bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of effective atomic number of paraspinal muscles in the prediction of acute vertebral fracture risk assessment: a cross-sectional case-control study
Authors: Mai Chunhua , Liu Yandong , Xu Dongfeng , Geng Jian , Wang Wenzhang , Zhu Kaibang , Lu Huoli , Zhou Fengyun , Wang Haoya , Zhang Zhenguang , Wang Ling
Published: June 2024

Objectives

We aim to investigate the relations among effective atomic number (Zeff), density, and area of paraspinal muscles, volumetric bone mineral density (vBMD), and acute vertebral fractures (VF) by using spectral base images (SBIs) and routine CT images.

Methods

A total of 223 patients (52 men and 171 women) with acute lumber VF and 776 subjects (286 men and 390 women) without VF of at least 60 years were enrolled and underwent dual-layer detector CT scans. We quantified the cross-sectional area, density (paraSMD), and Zeff of paraspinal muscles by CT images and SBIs and measured vBMD of the lumbar spine by quantitative CT.

Results

Higher vBMD was associated with lower VF risk in both sexes (adjusted OR, 0.33 and 0.43). After adjusting for age and body mass index, the associations of paraSMD with VF were not significant in men, and in women the association was borderline significant (OR, 0.80; 95% CI, 0.64-1.00). However, higher Zeff of paraspinal muscles was associated with lower VF risk in men (adjusted OR, 0.59; 0.36-0.96) but not in women. The associations of all muscle indexes with VF were not significant after further adjusting for vBMD.

Conclusions

A higher Zeff of paraspinal muscles is associated with lower VF risk in older men but not in older women. The density, area, and Zeff of paraspinal muscles were not vBMD independent risk factors for acute VF.

Advances in knowledge

The effective atomic number of paraspinal muscles might be a potential marker for VF risk prediction.
Focal cortical dysplasia II caused by brain somatic mutation of IRS-1 is associated with ERK signaling pathway activation
Authors: Li Xiao , Wang Tianshuang , Liu Nana , Cai Aojie , Zhang Junjiao , Zhang Fan , Liu Qingzhu , Wang Jingmin , Wu Ye , Gao Kai , Jiang Yu-Wu
Published: June 2024

Somatic mutations have been identified in 10% to 63% of focal cortical dysplasia type II samples, primarily linked to the mTOR pathway. When the causative genetic mutations are not identified, this opens the possibility of discovering new pathogenic genes or pathways that could be contributing to the condition. In our previous study, we identified a novel candidate pathogenic somatic variant of IRS-1 c.1791dupG in the brain tissue of a child with focal cortical dysplasia type II. This study further explored the variant’s role in causing type II focal cortical dysplasia through in vitro overexpression in 293T and SH-SY5Y cells and in vivo evaluation via in utero electroporation in fetal brains, assessing effects on neuronal migration, morphology, and network integrity. It was found that the mutant IRS-1 variant led to hyperactivity of p-ERK, increased cell volume, and was predominantly associated with the MAPK signaling pathway. In vivo, the IRS-1 c.1791dupG variant induced abnormal neuron migration, cytomegaly, and network hyperexcitability. Notably, the ERK inhibitor GDC-0994, rather than the mTOR inhibitor rapamycin, effectively rescued the neuronal defects. This study directly highlighted the ERK signaling pathway’s role in the pathogenesis of focal cortical dysplasia II and provided a new therapeutic target for cases of focal cortical dysplasia II that are not treatable by rapamycin analogs.
The Use of Long-term Antibiotics for Suppression of Bacterial Infections
Authors: Horne Molly , Woolley Ian , Lau Jillian S Y
Published: June 2024

Suppressive antibiotic therapy is prescribed when a patient has an infection that is presumed to be incurable by a defined course of therapy or source control. The cohort receiving suppressive antibiotic therapy is typically highly comorbid and the infections often involve retained prosthetic material. In part due to a lack of clear guidelines regarding the use of suppressive antibiotics, and in part due to the complex nature of the infections in question, patients are often prescribed suppressive antibiotics for extremely long, if not indefinite, courses. The risks of prolonged antibiotic exposure in this context are not fully characterized, but they include adverse drug effects ranging from mild to severe, the development of antibiotic-resistant organisms, and perturbations of the gastrointestinal microbiome. In this narrative review we present the available evidence for the use of suppressive antibiotic therapy in 4 common indications, examine the gaps in the current literature, and explore the known and potential risks of this therapy. We also make suggestions for improving the quality of evidence in future studies, particularly by highlighting the need for a standardized term to describe the use of long courses of antibiotics to suppress hard-to-treat infections.
Personalized peritoneal dialysis prescription—beyond clinical or analytical values
Authors: Slon-Roblero María Fernanda , Sanchez-Alvarez J Emilio , Bajo-Rubio Maria Auxiliadora
Published: June 2024

