bluuebunny/crossref_metadata_2025 huggingface dataset:
Population structure, residency, and abundance of whale sharks in the coastal waters off Nosy Be, north‐western Madagascar
Authors: Diamant Stella , Pierce Simon J. , Rohner Christoph A. , Graham Rachel T. , Guillemain d'Echon Arthur , Guillemain d'Echon Tanguy , Sourisseau Elina , Fidiarisandratra Léonce Costika , Bakary Gisèle , Trélanche Sylvia , Andriananrisoa Fanja , Kiszka Jeremy J.
Published: November 2021

Between September and December, whale sharks (Rhincodon typus) aggregate in the coastal waters off Nosy Be, an island in north‐western Madagascar. Swimming with these sharks has become an important tourism activity, but no formal protection is in place in Madagascar to protect this endangered species from the potential negative effects of tourism or other human impacts.

Boat‐based surveys (n = 405) were conducted from tourism vessels from September to December, 2015–2019. For most sightings (98%), whale sharks were sighted while foraging for bait fish at the surface, in association with mackerel tuna (Euthynnus affinis) and seabirds (Sternidae). A total of 408 individual whale sharks were individually photo‐identified over this period. All individuals were immature, and 82% of sexed sharks were male. Sharks ranged from 3.0 to 8.0 m in total length (TL), with a mean TL of 5.65 ± 0.94 m (n = 66) for females and 5.46 ± 1.09 m for males (n = 295).

Most sharks (72% of the identified individuals) were only identified once within the study period. Movement modelling showed an open population with a short mean residence time of 7.2 days. Resightings were recorded from up to 12 years apart (2007–2019). Ten sharks were seen in all five seasons during 2015–2019. A basic POPAN mark–recapture model estimated a total population size of 681 (608–763) sharks over the 2015–2019 period.

Nosy Be waters are an important foraging ground for juvenile whale sharks. Sighting data demonstrate that a high proportion of the sharks’ preferred habitat lies outside existing protected areas, but within an identified Key Biodiversity Area. National species‐level protection and increased spatial management is warranted to secure the continued presence of whale sharks in this region.
Presenilin is involved in larval‐pupal metamorphosis development of Bombyx mori
Authors: Qian Xiaoran , Chen Kai , Chen Lijuan , Song Hongsheng , Zhang Zhongjie
Published: November 2021

Disruption of the presenilin (ps) genes are the major genetic cause of familial Alzheimer's disease. The silkworm, Bombyx mori (B. mori), is an important model insect. The ps homologue gene in B. mori was identified and characterized. However, the role of ps in B. mori was poorly understood. Here, we found that Bmps was ubiquitously expressed in all the tested tissues during metamorphosis. In the current study, loss‐of‐function analysis of Bmps was performed by the binary transgenic CRISPR/cas9 system. Compared with the wild type, the developmental time of ∆Bmps animals were significantly delayed. In addition, ∆Bmps showed abnormal appendage including antenna, leg, wing and eye during pupal and adult stages. RNA‐seq analysis indicated that apoptosis and proliferation related pathways were affected in ∆Bmps. Moreover, the Hippo pathway was affected by Bmps depletion in brain and wing disc. Our results suggest that PS is essential for maintaining the dynamic balance of apoptosis and proliferation during metamorphosis.
Catalyst‐Controlled Regiodivergent Synthesis of α/β‐Dipeptide Derivatives via N‐Allylic Alkylation of O‐Alkyl Hydroxamates with MBH Carbonates
Authors: Wang Shutao , Zheng Lianyou , Song Shaoli , Wang Siyu , Zhang Zhuoqi , Xiang Jinbao
Published: November 2021

A controllable and regiodivergent N‐allylation reaction involving readily available O‐alkyl hydroxamates derived from natural α‐amino acids has been developed, allowing regiospecific access to α/β‐dipeptides containing α‐unsaturated β‐amino acids moieties in moderate to good yields. The regioselectivity could be conveniently switched by alternation of the catalysts and solvents.
Black hole masses from emission‐line widths
Authors: Dalla Bontà Elena , Peterson Bradley M.
Published: November 2021

Reverberation mapping and scaling relationships based on reverberation results provide the underpinning of all estimates of quasar black hole masses. When applying these scaling relationships, there are potential pitfalls that are widely unappreciated and can result in biases that can, in turn, lead to systematic errors in the black hole mass function and therefore conclusions about the evolution of black holes over time. Here we discuss specifically the suitability of various line‐width measures for estimating black hole masses.
Hemoglobin‐Inorganic Hybrid Nanoflowers with Different Metal Ions as Potential Oxygen Carrying Systems
Authors: Gulmez Canan , Altinkaynak Cevahir , Turk Merve , Ozdemir Nalan , Atakisi Onur
Published: November 2021

