bluuebunny/crossref_metadata_2025 huggingface dataset:
Gallium‐Based Liquid Metal Reaction Media for Interfacial Precipitation of Bismuth Nanomaterials with Controlled Phases and Morphologies
Authors: Mayyas Mohannad , Khoshmanesh Khashayar , Kumar Priyank , Mousavi Maedehsadat , Tang Jianbo , Ghasemian Mohammad B. , Yang Jiong , Wang Yifang , Baharfar Mahroo , Rahim Md. Arifur , Xie Wanjie , Allioux Francois‐Marie , Daiyan Rahman , Jalili Rouhollah , Esrafilzadeh Dorna , Kalantar‐Zadeh Kourosh
Published: November 2021

Liquid–liquid interfaces of liquid alloys with electrolytic solutions present fertile platforms for realizing exciting interfacial phenomena that can be devised to process alloys and produce nanomaterials. Here, such an interface is established by immersing a gallium–bismuth binary liquid alloy into aqueous electrolytes. It is shown that the application of a negative voltage to this interface results in a rapid and complete liberation of bismuth nanostructures from liquid gallium. The set of conditions that govern the chemistry of the interface can be adjusted to control the oxidation state, morphology, and crystal structure of the expelled bismuth. By changing the conditions; nanotubular, atomically thin plates, and sea‐urchin‐shaped bismuth oxide morphologies are obtained. The process can also control the crystal phase of bismuth oxide as monoclinic (α), tetragonal (β), or body‐centered cubic (γ). The addition of ascorbic acid to the electrolyte is observed to prevent the oxidation of the expelled entities, resulting in bismuth metal nanoparticles. Ab initio molecular dynamics and computational fluid dynamics simulations are performed to elucidate this rapid phase separation at the interface. This knowledge will potentially lead to new pathways for using alloys as reaction media to refine metals while simultaneously producing nanomaterials for various applications.
Emergent Photostability Synchronization in Coassembled Array Members for the Steady Multiple Discrimination of Explosives
Authors: Cheng Chuanqin , Cui Linfeng , Xiong Wei , Gong Yanjun , Ji Hongwei , Song Wenjing , Zhao Jincai , Che Yanke
Published: November 2021

The design of sensor array members with synchronous fluorescence and photostability is crucial to the reliable performance of sensor arrays in multiple detections and their service life. Herein, a strategy is reported for achieving synchronous fluorescence and photostability on two coassemblies fabricated from carbazole‐based energy donor hosts and a photostable energy acceptor. When a small number of the same energy acceptors are embedded into two carbazole‐based energy donor hosts, the excitation energy of the donors can be efficiently harvested by the acceptors through long‐range exciton migration and Förster resonance energy transfer (FRET) to achieve synchronous fluorescence and photostability in both coassemblies. More intriguingly, the synchronous photostability substantially improves the multiple discrimination capacity (e.g., 10 times more discriminations of TNT in two coassemblies have been achieved compared to the sensor array comprising two individual donor assemblies) and the working lifetime of the sensor array. The concept of optical synchronization (i.e., emission and photostability) of sensor array members can be extended to other sensor arrays for the steady multiple detection of certain hazardous chemicals.
On‐DNA Transfer Hydrogenolysis and Hydrogenation for the Synthesis of DNA‐Encoded Chemical Libraries
Authors: Stanway‐Gordon Harriet A. , Graham Jessica S. , Waring Michael J.
Published: November 2021

DNA‐encoded libraries (DELs) are an increasingly popular approach to finding small molecule ligands for proteins. Many DEL synthesis protocols hinge on sequential additions of monomers using split‐pool combinatorial methods. Therefore, compatible protecting group strategies that allow the unmasking of reactive functionality (e. g. amines and alcohols) prior to monomer coupling, or the removal of less desirable functionality (e. g., alkenes and alkynes) are highly desirable. Hydrogenation/hydrogenolysis procedures would achieve these ends but have not been amenable to DEL chemistry. We report a catalytic hydrogen transfer reaction using Pd/C, HCONH4 and the micelle‐forming surfactant, TPGS‐750‐M, which gives highly efficient conversions for hydrogenolysis of Cbz‐protected amines and benzyl protected alcohols and hydrogenation of nitros, halides, nitriles, aldehydes, alkenes and alkynes. Application to multicycle synthesis of an encoded compound was fully compatible with DNA‐amplification and sequencing, demonstrating its applicability to DEL synthesis. This method will enable synthetic DEL sequences using orthogonal protecting groups.
An example of project‐based learning with the support of a process simulator applied to the chemical engineering final course project
Authors: Vasconcelos Mateus K. , Guedes Matheus N. , Melo Pedro G. F. , Amore Clara R. , Linares José J.
Published: November 2021

As the culmination of the Chemical Engineering curriculum, students face the challenging and stimulating elaboration of a whole design project that integrates all the knowledge gained throughout the course. The subject is divided into two parts, gaining a theoretical background in the ninth semester and a proposed teamwork project design with the aid of a process simulator in the tenth semester. This paper presents the challenge of designing a whiskey distillery elected by a group of students applying the project‐based learning methodology. As a strategy for a more efficient design, the process is divided into three blocks: prefermentation, fermentation, and distillation. Calculations involve mass and energy balances and the design of the different units, including the optimization of a distillation column assisted by the ASPEN HYSYS® simulator. Students must publicly present their results in front of the class and a jury formed by chemical engineers. A survey was carried out to assess the student's satisfaction and feedback. The results manifested the significance of the subject for the future and the satisfaction of the proposed teaching strategy.
Romantic Relationships Assets among Minoritized Youth: Lessons from Child Welfare and Juvenile Justice Involved Adolescents
Authors: Collibee Charlene , Thamotharan Sneha
Published: November 2021

