bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurofilament light chain in drug development for amyotrophic lateral sclerosis: a critical appraisal
Authors: Benatar Michael , Wuu Joanne , Turner Martin R
Published: October 2022

Interest in amyotrophic lateral sclerosis (ALS) biomarkers has grown exponentially over the course of the last 25 years, with great hope that they might serve as tools to facilitate the development of meaningful therapies for this otherwise inexorably progressive and invariably fatal disease. Effective use of biomarkers, however, requires an understanding of what it means for them to be ‘fit-for-purpose’ as well as an appreciation of the nuances of the clinical context(s) in which they will be applied.

Neurofilament light chain (NfL) has emerged as a leading candidate with enormous potential to aid ALS therapy development; it is, however, also profoundly misunderstood. Within the conceptual framework of the BEST (Biomarkers, EndpointS, and other Tools) Resource, developed by the National Institutes of Health and the Food and Drug Administration in the USA, we consider the evidence supporting the use of NfL for a variety of purposes in different clinical contexts.

We conclude that: (i) it may serve as a susceptibility/risk biomarker in populations at elevated risk for ALS; (ii) it has value as a prognostic biomarker when measured early in the course of established disease, empowering stratification or dynamic randomization to amplify the signal-to-noise ratio of promising therapeutics; and (iii) there is sufficient evidence to support the use of a reduction in NfL in response to an experimental therapeutic as a pharmacodynamic biomarker that may aid in phase 2 trial go/no-go decisions. Moreover, the basis for expecting that a reduction in NfL is a reasonably likely surrogate end-point (i.e. reasonably likely to predict clinical benefit—which may be more than simply survival) is nuanced, and depends on when in the course of disease the experimental therapeutic is administered.
The top 10 most frequently involved genes in hereditary optic neuropathies in 2186 probands
Authors: Rocatcher Aude , Desquiret-Dumas Valérie , Charif Majida , Ferré Marc , Gohier Philippe , Mirebeau-Prunier Delphine , Verny Christophe , Milea Dan , Lenaers Guy ,   HON Collaborators Group, Vignal Catherine , Lamirel Cédric , Hage Rabih , Dollfus Hélène , Meunier Isabelle , Zanlonghi Xavier , Touitou Valérie , Lebranchu Pierre , Odent Sylvie , Tilikete Caroline Froment , Jeanjean Luc , Defoort-Dhellemmes Sabine , Drumare-Bouvet Isabelle , Smirnov Vasily , Vincent-Delorme Catherine , Biotti Damien , Varenne Fanny , Calvas Patrick , Chassaing Nicolas , Cohen Mickael , Orssaud Christophe , Mochel Fanny , Roubertie Agathe , Toutain Annick , Pollet-Villard Frédéric , Dupeyron Marie Noelle Bonnet , Boulicot Céline , Cochener Béatrice , Goldenberg Alice , Jacquemont Marie Line , Francannet Christine , Bonneau Dominique , Reynier Pascal , Amati-Bonneau Patrizia
Published: October 2022

Hereditary optic neuropathies are caused by the degeneration of retinal ganglion cells whose axons form the optic nerves, with a consistent genetic heterogeneity. As part of our diagnostic activity, we retrospectively evaluated the combination of Leber hereditary optic neuropathy mutations testing with the exon sequencing of 87 nuclear genes on 2186 patients referred for suspected hereditary optic neuropathies. The positive diagnosis rate in individuals referred for Leber hereditary optic neuropathy testing was 18% (199/1126 index cases), with 92% (184/199) carrying one of the three main pathogenic variants of mitochondrial DNA (m.11778G>A, 66.5%; m.3460G>A, 15% and m.14484T>C, 11%). The positive diagnosis rate in individuals referred for autosomal dominant or recessive optic neuropathies was 27% (451/1680 index cases), with 10 genes accounting together for 96% of this cohort. This represents an overall positive diagnostic rate of 30%. The identified top 10 nuclear genes included OPA1, WFS1, ACO2, SPG7, MFN2, AFG3L2, RTN4IP1, TMEM126A, NR2F1 and FDXR. Eleven additional genes, each accounting for less than 1% of cases, were identified in 17 individuals. Our results show that 10 major genes account for more than 96% of the cases diagnosed with our nuclear gene panel.
Imbalance of NRG1-ERBB2/3 signalling underlies altered myelination in Charcot–Marie–Tooth disease 4H
Authors: El-Bazzal Lara , Ghata Adeline , Estève Clothilde , Gadacha Jihane , Quintana Patrice , Castro Christel , Roeckel-Trévisiol Nathalie , Lembo Frédérique , Lenfant Nicolas , Mégarbané André , Borg Jean-Paul , Lévy Nicolas , Bartoli Marc , Poitelon Yannick , Roubertoux Pierre L , Delague Valérie , Bernard-Marissal Nathalie
Published: October 2022

