bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in voice characteristics in patients with heart failure (VENTURE) in Switzerland: Protocol for a longitudinal observational pilot study
Authors: Wu Fan , Nägele Matthias , Cleres David , Haider Thomas , Fleisch Elgar , Ruschitzka Frank , Flammer Andreas , Barata Filipe 
Published: March 2023

AbstractIntroductionHeart Failure (HF) is a major health and economic issue worldwide. HF-related expenses are largely driven by hospital admissions and re-admissions, many of which are potentially preventable. Current self-management programs, however, have failed to reduce hospital admissions. This may be explained by their low predictive power for decompensation and high adherence requirements. Slight alterations in the voice profile may allow to detect decompensation in HF patients at an earlier stage and reduce hospitalizations. This pilot study investigates the potential of voice as a digital biomarker to predict health status deterioration in HF patients.Methods and analysisIn a two-month longitudinal observational study, we collect voice samples and HF-related quality-of-life questionnaires from 35 stable HF patients. Patients use our developed study application installed on a tablet at home during the study period. From the collected data, we use signal processing to extract voice characteristics from the audio samples and associate them with the answers to the questionnaire data. The primary outcome will be the correlation between voice characteristics and HF-related quality-of-life health status.Ethics and disseminationThe study was reviewed and approved by the Cantonal Ethics Committee Zurich (BASEC ID:2022-00912). Results will be published in medical and technical peer-reviewed journals.
White matter connectivity in resilience in a general population sample of 12,516 individuals
Authors: de Vries Baukje S. , van der Wee Nic J.A. , van der Werff Steven J.A. 
Published: March 2023

AbstractObjectiveNeurobiological correlates of resilience to stress or trauma have not been investigated extensively. Studies on white matter connectivity in resilience, in particular, have been few and far between. This explorative study included 12,516 participants from the UK Biobank to investigate white matter connectivity in resilience in 13 selected regions of interest (ROIs).MethodsThe data for this cross-sectional cohort study were retrieved from UK Biobank, a large-scale biomedical database and research resource. The study included 40-69-year-old participants divided into three groups: a trauma-exposed, healthy (resilient) group, a trauma-exposed, mentally ill (vulnerable) group and a nonexposed, healthy (control) group. The primary outcome measures consisted of mean fractional anisotropy values in the following ROIs: cingulate gyrus, cingulum hippocampus, superior fronto-occipital fasciculus, uncinate fasciculus, corpus callosum body, genu, splenium, and tapetum. Group differences in fractional anisotropy were assessed using a one-way ANOVA.ResultsThis study did not find correlates of resilience in the investigated ROIs.ConclusionsThe results indicate that there is no association between resilience and white matter connectivity in the selected ROIs in this large population sample, which is in contrast with previous studies on morphometric and functional correlates of resilience. To corroborate this finding, the authors recommend collection of longitudinal data and utilization of voxelwise analysis, if possible, to improve sensitivity. The authors also suggest a whole-brain analysis in a similar study population to investigate other white matter tracts that might be implicated in resilience.
Can the ChatGPT and other Large Language Models with internet-connected database solve the questions and concerns of patient with prostate cancer?
Authors: Zhu Lingxuan , Mou Weiming , Chen Rui 
Published: March 2023

AbstractLarge language models (LLMs), such as ChatGPT, have shown impressive natural language processing capabilities in various fields, including medicine. However, the answers provided by these models may sometimes be incorrect, and they may not have access to the latest data. In this study, we aimed to evaluate the performance of five state-of-the-art LLMs in providing correct and comprehensive information on common questions raised by prostate cancer patients. We also examined whether LLMs with internet-connected databases could provide more up-to-date information than ChatGPT. We designed a set of 22 questions covering various aspects of prostate cancer and evaluated the accuracy, comprehensiveness, patient readability, and inclusion of humanistic care in the answers provided by each model. Our findings suggest that although the performance of different LLMs varied, these LLMs could provide accurate basic knowledge and have the ability to analyze specific situations to a certain extent. We also found that the overall performance of the LLM model with internet-connected dataset was not superior to ChatGPT, and the paid version of ChatGPT did not show superiority over the free version. Our study highlights the potential of LLMs in bridging the gap between patients and healthcare providers. Current LLMs have the potential to be applied for patient education and consultation, providing patient-friendly information. Shared decision-making with the doctors and patients could be achieved easier. We believed that with the rapid development of AI technology, LLMs have unlimited potential.
Biobank-scale methods and projections for sparse polygenic prediction from machine learning
Authors: Raben Timothy G. , Lello Louis , Widen Erik , Hsu Stephen D.H. 
Published: March 2023