Traditionally, dialysis adequacy has been assessed primarily by determining the clearance of a single small solute, urea. Nevertheless, it has become increasingly evident that numerous other factors play a crucial role in the overall well-being, outcomes and quality of life of dialysis patients. Consequently, in recent years, there has been a notable paradigm shift in guidelines and recommendations regarding dialysis adequacy. This shift represents a departure from a narrow focus only on the removal of specific toxins, embracing a more holistic, person-centered approach. This new perspective underscores the critical importance of improving the well-being of individuals undergoing dialysis while simultaneously minimizing the overall treatment burden. It is based on a double focus on both clinical outcomes and a comprehensive patient experience. To achieve this, a person-centered approach must be embraced when devising care strategies for each individual. This requires a close collaboration between the healthcare team and the patient, facilitating an in-depth understanding of the patient's unique goals, priorities and preferences while striving for the highest quality of care during treatment. The aim of this publication is to address the existing evidence on this all-encompassing approach to treatment care for patients undergoing peritoneal dialysis and provide a concise overview to promote a deeper understanding of this person-centered approach.
Use of eHealth and remote patient monitoring: a tool to support home dialysis patients, with an emphasis on peritoneal dialysis
Authors: Lew Susie Q , Ronco Claudio
Published: June 2024

Implementing eHealth requires technological advancement, universal broadband and internet access, and devices to conduct telemedicine and remote patient monitoring in end-stage kidney disease patients receiving home dialysis. Although eHealth was beginning to make inroads in this patient population, the COVID-19 pandemic spurred telemedicine usage when many regulations were waived during the Public Health Emergency to limit the spread of infection by endorsing social distancing. At the same time, two-way communication automatic peritoneal dialysis cyclers were introduced to advance remote patient monitoring. Despite the numerous advantages and potential benefits afforded by both procedures, challenges and untapped resources remain to be addressed. Continuing research to assess the use of eHealth and technological innovation can make eHealth a powerful tool in home dialysis. We review the past, present and future of eHealth and remote patient monitoring in supporting home dialysis.
Impact of Upadacitinib Induction and Maintenance Therapy on Health-related Quality of Life, Fatigue, and Work Productivity in Patients with Moderately-to-severely Active Crohn’s Disease
Authors: Ghosh Subrata , Feagan Brian G , Parra Rogério Serafim , Lopes Susana , Steinlauf Adam , Kakuta Yoichi , Joshi Namita , Lee Wan-Ju , Lacerda Ana P , Zhou Qian , Xuan Si , Kligys Kristina , Shukla Nidhi , Louis Edouard
Published: June 2024

Background and Aims

Quality of life in patients with active Crohn’s disease may be significantly reduced. We evaluated the effects of upadacitinib induction and maintenance therapy on fatigue, quality of life, and work productivity in the phase 3 trials U-EXCEL, U-EXCEED, and U-ENDURE.

Methods

Clinical responders to upadacitinib 45 mg in U-EXCEL and U-EXCEED induction trials were re-randomised 1:1:1 to upadacitinib 30 mg, 15 mg, or placebo for 52 weeks of maintenance in U-ENDURE. Clinically meaningful improvements in Inflammatory Bowel Disease Questionnaire [IBDQ] response, IBDQ remission, Functional Assessment of Chronic Illness Therapy–Fatigue [FACIT-Fatigue], and Work Productivity and Activity Impairment were evaluated. Percentages of patients achieving clinically meaningful improvements were assessed at induction Weeks 4 and 12 and maintenance Week 52.

Clinical Registration number

U-EXCEED induction trial [NCT03345836], U-EXCEL induction trial [NCT03345849], U-ENDURE maintenance trial [NCT03345823].

Results

Analysis included 1021 and 502 patients assessed at induction and maintenance, respectively. In U-EXCEL, greater improvements [all p ≤ 0.001] in IBDQ response [71.0% vs 50.2%], IBDQ remission [44.2% vs 23.7%], and FACIT-Fatigue [42.0% vs 27.0%] were observed in upadacitinib-treated patients versus placebo at Week 4. Improvements in IBDQ response, IBDQ remission, and FACIT-Fatigue were similar or greater at Week 12. Clinically meaningful improvement in overall work impairment [52.1% vs 38.1%, p ≤ 0.05] was demonstrated at Week 12. Similar results were observed in U-EXCEED. Improvements were sustained through 52 weeks of upadacitinib maintenance treatment.

Conclusions

In patients with active Crohn’s disease, upadacitinib treatment relative to placebo significantly improved fatigue, quality of life, and work productivity as early as Week 4. These effects were sustained through 52 weeks of maintenance.
Lung volume reduction surgery: a micro-costing analysis from a national tertiary referral centre
Authors: Mulryan Kathryn , Sorensen Jan , Waller David , Redmond Karen
Published: June 2024

OBJECTIVES

Lung volume reduction surgery (LVRS) is a clinically effective palliation procedure for patients with chronic obstructive pulmonary disease. LVRS has recently been commissioned by the NHS England. In this study, a costing model was developed to analyse cost and resource implications of different LVRS procedures.

METHODS

Three pathways were defined by their surgical procedures: bronchoscopic endobronchial valve insertion (EBV-LVRS), video-assisted thoracic surgery LVRS and robotic-assisted thoracic surgery LVRS. The costing model considered use of hospital resources from the LVRS decision until 90 days after hospital admission. The model was calibrated with data obtained from an observational study, electronic health records and expert opinion. Unit costs were obtained from the hospital finance department and reported in 2021 Euros.

RESULTS

Video-assisted thoracic surgery LVRS was associated with the lowest cost at €12 896 per patient. This compares to the costs of EBV-LVRS at €15 598 per patient and €13 305 per patient for robotic-assisted thoracic surgery LVRS. A large component of EBV-LVRS costs were accrued secondary to complications, including revision EBV-LVRS.

