bluuebunny/crossref_metadata_2025 huggingface dataset:
DAP5 enables translation re-initiation on structured messenger RNAs
Authors: Weber Ramona , Kleemann Leon , Hirschberg Insa , Chung Min-Yi , Valkov Eugene , Igreja Cátia
Published: January 2021

Half of mammalian transcripts contain short upstream open reading frames (uORFs) that potentially regulate translation of the downstream coding sequence (CDS). The molecular mechanisms governing these events remain poorly understood. Here we find that the non-canonical initiation factor Death-associated protein 5 (DAP5 or eIF4G2) is selectively required for re-initiation at the main CDS following uORF translation. Using ribosome profiling and luciferase-based reporters coupled with mutational analysis we show that DAP5-mediated re-initiation occurs on messenger RNAs (mRNAs) with long, structure-prone 5′ leader sequences and persistent uORF translation. These mRNAs preferentially code for signalling factors such as kinases and phosphatases. We also report that cap/eIF4F- and eIF4A-dependent recruitment of DAP5 to the mRNA facilitates re-initiation by unrecycled post-termination 40S subunits. Our study reveals important mechanistic insights into how a non-canonical translation initiation factor involved in stem cell fate shapes the synthesis of specific signalling factors.
Evolving Insights from SARS-CoV-2 Genome from 200K COVID-19 Patients
Authors: Desai Sanket , Rane Aishwarya , Joshi Asim , Dutt Amit
Published: January 2021

We present an updated version of our automated computational pipeline, Infection Pathogen Detector IPD 2.0 with a SARS-CoV-2 module, to perform genomic analysis to understand the pathogenesis and virulence of the virus. Analysing the currently available 208911 SARS-CoV2 genome sequences (as accessed on 28 Dec 2020), we generate an extensive database of sample- wise variants and clade annotation, which forms the core of the SARS-CoV-2 analysis module of the analysis pipeline. A comparative account of lineage-specific mutations in the newer SARS-CoV-2 strains emerging in the UK, South Africa and Brazil along with data reported from India identify overlapping and lineages specific acquired mutations suggesting a repetitive convergent and adaptive evolution. Thus, the persistence of pandemic may lead to the emergence of newer regional strains with improved fitness. IPD 2.0 also adopts the recent dynamic clade nomenclature and shows improvement in accuracy of clade assignment, processing time and portability, to its predecessor and thus could be a vital tool to help facilitate genomic surveillance in a population to identify variants involved in breakthrough infections.
Optimum growth temperature declines with body size within fish species
Authors: Lindmark Max , Ohlberger Jan , Gårdmark Anna
Published: January 2021

According to the temperature-size rule, warming of aquatic ecosystems is generally predicted to increase individual growth rates but reduce asymptotic body sizes of ectotherms. However, we lack a comprehensive understanding of how growth and key processes affecting it, such as consumption and metabolism, depend on both temperature and body mass within species. This limits our ability to inform growth models, link experimental data to observed growth patterns, and advance mechanistic food web models. To examine the combined effects of body size and temperature on individual growth, as well as the link between maximum consumption, metabolism and body growth, we conducted a systematic review and compiled experimental data on fishes from 52 studies that combined body mass and temperature treatments. By fitting hierarchical models accounting for variation between species, we estimated how maximum consumption and metabolic rate scale jointly with temperature and body mass within species. We found that whole-organism maximum consumption increases more slowly with body mass than metabolism, and is unimodal over the full temperature range, which leads to the prediction that optimum growth temperatures decline with body size. Using an independent dataset, we confirmed this negative relationship between optimum growth temperature and body size. Small individuals of a given population may therefore exhibit increased growth with initial warming, whereas larger conspecifics could be the first to experience negative impacts of warming on growth. These findings help advance mechanistic models of individual growth and food web dynamics and improve our understanding of how climate warming affects the growth and size structure of aquatic ectotherms.
Loss of the DYRK1A protein kinase results in reduction of ribosomal protein genes expression, ribosome mass and translation defects
Authors: Vona Chiara Di , Barba Laura , Ferrari Roberto , de la Luna Susana
Published: January 2021

Ribosomal proteins (RPs) are evolutionary conserved proteins that are essential for protein translation. RP expression must be tightly regulated to ensure the appropriate assembly of ribosomes and to respond to the growth demands of cells. The elements regulating the transcription of RP genes (RPGs) have been characterized in yeast andDrosophila, yet how cells regulate the production of RPs in mammals is less well understood. Here, we show that a subset of RPG promoters is characterized by the presence of the palindromic TCTCGCGAGA motif and marked by the recruitment of the protein kinase DYRK1A. The presence of DYRK1A at these promoters is associated with enhanced binding of the TATA-binding protein, TBP, and it is negatively correlated with the binding of the GABP transcription factor, establishing at least two clusters of RPGs that could be coordinately regulated. However, DYRK1A silencing leads to a global reduction of RPGs, mRNA pointing at DYRK1A activities beyond those dependent on its chromatin association. Significantly, cells in which DYRK1A is depleted have reduced RP levels, fewer ribosomes, reduced global protein synthesis and smaller size. We therefore propose a novel role for DYRK1A in coordinating the expression of genes encoding RPs, thereby controlling cell growth in mammals.
Purification and partial characterization of a high hemagglutinating chitin-binding lectin fromAponogeton natanstubers
Authors: Dara Shashikanth , Lavudi Harikrishna Naik , Rao Venkateswara , Badithi Nanibabu , Kottapalli Seshagirirao
Published: January 2021

