bluuebunny/crossref_metadata_2025 huggingface dataset:
A constitutively expressed fluorescence ubiquitin cell cycle indicator (FUCCI) in axolotls for studying tissue regeneration
Authors: Duerr Timothy J , Jeon Eun Kyung , Wells Kaylee M , Villanueva Antonio , Seifert Ashley W , McCusker Catherine D , Monaghan James R
Published: March 2021

Regulation of cell cycle progression is essential for cell proliferation during regeneration following injury. After appendage amputation, the axolotl (Ambystoma mexicanum) regenerates missing structures through an accumulation of proliferating cells known as the blastema. To study cell division during blastema growth, we generated a transgenic line of axolotls that ubiquitously expresses a bicistronic version of the Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI). We demonstrate near-ubiquitous expression of FUCCI expression in developing and adult tissues and validate these expression patterns with DNA synthesis and mitosis phase markers. We demonstrate the utility of FUCCI for live and whole-mount imaging, showing the predominantly local contribution of cells during limb and tail regeneration. We also show that spinal cord amputation results in increased proliferation at least 5 mm from the injury. Finally, we use multimodal staining to provide cell type information for cycling cells by combining fluorescencein-situhybridization, EdU click-chemistry, and immunohistochemistry on a single FUCCI tissue section. This new line of animals will be useful for studying cell cycle dynamics usingin-situendpoint assays andin-vivoimaging in developing and regenerating animals.

Summary statement

We generated a ubiquitous transgenic fluorescence ubiquitin cell cycle indicator (FUCCI) axolotl line for examination of cell cycle dynamics during tissue regeneration.
Depth-of-field extension in optical imaging for rapid crystal screening
Authors: Li Chen , Ding Changqin , Li Minghe , Rong Jiayue , Florian Hilary , Simpson Garth
Published: March 2021

The depth of field (DoF) was extended 2.8-fold to achieve rapid crystal screening by retrofitting a custom-designed micro-retarder array (µRA) in the optical beam path of a nonlinear optical microscope. The merits of the proposed strategy for DoF enhancement were assessed in applications of second-harmonic generation imaging of protein crystals. It was found that DoF extension increased the number of crystals detected while simultaneously reducing the number of `z-slices' required for screening. Experimental measurements of the wavelength-dependence of the extended DoF were in excellent agreement with theoretical predictions. These results provide a simple and broadly applicable approach to increase the throughput of existing nonlinear optical imaging methods for protein crystal screening.
Structure of the class XI myosin globular tail reveals evolutionary hallmarks for cargo recognition in plants
Authors: Turowski Valeria R. , Ruiz Diego M. , Nascimento Andrey F. Z. , Millán Claudia , Sammito Massimo D. , Juanhuix Judith , Cremonesi Aline Sampaio , Usón Isabel , Giuseppe Priscila O. , Murakami Mario T.
Published: March 2021

The plant-specific class XI myosins (MyoXIs) play key roles at the molecular, cellular and tissue levels, engaging diverse adaptor proteins to transport cargoes along actin filaments. To recognize their cargoes, MyoXIs have a C-terminal globular tail domain (GTD) that is evolutionarily related to those of class V myosins (MyoVs) from animals and fungi. Despite recent advances in understanding the functional roles played by MyoXI in plants, the structure of its GTD, and therefore the molecular determinants for cargo selectivity and recognition, remain elusive. In this study, the first crystal structure of a MyoXI GTD, that of MyoXI-K from Arabidopsis thaliana, was elucidated at 2.35 Å resolution using a low-identity and fragment-based phasing approach in ARCIMBOLDO_SHREDDER. The results reveal that both the composition and the length of the α5–α6 loop are distinctive features of MyoXI-K, providing evidence for a structural stabilizing role for this loop, which is otherwise carried out by a molecular zipper in MyoV GTDs. The crystal structure also shows that most of the characterized cargo-binding sites in MyoVs are not conserved in plant MyoXIs, pointing to plant-specific cargo-recognition mechanisms. Notably, the main elements involved in the self-regulation mechanism of MyoVs are conserved in plant MyoXIs, indicating this to be an ancient ancestral trait.
Identification of Mg2+ ions next to nucleotides in cryo-EM maps using electrostatic potential maps
Authors: Wang Jimin , Natchiar S. Kundhavai , Moore Peter B. , Klaholz Bruno P.
Published: March 2021

Cryo electron microscopy (cryo-EM) can produce maps of macromolecules that have resolutions that are sufficiently high that structural details such as chemical modifications, water molecules and bound metal ions can be discerned. However, those accustomed to interpreting the electron-density maps of macromolecules produced by X-ray crystallography need to be careful when assigning features such as these in cryo-EM maps because cations, for example, interact far more strongly with electrons than they do with X-rays. Using simulated electrostatic potential (ESP) maps as a tool led us to re-examine a recent cryo-EM map of the human ribosome, and we realized that some of the ESP peaks originally identified as novel groups covalently bonded to the N7, O6 or O4 atoms of several guanines, adenines or uridines, respectively, in this structure are likely to instead represent Mg2+ ions coordinated to these atoms, which provide only partial charge compensation compared with Mg2+ ions located next to phosphate groups. In addition, direct evidence is provided for a variation in the level of 2′-O ribose methylation of nucleotides in the human ribosome. ESP maps can thus help in identifying ions next to nucleotide bases, i.e. at positions that can be difficult to address in cryo-EM maps due to charge effects, which are specifically encountered in cryo-EM. This work is particularly relevant to nucleoprotein complexes and shows that it is important to consider charge effects when interpreting cryo-EM maps, thus opening possibilities for localizing charges in structures that may be relevant for enzymatic mechanisms and drug interactions.
Does effects of brand origin misperception jeopardize brand equity?
Authors: Tseng Ting-Hsiang , Chan Nga Cheng , Liu Matthew Tingchi , Lin Chieh-Yu
Published: March 2021

Purpose

The purpose of this study is to examine the effects of brand origin (BO) misperception (hereafter BOM) or non-identification on brand equity. Besides, the current study investigates the moderating role of brand strength in the relationship between BOM and brand equity.

