bluuebunny/crossref_metadata_2025 huggingface dataset:
Rotation plays a role in the generation of magnetic fields in single white dwarfs
Authors: Hernandez Mercedes S , Schreiber Matthias R , Landstreet John D , Bagnulo Stefano , Parsons Steven G , Chavarria Martin , Toloza Odette , Bell Keaton J
Published: February 2024

Recent surveys of close white dwarf binaries as well as single white dwarfs have provided evidence for the late appearance of magnetic fields in white dwarfs, and a possible generation mechanism, a crystallization and rotation-driven dynamo has been suggested. A key prediction of this dynamo is that magnetic white dwarfs rotate, at least on average, faster than their non-magnetic counterparts and/or that the magnetic field strength increases with rotation. Here we present rotation periods of ten white dwarfs within 40 pc measured using photometric variations. Eight of the light curves come from TESS observations and are thus not biased towards short periods, in contrast to most period estimates that have been reported previously in the literature. These TESS spin periods are indeed systematically shorter than those of non-magnetic white dwarfs. This means that the crystallization and rotation-driven dynamo could be responsible for a fraction of the magnetic fields in white dwarfs. However, the full sample of magnetic white dwarfs also contains slowly rotating strongly magnetic white dwarfs which indicates that another mechanism that leads to the late appearance of magnetic white dwarfs might be at work, either in addition to or instead of the dynamo. The fast-spinning and massive magnetic white dwarfs that appear in the literature form a small fraction of magnetic white dwarfs, and probably result from a channel related to white dwarf mergers.
Differentiable stochastic halo occupation distribution
Authors: Horowitz Benjamin , Hahn ChangHoon , Lanusse Francois , Modi Chirag , Ferraro Simone
Published: February 2024

In this work, we demonstrate how differentiable stochastic sampling techniques developed in the context of deep reinforcement learning can be used to perform efficient parameter inference over stochastic, simulation-based, forward models. As a particular example, we focus on the problem of estimating parameters of halo occupation distribution (HOD) models that are used to connect galaxies with their dark matter haloes. Using a combination of continuous relaxation and gradient re-parametrization techniques, we can obtain well-defined gradients with respect to HOD parameters through discrete galaxy catalogue realizations. Having access to these gradients allows us to leverage efficient sampling schemes, such as Hamiltonian Monte Carlo, and greatly speed up parameter inference. We demonstrate our technique on a mock galaxy catalogue generated from the Bolshoi simulation using a standard HOD model and find near-identical posteriors as standard Markov chain Monte Carlo techniques with an increase of ∼8× in convergence efficiency. Our differentiable HOD model also has broad applications in full forward model approaches to cosmic structure and cosmological analysis.
Conservation of Affinity Rather Than Sequence Underlies a Dynamic Evolution of the Motif-Mediated p53/MDM2 Interaction in Ray-Finned Fishes
Authors: Mihalič Filip , Arcila Dahiana , Pettersson Mats E , Farkhondehkish Pouria , Andersson Eva , Andersson Leif , Betancur-R Ricardo , Jemth Per
Published: February 2024

The transcription factor and cell cycle regulator p53 is marked for degradation by the ubiquitin ligase MDM2. The interaction between these 2 proteins is mediated by a conserved binding motif in the disordered p53 transactivation domain (p53TAD) and the folded SWIB domain in MDM2. The conserved motif in p53TAD from zebrafish displays a 20-fold weaker interaction with MDM2, compared to the interaction in human and chicken. To investigate this apparent difference, we tracked the molecular evolution of the p53TAD/MDM2 interaction among ray-finned fishes (Actinopterygii), the largest vertebrate clade. Intriguingly, phylogenetic analyses, ancestral sequence reconstructions, and binding experiments showed that different loss-of-affinity changes in the canonical binding motif within p53TAD have occurred repeatedly and convergently in different fish lineages, resulting in relatively low extant affinities (KD = 0.5 to 5 μM). However, for 11 different fish p53TAD/MDM2 interactions, nonconserved regions flanking the canonical motif increased the affinity 4- to 73-fold to be on par with the human interaction. Our findings suggest that compensating changes at conserved and nonconserved positions within the motif, as well as in flanking regions of low conservation, underlie a stabilizing selection of “functional affinity” in the p53TAD/MDM2 interaction. Such interplay complicates bioinformatic prediction of binding and calls for experimental validation. Motif-mediated protein–protein interactions involving short binding motifs and folded interaction domains are very common across multicellular life. It is likely that the evolution of affinity in motif-mediated interactions often involves an interplay between specific interactions made by conserved motif residues and nonspecific interactions by nonconserved disordered regions.
Long-term suboptimal dietary trace element supply does not affect trace element homeostasis in murine cerebellum
Authors: Friese Sharleen , Ranzini Giovanna , Tuchtenhagen Max , Lossow Kristina , Hertel Barbara , Pohl Gabriele , Ebert Franziska , Bornhorst Julia , Kipp Anna Patricia , Schwerdtle Tanja
Published: February 2024