Charcot–Marie–Tooth (CMT) disease is one of the most common inherited neurological disorders, affecting either axons from the motor and/or sensory neurons or Schwann cells of the peripheral nervous system (PNS) and caused by more than 100 genes. We previously identified mutations in FGD4 as responsible for CMT4H, an autosomal recessive demyelinating form of CMT disease. FGD4 encodes FRABIN, a GDP/GTP nucleotide exchange factor, particularly for the small GTPase Cdc42. Remarkably, nerves from patients with CMT4H display excessive redundant myelin figures called outfoldings that arise from focal hypermyelination, suggesting that FRABIN could play a role in the control of PNS myelination. To gain insights into the role of FGD4/FRABIN in Schwann cell myelination, we generated a knockout mouse model (Fgd4SC–/–), with conditional ablation of Fgd4 in Schwann cells. We show that the specific deletion of FRABIN in Schwann cells leads to aberrant myelination in vitro, in dorsal root ganglia neuron/Schwann cell co-cultures, as well as in vivo, in distal sciatic nerves from Fgd4SC–/– mice. We observed that those myelination defects are related to an upregulation of some interactors of the NRG1 type III/ERBB2/3 signalling pathway, which is known to ensure a proper level of myelination in the PNS. Based on a yeast two-hybrid screen, we identified SNX3 as a new partner of FRABIN, which is involved in the regulation of endocytic trafficking. Interestingly, we showed that the loss of FRABIN impairs endocytic trafficking, which may contribute to the defective NRG1 type III/ERBB2/3 signalling and myelination. Using RNA-Seq, in vitro, we identified new potential effectors of the deregulated pathways, such as ERBIN, RAB11FIP2 and MAF, thereby providing cues to understand how FRABIN contributes to proper ERBB2 trafficking or even myelin membrane addition through cholesterol synthesis. Finally, we showed that the re-establishment of proper levels of the NRG1 type III/ERBB2/3 pathway using niacin treatment reduces myelin outfoldings in nerves of CMT4H mice.

Overall, our work reveals a new role of FRABIN in the regulation of NRG1 type III/ERBB2/3 NRG1signalling and myelination and opens future therapeutic strategies based on the modulation of the NRG1 type III/ERBB2/3 pathway to reduce CMT4H pathology and more generally other demyelinating types of CMT disease.
TCL1A acts as a tumour suppressor by modulating gastric cancer autophagy via miR-181a-5p-TCL1A-Akt/mTOR-c-MYC loop
Authors: Hao Jialing , Mei Haitao , Luo Qingshan , Weng Junyong , Lu Jing , Liu Mingmin , Wen Yugang
Published: October 2022

Gastric cancer is the third most commonly cause of tumour-related death worldwide and one of the most prevalent malignancies in China. TCL1A, TCL1 family Akt coactivator A, can active Akt/mTOR pathway and regulate the autophagy. However, the action of TCL1A in gastric cancer is not well understood. The present study is investigating the mechanism of action of TCL1A in gastric cancer. TCL1A was lowly expressed in gastric cancer tissues. Subsequent experiments demonstrated that miR-181a-5p can regulate c-MYC through the TCL1A-Akt/mTOR pathway and c-MYC can in turn affect the expression of miR-181a-5p, thus confirming the existence of the miR-181a-5p-TCL1A-Akt/mTOR-c-MYC loop. Flow cytometric apoptosis assay and mRFP-eGFP-LC3 autophagy assay demonstrated that both miR-181a-5p and TCL1A can affect autophagy and apoptosis of gastric cancer cells through the loop. In vivo experiments confirmed that TCL1A can affect the proliferation of gastric cancer. These results illustrate that TCL1A can exert tumour suppressive effects and affect gastric cancer autophagy and progression via the miR-181a-5p-TCL1A-Akt/mTOR-c-MYC loop, which could be a potential therapeutic target for gastric cancer.
Neurovascular decoupling measured with quantitative susceptibility mapping is associated with cognitive decline in patients with type 2 diabetes
Authors: Ni Min-Hua , Li Ze-Yang , Sun Qian , Yu Ying , Yang Yang , Hu Bo , Ma Teng , Xie Hao , Li Si-Ning , Tao Lan-Qiu , Yuan Ding-Xin , Zhu Jun-Ling , Yan Lin-Feng , Cui Guang-Bin
Published: October 2022

Disturbance of neurovascular coupling (NVC) is suggested to be one potential mechanism in type 2 diabetes mellitus (T2DM) associated mild cognitive impairment (MCI). However, NVC evidence derived from functional magnetic resonance imaging ignores the relationship of neuronal activity with vascular injury. Twenty-seven T2DM patients without MCI and thirty healthy controls were prospectively enrolled. Brain regions with changed susceptibility detected by quantitative susceptibility mapping (QSM) were used as seeds for functional connectivity (FC) analysis. NVC coefficients were estimated using combined degree centrality (DC) with susceptibility or cerebral blood flow (CBF). Partial correlations between neuroimaging indicators and cognitive decline were investigated. In T2DM group, higher susceptibility values in right hippocampal gyrus (R.PHG) were found and were negatively correlated with Naming Ability of Montreal Cognitive Assessment. FC increased remarkably between R.PHG and right middle temporal gyrus (R.MTG), right calcarine gyrus (R.CAL). Both NVC coefficients (DC-QSM and DC-CBF) reduced in R.PHG and increased in R.MTG and R.CAL. Both NVC coefficients in R.PHG and R.MTG increased with the improvement of cognitive ability, especially for executive function. These demonstrated that QSM and DC-QSM coefficients can be promising biomarkers for early evaluation of cognitive decline in T2DM patients and help to better understand the mechanism of NVC.
Structural neuroplasticity in computer programming beginners
Authors: Hongo Takeshi , Yakou Takao , Yoshinaga Kenji , Kano Toshiharu , Miyazaki Michiko , Hanakawa Takashi
Published: October 2022