A novel chitin-binding lectin was isolated from the tubers of a plantAponogeton natansfrom the monocot family Aponogetonaceae, designated as ANTL (Aponogeton natanstuber lectin). The lectin agglutinated both untreated and trypsin-treated rabbit erythrocytes, as well as human blood cells of groups A, B and O with different specificities. Lectin activity is inhibited by the oligomers ofN-acetylglucosamine. ANTL is a dimeric glycoprotein with molecular weight of ∼66 KDa and has two identical sub-units of 33 KDa. The carbohydrate percent is 8.2% of the total lectin. The lectin was thermo stable up to 50°C with broad pH optima (pH 4–10). ANTL is found to be potent mitogen for normal murine and human lymphocytes at the concentration as low as 1 µg/ml. Cytotoxic studies of the lectin on human U 266 cell lines has revealed that there is 50% decrease in the proliferation. The confirmation of both the hemagglutination and mitogenic proliferation activity suggests that ANTL is a Chitin-binding lectin with diverse functions. The pharmacological relevance of ANTL as a potent mitogen with some cytotoxic effect in certain cell lines are reported for the first time.

Highlights

A novel chitin-binding lectin was purified from the tuber extracts ofAponogeton natans(ANTL) in a single step on chitin column by affinity chromatography.

ANTL is a dimeric glycoprotein with a molecular weight of ∼66 KDa with high hemagglutination activity towards rabbit erythrocytes.

The cytotoxic effect of ATNL on human cell lines U266 has shown 50 % inhibition of their proliferation.

ANTL displayed potent mitogenic response towards murine and human peripheral blood mononuclear cells.
Growth and reproduction trade‐offs can estimate previous reproductive history in alpine ungulates
Authors: Larue Benjamin , Pelletier Fanie , Côté Steeve D. , Hamel Sandra , Festa‐Bianchet Marco
Published: January 2021

Life‐history theory predicts energy allocation trade‐offs between traits when resources are limited. If females reduce allocation to growth when they reproduce, annual growth could reveal past reproductive effort, which would be useful to assess population dynamics and harvest sustainability. The potential and accuracy of growth measures for predicting reproductive success have rarely been evaluated with individuals with known reproductive history.

We used long‐term monitoring of annual growth and reproduction of marked female bighorn sheep and mountain goats, two species in which primiparity normally occurs well before growth completion, to evaluate growth versus reproduction trade‐offs and their potential for predicting reproductive history of young females using mixed models and 10‐fold block cross‐validation.

We documented a significant reduction in mass gain and horn growth in young reproducing females of both species. This trade‐off was affected by individual differences in energy acquisition and allocation because population density and previous allocation to growth affected the trade‐off. We then parameterized models to predict individual reproductive history of young females based on the growth traits subjected to a reproductive trade‐off.

The accuracy of predictive models ranged from 85.2% to 91.0% across species and traits, indicating that growth is a good predictor of reproductive history. This method is especially useful for population management of species with traits that form permanent visible yearly annuli because they retain a record of annual growth that allows retrospective estimation of reproductive history over multiple years.

Synthesis and applications. We show that because growth significantly decreased in years of allocation to reproduction, annual growth increments provide insights on reproductive history of young females. Population or temporal differences in reproduction of young females affect demographic rates and sustainable harvest. Growth measures of traits that form yearly annuli, such as teeth and horns, could be easily obtained at a low cost from animals harvested or found dead in multiple species. Thus, predictive models of reproductive history based on annual growth could assist conservation and management in a broad range of species.
FOUR MODES OF NEIGHBOURHOOD GOVERNANCE: The View from Nanjing, China
Authors: Wang Ying , Clarke Nick
Published: January 2021

In a context of global moves towards decentralization and neighbourhood governance, this article focuses on neighbourhood governance in Nanjing, China. We draw on interviews and observations in 32 neighbourhoods to examine how neighbourhood governance plays out in different neighbourhoods. We identify and describe four modes of governance—collective consumption, service privatization, civic provision and state‐sponsored—to argue that neighbourhood governance develops on the ground in diverse and complex ways, necessitating scholars to be cautious when seeking to generalize about it at the scale of the city, let alone that of the nation‐state or the globe. We argue that relationships between actors are important units of analysis when considering how effective governance is achieved in different neighbourhoods; diversity and complexity in neighbourhood governance partly reflect the role of the state in these relationships. In turn the role of the state partly reflects processes of policy evolution in particular neighbourhoods.
The Asymmetric Effect of Reporting Flexibility on Priced Risk
Authors: BLOOMFIELD MATTHEW J.
Published: January 2021

Most firms covary more positively with downmarkets than upmarkets—a phenomenon I refer to as “risk asymmetry.” I predict and find that risk asymmetry is caused, at least in part, by a firm's ability to selectively obfuscate poor performance. Risk asymmetry decreases significantly when firms are required to adhere to the more stringent auditing standards mandated under Section 404 of the Sarbanes‐Oxley Act, however this decrease is more muted for firms with weak internal controls. Consistent with my predictions, these patterns are stronger for more market‐sensitive firms and weaker for firms that include relative performance evaluation in their CEOs' pay packages. Taken together with prior literature (which documents that risk asymmetry is priced), my results suggest that a firm can lower its cost of capital by credibly reducing its ability to obfuscate value‐relevant information.
Comparative transcriptome analysis of thiamethoxam susceptible and resistant Asian citrus psyllid, Diaphorina citri (Hemiptera: Liviidae), using RNA‐sequencing
Authors: Chen Xue Dong , Neupane Surendra , Gill Torrence A. , Gossett Hunter , Pelz‐Stelinski Kirsten S. , Stelinski Lukasz L.
Published: January 2021

Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae), transmits the causal pathogen of huanglongbing and is a global pest of citrus. D. citri populations exhibit resistance to multiple insecticide modes of action in areas where these chemicals have been overused. We performed genome‐wide transcriptional analysis for two field populations of D. citri (Wauchula and Lake Alfred, Florida, USA) that exhibit 1300‐fold resistance to the neonicotinoid insecticide, thiamethoxam, and compared it to that of susceptible psyllids collected from the same area and without imposed selection. The Lake Alfred population responded to insecticide resistance by up‐regulation of 240 genes and down‐regulation of 148 others. The Wauchula population exhibited similar patterns to the Lake Alfred population with up‐regulation of 253 genes and down‐regulation of 115 others. Gene Ontology annotation associated with cellular processes, cell, and catalytic activity were assigned to differentially expressed genes (DEGs). The DEGs from Lake Alfred and Wauchula populations were mapped to Kyoto Encyclopedia of Gene and Genomes pathways and implicated enrichment of metabolic pathways, oxidative phosphorylation, extracellular matrix‐receptor interaction, terpenoid backbone biosynthesis, and insect hormone biosynthesis in the resistant populations. Up‐regulation of 60s ribosomal proteins, UDP‐gluscoyltransferases, cytochrome c oxidases, and CYP and ABC transporters among thiamethoxam‐resistant D. citri implicates a broad array of novel and conventionally understood resistance mechanisms.
Immune checkpoint inhibitors‐induced eosinophilic pneumonia: A case report
Authors: Hara Kanako , Yamasaki Kei , Tahara Masahiro , Kimuro Rieko , Yamaguchi Yudai , Suzuki Yu , Kawabata Hiroki , Kawanami Toshinori , Fujimoto Naohiro , Yatera Kazuhiro
Published: January 2021

A 78‐year‐old male with renal cell carcinoma was treated with combined immunotherapy of nivolumab and ipilimumab. After four courses of the treatment, a chest computed tomography (CT) revealed newly formed ground‐glass opacities (GGOs) in both the lower lung lobes; drug‐induced pneumonia was speculated. Eosinophil counts were elevated in both peripheral blood and bronchoalveolar lavage fluid. Both the immune checkpoint inhibitors (ICIs) were discontinued, following which the chest CT findings improved. Based on these findings, a diagnosis of ICI‐induced eosinophilic pneumonia was made. Hence, clinicians should be wary of the risk of eosinophilic pneumonia during ICI‐anticancer therapy.
Identifying prostate cancer in men with non‐suspicious multi‐parametric magnetic resonance imaging of the prostate
Authors: Doan Paul , Lahoud John , Kim Lawrence , Patel Manish I.
Published: January 2021

Background

To formulate clinical pathways for identifying clinically significant prostate cancer (csPC) and avoiding insignificant prostate cancer (isPC) in those without suspicious regions of interest on multi‐parametric magnetic resonance imaging (mpMRI) of the prostate.

Methods

A retrospective review identified patients with negative mpMRI who underwent subsequent transperineal prostate biopsy across two centres. Patient characteristics and association with biopsy results were evaluated using univariate and multivariate regression analyses.

Results

A total of 144 patients were identified as having negative mpMRI and undergoing subsequent transperineal prostate biopsy; 18% (25/144) of the cohort were found to have csPC. Logistic regression analysis failed to identify statistically significant predictive factors. In this cohort, if all patients with prostate‐specific antigen > 3.0 were biopsied the least amount of csPC is missed, at 20% (5/25) however all isPC would be diagnosed. The least amount of isPC is diagnosed with a biopsy threshold of >15% from the European Randomized Study of Screening for Prostate Cancer calculator with 20% (5/25) of isPC diagnoses made however only 10.5% (2/19) csPC would be diagnosed. A biopsy threshold of >5% risk reduces the number of csPC missed to 37% (7/19) however increases isPC diagnoses to 54% (13/24) of the population.

Conclusion

False‐negative rates of prostate MRI for csPC are significant within our cohort at 18%. The decision to biopsy should be made in conjunction with a risk profile acceptable by the patient and clinician. The current study demonstrates that there is a need to balance the risk of missing csPC and harm of diagnosing isPC.
Abdominal wall heterotopic ossification following damage control laparotomy: an unusual bone to pick
Authors: Jacob Mathew O. , Reddipogu Jonathan , Jacob Jacob
Published: January 2021

Background

Heterotopic ossification (HO) refers to the development of extra‐skeletal bone in muscle and soft tissues, following tissue insult secondary to surgery or trauma. This pathological process is considered as the result of severe inflammatory cell cascade initiated after local trauma and subsequent attempt at tissue repair involving resident mesenchymal cells. We present a series of 12 cases of abdominal HO (AHO), over 8 years, following damage control laparotomies (DCLs).

Methods

Medical records of 50 patients who underwent DCLs at Alice Springs Hospital between 2010 and 2018 were retrospectively reviewed for AHO. Demographic data were extracted. Abdominal X‐rays and computed tomography scans of 47 patients were reviewed for AHO.