The ageing process is associated with alterations of systemic trace element (TE) homeostasis increasing the risk, e.g. neurodegenerative diseases. Here, the impact of long-term modulation of dietary intake of copper, iron, selenium, and zinc was investigated in murine cerebellum. Four- and 40-wk-old mice of both sexes were supplied with different amounts of those TEs for 26 wk. In an adequate supply group, TE concentrations were in accordance with recommendations for laboratory mice while suboptimally supplied animals received only limited amounts of copper, iron, selenium, and zinc. An additional age-adjusted group was fed selenium and zinc in amounts exceeding recommendations. Cerebellar TE concentrations were measured by inductively coupled plasma–tandem mass spectrometry. Furthermore, the expression of genes involved in TE transport, DNA damage response, and DNA repair as well as selected markers of genomic stability [8-oxoguanine, incision efficiency toward 8-oxoguanine, 5-hydroxyuracil, and apurinic/apyrimidinic sites and global DNA (hydroxy)methylation] were analysed. Ageing resulted in a mild increase of iron and copper concentrations in the cerebellum, which was most pronounced in the suboptimally supplied groups. Thus, TE changes in the cerebellum were predominantly driven by age and less by nutritional intervention. Interestingly, deviation from adequate TE supply resulted in higher manganese concentrations of female mice even though the manganese supply itself was not modulated. Parameters of genomic stability were neither affected by age, sex, nor diet. Overall, this study revealed that suboptimal dietary TE supply does not substantially affect TE homeostasis in the murine cerebellum.
Uptake and accumulation mechanisms of hexachloroplatinate(IV) ions in the unicellular alga, Pseudococcomyxa simplex
Authors: Tokoro Masato , Imamura Yu , Kumagai Kazuhiro , Hokura Akiko
Published: February 2024

Platinum uptake was examined by adding hexachloroplatinate(IV) solution to the unicellular alga Pseudococcomyxa simplex. After the addition of platinum solution ([Pt] = 100 mg/kg, pH 3.2–3.4) for a certain time, the cells were quickly frozen and subjected to μ-XRF (X-ray fluorescence) analysis using synchrotron X-rays. The beam size of approximately 1 micrometer allowed visualization of the platinum distribution within a single cell. On the other hand, we examined platinum uptake in enzyme-treated protoplasts and lyophilized cells and found that the platinum uptake concentrations in these samples were higher than in living in-vivo cells. Cell wall and cell metabolism were presumed to interfere with the uptake of hexachloroplatinate(IV) ions. All platinum ions taken up by the cells were reduced to divalent form. The effect of light on platinum addition was also investigated. When platinum was added under light conditions, some samples showed higher platinum accumulation than under shade conditions.
Optimizing sequence design strategies for perturbation MPRAs: a computational evaluation framework
Authors: Liu Jiayi , Ashuach Tal , Inoue Fumitaka , Ahituv Nadav , Yosef Nir , Kreimer Anat
Published: February 2024

The advent of perturbation-based massively parallel reporter assays (MPRAs) technique has facilitated the delineation of the roles of non-coding regulatory elements in orchestrating gene expression. However, computational efforts remain scant to evaluate and establish guidelines for sequence design strategies for perturbation MPRAs. In this study, we propose a framework for evaluating and comparing various perturbation strategies for MPRA experiments. Within this framework, we benchmark three different perturbation approaches from the perspectives of alteration in motif-based profiles, consistency of MPRA outputs, and robustness of models that predict the activities of putative regulatory motifs. While our analyses show very similar results across multiple benchmarking metrics, the predictive modeling for the approach involving random nucleotide shuffling shows significant robustness compared with the other two approaches. Thus, we recommend designing sequences by randomly shuffling the nucleotides of the perturbed site in perturbation-MPRA, followed by a coherence check to prevent the introduction of other variations of the target motifs. In summary, our evaluation framework and the benchmarking findings create a resource of computational pipelines and highlight the potential of perturbation-MPRA in predicting non-coding regulatory activities.
RAVER1 hinders lethal EMT and modulates miR/RISC activity by the control of alternative splicing
Authors: Wedler Alice , Bley Nadine , Glaß Markus , Müller Simon , Rausch Alexander , Lederer Marcell , Urbainski Julia , Schian Laura , Obika Kingsley-Benjamin , Simon Theresa , Peters Lara Meret , Misiak Claudia , Fuchs Tommy , Köhn Marcel , Jacob Roland , Gutschner Tony , Ihling Christian , Sinz Andrea , Hüttelmaier Stefan
Published: February 2024

The RAVER1 protein serves as a co-factor in guiding the polypyrimidine tract-binding protein (PTBP)-dependent control of alternative splicing (AS). Whether RAVER1 solely acts in concert with PTBPs and how it affects cancer cell fate remained elusive. Here, we provide the first comprehensive investigation of RAVER1-controlled AS in cancer cell models. This reveals a pro-oncogenic role of RAVER1 in modulating tumor growth and epithelial-mesenchymal-transition (EMT). Splicing analyses and protein-association studies indicate that RAVER1 guides AS in association with other splicing regulators, including PTBPs and SRSFs. In cancer cells, one major function of RAVER1 is the stimulation of proliferation and restriction of apoptosis. This involves the modulation of AS events within the miR/RISC pathway. Disturbance of RAVER1 impairs miR/RISC activity resulting in severely deregulated gene expression, which promotes lethal TGFB-driven EMT. Among others, RAVER1-modulated splicing events affect the insertion of protein interaction modules in factors guiding miR/RISC-dependent gene silencing. Most prominently, in all three human TNRC6 proteins, RAVER1 controls AS of GW-enriched motifs, which are essential for AGO2-binding and the formation of active miR/RISC complexes. We propose, that RAVER1 is a key modulator of AS events in the miR/RISC pathway ensuring proper abundance and composition of miR/RISC effectors. This ensures balanced expression of TGFB signaling effectors and limits TGFB induced lethal EMT.
Mage transposon: a novel gene delivery system for mammalian cells
Authors: Tian Jinghan , Tong Doudou , Li Zhendong , Wang Erqiang , Yu Yifei , Lv Hangya , Hu Zhendan , Sun Fang , Wang Guoping , He Min , Xia Tian
Published: February 2024