Healthy romantic relationships are a critical, but an undervalued, aspect of adolescent development. Consequently, providers, teachers, and caregivers often struggle with what defines a healthy romantic relationship. Oftentimes, a healthy romantic relationship is understood from a problem behavior perspective, in which healthy aspects of romantic experiences are those that are negatively associated with problem behaviors, such as delinquency. By doing so, caregivers and providers emphasize the absence of “risky” romantic relationship features, rather than the presence of romantic strengths or assets. This pitfall is especially noteworthy among minoritized youth, including those who are systems‐involved through child protective services or juvenile justice.
Development of childhood asthma prediction models using machine learning approaches
Authors: Kothalawala Dilini M. , Murray Clare S. , Simpson Angela , Custovic Adnan , Tapper William J. , Arshad S. Hasan , Holloway John W. , Rezwan Faisal I. ,   STELAR/UNICORN investigators
Published: November 2021

Background

Respiratory symptoms are common in early life and often transient. It is difficult to identify in which children these will persist and result in asthma. Machine learning (ML) approaches have the potential for better predictive performance and generalisability over existing childhood asthma prediction models. This study applied ML approaches to predict school‐age asthma (age 10) in early life (Childhood Asthma Prediction in Early life, CAPE model) and at preschool age (Childhood Asthma Prediction at Preschool age, CAPP model).

Methods

Clinical and environmental exposure data was collected from children enrolled in the Isle of Wight Birth Cohort (N = 1368, ∼15% asthma prevalence). Recursive Feature Elimination (RFE) identified an optimal subset of features predictive of school‐age asthma for each model. Seven state‐of‐the‐art ML classification algorithms were used to develop prognostic models. Training was performed by applying fivefold cross‐validation, imputation, and resampling. Predictive performance was evaluated on the test set. Models were further externally validated in the Manchester Asthma and Allergy Study (MAAS) cohort.

Results

RFE identified eight and twelve predictors for the CAPE and CAPP models, respectively. Support Vector Machine (SVM) algorithms provided the best performance for both the CAPE (area under the receiver operating characteristic curve, AUC = 0.71) and CAPP (AUC = 0.82) models. Both models demonstrated good generalisability in MAAS (CAPE 8‐year = 0.71, 11‐year = 0.71, CAPP 8‐year = 0.83, 11‐year = 0.79) and excellent sensitivity to predict a subgroup of persistent wheezers.

Conclusion

Using ML approaches improved upon the predictive performance of existing regression‐based models, with good generalisability and ability to rule in asthma and predict persistent wheeze.
Biocatalytic Alkylation Chemistry: Building Molecular Complexity with High Selectivity
Authors: Ospina Felipe , Schülke Kai H. , Hammer Stephan C.
Published: November 2021

Biocatalysis has traditionally been viewed as a field that primarily enables access to chiral centers. This includes the synthesis of chiral alcohols, amines and carbonyl compounds, often through functional group interconversion via hydrolytic or oxidation‐reduction reactions. This limitation is partly being overcome by the design and evolution of new enzymes. Here, we provide an overview of a recently thriving research field that we summarize as biocatalytic alkylation chemistry. In the past 3–4 years, numerous new enzymes have been developed that catalyze sp3 C−C/N/O/S bond formations. These enzymes utilize different mechanisms to generate molecular complexity by coupling simple fragments with high activity and selectivity. In many cases, the engineered enzymes perform reactions that are difficult or impossible to achieve with current small‐molecule catalysts such as organocatalysts and transition‐metal complexes. This review further highlights that the design of new enzyme function is particularly successful when off‐the‐shelf synthetic reagents are utilized to access non‐natural reactive intermediates. This underscores how biocatalysis is gradually moving to a field that build molecules through selective bond forming reactions.
Isolation and Characterization of Both Human and Mouse Tfh/Tfr Cells
Authors: Tulyeu Janyerkye , Søndergaard Jonas N. , Sakaguchi Shimon , Wing James B.
Published: November 2021

Regulatory T cells (Tregs) expressing the transcription factor Foxp3 have a critical role for the control of immune homeostasis. The Treg subgroup T follicular regulatory cells (Tfr) have a specialized function to travel to the B cell follicle and control antibody responses. While Tfr may be identified by their protein or gene expression profiles, the use of in vitro functional assays to determine their suppressive capacity is important to further characterize these cells. Here we present methods for the identification and purification of Tfr from both mice and humans followed by co‐culture with B cells and T follicular helper cells (Tfh). The suppressive activity of the Tfr is then assessed by the ability to prevent Tfh‐dependent B cell class switching and plasma blast formation measured by flow cytometry and immunoglobulin production in culture supernatants measured by enzyme‐linked immunosorbent assay. These assays will also provide in‐depth characterization of the functional suppressive capacity of any isolated Tfr or Treg population. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: Isolation of murine T follicular regulatory cells

Basic Protocol 2: Measurement of murine T follicular regulatory cell suppressive function

Basic Protocol 3: Isolation of human T follicular regulatory cells

Basic Protocol 4: Measurement of human T follicular regulatory cell suppressive function
Development of a Sensor Based on Poly(1,2‐diaminoanthraquinone) for Individual and Simultaneous Determination of Mercury (II) and Bismuth (III)
Authors: Shalaby E. A. , Beltagi A. M. , Hathoot A. A. , Azzem M. Abdel
Published: November 2021