AbstractIn this paper we characterize the performance of linear models trained via widely-usedsparsemachine learning algorithms. We build polygenic scores and examine performance as a function of training set size, genetic ancestral background, and training method. We show that predictor performance is most strongly dependent on size of training data, with smaller gains from algorithmic improvements. We find that LASSO generally performs as well as the best methods, judged by a variety of metrics. We also investigate performance characteristics of predictors trained on one genetic ancestry group when applied to another. Using LASSO, we develop a novel method for projecting AUC and Correlation as a function of data size (i.e., for new biobanks) and characterize the asymptotic limit of performance. Additionally, for LASSO (compressed sensing) we show that performance metrics and predictor sparsity are in agreement with theoretical predictions from the Donoho-Tanner phase transition. Specifically, a predictor trained in the Taiwan Precision Medicine Initiative for asthma can achieve an AUC of 0.63(0.02)and for height a correlation of 0.648(0.009)for a Taiwanese population. This is above the measured values of 0.61(0.01)and 0.631(0.008), respectively, for UK Biobank trained predictors applied to a European population.
Predictors of mortality among post-COVID-19 discharged patients in Northern India
Authors: Arjun  , Jatteppanavar Basavaraj , Panda Prasan Kumar , Dhanger Pathik 
Published: March 2023

AbstractBackgroundThe one-year post-discharge all-cause mortality rate of COVID-19 disease is 7.87 % with the majority of patients’ readmission and mortality occurring within the first 30 days post-discharge.ObjectiveUnderstanding predictors of mortality will help in prioritising patient care and preventive approaches.MethodsOurs a single-centre unmatched case control study at a tertiary care centre in northern India, conducted from April 2020 to September 2022. The data was extracted retrospectively from the electronic hospital medical records of patients and by trained physicians using standardised data extraction sheet.ResultsA total of 184 patients were enrolled with 92 cases and 92 controls. The mean age of patients was 49.3 ± 17.53 years. The mortality group had a higher mean age (53.24 ± 18.53 yrs) as compared to the control group (45.37 ± 15.58 yrs) [p – 0.002]. Bivariate analysis revealed a significant difference in the two groups with respect to O2 saturation at admission [Case - 91.12 ± 12.49 %, control - 95.46 ± 5.01 %, p – 0.003); Maximum O2 flow rate [L/min] (Case – 11.01 ± 22.2, Control – 6.41 ± 13.31, P – 0.04); ICU need (p – 0.005), Cancer (p – 0.001), O2 need at discharge (p – 0.001) and AKI (p – 0.007). On multiple regression analysis, Cancer (aOR-2.469; 95% CI-1.183-5.150, p-0.016), ICU admission (aOR- 2.446; 95% CI-1.212-4.938, p- 0.013), Oxygen at discharge (aOR- 2.340; 95% CI-0.971-5.640, p-0.0586) and Acute kidney injury (aOR- 5.6; 95% CI-2.351-13.370, p-0.00) only found to be significant.ConclusionOxygen requirement at discharge (2.3 times), Malignancy (2.4 times), ICU admission (2.4 times), and Acute Kidney Injury (5.6 times) were risks of death among COVID-19-recovered patients, post discharge. The presence of these variables would warrant a close follow up for these patients in order to decrease post COVID mortality.
Gene Expression Profiling Unveils the Temporal Dynamics of CIGB-300-Regulated Transcriptome in AML Cells
Authors: Vázquez-Blomquist Dania , Ramón Ailyn C. , Rosales Mauro , Pérez George V. , Rosales Ailenis , Palenzuela Daniel , Perera Yasser , Perea Silvio E. 
Published: March 2023

