bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear reassembly defects after mitosis trigger apoptotic and p53-dependent safeguard mechanisms in Drosophila
Authors: Li Jingjing , Jordana Laia , Mehsen Haytham , Wang Xinyue , Archambault Vincent
Published: August 2024

In animals, mitosis involves the breakdown of the nuclear envelope and the sorting of individualized, condensed chromosomes. During mitotic exit, emerging nuclei reassemble a nuclear envelope around a single mass of interconnecting chromosomes. The molecular mechanisms of nuclear reassembly are incompletely understood. Moreover, the cellular and physiological consequences of defects in this process are largely unexplored. Here, we have characterized a mechanism essential for nuclear reassembly in Drosophila. We show that Ankle2 promotes the PP2A-dependent recruitment of BAF and Lamin at reassembling nuclei, and that failures in this mechanism result in severe nuclear defects after mitosis. We then took advantage of perturbations in this mechanism to investigate the physiological responses to nuclear reassembly defects during tissue development in vivo. Partial depletion of Ankle2, BAF, or Lamin in imaginal wing discs results in wing development defects accompanied by apoptosis. We found that blocking apoptosis strongly enhances developmental defects. Blocking p53 does not prevent apoptosis but enhances defects due to the loss of a cell cycle checkpoint. Our results suggest that apoptotic and p53-dependent responses play a crucial role in safeguarding tissue development in response to sporadic nuclear reassembly defects.
GetGenome: Overcoming inequalities in access to genomics technology
Authors: Canham James , Win Joe ,   GetGenome Network, Kamoun Sophien
Published: August 2024

Although genomics has become integral to life science research, inequitable access to genomics technology remains prevalent. GetGenome, a non-profit organization, aims to overcome this by providing equitable access to genomics technology and training.
MAGICAL: A multi-class classifier to predict synthetic lethal and viable interactions using protein-protein interaction network
Authors: Dey Anubha , Mudunuri Suresh , Kiran Manjari
Published: August 2024

Synthetic lethality (SL) and synthetic viability (SV) are commonly studied genetic interactions in the targeted therapy approach in cancer. In SL, inhibiting either of the genes does not affect the cancer cell survival, but inhibiting both leads to a lethal phenotype. In SV, inhibiting the vulnerable gene makes the cancer cell sick; inhibiting the partner gene rescues and promotes cell viability. Many low and high-throughput experimental approaches have been employed to identify SLs and SVs, but they are time-consuming and expensive. The computational tools for SL prediction involve statistical and machine-learning approaches. Almost all machine learning tools are binary classifiers and involve only identifying SL pairs. Most importantly, there are limited properties known that best describe and discriminate SL from SV. We developed MAGICAL (Multi-class Approach for Genetic Interaction in Cancer via Algorithm Learning), a multi-class random forest based machine learning model for genetic interaction prediction. Network properties of protein derived from physical protein-protein interactions are used as features to classify SL and SV. The model results in an accuracy of ~80% for the training dataset (CGIdb, BioGRID, and SynLethDB) and performs well on DepMap and other experimentally derived reported datasets. Amongst all the network properties, the shortest path, average neighbor2, average betweenness, average triangle, and adhesion have significant discriminatory power. MAGICAL is the first multi-class model to identify discriminatory features of synthetic lethal and viable interactions. MAGICAL can predict SL and SV interactions with better accuracy and precision than any existing binary classifier.
Regression convolutional neural network models implicate peripheral immune regulatory variants in the predisposition to Alzheimer’s disease
Authors: Ramamurthy Easwaran , Agarwal Snigdha , Toong Noelle , Sestili Heather , Kaplow Irene M. , Chen Ziheng , Phan BaDoi , Pfenning Andreas R.
Published: August 2024

Alzheimer’s disease (AD) involves aggregation of amyloid β and tau, neuron loss, cognitive decline, and neuroinflammatory responses. Both resident microglia and peripheral immune cells have been associated with the immune component of AD. However, the relative contribution of resident and peripheral immune cell types to AD predisposition has not been thoroughly explored due to their similarity in gene expression and function. To study the effects of AD-associated variants on cis-regulatory elements, we train convolutional neural network (CNN) regression models that link genome sequence to cell type-specific levels of open chromatin, a proxy for regulatory element activity. We then use in silico mutagenesis of regulatory sequences to predict the relative impact of candidate variants across these cell types. We develop and apply criteria for evaluating our models and refine our models using massively parallel reporter assay (MPRA) data. Our models identify multiple AD-associated variants with a greater predicted impact in peripheral cells relative to microglia or neurons. Our results support their use as models to study the effects of AD-associated variants and even suggest that peripheral immune cells themselves may mediate a component of AD predisposition. We make our library of CNN models and predictions available as a resource for the community to study immune and neurological disorders.
Benchmarking the negatives: Effect of negative data generation on the classification of miRNA-mRNA interactions
Authors: Cohen-Davidi Efrat , Veksler-Lublinsky Isana
Published: August 2024