CONCLUSIONS

This study presents a comprehensive model framework for the analysis of hospital-related resource use and costs for the 3 surgical modalities. In the future, service commissioning agencies, hospital management and clinicians can use this framework to determine their modifiable resource use (composition of surgical teams, use of staff and consumables, planned length of stay and revision rates for EBV-LVRS) and to assess the potential cost implications of changes in these parameters.
Take-home tests as an assessment for learning strategy
Authors: Hobbs Garry Bryn , Mourão Sandie
Published: June 2024

This article reports on an intervention study conducted to improve young Thai learners’ motivation and attitudes towards take-home tests. The traditional use of summative tests in education has often led to increased pressure and demotivation among students. Based on formative assessment practices and motivational strategies, the study aimed to improve students’ motivation and engagement when taking tests. The intervention involved regular, short take-home tests and motivational strategies over 25 weeks and collected data using a mixed methods approach. Results showed notable improvement in students’ intrinsic motivation, writing motivation and homework completion rate of take-home tests over the course of the intervention. The article highlights the importance of incorporating formative assessment practices, goal setting, collaborative learning and visual aids to promote student ownership of learning and increase their motivation to complete tests. The study contributes to the ongoing dialogue on effective assessment methods and student motivation in an educational context.
Health-related quality of life in elderly cardiac patients undergoing cardiac rehabilitation and the association with exercise capacity: the EU-CaRE study
Authors: Kjesbu Ingunn E , Sibilitz Kirstine L , Petersen Janne , Houben Vital J G , Wilhelm Matthias , Pena-Gil Carlos , Iliou Marie Christine , Zeymer Uwe , Ardissino Diego , Van’t Hof Arnoud W J , van der Velde Astrid E , de Kluiver Ed P , Prescott Eva
Published: June 2024

Aims

The ability to be physically active is pivotal to the quality of life in elderly patients. This study aims to describe the association between exercise capacity and health-related quality of life (HRQoL), anxiety, and depression following an exercise-based cardiac rehabilitation (CR) programme in elderly cardiac patients.

Methods and results

Patients aged ≥65 years with acute and chronic coronary syndrome or heart valve surgery were consecutively included from eight CR centres in seven European countries. Exercise capacity [VO2peak(mL/kg/min)] was assessed with a cardiopulmonary exercise test (97%) or a 6-min walk test. Outcome variables included HRQoL [36-item Short-Form Health Survey physical and mental component scores (PCS and MCS)], anxiety (Generalized Anxiety Disorder-7), and depression (Patient Health Questionnaire-9). Mixed models were used to address the association between baseline and the development in VO2peak, and outcome variables stratified on sex, and adjusted for baseline values, age, and CR centre. A total of 1633 patients were included (T0), 1523 (93%) completed end-of-CR assessment (T1), and 1457 (89%) were available for 1-year follow-up (T2). Women had higher percentage of predicted VO2peak but poorer scores in HRQoL, anxiety, and depression at all time points. All scores improved in both sexes at follow-up. We found significant associations between VO2peak at baseline as well as development in VO2peak and all outcome variables at T1 and T2 in men (all P < 0.001). In women, VO2peak was only associated with PCSs (P < 0.001).

Conclusion

Improvements in exercise capacity were strongly associated with improvements in HRQoL and mental health, however, with stronger associations in men. The results highlight the importance of physical fitness for HRQol and mental health. The findings from this study might be useful to better target individual CR programmes.
Physiological responses of a black locust plantation to drought stress based on a throughfall exclusion experiment in semi-arid northwestern China
Authors: Liu Binbin , Tang Xianhui , Wang Lele , Zhang Pengyi , He Junhao , Yue Chao
Published: June 2024

Drought poses a significant threat on the ecosystem stability of extensive areas of black locust (Robinia pseudoacacia L.) plantations in northwestern China. However, limited understanding of the physiological responses of black locust to drought has impeded the development of proactive measures to alleviate potential adverse effects of drought. This study investigated the physiological impacts of varying drought intensities, manipulated by a throughfall exclusion experiment, on a 20-year-old black locust plantation in northwestern China. The experiment involved 40% throughfall exclusion for moderate drought, 80% exclusion for extreme drought, and no exclusion for control. One year after the implementation of the experiment, both predawn (Ψpd) and midday (Ψmd) leaf water potentials were significantly lower under drought treatments compared to those in control (P < .01). Stomatal conductance (gs) exhibited a strong reduction, leading to decreased leaf transpiration and photosynthesis under drought. However, the reduction in gs did not effectively prevent the decrease in Ψmd. Instead, both Ψpd and Ψmd became more negative with increasing drought stress, but their difference remaining relatively constant (being ~1.1 MPa) across treatments. These results suggest that black locust adopts a balanced water regulatory strategy between isohydry and anisohydry to cope with drought stress. These results contribute to an enhanced understanding of the crucial physiological responses of black locust under drought stress, offering valuable insights for future management strategies aimed at sustaining the ecosystem stability of black locust plantations in an increasingly arid climate.
Exploring the Adaptation of Native Shrub Species to Different Levels of Shading: Augmenting their Sustainable Exploitation Framework
Authors: Karapatzak Eleftherios , Koularmanis Konstantinos , Papanastasi Katerina , Fotakis Dimitrios , Grigoriadou Katerina , Maloupa Eleni
Published: June 2024

