identifies Dysregulated Pathways and Potential Metabolic Biomarkers for Hyperuricemia and Gout
Authors: Shen Xia , Wang Can , Liang Ningning , Liu Zhen , Li Xinde , Zhu Zheng‐Jiang , Merriman Tony R. , Dalbeth Nicola , Terkeltaub Robert , Li Changgui , Yin Huiyong
Published: March 2021

Objective

To systematically profile metabolic alterations and dysregulated metabolic pathways in hyperuricemia and gout, and to identify potential metabolite biomarkers to discriminate gout from asymptomatic hyperuricemia.

Methods

Serum samples from 330 participants, including 109 with gout, 102 with asymptomatic hyperuricemia, and 119 normouricemic controls, were analyzed by high‐resolution mass spectrometry–based metabolomics. Multivariate principal components analysis and orthogonal partial least squares discriminant analysis were performed to explore differential metabolites and pathways. A multivariate methods with Unbiased Variable selection in R (MUVR) algorithm was performed to identify potential biomarkers and build multivariate diagnostic models using 3 machine learning algorithms: random forest, support vector machine, and logistic regression.

Results

Univariate analysis demonstrated that there was a greater difference between the metabolic profiles of patients with gout and normouricemic controls than between the metabolic profiles of individuals with hyperuricemia and normouricemic controls, while gout and hyperuricemia showed clear metabolomic differences. Pathway enrichment analysis found diverse significantly dysregulated pathways in individuals with hyperuricemia and patients with gout compared to normouricemic controls, among which arginine metabolism appeared to play a critical role. The multivariate diagnostic model using MUVR found 13 metabolites as potential biomarkers to differentiate hyperuricemia and gout from normouricemia. Two‐thirds of the samples were randomly selected as a training set, and the remainder were used as a validation set. Receiver operating characteristic analysis of 7 metabolites yielded an area under the curve of 0.83–0.87 in the training set and 0.78–0.84 in the validation set for distinguishing gout from asymptomatic hyperuricemia by 3 machine learning algorithms.

Conclusion

Gout and hyperuricemia have distinct serum metabolomic signatures. This diagnostic model has the potential to improve current gout care through early detection or prediction of progression to gout from hyperuricemia.
Association of Machine Learning–Based Predictions of Medial Knee Contact Force With Cartilage Loss Over 2.5 Years in Knee Osteoarthritis
Authors: Brisson Nicholas M. , Gatti Anthony A. , Damm Philipp , Duda Georg N. , Maly Monica R.
Published: March 2021

Objective

The relationship between in vivo knee load predictions and longitudinal cartilage changes has not been investigated. We undertook this study to develop an equation to predict the medial tibiofemoral contact force (MCF) peak during walking in persons with instrumented knee implants, and to apply this equation to determine the relationship between the predicted MCF peak and cartilage loss in patients with knee osteoarthritis (OA).

Methods

In adults with knee OA (39 women, 8 men; mean ± SD age 61.1 ± 6.8 years), baseline biomechanical gait analyses were performed, and annualized change in medial tibial cartilage volume (mm3/year) over 2.5 years was determined using magnetic resonance imaging. In a separate sample of patients with force‐measuring tibial prostheses (3 women, 6 men; mean ± SD age 70.3 ± 5.2 years), gait data plus in vivo knee loads were used to develop an equation to predict the MCF peak using machine learning. This equation was then applied to the knee OA group, and the relationship between the predicted MCF peak and annualized cartilage volume change was determined.

Results

The MCF peak was best predicted using gait speed, the knee adduction moment peak, and the vertical knee reaction force peak (root mean square error 132.88N; R2 = 0.81, P < 0.001). In participants with knee OA, the predicted MCF peak was related to cartilage volume change (R2 = 0.35, β = −0.119, P < 0.001).