Protein‐inorganic hybrid nanoflowers have tremendous potential in bionanotechnology due to their simple method of preparation, high stability and superior properties. Considering these features, the present study was designed to investigate the artificial blood substitution potentials of hemoglobin‐inorganic hybrid nanoflowers. In this context, hemoglobin‐inorganic hybrid nanoflowers (Cu‐NF, Co‐NF and Zn‐NF) were synthesized using with different metal ions (copper, cobalt and zinc), then their oxygen carrying capacity, the hemolytic studies, in vitro oxidant/antioxidant capacity levels and oxidative stress index were reported for the first time. The present findings have revealed that Zn‐NF had significant oxygen content and artificial oxygen carriers (AOC), as well as a significantly low percent hemolysis rate and a safe standard value. Also, hemolysis rate decreased along with the increases in hemoglobin content coupled with increments in nanoflower concentrations. The percentage hemolysis rate was lower than all nanoflowers at low free hemoglobin concentration, but hemolysis rates also increased with increments in concentration. The results showed that in general, Zn‐NF stands out with its high total antioxidant capacity and low total oxidant capacity and oxidative stress index. The obtained results showed that Cu‐NF and Co‐NF, especially Zn‐NF might be considered as a potential superior artificial oxygen carrier. Therefore, this nanoflower system might be act as an efficient material as a blood substitute in the near future.
Experiencing the reality of empathy
Authors: Cole Rebekah F.
Published: November 2021

This pretest/posttest experimental design study investigated the use of virtual reality to teach school counseling students empathy, as measured by the Empathy Quotient. An independent samples and paired‐samples t‐test were used to analyze students’ scores in the experimental and control groups. The study's results are discussed.
Flow Regimes in Gas‐Solid Fluidized Beds via Micro‐Foil Heat Flux Sensor
Authors: Taofeeq Haidar , Uribe Sebastián , Al-Dahhan Muthanna
Published: November 2021

The flow regime transitions in a gas‐solid fluidized bed were studied for the first time using a micro‐foil heat flux sensor. The time series of heat flux signals was analyzed by statistical and state space methods. The experimental measurements were performed in a lab‐scale gas‐solid fluidization column. Four different flow regimes, i.e., fixed‐bed flow regime, bubbling‐flow regime, slugging‐flow regime, and turbulent‐flow regime, and three intermediate transition velocities, i.e., minimum fluidizing velocity or minimum bubbling velocity, minimum slugging velocity, and minimum turbulent velocity, were successfully identified. The method based on the analysis of heat flux sensor measurements allowed to determine accurately the different flow regimes and the transition velocities.
Microorganism‐Assisted Biohydrogen Production and Bioreactors
Authors: Singh Himanshi , Paritosh Kunwar , Vivekanand Vivekanand , Pareek Nidhi
Published: November 2021

Microorganism‐assisted biohydrogen (BioH2) is an encouraging replacement of fossil‐based fuels as feasible preference for various chemical and mechanical processes. BioH2 is capable to reduce greenhouse gas emissions and solve environmental issues, therefore, numerous studies addressed optimization of operation design, microbial actions, certain addition of chemicals or nanoparticles, pretreatment of algal biomass, diminishing sensibility of enzymes towards O2, integration with different processes for biorefinery approach, reducing costs, bioelectrochemical cell membranes, and others. The present review focuses on model organisms employed for the microorganism‐assisted biohydrogen production. Metabolic pathways such as biophotolysis, photofermentation, and dark fermentation were discussed for providing deep insight of microorganism‐aided biohydrogen production.
Optimization of Operation Conditions for Zeolitic Imidazolate Framework/Polydimethylsiloxane Hybrid Pervaporation Membranes
Authors: Pan Yong , Zhu Chen , Fu Pei , Zeng Wenbin , Chen Chi , Xu Baoming
Published: November 2021

The separation performance of a membrane is not only related to the membrane, but also to the operating conditions. The operation conditions of superhydrophobic zeolitic imidazolate framework‐90 (S‐ZIF‐90)/polydimethylsiloxane hybrid membranes for pervaporation were optimized using response surface methodology. The separation performances of hybrid membranes were evaluated by regulating the rotation rate, operation temperature, and feed concentration. The regression equations between the operation variables and the separation performance of the hybrid membranes were established and applied to predict and optimize the separation performance of these membranes. The main effects, quadratic effects, and interactions of the three variables on the permeation flux and the separation factor of hybrid membranes were analyzed.
Effects of Flocculant Concentration and Temperature on the Membrane Separation Process in Microalgal Suspensions
Authors: Nishimura Thiago , Garcia Lesak Giuliana Varela , Alves Xavier Lorenna , Bruno Vieira Rafael , Bellin Mariano André
Published: November 2021

By using different flocculant concentrations and temperatures with a tannin‐based flocculant, chitosan, and ferric chloride, the performance of a combined flocculation and membrane separation process in microalgal suspensions was evaluated. Permeate flux experiments were conducted for 30 min, and the effects of the flocculant concentration and temperature were analyzed. The zeta potential of the culture with and without flocculant approached zero with increasing temperature, in favor of microalgal cell agglomeration. At 40 °C, crossflow microfiltration showed a 27 % improvement in the permeate flux compared to 20 °C. Overall, the results showed a significant potential use of flocculants with increasing temperature, by providing considerably higher permeated fluxes.
Orthogonal Catalysis for an Enantioselective Domino Inverse‐Electron Demand Diels−Alder/Substitution Reaction
Authors: Beeck Sebastian , Ahles Sebastian , Wegner Hermann A.
Published: November 2021