The environmental adaptation potential of regional wild germplasm resources should be investigated in a species-specific manner in terms of the sustainable exploitation of underutilized native species. In the current work, three fruit/ornamental shrub species (Rosa canina L., Sambucus nigra L. and Cornus sanguinea L.) originating from regional wild germplasm of Greece with a previously set domestication framework have been investigated in terms of their environmental adaptation to different levels of shading. To this end, targeted experimentation was conducted on ex situ adapted material by applying different shading levels (0%, 30% and 60% shading) in purpose-built netting tunnels. Rosa canina showed similar growth patterns among the shading levels applied but with increased chlorophyll fluorescence patterns and increased abaxial leaf stomatal density with increased shading. Sambucus nigra showed similar results to R. canina in photosynthetic efficiency and leaf stomatal density but with additional effects on plant growth patterns. Cornus sanguinea, on the other hand, was not affected by shading level in the measured parameters. These results outline the adaptation potential in a species-specific manner of the studied species to shading in terms of adding novel exploitation options for agroecosystems, agroforestry, and landscape management in peri-urban green spaces and peri-urban forest understory enrichment to mitigate climate change impacts in temperate and semi-arid climates.

Study Implications: This study explores the adaptation potential to increasing levels of shading of ex situ adapted germplasm of wild origin of three underutilized shrub species with known multifaceted value. The work builds on the sustainable utilization framework of the focal species in terms of novel exploitation options in landscape management for peri-urban green spaces and peri-urban forest understory enrichment for enhancing biodiversity and soil erosion protection. Therefore, this work offers an example of an underlying research line towards systematized screening and utilization of wild plant species for climate change impact mitigation in agroecosystems, agroforestry, and landscape management in temperate semi-arid climates.
Whole-genome sequencing analysis of soybean diversity across different countries and selection signature of Korean soybean accession
Authors: Cho Youngbeom , Kim Jae-Yoon , Kim Seon-Kyu , Kim Seon-Young , Kim Namshin , Lee Jinhyuk , Park Jong-Lyul
Published: June 2024

Soybean is an important agricultural crop known for its high protein and oil content, contributing to essential nutritional and health benefits for humans. Domesticated in China over 5,000 years ago, soybean has since adapted to diverse environments and spread worldwide. This study aimed to investigate the genomic characteristics and population structures of 2,317 publicly available soybean whole-genome sequences from diverse geographical regions, including China, Korea, Japan, Europe, North America, and South America. We used large-scale whole-genome sequencing data to perform high-resolution analyses to reveal the genetic characteristics of soybean accessions. Soybean accessions from China and Korea exhibited landrace characteristics, indicating higher genetic diversity and adaptation to local environments. On the other hand, soybean accessions from Japan, the European Union, and South America were found to have low genetic diversity due to artificial selection and breeding for agronomic traits. We also identified key variants and genes associated with the ability to adapt to different environments. In Korean soybean accessions, we observed strong selection signals for isoflavone synthesis, an adaptive trait critical for improving soybean adaptability, survival, and reproductive success by mitigating environmental stress. Identifying specific genomic regions showing unique patterns of selective sweeps for genes such as HIDH, CYP73A11, IFS1, and CYP81E11 associated with isoflavone synthesis provided valuable insights into potential adaptation mechanisms. Our research has significantly improved our understanding of soybean diversity at the genetic level. We have identified key genetic variants and genes influencing adaptability, laying the foundation for future advances in genomics-based breeding programs and crop improvement efforts.
OrthoPhyl—streamlining large-scale, orthology-based phylogenomic studies of bacteria at broad evolutionary scales
Authors: Middlebrook Earl A , Katani Robab , Fair Jeanne M
Published: June 2024

There are a staggering number of publicly available bacterial genome sequences (at writing, 2.0 million assemblies in NCBI's GenBank alone), and the deposition rate continues to increase. This wealth of data begs for phylogenetic analyses to place these sequences within an evolutionary context. A phylogenetic placement not only aids in taxonomic classification but informs the evolution of novel phenotypes, targets of selection, and horizontal gene transfer. Building trees from multi-gene codon alignments is a laborious task that requires bioinformatic expertise, rigorous curation of orthologs, and heavy computation. Compounding the problem is the lack of tools that can streamline these processes for building trees from large-scale genomic data. Here we present OrthoPhyl, which takes bacterial genome assemblies and reconstructs trees from whole genome codon alignments. The analysis pipeline can analyze an arbitrarily large number of input genomes (>1200 tested here) by identifying a diversity-spanning subset of assemblies and using these genomes to build gene models to infer orthologs in the full dataset. To illustrate the versatility of OrthoPhyl, we show three use cases: E. coli/Shigella, Brucella/Ochrobactrum and the order Rickettsiales. We compare trees generated with OrthoPhyl to trees generated with kSNP3 and GToTree along with published trees using alternative methods. We show that OrthoPhyl trees are consistent with other methods while incorporating more data, allowing for greater numbers of input genomes, and more flexibility of analysis.
Do I Have Symptoms of Dementia: A Discursive Study of Awareness and Shame Among People With Advanced Dementia
Authors: Kłosińska Urszula , Leszko Magdalena
Published: June 2024

Background and Objectives

This study explores the narrated experiences of individuals with advanced stages of late-onset dementia, focusing on their diagnosis awareness. Such framing is motivated by 2 reasons. Firstly, there is a lack of consensus regarding the prevalence of anosognosia among people with dementia. Secondly, research on anosognosia often neglects to address the important issues of shame and stigma associated with receiving a dementia diagnosis.