Results

Twelve patients (25%) developed AHO of varying diversity ranging from small insignificant lesions to clinically palpable lesions in the abdominal wall. Data revealed relatively younger male preponderance. DCL for severe acute pancreatitis (SAP) was associated with AHO (P < 0.1, 90% CI). Longer periods of ventilation, intensive care unit stay and admission to hospital were strongly associated with AHO (P < 0.01, 95% CI). Occurrence of AHO with SAP was significantly higher compared to patients without SAP (relative risk 3.54, P < 0.001). Only two patients required surgical excision of HO prior to definitive closure of the abdomen.

Conclusion

The authors conclude that AHO occurred more frequently in younger males. DCL for SAP was a significant risk factor. Extended periods of ventilation, intensive care unit stay and hospital admission were strongly associated with the development of AHO. Preoperative detection of HO is essential prior to planning definitive closure of the abdomen.
Disassembling Coal: Finance Capital, Environmental Law, and the Right to Information in South India
Authors: Kumar Mukul
Published: January 2021

Since the liberalisation of India’s energy sector began in the 1990s, the government has developed several novel techniques to make coal an attractive asset for investors. The pharaonic Ultra Mega Power Plant Project (UMPP) program is one such technique which secures finance capital, land, and environmental clearances for coal‐fired power plants. Drawing upon the analytic of assemblage, this paper tracks how the Cheyyur UMPP, one of the largest proposed coal‐fired power plants in the world, has been disassembled by a range of interdependent elements, from Right to Information (RTI) activism and environmental litigation to the perception of litigation risk and the materiality of coal. In pursuing an analysis of the events and elements which have led to the Cheyyur UMPP being disassembled, this paper calls for greater attention to the vulnerabilities, limits, and instabilities of coal assemblages.
Daily Ethnic/Racial Context in Peer Groups: Frequency, Structure, and Implications for Adolescent Outcomes
Authors: Wang Yijie
Published: January 2021

Ethnic/racial context in peer groups is poorly understood. Using daily data from 178 ethnically/racially diverse adolescents (Mage = 14.53) over 2 weeks, this study investigated peer processes related to ethnicity/race (peer ethnic/racial processes) in everyday life. On average, peer ethnic/racial processes occurred about 1 to 4 days over the 2 weeks. On days when adolescents reported more negative peer ethnic/racial processes (indicated by ethnic/racial teasing, discrimination, victimization, and partially by preparation for bias), they also reported lower school engagement. On days when adolescents reported more positive peer ethnic/racial processes (indicated by cultural socialization, support against discrimination, and partially by preparation for bias), they exhibited more prosocial behaviors and greater ethnic/racial identity private regard. Similar associations emerged at the between‐person level.
Behavioral Regulatory Problems Are Associated With a Lower Attentional Bias to Fearful Faces During Infancy
Authors: Eskola Eeva , Kataja Eeva‐Leena , Hyönä Jukka , Häikiö Tuomo , Pelto Juho , Karlsson Hasse , Karlsson Linnea , Korja Riikka
Published: January 2021

To investigate the role of early regulatory problems (RP), such as problems in feeding, sleeping, and calming down during later development, the association between parent‐reported RP at 3 months (no‐RP, n = 110; RP, n = 66) and attention to emotional faces at 8 months was studied. Eight‐month‐old infants had a strong tendency to look at faces and to specifically fearful faces, and the individual variance in this tendency was assessed with eye tracking using a face‐distractor paradigm. The early RPs were related to a lower attention bias to fearful faces compared to happy and neutral faces after controlling for temperamental negative affectivity. This suggests that early RPs are related to the processing of emotional information later during infancy.
What Counts? Sources of Knowledge in Children’s Acquisition of the Successor Function
Authors: Schneider Rose M. , Sullivan Jessica , Guo Kaiqi , Barner David
Published: January 2021

Although many U.S. children can count sets by 4 years, it is not until 5½–6 years that they understand how counting relates to number—that is, that adding 1 to a set necessitates counting up one number. This study examined two knowledge sources that 3½‐ to 6‐year‐olds (N = 136) may leverage to acquire this “successor function”: (a) mastery of productive rules governing count list generation; and (b) training with “+1” math facts. Both productive counting and “+1” math facts were related to understanding that adding 1 to sets entails counting up one number in the count list; however, even children with robust successor knowledge struggled with its arithmetic expression, suggesting they do not generalize the successor function from “+1” math facts.
Exhausted T cells in systemic lupus erythematosus patients in long-standing remission
Authors: Lima G , Treviño-Tello F , Atisha-Fregoso Y , Llorente L , Fragoso-Loyo H , Jakez-Ocampo J
Published: January 2021