We examined the structural neuroplastic changes associated with the learning of computer programming in university students with no previous programming experience. They participated in a 15-week course (26 lessons) on the “Processing” computer programming language. We have conducted a longitudinal analysis of gray matter volume (GMV) in the magnetic resonance images obtained before and after learning computer programming. Significant neuroplastic changes appeared in the following 8 sites: the left frontal pole; the right frontal pole; the right medial frontal gyrus; the left cuneus; the left lateral cerebellum (posterior lobule and tuber); the medial cerebellum (uvula and tonsil); the right pallidum; and the left pallidum. The amount of change in the GMV of the right frontal pole correlated positively with the final product score. Furthermore, the amount of change in the GMV of the right medial frontal gyrus and the bilateral pallidum correlated positively with the test scores. Thus, the right frontal pole was presumably associated with the function of persistent attempts to accomplish tasks (goal achievement-related function). The right medial frontal gyrus and the bilateral pallidum were presumably related to deduction and reward functions, respectively. Therefore, multiple brain regions appear to be involved in programming learning through different functions.
Employers’ Speech-Based First Impressions of Cochlear Implant Users
Authors: Freeman Valerie
Published: October 2022

This study is part of a series on speech-based first impressions of prelingually deaf cochlear implant (CI) users with differing speech intelligibility. Hiring managers with typical hearing (TH) rated CI users and TH young adults on various personality traits and suitability as job applicants after hearing recorded speech samples. Similar to prior peer listeners, managers rated TH speakers more positively than highly intelligible CI users (CI-Hi), with less-intelligible CI users rated even more negatively. Managers for white-collar or high-communication jobs rated CI-Hi lower than did managers of blue-collar or low-communication jobs. Positive attitudes and experience with deafness improved ratings of CI users. While underlining the importance of intelligibility, these patterns also highlight the impact of listeners’ underlying attitudes on their initial judgments of CI users, which could affect deaf employment opportunities. The study calls for workplace education about hearing loss and deaf communication to improve deaf inclusion and employment rates.
European Society of Cardiology quality indicators for the prevention and management of cancer therapy-related cardiovascular toxicity in cancer treatment
Authors: Lee G A , Aktaa S , Baker E , Gale C P , Yaseen Israa F , Gulati G , Asteggiano R , Szmit S , Cohen-Solal A , Abdin A , Jurczak W , Garrido Lopez P , Sverdlov A L , Tocchetti C G , Barac A , Parrini I , Zamorano P , Iakobishvili Z , Pudil R , Badimon L , Kirby A M , Blaes A H , Farmakis D , Curigliano G , Stephens R , Lyon A R , Lopez-Fernandez T
Published: October 2022

Aims

To develop quality indicators (QIs) for the evaluation of the prevention and management of cancer therapy-related cardiovascular toxicity.

Methods and results

We followed the European Society of Cardiology (ESC) methodology for QI development which comprises (i) identifying the key domains of care for the prevention and management of cancer therapy-related cardiovascular toxicity in patients on cancer treatment, (ii) performing a systematic review of the literature to develop candidate QIs, and (iii) selecting of the final set of QIs using a modified Delphi process. Work was undertaken in parallel with the writing of the 2022 ESC Guidelines on Cardio-Oncology and in collaboration with the European Haematology Association, the European Society for Therapeutic Radiology and Oncology and the International Cardio-Oncology Society. In total, 5 main and 9 secondary QIs were selected across five domains of care: (i) Structural framework, (ii) Baseline cardiovascular risk assessment, (iii) Cancer therapy related cardiovascular toxicity, (iv) Predictors of outcomes, and (v) Monitoring of cardiovascular complications during cancer therapy.

Conclusion

We present the ESC Cardio-Oncology QIs with their development process and provide an overview of the scientific rationale for their selection. These indicators are aimed at quantifying and improving the adherence to guideline-recommended clinical practice and improving patient outcomes.
Women Leaving the Playpen: the Emancipating Role of Female Suffrage
Authors: Slotwinski Michaela , Stutzer Alois
Published: October 2022

We study how political empowerment affected women’s emancipation as reflected in their life choices. The staggered introduction of female suffrage in Swiss states allows us to exploit the variation in the age at which women were exposed to the right to vote to estimate the differences in life choices between women who were socialised in a world with politically empowered women and those who were socialised before. Our empirical findings document that early exposure to female suffrage increased female labour force participation, weakened marital bonds and motivated human capital investment.
General practitioners’ views and experiences of communicating with older people about cancer screening: a qualitative study
Authors: Smith Jenna , Dodd Rachael H , Wallis Katharine A , Naganathan Vasi , Cvejic Erin , Jansen Jesse , McCaffery Kirsten J
Published: October 2022

Background

Older adults should be supported to make informed decisions about cancer screening. However, it is unknown how general practitioners (GPs) in Australia communicate about cancer screening with older people.

Aim

To investigate GPs’ views and experiences of communicating about cancer screening (breast, cervical, prostate, and bowel) with older people (≥70 years).

Design and setting

Qualitative, semi-structured interviews, Australia.

Method

Interviews were conducted with GPs practising in Australia (n = 28), recruited through practice-based research networks, primary health networks, social media, and email invitation. Interviews were audio-recorded and analysed thematically using Framework Analysis.

