bluuebunny/crossref_metadata_2025 huggingface dataset:
Necessary and sufficient conditions of the enforcement problem for various argumentation semantics
Authors: Zhang Huan , Zhang Songmao
Published: March 2024

In the research on dynamics of argumentation frameworks (AFs), the enforcement problem deals with changing an AF for the purpose of ensuring that a certain set of desired arguments becomes (part of) an extension. In this paper we focus on expansions of an AF where solely the addition of new arguments and attacks is allowed and the original framework remains unchanged. Existing results about the enforcement problem are all sufficient conditions, and we argue that necessary and sufficient conditions are essential concerning the solvability of the enforcement problem. A suite of jointly necessary and sufficient conditions are identified for the enforcement problem under normal expansion. These conditions are presented from multiple perspectives including the sub-strict versus non-strict problem, constructive versus eliminative conditions and arbitrary AFs versus even(odd)-length cycle free AFs, determined by the nature of various argumentation semantics. Such necessary and sufficient conditions are of the essence to the enforcement problem by defining requirements that are both minimum and absolute, which can be used to determine when the enforcement problem is (un)solvable. We further infer solely sufficient and solely necessary conditions based on the partial order relation (w.r.t. set-inclusion) among various types of AF extensions.
Bimodal orientation distribution and head-tail asymmetry of a sample of filamentary molecular clouds
Authors: Ge Wen , Du Fujun , Yuan Lixia
Published: March 2024

The morphology of molecular clouds is crucial for understanding their origin and evolution. In this work, we investigate the morphology of the filamentary molecular clouds (filaments for short) using a portion of the 12CO(J = 1 − 0) data from the Milky Way Imaging Scroll Painting project. The data cover an area spanning 104.75° < l < 150.25°, |b| < 5.25° in Galactic coordinates, with VLSR ranging from −95 to 25 kms−1. Our primary focus is on the orientation and morphological asymmetry of the filaments. To achieve this, we apply several criteria on the data to create a sample of filaments with well-defined straight shape, and we use elliptical fitting to obtain the orientation of each filament, with an estimated error of ∼1.6° for the orientation. We find that the filament orientation with respect to the Galactic plane exhibits a bimodal distribution, a double-Gaussian fitting of which has two centres located at −38.1° and 42.0°, with 1σ of the two Gaussian functions being 35.4° and 27.4°. We do not find significant correlation between the orientation and other parameters, including the Galactic coordinates, radial velocity, velocity width, and physical scale. A considerable fraction of filaments (≳40 per cent) display head-tail asymmetry, which suggests that mass concentration tends to occur at one end of the filaments.
Work participation and the COVID-19 pandemic: an observational study in people with inflammatory rheumatic diseases and population controls
Authors: Butink Maarten , Boekel Laura , Boonen Annelies , deRijk Angelique , Wolbink Gertjan , Webers Casper
Published: March 2024

Objective

During the coronavirus disease 2019 (COVID-19) crisis, people with inflammatory rheumatic diseases (iRDs) might have been more vulnerable for adverse work outcomes (AWOs) and restrictions in work ability and work performance. Our objectives were to compare AWOs during the pandemic and current work ability between iRD patients and controls, understand which patients are most vulnerable for these outcomes and (3) explore the role of work characteristics on work performance while working remotely.

Methods

Patients and population controls in a Dutch COVID-19 cohort study provided information in March 2022 on work participation in March 2020 (pre-pandemic, retrospective) and March 2022 (current). AWOs comprised withdrawal from paid work, working hours reduction or long-term sick leave. Multivariable logistic/linear regression analyses compared outcomes (AWOs/work ability) between groups (patients/controls) and within patients.

Results

Of the pre-pandemic working participants, 227/977 (23%) patients and 79/430 (18%) controls experienced AWOs following pandemic onset. A minority of AWOs (15%) were attributed to COVID-19. Patients were more likely to experience any-cause AWOs (odds ratio range 1.63–3.34) but not COVID-related AWOs, with female patients and patients with comorbidities or physically demanding jobs being most vulnerable. Current work ability was lower in female patients compared with controls [β = −0.66 (95% CI −0.92 to −0.40)]. In both groups, when working remotely, care for children and absence of colleagues had varying effects on work performance (positive 19% and 24%, negative 34% and 57%, respectively), while employer support and reduced commuting had mainly positive effects (83% and 86%, respectively).