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally. In animals, this regulation is achieved via base-pairing with partially complementary sequences on mainly 3’ UTR region of messenger RNAs (mRNAs). Computational approaches that predict miRNA target interactions (MTIs) facilitate the process of narrowing down potential targets for experimental validation. The availability of new datasets of high-throughput, direct MTIs has led to the development of machine learning (ML) based methods for MTI prediction. To train an ML algorithm, it is beneficial to provide entries from all class labels (i.e., positive and negative). Currently, no high-throughput assays exist for capturing negative examples. Therefore, current ML approaches must rely on either artificially generated or inferred negative examples deduced from experimentally identified positive miRNA-target datasets. Moreover, the lack of uniform standards for generating such data leads to biased results and hampers comparisons between studies. In this comprehensive study, we collected methods for generating negative data for animal miRNA–target interactions and investigated their impact on the classification of true human MTIs. Our study relies on training ML models on a fixed positive dataset in combination with different negative datasets and evaluating their intra- and cross-dataset performance. As a result, we were able to examine each method independently and evaluate ML models’ sensitivity to the methodologies utilized in negative data generation. To achieve a deep understanding of the performance results, we analyzed unique features that distinguish between datasets. In addition, we examined whether one-class classification models that utilize solely positive interactions for training are suitable for the task of MTI classification. We demonstrate the importance of negative data in MTI classification, analyze specific methodological characteristics that differentiate negative datasets, and highlight the challenge of ML models generalizing interaction rules from training to testing sets derived from different approaches. This study provides valuable insights into the computational prediction of MTIs that can be further used to establish standards in the field.
Modelling the water supply-demand relationship under climate change in the Buffalo River catchment, South Africa
Authors: Dlamini Nosipho , Senzanje Aidan , Mabhaudhi Tafadzwanashe
Published: August 2024

Climate change strains the global water supplies’ capability to meet demands, especially in regions like South Africa, where resources are already scarce. The interconnectedness of water, energy, and food (WEF) exacerbates this challenge, amplifying the impact of climate change on water resource management across these sectors. Thus, in strengthening the long-term resilience and reliability of water resources, a necessity in South Africa, research on climate change and the WEF nexus is needed for water resource planning and development. Employing the WEF nexus approach, we applied the Climate Land-Use Energy and Water Strategies (CLEWS) modelling framework to assess climate change impacts on the water supply-demand relationship, considering the domestic, agriculture (irrigation) and energy generation sectors, and adopting the Buffalo River catchment, KwaZulu-Natal, South Africa, as a case study. A threefold approach was utilized: (1) water supplies and demands and the total unmet demands were quantified; (2) the percentages of water demands covered per sector were derived; and (3) the reliability of the water system to meet each sector’s water demands was computed. The findings projected slight decreases (2%) in the Buffalo River catchment’s total water demands towards the end of the 21st century, mainly due to changes in land suitability for agriculture. While the water system is projected to be reliable for highly populated municipalities (demand coverage index > 70%; reliability index ≥ 20%), it is unreliable for sparsely populated and agriculturally intensive municipalities (demand coverage index ≤ 12%; reliability index = 0%). Such unreliability will strain agricultural production as more than 70% of irrigation water demands come from these municipalities. Nexus-smart water allocation and capacity development plans are recommended to manage these challenges and ensure a just and sustainable water supply-demand relationship in light of climate change.
VL-HIV co-infection with Leishmania containing skin lesions resembling para-kala-azar dermal leishmaniasis
Authors: Alves Natália O. , Oshiro Jéssica A. , Silva Yunna C. , Pacher Gabriela C. , Casaril Aline E. , Rizk Yasmin S. , Uehara Silvia N. O. , Paniago Anamaria M. M. , Andrade Isadora L. X. , Arruda Carla C. P. , Oliveira Alessandra G.
Published: August 2024

Leishmaniases are a group of neglected vector-borne infectious diseases that are among the six priority endemic diseases worldwide. Visceral leishmaniasis (VL) is the most severe clinical manifestation, characterized by systemic and chronic visceral involvement and high mortality in immunosuppressed and untreated patients. VL can be complicated into post-kala-azar dermal leishmaniasis (PKDL), and when dermatologic disorders occur simultaneously with active VL, an intermediate clinical form called para-kala-azar dermal leishmaniasis (para-KDL) occurs. This clinical form is of great epidemiological relevance, as humans act as a source of infection for vectorial transmission. In the Americas, Brazil is among the seven countries responsible for more than 90% of VL cases, though reports of PKDL and para-KDL are rare. This paper presents three cases of VL-HIV co-infection with Leishmania-containing skin lesions resembling para-kala-azar dermal leishmaniasis. The cases were investigated by the team from the Infectious Diseases Department of University Hospital (HUMAP/UFMS) in Mato Grosso do Sul, Brazil. The three patients exhibited skin lesions where amastigote forms of L. (L.) infantum were identified. All cases exhibited similar clinical manifestations of para-KDL, including fever, hepatosplenomegaly, pancytopenia, and disseminated skin lesions. The study described the prevalence of comorbidities, the incidence of VL relapse, and the therapeutic regimen in relation to the outcomes. The study underscores the importance of follow-up and secondary prophylaxis in patients with VL, which are essential for the efficacy of the treatment. Furthermore, the study provides insight into the potential epidemiological profile of para-KDL cases in Brazil, which contributes to the development of more efficient clinical management strategies for patients.
Protocol for Cerebellar Stimulation for Aphasia Rehabilitation (CeSAR): A randomized, double-blind, sham-controlled trial
Authors: Lammers Becky , Sydnor Myra J. , Cust Sarah , Kim Ji Hyun , Yenokyan Gayane , Hillis Argye E. , Sebastian Rajani
Published: August 2024