The mechanisms that drive systemic lupus erythematosus (SLE) patients to achieve remission are unknown; one possible explanation might be T cell exhaustion. The aim of the present study was to measure CD4+ and CD8+ T cell exhaustion in SLE patients in prolonged remission (PR-SLE) and compared them with patients with active SLE (Act-SLE) and healthy subjects. We included 15 PR-SLE patients, 15 Act-SLE and 29 healthy subjects. T cell exhaustion was determined by flow cytometry according to the expression of programmed cell death 1 (PD)-1, T cell immunoglobulin and mucin 3 (Tim-3), natural killer cell receptor (2B4), eomesodermin (EOMES) and T-box transcription factor TBX21 (T-bet) in CD4+ and CD8+ T cells. Dimensionality reduction using the T-distributed stochastic neighbor-embedding algorithm and clustering analysis was used for the identification of relevant populations. Percentages of CD3+, CD4+ and CD8+ T cells were similar among groups. We identified five subpopulations of CD8+ and seven of CD4+ cells. The CD4+T-bet+CD45RO+ cells identified in the unsupervised analysis were significantly increased in PR-SLE versus Act-SLE [median = 0·20, interquartile range (IQR) = 1·74–30·50 versus 1·68, IQR = 0·4–2·83; P < 0·01]. CD4+EOMES+ cells were also increased in PR-SLE versus Act-SLE (5·24, IQR = 3·38–14·70 versus 1·39, IQR = 0·48–2·87; P < 0·001). CD8+EOMES+ cells were increased in PR-SLE versus Act-SLE (37·6, IQR = 24·9–53·2 versus 8·13, IQR = 2·33–20·5; P < 0·001). Exhausted and activated T cells presented an increased frequency of PD-1, CD57 and EOMES in SLE patients versus healthy subjects. Some subpopulations of T cells expressing markers associated with exhaustion are increased in patients in remission, supporting T cell exhaustion as a tolerance mechanism in SLE. Exhaustion of specific populations of T cells might represent a potential therapeutic tool that will contribute to the goal of achieving sustained remission in these patients.
Treatment of myelin oligodendrocyte glycoprotein immunoglobulin G–associated disease
Authors: Healy Sarah , Elhadd Kariem Tarik , Gibbons Emily , Whittam Dan , Griffiths Michael , Jacob Anu , Huda Saif
Published: January 2021

Myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG)–associated disease (MOGAD) is increasingly recognized as a distinct nosological entity from aquaporin‐4 antibody IgG–positive neuromyelitis optica spectrum disorder (AQP4‐IgG NMOSD). The advent of highly specific MOG‐IgG cell‐based diagnostic assays have helped to refine our understanding of the clinical spectrum of MOGAD. To date, treatment approaches have been largely extrapolated from AQP4‐IgG NMOSD experience, but there is growing evidence of distinct differences in treatment response between these conditions. This review summarizes the current status and understanding of acute and chronic treatments for MOGAD. Timing and duration of treatment, pregnancy, and emerging therapies are also discussed.
Paediatric laryngeal squamous cell carcinoma: Systematic review and pooled analysis
Authors: Mur Taha , Jaleel Zaroug , Agarwal Pratima , Edwards Heather , Levi Jessica R.
Published: January 2021

Background

Paediatric squamous cell carcinoma (SCC) of the larynx is rare; however, recent data seem to support the notion that this pathology is increasing in incidence. Although this has been the case for several decades, treatment algorithms for this patient population remain identical to those of adults.

Methods

The study consists of a systematic review and pooled analysis of oncologic outcomes in paediatric laryngeal SCC from a comprehensive literature search on OVID MEDLINE and EMBASE.

Results

The average cohort age was 12.1 years. Nine (36%) had supraglottic primaries, and 16 (64%) had glottic primaries. Treatment included unimodal and combination therapy. No significant difference in survival was noted between surgically treated and non‐surgically treated patients (5‐year overall survival (OS): 68.2% vs 76.2%, P = .905), even when stratified for advanced‐stage and supraglottic disease.

Conclusions

Paediatric patients with laryngeal HNSCC may have different presentations and responses to therapy than their adult counterparts.
Lineage‐level distribution models lead to more realistic climate change predictions for a threatened crayfish
Authors: Zhang Zhixin , Kass Jamie M. , Mammola Stefano , Koizumi Itsuro , Li Xuecao , Tanaka Kazunori , Ikeda Kousuke , Suzuki Toru , Yokota Masashi , Usio Nisikawa
Published: January 2021

Aim

As climate change presents a major threat to biodiversity in the next decades, it is critical to assess its impact on species habitat suitability to inform biodiversity conservation. Species distribution models (SDMs) are a widely used tool to assess climate change impacts on species’ geographical distributions. As the name of these models suggests, the species level is the most commonly used taxonomic unit in SDMs. However, recently it has been demonstrated that SDMs considering taxonomic resolution below (or above) the species level can make more reliable predictions of biodiversity change when different populations exhibit local adaptation. Here, we tested this idea using the Japanese crayfish (Cambaroides japonicus), a threatened species encompassing two geographically structured and phylogenetically distinct genetic lineages.

Location

Northern Japan.

Methods

We first estimated niche differentiation between the two lineages of C. japonicus using n‐dimensional hypervolumes and then made climate change predictions of habitat suitability using SDMs constructed at two phylogenetic levels: species and intraspecific lineage.

Results

Our results showed only intermediate niche overlap, demonstrating measurable niche differences between the two lineages. The species‐level SDM made future predictions that predicted much broader and severe impacts of climate change. However, the lineage‐level SDMs led to reduced climate change impacts overall and also suggested that the eastern lineage may be more resilient to climate change than the western one.