An enantioselective domino process for the synthesis of substituted 1,2‐dihydronaphthalenes has been developed by the combination of chiral amines and a bidentate Lewis acid in an orthogonal catalysis. This new method is based on an inverse electron‐demand Diels−Alder and a subsequent group exchange reaction. An enamine is generated in situ from an aldehyde and a chiral secondary amine catalyst that reacts with phthalazine, activated by the coordination to a bidentate Lewis acid catalyst. The absolute configuration of the product is controlled by chiral information provided by the amine. The formed ortho‐quinodimethane intermediate is then transformed via a group exchange reaction with thiols. The new method shows a broad scope and tolerates a wide range of functional groups with enantiomeric ratios up to 91 : 9. All‐in‐all, this enantioselective synthesis tool provides an easy access to complex 1,2‐dihydronaphthalenes starting from readily available phthalazine, aldehydes and thiols in a combinatorial way.
Multigram‐scale enzymatic kinetic resolution of trans‐2‐azidocyclohexyl acetate and chiral reversed‐phase HPLC analysis of trans‐2‐azidocyclohexanol
Authors: Hebda Paulina , Wiśniowska Lilianna , Szafrański Przemysław W. , Cegła Marek
Published: November 2021

Lipase‐catalyzed hydrolytic kinetic resolution is a method of obtaining optically pure chiral alcohols and amines, which requires additional tools for determining enantiomerical purity. Herein, we present a study on multigram‐scale hydrolytic kinetic resolution of trans‐2‐azidocyclohexyl acetate using Pseudomonas cepacia lipase immobilized on Immobead support. We investigated several parameters of the preparative‐scale process: temperature, organic co‐solvent, and the influence of calcium ions. Moreover, we have developed an efficient fluorenylmethyloxycarbonyl chloride (Fmoc‐Cl) derivatization protocol for 2‐azidocyclohexanol, which enabled chiral reversed‐phase high‐performance liquid chromatography (RP‐HPLC) determination of enantiomeric excess.
Evaluation of viscoelastic surfactant‐based diverting agent during the chemical treatment of sandstone reservoirs
Authors: Nazari Moghaddam Rasoul , van Doorn Marcel , Dos Santos Auribel , Oskarsson Hans , Heck Kiernan , Ferm Paul
Published: November 2021

The challenges of diversion during the stimulations of carbonate formations have been widely studied for decades. It has been shown that viscoelastic surfactants (VES) are among the effective diverting solutions which can be used during the stimulation of carbonate formations. These chemicals benefit from the reaction products between the acid and the calcite to increase the viscosity of the acid, therefore reducing, temporarily, the permeability of the first invaded rock layer, which holds the highest permeability. This temporary blockage steers the remaining acid to the layers with lower permeability that need treatment. This is usually called self‐diverting acidizing treatment. However, the same approach may not necessarily be applied for sandstone formations that are not calcite rich. In such cases, combining acid stages with batches of diverting agents is still feasible. For this approach, VES is also a suitable, non‐damaging solution that is often overlooked. In this study, the application of VES as a diverting agent was investigated during the chemical treatment operations in sandstone formations. Several dual core‐flooding experiments were performed at high pressure and high temperature (HPHT) conditions using sandstone core samples with high permeability contrast.
AAV‐BR1 targets endothelial cells in the retina to reveal their morphological diversity and to deliver Cx43
Authors: Ivanova Elena , Corona Carlo , Eleftheriou Cyril G. , Stout Randy F. , Körbelin Jakob , Sagdullaev Botir T.
Published: November 2021

Endothelial cells (ECs) are key players in the development and maintenance of the vascular tree, the establishment of the blood–brain barrier and control of blood flow. Disruption in ECs is an early and active component of vascular pathogenesis. However, our ability to selectively target ECs in the CNS for identification and manipulation is limited. Here, in the mouse retina, a tractable model of the CNS, we utilized a recently developed AAV‐BR1 system to identify distinct classes of ECs along the vascular tree using a GFP reporter. We then developed an inducible EC‐specific ectopic Connexin 43 (Cx43) expression system using AAV‐BR1‐CAG‐DIO‐Cx43‐P2A‐DsRed2 in combination with a mouse line carrying inducible CreERT2 in ECs. We targeted Cx43 because its loss has been implicated in microvascular impairment in numerous diseases such as diabetic retinopathy and vascular edema. GFP‐labeled ECs were numerous, evenly distributed along the vascular tree and their morphology was polarized with respect to the direction of blood flow. After tamoxifen induction, ectopic Cx43 was specifically expressed in ECs. Similarly to endogenous Cx43, ectopic Cx43 was localized at the membrane contacts of ECs and it did not affect tight junction proteins. The ability to enhance gap junctions in ECs provides a precise and potentially powerful tool to treat microcirculation deficits, an early pathology in numerous diseases.
A standardised hERG phenotyping pipeline to evaluate KCNH2 genetic variant pathogenicity
Authors: Oliveira‐Mendes Barbara , Feliciangeli Sylvain , Ménard Mélissa , Chatelain Frank , Alameh Malak , Montnach Jérôme , Nicolas Sébastien , Ollivier Béatrice , Barc Julien , Baró Isabelle , Schott Jean‐Jacques , Probst Vincent , Kyndt Florence , Denjoy Isabelle , Lesage Florian , Loussouarn Gildas , De Waard Michel
Published: November 2021

Background and aims

Mutations in KCNH2 cause long or short QT syndromes (LQTS or SQTS) predisposing to life‐threatening arrhythmias. Over 1000 hERG variants have been described by clinicians, but most remain to be characterised. The objective is to standardise and accelerate the phenotyping process to contribute to clinician diagnosis and patient counselling. In silico evaluation was also included to characterise the structural impact of the variants.