Results

Findings across GPs were organized into 3 themes: (i) varied motivation to initiate cancer screening discussions; some GPs reported that they only initiated screening within recommended ages (<75 years), others described initiating discussions beyond recommended ages, and some experienced older patient-initiated discussions; (ii) GPs described the role they played in providing screening information, whereby detailed discussions about the benefits/risks of prostate screening were more likely than other nationally funded screening types (breast, cervical, and bowel); however, some GPs had limited knowledge of recommendations and found it challenging to explain why screening recommendations have upper ages; (iii) GPs reported providing tailored advice and discussion based on personal patient preferences, overall health/function, risk of cancer, and previous screening.

Conclusions

Strategies to support conversations between GPs and older people about the potential benefits and harms of screening in older age and rationale for upper age limits to screening programmes may be helpful. Further research in this area is needed.
Factors influencing the prioritization of vaccines by policymakers in low- and middle-income countries: a scoping review
Authors: Guillaume Dominique , Meyer Diane , Waheed Dur-e-Nayab , Schlieff Meike , Muralidharan Kirthini , Chou Victoria B , Limaye Rupali
Published: October 2022

Vaccination decision making in low- and middle-income countries (LMICs) has become increasingly complex, particularly in the context of numerous competing health challenges. LMICs have to make difficult choices on which vaccines to prioritize for introduction while considering a wide range of factors such as disease burden, vaccine impact, vaccine characteristics, financing and health care infrastructures, whilst adapting to each country’s specific contexts. Our scoping review reviewed the factors that influence decision-making among policymakers for the introduction of new vaccines in LMICs. We identified the specific data points that are factored into the decision-making process for new vaccine introduction, whilst also documenting whether there have been any changes in decision-making criteria in new vaccine introduction over the last two decades. A comprehensive database search was conducted using a search strategy consisting of key terms and Medical Subject Headings (MeSH) phrases related to policy, decision-making, vaccine introduction, immunization programmes and LMICs. Articles were screened following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 843 articles were identified, with 34 articles retained after abstract screening, full-text screening and grading with the mixed methods appraisal tool (MMAT). The Burchett framework for new vaccine introduction was used to identify indicators for vaccine-decision making and guided data extraction. Articles in our study represented a diverse range of perspectives and methodologies. Across articles, the importance of the disease, which included disease burden, costs of disease and political prioritization, coupled with economic factors related to vaccine price, affordability and financing were the most common criteria considered for new vaccine introduction. Our review identified two additional criteria in the decision-making process for vaccine introduction that were not included in the Burchett framework: communication and sociocultural considerations. Data from this review can support informed decision-making for vaccine introduction amongst policymakers and stakeholders in LMICs.
Reversing lysosome-ribosome circuit dysregulation mitigates C9FTD/ALS neurodegeneration and behaviors
Authors: Ma Li , Liang Chen , Wang Jing , Chang Qing , Wang Yuan , Zhang Wei , Du Yuanning , Sadan Jotham , Chen Jian-Fu
Published: October 2022

G4C2 repeat expansion in C9orf72 causes the most common familial frontotemporal dementia and amyotrophic lateral sclerosis (C9FTD/ALS). The pathogenesis includes haploinsufficiency of C9orf72, which forms a protein complex with Smcr8, as well as G4C2 repeat-induced gain of function including toxic dipeptide repeats (DPRs). The key in vivo disease-driving mechanisms and how loss- and gain-of-function interplay remain poorly understood. Here, we identified dysregulation of a lysosome-ribosome biogenesis circuit as an early and key disease mechanism using a physiologically relevant mouse model with combined loss- and gain-of-function across the aging process. C9orf72 deficiency exacerbates FTD/ALS-like pathologies and behaviors in C9ORF72 bacterial artificial chromosome (C9-BAC) mice with G4C2 repeats under endogenous regulatory elements from patients. Single nucleus RNA sequencing (snRNA-seq) and bulk RNA-seq revealed that C9orf72 depletion disrupts lysosomes in neurons and leads to transcriptional dysregulation of ribosomal protein genes, which are likely due to the proteotoxic stress response and resemble ribosomopathy defects. Importantly, ectopic expression of C9orf72 or its partner Smcr8 in C9FTD/ALS mutant mice promotes lysosomal functions and restores ribosome biogenesis gene transcription, resulting in the mitigation of DPR accumulation, neurodegeneration as well as FTD/ALS-like motor and cognitive behaviors. Therefore, we conclude that loss- and gain-of-function crosstalk in C9FTD/ALS converges on neuronal dysregulation of a lysosome-ribosome biogenesis circuit leading to proteotoxicity, neurodegeneration and behavioral defects.
AKLHL403’ UTR splice-altering variant causes milder NEM8, an under-appreciated disease mechanism
Authors: Dofash Lein N H , Monahan Gavin V , Servián-Morilla Emilia , Rivas Eloy , Faiz Fathimath , Sullivan Patricia , Oates Emily , Clayton Joshua , Taylor Rhonda L , Davis Mark R , Beilharz Traude , Laing Nigel G , Cabrera-Serrano Macarena , Ravenscroft Gianina
Published: October 2022