Design/methodology/approach

The current study adopted a 4 (BO identification: favorable BOM vs adverse BOM vs non-identification vs correct identification) × 2 (brand strength: strong vs weak) between-subjects design. A total number of 547 participants performed assessments on the automotive brand. The current study selected three strong brands and three weak brands for tests. In the experiment, respondents had to associate the brand with its country of origin. The assignment of BO conditions was based upon respondents' natural responses provided. ANOVA was used for data analysis.

Findings

The results indicate that as compared to correct BO identification, BOM (either adverse or favorable) or non-identification exerts a more negative impact on brand equity. Moreover, the study demonstrates that brand strength moderates the effect of perceived BO on brand equity.

Originality/value

This study provides empirical support to the notion that BOM is detrimental to brand equity. Specifically, when adverse BOM occurs, a strong brand suffers more from the negative consequences resulted than a weak brand does. Conversely, when consumers misattribute the BO to a country with a stronger image than its real origin (i.e. favorable BOM), the resulting negative effect is reversed. Moreover, the non-identification of BO hurts the brand equity of both strong and weak brands.
A novel fractional discrete nonlinear grey Bernoulli model for forecasting the wind turbine capacity of China
Authors: Wu Wen-Ze , Xie Wanli , Liu Chong , Zhang Tao
Published: March 2021

Purpose

A new method for forecasting wind turbine capacity of China is proposed through grey modelling technique.

Design/methodology/approach

First of all, the concepts of discrete grey model are introduced into the NGBM(1,1) model to reduce the discretization error from the differential equation to its discrete forms. Then incorporating the conformable fractional accumulation into the discrete NGBM(1,1) model is carried out to further improve the predictive performance. Finally, in order to effectively seek the emerging coefficients, namely, fractional order and nonlinear coefficient, the whale optimization algorithm (WOA) is employed to determine the emerging coefficients.

Findings

The empirical results show that the newly proposed model has a better prediction performance compared to benchmark models; the wind turbine capacity from 2019 to 2021 is expected to reach 275954.42 Megawatts in 2021. According to the forecasts, policy suggestions are provided for policy-makers.

Originality/value

By combing the fractional accumulation and the concepts of discrete grey model, a new method to improve the prediction performance of the NGBM(1,1) model is proposed. The newly proposed model is firstly applied to predict wind turbine capacity of China.
Fading and transformation: how a woman entrepreneur's multiple identities interact throughout her life
Authors: Cesaroni Francesca Maria , Sentuti Annalisa , Pediconi Maria Gabriella
Published: March 2021

Purpose

This paper aims to further the understanding of women entrepreneurs' multiple identities by exploring how they interact throughout women's life cycles.

Design/methodology/approach

This article combines a case study and a narrative analysis to investigate the experience of a woman who founded a business and retired after passing it on to her son. Data were collected by combining two different methods: biographical interview and follow-up interviews or conversations.

Findings

Findings show that interactions between a woman entrepreneur's multiple identities may evolve through two main processes of change: transformation and fading. In the transformation process, adverse interactions between identities turn into synergistic and fruitful relationships. In the fading process, conflicts between identities gradually disappear, giving way to peaceful coexistence. Women's agency proves paramount in making these processes possible and helping her achieve personal and professional fulfillment.

Originality/value

In prior studies, women entrepreneurs have mostly been observed at a specific time or stage in their life and entrepreneurial experience. This paper responds to the call for the adoption of a dynamic perspective in the analysis of interactions among a woman entrepreneur's multiple identities so as to show how they may evolve during her entrepreneurial experience.
Thymoquinone chemosensitizes human colorectal cancer cells to imatinib via uptake/efflux genes modulation
Authors: Thabet Nadia A. , El‐Khouly Dalia , Sayed‐Ahmed Mohamed M. , Omran Mervat M.
Published: March 2021

Imatinib (IM) is a pharmaceutical drug that inhibits tyrosine kinase enzymes that are responsible for the activation of many proteins by signal transduction cascades as c‐Abl, c‐Kit and the platelet‐derived growth factor (PDGF) receptor. Thymoquinone (TQ) is an active constituent of Nigella sativa seeds. Thymoquinone benefits are attributed to its medicinal uses as antioxidant, anticancer and antimicrobial agent. This study aimed to investigate the impact of using TQ with IM in the HCT116 human colorectal cancer cell line model. The HCT116 cells were treated with IM or/and TQ in non‐constant ratios, in which the fixed concentrations of TQ (5, 10 or 20 µmol/L) were co‐treated with various concentrations of IM (7.5–120 µmol/L) for 24, 48 and 72 hours. Imatinib‐TQ interaction was analysed using CompuSyn software. The IC50 values for IM were 105, 72 μmol/L after 48 and 72 hours, respectively, and were significantly reduced to 7.3, 7 and 5.5 μmol/L after combination with TQ (10 μmol/L) and to 5.8, 5.6 and 4.6 μmol/L after combination with TQ (20 μmol/L) to 24, 48 and 72 hours, respectively. The combination index (CI) and dose reduction index (DRI) values indicate a significant synergism in HCT‐116 cells at different treatment time points. Thymoquinone significantly enhances the cellular uptake of IM in HCT116 cells in a time and concentration‐dependent manner. A significant downregulation in ATP‐binding cassette (ABC) subfamily B member 1 (ABCB1), ABC subfamily G member 2 (ABCG2) and human organic cation transporter 1 (hOCT1) genes was observed in the cells exposed to IM+TQ combination as compared to IM alone, which resulted in a substantial elevation in uptake/efflux ratio in combination group. In conclusion, TQ potentiates IM efficacy on HCT116 cells via uptake/efflux genes modulation.
Media framing of fighting COVID‐19 in China
Authors: Gui Lili
Published: March 2021