Main conclusions

The two lineages of C. japonicus occupy different niche spaces. Compared with lineage‐level models, species‐level models can overestimate climate change impacts. These results not only have important implications for designing future conservation strategies for this threatened species, but also highlight the need for incorporating genetic information into SDMs to obtain realistic predictions of biodiversity change.
Outcomes of ixazomib/lenalidomide/dexamethasone for multiple myeloma: A multicenter retrospective analysis
Authors: Takakuwa Teruhito , Yamamura Ryosuke , Ohta Kensuke , Kaneko Hitomi , Imada Kazunori , Nakaya Aya , Fuchida Shin‐ichi , Shibayama Hirohiko , Matsuda Mitsuhiro , Shimazu Yutaka , Adachi Yoko , Kosugi Satoru , Uchiyama Hitoji , Tanaka Hirokazu , Hanamoto Hitoshi , Shimura Yuji , Kanda Junya , Onda Yoshiyuki , Uoshima Nobuhiko , Yagi Hideo , Yoshihara Satoshi , Hino Masayuki , Shimazaki Chihiro , Takaori‐Kondo Akifumi , Kuroda Junya , Matsumura Itaru , Kanakura Yuzuru , Nomura Shosaku
Published: January 2021

Objectives

This study aimed to investigate real‐world data of ixazomib plus lenalidomide and dexamethasone (IRd) therapy for patients with relapsed and refractory multiple myeloma (RRMM).

Methods

We retrospectively analyzed 122 patients treated with IRd at 16 centers from May 2017 to January 2019 by using the Kansai Myeloma Forum database.

Result

At the start of IRd, the median age was 72 years, 66.7% of patients had IgG type, and the median number of prior therapies was 4, comprising bortezomib (85.4%) and lenalidomide (89.3%)‐based regimens. Disease progression and adverse events accounted for treatment discontinuation in 46 and 32 patients, respectively. The median overall survival (OS) was not reached, and the median progression‐free survival (PFS) was 11.9 months. Sensitivity to bortezomib did not affect the PFS, whereas lenalidomide‐refractory patients had significantly lower PFS than lenalidomide‐sensitive patients, who were comparable to TOURMALINE‐MM1 study. The patients with IgG type had significantly better PFS and OS than those with non‐IgG type.

Conclusion

This study presents the largest real‐world data of patients treated with IRd in Asia. However, in real clinical practice, the patient background is different from the TOURMALINE‐MM1 study, and IRd showed poor efficacy, especially in the non‐IgG type and lenalidomide‐refractory patients with RRMM.
Delivering telemedicine consultations for patients with transient ischaemic attack during the COVID‐19 pandemic in a comprehensive tertiary stroke centre in the United Kingdom
Authors: D’Anna Lucio , Ellis Natalya , Bentley Paul , Brown Zoe , Halse Omid , Jamil Sohaa , Jenkins Harri , Malik Abid , Kalladka Dheeraj , Kwan Joseph , Venter Marius , Banerjee Soma
Published: January 2021

Background and purpose

The global COVID‐19 pandemic led many stroke centres worldwide to shift from in‐person to telemedicine consultations to assess patients with transient ischaemic attacks (TIAs). We aimed to investigate the impact of telemedicine during the COVID‐19 pandemic on the management and outcome of the patients with TIA.

Methods

We retrospectively analysed data from a registry of consecutive TIA patients assessed at the Stroke Department, Imperial College Health Care Trust, London, during the national lockdown period (between March 23 2020 and 30 June 2020). As controls, we evaluated the clinical reports and stroke quality metrics of patients presenting to the TIA clinic in the same period of 2019.

Results

Between 23 March 2020 and 30 June 2020, 136 patients were assessed using the telemedicine TIA clinic, compared to 180 patients evaluated with face‐to‐face consultation in the same period in 2019. Patients’ characteristics were similar in both groups. At 3 months after the TIA, there were no significant differences in the proportion of patients admitted to the hospital for recurrent TIA/stroke or any other cardiovascular cause from the 2020 period compared to the same period in 2019.

Conclusions

Our analysis showed that during the pandemic, our telemedicine consultations of TIA patients were not associated with an increased 3‐month rate of recurrent TIA/stroke or cardiovascular hospital admissions. More robust studies looking at this model of care will be needed to assess its long‐term effects on patients and health care systems.
The severe epilepsy syndromes of infancy: A population‐based study
Authors: Howell Katherine B. , Freeman Jeremy L. , Mackay Mark T. , Fahey Michael C. , Archer John , Berkovic Samuel F. , Chan Eunice , Dabscheck Gabriel , Eggers Stefanie , Hayman Michael , Holberton James , Hunt Rodney W. , Jacobs Susan E. , Kornberg Andrew J. , Leventer Richard J. , Mandelstam Simone , McMahon Jacinta M. , Mefford Heather C. , Panetta Julie , Riseley Jessica , Rodriguez‐Casero Victoria , Ryan Monique M. , Schneider Amy L. , Smith Lindsay J. , Stark Zornitza , Wong Flora , Yiu Eppie M. , Scheffer Ingrid E. , Harvey A. Simon
Published: January 2021

Objective

To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes.

Methods

A population‐based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes. Incidence, etiologies, and outcomes at age 2 years were determined.