Nemaline myopathy 8 (NEM8) is typically a severe autosomal recessive disorder associated with variants in the kelch-like family member 40 gene (KLHL40). Common features include fetal akinesia, fractures, contractures, dysphagia, respiratory failure and neonatal death. Here, we describe a 26-year-old man with relatively mild NEM8. He presented with hypotonia and bilateral femur fractures at birth, later developing bilateral Achilles’ contractures, scoliosis, and elbow and knee contractures. He had walking difficulties throughout childhood and became wheelchair bound from age 13 after prolonged immobilization. Muscle magnetic resonance imaging at age 13 indicated prominent fat replacement in his pelvic girdle, posterior compartments of thighs and vastus intermedius. Muscle biopsy revealed nemaline bodies and intranuclear rods. RNA sequencing and western blotting of patient skeletal muscle indicated significant reduction in KLHL40 mRNA and protein, respectively. Using gene panel screening, exome sequencing and RNA sequencing, we identified compound heterozygous variants in KLHL40; a truncating 10.9 kb deletion in trans with a likely pathogenic variant (c.*152G > T) in the 3′ untranslated region (UTR). Computational tools SpliceAI and Introme predicted the c.*152G > T variant created a cryptic donor splice site. RNA-seq and in vitro analyses indicated that the c.*152G > T variant induces multiple de novo splicing events that likely provoke nonsense mediated decay of KLHL40 mRNA explaining the loss of mRNA expression and protein abundance in the patient. Analysis of 3’ UTR variants in ClinVar suggests variants that introduce aberrant 3’ UTR splicing may be underrecognized in Mendelian disease. We encourage consideration of this mechanism during variant curation.
Total calcium, dairy foods and risk of colorectal cancer: a prospective cohort study of younger US women
Authors: Kim Hanseul , Hur Jinhee , Wu Kana , Song Mingyang , Wang Molin , Smith-Warner Stephanie A , Zhang Xuehong , Giovannucci Edward L
Published: October 2022

Background

Although colorectal cancer (CRC) incidence is declining among adults aged ≥65 years, CRC incidence in younger adults has been rising. The protective role of calcium in colorectal carcinogenesis has been well established, but evidence is lacking on whether the association varies by age at diagnosis. We investigated the association between total calcium intake and risk of overall CRC and CRC before age 55 years.

Methods

In the Nurses’ Health Study II (1991–2015), 94 205 women aged 25–42 years at baseline were included in the analysis. Diet was assessed every 4 years through validated food frequency questionnaires. Multivariable-adjusted hazard ratios (HRs) and 95% CIs for CRC were estimated using the Cox proportional hazards model.

Results

We documented 349 incident CRC cases during 2 202 604 person-years of follow-up. Higher total calcium intake was associated with a reduced risk of CRC. Compared with those with <750 mg/day of total calcium intake, the HR of CRC was 0.61 (95% CI, 0.38–0.97) for those who consumed ≥1500 mg/day (P for trend = 0.01). The HR per 300 mg/day increase was 0.85 (95% CI, 0.76–0.95). There was a suggestive inverse association between total calcium intake and CRC before age 55 years (HR per 300 mg/day increase, 0.87; 95% CI, 0.75–1.00), suggesting the importance of calcium intake in the younger population.

Conclusions

In a cohort of younger women, which reflects the birth cohorts, time periods and age ranges paralleling the recent rise in CRC, higher calcium intake was associated with a decreased risk of CRC.
RBP Image Database: A resource for the systematic characterization of the subcellular distribution properties of human RNA binding proteins
Authors: Benoit Bouvrette Louis Philip , Wang Xiaofeng , Boulais Jonathan , Kong Jian , Syed Easin Uddin , Blue Steven M , Zhan Lijun , Olson Sara , Stanton Rebecca , Wei Xintao , Yee Brian , Van Nostrand Eric L , Fu Xiang-Dong , Burge Christopher B , Graveley Brenton R , Yeo Gene W , Lécuyer Eric
Published: October 2022

RNA binding proteins (RBPs) are central regulators of gene expression implicated in all facets of RNA metabolism. As such, they play key roles in cellular physiology and disease etiology. Since different steps of post-transcriptional gene expression tend to occur in specific regions of the cell, including nuclear or cytoplasmic locations, defining the subcellular distribution properties of RBPs is an important step in assessing their potential functions. Here, we present the RBP Image Database, a resource that details the subcellular localization features of 301 RBPs in the human HepG2 and HeLa cell lines, based on the results of systematic immuno-fluorescence studies conducted using a highly validated collection of RBP antibodies and a panel of 12 markers for specific organelles and subcellular structures. The unique features of the RBP Image Database include: (i) hosting of comprehensive representative images for each RBP-marker pair, with ∼250,000 microscopy images; (ii) a manually curated controlled vocabulary of annotation terms detailing the localization features of each factor; and (iii) a user-friendly interface allowing the rapid querying of the data by target or annotation. The RBP Image Database is freely available at https://rnabiology.ircm.qc.ca/RBPImage/.
Post-transplant diabetes mellitus and renal cell cancer after renal transplantation
Authors: Porrini Esteban , Montero Nuria , Díaz Juan Manuel , Lauzurrica Ricardo , Rodríguez Juana Oramas , Torres Irene Silva , Moreso Francesc , Cruzado Josep M , Ruiz Rocío Benítez , Vilaró Meritxel Ibernon , Lima Maria Xixiang Molina , Ramchand Simran Khemlani , Ruiz Juan Carlos , Gainza de los Rios Francisco , Alvarez Carla Rodríguez , Guindo María del Carmen de Gracia , Macías Manuel , Vela David Bonet , Osuna Antonio , Bayés-Genís Beatriz , Sanchez Cristina Aleman , Ruiz María del Carmen , Rodríguez Ana Elena Rodríguez , Rollán Rosa Domínguez , Rinne Federico González , Sosa Alejandro Jiménez , Mallén Patricia Delgado , Rinne Ana González , Miranda Domingo Marrero , Torres Armando
Published: October 2022

Background

Diabetes is a risk factor for cancer in the general population. However, few data are available on the association between post-transplant diabetes mellitus (PTDM) and cancer after transplantation.