Contamination of natural water by mercury (Hg2+) and bismuth (Bi3+) metal ions have been extensively studied due to their toxic effects. A validated square‐wave anodic stripping voltammetry (SW‐ASV) method for determining Bi3+ and Hg2+ ions individually and simultaneously is described. A new electrochemical sensor was constructed using a gold (Au) electrode that has been modified with poly(1,2‐diaminoanthraquinone) (p‐1,2‐DAAQ). Scanning electron microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy were used to characterize the p‐1,2‐DAAQ/Au modified electrode. Factors such as the polymer film thickness, electrolyte, square wave parameters and preconcentration conditions were optimized to improve the performance of the modified Au electrode. Good linear responses were achieved in the concentration ranges of 1–200 μg L−1 and 1–50 μg L−1 forBi3+ and Hg2+, respectively, and the limits of detection were 0.27 μg L−1 (Bi3+) and 0.29 μg L−1 (Hg2+). The interference study results illustrated the high selectivity of the modified electrode for detection of Bi3+ and Hg2+. The proposed SW‐ASV method was successfully applied for Bi3+ and Hg2+analyses in different real water samples.
Complex single‐molecule and molecular scale entities in electrochemical environments: Mechanisms and challenges
Authors: Engelbrekt Christian , Nazmutdinov Renat R. , Shermukhamedov Shokirbek , Ulstrup Jens , Zinkicheva Tamara T. , Xiao Xinxin
Published: November 2021

Following a renaissance from the 1980s, electrochemistry has developed into sophisticated interdisciplinary science integrating solid‐state and surface science and further, biological sciences. Most remarkably, even the single‐molecule can now be addressed. Single‐molecule electrochemistry covers transition metal complexes, organic redox molecules, fragile biomolecules, and molecular‐scale hybrids between metallic nanoparticles and complex molecules, supported by new theoretical frames. We overview here selected areas of molecular scale electrochemistry. After a theoretical minimum, we address complex molecules in electron transfer, enzyme catalysis, and nanoparticle catalysis. Our focus is on issues not so much previously highlighted, such as competition between superexchange and sequential conduction, and resonance features in the transition between the two limits. Another aspect is coherent multi‐electron transfer for large bias voltages often needed to drive enough current through solute molecular junctions. We note finally some single‐molecule perspectives relating to DNA‐based molecules and to spin transitions via chiral molecules.
Investigation of thermal flow structure and performance heat transfer in three‐dimensional circular pipe using twisted tape based on Taguchi method analysis
Authors: Al‐Obaidi Ahmed Ramadhan
Published: November 2021

In the current investigation, the twisted tape inserts are considered as the augmentation thermal technique, the influence of a variety of twisted tape configurations on pressure drop characteristics, temperature differences, thermal performance of fluid flow structure, heat transfer improvement, and friction factor are numerically evaluated. The changed geometrical parameters employed for this study comprise twisted tape width, twisted tape thickness, number of turns, and inward thickness are the input parameters. Design of experiments method is applied to analyze the influence of latter various types of geometrical parameters on hydraulic thermofluid pattern and heat transfer improvement in the twisted tube heat exchanger as the output variables. For the experimental design optimization Taguchi analysis is based on investigate of alterations and performs the orthogonal arrays (OA). Moreover, the OA L16 is chosen as the plan of experimental study. It is found the best design of twisted tape in this study by using computational fluid dynamics numerical methodology complained with Taguchi method the enhancement in heat transfer and hence the overall performance evaluation factor is higher than 1.2.
Numerical approximation of solutions of the equations of quasistatic electroporoelasticity
Authors: Hu Yu , Meir Amnon Jacob
Published: November 2021

We describe a finite element‐based method for numerically approximating solutions of the equations of quasistatic electroporoelasticity, derive error estimates, and illustrate the effectiveness and accuracy of the proposed method by describing results from some numerical experiments.
Dietary weight loss in people with severe obesity stabilizes neuropathy and improves symptomatology
Authors: Callaghan Brian C. , Reynolds Evan L. , Banerjee Mousumi , Akinci Gulcin , Chant Ericka , Villegas‐Umana Emily , Rothberg Amy E. , Burant Charles F. , Feldman Eva L.
Published: November 2021

Objective

The aim of this study was to determine the effect of dietary weight loss on neuropathy outcomes in people with severe obesity.

Methods

A prospective cohort study of participants attending a medical weight‐management program was followed. Weight loss was achieved with meal replacement of 800 kcal/d for 12 weeks and then transitioning to 1,200 to 1,500 kcal/d. The coprimary outcomes were changes in intraepidermal nerve fiber density (IENFD) at the distal leg and proximal thigh. Secondary outcomes included nerve conduction studies, Michigan Neuropathy Screening Instrument questionnaire and exam, Quality of Life in Neurological Disorders, and quantitative sensory testing.

Results

Among 131 baseline participants, 72 (mean [SD] age: 50.1 [10.5] years, 51.4% female) completed 2 years of follow‐up. Participants lost 12.4 (11.8) kg. All metabolic syndrome components improved with the exception of blood pressure. IENFD in the distal leg (0.4 [3.3], p = 0.29), and proximal thigh (0.3 [6.3], p = 0.74) did not significantly change. Improvements were observed on the Michigan Neuropathy Screening Instrument questionnaire, two Quality of Life in Neurological Disorders subdomains, and quantitative sensory testing cold threshold.