Results

Seventy‐three of 114 (64%) infants fulfilled diagnostic criteria for epilepsy syndromes at presentation, and 16 (14%) had "variants" of epilepsy syndromes in which there was one missing or different feature, or where all classical features had not yet emerged. West syndrome (WS) and "WS‐like" epilepsy (infantile spasms without hypsarrhythmia or modified hypsarrhythmia) were the most common syndromes, with a combined incidence of 32.7/100 000 live births/year. The incidence of epilepsy of infancy with migrating focal seizures (EIMFS) was 4.5/100 000 and of early infantile epileptic encephalopathy (EIEE) was 3.6/100 000. Structural etiologies were common in "WS‐like" epilepsy (100%), unifocal epilepsy (83%), and WS (39%), whereas single gene disorders predominated in EIMFS, EIEE, and Dravet syndrome. Eighteen (16%) infants died before age 2 years. Development was delayed or borderline in 85 of 96 (89%) survivors, being severe–profound in 40 of 96 (42%). All infants with EIEE or EIMFS had severe–profound delay or were deceased, but only 19 of 64 (30%) infants with WS, "WS‐like," or "unifocal epilepsy" had severe–profound delay, and only two of 64 (3%) were deceased.

Significance

Three quarters of severe epilepsies of infancy could be assigned an epilepsy syndrome or "variant syndrome" at presentation. In this era of genomic testing and advanced brain imaging, diagnosing epilepsy syndromes at presentation remains clinically useful for guiding etiologic investigation, initial treatment, and prognostication.
Focal to bilateral tonic–clonic seizures are associated with widespread network abnormality in temporal lobe epilepsy
Authors: Sinha Nishant , Peternell Natalie , Schroeder Gabrielle M. , de Tisi Jane , Vos Sjoerd B. , Winston Gavin P. , Duncan John S. , Wang Yujiang , Taylor Peter N.
Published: January 2021

Objective

Our objective was to identify whether the whole‐brain structural network alterations in patients with temporal lobe epilepsy (TLE) and focal to bilateral tonic–clonic seizures (FBTCS) differ from alterations in patients without FBTCS.

Methods

We dichotomized a cohort of 83 drug‐resistant patients with TLE into those with and without FBTCS and compared each group to 29 healthy controls. For each subject, we used diffusion‐weighted magnetic resonance imaging to construct whole‐brain structural networks. First, we measured the extent of alterations by performing FBTCS‐negative (FBTCS−) versus control and FBTCS‐positive (FBTCS+) versus control comparisons, thereby delineating altered subnetworks of the whole‐brain structural network. Second, by standardizing each patient's networks using control networks, we measured the subject‐specific abnormality at every brain region in the network, thereby quantifying the spatial localization and the amount of abnormality in every patient.

Results

Both FBTCS+ and FBTCS− patient groups had altered subnetworks with reduced fractional anisotropy and increased mean diffusivity compared to controls. The altered subnetwork in FBTCS+ patients was more widespread than in FBTCS− patients (441 connections altered att > 3,p < .001 in FBTCS+ compared to 21 connections altered att > 3,p = .01 in FBTCS−). Significantly greater abnormalities—aggregated over the entire brain network as well as assessed at the resolution of individual brain areas—were present in FBTCS+ patients (p < .001,d = .82, 95% confidence interval = .32–1.3). In contrast, the fewer abnormalities present in FBTCS− patients were mainly localized to the temporal and frontal areas.

Significance

The whole‐brain structural network is altered to a greater and more widespread extent in patients with TLE and FBTCS. We suggest that these abnormal networks may serve as an underlying structural basis or consequence of the greater seizure spread observed in FBTCS.
The expected investment growth premium
Authors: Li Jun , Wang Huijun , Yu Jianfeng
Published: January 2021

We propose a novel measure of investment plans, namely expected investment growth (EIG), and find stocks with high EIG outperform stocks with low EIG by 17% per annum. This premium can be generated in a neoclassical model with the investment plan friction, in which a firm's expected returns increases with its planned investment due to an embedded leverage effect. We provide empirical evidence on the interaction of the cash flow effect and discount rate effect in driving this EIG premium. Our findings highlight the investment plan friction as an important economic channel to understand the cross‐sectional risk premium.
Di‐lysine motif‐like sequences formed by deleting the C‐terminal domain of aquaporin‐4 prevent its trafficking to the plasma membrane
Authors: Chau Simon , Fujii Atsushi , Wang Yingqi , Vandebroek Arno , Goda Wakami , Yasui Masato , Abe Yoichiro
Published: January 2021

Aquaporin‐4 is a transmembrane water channel protein, the C‐terminal domain of which is facing the cytosol. In the process of investigating the role of the C‐terminal domain of aquaporin‐4 with regard to intracellular trafficking, we observed that a derivative of aquaporin‐4, in which the C‐terminal 53 amino acids had been removed (Δ271‐323), was localized to intracellular compartments, including the endoplasmic reticulum, but was not expressed on the plasma membranes. This was determined by immunofluorescence staining and labeling of the cells with monoclonal antibody specifically recognizing the extracellular domain of aquaporin‐4, followed by confocal microscopy and flow cytometry. Deletion of additional amino acids in the C‐terminal domain of aquaporin‐4 led to its redistribution to the plasma membrane. This suggests that the effect of the 53‐amino acid deletion on the subcellular localization of aquaporin‐4 could be attributed to the formation of a signal at the C terminus that retained aquaporin‐4 in intracellular compartments, rather than the loss of a signal required for plasma membrane targeting. Substitution of the lysine at position 268 with alanine could rescue the Δ271‐323‐associated retention in the cytosol, suggesting that the C‐terminal sequence of the mutant served as a signal similar to a di‐lysine motif.
Mind the gap: line managers as effective or non‐effective talent spotters
Authors: Blanco María Rita , Golik Mariela N.
Published: January 2021