In this randomized, double-blind, sham-controlled trial of Cerebellar Stimulation for Aphasia Rehabilitation (CeSAR), we will determine the effectiveness of cathodal tDCS (transcranial direct current stimulation) to the right cerebellum for the treatment of chronic aphasia (>6 months post stroke). We will test the hypothesis that cerebellar tDCS in combination with an evidenced-based anomia treatment (semantic feature analysis, SFA) will be associated with greater improvement in naming untrained pictures (as measured by the change in Philadelphia Picture Naming Test), 1-week post-treatment, compared to sham plus SFA. We will also evaluate the effects of cerebellar tDCS on naming trained items as well as the effects on functional communication, content, efficiency, and word-retrieval of picture description, and quality of life. Finally, we will identify imaging and linguistic biomarkers to determine the characteristics of stroke patients that benefit from cerebellar tDCS and SFA treatment. We expect to enroll 60 participants over five years. Participants will receive 15, 25-minute sessions of cerebellar tDCS (3–5 sessions per week) or sham tDCS combined with 1 hour of SFA treatment. Participants will be evaluated prior to the start of treatment, one-week post-treatment, 1-, 3-, and 6-months post-treatment on primary and secondary outcome variables. The long-term aim of this study is to provide the basis for a Phase III randomized controlled trial of cerebellar tDCS vs sham with concurrent language therapy for treatment of chronic aphasia.

Trial registration: The trial is registered with ClinicalTrials.gov NCT05093673.
The impact of sarcopenia on the incidence of postoperative outcomes following spine surgery: Systematic review and meta-analysis
Authors: Luo Mingjiang , Mei Zubing , Tang Siliang , Huang Jinshan , Yuan Kun , Jiang Lingling , Tang Zhifeng , Li Keni , Su Mingxuan , Su Can , Shi Yuxin , Zhang Zihan , Chen Jiang , Zheng Yuan , Bin Peng , Yuan Zhengbing , Xu Guosong , Xiao Zhihong
Published: August 2024

Purpose

Sarcopenia is considered to be an important predictor of adverse outcomes following spinal surgery, but the specific relationship between the two is not clear. The purpose of this meta-analysis is to systematically review all relevant studies to evaluate the impact of sarcopenia on spinal surgery outcomes.

Methods

We systematically searched PubMed, Embase and the Cochrane Library for relevant articles published on or before January 9, 2023. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated in a random effects meta-analysis. The main outcome was the risk of adverse outcomes after spinal surgery, including adverse events and mortality. This systematic review and meta-analysis was conducted following the PRISMA guidelines to evaluate the impact of sarcopenia on spinal surgery outcomes. In addition, we also conducted a subgroup analysis and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results.

Results

Twenty-four cohort studies, with a total of 243,453 participants, met the inclusion criteria. The meta-analysis showed that sarcopenia was significantly associated with adverse events (OR 1.63, 95% CI 1.17–2.27, P < 0.001) but was no significantly associated with mortality (OR 1.17, 95% CI 0.93–1.46, P = 0.180), infection (OR 2.24, 95% CI 0.95–5.26, P < 0.001), 30-day reoperation (OR 1.47, 95% CI 0.92–2.36, P = 0.413), deep vein thrombosis (OR 1.78, 95% CI 0.69–4.61, P = 0.234), postoperative home discharge (OR 0.60, 95% CI 0.26–1.37, P = 0.002) and blood transfusion (OR 3.28, 95% CI 0.74–14.64, P = 0.015).

Conclusion

The current meta-analysis showed that patients with sarcopenia have an increased risk of adverse events and mortality after spinal surgery. However, these results must be carefully interpreted because the number of studies included is small and the studies are significantly different. These findings may help to increase the clinicians’ awareness of the risks concerning patients with sarcopenia to improve their prognosis.
Inductive cum targeted yield model-based integrated fertilizer prescription for sweet corn (Zea mays L. Saccharata) on Alfisols of Southern India
Authors: Rangaiah Krishna Murthy , Nagaraju Bhavya , Kasturappa Govinda , Nagendrachari Annappa Nevatoor , Kadappa Basavaraja Pujari , Narayanaswamy Uday Kumar Sugaturu , Sab Mohamed Saqeebulla Hussain , Veerabadraiah Gangamrutha Godekere , Srivastava Sanjay , Dey Pradip
Published: August 2024

