bluuebunny/crossref_metadata_2025 huggingface dataset:
Diogenes Laertius and Philosophical Lives
Authors: White Stephen
Published: January 2021

This chapter addresses Diogenes Laertius’ Lives of Eminent Philosophers, which recounts the doings, sayings, and writings of the leading figures of ancient Greek philosophy from its origins down to its rapid efflorescence and institutionalization in the fourth and third centuries bc, with occasional glimpses of its continuing vitality in the centuries beyond. Diogenes’ Lives is an exceptional work on many counts. For one, it is the single largest collection of Lives to survive from classical Antiquity, handily surpassing Plutarch in number and scope if not in depth or length, and so too Philostratus and Suetonius. It is also a key witness to the early stages of biographical literature in the fourth and third centuries bc. At the same time, it presents the single most comprehensive account of the origins and development of an entire discipline, and a distinctive form of intellectual history from a biographical perspective. It also, accordingly, represents a distinctive form of life-writing, framed by basic biographical data but lean, often very lean on the standard biographical fare—from a modern perspective at least—of incident and narrative, and governed instead by its disciplinary orientation, and its sustained focus on philosophy as a distinctive cultural practice and way to live.
Fifteenth-Century Eastern Reception of Aquinas
Authors: Golitsis Pantelis
Published: January 2021

The Eastern reception of Aquinas in the fifteenth century was determined by the theological repercussions that occurred in Byzantium in the preceding century, namely the association of Thomism with Barlaamism and Akindynism (the denial of a real distinction between God’s essence and energies or of God’s having energies at all), the use of Aristotle’s syllogistic theory in establishing the Filioque, and the vision of God’s essence in statu patriae. Nevertheless, Aquinas’ two Summae were used and tacitly excerpted (in the translations of the brothers Kydones) by Palamite theologians for settling other theological matters, whereas there was an open vindication of Aquinas both as a philosopher and as a reliable guide in the exposition of the Scriptures by George Scholarios (Patriarch Gennadios II).
Concentration and Visualization Techniques in Buddhist Meditation
Authors: Yamabe Nobuyoshi
Published: January 2021

This chapter outlines the early form and development of Buddhist meditation. First, it discusses the “application of mindfulness,” especially “mindfulness of the body,” which can be largely classified into two types of practice. One is “mindfulness per se,” without reflective thought, and the other is a more reflective or visual approach. “Mindfulness per se” (in particular, mindful breathing) was transmitted to East Asia and remains the cardinal method there. The chapter discusses close ties between traditional mindfulness and Japanese Sōtō practice. It then moves on to describe meditation on the decomposition of a corpse, which is a representative form of the more reflective and visual type of practice, involving the observation of a dead body in its stages of decomposition. This is found in early scriptures. Later texts came to teach a more elaborate method of “grasping the images” of a corpse. A notable development in visualization is that the images seen by the practitioner came to include ones that were more enigmatic. The discussion finally turns to another significant development in Buddhist meditation, one which involves Buddha visualization. Its undeveloped form is found in early Mahayana sutras, but a fully developed version employing statues as aides for visualization is found in later meditation texts from the fifth century onward. This type of visualization was inherited by Esoteric Buddhism and is still practiced today.
Did Theresa May Kill the War Powers Convention? Comparing Parliamentary Debates on UK Intervention in Syria in 2013 and 2018
Authors: Strong James
Published: January 2021

This article asks whether Prime Minister Theresa May’s decision to bypass the House of Commons and order military action in Syria in 2018 killed the UK’s nascent War Powers Convention, established most visibly when MPs vetoed an essentially similar operation under Prime Minister David Cameron in 2013. It finds that the War Powers Convention survives, but in a weakened state, subject to new caveats that significantly narrow its scope. What happens next depends on the dynamic, unpredictable interaction between what future prime ministers believe, what strategic questions arise and what MPs will accept.
Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis
Authors: Ruperto Nicolino , Brunner Hermine I , Pacheco-Tena César , Louw Ingrid , Vega-Cornejo Gabriel , Spindler Alberto J , Kingsbury Daniel J , Schmeling Heinrike , Borzutzky Arturo , Cuttica Rubén , Inman C J , Malievskiy Victor , Scott Christiaan , Keltsev Vladimir , Terreri Maria Teresa , Viola Diego Oscar , Xavier Ricardo M , Fernandes Taciana A Pedrosa , Velázquez María del Rocío Maldonado , Henrickson Michael , Clark Michael B , Bensley Karen A , Li Xiaoming , Lo Kim Hung , Leu Jocelyn H , Hsu Chyi-Hung , Hsia Elizabeth C , Xu Zhenhua , Martini Alberto , Lovell Daniel J ,   for the Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organisation (PRINTO), Appenzeller Simone , Oliveira Sheila , Silva Clóvis Arthur , Levy Deborah , Navarrete Carmen , Aviel Yonatan Butbul , Uziel Yosef , Alexeeva Ekaterina , Chasnyk Vladimir , Spivakovsky Yury , Gottlieb Beth , Rabinovich Egla , Zeft Andrew , Griffin Thomas , De Ranieri Deirdre , Carrasco Ruy
Published: January 2021

Objectives

To assess efficacy, pharmacokinetics (PK) and safety of intravenous (i.v.) golimumab in patients with polyarticular-course JIA (pc-JIA).

