bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly Crosslinked and Clickable Poly(divinylbenzene) Microspheres by Type II Photoinitiated Precipitation Polymerization
Authors: Bicak Tugrul Cem
Published: April 2021

A new method for the synthesis of highly crosslinked and in situ alkyne functionalized microspheres, by combining type II photoinitiation with precipitation polymerization, is reported. Using a benzophenone‐tertiary amine initiation system, the method allows the preparation of functional microspheres at room temperature by UV irradiation in the absence of stabilizers or surfactants of any kind. To demonstrate the presence and accessibility of the alkyne moiety on the polymer particles, fluorescent pyrene groups are attached to the microspheres by copper(I)‐catalyzed alkyne‐azide cycloaddition click reaction, using 1‐azidomethyl pyrene as a model compound. FT‐IR, fluorescence spectroscopy, fluorescence microscopy, and scanning electron microscopy are used for characterization of the particles and to monitor the click reaction.
Fluoxetine for the Symptomatic Treatment of Multiple System Atrophy: The MSA‐FLUO Trial
Authors: Rascol Olivier , Cochen de Cock Valérie , Pavy‐Le Traon Anne , Foubert‐Samier Alexandra , Thalamas Claire , Sommet Agnes , Rousseau Vanessa , Perez‐Lloret Santiago , Fabbri Margherita , Azulay Jean Philippe , Corvol Jean‐Christophe , Couratier Philippe , Damier Philippe , Defebvre Luc , Durif Franck , Geny Christian , Houeto Jean‐Luc , Remy Philippe , Tranchant Christine , Verin Marc , Tison François , Meissner Wassilios G. ,   for the MSA‐FLUO Study Group
Published: April 2021

Background

There are no effective treatments for multiple system atrophy (MSA).

Objective

The objective of this study was to assess the efficacy and safety of the serotonin reuptake inhibitor fluoxetine (40 mg/d) for the symptomatic treatment of MSA.

Methods

This was a double‐blind, parallel‐group, placebo‐controlled, randomized trial in patients with “probable” MSA. The primary outcome was the change from baseline to week 12 in the mean total score of the Unified MSA Rating Scale (UMSARS Parts I + II). Secondary outcomes included change from baseline to week 6 in total UMSARS, and change from baseline to week 12 in the Scales for Outcomes in Parkinson Disease–Autonomic Dysfunction, Beck Depression Inventory, and different domains of the MSA‐Quality of Life Questionnaire. Exploratory outcomes included change from baseline to week 12 in the UMSARS Parts I and II separately and change from baseline to week 24 in the total UMSARS score.

Results

A total of 81 patients were randomly assigned, with no significant difference in the primary outcome (−2.13 units [95% confidence interval, CI, −4.55 to 0.29]; P = 0.08). There was a greater reduction on fluoxetine in the change from baseline to 12‐week in UMSARS Part II (exploratory outcome: −1.41 units [95% CI, −2.84; 0.03]; p = 0.05) and in MSA‐QoL emotional/social dimension (secondary outcome: −6.99 units [95% CI, −13.40; −0.56]; p < 0.03). A total of 5 deaths occurred (3 on fluoxetine and 2 on placebo).

Conclusion

The MSA‐FLUO failed to demonstrate fluoxetine superiority over placebo on the total UMSARS score, whereas trends in motor and emotional secondary/exploratory outcomes deserve further investigation. © 2021 International Parkinson and Movement Disorder Society
Optimal control of a new mechanochemical model with state constraint
Authors: Liu Changchun , Zhang Xiaoli
Published: April 2021

In this paper, a state‐constrained optimal control problem is considered for the new mechanochemical model in biological patterns modelling the skin coating of some vertebrate marine animals. The model consists of the time‐dependent Ginzburg–Landau equation for the concentration difference of at least two pigments u coupled with the Swift–Hohenberg equation for the difference of dermal cellular densities of at least two types of cells. The objective is to force the state to be as close as possible to a desired state. Considering that the cost functional is discontinuous, which along with state constraint, we apply a new penalty functional to approximate the cost functional, in this case, so we first prove the existence of optimal control. Then we derive the necessary optimality conditions for the approximating optimal control problem. Finally, the necessary optimality conditions is obtained by considering the limits of the results for the approximating optimal control problem.
Positive solution and stability of the unstirred chemostat with variable yield
Authors: Liu Wen , Li Yanling
Published: April 2021

In this paper, we are mainly concerned with the unstirred chemostat model with variable yield. We first study positive steady‐state solution and its stability of the model by bifurcation theory and the fixed point index theory. Then we focus on the model with perturbation on diffusion rates, nonconstant yield rate, and nonzero death rate to obtain the existence and stability of the unique positive solution, whenever the constants are perturbed from the critical point.
Serum Metabolomics Reveals Underlying Mechanisms of Cholesterol‐Lowering Effects of Oat Consumption: A Randomized Controlled Trial in a Mildly Hypercholesterolemic Population
Authors: Xu Dengfeng , Wang Shaokang , Feng Meiyuan , Shete Varsha , Chu Yifang , Kamil Alison , Yang Chao , Liu Hechun , Xia Hui , Wang Xin , Sun Guiju , Yang Yuexin
Published: April 2021

Introduction

The purpose of this study is to examine the effects of oat supplementation on serum lipid in a population of adults with mild hypercholesterolemia and reveal the underlying mechanisms with serum untargeted metabolomics.