Conclusion

Machine learning was used to develop a novel equation for predicting the MCF peak from external biomechanical parameters. The predicted MCF peak was positively related to medial tibial cartilage volume loss in patients with knee OA.
Scientific considerations to move towards biowaiver for biopharmaceutical classification system class III drugs: How modeling and simulation can help
Authors: Wu Fang , Cristofoletti Rodrigo , Zhao Liang , Rostami‐Hodjegan Amin
Published: March 2021

The 2017 Guidance by U.S. Food and Drug Administration (FDA) has recommended the criteria to qualify for a Biopharmaceutical Classification System (BCS)‐based biowaiver that includes high solubility of the drug across the physiological pH range as well as the formulation considerations, e.g., being qualitatively the same and quantitatively very similar to the reference product. These were ratified by the International Council for Harmonization (ICH) in 2018. The FDA has used the similar verbiage when referring to the BCS‐based biowaiver option for BCS class III drugs (highly soluble but poorly permeable). However, establishing in vitro‐in vivo correlations (IVIVC) using conventional mass balance deconvolution approaches, which assumes a single absorption compartment, is not likely for very rapidly dissolving dosage forms containing BCS III drugs. Unlike conventional mass balance deconvolution techniques, physiologically based pharmacokinetic models are able to disentangle different processes contributing to the input function, e.g., dissolution, gastrointestinal transit, and permeation and to establish IVIVC using variants of the compartmental absorption and transit model, supporting biowaiver for formulations containing BCS III drugs. However, there are knowledge gaps that need to be filled. This review provides a systematic assessment of the advancements in applications of physiologically based pharmacokinetic (PBPK) models for IVIVC and biowaiver for such cases with the aim of identifying the most important gaps and hurdles. It concludes by calling for research efforts on the impact of excipients on dissolution and permeation, alongside the development of PBPK modeling to link these in vitro characteristics to in vivo bioequivalence outcomes through simulations of virtual clinical studies
Characterization and rational modification of aspartate 4‐decarboxylase from Acinetobacter radioresistens for the production of l‐alanine
Authors: Liu Zhongmei , Wang Xiangyu , Yu Jiayin , Han Laichuang , Zhou Zhemin
Published: March 2021

Enzymatic synthesis of l‐alanine has the advantages of less byproducts, strong stereoselectivity, and high catalytic efficiency. Aspartate 4‐decarboxylase (ASD) is used industrially in DL‐aspartic acid resolution and l‐alanine production because it catalyzes the decarboxylation of l‐aspartic acid. In this study, the ASD gene from Acinetobacter radioresistens (ArASD) was cloned, and its enzymatic properties were analyzed. ArASD is a dodecamer and has the highest enzyme activity ever reported to date. The optimal conditions for ArASD catalysis are 50°C and pH 4.5. Site‐directed mutagenesis was used to improve ArASD stability under acidic conditions to compensate for its weak acid resistance, and the variant N35D with higher catalytic ability was obtained. The conversion by N35 recombinant cells of l‐aspartic acid to l‐alanine was 92.5% at pH 4.5% and 99.9% at pH 6.0, whereas that of the wild‐type recombinant cells was 29.7% and 31.4%, respectively. Aspartase from Escherichia coli (AspA) was employed with ArASD to construct a dual‐enzyme system that catalyzes fumaric acid to l‐alanine, and the conversion reached 97.1% using recombinant cells harboring the dual‐enzyme system. This study explored the enzymatic properties of ArASD and an effective strategy for the acidic resistance modification of ASD. Moreover, the strain expressing the ArASD variant and AspA engineered in this study has great potential application for the l‐alanine production industry, especially in the case of high optical purity requirements.
Patients' physical activity in stroke units in Latvia and Sweden
Authors: Kārkliņa Agnese , Chen Erik , Bērziņa Guna , Stibrant Sunnerhagen Katharina
Published: March 2021

Objective

A prospective, observational study to describe levels of physical activity in patients with stroke in a comprehensive stroke unit in Sweden and Latvia, comparing data between countries.