Methods

Children aged 2 to <18 years with active pc-JIA despite MTX therapy for ≥2 months received 80 mg/m2 golimumab at weeks 0, 4, then every 8 weeks through week 52 plus MTX weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUCss) over an 8-week dosing interval at weeks 28 and 52, respectively. JIA ACR response and safety were also assessed.

Results

In total, 127 children were treated with i.v. golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70% and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUCss were 0.40 µg/ml and 399 µg ⋅ day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUCss were consistent across age categories and comparable to i.v. golimumab dosed 2 mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including one death due to septic shock.

Conclusion

Body surface area-based dosing of i.v. golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA.

ClinicalTrials.gov number NCT02277444
Metastatic Melanoma With Features of Desmoplastic Melanoma in a Patient With Primary Cutaneous Superficial Spreading Melanoma With Epithelioid Features
Authors: Modi Mitul B. , Moshiri Ata S. , Klein Walter M. , Karakousis Giorgos , Shafique Khurram , Xu Xiaowei
Published: January 2021

The synchronous incidence of 2 different subtypes of melanoma is very rare. Desmoplastic melanoma (DM) can be a diagnostic challenge because of its frequent appearance as a dermal banal spindle cell proliferation. We present a case of a 30-year-old man who developed an irregular, purple, tender plaque measuring 2.5 cm on the right pretibial region. Wide excision of the right leg lesion showed superficial spreading melanoma with epithelioid cells and no spindle cell component. Sentinel lymph node (SLN) biopsy showed an atypical melanocytic proliferation involving one inguinal lymph node with subcapsular and intraparenchymal components. There were spindled tumor cells in lymph node capsule with hyperchromatic nuclei, which were nested within desmoplastic stroma, and were S100- and SOX10-positive and MART1- and HMB-45 negative; in addition to epithelioid tumor cells, which were S100-, SOX10-, and MART1-positive. Multiple discontinuous foci, subcapsular atypical melanocytes, and extracapsular extension helped in excluding capsular nevus. These findings were consistent with DM. Herein, we present an unusual case of primary cutaneous superficial spreading melanoma of the right leg with a predominantly epithelioid morphology that developed metastases to the SLN. The metastasis exhibited divergent differentiation, including both epithelioid morphology identical to the primary, but with additional features of DM that were nonoverlapping with the primary lesion.
IFFS strategy 2017 and beyond
Authors: Kennedy Richard
Published: January 2021

Fertility rates are falling internationally. In contrast, infertility is one of the most common conditions in the world leading to moderate or severe disability. The International Federation of Fertility Societies, as a global actor in reproductive health, has as its core mission increasing knowledge in this field, particularly in developing and middle income countries. This commentary sets out the IFFS strategy for delivering this mission and its interdependencies with other organizations with a similar focus and the World Health Organisation.
Recurrent Choroidal Detachment in Peritoneal Dialysis Patient With Hypervolemia and Dilutional Hypoalbuminemia
Authors: Taechameekietichai Teerajet , Suvannachart Pukkapol , Kittiskulnam Piyawan , Chansangpetch Sunee
Published: January 2021

The following presents a case of recurrent choroidal detachments (CD) correlated with changes in serum albumin levels and the patient’s fluid status. A 71-year-old female patient presented with a 4-day history of blurry vision in her left eye. Pertinent medical history included end-stage renal disease treated with continuous ambulatory peritoneal dialysis. Previously, the patient’s left eye was treated for primary angle-closure glaucoma by trabeculectomy. While this resulted in a low baseline intraocular pressure (IOP) of 2 to 7 mm Hg, the patient never developed any hypotony-related complications for the past 6 years. After examination, CD was diagnosed and treated with transscleral surgical drainage. The patient further developed 2 additional episodes of CD in the same eye. All episodes were also associated with bilateral pitting edema, weight gain, and hypoalbuminemia. Thus, the patient was recommended to take a protein supplement and limit her fluid intake. In addition, the dialysis treatment regimen was altered to achieve greater daily fluid removal. After 12 weeks, there was no recurrent episode of CD, and the patient was clinically stable with a final visual acuity of 20/30 and an IOP of 3 mm Hg. The serum albumin levels improved slightly, and there were no signs of hypervolemia. In this case of recurrent CD, a possible association between the development of CD, hypoalbuminemia, and hypervolemia in patients with end-stage renal disease is demonstrated. Clinicians should be aware that these systemic factors can be tied with recurrent CDs, especially among patients with a low baseline IOP.
A Case of Secondary Pigment Dispersion Following Laser to Cosmetically Lighten the Irises
Authors: Ning Brigid , Baboolal Sandika , Gizzi Corrado , Nolan Winifred
Published: January 2021

Eye color is the latest physical attribute to be subject to alteration for cosmetic reasons. We report a rare case of bilateral secondary pigment dispersion following laser burns to the irises for cosmetic purposes. This case demonstrates a case of secondary pigment dispersion not previously reported in the literature to the best of our knowledge.
Chemosensing in enteroendocrine cells: mechanisms and therapeutic opportunities
Authors: Yang Ming , Reimann Frank , Gribble Fiona M.
Published: January 2021

Purpose of review

Enteroendocrine cells (EECs) are scattered chemosensory cells in the intestinal epithelium that release hormones with a wide range of actions on intestinal function, food intake and glucose homeostasis. The mechanisms by which gut hormones are secreted postprandially, or altered by antidiabetic agents and surgical interventions are of considerable interest for future therapeutic development.