Conclusions

Dietary weight loss was associated with improvements in all metabolic parameters except blood pressure, and both IENFD outcomes remained stable after 2 years. Given that natural history studies reveal decreases in IENFD over time, dietary weight loss may halt this progression, but randomized controlled trials are needed.
Chemical seed priming alleviates salinity stress and improves Sulla carnosa germination in the saline depression of Tunisia
Authors: Bouzidi Amal , Krouma Abdelmajid , Chaieb Mohamed
Published: November 2021

In the saline depressions (Sebkhas) of Tunisia, Sulla carnosa expresses anarchic distribution, sometimes in association with halophytes sometimes individually. In order to explain this distribution, we investigated the effects of salinity on seed germination, the osmotic and toxic limiting factors, and the importance of some stimulating agents (priming agents) in the improvement of the tolerance to salinity at the germinating stage. A study was conducted on seeds harvested from the natural biotope Sebkha d'El Kelbia (35°50′34″N, 10°16′18″E), and an increasing concentration of NaCl (0, 5, 10, 15, and 20 g L−1) was applied. Some priming agents were used to propose efficient, rapid, and low‐cost tools to improve the seed germination and tolerance of Sulla carnosa (Desf.) in saline depression. Salinity stress significantly decreased germination capacity and rate and delayed its initiation and maximum. Until 15‐g L−1 NaCl, the most limiting factor of seed germination is the osmotic effect. At 20‐g L−1 NaCl, the toxic effect dominates, and germination is irreversibly inhibited. Some priming agents have shown their efficiency in improving the germination capacity at 10‐g L−1 NaCl and conferring a salt tolerance of up to 15‐g L−1 NaCl.
The Surface Analysis Working Group at the Consultative Committee for Amount of Substance, Metrology in Chemistry and Biology: A successful initiative by Martin Seah
Authors: Unger Wolfgang E. S. , Fujimoto Toshiyuki
Published: November 2021

Dr Martin Seah, NPL, was the initiator, founder, and first chairman of the Surface Analysis Working Group (SAWG) at the Consultative Committee for Amount of Substance, Metrology in Chemistry and Biology (CCQM) at the Bureau International des Poids et Mesures (BIPM), the international organization established by the Metre Convention. This tribute letter summarizes his achievements during his chairmanship and his long‐running impact on the successful work of the group after his retirement.
Erratum to: Exact summation of leading logs around $$ T\overline{T} $$ deformation of O(N + 1)-symmetric 2D QFTs
Authors: Linzen Jonas , Polyakov Maxim V. , Semenov-Tian-Shansky Kirill M. , Sokolova Nika S.
Published: November 2021

A correction to this paper has been published: https://doi.org/10.1007/JHEP05(2021)266
Häufigkeitsverteilung und koordinative Umsetzung von Notfalloperationen in deutschen Krankenhäusern
Authors: Janda Matthias , Karaca O. , Brosin A. , Reuter D. A. , Schuster M.
Published: November 2021

Hintergrund

Die zeitgerechte Durchführung operativer Notfalleingriffe ist von enormer Bedeutung, da dies häufig direkten Einfluss auf die Morbidität und Letalität hat. Gemeinsame Empfehlungen der Fachverbände zur koordinativen Umsetzung liegen seit 2016 vor: N0 (Operation [Op.] sofort), N1 (Op.-Beginn im nächsten freien OP), N2 (Op.-Beginn ≤ 6 h), N3 (Op. am Ende des Elektivprogramms), N4/dringlich (Op. innerhalb von 12–24 h). Ziel dieser Studie war es, die Versorgungsrealität in deutschen Krankenhäusern unterschiedlicher Größe erstmals durch belastbare Daten differenziert zu beschreiben.

Methoden

Die Datenerhebung erfolgte in 26 Krankenhäusern unterschiedlicher Versorgungstypen über einen Zeitraum von 10 Tagen. Untersucht wurde die Häufigkeitsverteilung der einzelnen Notfallkategorien sowie die jeweilige Dauer von der Op.-Meldung bis zum Beginn der Anästhesie bzw. der Op. (Schnitt).

Ergebnisse

Insgesamt wurden 1603 Notfalleingriffe analysiert. Die durchschnittliche Dauer zwischen Op.-Meldung und Beginn der Anästhesie bzw. Schnitt betrug (min): N0 20,7 ± 14,3 bzw. 43,6 ± 31,8; N1 61,5 ± 48,7 bzw. 90,1 ± 56,1; N2 187,9 ± 152,0 bzw. 220,5 ± 153,4; N3 394,5 ± 392,3 bzw. 428,3 ± 397,9; N4/dringlich 494,8 ± 484,4 bzw. 519,6 ± 486,6. Die Verteilung der Notfallkategorien unterschied sich nicht signifikant zwischen Grund‑, Regel- und Schwerpunktversorgern im Vergleich zu Maximalversorgern, einschließlich Universitätskliniken, (p = 0,731). Die Zeitdauern bis zur Realisierung des Notfalls unterschieden sich in Abhängigkeit vom Versorgungstyp nur gering und zeigten sich nur für N1 beim Beginn der Anästhesie sowie N3 beim Beginn der Anästhesie und beim Schnitt als statistisch signifikant.