Methods

The study was performed at stroke units in one hospital in Sweden (data were acquired over a 2‐month period in 2017) and two hospitals in Latvia (data were acquired over a 3‐month period between 2016 and 2017). Patients with stroke were observed for 1 min every 10 min. The level of physical activity, location, and the people present were noted at each time‐point.

Results

A total of 27 patients were observed in Latvia and 25 patients in Sweden. Patients from both countries were in bed half of the time and spent the majority of the day in their bedroom and alone. Patients in Sweden had higher physical activity levels, spent more time outside their bedroom and spent more time with rehabilitation specialists and visitors.

Conclusion

Patients are inactive and alone for a majority of the time during hospitalization at a comprehensive stroke unit in both countries. There are differences in environment in the stroke unit between countries.
A heuristic study of the similarities and differences in offender characteristics across potential and successful serial sexual homicide offenders
Authors: Yaksic Enzo , Harrison Marissa , Konikoff Daniel , Mooney Robyn , Allely Clare , De Silva Raneesha , Matykiewicz Brenna , Inglis Melissa , Giannangelo Stephen J. , Daniels Steven , Sarteschi Christine M.
Published: March 2021

This heuristic study examined potential serial sexual homicide offenders (SSHOs), an unacknowledged offender group comprised of aspiring and probable SSHOs, and compared them with successful SSHOs. Data were collected on six aspiring SSHOs who each failed a single homicide attempt, 16 probable SSHOs who committed 17 homicides in separate events, and 13 successful SSHOs who killed 90 victims in separate events. The study results indicate that while potential SSHOs share more in common with successful SSHOs than they do with single‐victim nonsexual homicide offenders, and that there is an overlap between potential SSHOs and successful SSHOs, there is currently insufficient evidence to suggest that there are discreet transitions among categories. While few potential SSHOs strive to become successful SSHOs, this may be due to weak or nonexistent emotional triggers. Being a potential SSHO does not appear to be a predictable first step on a pathway towards becoming a successful SSHO, as potential SSHOs cannot reliably be thought of as prospective SSHOs if all things were equal. The present study could not foresee all potential SSHOs becoming successful ones. An as yet unidentified number of factors still appear to separate potential SSHOs from successful SSHOs.
A systematic review and meta‐analysis of the prognostic role of age in oral tongue cancer
Authors: Tagliabue Marta , Belloni Pietro , De Berardinis Rita , Gandini Sara , Chu Francesco , Zorzi Stefano , Fumagalli Caterina , Santoro Luigi , Chiocca Susanna , Ansarin Mohssen
Published: March 2021

While evidence suggests an increasing incidence of tongue cancer in young adults, published findings regarding the prognostic role of age at diagnosis are inconsistent. We performed a meta‐analysis of the literature to highlight key points that might help in understanding the association between age of oral tongue cancer patients at diagnosis and their prognosis. According to age at diagnosis, a systematic literature review of all published cohort studies assessing the recurrence risks and mortality associated with tongue cancer was conducted. We compared the risk estimates between patients aged >45 years and those aged <45 years at diagnosis. Random‐effects models were used to calculate summary relative risk estimates (SRRs) according to different clinical outcomes and sources of between‐study heterogeneity (I2) and bias. We included 31 independent cohort studies published between 1989 and 2019; these studies included a total of 28,288 patients. When risk estimations were not adjusted for confounders, no significant association was found between age at diagnosis and overall survival (OS). Conversely, after adjustment for confounders, older age at diagnosis was associated with a significantly increased risk of mortality. The difference between SRRs for adjusted and unadjusted estimates was significant (p < 0.01). Younger patients had a significantly higher risk of local recurrence. Younger patients with oral tongue cancer have better OS but a greater risk of recurrence than older patients. These findings should be validated in a large prospective cohort study which considers all confounders and prognostic factors.
4‐Aminoquinolines Bearing a 1,3‐Benzodioxole Moiety: Synthesis and Biological Evaluation as Potential Antifungal Agents
Authors: Yang Rui , Li Zhuolin , Xie Jialing , Liu Jianchuan , Qin Tianhong , Liu Junda , Du Haiying , Ye Haoyun
Published: March 2021