Striking the right nutrient balance is essential for sustainable farming and ecosystem health. In this regard, field experiments were conducted in three phases viz., fertility gradient experiment, main experiment and validation experiment through a soil test crop response approach to develop and validate fertilizer prescription equations for sweet corn in comparison with general recommended dose and soil fertility rating approach. The soil data, fresh cob yield, and NPK uptake were used for establishing four important basic parameters, viz., nutrient requirement (kg t-1), contribution of nutrients from fertilizers, soil, and organic manure. The results revealed that nutrients required to produce one tonne of fresh cob yield (NR) were 5.85 kg, 0.87 kg and 4.31kg for N, P and K, respectively under the STCR NPK alone approach and 6.07 kg, 0.92 kg and 4.33 kg for N, P and K, respectively under STCR NPK+FYM approach. In the validation experiment, STCR NPK+FYM approach for the targeted yield of 25 t ha−1 recorded higher fresh cob yield (23.38 t ha−1) and dry stover yield (35.07 t ha−1) which were significantly higher compared to general recommended dose and soil fertility rating approach. The developed STCR equations for the aforesaid crop are valid as the percent deviation of cob yield from the targeted yield was within ±10%. Similarly, highest nutrient use efficiency was achieved with the STCR approach, specifically when targeting a lower yield through an NPK+FYM mode. Thus, implementation of the STCR approach of fertilizer prescription, with or without FYM, at targeted yields of 25 and 22 t ha−1, not only surpassed the effects of the other fertilizer recommendation approach in terms of cob yields, but also increased NPK uptake, improved nutrient use efficiency and greater economic returns.
Trust under development: The Italian validation of the Epistemic Trust, Mistrust, and Credulity Questionnaire (ETMCQ) for adolescents
Authors: Milesi Alberto , Liotti Marianna , Locati Francesca , De Carli Pietro , Speranza Anna Maria , Campbell Chloe , Fonagy Peter , Lingiardi Vittorio , Parolin Laura
Published: August 2024

Introduction

In recent years, the concept of epistemic trust has emerged as a critical factor in understanding psychopathology, particularly within the context of personality disorders. A self-report instrument, the Epistemic Trust, Mistrust, and Credulity Questionnaire (ETMCQ), has demonstrated its validity among English and Italian adult populations. However, extending its applicability to adolescents is essential for comprehending the role of epistemic trust in the development of mental disorders. The aim of this study was to validate the ETMCQ within the Italian adolescent demographic.

Methods

Data were gathered from a wide selection of middle and high schools across Italy. The data collection started on 01/03/2022 and ended on 30/06/2022. Besides the ETMCQ (Study 1 = 662 participants, 12–18 years old, M = 15.56, SD = 2.20; 324 females, 338 males), we also administered other self-report instruments measuring mentalization, emotional dysregulation, general levels of psychopathology, and interpersonal trust in a smaller groups (Study 2 = 417 participants, aged from 12–19 years old, M = 15.64; SD = 2.08; 249 females, 168 males).

Results

Our findings provide empirical validation for the theoretical framework concerning the role of epistemic trust in psychological functioning and substantiate the validity of ETMCQ as a measure to assess it among teenagers.

Conclusions

The ETMCQ is a valid and promising instrument for adolescent populations; its ease and brevity of administration could make it a valuable tool both in clinical and research contexts, shedding light on the role of epistemic trust in mental health.
Development of nucleic acid lateral flow immunoassay for duplex detection of Leishmania martiniquensis and Leishmania orientalis in asymptomatic patients with HIV
Authors: Nawattanapaibool Namfon , Ruang-areerate Toon , Piyaraj Phunlerd , Leelayoova Saovanee , Mungthin Mathirut , Siripattanapipong Suradej
Published: August 2024

Leishmaniasis, a neglected tropical disease caused by parasitic protozoa of the Leishmania genus, remains a global health concern with significant morbidity and mortality. In Thailand, the rising incidence of autochthonous leishmaniasis cases involving Leishmania (Mundinia) martiniquensis and novel Leishmania (Mundinia) orientalis underscores the critical need for accurate diagnosis and effective control strategies. This study presents a sensitive and specific nucleic acid lateral flow immunoassay (NALFIA) that integrates a duplex PCR assay with a lateral flow device (LFD) strip format. Targeting the internal transcribed spacer 1 (ITS1) region, known for its unique combination of conserved and variable sequences, this assay employs primers labeled with biotin, digoxigenin, and fluorescein isothiocyanate (FITC) markers, enabling precise species identification and differentiation of these two Leishmania species. Remarkably, the assay achieves a sensitivity that surpasses agarose gel electrophoresis, detecting as few as 10−2 parasite/μL for L. martiniquensis and 10−4 parasite/μL for L. orientalis. Notably, the assay exhibited reliable specificity, revealing no cross-amplification with other major viscerotropic Leishmania species or reference organisms. Evaluation using 62 clinical samples further confirms the effectiveness of the PCR-LFD assay, with a sensitivity of 100% for L. martiniquensis and 83.3% for L. orientalis, and an excellent agreement (κ value = 0.948) with nested PCR. This integrated assay represents a promising advancement in diagnostic tools, offering rapid and accurate results that can significantly contribute to effective disease management and control. Given the increasing relevance of these Leishmania species in current public health scenarios, this assay serves as a valuable tool for both diagnostic and research applications.
Molecular characterization analysis of PANoptosis-related genes in colorectal cancer based on bioinformatic analysis
Authors: Zhang Mengyang , Li Wen , Zhao Yubo , Qi Ling , Xiao Yonglong , Liu Donglian , Peng TieLi
Published: August 2024