Methods

We selected 11 variants from known LQTS patients and two variants for which diagnosis was problematic. Using the Gibson assembly strategy, we efficiently introduced mutations in hERG cDNA despite GC‐rich sequences. A pH‐sensitive fluorescent tag was fused to hERG for efficient evaluation of channel trafficking. An optimised 35‐s patch‐clamp protocol was developed to evaluate hERG channel activity in transfected cells. R software was used to speed up analyses.

Results

In the present work, we observed a good correlation between cell surface expression, assessed by the pH‐sensitive tag, and current densities. Also, we showed that the new biophysical protocol allows a significant gain of time in recording ion channel properties and provides extensive information on WT and variant channel biophysical parameters, that can all be recapitulated in a single parameter defined herein as the repolarisation power. The impacts of the variants on channel structure were also reported where structural information was available. These three readouts (trafficking, repolarisation power and structural impact) define three pathogenicity indexes that may help clinical diagnosis.

Conclusions

Fast‐track characterisation of KCNH2 genetic variants shows its relevance to discriminate mutants that affect hERG channel activity from variants with undetectable effects. It also helped the diagnosis of two new variants. This information is meant to fill a patient database, as a basis for personalised medicine. The next steps will be to further accelerate the process using an automated patch‐clamp system.
The metabolism of the synthetic cannabinoids ADB‐BUTINACA and ADB‐4en‐PINACA and their detection in forensic toxicology casework and infused papers seized in prisons
Authors: Kronstrand Robert , Norman Caitlyn , Vikingsson Svante , Biemans Anoek , Valencia Crespo Bryan , Edwards Darren , Fletcher Daniel , Gilbert Nicolas , Persson Mattias , Reid Robert , Semenova Olga , Al Teneiji Faisal , Wu Xiongyu , Dahlén Johan , NicDaéid Niamh , Tarbah Fuad , Sutcliffe Oliver B. , McKenzie Craig , Gréen Henrik
Published: November 2021

Early warning systems detect new psychoactive substances (NPS), while dedicated monitoring programs and routine drug and toxicology testing identify fluctuations in prevalence. We report the increasing prevalence of the synthetic cannabinoid receptor agonist (SCRA) ADB‐BUTINACA (N‐[1‐amino‐3,3‐dimethyl‐1‐oxobutan‐2‐yl]‐1‐butyl‐1H‐indazole‐3‐carbox‐amide). ADB‐BUTINACA was first detected in a seizure in Sweden in 2019, and we report its detection in 13 routine Swedish forensic toxicology cases soon after. In January 2021, ADB‐BUTINACA was detected in SCRA‐infused papers seized in Scottish prisons and has rapidly increased in prevalence, being detected in 60.4% of the SCRA‐infused papers tested between January and July 2021. In this work, ADB‐BUTINACA was incubated with human hepatocytes (HHeps), and 21 metabolites were identified in vitro, 14 being detected in authentic case samples. The parent drug and metabolites B9 (mono‐hydroxylation on the n‐butyl tail) and B16 (mono‐hydroxylation on the indazole ring) are recommended biomarkers in blood, while metabolites B4 (dihydrodiol formation on the indazole core), B9, and B16 are suitable biomarkers in urine. ADB‐4en‐PINACA (N‐[1‐amino‐3,3‐dimethyl‐1‐oxobutan‐2‐yl]‐1‐[pent‐4‐en‐1‐yl]‐1H‐indazole‐3‐carboxamide) was detected in Scottish prisons in December 2020, but, unlike ADB‐BUTINACA, prevalence has remained low. ADB‐4en‐PINACA was incubated with HHeps, and 11 metabolites were identified. Metabolites E3 (dihydrodiol formed in the tail moiety) and E7 (hydroxylation on the linked/head group) are the most abundant metabolites in vitro and are suggested as urinary biomarkers. The in vitro potencies of ADB‐BUTINACA (EC50, 11.5 nM and ADB‐4en‐PINACA (EC50, 11.6 nM) are similar to that of MDMB‐4en‐PINACA (EC50, 4.3 nM). A third tert‐leucinamide SCRA, ADB‐HEXINACA was also detected in prison samples and warrants further investigation.
Rethinking positional information and digit identity: The role of late interdigit signaling
Authors: Huang Bau‐Lin , Mackem Susan
Published: November 2021

Seminal work from John Fallon's lab has illuminated how digit identity determination involves ongoing late regulation and occurs progressively during phalanx formation. Complementary genetic analyses in mice and several papers in this special issue have begun to flesh out how interdigit signaling accomplishes this, but major questions remain unaddressed, including how uncommitted progenitors from which phalanges arise are maintained, and what factors set limits on digit extension and phalanx number, particularly in mammals. This review summarizes what has been learned in the two decades since control of digit identity by late interdigit signals was first identified and what remains poorly understood, and will hopefully spark renewed interest in a process that is critical to evolutionary limb adaptations but nevertheless remains enigmatic.
Droplet digital PCR as a tool for investigating dynamics of cryptic symbionts
Authors: Hiillos Anna‐Lotta , Thonig Anne , Knott Karelyn Emily
Published: November 2021