Methods

We analyzed this issue in a Spanish cohort of patients without diabetes before transplantation. PTDM was diagnosed with consensus criteria at 12 months after transplantation and 12 months before the diagnosis of cancer. The association between PTDM and cancer (overall and specific types) was evaluated with regression analysis.

Results

During a follow-up of 12 years (interquartile range 8–14), 85 cases of 603 developed cancer (829/100 000/year) and 164 (27%) PTDM. The most frequent cancers were renal cell cancer (RCC) n = 15, 146/cases/100 000/year), lung (n = 12, 117/cases/100 000/year), colon (n = 9, 88/cases/100 000/year) and prostate (n = 9, 88/cases/100 000/year). In logistic regression, PTDM was not associated with cancer. Eight of the 164 patients with PTDM (4.9%) vs 7 of the 439 without PTDM developed RCC (1.6%) (P = .027). In multivariate analysis, PTDM was independently associated with RCC [odds ratio (OR) 2.92, confidence interval (CI) 1.03–8.27], adjusting for smoking (OR 4.020, 95% CI 1.34–12.02) and other covariates. PTDM was not associated with other types of cancer.

Conclusions

Patients with PTDM must be considered a population at risk for RCC and accordingly, the subject of active surveillance.
Towards a better understanding of arterial calcification disease progression in CKD: investigation of early pathological alterations
Authors: Van den Bergh Geoffrey , Opdebeeck Britt , Neutel Cédric , Guns Pieter-Jan , De Meyer Guido , D'Haese Patrick , Verhulst Anja
Published: October 2022

Background

Cardiovascular disease remains the leading cause of death in chronic kidney disease (CKD) patients, especially in those undergoing dialysis and kidney transplant surgery. CKD patients are at high risk of developing arterial media calcifications (AMC) and arterial stiffness. We hypothesized that investigation of disease progression at an early stage could provide novel insights in understanding AMC etiology.

Methods

An adenine diet was administered to male Wistar rats to induce AMC. Rats were sacrificed after 2, 4 and 8 weeks. AMC was measured by assessment of aortic calcium and visualized using histology. Arterial stiffness was measured in vivo by ultrasound and ex vivo by applying cyclic stretch of physiological magnitude on isolated arterial segments, allowing us to generate the corresponding pressure–diameter loops. Further, ex vivo arterial reactivity was assessed in organ baths at 2 and 4 weeks to investigate early alterations in biomechanics/cellular functionality.

Results

CKD rats showed a time-dependent increase in aortic calcium which was confirmed on histology. Accordingly, ex vivo arterial stiffness progressively worsened. Pressure–diameter loops showed a gradual loss of arterial compliance in CKD rats. Additionally, viscoelastic properties of isolated arterial segments were altered in CKD rats. Furthermore, after 2 and 4 weeks of adenine treatment, a progressive loss in basal, nitric oxide (NO) levels was observed, which was linked to an increased vessel tonus and translates into an increasing viscous modulus.

Conclusions

Our observations indicate that AMC-related vascular alterations develop early after CKD induction prior to media calcifications being present. Preventive action, related to restoration of NO bioavailability, might combat AMC development.
Mental health and wellbeing of border security personnel: scoping review
Authors: Brooks S K , Greenberg N
Published: October 2022

Background

Whilst the wellbeing of law enforcement personnel has been widely researched, border security personnel as a discrete group appear to be far less discussed, despite their roles frequently exposing them to potentially traumatic and challenging events such as contact with criminals or witnessing personal tragedies due to trafficking or smuggling.

Aims

This scoping review aimed to explore existing literature to better understand the mental health of border security personnel and the factors affecting their wellbeing.

Methods

Four electronic databases and grey literature were systematically searched for studies relevant to the review’s aims. Following the extraction of relevant data from each study, thematic analysis was used to synthesize findings.

Results

Thirteen studies included relevant data and were included in the review, identifying stressors including poor management; fatigue; negative public attitudes; inadequate staffing levels, resources, and training; poor opportunities for promotion; low pay; work overload; dangerous working environments; and work-related moral dilemmas.

Conclusions

The review found that there has been little academic attention paid to border security personnel as a specific branch of law enforcement. Many of the stressors identified in this review are those also reported by law enforcement generally, although negative attitudes from the public and exposure to moral dilemmas appear to be more relevant for border security staff. Directly addressing work-related stress (e.g. by fostering a supportive organizational culture, addressing mental health stigma, and encouraging help-seeking) may be useful in enhancing the resilience of border security personnel.
A Patient With Mycobacteremia Due to Two Different Nontuberculous Mycobacteria
Authors: Hill Eddie , Wooten Darcy
Published: October 2022

Disseminated nontuberculous mycobacterial infections are most common in patients with severe immunosuppression, such as people with human immunodeficiency virus (HIV) and low CD4+ T-cell counts. In this report, we present a rare case of a person with HIV who was hospitalized for mycobacteremia due to 2 different nontuberculous mycobacteria. We also provide a comprehensive summary of published case reports describing nontuberculous mycobacterial coinfections.
Timbre, Technology and Hybridation in the Music of Michaël Levinas
Authors: Campbell Edward
Published: October 2022