Research Design and Methods

For this qualitative study, a total of 27 participants ranging in age from 66 to 94 were involved. The data collected were analyzed using textual-oriented discourse analysis.

Results

Our findings indicated that individuals with dementia struggled to comprehend the medical terminology used to describe their experiences within biomedical standards. The interviewees utilized 5 negative discourses on dementia, which shaped their attitudes toward the condition and people diagnosed with it. These discourses depicted dementia as an illness, negative aging, a devaluation, a burden, and a life tragedy. Moreover, study participants did not outright reject the diagnosis but rather negotiated its acceptance within the context of shame associated with dementia.

Discussion and Implications

The concept of anosognosia can serve as a mechanism of social control and stigmatization of people with dementia within the dominant biomedical discourse.
RicePilaf: a post-GWAS/QTL dashboard to integrate pangenomic, coexpression, regulatory, epigenomic, ontology, pathway, and text-mining information to provide functional insights into rice QTLs and GWAS loci
Authors: Shrestha Anish M S , Gonzales Mark Edward M , Ong Phoebe Clare L , Larmande Pierre , Lee Hyun-Sook , Jeung Ji-Ung , Kohli Ajay , Chebotarov Dmytro , Mauleon Ramil P , Lee Jae-Sung , McNally Kenneth L
Published: June 2024

Background

As the number of genome-wide association study (GWAS) and quantitative trait locus (QTL) mappings in rice continues to grow, so does the already long list of genomic loci associated with important agronomic traits. Typically, loci implicated by GWAS/QTL analysis contain tens to hundreds to thousands of single-nucleotide polmorphisms (SNPs)/genes, not all of which are causal and many of which are in noncoding regions. Unraveling the biological mechanisms that tie the GWAS regions and QTLs to the trait of interest is challenging, especially since it requires collating functional genomics information about the loci from multiple, disparate data sources.

Results

We present RicePilaf, a web app for post-GWAS/QTL analysis, that performs a slew of novel bioinformatics analyses to cross-reference GWAS results and QTL mappings with a host of publicly available rice databases. In particular, it integrates (i) pangenomic information from high-quality genome builds of multiple rice varieties, (ii) coexpression information from genome-scale coexpression networks, (iii) ontology and pathway information, (iv) regulatory information from rice transcription factor databases, (v) epigenomic information from multiple high-throughput epigenetic experiments, and (vi) text-mining information extracted from scientific abstracts linking genes and traits. We demonstrate the utility of RicePilaf by applying it to analyze GWAS peaks of preharvest sprouting and genes underlying yield-under-drought QTLs.

Conclusions

RicePilaf enables rice scientists and breeders to shed functional light on their GWAS regions and QTLs, and it provides them with a means to prioritize SNPs/genes for further experiments. The source code, a Docker image, and a demo version of RicePilaf are publicly available at https://github.com/bioinfodlsu/rice-pilaf.
CheRRI—Accurate classification of the biological relevance of putative RNA–RNA interaction sites
Authors: Müller Teresa , Mautner Stefan , Videm Pavankumar , Eggenhofer Florian , Raden Martin , Backofen Rolf
Published: June 2024

Background

RNA–RNA interactions are key to a wide range of cellular functions. The detection of potential interactions helps to understand the underlying processes. However, potential interactions identified via in silico or experimental high-throughput methods can lack precision because of a high false-positive rate.

Results

We present CheRRI, the first tool to evaluate the biological relevance of putative RNA–RNA interaction sites. CheRRI filters candidates via a machine learning–based model trained on experimental RNA–RNA interactome data. Its unique setup combines interactome data and an established thermodynamic prediction tool to integrate experimental data with state-of-the-art computational models. Applying these data to an automated machine learning approach provides the opportunity to not only filter data for potential false positives but also tailor the underlying interaction site model to specific needs.

Conclusions

CheRRI is a stand-alone postprocessing tool to filter either predicted or experimentally identified potential RNA–RNA interactions on a genomic level to enhance the quality of interaction candidates. It is easy to install (via conda, pip packages), use (via Galaxy), and integrate into existing RNA–RNA interaction pipelines.
Genomic decoding of Theobroma grandiflorum (cupuassu) at chromosomal scale: evolutionary insights for horticultural innovation
Authors: Alves Rafael Moysés , de Abreu Vinicius A C , Oliveira Rafaely Pantoja , Almeida João Victor dos Anjos , de Oliveira Mauro de Medeiros , Silva Saura R , Paschoal Alexandre R , de Almeida Sintia S , de Souza Pedro A F , Ferro Jesus A , Miranda Vitor F O , Figueira Antonio , Domingues Douglas S , Varani Alessandro M
Published: June 2024

Background

Theobroma grandiflorum (Malvaceae), known as cupuassu, is a tree indigenous to the Amazon basin, valued for its large fruits and seed pulp, contributing notably to the Amazonian bioeconomy. The seed pulp is utilized in desserts and beverages, and its seed butter is used in cosmetics. Here, we present the sequenced telomere-to-telomere genome of cupuassu, disclosing its genomic structure, evolutionary features, and phylogenetic relationships within the Malvaceae family.