Colorectal cancer (CRC) ranks as the third most prevalent cancer globally and stands as the second principal contributor to cancer-related fatalities. Recently, emerging research has emphasized the role of pan apoptosis (PANoptosis) in tumor development and anti-tumor therapy. In the course of this investigation, we meticulously identified and conducted a correlation analysis between differentially expressed genes associated with PANoptosis in CRC (CPAN_DEGs) and the proportion of immune cells. Subsequently, we formulated a prognostic score based on the CPAN_DEGs. Further our analysis revealed a noteworthy reduction in UNC5D mRNA expression within HCT116, HT29 and SW480 cells, as validated by qRT-PCR assay. Furthermore, scrutinizing the TCGA database unveiled a distinctive trend wherein individuals with the low UNC5D expression exhibited significantly reduced overall survival compared to their counterparts with the high UNC5D levels. The drug susceptibility analysis of UNC5D was further performed, which showed that UNC5D was corassociated with the sensitivity of CRC to 6-Thioguanine. The outcomes of our investigation underscore the mechanisms by which PANoptosis influences immune dysregulation as well as prognostic outcome in CRC.
Development of a target product profile for new glucose self-monitoring technologies for use in low- and middle-income countries
Authors: Safary Elvis , Lepeska Molly , Beran David , Ewen Margaret , Zhaparova Aigerim , Rukare Jackie , Boulle Philippa , Aebischer Perone Sigiriya , Makohliso Solomzi , Pleus Stefan , Vetter Beatrice
Published: August 2024

Aims

Most glucose self-monitoring devices have been developed with high-income countries in mind. We developed a target product profile (TPP) for new glucose self-monitoring technologies for users in low- and middle-income countries (LMICs).

Methods

A draft TPP including 39 characteristics was developed by an expert group including diabetes specialists, device specialists, and people with diabetes, incorporating findings from qualitative research in LMICs. Each characteristic had minimal and optimal requirements for two use cases, frequent and sporadic use. Characteristics requiring refinement were identified via online survey. Characteristics with agreement level <90% for any requirement were reviewed by the expert group and amended as appropriate.

Results

One characteristic (shelf life) had agreement <75% (both requirements for both use cases). Characteristics with agreement ≥75% and <90% for the frequent use case included infrastructure level, measurement cycle, duration of use before replacement, interchangeability, and calibration (both requirements), and activity log and price per month to end payer (minimal requirement). Intended use (both requirements), accuracy, and price per month to end payer (optimal requirement) had agreement ≥75% and <90% for the sporadic use case.

Conclusions

This TPP will inform developers on requirements for glucose self-monitoring technologies for LMICs, and support decision-makers in evaluating existing devices.
Health promotion for dementia risk reduction in Indigenous populations of Canada, Aotearoa New Zealand, United States of America, and Australia: Scoping review protocol
Authors: Meldrum Kathryn , Hornby-Turner Yvonne , Wallace Valda , Russell Sarah G. , Quigley Rachel , Strivens Edward
Published: August 2024

Health promotion programs and strategies have the potential to support people to live healthier lives. Dementia, a collective name for brain disorders that impact thinking and memory, affects over 55 million people worldwide. Currently, there is no cure for dementia, so prevention is critical. Health promotion has the potential to reduce dementia by targeting the twelve potentially modifiable risk factors. A project currently being undertaken by the research team aims to strengthen the quality of clinical care and health services that specifically address dementia risk for Australian Aboriginal and Torres Strait Islander peoples. One of the intended strategies supporting the project’s aim is the need for appropriate and safe health promotion programs and resources that support dementia risk reduction. Consequently, the aim of this scoping review is to identify and determine the quality and appropriateness of existing health promotion programs and resources aimed at dementia risk reduction developed or modified for Indigenous populations of Canada, the USA, Aotearoa New Zealand, and Australia that could be incorporated into the broader project. The Joanna Briggs Institute method for scoping reviews will be used to identify programs and resources focussed on dementia risk reduction for Indigenous peoples. Searches will be limited to the English language and literature published since January 2010. Databases to be searched include: CINAHL, Medline, PsychInfo, PubMed, Scopus and Google. Data that answers the research questions will be extracted from the literature and recorded on a data charting form. A combination of quantitative and qualitative methods will be used to analyse the findings of the scoping review. Dissemination of the findings through continuing community engagement, conference presentations and publications will be led by Aboriginal and Torres Strait Islander members of the research team.
From many voices, one question: Community co-design of a population-based qualitative cancer research study
Authors: Ayre Susannah K. , Johnston Elizabeth A. , Bourdaniotis Xanthia E. , Zajdlewicz Leah , Beesley Vanessa L. , Pole Jason D. , Hansen Aaron , Gasper Harry , Cossio Danica , Lock Gemma , Goodwin Belinda C.
Published: August 2024

Purpose

This study formed the development stage of a population-based survey aiming to: (i) understand the needs and experiences of people affected by cancer in Queensland, Australia and (ii) recruit a pool of participants for ongoing cancer survivorship research. The current study aimed to co-design and test a single qualitative survey question and study invitation materials to maximise acceptability of, and participation in, the survey and future research.

Methods

Fifty-two community members, including cancer survivors and caregivers, participated across 15 co-design workshops and 20 pretest interviews. During workshops, participants generated and refined ideas for an open-ended survey question and provided feedback on a study invitation letter. The use of a single, open-ended question aims to minimise participant burden while collecting rich information about needs and experiences. The research team then shortlisted the question ideas and revised study invitation materials based on workshop feedback. Next, using interviews, community members were asked to respond to a shortlisted question to test its interpretability and relevance and to review revised invitation materials. Content analysis of participant feedback was used to identify principles for designing study materials.