Methods and Results

In this placebo‐controlled trial, 62 participants from Nanjing, China, with mild elevations in cholesterol are randomly assigned to receive 80 g oats (containing 3 g beta‐glucan) or rice daily for 45 days. Fasting blood samples are collected at the beginning, middle, and end of the trial. Compared with the rice group, oat consumption significantly decreases serum total cholesterol (TC) (‐8.41%, p = 0.005), low‐density lipoprotein cholesterol (LDL‐c) (‐13.93%, p = 0.001), and non high‐density lipoprotein cholesterol (non‐HDL‐c) (‐10.93%, p = 0.017) levels. There are no significant between‐group differences in serum triglyceride (TG), apolipoprotein B (Apo B), glycated albumin, or fasting blood glucose levels. An orthogonal partial least squares discriminant analysis (OPLS‐DA) suggests a clear separation in metabolic profiles between the groups after the intervention. Twenty‐one metabolites in the oat group are significantly different from those in the rice group, among which 14 metabolites show a decreased trend. In comparison, seven metabolites show an increased trend. Correlations analysis from both groups indicate that most metabolites [e.g., sphinganine and phosphatidylcholine (PC)(20:5(5Z,8Z,11Z,14Z,17Z)/20:1(11Z))] have positive correlations with serum cholesterol levels. Kyoto Encyclopedia of Gene and Genomes pathway analysis suggests that oat consumption regulated glycerophospholipid, alanine, aspartate and glutamate, sphingolipid, and retinol metabolism.

Conclusion

Oat consumption has beneficial effects on serum lipids profiles. The underlying mechanisms involve glycerophospholipid, alanine, aspartate and glutamate, sphingolipid, and retinol metabolism in adults.
Reduction of margin to compensate the respiratory tumor motion by the analysis of dosimetric internal target volume in lung SBRT with nonuniform volume prescription method
Authors: Masuda Hirokazu , Kawahara Daisuke , Saito Akito , Kimura Tomoki , Ozawa Shuichi , Nakashima Takeo , Nagata Yasushi
Published: April 2021

Purpose

To develop a dosimetric internal target volume (ITV) margin (DIM) for respiratory motion in lung stereotactic body radiotherapy (SBRT) and to evaluate DIM with a nonuniform volume prescription (NVP) and the point prescription (PP).

Methods

Volumetric modulated arc therapy (VMAT) treatment plans with PP and NVP were created on a heterogeneous programmable respiratory motion phantom, with a tumor (30‐mm diameter) inside a cylindrical lung insert. The tumor was defined as the gross tumor volume (GTV), equal to the clinical target volume (CTV). Five‐millimeter and 0‐mm margins were used for the ITV and setup margins, respectively. The phantom was moved in cranio‐caudal direction with a biquadratic sinusoidal waveform with a 4‐s cycle and an amplitude of ±5–10 mm. The interplay effect was evaluated by measuring the dose profile with a film in the sagittal plane for different respiratory periods and different initial respiratory phases. DIM was based on the respiratory motion amplitude that satisfied 100% and 95% coverage of the prescribed dose by the minimum dose of the CTV. Moreover, the absolute dose was measured with and without respiratory motion for NVP by a pinpoint chamber.

Results

The dose difference in the tumor region due to the interplay effect was within 1.0%. The gamma passing rate was over 95.1% for different respiratory periods and 98.6% for different initial respiratory phases. DIM with PP was almost equivalent to the margin of the respiratory motion. However, DIM with NVP was 2.0 and 1.8 times larger than the margin of the respiratory motion for the 100% and 95% coverage of the prescribed doses, respectively.

Conclusion

The interplay effects experienced between the MLC sequence and tumor motion were negligible for NVP. The DIM analysis revealed that the margin to compensate the respiratory tumor motion could be reduced by more than 44–50% for NVP in SBRT.
TS‐HDS and FGFR3 antibodies in small fiber neuropathy and Dysautonomia
Authors: Trevino Jorge A. , Novak Peter
Published: April 2021

Introduction

The specificity of trisulfated heparin disaccharide/fibroblast growth factor receptor 3 (TS‐HDS/FGFR3) antibodies in the diagnosis of autoimmune small fiber neuropathy (SFN) is unclear.

Methods

This was a retrospective study of patients evaluated for SFN and dysautonomia in the Brigham and Women's Faulkner Hospital Autonomic Laboratory in 2019–2020. Associations were assessed between TS‐HDS/FGFR3 antibodies and SFN markers, including epidermal nerve fiber density (ENFD), sweat gland nerve fiber density (SGNFD), and autonomic dysfunction assessed by Valsalva maneuver, deep breathing, sudomotor, and tilt testing.

Results

Of 322 patients; 28% had elevated anti‐TS‐HDS, 17% had elevated anti‐FGFR3, 96% had autonomic dysfunction, 71% had abnormal ENFD, and 49% had abnormal SGNFD. TS‐HDS/FGFR3 antibodies were present in patients with autonomic dysfunction irrespective of whether they had normal or abnormal skin biopsies unless ENFD/SGNFD were combined for anti‐FGFR3 seropositivity.