Transposons, as non-viral integration vectors, provide a secure and efficient method for stable gene delivery. In this study, we have discovered Mage (MG), a novel member of the piggyBac(PB) family, which exhibits strong transposability in a variety of mammalian cells and primary T cells. The wild-type MG showed a weaker insertion preference for near genes, transcription start sites (TSS), CpG islands, and DNaseI hypersensitive sites in comparison to PB, approaching the random insertion pattern. Utilizing in silico virtual screening and feasible combinatorial mutagenesis in vitro, we effectively produced the hyperactive MG transposase (hyMagease). This variant boasts a transposition rate 60% greater than its native counterpart without significantly altering its insertion pattern. Furthermore, we applied the hyMagease to efficiently deliver chimeric antigen receptor (CAR) into T cells, leading to stable high-level expression and inducing significant anti-tumor effects both in vitro and in xenograft mice models. These findings provide a compelling tool for gene transfer research, emphasizing its potential and prospects in the domains of genetic engineering and gene therapy.
Two birds with one stone: SGI1 can stabilize itself and expel the IncC helper by hijacking the plasmid parABS system
Authors: Murányi Gábor , Szabó Mónika , Acsai Károly , Kiss János
Published: February 2024

The SGI1 family integrative mobilizable elements, which are efficient agents in distribution of multidrug resistance in Gammaproteobacteria, have a complex, parasitic relationship with their IncC conjugative helper plasmids. Besides exploiting the transfer apparatus, SGI1 also hijacks IncC plasmid control mechanisms to time its own excision, replication and expression of self-encoded T4SS components, which provides advantages for SGI1 over its helpers in conjugal transfer and stable maintenance. Furthermore, SGI1 destabilizes its helpers in an unknown, replication-dependent way when they are concomitantly present in the same host. Here we report how SGI1 exploits the helper plasmid partitioning system to displace the plasmid and simultaneously increase its own stability. We show that SGI1 carries two copies of sequences mimicking the parS sites of IncC plasmids. These parS-like elements bind the ParB protein encoded by the plasmid and increase SGI1 stability by utilizing the parABS system of the plasmid for its own partitioning, through which SGI1 also destabilizes the helper plasmid. Furthermore, SGI1 expresses a small protein, Sci, which significantly strengthens this plasmid-destabilizing effect, as well as SGI1 maintenance. The plasmid-induced replication of SGI1 results in an increased copy-number of parS-like sequences and Sci expression leading to strong incompatibility with the helper plasmid.
CRUX, a platform for visualising, exploring and analysing cancer genome cohort data
Authors: El-Kamand Sam , Quinn Julian M W , Sareen Heena , Becker Therese M , Wong-Erasmus Marie , Cowley Mark J
Published: February 2024

To better understand how tumours develop, identify prognostic biomarkers and find new treatments, researchers have generated vast catalogues of cancer genome data. However, these datasets are complex, so interpreting their important features requires specialized computational skills and analytical tools, which presents a significant technical challenge. To address this, we developed CRUX, a platform for exploring genomic data from cancer cohorts. CRUX enables researchers to perform common analyses including cohort comparisons, biomarker discovery, survival analysis, and to create visualisations including oncoplots and lollipop charts. CRUX simplifies cancer genome analysis in several ways: (i) it has an easy-to-use graphical interface; (ii) it enables users to create custom cohorts, as well as analyse precompiled public and private user-created datasets; (iii) it allows analyses to be run locally to address data privacy concerns (though an online version is also available) and (iv) it makes it easy to use additional specialized tools by exporting data in the correct formats. We showcase CRUX’s capabilities with case studies employing different types of cancer genome analysis, demonstrating how it can be used flexibly to generate valuable insights into cancer biology. CRUX is freely available at https://github.com/CCICB/CRUX and https://ccicb.shinyapps.io/crux (DOI: 10.5281/zenodo.8015714).
Functional domain annotation by structural similarity
Authors: Borujeni Poorya Mirzavand , Salavati Reza
Published: February 2024

Traditional automated in silico functional annotation uses tools like Pfam that rely on sequence similarities for domain annotation. However, structural conservation often exceeds sequence conservation, suggesting an untapped potential for improved annotation through structural similarity. This approach was previously overlooked before the AlphaFold2 introduction due to the need for more high-quality protein structures. Leveraging structural information especially holds significant promise to enhance accurate annotation in diverse proteins across phylogenetic distances. In our study, we evaluated the feasibility of annotating Pfam domains based on structural similarity. To this end, we created a database from segmented full-length protein structures at their domain boundaries, representing the structure of Pfam seeds. We used Trypanosoma brucei, a phylogenetically distant protozoan parasite as our model organism. Its structome was aligned with our database using Foldseek, the ultra-fast structural alignment tool, and the top non-overlapping hits were annotated as domains. Our method identified over 400 new domains in the T. brucei proteome, surpassing the benchmark set by sequence-based tools, Pfam and Pfam-N, with some predictions validated manually. We have also addressed limitations and suggested avenues for further enhancing structure-based domain annotation.
First report of the rare tintinnid genus Stelidiella Kofoid and Campbell 1929 in the Indian Ocean
Authors: Sarun T P , Patil Jagadish S
Published: February 2024