Conclusion

During the pandemic, people with iRDs remained at increased risk of AWOs. COVID-related AWOs, however, were infrequent.
Cannabinoid CB2receptors in primary sensory neurons are implicated in CB2agonist-mediated suppression of paclitaxel-induced neuropathic nociception and sexually-dimorphic sparing of morphine tolerance
Authors: Guenther Kelsey G. , Lin Xiaoyan , Xu Zhili , Makriyannis Alexandros , Romero Julian , Hillard Cecilia J. , Mackie Ken , Hohmann Andrea G.
Published: March 2024

Cannabinoid CB2agonists show therapeutic efficacy without the unwanted side effects commonly associated with direct activation of CB1receptors. The G protein-biased CB2receptor agonist LY2828360 attenuates the maintenance of chemotherapy-induced neuropathic nociception in male mice and blocks the development of morphine tolerance in this model. However, the specific cell types involved in this phenomenon have never been investigated and whether this therapeutic profile is observed in female mice remains poorly understood. We used conditional deletion of CB2receptors from specific cell populations to determine the population(s) mediating the anti-allodynic and morphine-sparing effects of CB2agonists. Anti-allodynic effects of structurally distinct CB2agonists (LY2828360 and AM1710) were present in paclitaxel-treated CB2f/fmice of either sex. The anti-allodynic effect of the CB2agonists were absent in conditional knockout (KO) mice lacking CB2receptors in peripheral sensory neurons (AdvillinCRE/+; CB2f/f) but preserved in mice lacking CB2receptors in CX3CR1 expressing microglia/macrophages (CX3CR1CRE/+; CB2f/f). The morphine-sparing effect of LY28282360 occurred in a sexually-dimorphic manner, being present in male mice but absent in female mice of any genotype. In mice with established paclitaxel-induced neuropathy, prior LY2828360 treatment (3 mg/kg per day i.p. x 12 days) blocked the subsequent development of morphine tolerance in male CB2f/fmice but was absent in male (or female) AdvillinCRE/+; CB2f/fmice. LY2828360-induced sparing of morphine tolerance was preserved in male CX3CR1CRE/+; CB2f/fmice, but this effect was not observed in female CX3CR1CRE/+; CB2f/fmice. Similarly, co-administration of morphine with a low dose of LY2828360 (0.1 mg/kg per day i.p. x 6 days) reversed tolerance to the anti-allodynic efficacy of morphine in paclitaxel-treated male CB2f/fmice, but this effect was absent in female CB2f/fmice and AdvillinCRE/+; CB2f/fmice of either sex. Additionally, LY2828360 (3 mg/kg per day i.p. x 8 days) delayed, but did not prevent, the development of paclitaxel-induced mechanical and cold allodynia in either CB2f/for CX3CR1CRE/+; CB2f/fmice of either sex. Our studies reveal that CB2receptors in primary sensory neurons are required for the anti-allodynic effects of CB2agonists in a mouse model of paclitaxel-induced neuropathic nociception. We also find that CB2agonists acting on primary sensory neurons produce a sexually-dimorphic sparing of morphine tolerance in males, but not female, paclitaxel-treated mice.
Modeling spatial contrast sensitivity in responses of primate retinal ganglion cells to natural movies
Authors: Sridhar Shashwat , Vystrčilová Michaela , Khani Mohammad H. , Karamanlis Dimokratis , Schreyer Helene M. , Ramakrishna Varsha , Krüppel Steffen , Zapp Sören J. , Mietsch Matthias , Ecker Alexander , Gollisch Tim
Published: March 2024

Retinal ganglion cells, the output neurons of the vertebrate retina, often display nonlinear summation of visual signals over their receptive fields. This creates sensitivity to spatial contrast, letting the cells respond to spatially structured visual stimuli, such as a contrast-reversing grating, even when no net change in overall illumination of the receptive field occurs. Yet, computational models of ganglion cell responses are often based on linear receptive fields. Nonlinear extensions, on the other hand, such as subunit models, which separate receptive fields into smaller, nonlinearly combined subfields, are often cumbersome to fit to experimental data, in particular when natural stimuli are considered. Previous work in the salamander retina has shown that sensitivity to spatial contrast in response to flashed images can be partly captured by a model that combines signals from the mean and variance of luminance signals inside the receptive field. Here, we extend this spatial contrast model for application to spatiotemporal stimulation and explore its performance on spiking responses that we recorded from retinas of marmosets under artificial and natural movies. We show how the model can be fitted to experimental data and that it outperforms common models with linear spatial integration, in particular for parasol ganglion cells. Finally, we use the model framework to infer the cells’ spatial scale of nonlinear spatial integration and contrast sensitivity. Our work shows that the spatial contrast model provides a simple approach to capturing aspects of nonlinear spatial integration with only few free parameters, which can be used to assess the cells’ functional properties under natural stimulation and which provides a simple-to-obtain benchmark for comparison with more detailed nonlinear encoding models.
Multiple Isoforms of the Activin-like receptor Baboon differentially regulate proliferation and conversion behaviors of neuroblasts and neuroepithelial cells in theDrosophilalarval brain
Authors: Lee Gyunghee G. , Peterson Aidan J. , Kim Myung-Jun , O’Connor Michael B. , Park Jae H.
Published: March 2024