This chapter discusses some key aspects of the compositional development of Michaël Levinas with reference to a significant number of his compositions, including the operas Les Nègres and La Métamorphose. Levinas studied composition with Messiaen alongside Grisey and Murail, and he was a founding member of the group L’Itinéraire in 1973. While he describes his work as having progressed in parallel with his spectral colleagues, he came to recognize his distinctive contribution to the aesthetic over time. Levinas’s composition is marked by his idiosyncratic treatment of timbre, his use of technology including loudspeakers, and his interest in hybridizing musical sounds through the placement of sound bodies in vibration with one another. Achieved at first in more rudimentary ways, Levinas developed this with great sophistication at IRCAM in the 1990s to produce what he terms “the new mixity.” The chapter concludes with an exposition of the expressive potential of Levinas’s approach to sound.
Apollodorus the Mythographer, Bibliotheca
Authors: Trzaskoma Stephen M.
Published: October 2022

This chapter treats Apollodorus the Mythographer (regularly referred to as Ps.-Apollodorus), the probably 1st-century ce writer who produced the Bibliotheca (Library), the most complete—although not perfectly so—and finest work of systematizing mythographer to survive from antiquity. A summary account is provided of our knowledge of the otherwise unknown author, evidence for his date, the nature of his work, his literary and intellectual ambitions, and the nature of the narrative, which gives a broad overview of Greek myth arranged chronologically from primordial times to the generation after the Trojan War. Attention is given as well to the question of Apollodorus’s sources, which has dominated modern scholarship. An account of the state of the text and how it was passed down is sketched.
Cornutus, Survey of the Traditions of Greek Theology
Authors: Ramelli Ilaria L.E.
Published: October 2022

This chapter concentrates on the Roman Stoic Cornutus’s mythological allegoresis in his handbook of Greek theology. For each divinity, from Ouranos to Hades, Cornutus provides an allegorical-etymological interpretation of its names and epithets, attributes, aspects of its myths and rituals, and so on. Physical allegory (Zeus represents the ether; Hera, the air, etc.) is prevalent, although there are also examples of ethical and historical exegeses. Special attention is paid to the programmatic assertion that “the ancients were not people of no account, but they were also able to understand the nature of the cosmos and had the ability to philosophise on it by means of symbols and enigmata” (35). The ancients were nothing less than philosophers, since they were endowed with the understanding of the cosmos, of what exists. What they expressed allegorically are philosophical truths. Philosophical allegoresis interprets their expressions and finds philosophical tenets therein. The chapter then shows how Cornutus was strongly influenced by Chrysippus, Apollodorus, and Crates, and how Seneca, who was no allegorizer, probably polemicized with Cornutus. Finally, it demonstrates that the Stoic allegorists of myths Cornutus and Chaeremon influenced the greatest allegorist of biblical myths, Origen.
The Mythographus Homericus
Authors: Pagès Joan
Published: October 2022

Mythographus Homericus (MH) is a faute de mieux denomination for a now lost handbook of mythology from the Imperial period containing a collection of historiae fabulares, that is, summaries of myths, under Homeric lemmata. Fragments on papyri from the 1st century onward demonstrate the existence of the MH. Even though this work has not been preserved as such in medieval manuscripts, many historiae presumably derived from it survives as a substantial part of the minor scholia to the Iliad and the Odyssey, the so-called D-scholia and V-scholia respectively. The MH as we know it today was a hybrid work, a hypomnema or commentary on Homer based on abstracts of mythical narratives that could be considered a handbook of mythology as well. The reasons for the gathering of all this material as Homeric scholarship are not easy to elucidate: in some cases, they enable a better understanding of the Homeric context, but they are very often a sort of glossae explaining characters, epithets, place names, aetia and foundations.
Palaephatus, Unbelievable Tales
Authors: Koning Hugo H.
Published: October 2022

The ancient mythographer Palaephatus’s Unbelievable Tales is a collection of well-known myths and rationalizing explanations of them. The chapter offers an analysis of a) the philosophical notions underlying Palaephatus’s project, mostly articulated in his proem, b) the rigid structure of his entries, and c) the methods he employs to reconstruct the historical truth behind the myths under investigation, all hinging on plausibility and narrative logic—it is human misunderstanding that is at the core of all mythopoesis. Although Palaephatus’s historicizing approach perhaps seems simplistic and arbitrary, it is at the same time also systematic, coherent, and consistent. Palaephatus thus occupies a unique place in the history of mythography and the exegesis of myth. References to modern scholarship provide the status quaestionis; some long-held notions are, however, significantly qualified.
Pausanias, Description of Greece
Authors: Hutton William
Published: October 2022

Pausanias’s Description of Greece, an eyewitness account of the cities and sanctuaries of the Greek mainland in the second century ce, is one of our richest sources for Greek myth. Although not written as a compendium of myth, Pausanias’s work always includes information about the mythological traditions associated with the places he visits. Most of this information comes from literary sources, both primary sources and compendia, but Pausanias also includes the testimony of local informants whom he encountered on his travels, and much of this local material is unattested in other sources. Whether his sources are literary, epigraphic, or oral, Pausanias presents himself as an energetic and discerning researcher on mythical matters. He considers early epic, especially the poems of Homer, as the most genuine source, approaching later sources with varying degrees of skepticism. He tends to favor rationalized versions of heroic sagas and shows a general distaste for divine myths that involve supernatural occurrences or unethical behavior on the part of the gods. He admits, however, that even incredible stories can have valid allegorical significance.
Tragic Mythography
Authors: Meccariello Chiara
Published: October 2022