Results

Principles for designing qualitative survey questions were identified from participant feedback, including define the question timeframe and scope; provide reassurance that responses are valid and valued; and use simple wording. Principles for designing study invitation materials were also identified, including communicate empathy and sensitivity; facilitate reciprocal benefit; and include a ‘human element’. The qualitative survey question and study invitation materials created using these principles were considered relevant and acceptable for use in a population-based survey.

Conclusions

Through community consultation and co-design, this study identified principles for designing qualitative data collection and invitation materials for use in cancer survivorship research. These principles can be applied by other researchers to develop study materials that are sensitive to the needs and preferences of community members.
Uncovering structural variants in Creole cattle from Guadeloupe and their impact on environmental adaptation through whole genome sequencing
Authors: Ben-Jemaa Slim , Boussaha Mekki , Mandonnet Nathalie , Bardou Philippe , Naves Michel
Published: August 2024

Structural variants play an important role in evolutionary processes. Besides, they constitute a large source of inter individual genetic variation that might represent a major factor in the aetiology of complex, multifactorial traits. Their importance in adaptation is becoming increasingly evident in literature. Yet, the characterization of the genomic landscape of structural variants in local breeds remains scarce to date. Herein, we investigate patterns and gene annotation of structural variants in the Creole cattle from Guadeloupe breed using whole genome sequences from 23 bulls representative of the population. In total, we detected 32821 ascertained SV defining 15258 regions, representing ~ 17% of the Creole cattle genome. Among these, 6639 regions have not been previously reported in the Database of Genomic Variants archive. Average number of structural variants detected per individual in the studied population is in the same order of magnitude of that observed in indicine populations and higher than that reported in taurine breeds. We observe an important within-individual variability where approximately half of the detected structural variants have low frequency (MAF < 0.25). Most of the detected structural variants (55%) occurred in intergenic regions. Genic structural variants overlapped with 7793 genes and the predicted effect of most of them is ranked as “modifier”. Among the structural variants that were predicted to have a high functional impact on the protein, a 5.5 Kb in length, highly frequent deletion on chromosome 2, affects ALPI, a gene associated with the interaction between gut microbiota and host immune system. The 6639 newly identified structural variants regions include three deletions and three duplications shared by more than 80% of individuals that are significantly enriched for genes related to tRNA threonylcarbamoyladenosine metabolic process, important for temperature adaptation in thermophilic organisms, therefore suggesting a potential role in the thermotolerance of Creole cattle from Guadeloupe cattle to tropical climate. Overall, highly frequent structural variants that are specific to the Creole cattle population encompass olfactory receptor and immunity genes as well as genes involved in muscle tone, muscle development and contraction. Beyond mapping and characterizing structural variants in the Creole cattle from Guadeloupe breed, this study provides valuable information for a better understanding of the potential role of chromosomal rearrangements in adaptive traits in cattle.
Seroprevalence trends of anti-SARS-CoV-2 antibodies in the adult population of the São Paulo Municipality, Brazil: Results from seven serosurveys from June 2020 to April 2022. The SoroEpi MSP Study
Authors: Tess Beatriz Helena , Turchi Martelli Celina Maria , Goi Porto Alves Maria Cecília , Cortes Fanny , Ivata Bernal Regina Tomie , Vieira de Souza Wayner , de Albuquerque Luna Expedito José , da Cunha Rodrigues Laura , Cavallari Nunes Marcia , de Castro Reinach Fernando , Granato Celso Francisco Hernandes , Rizzatti Edgar Gil , Tostes Pintão Maria Carolina
Published: August 2024

Background

Sequential population-based household serosurveys of SARS-CoV-2 covering the COVID-19 pre- and post-vaccination periods are scarce in Brazil. This study investigated seropositivity trends in the municipality of São Paulo.

Methods

We conducted seven cross-sectional surveys of adult population-representative samples between June 2020 and April 2022. The study design included probabilistic sampling, test for SARS-CoV-2 antibodies using the Roche Elecsys anti-nucleocapsid assay, and statistical adjustments for population demographics and non-response. The weighted seroprevalences with 95% confidence intervals (CI) were estimated by sex, age group, race, schooling, and mean income study strata. Time trends in seropositivity were assessed using the Joinpoint model. We compared infection-induced seroprevalences with COVID-19 reported cases in the pre-vaccination period.

Results

The study sample comprised 8,134 adults. The overall SARS-CoV-2 seroprevalence increased from 11.4% (95%CI: 9.2–13.6) in June 2020 to 24.9% (95%CI: 21.0–28.7) in January 2021; from 38.1% (95%CI: 34.3–41.9) in April 2021 to 77.7% (95%CI: 74.4–81.0) in April 2022. The prevalence over time was higher in the subgroup 18–39 years old than in the older groups from Survey 3 onwards. The self-declared Black or mixed (Pardo) group showed a higher prevalence in all surveys compared to the White group. Monthly prevalence rose steeply from January 2021 onwards, particularly among those aged 60 years or older. The infection-to-case ratios ranged from 8.9 in June 2020 to 4.3 in January 2021.