InDrosophilacoordinated proliferation of two neural stem cells, neuroblasts (NB) and neuroepithelial (NE) cells, is pivotal for proper larval brain growth that ultimately determines the final size and performance of an adult brain. The larval brain growth displays two phases based on behaviors of NB and NEs: the first one in early larval stages, influenced by nutritional status and the second one in the last larval stage, promoted by ecdysone signaling after critical weight checkpoint. Mutations of thebaboon(babo) gene that produces three isoforms (BaboA-C), all acting as type-I receptors of Activin-type transforming growth factor β (TGF-β) signaling, cause a small brain phenotype due to severely reduced proliferation of the neural stem cells. In this study we show that loss ofbabofunction severely affects proliferation of NBs and NEs as well as conversion of NEs from both phases. By analyzingbabo-null and newly generated isoform-specific mutants by CRISPR mutagenesis as well as isoform-specific RNAi knockdowns in a cell- and stage-specific manner, we further demonstrate differential contributions of the isoforms for these cellular events with BaboA playing the major role. Our data show that stage-specific expression of EcR-B1 in the brain is also regulated primarily by BaboA along with function of the other isoforms. Blocking EcR function in both neural stem cells results in a small brain phenotype that is more severe thanbaboA-knockdown alone. In summary, our study proposes that the Babo-mediated signaling promotes proper behaviors of the neural stem cells in both phases and achieves this by acting upstream of EcR-B1 expression in the second phase.

Author Summary

Evolutionarily conserved TGF-β signaling pathway is widely utilized as a regulator of diverse processes of brain development in both vertebrates and invertebrates. A key element inDrosophilaActivin type TGF-β signaling pathway is the type-I receptor Babo. Thebabogene produces three isoforms, each with a unique ligand preference. Our study uncovers that Babo-mediated signaling promotes proper proliferation of NBs and NEs and conversion of NEs, together responsible for the magnitude of larval brain size growth. Three isoforms act individually or together to regulate these cellular events in coordination with developmental status. Our findings emphasize that Babo-mediated signaling is a crucial regulator of postembryonic neurogenesis that generates 90% of neuronal population for the adult brain.
SURVIVIN IN SYNERGY WITH BAF/SWI COMPLEX BINDS BIVALENT CHROMATIN REGIONS AND ACTIVATES DNA DAMAGE RESPONSE IN CD4+ T CELLS
Authors: Chandrasekaran Venkataragavan , Andersson Karin M.E. , Erlandsson Malin , Li Shuxiang , Garcia-Bonete Maria-Jose , Malmhäll-Bah Eric , Pegah Johansson , Katona Gergely , Bokarewa Maria I.
Published: March 2024

This study explores a regulatory role of oncoprotein survivin on the bivalent regions of chromatin (BvCR) characterized by concomitant deposition of trimethylated lysine of histone H3 at position 4 (H3K4me3) and 27 (H3K27me3).

Intersect between BvCR and chromatin sequences bound to survivin demonstrated their co-localization oncis-regulatory elements of genes which execute DNA damage control in primary human CD4+cells. Survivin anchored BRG1-complex to BvCR to repress DNA damage repair genes in IFNγ-stimulated CD4+cells. In contrast, survivin inhibition shifted the functional balance of BvCR in favor of H3K4me3, which activated DNA damage recognition and repair. Co-expression of BRG1, survivin and IFNγ in CD4+cells of patients with rheumatoid arthritis identified arthritogenic BRG1hicells abundant in autoimmune synovia. Immunomodulating drugs inhibited the subunits anchoring BRG1-complex to BvCR, which changed the arthritogenic profile.

Together, this study demonstrates the function of BvCR in DNA damage control of CD4+cells offering an epigenetic platform for survivin and BRG1-complex targeting interventions to combat autoimmunity.

This study shows that bivalent chromatin regions accommodate survivin which represses DNA repair enzymes in IFNγ-stimulated CD4+T cells. Survivin anchors BAF/SWI complex to these regions and supports autoimmune profile of T cells, providing novel targets for therapeutic intervention.
Microglia Depletion leads to Increased Susceptibility to Ocular Hypertension-Dependent Glaucoma
Authors: Diemler Cory A. , MacLean Michael , Heuer Sarah E. , Hewes Amanda A. , Marola Olivia J. , Libby Richard T. , Howell Gareth R.
Published: March 2024