Recent findings

EECs are electrically excitable and express a repertoire of G-protein coupled receptors that sense nutrient and nonnutrient stimuli, coupled to intracellular Ca2+ and cyclic adenosine monophosphate. Our knowledge of EEC function, previously developed using mouse models, has recently been extended to human cells. Gut hormone release in humans is enhanced by bariatric surgery, as well as by some antidiabetic agents including sodium-coupled glucose transporter inhibitors and metformin.

EECs are important potential therapeutic targets. A better understanding of their chemosensory mechanisms will enhance the development of new therapeutic strategies to treat metabolic and gastrointestinal diseases.
The Scope of Hospital-Based Simulation
Authors: Gilbert Marie , Waxman KT , Gilbert Gregory E. , Congenie Kari
Published: January 2021

BACKGROUND

Healthcare simulation has expanded dramatically; however, little is known about the scope of simulation in acute care hospitals.

METHODS

A descriptive, cross-sectional online survey was used. Participants included nurse executives from acute care hospitals in California.

RESULTS

Most organizations (96%) used simulation primarily for education, 37% used simulation for health system integration and systems testing, 30% used it for error investigation, 15% used it for research, and 15% used it for patient/family education.

CONCLUSIONS

Organizations have a substantial opportunity to increase the scope of simulation beyond education to include systems integration, clinical systems testing, and other translational simulation activities. This targeted focus on patient safety and quality will allow hospitals to improve financial performance and maximize scarce resources.
Hospital Nurses’ Willingness to Respond in a Disaster
Authors: Choi Hye Seung , Lee Jong-Eun
Published: January 2021

OBJECTIVE

This study examined the factors associated with nurses' willingness to respond in a disaster.

BACKGROUND

Nurses are key personnel in case of disasters, and therefore, understanding factors associated with willingness to respond is important.

METHODS

Questionnaires were distributed to 200 nurses recruited from 2 public hospitals in Seoul, Korea. Data were collected in January and February 2018 and 181 responses were analyzed.

RESULTS

Factors predicting willingness to respond in a disaster among public hospital nurses were level of education, self-efficacy, and disaster management competency.

CONCLUSIONS

Providing well-organized disaster preparedness and response training programs would enhance nurses' level of knowledge about disasters. In addition, training could improve nurses' self-efficacy and disaster management competency, which should enhance willingness to respond in a disaster.
Distinct Patterns of Emergence of SARS-CoV-2 Spike Variants including N501Y in Clinical Samples in Columbus Ohio
Authors: Tu Huolin , Avenarius Matthew R , Kubatko Laura , Hunt Matthew , Pan Xiaokang , Ru Peng , Garee Jason , Thomas Keelie , Mohler Peter , Pancholi Preeti , Jones Dan
Published: January 2021

Following the worldwide emergence of the p.Asp614Gly shift in the Spike (S) gene of SARS-CoV-2, there have been few recurring pathogenic shifts occurring during 2020, as assessed by genomic sequencing. This situation has evolved in the last several months with the emergence of several distinct variants (first identified in the United Kingdom and South Africa) that manifest multiple changes in the S gene, particularly p.Asn501Tyr (N501Y), that likely have clinical impact. We report here the emergence in Columbus, Ohio in December 2020 of two novel SARS-CoV-2 clade 20G variants. One variant, that has become the predominant virus found in nasopharyngeal swabs in the December 2020-January 2021 period, harbors S p.Gln677His (Q677H), affecting a consensus QTQTN domain near the S1/S2 furin cleavage site, nucleocapsid (N) p.Asp377Tyr (D377Y) and membrane glycoprotein (M) p.Ala85Ser (A85S) mutations, with additional S mutations in subsets. The other variant present in two samples, contains S N501Y, which is a marker of the UK-B.1.1.7 (clade 20I/501Y.V1) strain, but lacks all other mutations from that virus. The Ohio variant is from a different clade and shares multiple mutations with the clade 20G viruses circulating in the area prior to December 2020. These two SARS-CoV-2 viruses, which we show are also present and evolving currently in several other parts of North America, add to the diversity of S gene shifts occurring worldwide. These and other shifts in this period of the pandemic support multiple independent acquisition of functionally significant and potentially complementing mutations affecting the S QTQTN site (Q675H or Q677H) and certain receptor binding domain mutations (e.g., E484K and N501Y).
Spatio-temporal evolution of urban thermal environment and its driving factors: Case study of Nanjing, China
Authors: Menghan Zhang , Suocheng Dong , Hao Cheng , Fujia Li
Published: January 2021