Interactions among symbiotic organisms and their hosts are major drivers of ecological and evolutionary processes. Monitoring the infection patterns among natural populations and identifying factors affecting these interactions are critical for understanding symbiont–host relationships. However, many of these interactions remain understudied since the knowledge about the symbiont species is lacking, which hinders the development of appropriate tools. In this study, we developed a digital droplet PCR (ddPCR) assay based on apicomplexan COX1 gene to detect an undescribed agamococcidian symbiont. We show that the method gives precise and reproducible results and enables detecting cryptic symbionts in low target concentration. We further exemplify the assay's use to survey seasonally sampled natural host (Pygospio elegans) populations for symbiont infection dynamics. We found that symbiont prevalence differs spatially but does not show seasonal changes. Infection load differed between populations and was low in spring and significantly increased towards fall in all populations. We also found that the symbiont prevalence is affected by host length and population density. Larger hosts were more likely to be infected, and high host densities were found to have a lower probability of infection. The observed variations could be due to characteristics of both symbiont and host biology, especially the seasonal variation in encounter rates. Our findings show that the developed ddPCR assay is a robust tool for detecting undescribed symbionts that are otherwise difficult to quantify, enabling further insight into the impact cryptic symbionts have on their hosts.
Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure –A clinical practice Guideline Level 3
Authors: Assmann Alexander , Beckmann Andreas , Schmid Christof , Werdan Karl , Michels Guido , Miera Oliver , Schmidt Florian , Klotz Stefan , Starck Christoph , Pilarczyk Kevin , Rastan Ardawan , Burckhardt Marion , Nothacker Monika , Muellenbach Ralf , Zausig York , Haake Nils , Groesdonk Heinrich , Ferrari Markus , Buerke Michael , Hennersdorf Marcus , Rosenberg Mark , Schaible Thomas , Köditz Harald , Kluge Stefan , Janssens Uwe , Lubnow Matthias , Flemmer Andreas , Herber‐Jonat Susanne , Wessel Lucas , Buchwald Dirk , Maier Sven , Krüger Lars , Fründ Andreas , Jaksties Rolf , Fischer Stefan , Wiebe Karsten , Hartog Christiane S. , Dzemali Omer , Zimpfer Daniel , Ruttmann‐Ulmer Elfriede , Schlensak Christian , Kelm Malte , Ensminger Stephan , Boeken Udo
Published: November 2021

Aims Worldwide applications of extracorporeal circulation for mechanical support in cardiac and circulatory failure, which are referred to as extracorporeal life support (ECLS) or veno‐arterial extracorporeal membrane oxygenation (va‐ECMO), have dramatically increased over the past decade. In spite of the expanding use and the immense medical as well as socio‐economic impact of this therapeutic approach, there has been a lack of interdisciplinary recommendations considering the best available evidence for ECLS treatment.

Methods and Results In a multiprofessional, interdisciplinary scientific effort of all scientific societies involved in the treatment of patients with acute cardiac and circulatory failure, the first evidence‐ and expert consensus‐based guideline (level S3) on ECLS/ECMO therapy was developed in a structured approach under regulations of the AWMF (Association of the Scientific Medical Societies in Germany) and under use of GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. This article presents all recommendations created by the expert panel, addressing a multitude of aspects for ECLS initiation, continuation, weaning and aftercare as well as structural and personnel requirements.

Conclusions This first evidence‐ and expert consensus‐based guideline (level S3) on ECLS/ECMO therapy should be used to apply the best available care nationwide. Beyond clinical practice advice, remaining important research aspects for future scientific efforts are formulated.
Synthesis, Reactivity and Electronic Properties of Quinazolin‐2‐one‐Based N‐Heterocyclic Carbenes
Authors: Brüggemann Peter , Mzyk Karol , Molter Marius , Nellesen Joscha , Schaper Klaus , Ganter Christian
Published: November 2021

The electronic properties of a new member F of the family of cyclic (aryl)(amido)carbenes (CArAmC) have been determined. Suitable precursors can easily be obtained by a straightforward synthesis starting from 2‐nitrobenzaldehyde (5). Metal complexes (14, 15) and chalcogen adducts (12, 13) were prepared and their spectroscopic data were evaluated and compared with those reported for CArAmCs (C, D) and the mixed (amino)(amido)carbene E which is a constitutional isomer of the newly reported carbene F. The IR spectroscopic determination indicates an unexceptional TEP value of 2055 cm−1, whereas the strong π‐accepting character is reflected by a chemical shift of δ(77Se) 936 ppm for the Se‐adduct 12 a. However, a significant degree of electrophilic reactivity of the in situ‐generated carbene F was not observed, as, for example, no cyclopropanation reactions with olefins could be detected. DFT calculations provide a rationale for these experimental observations.
Decreasing anti‐elderly discriminatory attitudes: Conducting a ‘Stereotype Embodiment Theory’‐based intervention
Authors: Shimizu Yuho , Hashimoto Takaaki , Karasawa Kaori
Published: November 2021

Stereotype Embodiment Theory (SET) implies that people who hold negative attitudes towards the elderly are more likely to experience a decline in various cognitive/physical functions themselves. Anti‐elderly discriminatory attitudes, which negatively affect the elderly's health status, could be reduced by communicating the contents of SET to non‐elderly people. To weaken anti‐elderly discriminatory attitudes, in Study 1, we had participants read about SET and related empirical findings (SET intervention), which intended to increase their self‐interested motives for avoiding anti‐elderly discrimination. In Study 2, we conducted an ‘integrated intervention’ containing a SET intervention and one selected aspect of educational intervention (i.e., presenting some information about some commonly misunderstood aspects of the elderly). Consequently, the integrated/SET interventions reduced participants’ anti‐elderly discriminatory attitudes and these effects persisted for at least 1 week. Our new interventions will be useful for those who work with the elderly.
Sequential sampling approach to energy‐based multi‐objective design optimization of steel frames with correlated random parameters
Authors: Do Bach , Ohsaki Makoto
Published: November 2021

