bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid Perovskite Degradation from an Optical Perspective: A Spectroscopic Ellipsometry Study from the Deep Ultraviolet to the Middle Infrared
Authors: Tejada Alvaro , Peters Sven , Al‐Ashouri Amran , Turren‐Cruz Silver Hamill , Abate Antonio , Albrecht Steve , Ruske Florian , Rech Bernd , Guerra Jorge Andrés , Korte Lars
Published: November 2021

A quantitative analysis of the thermally induced degradation of various device‐relevant multi‐cation hybrid perovskite films is performed using spectroscopic ellipsometry, for temperatures between 80 and 120 °C. The studied compositions are a triple cation perovskite Cs0.05(MA0.17FA0.83)0.95Pb(Br0.17I0.83)3, a Rb‐containing variant Rb0.05Cs0.05(MA0.17FA0.83)0.90Pb(Br0.17I0.83)3, and a methylammonium‐free Rb0.05Cs0.10FA0.85PbI3 composition. A very wide combined spectral range of 200 nm to 25 μm is covered by combining the data from two separate instruments. The relative changes in organic cation concentrations are quantified from the middle infrared molecular absorption bands, leveraging the use of point‐by‐point fitting for increased sensitivity. Additionally, the formation of PbI2 and non‐perovskite δ‐CsPbI3 phases is evidenced from Bruggemann effective medium fits to the visible and ultraviolet complex refractive indices. Methylammonium is almost completely depleted from the relevant compositions within 100 to 285 min of thermal annealing. The MA‐free perovskite degrades faster at intermediate temperatures, which is attributed to phase instability due to the formation of δ‐CsPbI3 in addition to PbI2.
Retainable Bandgap Narrowing and Enhanced Photoluminescence in Mn‐Doped and Undoped Cs2NaBiCl6 Double Perovskites by Pressure Engineering
Authors: Zhang Long , Liu Zhengtao , Sun Xuening , Niu Guangming , Jiang Jutao , Fang Yuanyuan , Duan Defang , Wang Kai , Sui Laizhi , Yuan Kaijun , Wu Guorong , Zou Bo
Published: November 2021

Pressure engineering can access novel optoelectronic properties and crystal structures in halide perovskite materials with soft lattice. However, such pressure‐induced phenomena are commonly realized under large pressure or difficult to retain at atmospheric pressure, thus severely hindering their prospects in practical applications. Herein, the pressure‐treated Mn‐doped/undoped Cs2NaBiCl6 exhibits a largely retained bandgap narrowing of 12.2% relative to its initial state via compression–decompression cycles, along with durable stability at ambient conditions. This abnormal behavior is attributed to the disordered arrangement of inorganic [NaCl6]5−/[BiCl6]3− octahedra, which occurs in the metastable state of double perovskites from structural reconstruction during decompression processes, and is accompanied by a characteristic of long‐range order and short‐range disorder. A remarkable pressure‐induced emission enhancement from Mn2+ ions is discovered upon modest compression, especially at <0.5 GPa, which results from the increased energy transfer efficiency from Bi3+ to Mn2+ ions owing to more overlapped electronic wave functions from each other. This work can be extended to the design and synthesis of new semiconductor materials with enhanced optoelectronic properties.
Directed Regeneration of Osteochondral Tissue by Hierarchical Assembly of Spatially Organized Composite Spheroids
Authors: Lee Jinkyu , Lee Seoyun , Huh Seung Jae , Kang Byung‐Jae , Shin Heungsoo
Published: November 2021

The use of engineered scaffolds or stem cells is investigated widely in the repair of injured musculoskeletal tissue. However, the combined regeneration of hierarchical osteochondral tissue remains a challenge due to delamination between cartilage and subchondral bone or difficulty in spatial control over differentiation of transplanted stem cells. Here, two types of composite spheroids are prepared using adipose‐derived stem cells (hADSCs) and nanofibers coated with either transforming growth factor‐β3 or bone morphogenetic growth factor‐2 for chondrogenesis or osteogenesis, respectively. Each type of spheroid is then cultured within a 3D‐printed microchamber in a spatially arranged manner to recapitulate the bilayer structure of osteochondral tissue. The presence of inductive factors regionally modulates in vitro chondrogenic or osteogenic differentiation of hADSCs within the biphasic construct without dedifferentiation. Furthermore, hADSCs from each spheroid proliferate and sprout and successfully connect the two layers mimicking the osteochondral interface without apertures. In vivo transplantation of the biphasic construct onto a femoral trochlear groove defect in rabbit knee joint results in 21.2 ± 2.8% subchondral bone volume/total volume and a cartilage score of 25.0 ± 3.7. The present approach can be an effective therapeutic platform to engineer complex tissue.
Soft Actuators and Robotic Devices for Rehabilitation and Assistance
Authors: Pan Min , Yuan Chenggang , Liang Xianrong , Dong Tianyun , Liu Tao , Zhang Junhui , Zou Jun , Yang Huayong , Bowen Chris
Published: November 2021

Soft actuators and robotic devices have been increasingly applied to the field of rehabilitation and assistance, where safe human and machine interaction is of particular importance. Compared with their widely used rigid counterparts, soft actuators and robotic devices can provide a range of significant advantages; these include safe interaction, a range of complex motions, ease of fabrication, and resilience to a variety of environments. In recent decades, significant effort has been invested in the development of soft rehabilitation and assistive devices for improving a range of medical treatments and quality of life. This review provides an overview of the current state‐of‐the‐art in soft actuators and robotic devices for rehabilitation and assistance, in particular systems that achieve actuation by pneumatic and hydraulic fluid‐power, electrical motors, chemical reactions, and soft active materials such as dielectric elastomers, shape memory alloys, magnetoactive elastomers, liquid crystal elastomers, and piezoelectric materials. Current research on soft rehabilitation and assistive devices is in its infancy, and new device designs and control strategies for improved performance and safe human–machine interaction are identified as particularly untapped areas of research. Finally, insights into future research directions are outlined.
Let's talk teaching: Progressive pedagogy in anthropology courses
Authors: Kissel Marc , Blum Susan D.
Published: November 2021

Objectives

In this article, we discuss research from the science of teaching and learning and from progressive pedagogy, with the aim of discussing how these fields can help us all become better teachers.