In recent years, with the rapid urbanization, the urban underlying surface has changed dramatically. Various urban eco-environmental problems have emerged in the world, among which the urban heat island effect has become one of the most obvious urban eco-environmental problems. In this study, Nanjing, China is chosen as the study area. Based on the Landsat8 remote sensing image data in Nanjing from 2014 to 2018, the land surface temperature is retrieved, the spatiotemporal variation track and characteristics of the thermal environment pattern are systematically depicted, and its driving factors are revealed. The results show that: in the past five years, the spatial pattern of heat field in Nanjing has changed from scattered distribution in the periphery of the city to centralized in the center of the city, and the heat island intensity has increased year by year. The changes of administrative divisions, the layout of transportation trunk lines, the transfer of industrial centers, and ecological construction projects are important driving factors for the evolution of land surface thermal environment pattern of these regions. The research results will provide scientific and technological support for similar cities with typical heat island effect in the world to make urban planning and development decisions, and to govern and improve urban ecological environment.
Puberty timing and sex-specific trajectories of systolic blood pressure: a prospective cohort study
Authors: O’Neill Kate N , Bell Joshua A , Smith George Davey , Tilling Kate , Kearney Patricia M , O’Keeffe Linda M
Published: January 2021

Background

Sex differences in systolic blood pressure (SBP) emerge during adolescence but the role of puberty is not well understood. We examined sex-specific changes in SBP preceding and following puberty and examined the impact of puberty timing on SBP trajectories in females and males.

Methods

Trajectories of SBP before and after puberty and by timing of puberty in females and males in a contemporary English birth cohort study were analysed. Repeated measures of height from age 5 to 20 years were used to identify puberty timing (age at peak height velocity). SBP was measured on ten occasions from 3 to 24 years (N participants=4,062, repeated SBP measures=29,172). Analyses were preformed using linear spline multilevel models based on time before and after puberty and were adjusted for parental factors and early childhood factors including BMI gain from age one up to 9 years.

Results

Mean age at peak height velocity was 11.7 years (standard deviation (SD) =0.8) for females and 13.6 years (SD=0.9) for males. In adjusted models, females and males had similar SBP at age 3. Males had faster rates of increase in SBP before puberty leading to 10.19mmHg (95% CI: 6.80, 13.57) higher mean SBP at puberty which remained similar at 24 years [mean difference; 11.43mmHg (95% CI: 7.22, 15.63)]. Puberty timing was associated with small transient differences in SBP trajectories post-puberty in both sexes and small differences at 24 years in females only.

Conclusion

A large proportion of the higher SBP observed in males compared to females in early adulthood is accrued before puberty. Prevention of high SBP in adult males may therefore benefit from a life course approach starting from before puberty. Interventions targeting puberty timing are unlikely to greatly influence SBP in females and males in early adulthood.
An interplay of NOX1-derived ROS and oxygen determines the spermatogonial stem cell self-renewal efficiency under hypoxia
Authors: Morimoto Hiroko , Yamamoto Takuya , Miyazaki Takehiro , Ogonuki Narumi , Ogura Atsuo , Tanaka Takashi , Kanatsu-Shinohara Mito , Yabe-Nishimura Chihiro , Zhang Hongliang , Pommier Yves , Trumpp Andreas , Shinohara Takashi
Published: January 2021

Reactive oxygen species (ROS) produced by NADPH1 oxidase 1 (NOX1) are thought to drive spermatogonial stem cell (SSC) self-renewal through feed-forward production of ROS by the ROS-BCL6B-NOX1 pathway. Here we report the critical role of oxygen on ROS-induced self-renewal. Cultured SSCs proliferated poorly and lacked BCL6B expression under hypoxia despite increase in mitochondria-derived ROS. Due to lack of ROS amplification under hypoxia, NOX1-derived ROS were significantly reduced, andNox1-deficient SSCs proliferated poorly under hypoxia but normally under normoxia. NOX1-derived ROS also influenced hypoxic response in vivo becauseNox1-deficient undifferentiated spermatogonia showed significantly reduced expression of HIF1A, a master transcription factor for hypoxic response. Hypoxia-induced poor proliferation occurred despite activation of MYC and suppression of CDKN1A by HIF1A, whose deficiency exacerbated self-renewal efficiency. Impaired proliferation ofNox1- orHif1a-deficient SSCs under hypoxia was rescued byCdkn1adepletion. Consistent with these observations,Cdkn1a-deficient SSCs proliferated actively only under hypoxia but not under normoxia. On the other hand, chemical suppression of mitochondria-derived ROS orTop1mtmitochondria-specific topoisomerase deficiency did not influence SSC fate, suggesting that NOX1-derived ROS play a more important role in SSCs than mitochondria-derived ROS. These results underscore the importance of ROS origin and oxygen tension on SSC self-renewal.
ATDC binds to KEAP1 to drive NRF2-mediated tumorigenesis and chemoresistance in pancreatic cancer
Authors: Purohit Vinee , Wang Lidong , Yang Huibin , Li Jiufeng , Ney Gina M. , Gumkowski Erica R. , Vaidya Akash J. , Wang Annie , Bhardwaj Amit , Zhao Ende , Dolgalev Igor , Zamperone Andrea , Abel Ethan V. , Magliano Marina Pasca Di , Crawford Howard C. , Diolaiti Daniel , Papagiannakopoulos Thales Y. , Lyssiotis Costas A. , Simeone Diane M.
Published: January 2021