AbstractProtein kinase CK2 activity is implicated in the pathogenesis of various hematological malignancies like Acute Myeloid Leukemia (AML) that remains challenging concerning treatment. Consequently, here we used Illumina HT-12 microarray gene RNA expression profiling to study the molecular events that might support the anti-leukemic effect of CIGB-300 peptide which targets both CK2 substrates and the CK2α catalytic subunits on HL-60 and OCI-AML3 cell lines. As a result, 185 and 812 genes appeared significantly modulated in HL-60 cells at 30 min and 3 h of incubation with CIGB-300 for p< 0.01 and FC>│1.5│, respectively; while 222 and 332 genes appeared modulated in OCI-AML3 cells. Importantly, functional enrichment analysis evidenced that genes and transcription factors related to apoptosis, cell cycle, leukocyte differentiation, signaling by cytokines/interleukins, and NF-kB, TNF signaling pathways were significantly represented in AML cells transcriptomic profiles. The influence of CIGB-300 on these biological processes and pathways is dependent on the cellular background, in first place, and treatment duration. Of note, the impact of the peptide on NF-kB signaling was corroborated by the quantification of selected NF-kB target genes, as well as the measurement of p50 binding activity and soluble TNF-α induction. Quantification of CSF1/M-CSF and CDKN1A/P21 by PCR supports peptide effects on differentiation and cell cycle. Overall, here we explore for the first time the temporal dynamics of the gene expression profile regulated by CIGB-300 and provide fresh molecular clues concerning the antineoplastic effect of CIGB-300 in two relevant AML backgrounds.
AVibrioT6SS-mediated lethality in a marine animal model
Authors: Cohen Hadar , Gerlic Motti , Salomon Dor 
Published: March 2023

AbstractBacteria belonging to the genusVibrioinclude many known and emerging pathogens. Horizontal gene transfer of pathogenicity islands is a major contributor to the emergence of new pathogenicVibriostrains. In the current report, we use the brine shrimpArtemia salinaas a model to show that the marine bacteriumVibrio proteolyticususes a mobile type VI secretion system, T6SS3, to intoxicate eukaryotic hosts. Two T6SS3 effectors, which were previously shown to induce inflammasome-mediated pyroptotic cell death in mammalian phagocytic cells, contribute to this toxicity. Furthermore, we find a novel, widespread T6SS3 effector that also contributes to the lethality mediated by this system againstArtemia salina. Therefore, our results reveal a T6SS that is shared among diverse vibrios and mediates host lethality, indicating that it can lead to the emergence of new pathogenic strains.
Reprogramming an RNA-guided archaeal TnpB endonuclease for genome editing
Authors: Xu Ying , Liu Tao , Wang Jing , Xiong Binyang , Liu Ling , Peng Nan 
Published: March 2023

AbstractRNA-guided endonucleases developed for genome editing have been identified exclusively from bacteria until now. Recently, the RNA-guided TnpB endonucleases encoded by bacterial IS200/IS605 and IS607 families have been reprogrammed for genome editing. In fact, these insertion sequence families are also widely distributed in archaea. However, whether archaea-derived TnpB could be used for genome editing remains unclear. Here, we found that TnpB derived fromSulfolobus islandicusREY15A (SisTnpB1) was an Mg2+/Mn2+-dependent RNA-guided endonuclease, and it could cleave DNA next to the 5’ TTTAA transposon-associated motif (TAM) to generate double-stranded DNA breaks at the 3’-end. We also found that SisTnpB1 was active at 37-85°C and tolerant to variations of TAM. Moreover, SisTnpB1 could be reprogrammed to edit bacterial cells with an editing efficiency of 100% at 37°C or 45°C. In summary, our finding expanded the resources of RNA-guided endonucleases for genome editing, especially those derived from archaea, the third domain of life.
The effect of pulse shape in theta-burst stimulation: monophasic vs biphasic TMS
Authors: Wendt Karen , Sorkhabi Majid Memarian , Stagg Charlotte J. , Fleming Melanie K. , Denison Timothy , O’Shea Jacinta 
Published: March 2023