Conclusions

The overall seroprevalence rose significantly over time and with age and race subgroup variations. Increases in the 60 years or older age and the White groups were faster than in younger ages and Black or mixed (Pardo) race groups in the post-vaccination period. Our data may add to the understanding of the complex and changing population dynamics of the SARS-CoV-2 infection, including the impact of vaccination strategies and the modelling of future epidemiological scenarios.
“I’m not your grandpa”: Experiences of advanced age fathers raising their teenage children in Belgium, an interpretative phenomenological analysis
Authors: Piek Steven R. , Verghote Kato , Martani Andrea , Pennings Guido , Provoost Veerle
Published: August 2024

This study aims to gain more insight in the lived experience of men who became father at an advanced age (40 years or older). Advanced Parental Age (APA) is becoming an increasingly widespread phenomenon as the average age at which people have children has been increasing for decades now. However, the psychosocial dimension of APA-fatherhood in particular remains a highly understudied topic. This Interpretive Phenomenological Analysis presents findings from a qualitative interview study with seven men who fathered their (now teenage) children in their early 40s to early 50s. Interviews were semi-structured and focused on lived experiences of the participants and their normative stances regarding the topic of parenting at an advanced age. Three themes were identified: The fathers in our sample describe their APA as a result of life events rather than an intentional postponement. Second, they managed how they were perceived as APA-fathers by distancing themselves from ‘too old’ parents. However, these fathers did not perceive fatherhood at a younger age as better than their current APA. Three fathers, who also had an earlier fatherhood experience, provided a rich account of how they made sense of their fatherhood roles in both families. Third, the seven fathers encountered social stigma, leading to various coping strategies. These findings contribute to better understanding the psychosocial dimension of APA-fatherhood.
Fitness adaptations of Japanese encephalitis virus in pigs following vector-free serial passaging
Authors: Marti Andrea , Nater Alexander , Pego Magalhaes Jenny , Almeida Lea , Lewandowska Marta , Liniger Matthias , Ruggli Nicolas , Grau-Roma Llorenç , Brito Francisco , Alnaji Fadi G. , Vignuzzi Marco , García-Nicolás Obdulio , Summerfield Artur
Published: August 2024

Japanese encephalitis virus (JEV) is a zoonotic mosquito-transmitted Flavivirus circulating in birds and pigs. In humans, JEV can cause severe viral encephalitis with high mortality. Considering that vector-free direct virus transmission was observed in experimentally infected pigs, JEV introduction into an immunologically naïve pig population could result in a series of direct transmissions disrupting the alternating host cycling between vertebrates and mosquitoes. To assess the potential consequences of such a realistic scenario, we passaged JEV ten times in pigs. This resulted in higher in vivo viral replication, increased shedding, and stronger innate immune responses in pigs. Nevertheless, the viral tissue tropism remained similar, and frequency of direct transmission was not enhanced. Next generation sequencing showed single nucleotide deviations in 10% of the genome during passaging. In total, 25 point mutations were selected to reach a frequency of at least 35% in one of the passages. From these, six mutations resulted in amino acid changes located in the precursor of membrane, the envelope, the non-structural 3 and the non-structural 5 proteins. In a competition experiment with two lines of passaging, the mutation M374L in the envelope protein and N275D in the non-structural protein 5 showed a fitness advantage in pigs. Altogether, the interruption of the alternating host cycle of JEV caused a prominent selection of viral quasispecies as well as selection of de novo mutations associated with fitness gains in pigs, albeit without enhancing direct transmission frequency.
ORF48 is required for optimal lytic replication of Kaposi’s sarcoma-associated herpesvirus
Authors: Veronese Beatriz H. S. , Nguyen Amy , Patel Khushil , Paulsen Kimberly , Ma Zhe
Published: August 2024

Kaposi’s sarcoma-associated herpesvirus (KSHV) establishes persistent infection in the host by encoding a vast network of proteins that aid immune evasion. One of these targeted innate immunity pathways is the cGAS-STING pathway, which inhibits the reactivation of KSHV from latency. Previously, we identified multiple cGAS/STING inhibitors encoded by KSHV, suggesting that the counteractions of this pathway by viral proteins are critical for maintaining a successful KSHV life cycle. However, the detailed mechanisms of how these viral proteins block innate immunity and facilitate KSHV lytic replication remain largely unknown. In this study, we report that ORF48, a previously identified negative regulator of the cGAS/STING pathway, is required for optimal KSHV lytic replication. We used both siRNA and deletion-based systems to evaluate the importance of intact ORF48 in the KSHV lytic cycle. In both systems, loss of ORF48 resulted in defects in lytic gene transcription, lytic protein expression, viral genome replication and infectious virion production. ORF48 genome deletion caused more robust and global repression of the KSHV transcriptome, possibly due to the disruption of RTA promoter activity. Mechanistically, overexpressed ORF48 was found to colocalize and interact with endogenous STING in HEK293 cells. Endogenous ORF48 and STING interactions were also detected in reactivated iSLK.219 cells. Compared with the control cell line, HUVEC cells stably expressing ORF48 exhibited repressed STING-dependent innate immune signaling upon ISD or diABZI treatment. However, the loss of ORF48 in our iSLK-based lytic system failed to induce IFNβ production, suggesting a redundant role of ORF48 on STING signaling during the KSHV lytic phase. Thus, ORF48 is required for optimal KSHV lytic replication through additional mechanisms that need to be further explored.
Blockade of IKK signaling induces RIPK1-independent apoptosis in human macrophages
Authors: Nataraj Neha M. , Sillas Reyna Garcia , Herrmann Beatrice I. , Shin Sunny , Brodsky Igor E.
Published: August 2024