Pancreatic ductal adenocarcinoma is a lethal disease characterized by late diagnosis, propensity for early metastasis and resistance to chemotherapy. Little is known about the mechanisms that drive innate therapeutic resistance in pancreatic cancer. The ataxia-telangiectasia group D-associated gene (ATDC) is overexpressed in pancreatic cancer and promotes tumor growth and metastasis. Our study reveals that increased ATDC levels protect cancer cells from reactive oxygen species (ROS) via stabilization of nuclear factor erythroid 2-related factor 2 (NRF2). Mechanistically, ATDC binds to Kelch-like ECH-associated protein 1 (KEAP1), the principal regulator of NRF2 degradation, and thereby prevents degradation of NRF2 resulting in activation of a NRF2-dependent transcriptional program, reduced intracellular ROS and enhanced chemoresistance. Our findings define a novel role of ATDC in regulating redox balance and chemotherapeutic resistance by modulating NRF2 activity.
Esc2 orchestrates substrate-specific sumoylation by acting as a SUMO E2 cofactor in genome maintenance
Authors: Li Shibai , Bonner Jacob N. , Wan Bingbing , So Stephen , Mutchler Ashley , Gonzalez Leticia , Xue Xiaoyu , Zhao Xiaolan
Published: January 2021

SUMO modification regulates diverse cellular processes by targeting hundreds of proteins. However, the limited number of sumoylation enzymes raises the question of how such a large number of substrates are efficiently modified. Specifically, how genome maintenance factors are dynamically sumoylated at DNA replication and repair sites to modulate their functions is poorly understood. Here, we demonstrate a role for the conserved yeast Esc2 protein in this process by acting as a SUMO E2 cofactor. Esc2 is required for genome stability and binds to Holliday junctions and replication fork structures. Our targeted screen found that Esc2 promotes the sumoylation of a Holliday junction dissolution complex and specific replisome proteins. Esc2 does not elicit these effects via stable interactions with substrates or their common SUMO E3. Rather, we show that a SUMO-like domain of Esc2 stimulates sumoylation by exploiting a noncovalent SUMO binding site on the E2 enzyme. This role of Esc2 in sumoylation is required for Holliday junction clearance and genome stability. Our findings thus suggest that Esc2 acts as a SUMO E2 cofactor at distinct DNA structures to promote the sumoylation of specific substrates and genome maintenance.
Acute perturbation strategies in interrogating RNA polymerase II elongation factor function in gene expression
Authors: Zheng Bin , Aoi Yuki , Shah Avani P. , Iwanaszko Marta , Das Siddhartha , Rendleman Emily J. , Zha Didi , Khan Nabiha , Smith Edwin R. , Shilatifard Ali
Published: January 2021

The regulation of gene expression catalyzed by RNA polymerase II (Pol II) requires a host of accessory factors to ensure cell growth, differentiation, and survival under environmental stress. Here, using the auxin-inducible degradation (AID) system to study transcriptional activities of the bromodomain and extraterminal domain (BET) and super elongation complex (SEC) families, we found that the CDK9-containing BRD4 complex is required for the release of Pol II from promoter-proximal pausing for most genes, while the CDK9-containing SEC is required for activated transcription in the heat shock response. By using both the proteolysis targeting chimera (PROTAC) dBET6 and the AID system, we found that dBET6 treatment results in two major effects: increased pausing due to BRD4 loss, and reduced enhancer activity attributable to BRD2 loss. In the heat shock response, while auxin-mediated depletion of the AFF4 subunit of the SEC has a more severe defect than AFF1 depletion, simultaneous depletion of AFF1 and AFF4 leads to a stronger attenuation of the heat shock response, similar to treatment with the SEC inhibitor KL-1, suggesting a possible redundancy among SEC family members. This study highlights the usefulness of orthogonal acute depletion/inhibition strategies to identify distinct and redundant biological functions among Pol II elongation factor paralogs.
Contamination detection in sequencing studies using the mitochondrial phylogeny
Authors: Weissensteiner Hansi , Forer Lukas , Fendt Liane , Kheirkhah Azin , Salas Antonio , Kronenberg Florian , Schoenherr Sebastian
Published: January 2021

Within-species contamination is a major issue in sequencing studies, especially for mitochondrial studies. Contamination can be detected by analyzing the nuclear genome or by inspecting polymorphic sites in the mitochondrial genome (mtDNA). Existing methods using the nuclear genome are computationally expensive, and no appropriate tool for detecting sample contamination in large-scale mtDNA data sets is available. Here we present haplocheck, a tool that requires only the mtDNA to detect contamination in both targeted mitochondrial and whole-genome sequencing studies. Our in silico simulations and amplicon mixture experiments indicate that haplocheck detects mtDNA contamination accurately and is independent of the phylogenetic distance within a sample mixture. By applying haplocheck to The 1000 Genomes Project Consortium data, we further evaluate the application of haplocheck as a fast proxy tool for nDNA-based contamination detection using the mtDNA and identify the mitochondrial copy number within a mixture as a critical component for the overall accuracy. The haplocheck tool is available both as a command-line tool and as a cloud web service producing interactive reports that facilitates the navigation through the phylogeny of contaminated samples.
Accurate and efficient detection of gene fusions from RNA sequencing data
Authors: Uhrig Sebastian , Ellermann Julia , Walther Tatjana , Burkhardt Pauline , Fröhlich Martina , Hutter Barbara , Toprak Umut H. , Neumann Olaf , Stenzinger Albrecht , Scholl Claudia , Fröhling Stefan , Brors Benedikt
Published: January 2021