Schlussfolgerung

Notfälle mit hoher Dringlichkeit werden in den teilnehmenden Häusern sehr zeitnah operativ versorgt. Die Unterschiede im Zeitmanagement zur Realisierung von Notfällen zwischen Grund‑, Regel- und Schwerpunktversorgern im Vergleich zu Maximalversorgern, einschließlich Universitätskliniken, waren nur gering.
Comparison of LC-ESI, DART, and ASAP for the analysis of oligomers migration from biopolymer food packaging materials in food (simulants)
Authors: Osorio Jazmín , Aznar Margarita , Nerín Cristina , Elliott Christopher , Chevallier Olivier
Published: November 2021

Biopolymers based on polylactic acid (PLA) and starch have numerous advantages, such as coming from renewable sources or being compostable, though they can have deficiencies in mechanical properties, and for this reason, polyester resins are occasionally added to them in order to improve their properties. In this work, migration from a PLA sample and from another starch-based biopolymer to three different food simulants was studied. Attention was focused on the determination of oligomers. The analysis was first performed by ultraperformance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF–MS), which allowed the identification of the oligomers present in migration. Then, the samples were analyzed by two ambient desorption/ionization techniques directly coupled to mass spectrometry (ADI), direct analysis in real-time coupled to standardized voltage and pressure (DART-MS) and atmospheric pressure solids analysis probe (ASAP-MS). These methodologies were able to detect simultaneously the main oligomers migrants and their adducts in a very rapid and effective way. Nineteen different polyester oligomers, fourteen linear and five cyclic, composed of different combinations of adipic acid [AA], propylene glycol [PG], dipropylene glycol [DPG], 2,2-dibutyl-1,3-propanediol [DBPG], or isobutanol [i-BuOH] were detected in migration samples from PLA. In migration samples from starch-based biopolymer, fourteen oligomers from poly(butylene adipate co-terephthalate) polyester (PBAT) were identified, twelve cyclic and two linear. The results from ADI techniques showed that they are a very promising alternative tool to assess the safety and legal compliance of food packaging materials.

Graphical abstract
Safety, antitumor activity, and pharmacokinetics of dostarlimab, an anti-PD-1, in patients with advanced solid tumors: a dose–escalation phase 1 trial
Authors: Patnaik Amita , Weiss Glen J. , Rasco Drew W. , Blaydorn Lisa , Mirabella Amy , Beeram Murali , Guo Wei , Lu Sharon , Danaee Hadi , McEachern Kristen , Im Ellie , Sachdev Jasgit C.
Published: November 2021

Purpose

New immuno-oncology therapies targeting programmed cell death receptor 1 (PD-1) have improved patient outcomes in a broad range of cancers. The objective of this analysis was to evaluate the PK, pharmacodynamics (PDy), and safety of dostarlimab monotherapy in adult patients with previously-treated advanced solid tumors who participated in parts 1 and 2A of the phase 1 GARNET study.

Methods

Part 1 featured a 3 + 3 weight-based dose–escalation study, in which 21 patients received dostarlimab 1, 3, or 10 mg/kg intravenously every 2 weeks. The 2 fixed-dose nonweight-based dosing regimens of dostarlimab 500 mg every 3 weeks (Q3W) and 1000 mg every 6 weeks (Q6W) were evaluated using a modified 6 + 6 design in part 2A (n = 13). In parts 1 and 2A, treatment with dostarlimab could continue for up to 2 years or until progression, unacceptable toxicity, patient withdrawal, investigator’s decision, or death.

Results

The dostarlimab PK profile was dose proportional, and maximal achievable receptor occupancy (RO) was observed at all dose levels in the weight-based and fixed-dose cohorts. Trough dostarlimab concentration after administration of dostarlimab 500 mg Q3W was similar to that after dostarlimab 1000 mg Q6W, the values of which (≈40 µg/mL) projected well above the lowest dostarlimab concentration required for full peripheral RO. No dose-limiting toxicities were observed.

Conclusions

Dostarlimab demonstrated consistent and predictable PK and associated PDy. The observed safety profile was acceptable and characteristic of the anti-PD-1 drug class.

Trial registration: ClinicalTrials.gov, NCT02715284. Registration date: March 9, 2016.
Pointwise Remez inequality
Authors: Eichinger B. , Yuditskii P.
Published: November 2021

The standard well-known Remez inequality gives an upper estimate of the values of polynomials on $$[-1,1]$$

[
-
1
,
1
]

if they are bounded by 1 on a subset of $$[-1,1]$$

[
-
1
,
1
]

of fixed Lebesgue measure. The extremal solution is given by the rescaled Chebyshev polynomials for one interval. Andrievskii asked about the maximal value of polynomials at a fixed point, if they are again bounded by 1 on a set of fixed size. We show that the extremal polynomials are either Chebyshev (one interval) or Akhiezer polynomials (two intervals) and prove Totik–Widom bounds for the extremal value, thereby providing a complete asymptotic solution to the Andrievskii problem.
Statistics decrypted—a comprehensive review and smartphone-assisted five-step approach for good statistical practice
Authors: Guglielmetti Laura C. , Faber-Castell Fabio , Fink Lukas , Vuille-dit-Bille Raphael N.
Published: November 2021

Background

Statistic scripts are often made by mathematicians and cryptic for clinicians or non-mathematician scientists. Nevertheless, almost all research projects necessitate the application of some statistical tests or at least an understanding thereof. The present review aims on giving an overview of the most common statistical terms and concepts. It further ensures good statistical practice by providing a five-step approach guiding the reader to the correct statistical test.