This chapter surveys the intersections of Greek tragedy and mythography in antiquity. The first section focuses on passages and aspects of extant tragedies that betray the influence of mythography. The second deals with the production and use of mythography in the ancient study of tragedy, taking into account specialized works, introductory and interpretive material, and plot summaries. Finally, the third section examines the presence of tragedies as sources in the extant mythographical production. This survey suggests that the last two decades of the 5th century bce constitute a crucial period in what we may call “coevolution” of tragedy and mythography, as evidenced both by the density of mythographical patterns in the late plays of Euripides and by the emergence of myth-related research on tragedy between the 5th and 4th centuries bce.
Catasterisms
Authors: Zucker Arnaud
Published: October 2022

This chapter focuses on both the myths related to the constellations and the Hellenistic and Roman literary collections that catalogue and tell the origin of the celestial figures. This type of story, diffused throughout the literature since the classical period, is in the Hellenistic period (with Eratosthenes) organized in a true genre that conflates mythological content and astronomical data, and spreads widely in the Latin tradition. The labels “catasterism” and “catasterization” for this kind of scholarly literature refer to a cultural procedure (identifying the stars with heroic figures) and a narrative episode (i.e. the transfer of a hero or a meaningful object into the heavenly vault). The meaning and the context of the astral promotion of heroic figures are distinct from metamorphosis, apotheosis, or heroic death. These specific hybrid narratives try to link experience of the world and heritage stories and to turn diverse pictures, sometimes borrowed from other cultures, into a Greek synthetic general scheme. They reveal the function of the myth as a cultural catalyst, merging, in a cultural compromise, naturalistic observations, scholarly data, rational demands, and imagination. This chapter also emphasizes the originality and consistency of the astromythical program developed in antiquity and stresses the impact of astronomical knowledge in the shaping of traditional myths and innovative custom-made variants.
Mythography in the Latin West
Authors: Garstad Benjamin
Published: October 2022

In the Middle Ages in western Europe mythography was intended to set out in clear narrative terms and explain the body of myth that might only be alluded to in the corpus of Classical Latin literature that was still read throughout this period. It might have had the further intention of refuting the error of pagan belief about the gods and rendering myth innocuous by subjecting its unseemly tales to interpretation, especially through allegory. Much of the substance and method of medieval mythography was based on the seminal work of Fulgentius and Isidore of Seville, who wrote at the close of the classical epoch and the opening of the Middle Ages. The work of mythography was done in larger encyclopedias, histories, and commentaries, but there were also specialist treatises, most notably, the books of the three Vatican Mythographers and Conrad of Mure’s Fabularius. Heroic myths were also recounted, as well as thoroughly adapted and modified, in the popular literature of the period, perhaps most prominently in Benoît de Sainte Maure’s French poem Le Roman de Troie and its Latin prose translation by Guido delle Colonne.
Imperial Mythography
Authors: Delattre Charles
Published: October 2022

This chapter aims to describe what is specifically imperial in imperial mythography, in comparison with what can be reconstructed of Hellenistic mythographic practices. The sheer number of documents (papyri, complete texts) from the imperial era is a huge change and modifies our knowledge and even definition of mythography. The study focuses on the diversity of mythographic practices, and characterizes them as a specific mode of understanding, listing, and conveying information. Mythographic texts of the imperial time can be read as a kind of secondary literature, as summaries of or commentaries on a literary work, but they are also a way to organize and combine different sources into a common textual production that will be accessed in different forms. The study acknowledges that we cannot dismiss the proximity of mythography to other literary practices. In this respect, mythography is almost coextensive with cultured literacy. As a consequence, we can get access to some aspects of the social importance of mythography in the imperial elite circles. Mythography not as written text but as oral statement happens everywhere in elite circles, where erudition is not only a matter of taste but is also a way to gain social prestige. Some mythographic texts can be conceived as tools; others, as a reflection of a social rivalry embedded in mythological erudition.
Mythography in Latin
Authors: Smith R. Scott
Published: October 2022

This chapter provides a survey of the various ways that Greek mythographical information was transmitted in Latin. The first section offers an overview of the surviving collections devoted almost entirely to mythographical material, the Fabulae and the second book of De Astronomia, both attributed to someone named Hyginus, as well as the collection of mostly star myths embedded in the so-called Germanicus scholia. The second half of the chapter provides a review of the mythographical material found in the surviving exegetical traditions for major Roman poets, Vergil, Statius, and the Ovidian Narrationes, all of which was transmitted in Latin to match the target text of study.
A study of the agallamh tradition: two Munster agallaimh (dialogue songs) collected by James Goodman
Authors: Uí Dhonnabháin Miriam
Published: October 2022

This chapter examines two sung agallaimh or dialogue songs, called ‘Seaghanín Aorach’ and ‘William O’Reilly’, collected by James Goodman in Munster in the mid-nineteenth century. It considers the genre of the agallamh in cross-cultural contexts, its considerable longevity across more than eight centuries in Ireland, the particular interest in the genre displayed by James Goodman’s nineteenth-century collection, and the ways in which sung agallaimh can be distinguished from other, associated forms. Ultimately, the agallamh is shown to be descended from an ancient tradition, but one which was still a part of the everyday culture of the people of Munster in the nineteenth century.