In recent years, microglia have been highlighted for playing integral roles in neurodegenerative diseases, like glaucoma. To better understand the role of microglia during chronic ocular hypertension, we depleted microglia from aged (9-12 months old) DBA/2J (D2) mice, which exhibit age-related increases in intraocular pressure, using a dietary CSF1R antagonist, PLX5622. Retinal ganglion cell (RGC) somas were counted, and optic nerve cross-sections stained and assessed for glaucomatous damage. Sustained administration of dietary PLX5622 significantly reduced the numbers of retinal microglia. Dietary PLX5622 did not lead to changes in intraocular pressure in D2 or normotensive DBA/2J-Gpnmb+(D2-Gpnmb+) control mice. While PLX5622-treated D2-Gpnmb+did not develop optic nerve damage, PLX5622-treated D2 mice showed a significant increase in moderate-to-severe optic nerve damage compared to D2 mice fed a control diet. In conclusion, global reduction of microglia exacerbated glaucomatous neurodegeneration in D2 mice suggesting microglia play an overall beneficial role in protecting from ocular hypertension associated RGC loss.
Unravelling the Interplay of Nitrogen Nutrition and theBotrytis cinereapectin lyase BcPNL1 in ModulatingArabidopsis thalianaSusceptibility
Authors: Davière Antoine , Voxeur Aline , Jolivet Sylvie , Vernhettes Samantha , Soulié Marie-Christine , Fagard Mathilde
Published: March 2024

In this study, we investigated the intricate interplay between nitrogen nutrition, and the dynamics of pectin degradation during plant-pathogen interactions, usingArabidopsis thalianaandBotrytis cinereaas a model pathosystem. Our findings revealed a noteworthy impact of nitrogen availability on the pectin degrading activity of theB. cinereapectin lyase 1 (PNL) for which the mutant strains presented a reduced pathogenicity restored by complementation. More precisely, infected nitrogen-sufficient (high N) plants exhibited an increased release of PNL-derived oligogalacturonides compared to infected nitrogen-deficient (low N) plants. This correlated with an elevated expression of jasmonic acid repressor genes in high N plants, rendering them more susceptible toB. cinerea. UsingΔBcpnl1deletion mutants, we demonstrated that the increased production of BcPNL1 -derived oligogalacturonides under high N conditions was responsible for the increased expression of jasmonic acid repressor genes, significantly contributing to the higher susceptibility of high N plantstoB. cinerea.In conclusion, we demonstrated that BcPNL1 is a major pathogenicity factor duringB. cinereainteraction that is affected by the plant’s N nutrition conditions.
MASCOT-Skyline integrates population and migration dynamics to enhance phylogeographic reconstructions
Authors: Müller Nicola Felix , Bouckaert Remco R , Wu Chieh-Hsi , Bedford Trevor Felix
Published: March 2024

The spread of infectious diseases is shaped by spatial and temporal aspects, such as host population structure or changes in the transmission rate or number of infected individuals over time. These spatiotemporal dynamics are imprinted in the genome of pathogens and can be recovered from those genomes using phylodynamics methods. However, phylodynamic methods typically quantify either the temporal or spatial transmission dynamics, which leads to unclear biases, as one can potentially not be inferred without the other. Here, we address this challenge by introducing a structured coalescent skyline approach, MASCOT-Skyline that allows us to jointly infer spatial and temporal transmission dynamics of infectious diseases using Markov chain Monte Carlo inference. To do so, we model the effective population size dynamics in different locations using a non-parametric function, allowing us to approximate a range of population size dynamics. We show, using a range of different viral outbreak datasets, potential issues with phylogeographic methods. We then use these viral datasets to motivate simulations of outbreaks that illuminate the nature of biases present in the different phylogeographic methods. We show that spatial and temporal dynamics should be modeled jointly even if one seeks to recover just one of the two. Further, we showcase conditions under which we can expect phylogeographic analyses to be biased, particularly different subsampling approaches, as well as provide recommendations of when we can expect them to perform well. We implemented MASCOT-Skyline as part of the open-source software package MASCOT for the Bayesian phylodynamics platform BEAST2.
Convolutional neural network models of the primate retina reveal adaptation to natural stimulus statistics
Authors: Vystrčilová Michaela , Sridhar Shashwat , Burg Max F. , Gollisch Tim , Ecker Alexander S.
Published: March 2024

The diverse nature of visual environments demands that the retina, the ﬁrst stage of the visual system, encodes a vast range of stimuli with various statistics. The retina adapts its computations to some speciﬁc features of the input, such as brightness, contrast or motion. However, it is less clear whether it also adapts to the statistics of natural scenes compared to white noise, the latter of which is often used to infer models of retinal computation. To address this question, we analyzed neural activity of retinal ganglion cells (RGCs) in response to both white noise and naturalistic movie stimuli. We performed a systematic comparative analysis of traditional linear-nonlinear (LN) and recent convolutional neural network (CNN) models and tested their generalization across stimulus domains. We found that no model type trained on one stimulus ensemble was able to accurately predict neural activity on the other, suggesting that retinal processing depends on the stimulus statistics. Under white noise stimulation, the receptive ﬁelds of the neurons were mostly lowpass, while under natural image statistics they exhibited a more pronounced surround resembling the whitening ﬁlters predicted by efficient coding. Together, these results suggest that retinal processing dynamically adapts to the stimulus statistics.
Sexual Dimorphism in Age-Dependent Neurodegeneration After Mild Head Trauma inDrosophila: Unveiling the Adverse Impact of Female Reproductive Signaling
Authors: Ye Changtian , Ho Ryan , Moberg Kenneth H. , Zheng James Q.
Published: March 2024