This study focuses on media framings of COVID‐19 in Chinese social and cultural contexts. After analysing nine weeks’ news reports of Xinwen Lianbo, one of China's mainstream media, we discovered that the metaphorical war frame dominated throughout the corpus but it did not remain the same. Some of its semantic concepts like the type of war evolved over time. There are also several minor metaphors such as race, challenge, chess and combination blow metaphors, which are not as dominant as the war metaphor but should by no means be neglected. The race and challenge metaphors are complementary with the war metaphor to frame COVID‐19, while the chess and combination blow metaphors are culturally loaded. What's more, literal frames like responsibility and collaboration were also found in the corpus. All frames, whether metaphorical or literal, work together to shape what COVID‐19 was, what roles people should play and what people could do. In this study, we intend to explore how media framings of COVID‐19 were related to media and government's responses as well as how they might have contributed to the public's responses. The media is an important source of information, whose role in public health emergencies deserves our attention.
Less Information, More Comparison, and Better Performance: Evidence from a Field Experiment
Authors: EYRING HENRY , FERGUSON PATRICK J. , KOPPERS SEBASTIAN
Published: March 2021

We use a field experiment in professional sports to compare effects of providing absolute, relative, or both absolute and relative measures in performance reports for employees. Although studies have documented that the provision of these types of measures can benefit performance, theory from economic and accounting literature suggests that it may be optimal for firms to direct employees’ attention to some types of measures by omitting others. In line with this theory, we find that relative performance information alone yields the best performance effects in our setting—that is, that a subset of information (relative performance information) dominates the full information set (absolute and relative performance information together) in boosting performance. In cross‐sectional and survey‐data analyses, we do not find that restricting the number of measures shown per se benefits performance. Rather, we find that restricting the type of measures shown to convey only relative information increases involvement in peer‐performance comparison, benefitting performance. Our findings extend research on weighting of and responses to measures in performance reports.
A proctolin‐like peptide is regulated after baculovirus infection and mediates in caterpillar locomotion and digestion
Authors: Llopis‐Giménez Angel , Parenti Stefano , Han Yue , Ros Vera I. D. , Herrero Salvador
Published: March 2021

Baculoviruses constitute a large group of invertebrate DNA viruses, predominantly infecting larvae of the insect order Lepidoptera. During a baculovirus infection, the virus spreads throughout the insect body producing a systemic infection in multiple larval tissues, included the central nervous system (CNS). As a main component of the CNS, neuropeptides are small protein‐like molecules functioning as neurohormones, neurotransmitters, or neuromodulators. These peptides are involved in regulating animal physiology and behavior and could be altered after baculovirus infection. In this study, we have investigated the effect of Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) infection on expression of Spodoptera exigua neuropeptides and neuropeptide‐like genes. Expression of the gene encoding a polypeptide that resembles the well‐known insect neuropeptide proctolin and named as proctolin‐like peptide (PLP), was downregulated in the larval brain following infection and was chosen for further analysis. A recombinant Autographa californica multiple nucleopolyhedrovirus (AcMNPV) overexpressing the C‐terminal part of the PLP was generated and used in bioassays using S. exigua larvae to study its influence on the viral infection and insect behavior. AcMNPV‐PLP‐infected larvae showed less locomotion activity and a reduction in growth compared to larvae infected with wild type AcMNPV or mock‐infected larvae. These results are indicative of this new peptide as a neuromodulator that regulates visceral and skeletal muscle contractions and offers a novel effector involved in the behavioral changes during baculovirus infection.
Fluid‐driven Hydrovolcanic Activity along Fracture Zones and near Seamounts: Evidence from Deep‐sea Fe‐rich Spherules, Central Indian Ocean Basin
Authors: AMONKAR Ankeeta , IYER Sridhar D. , BABU Elapavalooru V.S.S.K. , SHAILAJHA Natarajan , SARDAR Areef , MANJU S.
Published: March 2021

An insight on occurrence of Fe‐rich spherules from the Central Indian Ocean Basin (CIOB) provides an understanding of their distribution at a water depth of >5,000 m. In the present study, Fe‐rich spherules are identified to occur in two different sediment types (i.e., siliceous and pelagic) and tectonic settings (i.e. near seamounts and fracture zones). These are single spheres or aggregates, of different sizes (63 to 390 μm) and show textural variability (smooth/quenched, brickwork, corkscrew, interlocking and dendritic). A comparative study based on physical morphology and chemical composition suggests a common mechanism of formation. The association of spherules with fracture zones (FZ) and seamounts signifies that morpho‐tectonic features play an important role in fluid‐driven hydrovolcanism. Based on the evidence and geologic conditions existing in the basin, we conclude that molten fuel‐coolant interaction (MFCI) coupled with submarine hydrothermal exhalations could be an ideal mechanism for the formation of spherules and Fe‐particles. The accretion of the spherules on the surface sediments could be a result of recent volcanic phenomena, while those occurring at different depths (280–355, and 460–475 cm‐bsf) within the sediment core indicate two different episodes. The study provides a global implication in understanding fluid‐driven magmatism in a deep‐sea intraplate environment.
Geochemistry and Geochronology of the Jinghong Ophiolites: Implications for the Tectonic Evolution of the Eastern Paleo‐Tethys
Authors: ZHU Jianjiang , LIU Fulai , WANG Fang , XIE Shiwen , CAI Jia , JI Lei , WANG Huining
Published: March 2021