Discussion

TS‐HDS/FGFR3 antibodies are present in patients with evidence of autonomic dysfunction. Further studies are needed to document the clinical value of these antibodies in assessment of immune mediated dysautonomia.
Laborarbeit: mehr Ästhetik
Authors: Ehrensberger Christian
Published: April 2021

Gefäße, Geräte und Versorgungseinrichtungen sind in der Regel funktional gestaltet, oft mit praktischen Details – doch dürfen solche Gegenstände und Möbel auch einladend wirken?
April, April: Bitcoinsches Atommodell
Authors: Zbikowski Frauke
Published: April 2021

Über Alkohol, nützliche Photonen, sehr viel Stickstoff, neue Strukturvorschläge und Trends aus dem Periodensystem, die uns am Ende alle dem Stein der Weisen näher bringen.
Planeten, Elemente, Prinzipien
Authors: Gaede Jonathan
Published: April 2021

Strukturformeln und die Abkürzungen im Periodensystem der Elemente gehören zum chemischen Grundwissen. Doch wie wurden früher die Stoffe und Elemente in der Chemie dargestellt?
Bilanz 2020: BASF
Authors: Bulmahn Maren
Published: April 2021

Das Ludwigshafener Chemieunternehmen BASF setzte im vierten Quartal 2020 ähnlich viel um wie im ersten Quartal und insgesamt etwa so viel wie im Vorjahr.
Nachhaltigkeitsinitiative: Weniger Treibhausgase
Authors: Hansen Jan
Published: April 2021

Der Chemikaliendistributor Matsen hat sich schon bei der Gründung vor fünf Jahren auf drei Ziele der Vereinten Nationen zur Nachhaltigkeit festgelegt. Welche das sind und wie das Start‐up sie umsetzt.
Stellschrauben für die präparative Chromatographie
Authors: Kuhlmann Christopher
Published: April 2021

Methoden für die chromatographische Trennung und Reinigung von Substanzen so entwickeln, dass sie sich vom analytischen auf den präparativen Maßstab hochskalieren lassen.
Trendbericht: Kernmagnetische Resonanz
Authors: Seidel Karsten , Matysik Jörg , Luy Burkhard
Published: April 2021

Der gesellschaftliche Diskurs ist derzeit geprägt durch Themen wie Gesundheit und Nachhaltigkeit. Damit einher geht der Bedarf, Strukturen und Eigenschaften von Proteinen, RNA, Wirkstoffen und Zellen besser zu verstehen, ebenso wie Materialien, Rohstofftransformation, Energiespeicherung und Produktionsprozesse. Fortschritte in Technik und Methodik der NMR tragen dazu bei.
Bilanz 2020: Roche
Authors: Bulmahn Maren
Published: April 2021

Das Schweizer Pharmaunternehmen Roche verkaufte im Jahr 2020 kaum mehr als im Jahr zuvor. Dies lag an der großen Menge an preisgünstigen Biosimilars auf dem Markt und der Covid‐19‐Pandemie.
Unaufgeregt statt unbunt
Authors: Bulmahn Maren
Published: April 2021

Im vergangenen Jahr waren Neuwagen oft weiß, schwarz, silber oder grau lackiert. Demnächst soll es mehr Blau und Grün geben.
Size-Specific Exploitation of Flathead Catfish and Blue Catfish by Recreational and Commercial Fishers in the Missouri and Mississippi Rivers, Missouri
Authors: Winders Kyle Robert , McMullen Joseph A.
Published: April 2021

Size-selective harvest in a fishery is a growing point of contention among different catfish anglers. In response to these concerns, size-specific exploitation rates of Flathead Catfish Pylodictus olivaris and Blue Catfish Ictalurus furcatus by recreational anglers and commercial fishers were quantified. Eight study reaches were randomly selected on the Missouri River (4 reaches; recreational harvest only) and the Mississippi River (4 reaches; recreational and commercial fishing allowed). Fish were captured by electrofishing in 2015 and 2016 and were tagged with Carlin dangler reward tags. A total of 3,370 tags were distributed among 12 size-groups starting at 381 mm TL, of which 609 tags were reported during the study period. High-reward (US$150) tags were used to estimate nonreporting of standard ($25) tags. Reporting rates varied by reach and constituency group and ranged from 19% to 100%. Overall exploitation rates of Flathead Catfish were comparable to those in other studies (0.10–0.19) but were highly variable among sizes and among reaches. Commercial fishers did not harvest any fish smaller than 584 mm, and they tended to be more size selective than recreational anglers. Exploitation of Blue Catfish by recreational anglers was highest for 840–890-mm fish (0.34–0.43) in the Missouri River and for 891–1,015-mm fish (0.24–0.28) in the Mississippi River. Commercial harvest of Blue Catfish was not significantly different among size-groups and was much lower than recreational harvest. These data indicated that recreational anglers and commercial fishers were often selective for mid- to larger-size fish rather than for small sizes. Understanding the levels and potential range of size-specific exploitation of catfish in larger rivers will aid managers when setting appropriate regulations and balancing the competing objectives of these fisheries.
Reduction of external pressure on all‐solid‐state battery using SnO2‐embedded porous carbon by CNT assistance
Authors: Notohara Hiroo , Urita Koki , Moriguchi Isamu
Published: April 2021

All‐solid‐state batteries (ASSBs) using non‐flammable inorganic solid electrolyte are expected as a safety energy storage system that exhibits a high energy density. Since external pressure is required to maintain stable interface between active materials and solid electrolyte, the pressure applicable system make the cell modules larger and heavier, and it prevents the practical realization. In the present study, an ASSB system reduced external pressure was achieved by using single‐walled carbon nanotube (SWCNT) assistance. The ASSB electrode mixed with SWCNTs showed high capacity and stable cycle performance even under a coin‐type cell without additional external pressure which is conventionally used on an organic liquid electrolyte system. The unique characters of SWCNT which is high electrical conductivity and self‐supporting force are effective to reduce external pressure of ASSBs. This result opens a new route to design a downsized battery cell.
Contemporary Risk Stratification and Treatment of Chronic Myelomonocytic Leukemia
Authors: Tremblay Douglas , Rippel Noa , Feld Jonathan , El Jamal Siraj M. , Mascarenhas John
Published: April 2021