Environmental insults, including mild head trauma, significantly increase the risk of neurodegeneration. However, it remains challenging to establish a causative connection between early-life exposure to mild head trauma and late-life emergence of neurodegenerative deficits, nor do we know how sex and age compound the outcome. Using aDrosophilamodel, we demonstrate that exposure to mild head trauma causes neurodegenerative conditions that emerge late in life and disproportionately affect females. Increasing age-at-injury further exacerbates this effect in a sexually dimorphic manner. We further identify Sex Peptide (SP) signaling as a key factor in female susceptibility to post-injury brain deficits. RNA sequencing highlights a reduction in innate immune defense transcripts specifically in mated females during late life. Our findings establish a causal relationship between early head trauma and late-life neurodegeneration, emphasizing sex differences in injury response and the impact of age-at-injury. Finally, our findings reveal that reproductive signaling adversely impacts female response to mild head insults and elevates vulnerability to late-life neurodegeneration.
A truncation mutant of adenomatous polyposis coli (APC) impairs apical cell extrusion through elevated epithelial tissue tension
Authors: Gan Wan J. , Giri Rabina , Begun Jakob , Abud Helen E. , Hardeman Edna C. , Gunning Peter W. , Yap Alpha S. , Noordstra Ivar
Published: March 2024

Tissue tension encompasses the mechanical forces exerted on solid tissues within animal bodies, originating from various sources such as cellular contractility, interactions with neighbouring cells and the extracellular matrix. Emerging evidence indicates that an imbalance in tissue tension can influence structural organisation, homeostasis and potentially contribute to disease. For instance, heightened tissue tension can impede apical cell extrusion, leading to the retention of apoptotic or transformed cells. In this study, we investigate the potential role of adenomatous polyposis coli (APC) in modulating tissue tension. Our findings reveal that expression of an APC truncation mutant elevates epithelial tension via the RhoA/ROCK pathway. This elevation induces morphological alterations and hampers apoptotic cell extrusion in cultured epithelial cells and organoids, both of which could be mitigated by pharmacologically restoring the tissue tension. This raises the possibility that APC mutations may exert pathogenetic effects by altering tissue mechanics.
Graph connection Laplacian allows for enhanced outcomes of consumer camera based photoplethysmography imaging
Authors: Borik Stefan , Wu Hau-Tieng , Shelley Kirk H. , Alian Aymen A.
Published: March 2024

Object

This work introduces a novel method to minimize the effect of global phase deviation that is inherent in photoplethysmographic images (PPGI) captured by video.

Method

We analyzed the facial vascular network obtained from a consumer camera as a two-dimensional manifold. Subtle phase variations across skin sites are due to complex dynamics of the vascular tree. Utilizing PPGI, the phase is modeled as a vector field of the facial manifold. The phase variations over different skin sites are caused by different blood volume modulations. We propose using the Graph Connection Laplacian (GCL) technique to quantify the global phase deviation, with the hope that correcting for this deviation could improve the quality of the PPGI signal. It is also postulated that study of this phase deviation might reveal valuable anatomical and physiological information.

Result

The proposed algorithm appears to yield a higher-quality global PPGI signal. By correcting the global phase deviation estimated by GCL waveform features such as the dicrotic notch are emphasized. The perfusion map, with the global phase deviation (estimated by GCL as intensity), appears to reflect skin perfusion dynamics.

Conclusion

This algorithm enhances the quality of the global PPGI signal, facilitating the analysis of morphological parameters and showing promise for advancing PPGI applications in scientific research and clinical practice.
Zapping the brain to enhance sport performance? Evidence from an umbrella review of the effect of transcranial direct current stimulation on physical performance
Authors: Holgado Darías , Sanabria Daniel , Vadillo Miguel A. , Román-Caballero Rafael
Published: March 2024