The Jinghong mafic–ultramafic complex, exposed in the eastern margin of the Lancangjiang tectonic belt, is related to the subduction of the Paleo‐Tethys Ocean. Its petrogenesis plays a key role in constraining the tectonic evolution of the eastern Paleo‐Tethys Ocean in southwestern China. In this study, we present petrological, geochemical and geochronological results of the Jinghong complex rocks, in order to decipher their origin and tectonic significance. The Jinghong mafic–ultramafic complex was composed of peridotite, gabbro, basalt and minor plagiogranite. Whole‐rock geochemical data of the mafic rocks indicate that they have both MORB and IAB affinities and plot in the back‐arc basin basalt (BABB) field in the FeO∗/MgO vs. TiO2 diagram. Combined with their trace element characteristics, it can be concluded that the Jinghong mafic–ultramafic complex represents an ophiolite suite that was formed in a back‐arc ocean basin. Precise LA‐ICP‐MS zircon U‐Pb dating yielded weighted mean 206Pb/238U ages of 298.4 ± 1.7 Ma, 294.3 ± 1.6 Ma, and 292.8 ± 2.0 Ma for gabbroic rocks from this complex, which indicates that the Jinghong ophiolites were formed during the early Permian (298–293 Ma). We propose that during subduction of the main Paleo‐Tethys Ocean, a back‐arc ocean basin was formed at the east of the Lancangjiang tectonic belt.
Geology and Mineral Chemistry of Uranium‐ and Thorium‐bearing Minerals in Rare‐Metal (NYF) Pegmatites of Um Solimate, South Eastern Desert, Egypt
Authors: ALI Mohamed A. , ABDEL GAWAD Ahmed E. , GHONEIM Mohamed M.
Published: March 2021

The garnet muscovite granitic pegmatite of Um Solimate, in southern Egypt, represents a promising asset for strategic and economic metals, especially Bi–Ni–Ag–Nb–Ta as well as U and Th. The ore bodies occur as large masses, pockets and/or veins of very coarse‐grained pegmatites, which consist mainly of K‐feldspar, quartz and albite with subordinate muscovite, garnet, and biotite. Radiometric data revealed that eU‐ and eTh‐contents of the pegmatites reach up to 39 ppm and 82 ppm, respectively. The studied pegmatites are enriched in primary U and Th minerals (uraninite, coffinite, thorianite and uranothorite) as well as Hf‐rich zircon and monazite, which give rise to anomalous radioactive zones. Niobium‐tantalium‐bearing minerals (i.e. ferrocolumbite, microlite and uranopyrochlore), xenotime, barite, galena, fluorite, and apatite are ubiquitous, and, consequently, the studied pegmatites belong tothe Niobium–Yttrium–Fluorine‐type (NYF) family. The noble metal mineralization includes argentite (Ag2S), native Ni and Bi as well as bismite and bismoclite. In addition, beryl and tourmaline are observed in pegmatites near the contact with metasediments and ultramafic bodies. The observed compositional variations of Ta/(Ta+Nb) and Mn/(Mn+Fe) ratios in columbite (0.08–0.45 and 0.11–0.57, respectively) and Hf contents in zircon (3.54–6.46 wt%) may reflectan extreme degree of magmatic fractionation leading to formation of the pegmatite orebody.
MicroRNA‐targeting in spermatogenesis: Over‐expressions of microRNA‐23a/b‐3p and its affected targeting of the genes ODF2 and UBQLN3 in spermatozoa of patients with oligoasthenozoospermia
Authors: Abu‐Halima Masood , Belkacemi Anouar , Ayesh Basim M. , Simone Becker Lea , Sindiani Amer M. , Fischer Ulrike , Hammadeh Mohamad , Keller Andreas , Meese Eckart
Published: March 2021

Background

Male infertility is a multifactorial syndrome with diverse phenotypic representations. MicroRNAs (miRNAs) are small, non‐coding RNAs that are involved in the post‐transcriptional regulation of gene expression. Altered abundance levels of ODF2 and UBQLN3 have been reported in patients with different spermatogenic impairments. However, the transcriptional regulation of these two genes by miR‐23a/b‐3p is still unclear.

Objectives

To investigate experimentally whether miR‐23a/b‐3p targets the genes ODF2 and UBQLN3 and whether this targeting impacts abundance levels of ODF2 and UBQLN3 in patients with oligoasthenozoospermia.

Materials and methods

A total of 92 men attending a fertility clinic were included in the study, including 46 oligoasthenozoospermic men and 46 age‐matched normozoospermic volunteers who served as controls. Reverse transcription‐quantitative PCR (RT‐qPCR), Western blot, and dual‐luciferase (Firefly‐Renilla) assays were used to validate the miRNAs and their target genes.

Results

RT‐qPCR revealed that miR‐23a/b‐3p was more abundant and ODF2 and UBQLN3 targets were less abundant in men with impaired spermatogenesis. Besides, Western blot shows that ODF2 and UBQLN3 protein levels were reduced in men with impaired spermatogenesis. In silico prediction and dual‐luciferase assays revealed that potential links exist between the higher abundance level of miR‐23a/b‐3p and the lower abundance level of ODF2 and UBQLN3 targets. Mutations in the miR‐23a/b‐3p‐binding site within the 3ˊUTRs (3ˊuntranslated regions) of ODF2 and UBQLN3 genes resulted in abrogated responsiveness to miR‐23a/b‐3p. Correlation analysis showed that sperm count, motility, and morphology were negatively correlated with miR‐23a/b‐3p and positively correlated with the lower abundance level of UBQLN3, while ODF lower abundance level was positively correlated with sperm motility.