Methods and results

First, different types of variables and measurements to describe a data set with means of descriptive statistics are introduced. The basic thoughts and tools of interferential statistics are presented, and different types of bias are discussed. Then in the final paragraph, the most commonly used statistical tests are described. A smartphone app accessible via QR code finally guides the reader in five steps to the correct statistical test, depending on the data used in order to avoid commonly performed mistakes.

Conclusions

The five-step approach sets a new minimal standard for good statistical practice.
A proposal of model for a quality management system in research testing laboratories
Authors: Martínez-Perales Silvia , Ortiz-Marcos Isabel , Ruiz Jesús Juan
Published: November 2021

There is a broad consensus on the importance and advisability of testing laboratories adopting a Quality Management System (QMS) to support their work, no matter they are industrial or research oriented. However, laboratories involved in R&D have specific difficulties to implement a QMS due to the peculiar nature of their activity. This paper analyzes the main challenges and difficulties found by professionals when implementing a QMS in a research testing laboratory, based on the literature review and a questionnaire with 86 laboratories participating performed in collaboration with RedLab (Red de Laboratorios de la Comunidad de Madrid). After this analysis, a set of requirements for the competence of research testing laboratories based on ISO/IEC 17025 and UNE 166002 is defined, and an agile methodology for the fulfilment of these requirements is proposed.
Calcium channel blocker in patients with chronic kidney disease
Authors: Ohno Shoko , Ishii Akira , Yanagita Motoko , Yokoi Hideki
Published: November 2021

Background

Chronic kidney disease (CKD) is involved in a progressive deterioration in renal function over the years and is now a global public health problem. Currently, reducing the number of patients progressing to end-stage renal failure is urgently necessary. Hypertension and CKD interact with each other, and good control of blood pressure (BP) can improve CKD patients’ prognosis. With the current global trend for more strict BP control, the importance of BP management and the need for medication to achieve this strict goal are increasing. Calcium channel blockers (CCBs), which target voltage-dependent calcium channels, are frequently used in combination with renin–angiotensin–aldosterone system inhibitors for CKD patients because of their strong BP-lowering properties and relatively few adverse side effects. Calcium channels have several subtypes, including L, N, T, P/Q, and R, and three types of CCBs, L-type CCBs, L-/T-type CCBs, and L-/N-type CCBs, that are available. Nowadays, the new functions and effects of the CCBs are being elucidated.

Conclusion

We should use different types of CCBs properly depending on their pharmacological effects, such as the strength of antihypertensive effects and the organ protection effects, taking into account the pathophysiology of the patients. In this article, the role and the use of CCBs in CKD patients are reviewed.
Developing Authenticity, Building Connections: Exploring Research Methodologies in Asia
Authors: Atkinson-Sheppard Sally
Published: November 2021

The article considers the methodological opportunities and challenges associated with three large-scale ethnographic studies conducted in Bangladesh, China, and Nepal. It reflects on how locally and regionally embedded cultural practises and meanings shape Asian criminological research projects. The article argues that conducting research in certain Asian contexts benefits from an awareness and sensitivity to specific modalities of culture in these regions. The following deliberations reflect on the importance of developing authenticity and building connections, embedded within concepts specific, and relevant to research in Asia—relationality, guanxi, patronage, and adda. The challenges of the research projects, of which there were many, are also discussed and include dichotomies between research conducted in the global North and global South, coloniality, ethics, and issues faced by a British researcher, conducting research in Asia.
Scutellarin Reduces Cerebral Ischemia Reperfusion Injury Involving in Vascular Endothelium Protection and PKG Signal
Authors: Chen Ya-Juan , Chen Chen , Li Meng-Yuan , Li Qing-Qing , Zhang Xiu-Juan , Huang Rong , Zhu Xing-Wei , Bai Chun-Yun , Zhang Liu-Yi , Peng Pei-Hua , Yang Wei-Min
Published: November 2021

Flavonoid glycoside scutellarin (SCU) has been widely applied in the treatment of cerebral ischemic diseases in China. In this article, we conducted research on the working mechanisms of SCU in hypoxia reoxygenation (HR) injury of isolated cerebral basilar artery (BA) and erebral ischemia reperfusion (CIR) injury in rat models. In isolated rat BA rings, HR causes endothelial dysfunction (ED) and acetylcholine (ACh) induces endothelium-dependent vasodilation. The myography result showed that SCU (100 µM) was able to significantly improve the endothelium-dependent vasodilation induced by Ach. However, SCU did not affect the ACh-induced relaxation in normal BA. Further studies suggested that SCU (10–1000 µM) dose-dependently induced relaxation in isolated BA rings which were significantly blocked by the cGMP dependent protein kinase (PKG) inhibitor Rp-8-Br-cGMPs (PKGI-rp, 4 µM). Pre-incubation with SCU (500 µM) reversed the impairment of endothelium-dependent vasodilation induced by HR, but the reversing effect was blocked if PKGI-rp (4 µM) was added. The brain slice staining test in rats’ model of middle cerebral artery occlusion (MCAO) induced CIR proved that the administration of SCU (45, 90 mg/kg, iv) significantly reduced the area of cerebral infarction. The Western blot assay result showed that SCU (45 mg/kg, iv) increased brain PKG activity and PKG protein level after CIR surgery. In conclusion, our findings suggested that SCU possesses the ability of protecting brain cells against CIR injury through vascular endothelium protection and PKG signal.