Findings

The cupuassu genome spans 423 Mb, encodes 31,381 genes distributed in 10 chromosomes, and exhibits approximately 65% gene synteny with the Theobroma cacao genome, reflecting a conserved evolutionary history, albeit punctuated with unique genomic variations. The main changes are pronounced by bursts of long-terminal repeat retrotransposons at postspecies divergence, retrocopied and singleton genes, and gene families displaying distinctive patterns of expansion and contraction. Furthermore, positively selected genes are evident, particularly among retained and dispersed tandem and proximal duplicated genes associated with general fruit and seed traits and defense mechanisms, supporting the hypothesis of potential episodes of subfunctionalization and neofunctionalization following duplication, as well as impact from distinct domestication process. These genomic variations may underpin the differences observed in fruit and seed morphology, ripening, and disease resistance between cupuassu and the other Malvaceae species.

Conclusions

The cupuassu genome offers a foundational resource for both breeding improvement and conservation biology, yielding insights into the evolution and diversity within the genus Theobroma.
Extended haplotype with rs41524547-G defines the ancestral origin of SCA10
Authors: McFarland Karen N , Tiwari Anjana , Hashem Vera , Zhang Linwei , Zeng Desmond , Vincent Justin , Arredondo Maria J , Johnson Kristy L , Gan Shi Rui , Yabe Ichiro , Skov Laurits , Rasmussen Astrid , Ashizawa Tetsuo
Published: June 2024

Spinocerebellar ataxia type 10 (SCA10) is a rare autosomal dominant ataxia caused by a large expansion of the (ATTCT)n repeat in ATXN10. SCA10 was described in Native American and Asian individuals which prompted a search for an expanded haplotype to confirm a common ancestral origin for the expansion event. All patients with SCA10 expansions in our cohort share a single haplotype defined at the 5′-end by the minor allele of rs41524547, located ~35 kb upstream of the SCA10 expansion. Intriguingly, rs41524547 is located within the miRNA gene, MIR4762, within its DROSHA cleavage site and just outside the seed sequence for mir4792-5p. The world-wide frequency of rs41524547-G is less than 5% and found almost exclusively in the Americas and East Asia—a geographic distribution that mirrors reported SCA10 cases. We identified rs41524547-G(+) DNA from the 1000 Genomes/International Genome Sample Resource and our own general population samples and identified SCA10 repeat expansions in up to 25% of these samples. The reduced penetrance of these SCA10 expansions may be explained by a young (pre-onset) age at sample collection, a small repeat size, purity of repeat units, or the disruption of miR4762-5p function. We conclude that rs41524547-G is the most robust at-risk SNP allele for SCA10, is useful for screening of SCA10 expansions in population genetics studies and provides the most compelling evidence to date for a single, prehistoric origin of SCA10 expansions sometime prior to or during the migration of individuals across the Bering Land Bridge into the Americas.
Diagnosis of Inflammatory Bowel Disease–Associated Peripheral Arthritis: A Systematic Review
Authors: Falloon Katherine , Dossaji Zahra , Mude Pooja , Abushamma Suha , Ananthakrishnan Ashwin , Barnes Edward L , Bhalla Jaideep , Bhattacharya Abhik , Cheemalavagu Shashank , Colombel Jean-Fred , Cross Raymond K , Ermann Joerg , Ha Christina , Herfarth Hans , Horst Sara , Hou Jason , Husni M Elaine , Kline Theresa M , Kuhn Kristine A , Long Millie D , Loftus Edward V , Lukin Dana J , Patel Aditi , Rubin David T , Scherl Ellen J , Shah Samir A , Siaton Bernadette C , Sleiman Joseph , Qazi Taha , Weisman Michael H , Cohen Benjamin L , Feagan Brian G , Rieder Florian
Published: June 2024

Background

Inflammatory bowel disease (IBD)–associated peripheral spondyloarthritis (pSpA) decreases quality of life and remains poorly understood. Given the prevalence of this condition and its negative impact, it is surprising that evidence-based disease definitions and diagnostic strategies are lacking. This systematic review summarizes available data to facilitate development and validation of diagnostics, patient-reported outcomes, and imaging indices specific to this condition.

Methods

A literature search was conducted. Consensus or classification criteria, case series, cross-sectional studies, cohort studies, and randomized controlled trials related to diagnosis were included.

Results

A total of 44 studies reporting data on approximately 1500 patients with pSpA were eligible for analysis. Data quality across studies was only graded as fair to good. Due to large heterogeneity, meta-analysis was not possible. The majority of studies incorporated patient-reported outcomes and a physical examination. A total of 13 studies proposed or validated screening tools, consensus, classification, or consensus criteria. A total of 28 studies assessed the role of laboratory tests, none of which were considered sufficiently accurate for use in diagnosis. A total of 17 studies assessed the role of imaging, with the available literature insufficient to fully endorse any imaging modality as a robust diagnostic tool.