Conclusion

Findings indicate that the higher abundance level of miR‐23a/b‐3p and the lower abundance level of ODF2 and UBQLN3 targets are associated with oligoasthenozoospermia and male subfertility.
Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort
Authors: Cerván‐Martín Miriam , Bossini‐Castillo Lara , Rivera‐Egea Rocío , Garrido Nicolás , Luján Saturnino , Romeu Gema , Santos‐Ribeiro Samuel ,   IVIRMA Group, Lisbon Clinical Group, Castilla José A. , Gonzalvo María del Carmen , Clavero Ana , Vicente Francisco Javier , Guzmán‐Jiménez Andrea , Burgos Miguel , Barrionuevo Francisco Javier , Jiménez Rafael , Sánchez‐Curbelo Josvany , López‐Rodrigo Olga , Peraza María Fernanda , Pereira‐Caetano Iris , Marques Patrícia Isabel , Carvalho Filipa , Barros Alberto , Bassas Lluís , Seixas Susana , Gonçalves João , Larriba Sara , Lopes Alexandra Manuel , Carmona Francisco David , Palomino‐Morales Rogelio Jesús
Published: March 2021

Background

Severe spermatogenic failure (SpF) represents the most extreme manifestation of male infertility, as it decreases drastically the semen quality leading to either severe oligospermia (SO, <5 million spermatozoa/mL semen) or non‐obstructive azoospermia (NOA, complete lack of spermatozoa in the ejaculate without obstructive causes).

Objectives

The main objective of the present study is to analyze in the Iberian population the effect of 6 single‐nucleotide polymorphisms (SNPs) previously associated with NOA in Han Chinese through genome‐wide association studies (GWAS) and to establish their possible functional relevance in the development of specific SpF patterns.

Materials and methods

We genotyped 674 Iberian infertile men (including 480 NOA and 194 SO patients) and 1058 matched unaffected controls for the GWAS‐associated variants PRMT6‐rs12097821, PEX10‐rs2477686, CDC42BPA‐rs3000811, IL17A‐rs13206743, ABLIM1‐rs7099208, and SOX5‐rs10842262. Their association with SpF, SO, NOA, and different NOA phenotypes was evaluated by logistic regression models, and their functional relevance was defined by comprehensive interrogation of public resources.

Results

ABLIM1‐rs7099208 was associated with SpF under both additive (OR = 0.86, p = 0.036) and dominant models (OR = 0.78, p = 0.026). The CDC42BPA‐rs3000811 minor allele frequency was significantly increased in the subgroup of NOA patients showing maturation arrest (MA) of germ cells compared to the remaining NOA cases under the recessive model (OR = 4.45, p = 0.044). The PEX10‐rs2477686 SNP was associated with a negative testicular sperm extraction (TESE) outcome under the additive model (OR = 1.32, p = 0.034). The analysis of functional annotations suggested that these variants affect the testis‐specific expression of nearby genes and that lincRNA may play a role in SpF.

Conclusions

Our data support the association of three previously reported NOA risk variants in Asians (ABLIM1‐rs7099208, CDC42BPA‐rs3000811, and PEX10‐rs2477686) with different manifestations of SpF in Iberians of European descent, likely by influencing gene expression and lincRNA deregulation.
How to do a Fistula tract Laser Closure (FiLaC) for trans‐sphincteric fistula‐in‐ano
Authors: Suhardja Thomas S. , Lim James Tow‐Hing , Duieb Zeev , Nguyen Thang Chien , Teoh William M. K. , Chouhan Hanumant
Published: March 2021

Sphincter‐preserving surgery for the treatment fistula‐in‐ano has always been an attractive option for complex fistulae where a significant proportion of the anal sphincter is involved. FiLaC™ is a promising approach due to its easy application, minimal side effects and preservation of functional outcome. Our center is an early adopter of FiLaC™ in Australia. We describe our approach to FiLaC™ for trans‐sphincteric fistula‐in‐ano in detailed steps.
More‐Than‐Human and Deeply Human Perspectives on COVID‐19
Authors: Lunstrum Elizabeth , Ahuja Neel , Braun Bruce , Collard Rosemary , Lopez Patricia J. , Wong Rebecca W.Y.
Published: March 2021

This multi‐authored contribution explores what the COVID‐19 pandemic demands of critical inquiry with a focus on the more‐than‐human. We show how COVID‐19 is a complex series of multispecies encounters shaped by humans, non‐human animals, and of course viruses. Central to these encounters is a politics of difference in which certain human lives are protected and helped to flourish while others, both human and animal, are forgotten if not sacrificed. Such difference encompasses practices of racialisation and racism, healthcare austerity, the circulation of capital, border‐making, intervention into non‐human nature, wildlife trade bans, anthropocentrism, and the exploitation of animal test subjects. The contributions highlight how COVID‐19 provides a needed opportunity to unite new materialist and anti‐racist, anti‐colonial scholarship as well as reimagine more radically sustainable multispecies futures. This requires embracing anti‐colonial humility, confronting debts owed to lab animal frontline workers, and rethinking economic systems that helped unleash COVID‐19 and ensured it became a disaster.
From ability to behavior: A scenario‐based assessment of health competence predicts daily health behaviors
Authors: Irvin Roberta L. , Persich Michelle R. , Robinson Michael D.
Published: March 2021