This work presents a novel sequential sampling approach to the multi‐objective reliability‐based design optimization of moment‐resisting steel frames subjected to earthquake excitation. The optimization problem is formulated with two objective functions, namely, the total mass and the energy dissipated by beam members of the frame, and subject to uncorrelated probabilistic constraints on dynamic responses under the effects of correlated random parameters of floor masses, external loads, and material properties. The dynamic responses for a small number of designs are found by nonlinear response history analysis and further approximated by Gaussian process (GP) models to mitigate the computational burden during the optimization process. Approximate solutions sorted among existing candidate solutions are updated after each optimization iteration using discrete random local and global searches. The GP models are also refined after each optimization iteration by specifying new sampling points that lie on the Pareto front of a bi‐objective deterministic maximization problem formulated for the improvement in the current approximate solutions and the feasibility of the new sampling points. As demonstrated in a test problem, the new sampling points tend to distribute in the neighborhood of the exact solutions, thereby underpinning a quick termination as well as the robustness of the proposed method. Optimization results from the test problem and a design example show that good approximate solutions are always obtained as the solution quality converges.
Microbiota links to neural dynamics supporting threat processing
Authors: Hall Caitlin V. , Harrison Ben J. , Iyer Kartik K. , Savage Hannah S. , Zakrzewski Martha , Simms Lisa A. , Radford‐Smith Graham , Moran Rosalyn J. , Cocchi Luca
Published: November 2021

There is growing recognition that the composition of the gut microbiota influences behaviour, including responses to threat. The cognitive‐interoceptive appraisal of threat‐related stimuli relies on dynamic neural computations between the anterior insular (AIC) and the dorsal anterior cingulate (dACC) cortices. If, to what extent, and how microbial consortia influence the activity of this cortical threat processing circuitry is unclear. We addressed this question by combining a threat processing task, neuroimaging, 16S rRNA profiling and computational modelling in healthy participants. Results showed interactions between high‐level ecological indices with threat‐related AIC‐dACC neural dynamics. At finer taxonomic resolutions, the abundance of Ruminococcus was differentially linked to connectivity between, and activity within the AIC and dACC during threat updating. Functional inference analysis provides a strong rationale to motivate future investigations of microbiota‐derived metabolites in the observed relationship with threat‐related brain processes.
Three‐way parallel group independent component analysis: Fusion of spatial and spatiotemporal magnetic resonance imaging data
Authors: Qi Shile , Silva Rogers F. , Zhang Daoqiang , Plis Sergey M. , Miller Robyn , Vergara Victor M. , Jiang Rongtao , Zhi Dongmei , Sui Jing , Calhoun Vince D.
Published: November 2021

Advances in imaging acquisition techniques allow multiple imaging modalities to be collected from the same subject. Each individual modality offers limited yet unique views of the functional, structural, or dynamic temporal features of the brain. Multimodal fusion provides effective ways to leverage these complementary perspectives from multiple modalities. However, the majority of current multimodal fusion approaches involving functional magnetic resonance imaging (fMRI) are limited to 3D feature summaries that do not incorporate its rich temporal information. Thus, we propose a novel three‐way parallel group independent component analysis (pGICA) fusion method that incorporates the first‐level 4D fMRI data (temporal information included) by parallelizing group ICA into parallel ICA via a unified optimization framework. A new variability matrix was defined to capture subject‐wise functional variability and then link it to the mixing matrices of the other two modalities. Simulation results show that the three‐way pGICA provides highly accurate cross‐modality linkage estimation under both weakly and strongly correlated conditions, as well as comparable source estimation under different noise levels. Results using real brain imaging data identified one linked functional–structural–diffusion component associated to differences between schizophrenia and controls. This was replicated in an independent cohort, and the identified components were also correlated with major cognitive domains. Functional network connectivity revealed visual–subcortical and default mode‐cerebellum pairs that discriminate between schizophrenia and controls. Overall, both simulation and real data results support the use of three‐way pGICA to identify multimodal spatiotemporal links and to pursue the study of brain disorders under a single unifying multimodal framework.
Navigating the era of disruption: How emotions can prompt job crafting behaviors
Authors: Barclay Laurie J. , Kiefer Tina , El Mansouri Mouna
Published: November 2021

Environmental disruptions can disturb the status quo. This can create the need for employees to navigate rapidly evolving demands in their work environment, often before formalized strategic plans can be developed and/or implemented. As such, understanding how employees experience and respond to these disruptions is critical for effective strategic human resource management. Drawing on appraisal theories of emotion, we argue that employees' appraisals of how the disruption has impacted their work can elicit discrete emotions (e.g., frustration and pride). In turn, these emotions can encourage employees to address challenges and opportunities by engaging in job crafting behaviors. Importantly, job crafting behaviors can have implications for subsequent employee outcomes (e.g., performance and well‐being). We test our predictions using a three‐wave survey (N = 402) in the context of the COVID‐19 pandemic—an unexpected environmental disruption that sparked rapid change. Theoretically, our findings provide insight into why and how employees can self‐initiate changes to their jobs in response to environmental disruptions as well as how job crafting behaviors impact employee outcomes. Practically, our findings provide insight and guidance to SHRM practitioners on how to effectively support and manage employees before, during, and after environmental disruptions.
Cofactors and pathogens: Flavin mononucleotide and flavin adenine dinucleotide (FAD) biosynthesis by the FAD synthase from Brucella ovis
Authors: Moreno Andrea , Taleb Victor , Sebastián María , Anoz‐Carbonell Ernesto , Martínez‐Júlvez Marta , Medina Milagros
Published: November 2021