The identification of gene fusions from RNA sequencing data is a routine task in cancer research and precision oncology. However, despite the availability of many computational tools, fusion detection remains challenging. Existing methods suffer from poor prediction accuracy and are computationally demanding. We developed Arriba, a novel fusion detection algorithm with high sensitivity and short runtime. When applied to a large collection of published pancreatic cancer samples (n= 803), Arriba identified a variety of driver fusions, many of which affected druggable proteins, including ALK, BRAF, FGFR2, NRG1, NTRK1, NTRK3, RET, and ROS1. The fusions were significantly associated withKRASwild-type tumors and involved proteins stimulating the MAPK signaling pathway, suggesting that they substitute for activating mutations inKRAS. In addition, we confirmed the transforming potential of two novel fusions,RRBP1-RAF1andRASGRP1-ATP1A1, in cellular assays. These results show Arriba's utility in both basic cancer research and clinical translation.
Allele-specific alternative splicing and its functional genetic variants in human tissues
Authors: Amoah Kofi , Hsiao Yun-Hua Esther , Bahn Jae Hoon , Sun Yiwei , Burghard Christina , Tan Boon Xin , Yang Ei-Wen , Xiao Xinshu
Published: January 2021

Alternative splicing is an RNA processing mechanism that affects most genes in human, contributing to disease mechanisms and phenotypic diversity. The regulation of splicing involves an intricate network ofcis-regulatory elements andtrans-acting factors. Due to their high sequence specificity,cis-regulation of splicing can be altered by genetic variants, significantly affecting splicing outcomes. Recently, multiple methods have been applied to understanding the regulatory effects of genetic variants on splicing. However, it is still challenging to go beyond apparent association to pinpoint functional variants. To fill in this gap, we utilized large-scale data sets of the Genotype-Tissue Expression (GTEx) project to study genetically modulated alternative splicing (GMAS) via identification of allele-specific splicing events. We demonstrate that GMAS events are shared across tissues and individuals more often than expected by chance, consistent with their genetically driven nature. Moreover, although the allelic bias of GMAS exons varies across samples, the degree of variation is similar across tissues versus individuals. Thus, genetic background drives the GMAS pattern to a similar degree as tissue-specific splicing mechanisms. Leveraging the genetically driven nature of GMAS, we developed a new method to predict functional splicing-altering variants, built upon a genotype-phenotype concordance model across samples. Complemented by experimental validations, this method predicted >1000 functional variants, many of which may alter RNA-protein interactions. Lastly, 72% of GMAS-associated SNPs were in linkage disequilibrium with GWAS-reported SNPs, and such association was enriched in tissues of relevance for specific traits/diseases. Our study enables a comprehensive view of genetically driven splicing variations in human tissues.
Blood-derived mitochondrial DNA copy number is associated with gene expression across multiple tissues and is predictive for incident neurodegenerative disease
Authors: Yang Stephanie Y. , Castellani Christina A. , Longchamps Ryan J. , Pillalamarri Vamsee K. , O'Rourke Brian , Guallar Eliseo , Arking Dan E.
Published: January 2021

Mitochondrial DNA copy number (mtDNA-CN) is a proxy for mitochondrial function and is associated with aging-related diseases. However, it is unclear how mtDNA-CN measured in blood can reflect diseases that primarily manifest in other tissues. Using the Genotype-Tissue Expression Project, we interrogated relationships between mtDNA-CN measured in whole blood and gene expression from whole blood and 47 additional tissues in 419 individuals. mtDNA-CN was significantly associated with expression of 700 genes in whole blood, including nuclear genes required for mtDNA replication. Significant enrichment was observed for splicing and ubiquitin-mediated proteolysis pathways, as well as target genes for the mitochondrial transcription factor NRF1. In nonblood tissues, there were more significantly associated genes than expected in 30 tissues, suggesting that global gene expression in those tissues is correlated with blood-derived mtDNA-CN. Neurodegenerative disease pathways were significantly associated in multiple tissues, and in an independent data set, the UK Biobank, we observed that higher mtDNA-CN was significantly associated with lower rates of both prevalent (OR = 0.89, CI = 0.83; 0.96) and incident neurodegenerative disease (HR = 0.95, 95% CI = 0.91;0.98). The observation that mtDNA-CN measured in blood is associated with gene expression in other tissues suggests that blood-derived mtDNA-CN can reflect metabolic health across multiple tissues. Identification of key pathways including splicing, RNA binding, and catalysis reinforces the importance of mitochondria in maintaining cellular homeostasis. Finally, validation of the role of mtDNA CN in neurodegenerative disease in a large independent cohort study solidifies the link between blood-derived mtDNA-CN, altered gene expression in multiple tissues, and aging-related disease.
Temporal proximity to the elicitation of curiosity is key for enhancing memory for incidental information
Authors: Murphy Charlotte , Dehmelt Vera , Yonelinas Andrew P. , Ranganath Charan , Gruber Matthias J.
Published: January 2021

Curiosity states benefit memory for target information, but also incidental information presented during curiosity states. However, it is not known whether incidental curiosity-enhanced memory depends on when incidental information during curiosity states is encountered. Here, participants incidentally encoded unrelated face images at different time points while they anticipated answers to trivia questions. Across two experiments, we found memory enhancements for unrelated faces presented during high-curiosity compared with low-curiosity states, but only when presented shortly after a trivia question. This suggests processes associated with the elicitation of curiosity—but not sustained anticipation or the satisfaction of curiosity—enhance memory for incidental information.
The stabilizing effects of economic policies in Spain in times of COVID-19
Authors: Boscá J.E. , Doménech R. , Ferri J. , García J.R. , Ulloa C.
Published: January 2021

Purpose

This paper aims to analyse the stabilizing macroeconomic effects of economic policies during the COVID-19 crisis in Spain.