Recent findings have suggested that we can gain new insights into health decision‐making and behavior through the use of a scenario‐based approach to health competence (HC). The present research sought to investigate whether and how such individual differences would matter in the conduct of daily life, within two daily diary studies (N = 260). In Study 1, participants receiving higher HC scores were more active in dealing with daily stressors or problems; by contrast, low‐HC individuals were more prone to impulsive and antisocial behaviors. Based on these promising results, the Study 2 protocol was a more extensive one. Participants who received higher HC scores thought about their health more often and engaged in diverse healthy behaviors more frequently. Conversely, low‐HC individuals were prone to risky and unhealthy daily behaviors. In total, the findings provide key evidence in favor of a new approach to HC and its behavioral manifestations.
The utility of Google Trends as a tool for evaluating flooding in data‐scarce places
Authors: Thompson Joshua J. , Wilby Robert L. , Matthews Tom , Murphy Conor
Published: March 2021

Google Trends (GT) offers a historical database of global internet searches with the potential to complement conventional records of environmental hazards, especially in regions where formal hydrometeorological data are scarce. We evaluate the extent to which GT can discern heavy rainfall and floods in Kenya and Uganda during the period 2014 to 2018. We triangulate counts of flood searches from GT with available rainfall records and media reports to build an inventory of extreme events. The Spearman rank correlation (ρ) between monthly mean search interest for flooding and monthly Climate Hazards Group InfraRed Precipitation with Station (CHIRPS) rainfall totals was ρ = +0.38 (p < 0.005) for Kenya and ρ = +0.64 (p < 0.001) for Uganda. Media reports of flooding were used to specify a threshold of detectability to give the same overall frequency of floods based on GT search interest. When the GT search index threshold was set at ≥15 and ≥29, the correct detection rate was 75% and 64% within a five‐day window of known flood events in Kenya and Uganda, respectively. From these preliminary explorations we conclude that GT has potential as a proxy data source, but greater skill may emerge in places with larger search volumes and by linking to historical information about environmental hazards at sub‐national scales. Wider applicability of the GT platform might be possible if there is greater transparency about how Google algorithms determine topics.
Successful tyrosine kinase inhibitor discontinuation outside clinical trials — data from the population‐based Swedish chronic myeloid leukaemia registry
Authors: Flygt Hjalmar , Sandin Fredrik , Dahlén Torsten , Dremaine Arta , Lübking Anna , Markevärn Berit , Myhr‐Eriksson Kristina , Olsson Karin , Olsson‐Strömberg Ulla , Själander Anders , Söderlund Stina , Wennström Lovisa , Wadenvik Hans , Stenke Leif , Höglund Martin , Richter Johan
Published: March 2021

Clinical trials show that tyrosine kinase inhibitor (TKI) treatment can be discontinued in selected patients with chronic myeloid leukaemia (CML). Although updated CML guidelines support such procedure in clinical routine, data on TKI stopping outside clinical trials are limited. In this retrospective study utilising the Swedish CML registry, we examined TKI discontinuation in a population‐based setting. Out of 584 patients diagnosed with chronic‐phase CML (CML‐CP) in 2007–2012, 548 had evaluable information on TKI discontinuation. With a median follow‐up of nine years from diagnosis, 128 (23%) discontinued TKI therapy (≥1 month) due to achieving a DMR (deep molecular response) and 107 (20%) due to other causes (adverse events, allogeneic stem cell transplant, pregnancy, etc). Among those stopping in DMR, 49% re‐initiated TKI treatment (median time to restart 4·8 months). In all, 38 patients stopped TKI within a clinical study and 90 outside a study. After 24 months 41·1% of patients discontinuing outside a study had re‐initiated TKI treatment. TKI treatment duration pre‐stop was longer and proportion treated with second‐generation TKI slightly higher outside studies, conceivably affecting the clinical outcome. In summary we show that TKI discontinuation in CML in clinical practice is common and feasible and may be just as successful as when performed within a clinical trial.
Differential mode of cholesterol inclusion with 2‐hydroxypropyl‐cyclodextrins increases safety margin in treatment of Niemann‐Pick disease type C
Authors: Yamada Yusei , Ishitsuka Yoichi , Kondo Yuki , Nakahara Shuichi , Nishiyama Asami , Takeo Toru , Nakagata Naomi , Motoyama Keiichi , Higashi Taishi , Arima Hidetoshi , Kamei Shunsuke , Shuto Tsuyoshi , Kai Hirofumi , Hayashino Yuji , Sugita Masatake , Kikuchi Takeshi , Hirata Fumio , Miwa Toru , Takeda Hiroki , Orita Yorihisa , Seki Takahiro , Ohta Tomoko , Kurauchi Yuki , Katsuki Hiroshi , Matsuo Muneaki , Higaki Katsumi , Ohno Kousaku , Matsumoto Shirou , Era Takumi , Irie Tetsumi
Published: March 2021

Background and Purpose

Niemann‐Pick disease type C (NPC) is a lysosomal storage disorder with disrupted intracellular cholesterol trafficking. A cyclic heptasaccharide, 2‐hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD), is a cholesterol solubilizer that is being developed to treat NPC, but its ototoxicity and pulmonary toxicity remain important issues. We have characterized 2‐hydroxypropyl‐γ‐cyclodextrin (HP‐γ‐CD), a cyclic octasaccharide with a larger cavity than HP‐β‐CD, as a candidate drug to treat NPC. However, the molecular target of HP‐γ‐CD with respect to NPC and its potential for clinical application are still unclear.

Experimental Approach

We investigated the mode of interaction between HP‐γ‐CD and cholesterol by phase‐solubility analysis, proton NMR spectroscopy and molecular dynamics simulations. We then evaluated the therapeutic effects of HP‐γ‐CD compared with HP‐β‐CD using cellular and murine NPC models. Mouse auditory and pulmonary function tests were also conducted.