The biosynthesis of the flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), cofactors used by 2% of proteins, occurs through the sequential action of two ubiquitous activities: a riboflavinkinase (RFK) that phosphorylates the riboflavin (RF) precursor to FMN, and a FMN:adenylyltransferase (FMNAT) that transforms FMN into FAD. In most mammals two different monofunctional enzymes have each of these activities, but in prokaryotes a single bifunctional enzyme, FAD synthase (FADS), holds them. Differential structural and functional traits for RFK and FMNAT catalysis between bacteria and mammals, as well as within the few bacterial FADSs so far characterized, has envisaged the potentiality of FADSs from pathogens as targets for the development of species‐specific inhibitors. Here, we particularly characterize the FADS from the ovine pathogen Brucella ovis (BoFADS), causative agent of brucellosis. We show that BoFADS has RFK activity independently of the media redox status, but its FMNAT activity (in both forward and reverse senses) only occurs under strong reducing conditions. Moreover, kinetics for flavin and adenine nucleotides binding to the RFK site show that BoFADS binds preferentially the substrates of the RFK reaction over the products and that the adenine nucleotide must bind prior to flavin entrapment. These results, together with multiple sequence alignments and phylogenetic analysis, point to variability in the less conserved regions as contributing to the species‐specific features in prokaryotic FADSs, including those from pathogens, that allow them to adopt alternative strategies in FMN and FAD biosynthesis and overall flavin homeostasis.
Opportunistic Osteoporosis Screening Using Chest Radiographs With Deep Learning: Development and External Validation With a Cohort Dataset
Authors: Jang Miso , Kim Mingyu , Bae Sung Jin , Lee Seung Hun , Koh Jung-Min , Kim Namkug
Published: November 2021

Osteoporosis is a common, but silent disease until it is complicated by fractures that are associated with morbidity and mortality. Over the past few years, although deep learning-based disease diagnosis on chest radiographs has yielded promising results, osteoporosis screening remains unexplored. Paired data with 13,026 chest radiographs and dual-energy X-ray absorptiometry (DXA) results from the Health Screening and Promotion Center of Asan Medical Center, between 2012 and 2019, were used as the primary dataset in this study. For the external test, we additionally used the Asan osteoporosis cohort dataset (1089 chest radiographs, 2010 and 2017). Using a well-performed deep learning model, we trained the OsPor-screen model with labels defined by DXA based diagnosis of osteoporosis (lumbar spine, femoral neck, or total hip T-score ≤ −2.5) in a supervised learning manner. The OsPor-screen model was assessed in the internal and external test sets. We performed substudies for evaluating the effect of various anatomical subregions and image sizes of input images. OsPor-screen model performances including sensitivity, specificity, and area under the curve (AUC) were measured in the internal and external test sets. In addition, visual explanations of the model to predict each class were expressed in gradient-weighted class activation maps (Grad-CAMs). The OsPor-screen model showed promising performances. Osteoporosis screening with the OsPor-screen model achieved an AUC of 0.91 (95% confidence interval [CI], 0.90–0.92) and an AUC of 0.88 (95% CI, 0.85–0.90) in the internal and external test set, respectively. Even though the medical relevance of these average Grad-CAMs is unclear, these results suggest that a deep learning-based model using chest radiographs could have the potential to be used for opportunistic automated screening of patients with osteoporosis in clinical settings. © 2021 American Society for Bone and Mineral Research (ASBMR).
A qualitative examination of bi/multilingual counselor training and experiences
Authors: Pope Amber L. , Sunal Zahide , Gantt Alexandra C. , Zimmerman Betsy , Corey Ali K. , Nuosce Mary , Araujo Lourdes
Published: November 2021

There is an increased need for bi/multilingual counseling services to meet the growing linguistic diversity of the US population. Despite this need, the counseling profession has made little progress on systemically integrating language factors and bi/multilingual counseling skills into counselor training and professional development. Using consensual qualitative research (CQR), we interviewed 14 bi/multilingual counselors (BMCs) and identified five domains: counseling experience, counselor training and preparation (during master's), supervision and continuing education (post master's), recommendations, and other bi/multilingual counseling‐related experience. These domains provide insight into BMCs’ clinical experiences and training, along with strategies to improve counselor education, professional development, and resources for BMCs. Implications for counseling and counselor education, limitations, and suggestions for future research are discussed.
Quantitative detections of TP53 gene mutations improve the diagnosis and prognostic prediction of biliary tract cancers using droplet digital PCR
Authors: Xiao Xiao , Zhou Jun , Fang Meng , Ji Jun , Huang Chenjun , Du Fei , Ai Wenchao , Wang Ying , Gao Zhiyuang , Qiu Zhiquan , Gao Chunfang
Published: November 2021

Objective

Biliary tract cancer (BTC) is a rare malignancy and lack of effective diagnostic and prognostic marker. Here, we aimed to investigate the clinical implication of TP53 mutation detection in BTC using droplet digital PCR (ddPCR).