Methods

Our methods were based on assessment of the literature and our in‐class practices.

Results

We find that the practices of critical progressive pedagogy are rooted in good research practices and are based both on new research and on fundamental aspects of teaching and learning.

Conclusions

While some of the ideas mentioned in this piece might be seen as radical, we argue that everyone can benefit from a discussion of these concepts and ideas. Teaching is something that we all do in various ways. Progressive pedagogy allows us to create classrooms as a space to welcome all learners and also pushes educators toward creating a more diverse, inclusive, and equitable classroom.
Sanfilippo syndrome type B: Analysis of patients diagnosed by the MPS Brazil Network
Authors: Montenegro Yorran Hardman Araújo , de Souza Carolina Fischinger Moura , Kubaski Francyne , Trapp Franciele Barbosa , Burin Maira Graeff , Michelin‐Tirelli Kristiane , Leistner‐Segal Sandra , Facchin Ana Carolina Brusius , Medeiros Fernanda S. , Giugliani Luciana , Ribeiro Erlane Marques , Lourenço Charles Marques , Cardoso‐dos‐Santos Augusto César , Ribeiro Márcia Gonçalves , Kim Chong Ae , Castro Matheus Augusto Araújo , Embiruçu Emília Katiane , Steiner Carlos Eduardo , Moreira Maria Lucia Castro , Montano Hector Quintero , Baldo Guilherme , Giugliani Roberto
Published: November 2021

Mucopolysaccharidosis type IIIB is a rare autosomal recessive disorder characterized by deficiency of the enzyme N‐acetyl‐alpha‐d‐glucosaminidase (NAGLU), caused by biallelic pathogenic variants in the NAGLU gene, which leads to storage of heparan sulfate and a series of clinical consequences which hallmark is neurodegeneration. In this study clinical, epidemiological, and biochemical data were obtained from MPS IIIB patients diagnosed from 2004–2019 by the MPS Brazil Network (“Rede MPS Brasil”), which was created with the goal to provide an easily accessible and comprehensive investigation of all MPS types. One hundred and ten MPS IIIB patients were diagnosed during this period. Mean age at diagnosis was 10.9 years. Patients were from all over Brazil, with a few from abroad, with a possible cluster of MPS IIIB identified in Ecuador. All patients had increased urinary levels of glycosaminoglycans and low NAGLU activity in blood. Main clinical symptoms reported at diagnosis were coarse facies and neurocognitive regression. The most common variant was p.Leu496Pro (30% of alleles). MPS IIIB seems to be relatively frequent in Brazil, but patients are diagnosed later than in other countries, and reasons for that probably include the limited awareness about the disease by health professionals and the difficulties to access diagnostic tests, factors that the MPS Brazil Network is trying to mitigate.
A Phenanthrocarbazole‐Based Dopant‐Free Hole‐Transport Polymer with Noncovalent Conformational Locking for Efficient Perovskite Solar Cells
Authors: Guo Yaxiao , He Lanlan , Guo Jiaxin , Guo Yu , Zhang Fuguo , Wang Linqin , Yang Hao , Xiao Chenhao , Liu Yi , Chen Yongsheng , Yao Zhaoyang , Sun Licheng
Published: November 2021

Adequate hole mobility is the prerequisite for dopant‐free polymeric hole‐transport materials (HTMs). Constraining the configurational variation of polymer chains to afford a rigid and planar backbone can reduce unfavorable reorganization energy and improve hole mobility. Herein, a noncovalent conformational locking via S–O secondary interaction is exploited in a phenanthrocarbazole (PC) based polymeric HTM, PC6, to fix the molecular geometry and significantly reduce reorganization energy. Systematic studies on structurally explicit repeats to targeted polymers reveals that the broad and planar backbone of PC remarkably enhances π–π stacking of adjacent polymers, facilitating intermolecular charge transfer greatly. The inserted “Lewis soft” oxygen atoms passivate the trap sites efficiently at the perovskite/HTM interface and further suppress interfacial recombination. Consequently, a PSC employing PC6 as a dopant‐free HTM offers an excellent power conversion efficiency of 22.2 % and significantly improved longevity, rendering it as one of the best PSCs based on dopant‐free HTMs.
Thermo‐Responsive Jamming of Nanoparticle Dense Suspensions towards Macroscopic Liquid–Solid Switchable Materials
Authors: Liu Mingqian , Wan Xizi , Yang Man , Wang Zhao , Bao Han , Dai Bing , Liu Huan , Wang Shutao
Published: November 2021

Nanoparticle aggregation for constructing functional materials has shown enormous advantages in various applications. Most efforts focused on ordered nanoparticle aggregation for specific functions but were often limited to irreversible aggregation processes due to the thermodynamic equilibrium. Herein, we report a reversible disordered aggregation of SiO2‐PNIPAAm nanoparticles (SPNPs) through thermo‐responsive jamming, obtaining smart liquid–solid switchable materials. The smart materials can display a switch between liquid‐like state and solid‐like state responding to a temperature change. This unique macroscopic behavior originates from the reversible disordered aggregation modulated by temperature‐dependent hydrophobic interactions among the SPNPs. Notably, the materials at the solid‐like state show anti‐impact properties and can withstand the impact of a steel sphere with a speed of 328 cm s−1. We envision that this finding offers inspiration to design smart liquid–solid switchable materials for impact protection.
Polynuclear (α‐diimine) nickel(II) complex as catalyst for ethylene oligomerization
Authors: Li Dan , Ma Fengmin , Guo Lijun , Huang Jin , Zhang Yu , Li Feng , Li Cuiqin
Published: November 2021