Design/methodology/approach

The contribution of the structural shocks that explain the behaviour of the main macroeconomic aggregates during 2020 are estimated, and the effects of economic policies are simulated using a dynamic stochastic general equilibrium (DSGE) model estimated for the Spanish economy.

Findings

The results highlight the importance of supply and demand shocks in explaining the COVID-19 crisis. The annual fall in gross domestic product (GDP) moderates at least by 7.6 points in the most intense period of the crisis, thanks to these stabilizing policies. Finally, the potential effects of Next Generation EU in the Spanish economy are estimated. Assuming that Spain may receive from the EU between 1.5 and 2.25 percentage points (pp) of GDP, activity could increase to between 2 and 3 pp in 2024.

Originality/value

To the best of the authors’ knowledge, the exercises and findings are original. All these results show the usefulness of a DSGE model, such as the estimated rational expectation model for Spain, as a practical tool for the applied economic analysis, the macroeconomic assessment of economic policies and the understanding of the Spanish economy.
Self-efficacy in cooking and consuming fruits and vegetables among Brazilian university students: the relationship with sociodemographic characteristics
Authors: de Borba Thaís Peiter , da Silva Manoella Vieira , Jomori Manuela Mika , Bernardo Greyce Luci , Fernandes Ana Carolina , Proença Rossana Pacheco da Costa , Rockenbach Gabriele , Uggioni Paula Lazzarin
Published: January 2021

Purpose

Self-efficacy in cooking and consuming fruits and vegetables is one of the dimensions that compose cooking skills. This cross-sectional study aimed to assess the self-efficacy of Brazilian university students in cooking and consuming fruits and vegetables and examine the relationship of self-efficacy with sociodemographic and lifestyle characteristics.

Design/methodology/approach

Data were collected through an online questionnaire, which was culturally adapted and validated for the studied population. Questions about self-efficacy for using basic cooking techniques (SECT), self-efficacy for using fruits, vegetables, and seasonings (SEFVS) and produce consumption self-efficacy (SEPC) were rated on a five-point Likert scale. Differences in median self-efficacy score between groups were compared using the Mann–Whitney U test or the Kruskal–Wallis test followed by the Mann–Whitney U test.

Findings

766 subjects participated in the study. The mean age was 21 ± 5.6 years, most respondents were female (60%), reported to know how to cook (72%), and lived with parents and/or grandparents (45%). The median SECT and SEFVS scores were 3.55, and the median SEPC score was 3.33. Female students, individuals aged more than 25 years, and students who did not live with their parents or grandparents had higher (p < 0.005) self-efficacy scores. Low SECT, SEFVS and SEPC scores were associated with having less than one hour a day to cook (p = 0.023, 0.01, and 0.002, respectively) and not knowing how to cook (p < 0.001). There was no relationship of median self-efficacy scores with source of knowledge about cooking skills or parental education.

Originality/value

The results of this study can guide interventions and public policies aimed at health promotion in the university setting.
Leadership without “the led”: a case study of the South Wales Valleys
Authors: Harding Nancy
Published: January 2021

Purpose

This paper aims to disrupt assumptions about leadership by arguing those who are ostensibly “followers” may be utterly insouciant towards the existence of people categorised as “leaders”. It contributes to anti-leadership theories.

Design/methodology/approach

This article uses an immersive, highly reflexive methodology to explore subjective meanings of leadership at community levels ostensibly governed by local government leaders. It uses a case study of the South Wales Valleys, one of the hubs of the Industrial Revolution in the 19th century but now economically deprived.

Findings

Through drawing on their rich and complex history, the author shows how in these communities there is a culture of neo-communitarianism that is anti-leadership and suspicious of attempts to establish hierarchies of superior over inferior. The author explores the complex webs of meaning through which ancient experiences reverberate like dead metaphors, informing contemporary understandings without conscious awareness of such a heritage. This is a history in which “leaders” betrayed or oppressed and exploited the population, which in response turned against hierarchies and evolved practices of self-government that continue today, invisible and unrepresentable within the wider culture.

Research limitations/implications

The study draws on contemporary feminist research methods that emphasise subjectivity, flux and change. These are often not understood by readers not accustomed to stepping out of a positivist onto-epistemological frame.

Practical implications

The paper challenges the universalising tendencies of leadership theories that assume a shapeless mass; “followers” await the advent of a leader before they can become agentive.

Social implications

The paper offers insights into a day-to-day world that is rarely explored.