Due to the centrality of line managers’ role in the talent identification process, this qualitative study aims to determine what effective and non‐effective talent spotters do differently from one another in relation with an ‘ideal’ talent identification model offered by the literature. A double‐blind design was applied to the sample designated by the Corporate Talent Management Director of a Latin American multinational firm. 20 senior and middle managers, some effective and some others non‐effective, who work in different countries, participated in the study. Findings show that effective talent spotters perform three key stages of the talent identification model and they do it extremely well: differentiation of potential from performance, matching process and design of developmental challenges. The clear differentiation of potential from performance constitutes the crucial stage since a fuzzy differentiation taints the following stages. Not only is it necessary to perform these key stages but they should be executed in line with the principles of the talent management literature. Recommendations for practice, including specific guidelines for Talent Managers are proposed.
Protocol driven periprocedural anticoagulation for left atrial ablation
Authors: Bradley Christopher J. , Williamson Brian D. , George Julie , Haines David E.
Published: January 2021

Introduction

A weight‐based heparin dosing policy adjusted for preprocedural oral anticoagulation was implemented to reduce the likelihood of subtherapeutic dosing during left atrial catheter ablation procedures. We hypothesized that initiation of the protocol would result in a greater prevalence of therapeutic activated clotting time (ACT) values and decreased time to therapeutic ACT during left atrial ablation procedures.

Methods

A departmental protocol was initiated for which subjects received intravenous unfractionated heparin (UFH) to achieve and maintain a goal of ACT >300 s. Initial bolus dose was adjusted for pre‐procedure oral anticoagulation and weight as follows: 50 units/kg for those receiving warfarin, 75 units/kg for those not anticoagulated, and 120 units/kg for those on direct oral anticoagulants (DOACs). A UFH infusion was initiated at 10% of the bolus per hour. One hundred consecutive left atrial ablation procedures treated with Protocol Guided heparin dosing were compared with a retrospective consecutive cohort of Usual Care heparin dosing.

Results

When the Usual Care and Protocol Guided cohorts were compared, significant findings were limited to those on pre‐procedure DOAC. The initial UFH bolus increased from 99.3 ± 24.8 to 118.2 ± 22.8 units/kg (p < .001), the proportion of therapeutic ACT on the first draw after heparin administration increased from 57.7% to 76.6% (p = .010), and the time to therapeutic ACT after UFH administration decreased from 37.8 ± 19.8 to 30.2 ± 16.4 min (p = .032).

Conclusion

A weight‐based protocol for periprocedural UFH administration resulted in a higher proportion of therapeutic ACT values and decreased the time to therapeutic ACT for those on pre‐procedure DOAC.
Entrapment of diagnostic catheter within Advisor HD grid mapping catheter
Authors: Mar Philip L. , Chong Luke , Perez Arturo , Lakkireddy Dhanunjaya , Gopinathannair Rakesh
Published: January 2021

The potential for catheter entanglement with the HD Grid mapping catheter is explicitly stated in the manufacturer's product manual. A case of an entrapped 6 French quadripolar diagnostic catheter within an HD Grid mapping catheter is presented. We discuss the diagnosis, management, and resolution of this complication in our patient. The patient's arrhythmia was successfully eliminated, and no vascular complication in the postprocedural setting nor arrhythmia recurrence at follow‐up were observed. Strategies to prevent and safely manage this complication, while salvaging access, are also discussed.
An increased burden of rare exonic variants in NRXN1 microdeletion carriers is likely to enhance the penetrance for autism spectrum disorder
Authors: Cameli Cinzia , Viggiano Marta , Rochat Magali J. , Maresca Alessandra , Caporali Leonardo , Fiorini Claudio , Palombo Flavia , Magini Pamela , Duardo Renée C. , Ceroni Fabiola , Scaduto Maria C. , Posar Annio , Seri Marco , Carelli Valerio , Visconti Paola , Bacchelli Elena , Maestrini Elena
Published: January 2021

Autism spectrum disorder (ASD) is characterized by a complex polygenic background, but with the unique feature of a subset of cases (~15%‐30%) presenting a rare large‐effect variant. However, clinical interpretation in these cases is often complicated by incomplete penetrance, variable expressivity and different neurodevelopmental trajectories. NRXN1 intragenic deletions represent the prototype of such ASD‐associated susceptibility variants. From chromosomal microarrays analysis of 104 ASD individuals, we identified an inherited NRXN1 deletion in a trio family. We carried out whole‐exome sequencing and deep sequencing of mitochondrial DNA (mtDNA) in this family, to evaluate the burden of rare variants which may contribute to the phenotypic outcome in NRXN1 deletion carriers. We identified an increased burden of exonic rare variants in the ASD child compared to the unaffected NRXN1 deletion‐transmitting mother, which remains significant if we restrict the analysis to potentially deleterious rare variants only (P = 6.07 × 10−5). We also detected significant interaction enrichment among genes with damaging variants in the proband, suggesting that additional rare variants in interacting genes collectively contribute to cross the liability threshold for ASD. Finally, the proband's mtDNA presented five low‐level heteroplasmic mtDNA variants that were absent in the mother, and two maternally inherited variants with increased heteroplasmic load. This study underlines the importance of a comprehensive assessment of the genomic background in carriers of large‐effect variants, as penetrance modulation by additional interacting rare variants to might represent a widespread mechanism in neurodevelopmental disorders.