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy characterized by absolute monocytosis, one or more lineage dysplasia, and proliferative features including myeloid hyperplasia, splenomegaly, and constitutional symptoms. Because of vast clinical heterogeneity in presentation and course, risk stratification is used for a risk-adapted treatment strategy. Numerous prognostic scoring systems exist, some of which incorporate mutational information. Treatment ranges from observation to allogeneic hematopoietic stem cell transplantation. Therapies include hydroxyurea for cytoreduction, hypomethylating agents, and the JAK1/2 inhibitor ruxolitinib to address splenomegaly and constitutional symptoms. Recently, oral decitabine with cedazuridine was approved and represents a convenient treatment option for CMML patients. Although novel therapeutics are in development for CMML, further work is needed to elucidate possible targets unique to the CMML clone. In this review, we will detail the pathophysiology, risk stratification, available treatment modalities, and novel therapies for CMML, and propose a modern treatment algorithm.

Implications for Practice

Chronic myelomonocytic leukemia (CMML) is a clinically heterogenous disease, which poses significant management challenges. The diagnosis of CMML requires bone marrow biopsy and aspirate with thorough evaluation. Risk stratification and symptom assessment are essential to designing an effective treatment plan, which may include hypomethylating agents (HMAs) in intermediate or high-risk patients. The recently approved oral decitabine/cedazuridine provides a convenient alternative to parenteral HMAs. Ruxolitinib may be effective in ameliorating proliferative symptoms and splenomegaly. Allogeneic stem cell transplantation remains the only treatment with curative potential; however, novel therapies are in clinical development which may significantly alter the therapeutic landscape of CMML.
Lenvatinib with or Without Everolimus in Patients with Metastatic Renal Cell Carcinoma After Immune Checkpoint Inhibitors and Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor Therapies
Authors: Wiele Andrew J. , Bathala Tharakeswara K. , Hahn Andrew W. , Xiao Lianchun , Duran Munevver , Ross Jeremy A. , Jonasch Eric , Shah Amishi Y. , Campbell Matthew T. , Msaouel Pavlos , Tannir Nizar M.
Published: April 2021

Introduction

Lenvatinib (Len) plus everolimus (Eve) is an approved therapy for metastatic renal cell carcinoma (mRCC) after first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), but limited data exist on the efficacy of Len ± Eve after progression on immune checkpoint inhibitors (ICIs) and VEGFR-TKIs.

Methods

We retrospectively reviewed the records of patients with mRCC at our institution who were treated with Len ± Eve after ICI and VEGFR-TKI. A blinded radiologist assessed objective response as defined by RECIST version 1.1. Descriptive statistics and the Kaplan-Meier method were used.

Results

Fifty-five patients were included in the analysis. Of these patients, 81.8% had clear-cell histology (ccRCC), and 76.4% had International Metastatic RCC Database Consortium intermediate-risk disease. Median number of prior therapies was four (range, 2–10); all patients had prior ICIs and VEGFR-TKIs, and 80% were previously treated with ICI and at least two VEGFR-TKIs, including cabozantinib. One patient (1.8%) achieved a complete response, and 11 patients (20.0%) achieved a partial response, for an overall response rate (ORR) of 21.8%; 35 patients (63.6%) achieved stable disease. In all patients, median progression-free survival (PFS) was 6.2 months (95% confidence interval [CI], 4.8–9.4) and median overall survival (OS) was 12.1 months (95% CI, 8.8–16.0). In patients with ccRCC, ORR was 24.4%, PFS was 7.1 months (95% CI, 5.0–10.5), and OS was 11.7 months (95% CI, 7.9–16.1). 50.9% of patients required dose reductions and 7.3% discontinued treatment because of toxicity.

Conclusion

Len ± Eve demonstrated meaningful clinical activity and tolerability in heavily pretreated patients with mRCC after disease progression with prior ICIs and VEGFR-TKIs.

Implications for Practice

As the therapeutic landscape for patients with metastatic renal cell carcinoma continues to evolve, this single-center, retrospective review highlights the real-world efficacy of lenvatinib with or without everolimus in heavily pretreated patients. This article supports the use of lenvatinib with or without everolimus as a viable salvage strategy for patients whose disease progresses after treatment with immune checkpoint inhibitors and vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies, including cabozantinib.
Crystal structure and supramolecular arrangement of heterochiral tripeptides
Authors: Dolai Gobinda , Giri Rajat Subhra , Roy Sayanta , Mandal Bhubaneswar
Published: April 2021

The self‐assembly properties of all possible stereoisomers of terminally protected Boc‐Val‐Phe‐Phe‐OMe, having sequence homogeneity with Alzheimer's amyloid‐beta (Aβ18‐20) peptide was investigated. The morphology analysis by field emission scanning microscope (FE‐SEM) revealed that protected VFF and vff (small letters denote one letter code ofd‐amino acids) exhibited a ribbon‐like fibrous network, vFF, Vff, VfF, and vFf formed rod‐like structures. Although VFf exhibited a mixture of two morphologies (rod‐like and spherical), vfF showed spherical structures predominantly. The single‐crystal X‐ray diffraction (SC‐XRD) indicated that five of the stereoisomers formed a parallel beta‐sheet arrangement. In higher‐order packing, while Vff, VfF, and vFf exhibited supramolecular sheet‐like architecture, VFf and vfF pair showed helical sheet‐like arrangement. All corresponding enantiomers displayed identical morphology but opposite conformation. The chirality of amino acids in peptides played a significant role in their supramolecular arrangements. Interestingly, all self‐aggregated peptides can bind with amyloid binding dye thioflavin T.
A novel role for milk fat globule‐EGF factor 8 protein (MFGE8) in the mediation of mouse sperm–extracellular vesicle interactions
Authors: Trigg Natalie A. , Stanger Simone J. , Zhou Wei , Skerrett‐Byrne David A. , Sipilä Petra , Dun Matthew D. , Eamens Andrew L. , De Iuliis Geoffry N. , Bromfield Elizabeth G. , Roman Shaun D. , Nixon Brett
Published: April 2021