AbstractBackgroundIntermittent theta-burst stimulation (i)(TBS) is a transcranial magnetic stimulation (TMS) plasticity protocol. Conventionally, TBS is applied using biphasic pulses due to hardware limitations. However, monophasic pulses are hypothesised to recruit cortical neurons more selectively than biphasic pulses, thus yielding stronger plasticity effects. Monophasic and biphasic TBS can be generated using a custom-made pulse-width modulation-based TMS device (pTMS).ObjectiveUsing pTMS, we tested the hypothesis that monophasic iTBS would induce greater plasticity effects than biphasic, measured as induced changes in motor corticospinal excitability.MethodsIn a repeated-measures design, thirty healthy volunteers participated in three separate sessions, where monophasic and biphasic iTBS was applied to the primary motor cortex (M1 condition) or the vertex (control condition). Plasticity was quantified as changes in motor corticospinal excitability after versus before iTBS, by comparing peak-to-peak amplitudes of motor evoked potentials (MEP) measured at baseline and over 60 minutes after iTBS.ResultsBoth monophasic and biphasic M1 iTBS led to significant increases in MEP amplitude. As predicted, monophasic iTBS induced a significantly larger effect than biphasic iTBS (linear mixed effect model analysis: (χ2(1) = 7.48, p = 0.006), which persisted even after subtracting each individual’s control (vertex) condition data from the M1 conditions (χ2(1) = 5.48, p = 0.019).ConclusionsIn this study, monophasic iTBS induced a stronger motor corticospinal excitability increase than biphasic within participants. This greater physiological effect suggests that monophasic iTBS may also have potential for greater functional impact, of interest for future fundamental and clinical applications of TBS.
Reactive blue 2 labels protamine in late-haploid spermatids and spermatozoa and can be used for toxicity evaluation
Authors: Yokota Satoshi , Wakayama Tomohiko , Miyaso Hidenobu , Suga Kousuke , Fujinoki Masakatsu , Kaneko Satoru , Kitajima Satoshi 
Published: March 2023

AbstractBackgroundReactive blue 2 (RB2) dye specifically binds to the nuclei of human spermatozoa under weakly alkaline conditions, thus providing a new method to assess sperm quality. However, this technique has not yet been applied to other mammalian species, such as well-established rodent models, which could enable evaluation of the male reproductive toxicity of drug candidates in non-clinical studies.ObjectivesWe aimed to evaluate the usefulness of RB2 staining in assessing testicular and epididymal sperm toxicity in mice using a busulfan-induced infertility model.MethodsMale C57BL/6J mice were intraperitoneally administered 40 mg/kg of busulfan. After 28 days, the testes and epididymis were collected and stained with RB2 at pH 10. In vitro evaluations were conducted on uncoated glass slides with RB2 mixed with either protamines extracted from the spermatozoa or intracellular protein components from somatic cells without protamines.ResultsFollowing peanut agglutinin (PNA) lectin histochemistry, RB2-positive cells were observed in elongating and elongated spermatids at all stages except for stages IX–XI of the seminiferous epithelium. After busulfan administration, the proportion of RB2-positive germ cells in the seminiferous tubules decreased significantly, and no RB2-positive spermatozoa were found in the caput epididymis of treated mice. Aggregates were observed in the mixture of RB2 dye (pH 10) with protamines but not in the mixture of intracellular protein components without protamines, and this specificity was lost at neutral pH.Discussion and ConclusionOur study demonstrates that RB2 specifically stains steps 12–16 spermatids, indicating specific binding to protamine expressed in these spermatids. The RB2 staining technique has potential as a biomarker for male reproductive toxicity, allowing for the rapid visualization of protamination.
Loss of kinase Atg1 increases yeast maintenance energy requirement
Authors: Chen Xin , van Aalst Aafke C. A. , Petranovic Dina , Bisschops Markus M.M. 
Published: March 2023

AbstractMaintenance of cellular homeostasis underlies healthy aging. The processes involved in homeostasis rely on the so-called maintenance energy requirement and changes in this maintenance energy requirement impact aging and survival. Among maintenance processes, autophagy plays a crucial role as it is involved in the turn-over and recycling of damaged cellular material, such as organelles or proteins. The contribution of autophagy to the maintenance energy requirement is however unknown. Taking advantage of the high degree of conservation of autophagy between humans andSaccharomyces cerevisiae, we have used this yeast as a model organism to study the impact of macroautophagy on the maintenance energy requirement. The combination of the GFP-Atg8 cleavage assay with yeast retentostat cultures showed that autophagy is highly active in chronologically aging yeast cells, in non-dividing, but non-starving conditions. Deletion of the autophagy-activating kinaseATG1, homolog of humanULK1, resulted in a 60% increase in the maintenance energy requirement and doubled the specific death rate. Both these increases cannot be solely attributed to an observed increase in loss of respiratory capacity. Intriguingly, loss of Atg1 only reduced GFP-Atg8 cleavage by 20% under these conditions, indicating that Atg1-indendent modes of autophagy might be active. Overall, we illustrate the importance of autophagy on the energetics of aging cells and propose an alternative system for the widely applied yeast stationary phase cultures in chronological aging studies.
Maternal diet and gut microbiome composition modulate early life immune development
Authors: Grant Erica T , Boudaud Marie , Muller Arnaud , Macpherson Andrew J , Desai Mahesh S 
Published: March 2023