Methods

TP53 gene (loci p.R175H, p.R248Q, p.R248W, and p.R273H) mutation frequencies of 45 pairs of tumor tissues (TTs) and adjacent normal tissues (ANTTs) were analyzed, respectively, using ddPCR. Meanwhile, the same detections were conducted in plasma cell‐free DNA (cfNDA) of 156 subjects including BTC, disease control (DC), and healthy controls (HC). The logistic regression algorithm was established to identify BTC. The correlations between mutations and clinicopathological features as well as the effects of TP53 mutation frequency on BTC prognosis were assessed.

Results

The higher mutation of p.R175H was found in TTs compared with ANTT (p = 0.006). The mutation at p.R273H in cfDNA was also higher in BTC when compared with DC and HC (p < 0.05). The logistic algorithms combining p.R273H mutation demonstrated the higher diagnostic efficacy trend than carbohydrate antigen 19–9 (CA19‐9), carcinoembryonic antigen (CEA), and alpha‐fetoprotein (AFP) in identifying BTC from DC (the area under the curves of the algorithm: 0.845, 95% CI:0.775–0.914). The median overall survival (OS) and progression‐free survival (PFS) were significantly shorter when the BTC patients harboring the p.R273H mutation (OS: p = 0.032; PFS: p = 0.046).

Conclusion

This study revealed for the first time that the quantitative TP53 mutations using the ddPCR might serve as a potential genetic biomarker for BTC diagnosis and prognosis assessment.
Circ_0000463 contributes to the progression and glutamine metabolism of non‐small‐cell lung cancer by targeting miR‐924/SLC1A5 signaling
Authors: Liu Yunzhong , Wang Shujun , Pan Songli , Yan Qingfeng , Li Yueping , Zhao Ying
Published: November 2021

Background

Circular RNAs (circRNAs) have shown pivotal regulatory roles in the pathology of non‐small cell lung cancer (NSCLC). However, the role of circ_0000463 in NSCLC progression and its associated molecular mechanism remain to be illustrated.

Methods

Cell proliferation ability was analyzed by colony formation assay and 5‐ethynyl‐2’‐deoxyuridine (EdU) assay. Cell migration and invasion abilities were assessed by scratch test and transwell invasion assay. Flow cytometry was employed to analyze cell apoptotic rate. The interaction between microRNA‐924 (miR‐924) and circ_0000463 or solute carrier family 1 member 5 (SLC1A5) was confirmed by dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The uptake of glutamine and the production of glutamate and α‐ketoglutarate were analyzed using their corresponding kits. Xenograft model in vivo was established to analyze the role of circ_0000463 in tumor growth.

Results

Circ_0000463 expression was elevated in NSCLC tissues and cell lines. Circ_0000463 knockdown suppressed the proliferation, migration, and invasion and promoted the apoptosis of NSCLC cells. Circ_0000463 acted as a molecular sponge for miR‐924, and circ_0000463 interference‐mediated anti‐tumor effects were largely reversed by the silence of miR‐924 in NSCLC cells. miR‐924 interacted with the 3’ untranslated region (3’UTR) of SLC1A5, and SLC1A5 overexpression largely overturned miR‐924 overexpression‐mediated anti‐tumor effects in NSCLC cells. Moreover, circ_0000463 absence suppressed the glutamine metabolism of NSCLC cells by targeting miR‐924/SLC1A5 axis. Circ_0000463 knockdown suppressed xenograft tumor growth in vivo.

Conclusion

Circ_0000463 absence suppressed the malignant behaviors and glutamine metabolism of NSCLC cells through mediating miR‐924/SLC1A5 axis.
Expression and prognostic significance of m6A‐related genes in TP53‐mutant non‐small‐cell lung cancer
Authors: Zhao Zhuochen , Wan Junhu , Guo Manman , Wang Yangxia , Yang Zhengwu , Zhou Fuyou , Li Zhuofang , Ming Liang
Published: November 2021

Background

TP53 is an important tumor suppressor gene on human 17th chromosome with its mutations more than 60% in tumor cells. Lung cancer is the highest incidence malignancy in men around the world. N‐6 methylase (m6A) is an enzyme that plays an important role in mRNA splicing, translation, and stabilization. However, its role in TP53‐mutant non‐small‐cell lung cancer (NSCLC) remains unknown.

Method

First, we investigated 17 common m6A regulators' prognostic values in NSCLC. Then, after the establishment of risk signature, we explored the diagnostic value of m6A in TP53‐mutant NSCLC. Finally, gene set enrichment analysis (GSEA), gene ontology (GO) enrichment analysis, and differential expression analysis were used to reveal the possible mechanism of m6A regulators affecting TP53‐mutant NSCLC patients.

Results

Study showed that nine m6A regulators (YTHDC2, METTL14, FTO, METTL16, YTHDF1, HNRNPA2B1, RBM15, KIAA1429, and WTAP) were expressed differently between TP53‐mutant and wild‐type NSCLC (p < 0.05); and ALKBH5 and HNRNPA2B1 were associated with the prognostic of TP53‐mutant patients. After construction of the risk signature combined ALKBH5 and HNRNPA2B1, we divided patients with TP53 mutations into high‐ and low‐risk groups, and there was a significant survival difference between two groups. Finally, 338 differentially expression genes (DEGs) were found between high‐ and low‐risk groups. GO enrichment analysis, PPI network, and GSEA enrichment analysis showed that m6A may affect the immune environment in extracellular and change the stability of mRNA.

Conclusion

In conclusion, m6A regulators can be used as prognostic predictors in TP53‐mutant patients.