Spermatozoa transition to functional maturity as they are conveyed through the epididymis, a highly specialized region of the male excurrent duct system. Owing to their transcriptionally and translationally inert state, this transformation into fertilization competent cells is driven by complex mechanisms of intercellular communication with the secretory epithelium that delineates the epididymal tubule. Chief among these mechanisms are the release of extracellular vesicles (EV), which have been implicated in the exchange of varied macromolecular cargo with spermatozoa. Here, we describe the optimization of a tractable cell culture model to study the mechanistic basis of sperm–extracellular vesicle interactions. In tandem with receptor inhibition strategies, our data demonstrate the importance of milk fat globule‐EGF factor 8 (MFGE8) protein in mediating the efficient exchange of macromolecular EV cargo with mouse spermatozoa; with the MFGE8 integrin‐binding Arg‐Gly‐Asp (RGD) tripeptide motif identified as being of particular importance. Specifically, complementary strategies involving MFGE8 RGD domain ablation, competitive RGD‐peptide inhibition and antibody‐masking of alpha V integrin receptors, all significantly inhibited the uptake and redistribution of EV‐delivered proteins into immature mouse spermatozoa. These collective data implicate the MFGE8 ligand and its cognate integrin receptor in the mediation of the EV interactions that underpin sperm maturation.
Investigation on the products distribution, reaction pathway, and discharge mechanism of low‐pressure CO2 discharge by employing a 1D simulation model
Authors: Wang Cong , Fu Qiang , Chang Zhengshi , Zhang Guanjun
Published: April 2021

Mars has a special carbon dioxide environment. The surface and atmosphere of Mars contain a large amount of solid and gaseous carbon dioxide, which makes the in‐situ resource utilization of Martian carbon dioxide attract widespread attention. The conversion of carbon dioxide into fuel or high value‐added products through electrical discharge has become a research focus, in which numerical simulation is one of the important means to explain the experimental phenomenon and the mechanism. Therefore, a one‐dimensional fluid model was established in this paper to simulate the discharge and conversion of carbon dioxide under simulated Martian atmospheric pressure. The discharge mode, particle distribution, and discharge mechanism were studied by considering CO2 vibrational states and vibration relaxation reaction in the model. The results show that the discharge mode is glow discharge with an obvious cathode fall region, negative glow space, and positive column. The density of the four discharge products, C, O2, CO, and O, shows a step‐up trend, showing a significant cumulative effect, and the peak values appear near both electrodes. The density of vibrational states of CO2 molecule, which is highest in the neutral products, increases during the discharge stage and decreases after the discharge is extinguished. The temporal and spatial distribution of reaction rates shows that vibrational excitation, electronic excitation, and vibrational relaxation reactions dominate the loss and formation of CO2. The density of ground‐state CO2 decreases obviously in the discharge stage, and the minimum density appears near the instantaneous cathode. After the discharge is extinguished, the CO2 near the instantaneous cathode increases gradually.
Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer
Authors: Ledet Elisa M. , Burgess Earle F. , Sokolova Alexandra O. , Jaeger Ellen B. , Hatton Whitley , Moses Marcus , Miller Patrick , Cotogno Patrick , Layton Jodi , Barata Pedro , Lewis Brian E. , Nakazawa Mari , Zhu Jason , Dellinger Beth , Elrefai Sara , Nafissi Nellie N. , Egan Jan B. , Shore Neal , McKay Rana R. , Bryce Alan H. , Cheng Heather H. , Antonarakis Emmanuel S. , Sartor Oliver
Published: April 2021

Background

The goal of this study is to evaluate germline genetic variants in African American men with metastatic prostate cancer as compared to those in Caucasian men with metastatic prostate cancer in an effort to understand the role of genetic factors in these populations.

Methods

African American and Caucasian men with metastatic prostate cancer who had germline testing using multigene panels were used to generate comparisons. Germline genetic results, clinical parameters, and family histories between the two populations were analyzed.

Results

A total of 867 patients were included in this retrospective study, including 188 African American and 669 Caucasian patients. There was no significant difference in the likelihood of a pathogenic or likely‐pathogenic variants (PV/LPVs) between African American and Caucasian patients (p = .09). African American patients were more likely to have a variant of unknown significance than Caucasians (odds ratio [OR] = 1.95; p < .0001). BRCA1 PV/LPVs were higher in African Americans (OR = 4.86; p = .04). African American patients were less likely to have a PV/LPV in non‐BRCA DNA repair genes (OR = 0.30; p = .008). Family history of breast (OR = 2.09; p = .002) or ovarian cancer (OR = 2.33; p = .04) predicted PV/LPVs in Caucasians but not African‐Americans. This underscores the limitations of family history in AA men and the importance of personal history to guide germline testing in AA men.