Key Results

HP‐γ‐CD solely formed a 1:1 inclusion complex with cholesterol with an affinity similar to that of HP‐β‐CD. In vitro, HP‐γ‐CD and HP‐β‐CD amelioration of NPC‐related manifestations was almost equivalent at lower concentrations. However, at higher concentrations, the cholesterol inclusion mode of HP‐β‐CD shifted to the highly soluble 2:1 complex whereas that of HP‐γ‐CD maintained solely the 1:1 complex. The constant lower cholesterol solubilizing ability of HP‐γ‐CD conferred it with significantly reduced toxicity compared with HP‐β‐CD, but equal efficacy in treating a mouse model of NPC.

Conclusions and Implications

HP‐γ‐CD can serve as a fine‐tuned cholesterol solubilizer for the treatment of NPC with a wider safety margin than HP‐β‐CD in terms of ototoxicity and pulmonary toxicity.
Differentiation of Two Working Memory Tasks Normed on a Large U.S. Sample of Children 2–7 Years Old
Authors: Cowan Nelson
Published: March 2021

The Wechsler Preschool and Primary Scale of Intelligence, 4th ed. includes two measures of working memory normed on children 2;6–7;7. The present analyses of the typically developing children (N = 1,591, 812 female, 779 male, with an ethnic distribution approximating the United States) provide new, theoretically important information about these working memory tasks, Picture Memory and Zoo Locations. These new analyses establish developmental trends, individual‐difference properties, and cognitive task properties. They show comparable developmental trends for the two tasks, but Picture Memory picks up more individual‐difference variation and is more sensitive to knowledge. This analysis of normed tasks starting very young makes possible new methods for research on the early stages of childhood working memory development, about which little is currently known.
COVID‐19 and the Canadian cattle/beef sector: A second look
Authors: Rude James
Published: March 2021

After a year of adjusting to the shocks associated with COVID‐19 the Canadian cattle and beef sector faces a relatively optimistic future. This note examines the past year for this supply chain from the perspective of the consumer up to the cow‐calf producer by considering consumer reactions, labor market constraints, and supply responses. In the second quarter of 2020, the sector faced a significant challenge with continent wide shutdowns of beef packers reducing the U.S. beef supply by one‐third and Canadian beef slaughter by almost 60%. These shutdowns resulted in a sharp divergence between wholesale beef prices, which more than doubled, and fed steer prices, which declined by one third. Despite these dramatic shocks, the sector has returned to near normal conditions with prices and production levels similar to those observed prior to the pandemic. The near term prospects for 2021 are very similar to the current market situation.
Recipient age and outcomes following simultaneous pancreas‐kidney transplantation in the new millennium: Single‐center experience and review of the literature
Authors: Gurung Komal , Alejo Jennifer , Rogers Jeffrey , Farney Alan C. , Orlando Giuseppe , Jay Colleen , Reeves‐Daniel Amber , Mena‐Gutierrez Alejandra , Sakhovskaya Natalia , Doares William , Kaczmorski Scott , Gautreaux Michael D. , Stratta Robert J.
Published: March 2021

The influence of recipient age on outcomes following simultaneous pancreas‐kidney transplantation (SPKT) in the modern era is uncertain.

Methods

We retrospectively studied 255 patients undergoing SPKT from 11/01 to 8/20. Recipients were stratified according to age group: age <30 years (n = 16); age 30–39 years (n = 91); age 40–49 years (n = 86) and age ≥50 years (n = 62 [24.3%], including 9 patients ≥60 years of age).

Results

Three‐month and one‐year outcomes were comparable. The eight‐year patient survival rate was lowest in the oldest age group (47.6% vs 78% in the 3 younger groups combined, p < .001). However, eight‐year kidney and pancreas graft survival rates were comparable in the youngest and oldest age groups combined (36.5% and 32.7%, respectively), but inferior to those in the middle 2 groups combined (62% and 50%, respectively, both p < .05). Death‐censored kidney and pancreas graft survival rates increased from youngest to oldest recipient age category because of a higher incidence of death with functioning grafts (22.6% in oldest group compared to 8.3% in the 3 younger groups combined, p = .005).

Conclusions

Recipient age did not appear to significantly influence early outcomes following SPKT. Late outcomes are similar in younger and older recipients, but inferior to the middle 2 age groups.
Advancing the science on cannabis concentrates and behavioural health
Authors: Bidwell L. Cinnamon , Martin‐Willett Renée , Karoly Hollis C.
Published: March 2021

Issues

The Cannabis sativa L. plant contains hundreds of phytocannabinoids, but putatively of highest importance to public health risk is the psychoactive cannabinoid delta‐9‐tetrahydrocannabinol (THC), which is associated with risk for cannabis use disorder, affective disturbance, cognitive harm and psychomotor impairment. Recently, there has been an increase in the use and availability of concentrated cannabis products (or ‘concentrates’) that are made by extracting cannabinoids from the plant to form a product with THC concentrations as high as 90–95%. These products are increasingly popular nationwide. The literature on these widely available high potency concentrates is limited and there are many unknowns about their potential harms.

Approach

This review covers the state of the research on cannabis concentrates and behavioural health‐related outcomes and makes recommendations for advancing the science with studies focused on accurately testing the risks in relation to critical public and behavioural health questions.

Key Findings

Data point to unique behavioural health implications of concentrate use. However, causal, controlled and representative research on the effects of cannabis concentrates is currently limited.

Implications

Future research is needed to explore chronic, acute and developmental effects of concentrates, as well as effects on pulmonary function. We also highlight the need to explore these relationships in diverse populations.