In search of new environmentally friendly and effective antifungal agents, a series of 4‐aminoquinolines bearing a 1,3‐benzodioxole moiety were prepared and their structures were fully elucidated by spectroscopic analyses. The antifungal activities of all the target compounds against five phytopathogenic fungi were evaluated in vitro. The results revealed that most of the newly synthesized compounds exhibited obvious inhibitory activities at the concentration of 50 μg/mL. Among them, 6‐(furan‐2‐yl)‐N‐(4‐methylphenyl)‐2H‐[1,3]dioxolo[4,5‐g]quinolin‐8‐amine hydrochloride (7m) displayed more promising antifungal potency with EC50 values of 10.3 and 14.0 μg/mL against C. lunata and A. alternate, respectively. Particularly, the EC50 value of 7m against C. lunata was 7.3‐fold as potent as the standard azoxystrobin. There were some significant morphological alterations in the mycelia of C. lunata when treated with 7m at 50 μg/mL. Additionally, the preliminary structure–activity relationships (SARs) were also discussed. Thus, this study suggests that 4‐aminoquinolines bearing a 1,3‐benzodioxole moiety are interesting scaffolds for the development of novel antifungal agents.
Treatment of toxoplasmic encephalitis with the combination of clindamycin plus azithromycin in an HIV‐infected patient: A case report
Authors: Mohammadi Keyhan , Khalili Hossein , Jafari Sirous , Yaribash Shakila
Published: March 2021

The existence of alternative oral therapies could help clinicians to treat toxoplasmic encephalitis (TE) in the HIV patients. The combination of azithromycin and clindamycin may serve as an effective treatment for TE in HIV‐infected patients.
Imaging meets chemistry: The application of a thermal imaging camera in chemistry classes of secondary schools first stage
Authors: Wagner Tom , Kempke Tom
Published: March 2021

Die Temperatur lässt sich nicht nur numerisch angeben, sondern durch die Thermografie auch bildhaft darstellen. Vorgestellt werden einfache Experimente für den Chemieunterricht der Sekundarstufe I mit einer vergleichsweise kostengünstigen Wärmebildkamera für Smartphones. Hierbei liegt der Fokus auf Experimenten zur digitalen Darstellung von Wärmeeffekten bei exothermen und endothermen Prozessen.
Percutaneous edge‐to‐edge repair of severe mitral regurgitation using the MitraClip XTR versus NTR system
Authors: Doldi Philipp M. , Brinkmann Isabel , Orban Mathias , Stolz Lukas , Orban Martin , Stocker Thomas , Loew Kornelia , Buech Joscha , Nabauer Michael , Illigens Ben , Cerqueira Tiago Lemos , Siepmann Timo , Massberg Steffen , Hausleiter Joerg , Braun Daniel
Published: March 2021

Background

Transcatheter mitral valve repair (TMVR) has shown to improve symptoms and functional capacity in patients with severe mitral valve regurgitation (MR). Novel device developments provide the technology to treat patients with complex anatomies and large coaptation gaps. Nevertheless, the question of superiority of one device remains unanswered. We aimed to compare the MitraClip XTR and MitraClip NTR system in a real world setting.

Hypothesis

TMVR with the MitraClip XTR system is equally effective, but associated with a higher risk of leaflet injury.

Methods

We retrospectively analyzed peri‐procedural and mid‐term clinical and echocardiographic outcomes of 113 patients treated for severe MR between March 2018 and August 2019 at the University Hospital of Munich.