Conclusions

In metastatic prostate cancer patients, PV/LPVs of tested genes did not vary by race, BRCA1 PV/LPVs were more common in the African American subset. However, PV/LPVs in non‐BRCA DNA repair genes were less likely to be encountered in African Americans. Family history associated with genetic testing results in Caucasians only.
A whole‐body circulatory neutrophil model with application to predicting clinical neutropenia from in vitro studies
Authors: Chen Wenbo , Boras Britton , Sung Tae , Hu Wenyue , Spilker Mary E. , D’Argenio David Z.
Published: April 2021

A circulatory model of granulopoiesis and its regulation is presented that includes neutrophil trafficking in the lungs, liver, spleen, bone marrow, lymph nodes, and blood. In each organ, neutrophils undergo transendothelial migration from vascular to interstitial space, clearance due to apoptosis, and recycling via the lymphatic flow. The model includes cell cycling of progenitor cells in the bone marrow, granulocyte colony‐stimulating factor (G‐CSF) kinetics and its neutrophil regulatory action, as well as neutrophil margination in the blood. From previously reported studies, 111In‐labeled neutrophil kinetic data in the blood and sampled organs were used to estimate the organ trafficking parameters in the model. The model was further developed and evaluated using absolute neutrophil count (ANC), band cell, and segmented neutrophil time course data from healthy volunteers following four dose levels of pegfilgrastim (r2 = 0.77–0.99), along with ANC time course responses following filgrastim (r2 = 0.96). The baseline values of various cell types in bone marrow and blood, as well as G‐CSF concentration in the blood, predicted by the model are consistent with available literature reports. After incorporating the mechanism of action of both paclitaxel and carboplatin, as determined from an in vitro bone marrow studies, the model reliably predicted the observed ANC time course following paclitaxel plus carboplatin observed in a phase I trial of 46 patients (r2 = 0.70). The circulatory neutrophil model may provide a mechanistic framework for predicting multi‐organ neutrophil homeostasis and dynamics in response to therapeutic agents that target neutrophil dynamics and trafficking in different organs.
Effect of Hydrogen on Hafnium Zirconium Oxide Fabricated by Atomic Layer Deposition Using H2O2 Oxidant
Authors: Kim Hyoungkyu , Yun Seokjung , Kim Tae Ho , Kim Hoon , Bae Changdeuck , Jeon Sanghun , Hong Seungbum
Published: April 2021

Hafnium zirconium oxide (HZO) has been studied intensively due to its potential application to memory and logic devices based on its outstanding dielectric and ferroelectric properties. Because many process factors can significantly impact the properties of HZO thin film, an optimized process or post‐treatment is necessary to ensure its performance. Herein, the effect of hydrogen on HZO thin film can make the film degraded. Analysis of the polarization–voltage hysteresis loops and I–V measurements indicate a leaky behavior in the film. To address this issue, post‐oxygen‐plasma treatment is performed on the film, which results in the decrease in hydrogen ions inside the film and consequently reduces the leakage current density. This finding can provide new insight into the effect of hydrogen incorporation for HZO thin films and methodology to remove leaky components inside ferroelectric films using O2 plasma treatment.
Interface‐Driven Thermoelectric Switching Performance of VO+‐Diffused Soda‐Lime Glass
Authors: Alphonse Carmel Mary Esther , Garlapati Mohan Muralikrishna , Tyler Bonnie J. , Arlinghaus Heinrich F. , Divinski Sergiy V. , Wilde Gerhard
Published: April 2021

Strongly confined NaVO+ segregation and its thermoresponsive functionality at the interface between simple sputter‐deposited amorphous vanadium oxide thin films and soda‐lime glass is substantiated in this work by in situ temperature‐controlled time‐of‐flight secondary‐ion mass spectrometry (ToF‐SIMS). The obtained ToF‐SIMS depth profiles provide unambiguous evidence for a reversible transformation that causes systematic switching of the NaVO+/Na+ and Na+/VO+ intensities upon cycling the temperature between 25 and 340 °C. Subsequently, NaVO complexes are found to be reversibly formed (at 300 °C) in vanadium oxide‐diffused glass, leading to thermoresponsive electrical behavior of the thin‐film glass system. This new segregation and diffusion‐dependent multifunctionality of NaVO+ point toward applications as an advanced material for thermoelectrical/optical switches, in smart windows or in thermal sensors.
Incorporating historical information to improve phase I clinical trials
Authors: Zhou Yanhong , Lee J. Jack , Wang Shunguang , Bailey Stuart , Yuan Ying
Published: April 2021

Incorporating historical data has a great potential to improve the efficiency of phase I clinical trials and to accelerate drug development. For model‐based designs, such as the continuous reassessment method (CRM), this can be conveniently carried out by specifying a “skeleton,” that is, the prior estimate of dose limiting toxicity (DLT) probability at each dose. In contrast, little work has been done to incorporate historical data into model‐assisted designs, such as the Bayesian optimal interval (BOIN), Keyboard, and modified toxicity probability interval (mTPI) designs. This has led to the misconception that model‐assisted designs cannot incorporate prior information. In this paper, we propose a unified framework that allows for incorporating historical data into model‐assisted designs. The proposed approach uses the well‐established “skeleton” approach, combined with the concept of prior effective sample size, thus it is easy to understand and use. More importantly, our approach maintains the hallmark of model‐assisted designs: simplicity—the dose escalation/de‐escalation rule can be tabulated prior to the trial conduct. Extensive simulation studies show that the proposed method can effectively incorporate prior information to improve the operating characteristics of model‐assisted designs, similarly to model‐based designs.
Improving sample size recalculation in adaptive clinical trials by resampling
Authors: Herrmann Carolin , Kluge Corinna , Pilz Maximilian , Kieser Meinhard , Rauch Geraldine
Published: April 2021