This study provides detailed information on the morphometry and distribution of some rare tintinnids species found in the Indian Ocean. The morphological features (scabbard-shaped with a fenestrated collar) reported here resemble those of the genus Stelidiella. Here, lorica morphology (fenestra arrangement and oral margin (OM) pattern) was the sole criteria for Stelidiella species identification. The dimensions and morphology (presence of two layers of fenestrae rings with smooth OMs) resemble the original description of Stelidiella fenestrata, a warm-water species. We found both small (260 μm long) and large S. fenestrata (309 μm long) with smaller and larger bowls in the former and latter, respectively. In the Indian Ocean, S. fenestrata was more abundant (i) between 12oN and 18oS (particularly, central Indian Ocean) similar to that reported in the Pacific Ocean; (ii) in the mesopelagic zone (100–1000 m) than the epipelagic zone (0–100 m) and (iii) in the winter season of December 2021–January 2022 than in spring inter-monsoon of March–May 2021. The S. fenestrata, despite being in low abundance (2–26 individuals 10 m−3), is widespread in the region, and their role in the ecosystem merits further investigation.
Measuring stomatal and guard cell metrics for plant physiology and growth using StoManager1
Authors: Wang Jiaxin , Renninger Heidi J , Ma Qin , Jin Shichao
Published: February 2024

Automated guard cell detection and measurement are vital for understanding plant physiological performance and ecological functioning in global water and carbon cycles. Most current methods for measuring guard cells and stomata are laborious, time-consuming, prone to bias, and limited in scale. We developed StoManager1, a high-throughput tool utilizing geometrical, mathematical algorithms, and convolutional neural networks to automatically detect, count, and measure over 30 guard cell and stomatal metrics, including guard cell and stomatal area, length, width, stomatal aperture area/guard cell area, orientation, stomatal evenness, divergence, and aggregation index. Combined with leaf functional traits, some of these StoManager1-measured guard cell and stomatal metrics explained 90% and 82% of tree biomass and intrinsic water use efficiency (iWUE) variances in hardwoods, making them substantial factors in leaf physiology and tree growth. StoManager1 demonstrated exceptional precision and recall (mAP@0.5 over 0.96), effectively capturing diverse stomatal properties across over 100 species. StoManager1 facilitates the automation of measuring leaf stomatal and guard cells, enabling broader exploration of stomatal control in plant growth and adaptation to environmental stress and climate change. This has implications for global gross primary productivity (GPP) modeling and estimation, as integrating stomatal metrics can enhance predictions of plant growth and resource usage worldwide. Easily accessible open-source code and standalone Windows executable applications are available on a GitHub repository (https://github.com/JiaxinWang123/StoManager1) and Zenodo (https://doi.org/10.5281/zenodo.7686022).
The effect of socioeconomic status and training programmes on burnout in postgraduate trainees in the United Kingdom: a cross-sectional analysis
Authors: Super Jonathan , Vinnicombe Zak , Little Max , Gunnee Matthew , Anakwe Raymond
Published: February 2024

Purpose

Burnout is described as a state of mental exhaustion caused by one’s professional life and is characterised by three domains: emotional exhaustion, depersonalisation, and a reduced sense of accomplishment. The prevalence of stress is high amongst doctors and varies by specialty, gender, trainee level, and socioeconomic status. The authors set out to examine the scale of the problem, as well as to determine the influence of both socioeconomic status and chosen training programme on burnout amongst postgraduate trainees. This would identify at-risk groups and aid in future targeted interventions.

Methods

Cross-sectional data were obtained, following approval from the General Medical Council, from The National Training Survey, completed annually by all trainees in the United Kingdom. Data were then anonymised and analysed. Burnout scores were derived from the Copenhagen Burnout Inventory and are positively framed (higher scores equal lower burnout).

Results

The questionnaire was completed by 63 122 participants from 2019 to 2020. Mean burnout amongst all trainees was 52.4 (SD = 19.3). Burnout scores from the most deprived quintile was significantly lower compared with those from the least deprived quintile: 51.0 (SD = 20.6) versus 52.9 (SD = 18.9), respectively (P < 0.001). The highest levels of burnout were reported in Internal Medical Training, Emergency Medicine, Obstetrics and Gynaecology, and Core Surgical Training, respectively.

Conclusion

Postgraduates from lower socioeconomic backgrounds are more likely to encounter burnout during training. At-risk groups who may also benefit from targeted intervention have been identified, requiring further examination through future studies.
Positive Effects of Uric Acid on White Matter Microstructures and Treatment Response in Patients With Schizophrenia
Authors: Bang Minji , Heo Yul , Choi Tai Kiu , Lee Sang-Hyuk
Published: February 2024

Background and Hypothesis

Schizophrenia involves microstructural changes in white matter (WM) tracts. Oxidative stress is a key factor causing WM damage by hindering oligodendrocyte development and myelin maturation. Uric acid (UA), an endogenous antioxidant, may protect against oxidative stress. We investigated the effect of UA on WM connectivity in antipsychotic-naive or -free patients with early- or chronic-stage schizophrenia.

Study Design

A total of 192 patients with schizophrenia (122 recent-onset [ROS] and 70 chronic [CS]) and 107 healthy controls (HCs) participated in this study. Diffusion tensor imaging data and serum UA levels at baseline were obtained.