Results

Postprocedural MR reduction to ≤2+ was comparable in both groups (XTR: 96.1% vs. NTR: 97.6%, p = .38). There was a significant difference in a composite safety endpoint of periprocedural Major adverse cardiac and cerebrovascular events (MACCE) including leaflet injury between groups (XTR 14.6% vs. NTR 1.7%, 95% CI [2.7, 24.6], p = .012). After a median follow‐up of 8.5 (4.4, 14.0) months, durable reduction of MR was confirmed (XTR: in 91.9% vs. NTR: 96.8%, p = .31) and clinical and symptomatic improvement was comparable in both groups accordingly.

Conclusion

While efficacy was comparable in both treatment groups, patients treated with the MitraClip XTR systems showed more events of acute leaflet tear and single leaflet device attachment (SLDA). A detailed echocardiographic assessment should be done to identify risk candidates for acute leaflet injury.
Sarcopenia and modified Glasgow Prognostic Score predict postsurgical outcomes in localized renal cell carcinoma
Authors: Higgins Michelle I. , Martini Dylan J. , Patil Dattatraya H. , Nabavizadeh Reza , Steele Sean , Williams Milton , Joshi Shreyas S. , Narayan Vikram M. , Sekhar Aarti , Psutka Sarah P. , Ogan Kenneth , Bilen Mehmet Asim , Master Viraj A.
Published: March 2021

BACKGROUND

Body composition and inflammation are gaining importance for prognostication in cancer. This study investigated the individual and combined utility of the preoperative skeletal muscle index (SMI) and the modified Glasgow Prognostic Score (mGPS) for estimating postoperative outcomes in patients with localized renal cell carcinoma (RCC) undergoing nephrectomy.

METHODS

The authors performed a retrospective review of 352 patients with localized RCC. SMI was measured via computed tomography or magnetic resonance imaging. Patients met the criteria for sarcopenia by body mass index– and sex‐stratified thresholds. Multivariable and Kaplan‐Meier analyses of associations of sarcopenia and mGPS with overall survival (OS), recurrence‐free survival (RFS), and cancer‐specific survival (CSS) were performed. Variables were analyzed independently and combined into risk groups: low risk (nonsarcopenic, low mGPS), medium risk (sarcopenia only), medium risk (inflammation only), and high risk (sarcopenic, high mGPS). Receiver operating characteristic (ROC) curves were used to analyze risk groups in comparison with the Stage, Size, Grade, and Necrosis (SSIGN) score and the modified International Metastatic RCC Database Consortium (IMDC) score.

RESULTS

The majority of the patients were at stage pT3 (63%), 39.5% of the patients were sarcopenic, and 19.3% had an elevated mGPS at the baseline. The median follow‐up time was 30.4 months. Sarcopenia and mGPS were independently associated with worse OS (hazard ratio for sarcopenia, 1.64; P = .006; hazard ratio for mGPS, 1.72; P = .012), CSS, and RFS. Risk groups had an increasing association with worse RFS (P = .015) and CSS (P = .004) but not OS (P = .087). ROC analyses demonstrated a higher area under the curve for risk groups in comparison with the SSIGN and IMDC scores at 5 years.

CONCLUSIONS

Sarcopenia and an elevated mGPS were associated with worse clinical outcomes in this study of patients with localized RCC. This has implications for preoperative prognostication and treatment decision‐making.

LAY SUMMARY

Kidney cancer is a disease with a wide variety of outcomes. Among patients undergoing surgical removal of the kidney for cancer that has not spread beyond the kidney, many are cured, but some experience recurrence.

Physicians are seeking ways to better predict who is at risk for recurrence or death from kidney cancer.

This study has evaluated body composition and markers of inflammation before surgery to predict the risk of recurrence or death after surgery. Specifically, low muscle mass and an elevated inflammation score (the modified Glasgow Prognostic Score) have been associated with an increased likelihood of recurrence of kidney cancer and death.