Conclusion

While the literature hints at the potential for these highly potent products to increase cannabis‐related behavioural health harms, it is important to carefully design studies that more comprehensively evaluate the impact of concentrates on THC exposure and short‐ and long‐term effects across user groups.
Play among the stars: Astrobiology and intra‐action in Pryor's Living with Tiny Aliens
Authors: John Mix Lucas
Published: March 2021

Pryor's new book, Living with Tiny Aliens: The Image of God for the Anthropocene, uses astrobiology to explore integrated and nonanthropocentric views of the IMAGO DEI with a particular emphasis on planetarity and intra‐action. This review and reflection articulates and amplifies Pryor's view of humans in the context of Earth, arguing for ideas of both Anthropocene and IMAGO DEI that are anthropic (aware of the human context) but not anthropocentric (over‐valuing humanity). It raises a caution about how historical and normative claims of progress and transcendence than can color both in unhelpful ways.
Sex differences in risk factors for cognitive decline and dementia, including death as a competing risk, in individuals with diabetes: Results from the ADVANCE trial
Authors: Gong Jessica , Harris Katie , Hackett Maree , Peters Sanne A. E. , Brodaty Henry , Cooper Mark , Hamet Pavel , Harrap Stephen , Mancia Giuseppe , MacMahon Stephen , Chalmers John , Woodward Mark
Published: March 2021

Aim

To estimate the associations between risk factors and cognitive decline (CD)/dementia, and the sex differences in these risk factors in individuals with type 2 diabetes, while accounting for the competing risk of death.

Materials and Methods

The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial of 11,140 individuals with type 2 diabetes was used to estimate the odds of CD/dementia using multinomial logistic regression.

Results

During a median 5‐year follow‐up, 1827 participants (43.2% women) had CD/dementia (1718 with CD only; 21 with dementia only; 88 with CD and dementia), and 929 (31.0% women) died without CD/dementia. Women had lower odds of CD/dementia than men (odds ratio [OR] [95% confidence interval], 0.88 [0.77, 1.00]); older age, higher total cholesterol, HbA1c, waist circumference, waist‐to‐height ratio, moderately increased albumin‐creatinine ratio, stroke/transient ischaemic attack and retinal disease were each associated with greater odds of CD/dementia; higher years at education completion, baseline cognitive function, taller stature and current alcohol use were inversely associated. Higher waist circumference (women‐to‐men ratio of ORs [ROR], 1.05 [1.00, 1.10] per 5 cm) and presence of anxiety/depression (ROR, 1.28 [1.01, 1.63]) were associated with greater ORs for CD/dementia in women than men.

Conclusions

Several risk factors were associated with CD/dementia. Higher waist circumference and mental health symptoms were more strongly associated with CD/dementia in women than men. Further studies should examine the mechanisms that underlie these sex differences.
Efficacy and safety of LY2963016 insulin glargine versus insulin glargine (Lantus) in Chinese adults with type 2 diabetes: A phase III, randomized, open‐label, controlled trial
Authors: Feng Wenhuan , Chen Wei , Jiang Shan , Du Liying , Zhu Dalong
Published: March 2021

Aim

To compare the efficacy and safety of LY2963016 insulin glargine (LY IGlar) with insulin glargine (Lantus; IGlar) combined with oral antihyperglycaemic medications (OAMs) in insulin‐naive Chinese patients with type 2 diabetes (T2D).

Materials and Methods

In this phase III, open‐label trial, adult patients with T2D receiving two or more OAMs at stable doses for 12 weeks or longer, with HbA1c of 7.0% or more and 11.0% or less, were randomized (2:1) to receive once‐daily LY IGlar or IGlar for 24 weeks. The primary outcome was non‐inferiority of LY IGlar to IGlar at a 0.4% margin, and a gated secondary endpoint tested non‐inferiority of IGlar to LY IGlar (−0.4% margin), assessed by least squares (LS) mean change in HbA1c from baseline to 24 weeks.

Results

Patients assigned to LY IGlar (n = 359) and IGlar (n = 177) achieved similar and significant reductions (p < .001) in HbA1c from baseline. LY IGlar was non‐inferior to IGlar for change in HbA1c from baseline to week 24 (−1.27% vs. −1.23%; LS mean difference: −0.05% [95% CI, −0.19% to 0.10%]) and IGlar was non‐inferior to LY IGlar. The study therefore showed equivalence of LY IGlar and IGlar for the primary endpoint. At week 24, there were no between‐group differences in the proportion of patients achieving an HbA1c of less than 7.0%, seven‐point self‐measured blood glucose, insulin dose or weight gain. Adverse events, allergic reactions, hypoglycaemia and insulin antibodies were similar in the two groups.

Conclusions

Once‐daily LY IGlar and IGlar, combined with OAMs, provide effective and similar glycaemic control with comparable safety profiles in insulin‐naive Chinese patients with T2D.
First report on the occurrence of Phytophthoraobscura on Acerpseudoplatanus in Slovakia
Authors: Tkaczyk Miłosz , Sikora Katarzyna , Kunca Andrej
Published: March 2021

Sycamore maple is a valuable admixture species in many European countries, including Slovakia. As most species belonging to the genus Acer, it is susceptible to several pathogenic organisms including species of Oomycetes. To determine whether the decline of Acer pseudoplatanus in Slovakia is caused by pathogenic Oomycetes, soil samples were taken from the rhizosphere in three sycamore maple stands. Isolation from leaf baits and subsequent identification based on sequencing of the ITS showed the presence of three species: Pythium intermedium, Phytophthora plurivora and Phytophthora obscura. This is the first report on the occurrence of P. plurivora and P. obscura in the rhizosphere of declining sycamore maple stands in Slovakia.