Conclusions

This review highlights existing inconsistency and lack of a clear diagnostic approach for IBD-associated pSpA. Given the absence of an evidence-based approach, a combination of existing criteria and physician assessment should be utilized. To address this issue comprehensively, our future efforts will be directed toward pursuit of a multidisciplinary approach aimed at standardizing evaluation and diagnosis of IBD-associated pSpA.
Definitions of Suffixed Loanwords in Dictionaries of Foreign Words in Slovak
Authors: Panocová Renáta
Published: June 2024

Dictionaries of foreign words in Slovak have a tradition of publication that can be traced for more than one hundred years. Their popularity among users is closely connected to a general interest in so-called language cultivation, which includes a good knowledge of frequently used words of non-native origin. Here, special attention will be paid to suffixed loanwords. In the case of larger sets of loanwords with the same suffix, speakers recognize their similarity and regularity. The central aim of this paper is to investigate how the lexicographic representation of suffixed loanwords in Slovak dictionaries of foreign words developed in the past one hundred years. The analysis focuses on a set of loanwords with three non-native suffixes, namely -ácia (‘-ation’), -izmus (‘-ism’), and -ita (‘-ity’), each of which stands in competition with a corresponding native suffix. It was investigated how the emergence of a competing variant with a native suffix attached to the same foreign base influences the information given by dictionaries. For the analysis, I used five dictionaries of foreign words in Slovak published between 1939 and 2005. Based on a sample of entries from these dictionaries, I distinguish four types of dictionary definitions used to describe suffixed loanwords. Then I propose a model explaining the historical and logical relationships between these four definition types.
Subanesthetic Ketamine Suppresses Locus Coeruleus–Mediated Alertness Effects: A 7T fMRI Study
Authors: Liebe Thomas , Danyeli Lena Vera , Sen Zümrüt Duygu , Li Meng , Kaufmann Jörn , Walter Martin
Published: June 2024

Background

The NMDA antagonist S-ketamine is gaining increasing use as a rapid-acting antidepressant, although its exact mechanisms of action are still unknown. In this study, we investigated ketamine in respect to its properties toward central noradrenergic mechanisms and how they influence alertness behavior.

Methods

We investigated the influence of S-ketamine on the locus coeruleus (LC) brain network in a placebo-controlled, cross-over, 7T functional, pharmacological MRI study in 35 healthy male participants (25.1 ± 4.2 years) in conjunction with the attention network task to measure LC-related alertness behavioral changes.

Results

We could show that acute disruption of the LC alertness network to the thalamus by ketamine is related to a behavioral alertness reduction.

Conclusion

The results shed new light on the neural correlates of ketamine beyond the glutamatergic system and underpin a new concept of how it may unfold its antidepressant effects.
Stratification in drying films: diffusiophoresis driven by nanoparticles and their counterions
Authors: Rees-Zimmerman Clare R , Routh Alexander F
Published: June 2024

Recent experimental work has highlighted that electrolyte-driven diffusiophoresis is likely to be the most significant phoretic motion in a mixture of silica nanoparticles and relatively large latex particles, which are commonly used in coatings. In this work, this diffusiophoretic effect, powered by gradients in the nanoparticles and their stabilizing cations, is modelled in drying films. A continuum hydrodynamic model is derived, and the resulting partial differential equations solved numerically. An asymptotic solution is found for high evaporation rate. It is found that the final film structure is governed by the relative magnitudes of the diffusive and diffusiophoretic terms. Two methods are discovered to control the resulting stratification: (i) setting the surface charge on the particles, and (ii) setting the background salt concentration. Either of these can be used to select either small- or large-on-top stratification or a homogenous film. The diffusiophoretic term promotes small-on-top stratification, and so may account for experimental observations of accumulated small particles at the top surface of dried films.
Asymptotic Insights for Projection, Gordon–Lewis, and Sidon Constants in Boolean Cube Function Spaces
Authors: Defant A , Galicer D , Mansilla M , Mastyło M , Muro S
Published: June 2024

The main aim of this work is to study important local Banach space constants for Boolean cube function spaces. Specifically, we focus on $\mathcal{B}_{\mathcal{S}}^{N}$, the finite-dimensional Banach space of all real-valued functions defined on the $N$-dimensional Boolean cube $\{-1, +1\}^{N}$ that have Fourier–Walsh expansions supported on a fixed family $\mathcal{S}$ of subsets of $\{1, \ldots , N\}$. Our investigation centers on the projection, Sidon, and Gordon–Lewis constants of this function space. We combine tools from different areas to derive exact formulas and asymptotic estimates of these parameters for special types of families $\mathcal{S}$ depending on the dimension $N$ of the Boolean cube and other complexity characteristics of the support set $\mathcal{S}$. Using local Banach space theory, we establish the intimate relationship among these three important constants.
Pharmacokinetics and Safety of Remdesivir in Pregnant and Nonpregnant Women With COVID-19: Results From IMPAACT 2032
Authors: Brooks Kristina M , Baltrusaitis Kristin , Clarke Diana F , Nachman Sharon , Jao Jennifer , Purswani Murli U , Agwu Allison , Beneri Christy , Deville Jaime G , Powis Kathleen M , Stek Alice M , Eke Ahizechukwu C , Shapiro David E , Capparelli Edmund , Greene Elizabeth , George Kathleen , Yin Dwight E , Jean-Philippe Patrick , Chakhtoura Nahida , Bone Frederic , Bacon Kira , Johnston Benjamin , Reding Christina , Kersey Kathryn , Humeniuk Rita , Best Brookie M , Mirochnick Mark , Momper Jeremiah D ,   IMPAACT 2032 Study Team, Lartey Emanuela , Kalra Rohit , Yee Lynn , Stewart James Etta , Cavallo Martha , Baig Mirza , Collinson-Streng Aleisha , Anderson Thuy , Addison Bonnie , Chakraborty Barsha , Avila Cecilia , Caso Giuseppe , Janzen Carla , Carter Michele F , Paul Mary , Eser-Jose Ruth , Pontifes Mariam , Jackson Chivon McMullen , Gomez Nicolette , Alvarez Grace , Mitchell Charles , Potter JoNell , Badell Martina L , Jordan-Thompson Sierra , Floyd Riaun , Thomas-Seaton LaTeshia , Weinberg Adriana , Curran-Hays Shane , Kwon Christine , Glenny Carrie , Aziz Mariam , McNichols Maureen
Published: June 2024