Late transition metal catalysts with single or multiple active centers have great attention in the ethylene oligomerization application owing to their unique properties. A new polynuclear (α‐diimine) nickel(II) complex (PS‐Ni complex) bearing the conjugated poly(Schiff‐base) ligand (PS‐ligand) was synthesized. The structures and the composition of the PS‐ligand and the PS‐Ni complex were characterized by Fourier transform infrared (FTIR) analysis, X‐ray diffraction (XRD), X‐ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), thermogravimetric (TG) analysis, nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The PS‐Ni complex was used as precatalyst in ethylene oligomerization combined with methylaluminoxane (MAO) and has good catalytic activity for ethylene oligomerization under mild conditions. Compared with the corresponding mononuclear (α‐diimine) nickel(II) complex, the PS‐Ni complex showed higher activity of 17.62 × 105 g/(mol Ni•h), and the main products were C4 and C6 olefins in cyclohexane when the dosage of precatalyst was 2 μmol, the Al/Ni molar ratio was 500, the ethylene pressure was 0.5 MPa, the reaction time was 60 min, and the reaction temperature was 25°C. The main oligomers were α‐olefins, and the selectivity was up to 98.68%, due to the more electron‐deficient catalytic centers of the conjugated structure of poly(Schiff‐base) ligand.
Investigating the role of copper and zinc oxide nanomaterials in abatement of biofouling of ultrafiltration membrane in dynamic conditions
Authors: Srivastava Ashish , Raval Hiren D.
Published: November 2021

In the present work, we demonstrate the synthesis, characterization, and biofouling study of polysulfone‐based mixed matrix membranes prepared with hydrophilic CuO and ZnO nanomaterial as antibacterial agents. Permeate flux was increased to 462.2 LMH for PSf/CuO (0.1%) and 472.5 LMH for PSf/ZnO (1.0%) from 191.2 LMH for pure PSf and BSA rejections were enhanced (from 70.91% to 95.73% for PSf/CuO (0.1%), from 70.91% to 93.47% for PSf/ZnO (1.0%). Biofilm growth over the modified membrane (was very less significant as correlated by lower pressure drop compared to pure polysulfone membrane in membrane fouling simulator (MFS) for 48 h. Adhesions of the Escherichia coli bacteria over the membrane surface were analyzed through an alcian blue test followed by a scanning electron micrograph. It was seen that the modified membrane showed a significant anti‐biofouling property with less adherence of alcian blue dye on the membrane surface and scanning electron micrographs demonstrated significantly lower biofouling. Mechanical strength of modified membrane increased up to 62.55 MPa for PSf/CuO (2%) and 55.41 MPa for PSf/ZnO (2%) as compared to 16.41 MPa of PSf membrane.
Borderline personality disorder traits in adolescents with anorexia nervosa
Authors: Lekgabe Edna , Pogos Danielle , Sawyer Susan M. , Court Andrew , Hughes Elizabeth K.
Published: November 2021

Objective

To examine the correlation between eating disorder (ED) symptoms and borderline personality disorder (BPD) traits in a sample of adolescents with eating disorders.

Method

There were 168 participants (Mage = 16.0 years; SD = 1.16) with a diagnosis of anorexia nervosa (AN) or Eating Disorder Not Otherwise Specified—AN type. Eating Disorder Examination (EDE) and the Borderline Personality Questionnaire (BPQ) were used to assess ED symptoms and BPD traits.

Results

A total of 10 participants (6.6%) scored above the clinical cut‐off for a likely diagnosis of BPD. A positive correlation was observed between BPQ total score and EDE global (rs = 0.64, p < .001). There were also positive correlations between the BPQ self‐image and emptiness subscales and all EDE subscales. Similarly, the EDE eating concern subscale was correlated with all BPQ subscales.

Discussion

Previous studies have demonstrated that some BPD traits (i.e., suicidality, impulsivity, anger) are co‐morbid with ED but the link with other BPD traits has been poorly studied in adolescents and those with AN. These findings indicate that while the prevalence of BPD in adolescents with AN may be relatively low, ED symptom severity is closely related to severity of BPD traits, particularly identity disturbance and feelings of emptiness.
The effect of tempering on protein properties and arabinoxylan contents of intermediate wheatgrass (Thinopyrum intermedium) flour
Authors: Bharathi Radhika , Dai Yaxi , Tyl Catrin , Schoenfuss Tonya , Annor George Amponsah
Published: November 2021

Background and objectives

To benefit from ecosystem services provided by intermediate wheatgrass (IWG, Thinopyrum intermedium) cultivation, its processing conditions require optimization to facilitate its use in foods. This study assessed tempering as a strategy to improve IWG flour properties relevant for dough making.

Findings

Tempered IWG samples had significantly higher maximum torque in the GlutoPeak, which strongly correlated with lower contents in total and water‐extractable arabinoxylans (p < .05, r = −0.481; p < .01, r = −0.611) and phosphate buffer‐soluble proteins (p < .01, r = −0.893). While higher maximum torque was observed when IWG was tempered to 14% (compared to 12%), target moisture and tempering time did not have any effect. Tempering induced significant reductions in accessible thiols, which also negatively correlated with maximum torque (p < .05, r = −0.473). SDS‐PAGE analysis, however, did not indicate a shift in flour protein profiles.