Concepts such as "neuro-doping" or brain doping have contributed to an expansion in the area of transcranial direct current stimulation (tDCS) and its impact over exercise and physical performance in recent years. Here we assess the evidence supporting the healthy population using an umbrella review of meta-analyses investigating the role of tDCS to enhance exercise performance. We identified 9 meta-analyses encompassing 50 crossover studies and 683 participants that met our inclusion criteria. Despite the fact that most meta-analyses reported a positive effect of tDCS, our analyses revealed overly low statistical power in the primary studies, publication bias, and large variability in pre-processing and analytic decisions. Indeed, a specification-curve analysis showed that the final effect could range fromg= −0.23 tog= 0.33, depending on decisions such as the formula used for estimating the effect size and multiple additional analytic steps. Moreover, a meta-analysis of all the primary studies included in the umbrella review showed a small effect of tDCS (gz= 0.28, 95%CI [0.18, 0.39]) that became substantially smaller and inconclusive after accounting for publication bias,grm= 0.10, 95%CrI [−0.04, 0.20],BF10= 0.99. In summary, our findings highlight that current evidence, from both individual studies and meta-analyses, does not conclusively support the idea that tDCS enhances performance outcomes.
Lipoprotein(a) testing in Patients with Atherosclerotic Cardiovascular Disease in Five Large U.S. Health Systems
Authors: Shah Nishant P. , Mulder Hillary , Lydon Betsy , Chiswell Karen , Hu Xingdi , Lampron Zachary , Cohen Lauren , Patel Manesh R. , Taubes Susan , Song Wenliang , Mulukutla Suresh R. , Saeed Anum , Morin Daniel P. , Bradley Steven M. , Hernandez Adrian F. , Pagidipati Neha J.
Published: March 2024

Introduction

Lipoprotein (a) [Lp(a)] is an independent, causal risk factor for atherosclerotic cardiovascular disease (ASCVD). However, testing patterns remain variable and it is unclear what patient level factors are associated with Lp(a) testing, and if testing changes clinical management.

Methods

A retrospective study using electronic medical record data from five health systems in the CardioHealth Alliance identified an ASCVD cohort that was divided into those with a Lp(a) test and those without a Lp(a) test between 2019-2021. Baseline characteristics and initiation of lipid lowering therapy (LLT) was assessed. Multivariable regression modeling was used to determine factors associated with Lp(a) testing.

Results

Among 595,684 ASCVD patients, only 2,587 (0.4%) were tested for Lp(a) between 2019 and 2021. In adjusted models, those who were older or Black were less likely to have Lp(a) testing, while those with familial hypercholesterolemia, ischemic stroke/TIA, PAD, prior LLT, or LDL-C ≥130mg/dL were more likely to be tested. Those with a Lp(a) test, regardless of the Lp(a) value, were more frequently initiated on any statin therapy (30.3% vs. 10.6%, p<0.001), ezetimibe (7.65 vs. 0.8%, p <0.001), or PCSK9i (6.7% vs. 0.3%, p <0.001) compared with those without a test. Those with an elevated Lp(a) level more frequently initiated ezetimibe (11.5% vs. 5.9%, P <0.001) or PCSK9i (10.9% vs. 4.8%, P <0.001), but not statin therapy.

Conclusions

Lp(a) testing in ASCVD patients is infrequent, with evidence of disparities among older or Black individuals. Testing for Lp(a), regardless of level, is associated with greater initiation of any LLT, while elevated Lp(a) is associated with greater initiation of non-statin LLT. Overall, initiation of LLT remained low, despite guideline indications for LLT in ASCVD patients. There is a critical need for multidisciplinary and inclusive approaches to raise awareness for Lp(a) testing and its implications on management.
Assessment of Psychometric Vigilance on Neonatal Transport: A Western Australian Experience
Authors: Wilson Alexander , McDonald Kylie , Cooper Matthew , Stevenson Paul , Davis Jonathan , Patole Sanjay
Published: March 2024

Objectives To assess whether undertaking retrieval was associated with fatigue independent of sleep and circadian disruption. Background Fatigue is associated impaired clinician performance and safety. The association between shift work, sleep deprivation and circadian disruption is well established. No studies have specifi-cally assessed the independent effect of the retrieval environment on fatigue. Method Medical and nursing staff of the neonatal retrieval team were prospectively recruited over a 12-month period. Simple reaction times (RT) were recorded at the start and end of a day shift using a validated 3-min Psychometric Vigilance Test (PVT). Results End of shift RT increased by 6.38ms (95% CI: -2.17 to 14.92ms, p = 0.149) when retrieval was undertaken. A 1ms increase in RT increased the odds of being in a subjective sleepy cate-gory by 0.57% (log odds: 0.0057, 95% CI: 0.0036 to 0.0078). Consuming caffeine during the shift increased mean RT by 16.26 ms (95% CI: 4.43 to 28.1 ms, p <0.01). Conclusion The 3-min PVT was found to be an easy method of objectively assessing fatigue in the re-trieval setting. The effects of caffeine consumption on RT warrants further investigation.
Setting up a Hospital Based Diarrhoea Surveillance System in a Low- and Middle-Income Country: Lessons Learned
Authors: Miti Sam , Chisenga Caroline C , Mubanga Cynthia , Msimuko Lusungu , Manda Chipo , Zulu Catherine , Kalaba Naomi Muleba , Niyongabo Christian Musilikare , Chisapi Lydia , Thole David , Nachamba Mwizukanji , Moono Roy , Chakopo Moses , Chibwe Dorcas , Kabungo Theresa , Chibesa Kayayi , Nanyangwe Vivian , Nduna Bwendo , Chongwe Gershom , Chileshe Justine , Cohen Dani , Chilengi Roma , Siziya Seter , Simuyandi Michelo
Published: March 2024

Background

Acute diarrhoea is a major cause of morbidity and mortality among children in low-resource settings. Establishing effective surveillance systems is crucial for monitoring and responding to diarrhoeal outbreaks.