Sample size calculations in clinical trials need to be based on profound parameter assumptions. Wrong parameter choices may lead to too small or too high sample sizes and can have severe ethical and economical consequences. Adaptive group sequential study designs are one solution to deal with planning uncertainties. Here, the sample size can be updated during an ongoing trial based on the observed interim effect. However, the observed interim effect is a random variable and thus does not necessarily correspond to the true effect. One way of dealing with the uncertainty related to this random variable is to include resampling elements in the recalculation strategy. In this paper, we focus on clinical trials with a normally distributed endpoint. We consider resampling of the observed interim test statistic and apply this principle to several established sample size recalculation approaches. The resulting recalculation rules are smoother than the original ones and thus the variability in sample size is lower. In particular, we found that some resampling approaches mimic a group sequential design. In general, incorporating resampling of the interim test statistic in existing sample size recalculation rules results in a substantial performance improvement with respect to a recently published conditional performance score.
Dauricine inhibits proliferation and promotes death of melanoma cells via inhibition of Src/STAT3 signaling
Authors: Deng Bo , Jiang Xiao‐Li , Tan Zhang‐Bin , Cai Min , Deng Sui‐Hui , Ding Wen‐Jun , Xu You‐Cai , Wu Yu‐Ting , Zhang Shuang‐Wei , Chen Rui‐Xue , Kan Jun , Zhang En‐Xin , Liu Bin , Zhang Jing‐Zhi
Published: April 2021

Melanoma is the most common type of skin cancer. Signal transducer and activator of transcription 3 (STAT3) signaling has been demonstrated to be a therapeutic target for melanoma. Dauricine (Dau), an alkaloid compound isolated from the root of Menispermum dauricum DC., has shown tumor‐suppressing effects in multiple human cancers, but its potential in melanoma remains unexplored. In this study, we demonstrated that Dau significantly inhibited the viability and proliferation of A375 and A2058 melanoma cells. Death of melanoma cells was also markedly promoted by Dau. Moreover, Dau inhibited phosphorylation‐mediated activation of STAT3 and Src in a dose‐dependent manner. Notably, constitutive activation of Src partially abolished the antiproliferative and cytotoxic activities of Dau on melanoma cells. Molecular docking showed that Dau could dock on the kinase domain of Src with a binding energy of −10.42 kcal/mol. Molecular dynamics simulations showed that Src–Dau binding was stable. Surface plasmon resonance imaging analysis also showed that Dau has a strong binding affinity to Src. In addition, Dau suppressed the growth of melanoma cells and downregulated the activation of Src/STAT3 in a xenograft model in vivo. These data demonstrated that Dau inhibits proliferation and promotes cell death in melanoma cells by inhibiting the Src/STAT3 pathways.
A status report with critical analysis of research trends in exploring medicinal plants as antiviral: Let us dig into the history to predict the future
Authors: Mukherjee Souvik , Chouhan Kavi Bhushan Singh , Tandey Roshni , Yadav Neelima , Dhobi Mahaveer , Mandal Vivekananda
Published: April 2021

The review article serves as a mini directory of medicinal plants (662 medicinal plants have been identified) that have been investigated for antiviral property between 2015 and 2019. Data have been extracted from Scopus using specific keywords followed by manual sorting to avoid any duplication. Critical analyses of handpicked data have been presented. Mapping of medicinal plants, followed by critical analysis on the families and plant parts investigated in the said tenure, and its correlation with the participating countries and virus types have been critically analyzed. Interceptive role of phytochemicals in impeding viral replication has also been taken note of. Emphasis on India's exploration of various medicinal plants has also been given. Also presents a tutelage, which is likely to revive the interest in natural products for search of potential antivirals. This review is expected to serve as a rich data bank and as a guiding principle for researchers who are planning to explore medicinal plants in search for potential antiviral. It is time that researchers need to revisit their countries' own history of traditional medicine to predict something worthful in future.
The effects and mechanisms of aloe‐emodin on reversing adriamycin‐induced resistance of MCF‐7/ADR cells
Authors: Cheng Guorong , Pi Zifeng , Zhuang Xiaoyu , Zheng Zhong , Liu Shu , Liu Zhiqiang , Song Fengrui
Published: April 2021

Multidrug resistance (MDR) is one of the major obstacles for clinical effective chemotherapy. In this study, the effects and possible mechanisms of aloe‐emodin (AE) were investigated on reversing the adriamycin (ADR)‐induced resistance of MCF‐7/ADR cells. AE could significantly reverse the ADR resistance in MCF‐7/ADR cells. The combination of AE (20 μM) and ADR had no effect on the P‐glycoprotein (P‐gp) level, but notably promoted the accumulation of ADR in drug‐resistant cells. The efflux function of P‐gp required ATP, but AE reduced the intracellular ATP level. AE played a reversal role might through inhibiting the efflux function of P‐gp. The research result of energy metabolism pathways indicated that combination of AE and ADR could inhibit glycolysis, tricarboxylic acid (TCA) cycle, glutamine metabolism, and related amino acid synthesis pathways. Moreover, we found AE not only reversed ADR‐induced resistant but also induced autophagy as a defense mechanism. In addition, the combination of AE and ADR arrested G2/M cell cycle and induced apoptosis through DNA damage, ROS generation, caspase‐3 activation. Our study indicated that AE could be a potential reversal agent to resensitize ADR resistant in tumor chemotherapy and inhibiting autophagy might be an effective strategy to further enhance the reversal activity of AE.
Plant species used in Brazil and Asia regions with toxic properties
Authors: Marmitt Diorge Jônatas , Shahrajabian Mohamad Hesam
Published: April 2021