Conclusions

Tempering significantly increased maximum torque and significantly reduced the contents of phosphate buffer‐soluble proteins, accessible thiols, and arabinoxylans. Together, these findings imply increased protein aggregation and an improved IWG protein network.

Significance and novelty

This work demonstrates that the interaction between proteins and arabinoxylans is crucial for IWG dough properties and can be influenced by processing methods.
Revealing the Effect of Mass Transfer on Direct Dehydrogenation of Ethylbenzene Catalyzed by Phosphorous‐doped Boron Nitride: Comparative Study
Authors: Liu Yuwei , Xu Fan , Yuan Nicui , Lin Baining , Zhou Yonghua
Published: November 2021

Phosphorous‐doped boron nitride (PBN) was previously confirmed to be an effective metal‐free catalyst for the challenging topic of ethylbenzene direct dehydrogenation (DDH) to styrene. Here, the effect of mass transfer factors including the porosity and surface exposure degree of mesoporous‐PBN (m‐PBN) on its performance over DDH was investigated by control experiments. The central pore size of m‐PBN was closely dependent on the thiourea amount and heating rate. The m‐PBN with optimal pore size delivered a significantly improved styrene production rate of 21.47 mmolST g−1 h−1 and styrene selectivity over 98 %. Further, when m‐PBN was in‐situ grown on cordierite, the activity and stability of catalyst could be further enhanced to 27.08 mmolST g−1 h−1 for 50 h stable run, which presented a promising industrial application prospect. This paper justified that the mass transfer factors involved in two‐dimensional metal‐free catalysts were crucial for DDH of ethylbenzene.
Three‐dimensionally Ordered Macro‐porous Metal‐organic Framework for High‐performance Lithium‐sulfur Battery
Authors: Wang Tong , Liu Yanyu , Liu Xin , Cui Guoliang , Zhang Yongguang , Wang Xin
Published: November 2021

The commercial application of lithium‐sulfur (Li−S) battery is greatly hampered by the shuttling of lithium polysulfide (LiPS). In this work, a double‐solution‐induced method is proposed to synthesize multifunctional three‐dimensionally ordered macro‐micro porous MOFs (3DOM ZIF67) as an efficient promotor to achieve excellent electrochemical performance. The unique ordered macro‐porous structure not only accelerates ion diffusion and charge transfer, but also enlarges the active interfaces. In addition, the nanometric ZIF67 unit with high porosity can achieve strong sulfur immobilization and catalysis by chemical interaction with LiPS, which vastly inhibited shuttle effect and promoted the rapid redox kinetics. As expected, the S/3DOM ZIF67 cathode achieves a high capacity of 920.7 mAh g−1 at 1.0 C and excellent cycle performance over 500 cycles. This design offers a feasible way to develop MOF‐based materials with efficient adsorption and electrocatalysis for high‐performance Li−S battery.
Mn12‐Acetate Complexes Studied as Single Molecules
Authors: Tombers Matthias , Meyer Jennifer , Meyer Jonathan , Lawicki Arkadiusz , Zamudio‐Bayer Vicente , Hirsch Konstantin , Lau J. Tobias , von Issendorff Bernd , Terasaki Akira , Schlathölter Thomas A. , Hoekstra Ronnie A. , Schmidt Sebastian , Powell Annie K. , Kessler Eva , Prosenc Marc H. , van Wüllen Christoph , Niedner‐Schatteburg Gereon
Published: November 2021

The phenomenon of single molecule magnet (SMM) behavior of mixed valent Mn12 coordination clusters of general formula [MnIII8MnIV4O12(RCOO)16(H2O)4] had been exemplified by bulk samples of the archetypal [MnIII8MnIV4O12(CH3COO)16(H2O)4] (4) molecule, and the molecular origin of the observed magnetic behavior has found support from extensive studies on the Mn12 system within crystalline material or on molecules attached to a variety of surfaces. Here we report the magnetic signature of the isolated cationic species [Mn12O12(CH3COO)15(CH3CN)]+ (1) by gas phase X‐ray Magnetic Circular Dichroism (XMCD) spectroscopy, and we find it closely resembling that of the corresponding bulk samples. Furthermore, we report broken symmetry DFT calculations of spin densities and single ion tensors of the isolated, optimized complexes [Mn12O12(CH3COO)15(CH3CN)]+ (1), [Mn12O12(CH3COO)16] (2), [Mn12O12(CH3COO)16(H2O)4] (3), and the complex in bulk geometry [MnIII8MnIV4O12(CH3COO)16(H2O)4] (5). The found magnetic fingerprints – experiment and theory alike – are of a remarkable robustness: The MnIV4 core bears almost no magnetic anisotropy while the surrounding MnIII8 ring is highly anisotropic. These signatures are truly intrinsic properties of the Mn12 core scaffold within all of these complexes and largely void of the environment. This likely holds irrespective of bulk packing effects.
Low‐Threshold Amplified Spontaneous Emission from Air‐Stable CsPbBr3 Perovskite Films Containing Trace Amounts of Polyethylene Oxide
Authors: Tian Kun , Lu Yannan , Liu Ruqing , Loh Xian Jun , Young David James
Published: November 2021