Study Results

Fractional anisotropy was lower in the widespread WM regions across the whole brain, and diffusivity measures were higher in both schizophrenia groups than in HCs. The CS group showed lower diffusivity in some WM tracts than the ROS or HC groups. The linear relationship of serum UA levels with axial and mean diffusivity in the right frontal region was significantly different between schizophrenia stages, which was driven by a negative association in the CS group. WM diffusivity associated with serum UA levels correlated with 8-week treatment responses only in patients with CS, suggesting UA to be protective against long-term schizophrenia.

Conclusions

UA may protect against the WM damage associated with the progression of schizophrenia by reducing oxidative stress and supporting WM repair against oxidative damage. These results provide insights into the positive role of UA and may facilitate the development of novel disease-modifying therapies.
Omega-3 Supplementation Reduces Schizotypal Personality in Children: A Randomized Controlled Trial
Authors: Raine Adrian , Gur Ruben C , Gur Raquel E , Richmond Therese S , Hibbeln Joseph , Liu Jianghong
Published: February 2024

Background and Hypothesis

Based on a childhood intervention from ages 3 to 5 years that included additional fish consumption and which resulted in reduced schizotypal personality at age 23, we had previously hypothesized that omega-3 could reduce schizotypy. The current study tests the hypothesis that omega-3 supplementation reduces schizotypy in children.

Study Design

In this intention-to-treat, randomized, single-blind, stratified, factorial trial, a community sample of 290 children aged 11–12 years were randomized into Omega-3 Only, Cognitive Behavioral Therapy (CBT) Only, Omega-3 + CBT, and Control groups. Schizotypy was assessed using the SPQ-C (Schizotypal Personality Questionnaire for Children) at 0 months (baseline), 3 months (end of treatment), 6 months (3 months post-treatment), and 12 months (9 months post-treatment).

Study Results

A significant group × time interaction (P = .013) indicated that, compared with Controls, total schizotypy scores were reduced in both Omega-3 Only and Omega-3 + CBT groups immediately post-treatment (d = 0.56 and 0.47, respectively), and also 3 months after supplementation terminated (d = 0.49, d = 0.70). Stronger findings were observed for the interpersonal schizotypy factor, with both omega-3 groups showing reductions 9 months post-treatment compared with the CBT Only group. Schizotypy reductions were significantly stronger for those with higher dietary intake of omega-3 at intake. Sensitivity analyses confirmed findings.

Conclusions

Results are unique in the field and suggest that omega-3 can help reduce schizotypal personality in community-residing children. From an epidemiological standpoint, if replicated and extended, these findings could have implications for early prevention of more significant schizotypal features developing later in adolescence.

Clinical Trial Registration

“Healthy Brains & Behavior: Understanding and Treating Youth Aggression (HBB).” ClinicalTrials.gov Identifier: NCT00842439, https://clinicaltrials.gov/ct2/show/NCT00842439.
Racial Justice and Racialized Religion: Are Progressive White Christians Getting It Right?
Authors: Martí Gerardo
Published: February 2024

The core question guiding this research is: What happens when the project of racial justice, specifically, anti-black racism, is taken on by white progressive Christians and their churches? Acknowledging religion as racialized allows our scholarship to be more discerning and less naive, especially regarding the true potential of racial justice—even among those who are most faithfully attempting to become antiracist. Drawing from preliminary data collected from congregations in the United States and Canada aligned with the Alliance of Baptists, a denomination explicitly committed to antiracism, I focus on a few significant dynamics, briefly summarized under seven themes: (1) Getting It Right, (2) The Volunteer Antiracist, (3) Congregational Politics, (4) Encountering Resistance, (5) Soliciting Cooperation, (6) Instrumentalizing Whiteness as a Ready Tool, and (7) Affirmation from Black Members. As data collection continues, this research remains open to developing more insights and revising tentative conclusions as the analysis proceeds further.
Long-term impacts of 48-h water and feed deprivation on blood and performance responses of grazing Bos indicus Nellore heifers
Authors: Abreu Mateus J I , Marques Rodrigo S , Cidrini Iorrano A , Batista Luis H C , Ferreira Igor M , Oliveira Karla A , Cruz Vinicius A , Limede Arnaldo C , Sousa Luciana M , França Matheus Q S , Bísio Gustavo H M , Siqueira Gustavo R , Resende Flávio D
Published: February 2024