Originality/value

The article demonstrates how emerging forms of qualitative research give insights into communities that undermine dominant, universalising theories of leadership, followership and government more generally.
Impact of consumer innovativeness on really new product adoption
Authors: Seyed Esfahani Mona , Reynolds Nina
Published: January 2021

Purpose

The purpose of this study is to explore consumer innovativeness as a personality trait and addresses the hedonic, social, cognitive and functional motivational elements that lie behind consumer innovativeness. It explores the weak relationship between consumer innovativeness and really new product (novel innovation) adoption and challenges the classic relationship between consumer learning, attitude and intention.

Design/methodology/approach

This study adopts a quantitative approach, gathering survey data via an institutional online platform. A total of 300 participants were recruited. Participants were directed to a website presenting the information of the product with the inclusion of 2D and 3D images and an avatar. For data analysis, CFA and structural equation modelling (SEM) were used.

Findings

Results indicate a positive impact of attitude on comprehension and intention. In addition, hedonic innovativeness positively impacts customer's attitude, whereas there is a negative relationship between social innovativeness and attitude. Motivational elements of innovation, with the exception of hedonic motivation, positively influence purchase intention.

Research limitations/implications

The main limitation of the study lies in the measurement of purchase intention, as actual purchases cannot be assessed as the products are not yet available. The findings encourage marketers to target innovators first, ideally innovators motivated by hedonic needs.

Practical implications

The findings encourage marketers to target innovators first, perhaps for a long-term, innovators motivated by hedonic needs, as they are the ones who change their attitude positively towards novel innovation when presented in an aesthetically pleasant manner.

Originality/value

This study challenges the classic theories identifying the link between comprehension, attitude and purchase intention within the field of innovation. The findings indicate that while interacting with really new products, comprehension does not necessarily lead to attitude and intention but attitude does positively influence both intention and comprehension.
Epidemiological study of terbinafine‐resistant dermatophytes isolated from Japanese patients
Authors: Hiruma Junichiro , Noguchi Hiromitsu , Hase Midori , Tokuhisa Yumie , Shimizu Tatsuya , Ogawa Takasuke , Hiruma Masataro , Harada Kazutoshi , Kano Rui
Published: January 2021

Terbinafine (TRF) has been used in the treatment of fungal infections for more than 20 years. Recently, TRF‐resistant Trichophyton interdigitale and T. rubrum strains have been isolated from human patients worldwide. However, an epidemiological study of TRF‐resistant strains in Japanese patients has not been investigated. In the present study, antifungal susceptibility testing was performed on clinical isolates from Japanese patients to assess TRF‐resistance patterns of T. interdigitale and T. rubrum strains. We also sequenced the squalene epoxidase (SQLE) encoding gene of TRF‐resistant T. rubrum strains. Two hundred and ten T. interdigitale and T. rubrum clinical isolates were obtained from 210 human cases of tinea pedis, tinea corporis, tinea unguium, tinea cruris, tinea manuum, tinea faciei and tinea capitis in Tokyo, Saitama, Chiba, Hyogo and Kumamoto, Japan, in 2020. Five T. rubrum isolates (N74, N79, N99, H30 and K2) grew on Sabouraud's dextrose agar (SDA) containing 1 mg/L of TRF. All five strains exhibited TRF minimum inhibitory concentrations (MICs) ≥32 mg/L but remained susceptible to azoles. We determined SQLE sequences in these TRF‐resistant T. rubrum strains and found that all strains harbored missense mutations (L393F) in the SQLE‐encoding gene.
Evolutionary constraints on tree size and above‐ground biomass in tropical dry forests
Authors: de Aguiar‐Campos Natalia , Coelho de Souza Fernanda , Maia Vinícius Andrade , Rezende Vanessa Leite , de Souza Cleber Rodrigo , de Paula Gabriela Gomes Pires , Santos Paola Ferreira , de Oliveira Menino Gisele Cristina , da Silva Wilder Bento , dos Santos Rubens Manoel
Published: January 2021

The extent (or lack) of phylogenetic signal for key ecological traits reveals the role of evolutionary processes on present‐day ecosystem function and hints on future ecological trends under climate change scenarios. This approach has been applied to South American tropical moist forests, but not to the highly threatened seasonally dry tropical forests (SDTF), despite the acknowledgement of their unique evolutionary history. To fill this knowledge gap, we investigated the legacy of evolutionary processes on vital ecological characteristics among SDTF trees: regional dominance, tree size and soil preference.

We used tree community data on 313 plots of SDTF (12.52 ha) and locally collected soil data in central‐eastern Brazil. For each assessed trait (three for regional dominance, three for tree size and nine for soil preference), we investigated the legacy of evolution using two different approaches: calculating the extent of phylogenetic signal and comparing the fit of four different models of evolution.

Above‐ground woody biomass and tree size showed strong phylogenetic signal. Most of the SDTF biomass stock was concentrated on a few large‐sized and closely related tree genera. Among the soil preference variables, only phosphorus displayed significant, albeit weak, phylogenetic signal.

Synthesis. Our study is the first to show that evolutionary constraints related to tree size significantly determine regional biomass stocks of seasonally dry tropical forests (SDTF) in a few closely related tree lineages. This suggests that even isolated SDTF fragments with low taxonomic and phylogenetic diversity can play an important role in the global carbon cycle, storing disproportionally large amounts of carbon in trees that belong to high‐biomass lineages. Whether these lineages also share climate change‐induced mortality risk deserves future investigation, as they are largely responsible for the maintenance of regional SDTF biomass stocks.