Organic additives can enhance the amplified spontaneous emission (ASE) performance of inorganic cesium lead halide perovskites (CsPbBr3) but volatility, potential hygroscopicity and oxidative degradation of these additives jeopardizes the thermal stability and shelf‐life of blended CsPbBr3 films. To address this problem, we have fabricated perovskite films in a two‐step solution protocol involving as little added polyethylene oxide (PEO) as possible. These films exhibited enhanced crystallization, improved photoluminescence (PL) intensity and prolonged lifetimes. Their hierarchical morphology and surface passivation lowered the ASE threshold from 278 to 176 μЈ/cm2 under one‐photon nanosecond laser excitation. The proportion of added PEO was 0.3 wt% and was subsequently almost fully removed, thereby reducing its adverse influence on the stability of resulting films under continuous pulsed laser excitation. Stable ASE spectra could be stimulated after storage in air for 10 months.
Dropout in brief psychotherapy for major depressive disorder: Randomized clinical trial
Authors: da Silva Machado Rosiene , Vieira Igor Soares , Mondin Thaise C. , Scaini Carolina Rheingantz , Molina Mariane Lopez , Jansen Karen , de Mattos Souza Luciano Dias , Duarte Malu Ribeiro , Simjanoski Mario , da Silva Ricardo Azevedo
Published: November 2021

The aim of this paper is to analyse the factors associated with the dropout from brief psychotherapy for adults with major depressive disorder (MDD) treated at a mental health outpatient clinic. This is a randomized clinical trial with two models of psychotherapy: cognitive behavioural therapy (CBT) and supportive expressive dynamic psychotherapy (SEDP). MDD and anxiety disorders were evaluated through the Mini International Neuropsychiatric Interview‐Plus. The personality disorders were evaluated by the Millon Clinical Multiaxial Inventory‐III. The severity of depressive symptoms was measured using the Beck Depression Inventory‐II and resilience through Resilience Scale. Of the 215 participants, 41.9% abandoned psychotherapy (n = 90), and, of these, 54.4% (n = 49) abandoned after the fourth session. The proportion of psychotherapy dropout was higher among those with nonwhite skin colour, belonging to economic classes C and D, who had children and whose depressive symptoms were moderate. Presence of obsessive–compulsive personality trait was protective against dropout. The damage caused by this abrupt interruption is evident for all those involved in the psychotherapeutic process, so the clinician should pay attention to the predictors found in this study in order to develop strategies that promote therapeutic adherence.
Model‐Informed Drug Development Approaches to Assist New Drug Development in the COVID‐19 Pandemic
Authors: Xiong Ye , Fan Jianghong , Kitabi Eliford , Zhang Xinyuan , Bi Youwei , Grimstein Manuela , Yang Yuching , Earp Justin C. , Zheng Nan , Liu Jiang , Wang Yaning , Zhu Hao
Published: November 2021

Leveraging limited clinical and nonclinical data through modeling approaches facilitates new drug development and regulatory decision making amid the coronavirus disease 2019 (COVID‐19) pandemic. Model‐informed drug development (MIDD) is an essential tool to integrate those data and generate evidence to (i) provide support for effectiveness in repurposed or new compounds to combat COVID‐19 and dose selection when clinical data are lacking; (ii) assess efficacy under practical situations such as dose reduction to overcome supply issues or emergence of resistant variant strains; (iii) demonstrate applicability of MIDD for full extrapolation to adolescents and sometimes to young pediatric patients; and (iv) evaluate the appropriateness for prolonging a dosing interval to reduce the frequency of hospital visits during the pandemic. Ongoing research activities of MIDD reflect our continuous effort and commitment in bridging knowledge gaps that leads to the availability of effective treatments through innovation. Case examples are presented to illustrate how MIDD has been used in various stages of drug development and has the potential to inform regulatory decision making.
The impact of comorbidities on selexipag treatment effect in patients with pulmonary arterial hypertension: insights from the GRIPHON study
Authors: Rosenkranz Stephan , Channick Richard , Chin Kelly M. , Jenner Bartosz , Gaine Sean , Galiè Nazzareno , Ghofrani Hossein‐Ardeschir , Hoeper Marius M. , McLaughlin Vallerie V. , Du Roure Camille , Rubin Lewis J. , Sitbon Olivier , Tapson Victor , Lang Irene M.
Published: November 2021

Aims

The number of pulmonary arterial hypertension (PAH) patients with comorbidities is increasing and there are limited data on response to PAH‐targeted therapies in this population. These post hoc analyses explored the effect of selexipag in PAH patients with cardiovascular comorbidities in the GRIPHON study.

Methods and results

Randomized patients (n = 1156) were classified using three methods: (i) by subgroups defined according to previously published comorbidity count and restrictive haemodynamic criteria: Subgroup A (<3 comorbidities and haemodynamic criteria met; n = 962) and Subgroup B (≥3 comorbidities and/or haemodynamic criteria not met; n = 144); comorbidities included body mass index ≥30 kg/m2, essential hypertension, diabetes, history of coronary artery disease; (ii) by number of comorbidities, with addition of atrial fibrillation (0, 1, 2, 3, 4, or 5); (iii) by presence of individual comorbidities. Selexipag to placebo hazard ratios (HR) and 95% confidence intervals (CI) for morbidity/mortality (primary composite endpoint) were estimated using Cox regression adjusting selexipag effect for baseline covariates. Approximately half of the patients in GRIPHON (n = 584; 50.5%) had comorbidities. Selexipag reduced the risk of a morbidity/mortality event compared with placebo in both Subgroup A (HR 0.66, 95% CI 0.53, 0.82) and Subgroup B (HR 0.50, 95% CI 0.26, 0.96), with no evidence of an inconsistent treatment effect between subgroups (interaction p = 0.432). Consistent results were observed in analyses by number and by specific type of comorbidity.