The study investigated the effects of 48-h water and feed deprivation on blood and the performance of grazing Nellore (Bos indicus) heifers. Twenty-four Nellore heifers (initial body weight [BW] = 238 ± 10 kg; age = 16 ± 2 mo), were ranked by initial BW and age and randomly assigned to one of the two treatments: (1) grazing animals with free access to pasture, water, and mineral-mix (CON; n = 12), or (2) the same grazing conditions but deprived of pasture, water, and mineral-mix for 48 h (DPR; n = 12). The paddocks consisted of Urochloa brizantha cv. Marandu, using a continuous and fixed stocking rate. The experiment lasted 225 d, with the first 14 d considered as the adaptation period (days −14 to −1) and the subsequent 211 d as the evaluation period (days 0 to 211). From days 0 to 2, treatments were applied by keeping the DPR heifers in pens and reintegrating them into the experimental area after a 48-h water and feed deprivation. Individual full BW was recorded on days −14, −13, −1, before (day 0) and after (day 2) treatment application, and on days 6, 11, 12, 41, 42, 210, and 211. Blood samples were collected in the morning on days 0, 2, 6, 12, and 211. A treatment effect was detected (P < 0.001) for shrink BW from days 0 to 2, which was greater (P < 0.001) in DPR vs. CON heifers. Subsequently, DPR animals were lighter (P < 0.001) compared with CON heifers by the end of the deprivation period (day 2). From days 4 to 211, DPR was lighter (P < 0.001) compared with CON heifers after treatment application and for the entire experimental period. In the first 10 d after treatment application (days 2 to 12), DPR heifers showed a partial compensatory average daily gain (ADG; P < 0.001) compared with CON heifers, while no significant differences were observed in ADG between the treatments from days 12 to 42 and 42 to 211 (P > 0.420). Overall ADG (days 2 to 211) was greater (P < 0.001) for DPR vs. CON heifers. All serum variables, except AST, were higher (P < 0.001) in DPR than in CON heifers on day 2 after treatment application. Our study demonstrates that grazing Nellore heifers subjected to 48-h water and feed deprivation experienced significant alterations in their blood metabolites and BW immediately after the stressful event. Although the deprived heifers partially compensated for their BW loss in the early days post-deprivation, they remained 12 kg lighter than the non-deprived animals throughout the production cycle.
Contemporary and historical human migration patterns shape hepatitis B virus diversity
Authors: Potter Barney I , Thijssen Marijn , Trovão Nídia Sequeira , Pineda-Peña Andrea , Reynders Marijke , Mina Thomas , Alvarez Carolina , Amini-Bavil-Olyaee Samad , Nevens Frederik , Maes Piet , Lemey Philippe , Van Ranst Marc , Baele Guy , Pourkarim Mahmoud Reza
Published: February 2024

Infection by hepatitis B virus (HBV) is responsible for approximately 296 million chronic cases of hepatitis B, and roughly 880,000 deaths annually. The global burden of HBV is distributed unevenly, largely owing to the heterogeneous geographic distribution of its subtypes, each of which demonstrates different severity and responsiveness to antiviral therapy. It is therefore crucial to the global public health response to HBV that the spatiotemporal spread of each genotype is well characterized. In this study, we describe a collection of 133 newly sequenced HBV strains from recent African immigrants upon their arrival in Belgium. We incorporate these sequences—all of which we determine to come from genotypes A, D, and E—into a large-scale phylogeographic study with genomes sampled across the globe. We focus on investigating the spatio-temporal processes shaping the evolutionary history of the three genotypes we observe. We incorporate several recently published ancient HBV genomes for genotypes A and D to aid our analysis. We show that different spatio-temporal processes underlie the A, D, and E genotypes with the former two having originated in southeastern Asia, after which they spread across the world. The HBV E genotype is estimated to have originated in Africa, after which it spread to Europe and the Americas. Our results highlight the use of phylogeographic reconstruction as a tool to understand the recent spatiotemporal dynamics of HBV, and highlight the importance of supporting vulnerable populations in accordance with the needs presented by specific HBV genotypes.
Emerging biologic therapies for systemic lupus erythematosus
Authors: Kato Hiroshi , Kahlenberg J. Michelle
Published: February 2024

Purpose of review

The approval of belimumab and anifrolumab has expanded the scope of treatment for systemic lupus erythematosus (SLE) patients. However, many patients remain refractory to currently available therapies and suffer from drug toxicities. This review will discuss approved and target-specific therapeutics in development that bring hope for better SLE treatments.

Recent findings

Since the last review on this subject in the journal, the FDA has approved anifrolumab and belimumab for SLE and lupus nephritis (LN), respectively. A fully humanized anti-CD20, obinutuzumab, met the primary end point in a phase II trial in LN. A Tyk2 inhibitor, deucravacitinib, and an antibody targeting plasmacytoid dendritic cells, litifilimab, met the primary end point in phase II trials in SLE and cutaneous lupus erythematosus (CLE). Ustekinumab and baricitinib met the primary end point in phase II but not in phase III trials.

While many drug candidates which met the end points in phase II trials have failed phase III trials, the number of target-specific therapies for SLE has continued to expand.
MRI of the Spine in Patients who Toe Walk: Is There a Role?
Authors: Flaugh Rachel A. , May Collin J. , Curran Patrick , Miller Patricia E. , Kasser James R. , Shore Benjamin J.
Published: February 2024

Background:

Little is known about the prevalence of intraspinal pathology in children who toe walk, but magnetic resonance imaging (MRI) may be part of the diagnostic workup. The purpose of this study was to examine the role of MRI for children who toe walk with a focus on the rate of positive findings and associated neurosurgical interventions performed for children with said MRI findings.

Methods:

A single-center tertiary hospital database was queried to identify a cohort of 118 subjects with a diagnosis of toe walking who underwent spinal MRI during a 5-year period. Patient and MRI characteristics were summarized and compared between subjects with a major abnormality, minor abnormality, or no abnormality on MRI using multivariable logistic regression. Major MRI abnormalities included those with a clear spinal etiology, such as fatty filum, tethered cord, syrinx, and Chiari malformation, while minor abnormalities had unclear associations with toe walking.

Results:

The most common primary indications for MRI were failure to improve with conservative treatment, severe contracture, and abnormal reflexes. The prevalence of major MRI abnormalities was 25% (30/118), minor MRI abnormalities was 19% (22/118), and normal MRI was 56% (66/118). Patients with delayed onset of toe walking were significantly more likely to have a major abnormality on MRI (P=0.009). The presence of abnormal reflexes, severe contracture, back pain, bladder incontinence, and failure to improve with conservative treatment were not significantly associated with an increased likelihood of major abnormality on MRI. Twenty-nine (25%) subjects underwent tendon lengthening, and 5 (4%) underwent neurosurgical intervention, the most frequent of which was detethering and sectioning of fatty filum.