Background

Pregnant people with coronavirus disease 2019 (COVID-19) experience higher risk for severe disease and adverse pregnancy outcomes, but no pharmacokinetic (PK) data exist to support dosing of COVID-19 therapeutics during pregnancy. We report PK and safety data for intravenous remdesivir in pregnancy.

Methods

IMPAACT 2032 was a phase 4 prospective, open-label, nonrandomized opportunistic study of hospitalized pregnant and nonpregnant women receiving intravenous remdesivir as part of clinical care. Intensive PK sampling was performed on infusion days 3, 4, or 5 with collection of plasma and peripheral blood mononuclear cells (PBMCs). Safety data were recorded from first infusion through 4 weeks after last infusion and at delivery. Geometric mean ratios (GMR) (90% confidence intervals [CI]) of PK parameters between pregnant and nonpregnant women were calculated.

Results

Fifty-three participants initiated remdesivir (25 pregnant; median gestational age, 27.6 weeks; interquartile range, 24.9–31.0 weeks). Plasma exposures of remdesivir, its 2 major metabolites (GS-704277 and GS-441524), and the free remdesivir fraction were similar between pregnant and nonpregnant participants. Concentrations of the active triphosphate (GS-443902) in PBMCs increased 2.04-fold (90% CI, 1.35–3.03) with each additional infusion in nonpregnant versus pregnant participants. Three adverse events in nonpregnant participants were related to treatment (1 grade 3; 2 grade 2 resulting in treatment discontinuation). There were no treatment-related adverse pregnancy outcomes or congenital anomalies detected.

Conclusions

Plasma remdesivir PK parameters were comparable between pregnant and nonpregnant women, and no safety concerns were identified based on our limited data. These findings suggest no dose adjustments are indicated for intravenous remdesivir during pregnancy.

Clinical Trials Registration

NCT04582266.
Impact of Hypoxia-Inducible Factor-1α on Host Immune Metabolism and Tissue Damage During Mycobacterium bovis Infection
Authors: Nan Yue , Wang Yuanzhi , Dong Yuhui , Liu Yiduo , Ge Xin , Chen Yulan , Long Meizhen , Zhou Xiangmei
Published: June 2024

Hypoxia-inducible factor-1α (HIF-1α) is a pivotal regulator of metabolic and inflammatory responses. This study investigated the role of HIF-1α in Mycobacterium bovis infection and its effects on host immune metabolism and tissue damage. We evaluated the expression of immunometabolism markers and matrix metalloproteinases (MMPs) in cells infected with M. bovis, and following HIF-1α inhibition in vitro. To understand the implications of HIF-1α inhibition on disease progression, mice at different infection stages were treated with the HIF-1α inhibitor, YC-1. Our results revealed an upregulation of HIF-1α in macrophages after M. bovis infection, facilitating enhanced M1 macrophage polarization. Blockade of HIF-1α moderated these responses but escalated MMP activity, hindering bacterial control. Consistent with our in vitro results, early-stage treatment of mice with YC-1 aggravated pathological alterations and tissue damage, while late-stage HIF-1α inhibition proved beneficial in managing the disease. Our findings underscored the nuanced role of HIF-1α across different phases of M. bovis infection.
The Spirit of the Pluriverse: Africana Spirit-Based Epistemologies and Interepistemic Thinking
Authors: Wumkes Jake
Published: June 2024

In this article, I argue that interepistemic thinking is characteristic of Africana spirit-based epistemologies and that such thinking is essential to the construction of the pluriverse. I demonstrate that the spiritual basis of many Africana epistemologies facilitates interepistemic thinking and the making of a more equitable, functional, and healthy “modernity.” This is despite narratives of modernity, such as that of Max Weber, that are embedded in a secular-rationalist ideology, which tend to mark spirituality as an invalid means of accessing, representing, or (re)producing truth, marking it as “primitive,” destined to disappear, and as incompatible with the so-called modern world. For this reason, decoloniality as it applies to an analysis of Africana spirit-based epistemologies must demonstrate the limited, Eurocentric nature of the secular-rationalist paradigm. I support these arguments through an analysis of the role of interepistemic thinking in the spirit-based epistemologies apparent in what are commonly referred to as African diasporic religions. In doing so, I will also offer a critical perspective on the application of religion as a conceptual category to the realities of the peoples of the African diaspora, following important recent scholarship in the study of religion. I will begin with a review of the nature of the pluriverse and a brief description of Nelson Maldonado-Torres’s (2008) critique of secularism, followed by an analysis of interepistemic thinking as it can be observed within Africana spirit-based epistemologies, and conclude with an explanation of how this may inform a critical reconsideration of the epistemic bases that undergird the modern/colonial world system.