Conclusion

Selexipag reduces the risk of a morbidity/mortality event vs. placebo irrespective of patient comorbidity status, suggesting that comorbidity status does not influence the treatment effect of selexipag.
Total Synthesis of Entrectinib with Key Photo‐Redox Mediated Cross‐Coupling in Flow
Authors: Cordell Morgan J. , Adams Matt R. , Vincent‐Rocan Jean‐François , Riley John G.
Published: November 2021

By using photo‐redox catalysis in flow the newly marketed drug entrectinib (referred to by the brand name Rozlytrek) was synthesized in 6 linear steps from readily available building blocks under mild conditions. Evaluation of multiple intermediates for their use in the critical C−N amination step in flow led to the finding that more electron deficient aryl‐halides achieve higher conversion to the desired product. Data supports that more electron rich aryl‐halides undergo a significant amount of hydro‐dehalogenation compared to the productive C−N bond formation. Through evaluating various entry points into the synthesis of entrectinib, shorter routes were identified albeit in low yields. The modularity of this route will allow chemists to rapidly synthesize a diverse library of compounds through this route. Via different synthetic intermediates, a scale‐up route was discovered for the synthesis of entrectinib using photo‐redox in flow in less steps than previously reported, highlighting the utility of flow chemistry in the pharmaceutical industry.
Ferrocene Decorated N‐doped Carbon Modified Electrode with Enhanced Electrocatalytic Activity towards Non‐enzymatic Glucose Detection
Authors: Mathi Selvam , Karthikeyan Venkatraman , Jayabharathi Jayaraman
Published: November 2021

The nitrogen doped carbon (NDCN) have been synthesized by flame synthetic method to prepare ferrocene decorated NDCN. The hydrolysis product (FC‐SH) of ferrocene benzyne derivative (FC‐SAc) was immobilized onto NDCN modified GCE and used for glucose detection with high sensitivity. Cyclic voltammetric analysis reveal that FC‐S‐NDCN/GCE exhibit excellent activity for glucose oxidation when compared to FC/GCE. The FC‐S‐NDCN/GCE with wide linear responses range from 0.001 to 0.01 mM with the regression co‐efficient of 0.998. The FC‐S‐NDCN/GCE show low detection limit (LOD) of 0.08 μM and exhibit sensitivity of 1580 μA mM−1 cm−2. The FC‐S‐NDCN glucose sensor exhibit wide linear range, high sensitivity and lower detection limit on determination of glucose.
Response of Crustacean Zooplankton and Benthic Macroinvertebrate Communities to Selenium Additions in a Boreal Lake
Authors: Graves Stephanie D. , Liber Karsten , Palace Vince , Hecker Markus , Janz David M.
Published: November 2021

Selenium (Se) is a contaminant of concern in Canada mainly due to its teratogenic effects on fish and birds. However, few studies have assessed the effects of Se on invertebrates in a field setting. The objective of this experiment was to assess potential community-level impacts of Se additions on zooplankton and benthic macroinvertebrates in a boreal lake ecosystem. From June to August 2018, Se (as selenite) was added to six limnocorrals in Lake 239 at the International Institute for Sustainable Development–Experimental Lakes Area, Northwestern Ontario, Canada, to achieve mean measured aqueous concentrations of 0.4, 0.8, 1.6, 3.4, 5.6 and 7.9 µg Se/L, with three untreated limnocorrals serving as controls (background Se = 0.08–0.09 µg/L). Periphyton, phytoplankton, and invertebrates (zooplankton and benthos) were monitored for 63 days. Zooplankton community composition shifted as a function of Se exposure, with Cladocera biomass and density decreasing with increasing Se concentrations. Similarly, cumulative abundance and biomass of Heptageniidae decreased with increasing Se treatment throughout the experimental period. The present study demonstrated that Se can have impacts on aquatic invertebrates at environmentally relevant exposure levels, and that future ecological risk assessments should consider the impacts of Se on both vertebrates and invertebrates. Environ Toxicol Chem 2022;41:95–107. © 2021 SETAC
Velocity slip, chemical reaction, and suction/injection effects on two‐dimensional unsteady MHD mass transfer flow over a stretching surface in the presence of thermal radiation and viscous dissipation
Authors: Reddy Nalivela Nagi , Rao Vempati Srinivasa , Reddy Bolla Ravindra
Published: November 2021

The purpose of this study is to analyze the impact of velocity slip, chemical reaction, and suction/injection on two‐dimensional mass transfer effects on unsteady MHD flow over a stretching surface in the presence of thermal radiation and viscous dissipation. The governing time‐dependent nonlinear partial differential equations are transformed into nonlinear ordinary differential equations by using similarity transformations. The converted equations are solved using the numerical technique with the help of Keller‐Box method. The effect of nondimensional variables is studied and graphically illustrated on velocity, temperature, concentration, friction factor, Nusselt number, and Sherwood number. Concentration and temperature profiles are enhanced and the contrasting pattern for velocity profiles as increasing the velocity slip and magnetic parameter. The concentration profile is diminished as the Schmidt number (Sc) and chemical reaction (Cr) increase. The concentration, velocity, and temperature profiles display a reversal pattern, as the suction and unsteady parameter (A) increase. The findings of this study are very well‐acknowledged with current research.
Laboratory management for large‐scale population screening for SARS‐CoV‐2
Authors: Duan Xiuzhi , Lv Dingfeng , Wang Lin , Liu Yanchao , Zhang Shu , Liu Weiwei , Xie Jiamin , Gu Chunqiang , Li Xiaosi , Tao Zhihua , Chen Xiang , Yao Qiang
Published: November 2021

Introduction

The aim of this study was to investigate the improvements in laboratory testing procedures and the quality and safety management for large‐scale population screening for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2).

Methods

Because of epidemic prevention and control needs in Hebei Province, on January 7, 2021, the Health Commission of Zhejiang Province sent a medical team to Hebei Province, to carry out SARS‐CoV‐2 nucleic acid testing. Screening for the SARS‐CoV‐2 nucleic acid test was performed using reverse‐transcription polymerase chain reaction (RT‐PCR). Practical tests and repeated process optimization were adopted to explore the optimal solution for improving laboratory testing procedures and the quality of and safety management for large‐scale population screening for SARS‐CoV‐2.