Conclusions:

Spinal MRI in patients who toe walk has a high rate of major positive findings, some of which require neurosurgical intervention. The most significant predictor of intraspinal pathology was the late onset of toe walking after the child had initiated walking. MRI of the spine should be considered by pediatric orthopedic surgeons in patients with toe walking who present late with an abnormal clinical course.

Level of Evidence:

Level III Retrospective Comparative Study.
Digital Literacy and Associated Factors in Older Adults Living in Urban South Korea
Authors: Baek Jiwon , Kim Heejung , Choi Seongmi , Hong Soyun , Kim Yesol , Kim Eunkyung , Lee Taewha , Chu Sang Hui , Choi JiYeon
Published: February 2024

This study aimed to explore digital literacy among community-dwelling older adults in urban South Korea. A semistructured interview guide was developed using the Digital Competence ( 2.0 framework, which emphasizes the competencies for full digital participation in five categories: information and data literacy, communication and collaboration, content creation, safety, and problem-solving. The data were analyzed using combined inductive and deductive content analysis. Inductive analysis identified three main categories: perceived ability to use digital technology, responses to digital technology, and contextual factors. In the results of deductive analysis, participants reported varying abilities in using digital technologies for information and data literacy, communication or collaboration, and problem-solving. However, their abilities were limited in handling the safety or security of digital technology and lacked in creating digital content. Responses to digital technology contain subcategories of perception (positive or negative) and behavior (trying or avoidance). Regarding contextual factors, aging-related physical and cognitive changes were identified as barriers to digital literacy. The influence of families or peers was viewed as both a facilitator and a barrier. Our participants recognized the importance of using digital devices to keep up with the trend of digitalization, but their digital literacy was mostly limited to relatively simple levels.
Outcomes in Heart Transplant Recipients by Bridge to Transplant Strategy When Using the SherpaPak Cardiac Transport System
Authors: Silvestry Scott , Leacche Marzia , Meyer Dan M. , Shudo Yasuhiro , Kawabori Masashi , Mahesh Balakrishnan , Zuckermann Andreas , D’Alessandro David , Schroder Jacob
Published: February 2024

The last several years have seen a rise in use of mechanical circulatory support (MCS) to bridge heart transplant recipients. A controlled hypothermic organ preservation system, the SherpaPak Cardiac Transport System (SCTS), was introduced in 2018 and has grown in utilization with reports of improved posttransplant outcomes. The Global Utilization And Registry Database for Improved heArt preservatioN (GUARDIAN)-Heart registry is an international, multicenter registry assessing outcomes after transplant using the SCTS. This analysis examines outcomes in recipients bridged with various MCS devices in the GUARDIAN-Heart Registry. A total of 422 recipients with donor hearts transported using SCTS were included and identified. Durable ventricular assist devices (VADs) were used exclusively in 179 recipients, temporary VADs or intra-aortic balloon pump (IABP) in 197, and extracorporeal membrane oxygenation (ECMO) in 14 recipients. Average ischemic times were over 3.5 hours in all cohorts. Severe primary graft dysfunction (PGD) posttransplant increased across groups (4.5% VAD, 5.1% temporary support, 21.4% ECMO), whereas intensive care unit (ICU) length of stay (18.2 days) and total hospital stay (39.4 days) was longer in the ECMO cohort than the VAD and IABP groups. A comparison of outcomes of MCS bridging in SCTS versus traditional ice revealed significantly lower rates of both moderate/severe right ventricular (RV) dysfunction and severe PGD in the SCTS cohort; however, upon propensity matching only the reductions in moderate/severe RV dysfunction were statistically significant. Use of SCTS in transplant recipients with various bridging strategies results in excellent outcomes.
Feasibility of Arteriograph 24 for evaluation of 24-hour pulse wave velocity and central blood pressure in patients with type 2 diabetes and non-diabetic controls
Authors: Laugesen Esben , Svendsen Amalie Nørkjær , Vernstrøm Liv , Halkjær Lene , Dons-Jensen Anna , Funck Kristian L. , Hansen Klavs Würgler , Poulsen Per Løgstrup
Published: February 2024

The objective of this study was to assess the feasibility of the Arteriograph 24 device to measure 24-hour PWV and central systolic blood pressure (cSBP) in patients with type 2 diabetes (T2DM) and non-diabetic controls and compare daytime and nighttime characteristics in the two groups. Twenty-four-hour PWV and cSBP was measured in 58 patients with T2DM (mean age: 66 ± 9 years, 50% women, mean duration of T2DM: 7.8 ± 1.5 years) and 62 age- and sex-matched controls. Seventy percent of participants (71% T2DM patients and 69% controls) had sufficient readings to generate an acceptable 24-hour report (≥14 day and ≥7 night readings). Lower nocturnal than daytime PWV and cSBP were observed in both groups. Nocturnal PWV and cSBP dipping were attenuated in T2DM patients compared to controls (PWV: −0.3 ± 0.9 vs. −0.7 ± 0.9 m/s, P = 0.04, cSBP: −8 ± 14 vs. −18 ± 18 mmHg, P < 0.01). No group differences in PWV or cSBP were observed during daytime (T2D vs. controls, PWV: 9.2 ± 1.1 vs. 9.2 ± 1.3 m/s, P = 0.99, cSBP: 133 ± 19 vs. 137 ± 25 mmHg, P = 0.42) or nighttime (PWV: 8.9 ± 1.3 vs. 8.4 ± 1.3 m/s, P = 0.14, cSBP 124 ± 20 vs. 118 ± 27 mmHg, P = 0.26). The study findings indicate that the nocturnal dipping of PWV and cSBP is attenuated in T2DM patients. The significant number of missing measurements raises concerns regarding the clinical utility of the Arteriograph 24 device.
Blood pressure responsiveness to resistance training in the hypertensive older adult: a randomized controlled study
Authors: Abrahin Odilon , Abrahin Rejane Pequeno , Guimarães Mayko , de Holanda Vitor Bruno Teixeira , Figueiredo Fernanda Andreza De Pinho Lott , Viana Rosa Bruno , de Sousa Neto Ivo Vieira , Rolnick Nicholas , de Melo Gislane Ferreira , Prestes Emanuelle Fernandes , da Cunha Nascimento Dahan
Published: February 2024