Objective

This manuscript presents the lessons learned during the setup of a hospital-based diarrhoea surveillance system at Arthur Davison Children’s Hospital in Ndola, Zambia. Specifically, the reasons for the delays in processing stool samples from collection to reporting of laboratory results were explored.

Methods

The setup of the surveillance system involved several key steps, including stakeholder engagement, training of healthcare workers, development of data collection tools, and establishment of reporting mechanisms. The system aims to capture data on diarrhoea cases admitted to the hospital, including demographic information, clinical presentation and laboratory results.

Results

Numerous obstacles were encountered during the implementation of the surveillance. There were three points of delay identified in the ADCH diarrhoea sample handling process from collection to processing: 1) Stool sample collection and packaging 2) Sample transfer from the clinical area to the laboratory 3) Handling and processing in the laboratory. Gaps identified in the three delays related to 1) Staff attitudes and perceptions 2) Health systems infrastructure 3) Operational issues 4) Data management. The following key elements are recommended for setting up a robust, locally owned diarrhoea surveillance system: Implementation of cross-cutting intervention across domains, and a human-centered approach targeted at behavioral change, creating local leadership and ownership of surveillance activities, systematic capacity building through ongoing training/orientation/local data sharing platforms for healthcare personnel, establishing reliable data collection and reporting procedures, addressing infrastructure limitations, and integrating the surveillance system into existing health information systems.

Conclusion

We established a hospital-based diarrhoea surveillance system at ADCH in Ndola, Zambia. Several obstacles were identified and resolved, which provide valuable lessons for future implementing of diarrhoea surveillance systems in low resource settings. Successful implementation requires engaging of hospital and laboratory staff, adaptable and easy to use surveillance tools including entering sample information in an electronic laboratory information system and committed leadership.
WITHDRAWN: Let’s talk about sex: college students’ attitudes towards Sexuality Education in a Spanish University
Authors: Lahoz-García Clara , Jimenez José María , Castro María José , Parejo José-Luis
Published: March 2024

Withdrawal Statement

The authors have withdrawn this manuscript because since its initial submission, the manuscript has undergone substantial modifications, including an expansion of the study, refinement of the methodology, and revisions to the conclusions. These changes have resulted in a different version of the work, which is now being submitted as an original and unpublished manuscript for peer review in a scientific journal. Given that the preprint no longer reflects the findings and conclusions we stand by, we respectfully request its withdrawal.

We fully acknowledge MedRxiv’s policy that preprints remain part of the scientific record and appreciate that the original manuscript will remain accessible with a “Withdrawn” watermark.

Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Estimation equation of limb lean soft tissue mass in Asian athletes using bioelectrical impedance analysis
Authors: Lai Yeong-Kang , Ho Chu-Ying , Huang Ai-Chun , Lu Hsueh-Kuan , Hsieh Kuen-Chang
Published: March 2024

Background

The lean soft tissue mass (LSTM) of the limbs is approximately 63% of total skeletal muscle mass. For athletes, measurement of limb LSTM is the basis for rapid estimation of skeletal muscle mass. This study aimed to establish the estimation equation of LSTM in Asian athletes using bioelectrical impedance analysis (BIA).

Methods

A total of 198 athletes (121 males, 77 females; mean age 22.04 ± 5.57 years) from different sports in Taiwan were enrolled. A modeling group (MG) of 2/3 (n = 132) of subjects and a validation group (VG) of 1/3 (n = 68) were randomly assigned. Resistance (R) and reactance (Xc) were measured using 50KHz current measurement in whole-body mode. Predictor variables were height (h), weight (W), age, gender, Xc, resistance index (RI; RI = h2/ R). LSTM of arms and legs measured by dual-energy X-ray absorptiometry (DXA) was the response variable. Multivariate stepwise regression analysis method was used to establish BIA estimation equations as ArmsLSTMBIA-Asianand LegsLSTMBIA-Asian. Estimation equations performance was confirmed by cross-validation.

Results

Estimation equation “ArmsLSTMBIA-Asian= 0.096 h2/R – 1.132 gender + 0.030 Weight + 0.022 Xc – 0.022 h + 0.905, r2= 0.855, SEE = 0.757 kg, n = 132” and “LegsLSTMBIAAsian= 0.197h2/R” + 0.120 h – 1.242 gender + 0.055 Weight – 0.052 Age + 0.033 Xc –16.136, r2= 0.916, SEE = 1.431 kg, n = 132” were obtained from MG. Using DXA measurement results of VG for correlation analysis and Limit of Agreement (LOA) of Bland-Altman Plot, ArmsLST is 0.924, -1.53 to 1.43 kg, and LegsLST is 0.957, -2.68 to 2.90 kg.