Graphic Abstract
Graph convolutional and attention models for entity classification in multilayer networks
Authors: Zangari Lorenzo , Interdonato Roberto , Calió Antonio , Tagarelli Andrea
Published: November 2021

Graph Neural Networks (GNNs) are powerful tools that are nowadays reaching state of the art performances in a plethora of different tasks such as node classification, link prediction and graph classification. A challenging aspect in this context is to redefine basic deep learning operations, such as convolution, on graph-like structures, where nodes generally have unordered neighborhoods of varying size. State-of-the-art GNN approaches such as Graph Convolutional Networks (GCNs) and Graph Attention Networks (GATs) work on monoplex networks only, i.e., on networks modeling a single type of relation among an homogeneous set of nodes. The aim of this work is to generalize such approaches by proposing a GNN framework for representation learning and semi-supervised classification in multilayer networks with attributed entities, and arbitrary number of layers and intra-layer and inter-layer connections between nodes. We instantiate our framework with two new formulations of GAT and GCN models, namely and , specifically devised for general, attributed multilayer networks. The proposed approaches are evaluated on an entity classification task on nine widely used real-world network datasets coming from different domains and with different structural characteristics. Results show that both our proposed and methods provide effective and efficient solutions to the problem of entity classification in multilayer attributed networks, being faster to learn and offering better accuracy than the competitors. Furthermore, results show how our methods are able to take advantage of the presence of real attributes for the entities, in addition to arbitrary inter-layer connections between the nodes in the various layers.
The role of higher education in spatial mobility
Authors: Kosztyán Zsolt Tibor , Csányi Vivien Valéria , Banász Zsuzsanna , Jakobi Ákos , Neumanné-Virág Ildikó , Telcs András
Published: November 2021

The role of higher education in social and spatial mobility has attracted considerable attention. However, there are very few countrywide databases that follow the career paths of graduates from their place of birth, through their enrollment in university, and ultimately to their workplace. However, in Hungary, there is an excellent source maintained by the government’s Education Authority containing information on career tracks, which allows one to follow all students from their place of birth, through their choice of higher education institution, to their workplace. With the combination of gravity-like economic models and the proposed mobility network, this paper examines the mediating and retaining role of institutions. This paper also proposes how to calculate the added value of location and institution in salaries and how to use these values to explain mobility between locations. The paper also shows how economic inequities influence revealed application preferences through the asymmetry of the mobility network.
Open hardware microsecond dispersive transient absorption spectrometer for linear optical response
Authors: Hutchison Christopher D. M. , Parker Susan , Chukhutsina Volha , van Thor Jasper J.
Published: November 2021

An open hardware design and implementation for a transient absorption spectrometer are presented that has microsecond time resolution and measures full difference spectra in the visible spectral region from 380 to 750 nm. The instrument has been designed to allow transient absorption spectroscopy measurements of either low or high quantum yield processes by combining intense sub-microsecond excitation flashes using a xenon lamp together with stroboscopic non-actinic white light probing using LED sources driven under high pulsed current from a capacitor bank. The instrument is sensitive to resolve 0.15 mOD flash-induced differences within 1000 measurements at 20 Hz repetition rate using an inexpensive CCD sensor with 200 μm pixel dimension, 40 K electrons full well capacity and a dynamic range of 1800. The excitation flash has 230 ns pulse duration and the 2 mJ flash energy allows spectral filtering while retaining high power density with focussing to generate mOD signals in the 10–4–10–1 ΔOD range. We present the full electronics design and construction of the flash and probe sources, the optics as well as the timing electronics and CCD spectrometer operation and modification for internal signal referencing. The performance characterisation and example measurements are demonstrated using microsecond TAS of Congo red dye, as an example of a low quantum yield photoreaction at 2% with up to 78% of molecules excited. The instrument is fully open hardware and combines inexpensive selection of commercial components, optics and electronics and allows linear response measurements of photoinduced reactions for the purpose of accurate global analysis of chemical dynamics.

Graphical abstract
Judicialization of the Sea: A Judge's View
Authors: Kittichaisaree Kriangsak
Published: November 2021

In “Judicialization of the Sea: Bargaining in the Shadow of UNCLOS,” Sara Mitchell and Andrew Owsiak define “legalization” as international legal constraints, and “judicialization” of the law of the sea as states’ sense that their policy options are legally bounded, and that courts have gained the authority to define the meaning of the law of the sea. The authors are generally correct that the processes of legalization and judicialization under the UN Convention on the Law of the Sea (UNCLOS) fundamentally alter interstate behavior in significant ways, whatever the choice of dispute settlement mechanisms a state party to UNCLOS has made. However, as I explain in this essay, the International Tribunal for the Law of the Sea (ITLOS) should be the most often utilized mechanism to settle UNCLOS disputes, and its potential as a dispute settlement mechanism has yet to be used to the fullest extent.
Hemodynamic and Anatomical Factors in Arteriovenous Malformation Clinical Presentation: 45 Case Studies
Authors: Chalil Alan , Raupp Eduardo F. , Duckwiler Gary R. , Viñuela Fernando , Lownie Stephen P.
Published: November 2021

Background:

Hemodynamic factors have been implicated in hemorrhage from cerebral arteriovenous malformations (AVMs). The goal of this endovascular study is to analyze the hemodynamic variability in AVM feeders in a balanced group of ruptured and unruptured AVMs of various sizes and at both superficial and deep locations.

Methods:

We monitored feeder artery pressure (FP) using microcatheters in 45 patients with AVMs (16 with hemorrhage, 29 without) during superselective angiography and AVM embolization.