Results

The Zhejiang medical team completed 250,000 pooled SARS‐CoV‐2 nucleic acid samples in 24 days in Shijiazhuang, with a peak daily testing capacity of 40,246 samples testing. There were no false‐negative or false‐positive results, and no laboratory personnel was infected with SARS‐CoV‐2. Significant achievements have been made in SARS‐CoV‐2 prevention and control.

Conclusions

This report summarizes the effort of the medical team regarding their management of the quality and safety of laboratory tests and proposes corresponding empirical recommendations to provide a reference for future large‐scale population screening SARS‐CoV‐2.
Misidentified biomedical resources: Journal guidelines are not a quick fix
Authors: Hepkema Wytske M. , Horbach Serge P. J. M. , Hoek Joyce M. , Halffman Willem
Published: November 2021

Biomedical researchers routinely use a variety of biological models and resources, such as cultured cell lines, antibodies and laboratory animals. Unfortunately, these resources are not flawless: cell lines can be misidentified; for antibodies, problems with specificity, lot‐to‐lot consistency and sensitivity are common; and the reliability of animal models is questioned due to poor translation of animal studies to human clinical trials. In some cases, these problems can render the results of a study meaningless. As a response, some journals have implemented guidelines regarding the use and reporting of cell lines, antibodies and laboratory animals. In our study we use a portfolio of existing and newly created datasets to investigate identification and authentication information of cell lines, antibodies and organisms before and after guideline introduction, compared to journals without guidelines. We observed a general improvement of reporting quality over time, which the implementation of guidelines accelerated only in some cases. We therefore conclude that the effectiveness of journal guidelines is likely to be context dependent, affected by factors such as implementation conditions, research community support and monitoring and resource availability. Hence, journal reporting guidelines in themselves are not a quick fix to repair shortcomings in biomedical resource documentation, even though they can be part of the solution.
Situational judgment tests: An introduction for clinician educators
Authors: Reed Brent N. , Smith Kathryn J. , Robinson Jennifer D. , Haines Stuart T. , Farland Michelle Z.
Published: November 2021

Although numerous tools exist to assess the clinical knowledge and skills of learners as they progress throughout the health professions curriculum, the measurement of professional attitudes, and behaviors (eg, empathy, integrity, teamwork) remains a challenge for educators. Situational judgment tests (SJTs) are a methodology for assessing how an individual's underlying knowledge, skills, traits, and other attributes are expressed when making decisions about job‐related scenarios. Studies have shown that SJTs can be a valuable predictor of future job performance among health professionals and recent research suggests that they may also be useful for the development of professional attitudes and behaviors. The primary advantage of SJTs is that they permit an assessment of these complex constructs among large groups of test‐takers, making them an appealing alternative or supplement to more resource‐intensive methods, such as situational interviews or objective structured clinical examinations. However, SJT development is a complex process and requires a set of knowledge and skills that may be unfamiliar to many clinician educators (eg, job analysis, assessments of validity, and reliability). The purpose of this review is to provide readers with an introduction to SJTs, including an overview of research to support their use, considerations regarding their content and development, and implications for practice and education.
Strategies for induction of HIV‐1 envelope‐reactive broadly neutralizing antibodies
Authors: Williams Wilton B. , Wiehe Kevin , Saunders Kevin O. , Haynes Barton F.
Published: November 2021

Introduction

A primary focus of HIV‐1 vaccine development is the activation of B cell receptors for naïve or precursor broadly neutralizing antibodies (bnAbs), followed by expansion and maturation of bnAb B cell lineage intermediates leading to highly affinity‐matured bnAbs. HIV‐1 envelope (Env) encodes epitopes for bnAbs of different specificities. Design of immunogens to induce bnAb precursors of different specificities and mature them into bnAb status is a goal for HIV‐1 vaccine development. We review vaccine strategies for bnAb lineages development and highlight the immunological barriers that these strategies must overcome to generate bnAbs.

Methods

We provide perspectives based on published research articles and reviews.

Discussion

The recent Antibody Mediated Protection (AMP) trial that tested the protective efficacy of one HIV‐1 Env bnAb specificity demonstrated that relatively high levels of long‐lasting serum titers of multiple specificities of bnAbs will be required for protection from HIV‐1 transmission. Current vaccine efforts for induction of bnAb lineages are focused on immunogens designed to expand naïve HIV‐1 bnAb precursor B cells following the recent success of vaccine‐induction of bnAb precursor B cells in macaques and humans. BnAb precursor B cells serve as templates for priming‐immunogen design. However, design of boosting immunogens for bnAb maturation requires knowledge of the optimal immunogen design and immunological environment for bnAb B cell lineage affinity maturation. BnAb lineages acquire rare genetic changes as mutations during B cell maturation. Moreover, the immunological environment that supports bnAb development during HIV‐1 infection is perturbed with an altered B cell repertoire and dysfunctional immunoregulatory controls, suggesting that in normal settings, bnAb development will be disfavoured. Thus, strategies for vaccine induction of bnAbs must circumvent immunological barriers for bnAb development that normally constrain bnAb B cell affinity maturation.

Conclusions

A fully protective HIV‐1 vaccine needs to induce durable high titers of bnAbs that can be generated by a sequential set of Env immunogens for expansion and maturation of bnAb B cell lineages in a permitted immunological environment. Moreover, multiple specificities of bnAbs will be required to be sufficiently broad to prevent the escape of HIV‐1 strains during transmission.
Pro‐inflammatory profiles in cardiovascular disease patients with peri‐implantitis
Authors: Wang I‐Ching , Sugai Jim V. , Majzoub Jad , Johnston Jeffery , Giannobile William V. , Wang Hom‐Lay
Published: November 2021

Background

To investigate the pro‐inflammatory cytokine profiles in patients with or without cardiovascular disease (CVD) and with or without peri‐implantitis.