Many efforts are being made to find biomolecules extracted from plants to be useful therapeutic agents to replace the drugs traditionally used in clinical medicine with known side effects and high financial investment, thus offering greater safety and less risk to the population. However, the presence of toxic substances such as alkaloids, amino acids, amides, glycosides, saponins, and tannins are the main reasons for the poisonous activity of some medicinal plants. In this sense, understanding plants constituents and lethal doses can be important source in managing several diseases in human life. This review aimed to present extracts, fractions, and/or compounds of plants of Brazil and Asia regions that have reported toxicity to in vitro and in vivo models. The results presented here contribute to warning the population about the toxicological characterization of some plants, however, further high‐quality studies are needed to firmly establish the clinical efficacy of the plants (or compounds).
A case of multiple squamous papillomas in the trachea treated by rigid bronchoscopy
Authors: Torii Atsushi , Nishimura Rieko , Oki Masahide
Published: April 2021

Key message

Tracheal papilloma is a rare benign lung tumour. It often recurs and sometimes transforms into a malignant tumour. While historically radical resection has been the primary treatment, endobronchial resection, a less invasive procedure to manage the airway using a flexible and rigid bronchoscope, was effectively used in our patient.
Features of HLA class I expression and its clinical relevance in SARS‐CoV‐2: What do we know so far?
Authors: Bouayad Abdellatif
Published: April 2021

Modifications in HLA‐I expression are found in many viral diseases. They represent one of the immune evasion strategies most widely used by viruses to block antigen presentation and NK cell response, and SARS‐CoV‐2 is no exception. These alterations result from a combination of virus‐specific factors, genetically encoded mechanisms, and the status of host defences and range from loss or upregulation of HLA‐I molecules to selective increases of HLA‐I alleles. In this review, I will first analyse characteristic features of altered HLA‐I expression found in SARS‐CoV‐2. I will then discuss the potential factors underlying these defects, focussing on HLA‐E and class‐I‐related (like) molecules and their receptors, the most documented HLA‐I alterations. I will also draw attention to potential differences between cells transfected to express viral proteins and those presented as part of authentic infection. Consideration of these factors and others affecting HLA‐I expression may provide us with improved possibilities for research into cellular immunity against viral variants.
Gift economy and well‐being: A mode of economy playing out in recovery from Rwandan tragedies
Authors: Otake Yuko , Hagenimana Fabien
Published: April 2021

Previous studies challenge the assumption that economic growth improves subjective well‐being, and argue that economic growth is incompatible with not only nature conservation but also subjective well‐being. To achieve SDGs, a mode of economy that sustains both subjective well‐being and the natural environment needs to be investigated. This ethnographic study explored community‐based economy systems in post‐genocide Rwanda, and elaborated the process and mechanisms by which the contemporary gift economy facilitated subjective well‐being in culture and natural landscape. Findings showed that subjective well‐being can be achieved by applying alternative modes of economy (gift economy, sharing economy) and having access to direct sources of well‐being (natural environment, social cohesion, cultural identity, and spirituality), when basic needs are satisfied by well‐established infrastructure and social services. This study contributes to understanding why and how people can be happy without money, and illuminate a mode of economy that can benefit the sustainable development of local communities.
A simple yet powerful test for assessing goodness‐of‐fit of high‐dimensional linear models
Authors: Zhang Qi , Chen Feifei , Wu Shunyao , Liang Hua
Published: April 2021

We evaluate the validity of a projection‐based test checking linear models when the number of covariates tends to infinity, and analyze two gene expression datasets. We show that the test is still consistent and derive the asymptotic distributions under the null and alternative hypotheses. The asymptotic properties are almost the same as those when the number of covariates is fixed as long as p/n → 0 with additional mild assumptions. The test dramatically gains dimension reduction, and its numerical performance is remarkable.
Sex Disparity in Skin Carcinogenesis and Potential Influence of Sex Hormones
Authors: Collier V. , Musicante M. , Patel T. , Liu-Smith F.
Published: April 2021

Background

Sex or gender disparity in skin cancer has been documented for a long time at the population level. UV radiation (UVR) is a common environmental risk for all three major types of skin cancer: cutaneous melanoma (CM), basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). The underlying mechanism for sex disparity has been largely attributed to sex-differentiated behaviour patterns related to UVR. Non-UVR factors such as intrinsic physiological differences have been suggested but remain understudied.

Aims, Materials and Methods

This review summarizes and compares the known sex differences in three skin cancer types with regard to body site distribution and age influence.

Results

We found a similar age-dependent sex difference pattern in CM and BCC. Specifically, CM and BCC tend to show higher incidence in young women and old men, with a switching age around menopause. The switching age suggests involvement of sex hormones, which has shown controversial influence on skin cancers at epidemiological level. Literatures regarding sex hormone receptors for oestrogen, androgen and progesterone are summarized for potential explanations at molecular level.

Discussion

Overall, more and more evidence suggests non-UVR factors such as sex hormones play critical roles in skin cancer (especially CM and BCC), yet solid population and molecular evidence are required. Incidences of skin cancer are increasing which suggests limited effect for the current UVR-avoidance prevention methods.

Conclusion

Fully understanding the causes of sex disparities in incidence is necessary for developing a comprehensive prevention strategy.