AbstractIn early life, the intestinal mucosa and immune system undergo a critical developmental process to contain the expanding gut microbiome while promoting tolerance towards commensals, yet the influence of maternal diet and gut microbial composition on offspring immune maturation remains poorly understood. We colonized gnotobiotic mice with a defined consortium of 14 strains, fed them a standard fiber-rich chow or a fiber-free diet, and then longitudinally assessed offspring development during the weaning period. Unlike pups born to dams fed the fiber-rich diet, pups of fiber-deprived dams demonstrated delayed colonization withAkkermansia muciniphila, a mucin-foraging bacterium that can also utilize milk oligosaccharides. The pups of fiber-deprived dams exhibited an enrichment of colonic tissue transcripts corresponding to defense response pathways and a peak inIl22expression at weaning. Removal ofA.muciniphilafrom the community, but maintenance on the fiber-rich diet, was associated with reduced proportions of RORγt-positive innate and adaptive immune cell subsets. Our results highlight the potent influence of maternal dietary fiber intake and discrete changes in microbial composition on the postnatal microbiome assemblage and early immune development.
Active self-touch restores bodily self-awareness following disruption by “rubber hand illusion”
Authors: Crivelli Damiano , Cataldo Antonio , Bottini Gabriella , Gomi Hiroaki , Haggard Patrick 
Published: March 2023

AbstractBodily self-awareness relies on a constant integration of visual, tactile, proprioceptive, and motor signals. In the “Rubber Hand Illusion” (RHI), conflicting visuo-tactile stimuli lead to changes in self- awareness. It remains unclear whether other, somatic signals could compensate for the alterations in self-awareness caused by visual information about the body. Here, we used the RHI in combination with robot-mediated self-touch to systematically investigate the role of tactile, proprioceptive, and motor signals in protecting and restoring bodily self-awareness. Participants moved the handle of a leader robot with their right hand and simultaneously received corresponding tactile feedback on their left hand from a follower robot. This self-touch stimulation was performed either before or after the induction of a classical RHI. Across three experiments, active self-touch delivered after – but not before – the RHI, significantly reduced the proprioceptive drift caused by RHI, supporting a restorative role of active self-touch on bodily self-awareness. The effect was not present during involuntary self-touch, where the participants’ hand was passively moved, suggesting that the restorative effect depends on the presence of a voluntary motor command, and that synchrony of bilateral sensory events is insufficient. Unimodal control conditions confirmed that the coordination of both tactile and motor components of self-touch was necessary to restore bodily self-awareness. These results suggest that voluntary self-touch can restore an intrinsic representation of the body following visual capture during RHI.
Engineering and implementation of synthetic molecular tools in the basidiomycete fungusUstilago maydis
Authors: Heucken Nicole , Tang Kun , Hüsemann Lisa , Heßler Natascha , Müntjes Kira , Feldbrügge Michael , Göhre Vera , Zurbriggen Matias D. 
Published: March 2023

AbstractThe basidiomyceteUstilago maydisis a well-characterized model organism for studying pathogen-host interactions and of great interest for a broad spectrum of biotechnological applications. To facilitate research and enable applications, in this study, three luminescence-based and one enzymatic quantitative reporter were implemented and characterized. We generated dual-reporter constructs for ratiometric normalization that can be used as a fast-screening platform for reporter gene expression, applicable toin vitroandin vivodetection. Furthermore, we constructed and implemented synthetic bi-directional promoters, that enable bicisitronic expression for gene expression studies and engineering strategies. These non-invasive, quantitative reporters and expression tools will widen significantly the application range of biotechnology inU. maydisand enable in planta detection of fungal infection.