Results:

Mean FP was 49 mm Hg. Significant determinants of FP were the systemic pressure (p < 0.001), AVM size (p = 0.03), and the distance of the microcatheter tip from the Circle of Willis (p = 0.06), but not the presence of hemorrhage, patient age, or feeder artery diameter. The FP in ruptured AVMs was 7 mm Hg higher than in unruptured ones (53.8 mm Hg vs. 47.1 mm Hg, p = 0.032). The presence or absence of venous outflow stenosis and the position of the AVM nidus (superficial or deep to the cortical surface) were important anatomical predictors of AVM presentation.

Conclusion:

The pressure in the feeding artery supplying an AVM is the result of factors which include the systemic arterial pressure, the size of the AVM nidus, and the distance of the AVM from the Circle of Willis. The correlation between these variables makes it difficult to study the risk of hemorrhage as a function of a single factor, which may account for the variation in the conclusions of previous studies.
Secondary vortex, laminar separation bubble and vortex shedding in flow past a low aspect ratio circular cylinder
Authors: Chopra Gaurav , Mittal Sanjay
Published: November 2021

Large eddy simulation of flow past a circular cylinder of low aspect ratio (

$AR=1$

and

$3$

), spanning subcritical, critical and supercritical regimes, is carried out for

$2\times 10^3 \le Re \le 4\times 10^5$

. The end walls restrict three-dimensionality of the flow. The critical

$Re$

for the onset of the critical regime is significantly lower for small aspect ratio cylinders. The evolution of secondary vortex (SV), laminar separation bubble (LSB) and the related transition of boundary layer with

$Re$

is investigated. The plateau in the surface pressure due to LSB is modified by the presence of SV. Proper orthogonal decomposition of surface pressure reveals that although the vortex shedding mode is most dominant throughout the

$Re$

regime studied, significant energy of the flow lies in a symmetric mode that corresponds to expansion–contraction of the vortex formation region and is responsible for bursts of weak vortex shedding. A triple decomposition of the time signals comprising of contributions from shear layer vortices, von Kármán vortex shedding and low frequency modulation due to the symmetric mode of flow is proposed. A moving average, with appropriate size of window, is utilized to estimate the component due to vortex shedding. It is used to assess the variation, with

$Re$

, of strength of vortex shedding as well as its coherence along the span. Weakening of vortex shedding in the high subcritical and critical regime is followed by its rejuvenation in the supercritical regime. Its spanwise correlation is high in the subcritical regime, decreases in the critical regime and improves again in the supercritical regime.
Against the Grain: Spanish Trade Policy in the Interwar Years
Authors: Betrán Concepción , Huberman Michael
Published: November 2021

We study the effects of domestic conflict and external shocks on Spanish trade policy in the interwar period. Our account mobilizes a new granular dataset on exports and imports, and good-country level information on tariffs, trade agreements, and quotas. Into the Depression, the mainstay of policy was the tariff. The establishment of the Second Republic in 1931 was a turning point in policymaking. The new regime initiated bilateral trade negotiations. The Republic’s dilemma was to find countries willing to exchange market access. In a daunting international environment, the Spanish case offers a poignant reminder of the perils of going against the grain.
BAROQUE AROUND THE CLOCK: DANIELLO BARTOLI SJ (1608–1685) AND THE USES OF GLOBAL HISTORY
Authors: Ditchfield Simon
Published: November 2021

Right from its foundation in 1540, the Society of Jesus recognised the value and role of visual description (ekphrasis) in the persuasive rhetoric of Jesuit missionary accounts. Over a century later, when Jesuit missions were to be found on all the inhabited continents of the world then known to Europeans, descriptions of the new-found lands were being read for the entertainment as well as the edification of their Old World audiences. The first official history of the Society's missions in the vernacular, the volumes authored by Daniello Bartoli (1608–1685), played an important role in communicating a sense of the distinctiveness of the order's global mission. Referred to by Giacomo Leopardi (1798–1837) as the ‘Dante of baroque prose’, Bartoli developed a particularly variegated and intensely visual idiom to meet the challenge of describing parts of the world which the majority of his readers, including himself, would never visit.
Progressing the development of a food literacy questionnaire using cognitive interviews
Authors: Thompson Courtney , Adams Jean , Vidgen Helen Anna
Published: November 2021

Objective:

Food literacy is the knowledge, skills and behaviours needed to meet food needs and determine intake and is conceptualised as eleven components under four domains of planning and managing, selecting, preparing, and eating. Previous measures of food literacy vary in their adherence to the conceptualisation and ability to capture totality of eating. This study aimed to determine items for inclusion and exclusion in a food literacy item pool and capture the general public’s interpretation of everyday food literacy practices.

Design:

Beginning with an item pool from previous studies, cognitive interviews were conducted using think-aloud and verbal probing methods. Data were first analysed for applicability, clarity, ambiguity and logic, then for emergent themes to ensure items captured the totality of the participant’s eating.

Setting:

Australia

Participants:

Australian residents over 18 years of age recruited via Facebook residential groups (n 20).

Results:

Of the original 116 items, 11 items had limited applicability; 13 items had unclear references; 32 items had lexical problems and 11 items had logical problems. In total, 29 items were deleted, 31 retained and 56 revised. Thematic analysis revealed participants limited their responses to consider only conventional practices such as grocery shopping, cooking and planned meals rather than the totality of their eating. An additional eighty-four items were developed to address eating out, incidental eating occasions and inconsistencies between participants assumed correct knowledge and that of public health guidelines. This resulted in a refined 171-item pool.

Conclusions:

This study progresses the development towards a comprehensive, validated food literacy questionnaire.