Different lifestyle changes have been employed to improve clinical hypertension. However, there is scarce evidence on the blood pressure responsiveness to resistance training (RT) in hypertensive older adults. Consequently, little is known about some participants clinically reducing blood pressure and others not. Thus, we investigate the effects and responsiveness of RT on blood pressure in hypertensive older adults. We secondarily evaluated the biochemical risk factors for cardiovascular disease and functional performance. Older participants with hypertension were randomly assigned into RT (n = 27) and control group (n = 25). Blood pressure, functional performance (timed up and go, handgrip strength, biceps curl and sit-to-stand), fasting glucose, and lipid profiles were evaluated preintervention and postintervention. The statistic was performed in a single-blind manner, the statistician did not know who was the control and RT. RT was effective in reducing systolic blood pressure (SBP) (pre 135.7 ± 14.7; post 124.7 ± 11.0; P < 0.001) and the responses to RT stimuli varied noticeably between hypertensive older adults after 12 weeks. For example, 13 and 1 responders displayed a minimal clinical important difference for SBP attenuation (10.9 mmHg) in the RT and control groups, respectively. RT improved the functional performance of older people with hypertension, while no differences were found in biochemical parameters (triglycerides, HDL, LDL, fasting glucose) after 12 weeks. In conclusion, responses to RT stimuli varied noticeably between hypertensive individuals and RT was effective in reducing SBP.
Social isolation and its influencing factors among age-related hearing loss patients: A cross-sectional study
Authors: Lee Hyunjung , Ha Jiyeon
Published: February 2024

Hearing loss is considered one of the most common symptoms of aging worldwide, and age-related hearing loss is one of the three major chronic illnesses that affect older adults. This study examined social isolation among age-related hearing loss patients and its influencing factors. This cross-sectional descriptive study collected data from older adults with hearing loss from March 2019 to February 2020 at a university hospital. Social isolation, subjective hearing handicap, and communication-related life satisfaction were measured using a structured questionnaire. Objective hearing function was evaluated using an audiometer (Madsen Asterao 2). The independent t test, one-way analysis of variance, and multiple linear regression analysis were used to analyze the data. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was used for reporting this study. Almost half (49.9%) of 203 age-related hearing loss patients aged 60 to 92, with a mean age of 71.6 ± 7.95 years, experienced social isolation. Factors predicting social isolation were communication-related life satisfaction (P < .001), religiosity (P = 001), experience using hearing aids (P = .006), and subjective hearing handicap (P = .047). The explanatory power of the model was 58.2%. Interventions to reduce social isolation among age-related hearing loss patients should be implemented in an effort to develop effective, appropriate, and comprehensive strategies targeting this high-risk group.
Study of height, sitting height, lower extremity length, and the prevalence of short stature among elementary school students in the Tianyuan District of Zhuzhou City
Authors: Tang Qiong , Gong Dai , Ye Xiao-Min , Zhang Jiao , Xu Jun-Ru , Yang Yi-Can , Yan Li-Juan , Zou Li , Wen Xiang-Lan
Published: February 2024

In this study, the height, sitting height, lower extremity length, growth status, and body proportions of elementary school students aged 6 to 12 years in Tianyuan District of Zhuzhou City, China, were analyzed. A total of 41,156 children from 38 elementary schools in the Tianyuan District of Zhuzhou City were selected for height measurement, employing the cluster sampling method. After the cluster data were obtained, the height and sitting height information were extracted, and calculations were performed for lower extremity length, sitting height-to-lower extremity length ratio, and sitting height-to-height ratio. Statistical analysis was conducted using SPSS 23.0 software. The height and sitting height measurements of boys and girls aged 6 to 12 years in Tianyuan District surpassed the 2005 national standard set for 9 cities, while the lower extremities of children within the 7 to 9 age range fell below the national standard. In alignment with the national average, the fitted curve representing height for both boys and girls aged 6 to 12 years in Tianyuan District exhibited an intersection point around 10 to 10.5 years. No discernible distinction was observed in the incidence of short stature, as analyzed through the P3 standard, between the fitted curve for Tianyuan District and the national standard. Moreover, tall children exhibited a significantly lower sitting height-to-height ratio compared to their shorter counterparts. The fitted height curve in Tianyuan District, Zhuzhou City, proves effective in discerning shorter-statured children within the region. Nevertheless, further research is warranted to elucidate the factors contributing to the comparatively shorter lower extremities observed in children from Tianyuan District, Zhuzhou City, in contrast to the national average.