Regulated cell death in response to microbial infection plays an important role in immune defense and is triggered by pathogen disruption of essential cellular pathways. Gram-negative bacterial pathogens in the Yersinia genus disrupt NF-κB signaling via translocated effectors injected by a type III secretion system, thereby preventing induction of cytokine production and antimicrobial defense. In murine models of infection, Yersinia blockade of NF-κB signaling triggers cell-extrinsic apoptosis through Receptor Interacting Serine-Threonine Protein Kinase 1 (RIPK1) and caspase-8, which is required for bacterial clearance and host survival. Unexpectedly, we find that human macrophages undergo apoptosis independently of RIPK1 in response to Yersinia or chemical blockade of IKKβ. Instead, IKK blockade led to decreased cFLIP expression, and overexpression of cFLIP contributed to protection from IKK blockade-induced apoptosis in human macrophages. We found that IKK blockade also induces RIPK1 kinase activity-independent apoptosis in human T cells and human pancreatic cells. Altogether, our data indicate that, in contrast to murine cells, blockade of IKK activity in human cells triggers a distinct apoptosis pathway that is independent of RIPK1 kinase activity. These findings have implications for the contribution of RIPK1 to cell death in human cells and the efficacy of RIPK1 inhibition in human diseases.
Espacio público y accesibilidad
Authors: Wilkinson Alan Francis
Published: August 2024

¿Ha pensado cómo experimenta la ciudad una persona con movilidad reducida (y más aún si posee discapacidad física/motriz)? En este trabajo nos interesa abordar la problemática desde la perspectiva de las personas con movilidad reducida.
Descripción del Autoconcepto en pacientes con trastorno bipolar.
Authors: Delgado Reyes Andres Camilo , Castaño Ramírez Oscar Mauricio , Sánchez López Jessica Valeria
Published: August 2024

El autoconcepto se concibe como la idea que una persona ha construido de su sí mismo, producto de la auto-observación de sus capacidades y limitaciones propias. El objetivo del presente trabajo es describir el autoconcepto en una muestra de pacientes con trastorno bipolar. Estudio de corte transversal, de característica descriptiva. Muestreo intencional, se evaluaron 36 personas por medio del cuestionario AF5. Al realizar una comparación de medias entre grupos no se hallaron diferencias estadísticamente significativas para ninguna de las dimensiones. Las mujeres puntuaron por debajo del baremo en las dimensiones emocional y familiar y los hombres puntuaron por debajo en la dimensión social y familiar. Los resultados se discuten a la luz de la literatura científica sobre el tema.
Relações entre Bem-Estar Subjetivo, Fear of Missing Out e Uso de Redes Sociais
Authors: Padilha Sandra , Piazentim Tatiana Goldschmidt , Matteo Ambiel Rodolfo Augusto , Henrique Martins Gustavo
Published: August 2024

O objetivo deste estudo foi testar as relações entre bem-estar subjetivo (BES), Fear of Missing Out (FoMO), quantidade e frequência de uso de redes sociais bem como investigar o papel preditor dessas variáveis sobre o BES. Para tanto, a pesquisa foi realizada em formato on-line e contou com 265 participantes de ambos os sexos, entre 18 e 73 anos. Os resultados apontaram correlação negativa entre FoMO e BES, correlação positiva entre quantidade e frequência de uso de redes sociais com FoMO e correlação negativa entre quantidade e frequência de uso de redes sociais com BES. Ademais, em relação aos resultados da regressão FoMO Pertencimento foi preditor negativo dos três componentes do BES. Diante disso, observou-se que tanto os sentimentos decorrentes do FoMO quanto quantidade e frequência de uso de redes sociais tendem a impactar negativamente o BES dentro do contexto brasileiro.
Prevalencia de ciberviolencia de género en el noviazgo en dos universidades de Bucaramanga y su área metropolitana
Authors: Peña Paula Daniela , Mahecha Angarita Jeimmy Johanna , Redondo Pacheco Jesús , Luzardo Briceño Marianela
Published: August 2024

Las Tecnologías de Información y Comunicación (TICs) se han transformado en una herramienta de interacción y entretenimiento que se evidencia en diferentes ámbitos de la vida, facilitando, al mismo tiempo, un espacio tecnológico para establecer y mantener relaciones de noviazgo en los jóvenes por medio del uso frecuente de las redes sociales, y favoreciendo elementos de control, aislamiento, dominación, sometimiento e imposición. La presente investigación identifica la prevalencia de ciberviolencia de género en el noviazgo en jóvenes universitarios, mediante un enfoque cuantitativo con un diseño no experimental de tipo descriptivo transversal, a través de una muestra conformada por 329 estudiantes universitarios, 196 mujeres y 133 hombres, con edades comprendidas entre 18 y 26 años. Para la evaluación se empleó el Cyber Dating Abuse Questionnaire (CDAQ) el cual está compuesto por 40 reactivos que evalúan de forma paralela victimización y perpetración en dos escalas: agresión directa y control/monitoreo. Los resultados mostraron que las conductas que más se repiten, tanto en el rol de víctima como en el de agresor, son las de control y monitoreo, evidenciándose además que no existen diferencias estadísticamente significativas respecto al porcentaje de las subescalas según sexo; reafirmándose la necesidad de continuar investigando y generando herramientas que respondan a este fenómeno.