Methods

Serum, peri‐implant crevicular fluid (PICF), and gingival crevicular fluid (GCF) were collected from patients with (n = 82) or without CVD (n = 46) at the most severe peri‐implantitis site including sites with periodontitis. A panel of proinflammatory molecules including high‐sensitivity C‐reactive protein (hsCRP), fibrinogen, interleukin‐1 beta (IL‐1β), IL‐6, plasma tumor necrosis factor‐alpha (TNF‐α), matrix metallo‐proteinase‐8 (MMP‐8), osteoprotegerin (OPG), vascular endothelial growth factor (VEGF), IL‐17, IL‐8, tissue inhibitor of metalloproteinase‐2 (TIMP‐2), myeloperoxidase (MPO), and prostaglandin E2 (PGE2) were analyzed using human custom Quantibody arrays. Krunskal‐Wallis test was used to compare groups. The diagnostic ability of each biomarker was assessed using chi‐square test and ROC analysis.

Results

Serum IL‐1β, TNF‐α and fibrinogen were significantly higher in CVD patients than those without. Serum fibrinogen displayed a trend of higher concentration in patients with radiographic bone loss (RBL) ≥2 mm (P = 0.08). PICF TNF‐α exhibited a significantly higher detection level in the CVD patients that is coincided with the local peri‐implant inflammation. In addition, PICF MMP‐8 was significantly higher in the RBL ≥2 mm sites than the healthy implants; whereas IL‐1β, IL‐8, MMP‐8, and TIMP‐2 proved to be the significant predictors for peri‐implant disease. GCF TNF‐α collected from patients with periodontitis was significantly associated with CVD cases.

Conclusion

The augmented expression of local and systemic pro‐inflammatory cytokines found in the current study supports the weak association between the chronic peri‐implantitis with increasing severity and CVD.
Outcome of Extended Right Lobe Liver Transplantations
Authors: Lozanovski Vladimir J. , Unterrainer Christian , Döhler Bernd , Süsal Caner , Mehrabi Arianeb
Published: November 2021

Split‐liver transplantation offers a solution to the organ shortage problem. However, the outcomes of extended right lobe liver transplantation (ERLT) and whether it is a suitable alternative to full‐size liver transplantation (FSLT) remain controversial. We compared the outcomes of ERLT and FSLT in adult recipients of 43,409 first deceased donor liver transplantations using Cox regression. We also analyzed 612 ERLT and 1224 FSLT 1:2 matched cases to identify factors that affect ERLT outcome. The risk of graft loss was significantly higher following ERLT than following FSLT during the first posttransplantation year in the matched and unmatched collective (hazard ratio [HR], 1.39 and 1.27 and P = 0.01 and 0.006, respectively). Every additional hour of cold ischemia time (CIT) increased the risk of 1‐year graft loss by 10% in the ERLT group compared with only 3% in the FSLT group (P = 0.003 and <0.001, respectively). Importantly, the outcome of ERLT and FSLT did not differ significantly if the CIT was below 10 hours (HR, 0.71; P = 0.22). One‐year graft and patient survival were lower in high‐risk ERLT recipients with a Model for End‐Stage Liver Disease (MELD) score of ≥20 (HR, 1.88; P = 0.03 and HR, 2.03; P = 0.02). In the male recipient–male donor combination, ERLT recipients had a higher risk of 1‐year graft loss than FSLT recipients (HR, 2.44; P = 0.006). This was probably because of the significantly higher MELD score in ERLT recipients (P = 0.004). ERLT in adults is an adequate alternative to FSLT and offers an elegant solution to the problem of organ shortage as long as the cold storage is less than 10 hours and the recipient’s MELD score is <20.
Fog probabilistic forecasting using an ensemble prediction system at six airports in Iran for 10 fog events
Authors: Pahlavan R. , Moradi M. , Tajbakhsh S. , Azadi M. , Rahnama M.
Published: November 2021

Low visibility conditions due to fog affect air traffic and, in some cases, are the leading cause of aviation accidents. Accurate forecasting of fog can lead to a significant reduction of human and financial losses. Numerical weather prediction (NWP) models have limitations in simulating fog accurately for operational purposes. However, recent studies have confirmed that ensemble‐based forecasts are effective in fog forecasting. In this study, a multi‐physics ensemble prediction system (EPS) was used to simulate the occurrence of several radiation, cloud base lowering (CBL), and advection fog events that occurred at Arak, Ardebil, Hamedan, Orumiyeh, Rasht and Shahrekord airports located across Iran, during January and December 2015. The multi‐physics EPS including a reference deterministic forecast consists of 16 different configurations of the weather research and forecasting (WRF) model and was run from 12 UTC 12 January to 12 UTC 16 January 2015 and from 00 UTC 27 December to 12 UTC 31 December 2015 to simulate fog occurrences at six airports. SW99 and G2009 visibility algorithms were applied to the EPS outputs to predict the fog. The advantages of probabilistic fog forecasting in this study were shown by comparing the reference forecast and the ensemble‐based forecasts of fog events. The results showed that by considering a probability threshold of 37.5%, 50% and 62.5% for the ensemble forecasts, the EPS outperformed the deterministic fog forecasts obtained from a deterministic reference forecast. Such that, with 37.5% and 50% probability thresholds, the equitable threat score (ETS) was much higher than the ETS for the reference deterministic fog forecast. Also, the EPS with 37.5% and 50% probability thresholds could correctly predict 3 and 4 (out of 10) more fog events compared with the reference deterministic forecast.