Conclusion

The established single-frequency BIA hand-to-foot estimation equation quickly and accurately measures LSTM of the arms and legs of Asian athletes.
Iron status in a representative sample of US pregnant women is not associated with pre-pregnancy BMI: results from the NHANES (1999-2010) study
Authors: Ciulei Mihaela A. , Gallagher Kelly , Ba Djibril , Beck Celeste , Pobee Ruth A. , Gernand Alison D. , Walker Rachel E.
Published: March 2024

Iron deficiency in pregnancy is related to many poor health outcomes, including anemia and low birth weight. A small number of previous studies have identified maternal body mass index (BMI) as potential risk factors for poor iron status. Our objective was to examine the association between pre-pregnancy BMI and iron status in a nationally representative sample of US adult women. We used data from the National Health and Nutrition Examination Survey (NHANES; 1999-2010) for pregnant women ages 18-49 years (n=1156). BMI (kg/m2) was calculated using pre-pregnancy weight (self-reported) and height (measured at examination). Iron deficiency (ID) was defined as total body iron (calculated from serum ferritin and transferrin receptor using Cook’s equation) < 0 mg/kg and anemia as hemoglobin < 11 g/dL. Associations were examined using weighted Poisson regression models, adjusted for confounders (age, race/ethnicity, education, family income, and trimester). Approximately 14% of pregnant women had ID and 8% had anemia in this sample. There were no differences in the prevalence of ID or anemia in women with pre-pregnancy overweight and obesity (ID: overweight, adjusted prevalence ratio (PR)=1.28, 95%CI: 0.89-1.83; obesity, PR=0.75, 95%CI: 0.39-1.45; anemia: overweight, PR=1.08, 95%CI: 0.53-2.19; obesity, PR=0.99, 95%CI: 0.49-2.01) compared to women with a normal BMI. Findings from these US nationally representative data indicate that iron status in pregnancy does not differ by pre-pregnancy BMI. Since iron deficiency during pregnancy remains a significant public health concern, NHANES should consider measuring current iron status in upcoming cycles.
Advancing Rheumatology Practice: Systematic Review of Natural Language Processing Applications
Authors: Omar Mahmud , Glicksberg Benjamin S. , Reuveni Hagar , Nadkarni Girish N. , Klang Eyal
Published: March 2024

Background

With the advent of large language models (LLM), such as ChatGPT, natural language processing (NLP) is revolutionizing healthcare. We systematically reviewed NLP’s role in rheumatology and assessed its impact on diagnostics, disease monitoring, and treatment strategies.

Methods

Following PRISMA guidelines, we conducted a systematic search to identify original research articles exploring NLP applications in rheumatology. This search was performed in PubMed, Embase, Web of Science, and Scopus until January 2024.

Results

Our search produced 17 studies that showcased diverse applications of NLP in rheumatology, addressing disease diagnosis, data handling, and monitoring.

Notably, GPT-4 demonstrated strong performance in diagnosing and managing rheumatic diseases. Performance metrics indicated high accuracy and reliability in various tasks. However, challenges like data dependency and limited generalizability were noted.

Conclusion

NLP, and especially LLM, show promise in advancing rheumatology practice, enhancing diagnostic precision, data handling, and patient care. Future research should address current limitations, focusing on data integrity and model generalizability.
Multifaceted Representation of Genes via Deep Learning of Gene Expression Networks
Authors: Su Zheng , Fang Mingyan , Smolnikov Andrei , Dinger Marcel E. , Oates Emily C. , Vafaee Fatemeh
Published: March 2024

Accurate predictive modeling of human gene relationships would fundamentally transform our ability to uncover the molecular mechanisms that underpin key biological and disease processes. Recent studies have employed advanced AI techniques to model the complexities of gene networks using large gene expression datasets1–11. However, the extent and nature of the biological information these models can learn is not fully understood. Furthermore, the potential for improving model performance by using alternative data types, model architectures, and methodologies remains underexplored. Here, we developed GeneRAIN models by training on a large dataset of 410K human bulk RNA-seq samples, rather than single-cell RNA-seq datasets used by most previous studies. We showed that although the models were trained only on gene expression data, they learned a wide range of biological information well beyond gene expression. We introduced GeneRAIN-vec, a state-of-the-art, multifaceted vectorized representation of genes. Further, we demonstrated the capabilities and broad applicability of this approach by making 4,797 biological attribute predictions for each of 13,030 long non-coding RNAs (62.5 million predictions in total). These achievements stem from various methodological innovations, including experimenting with multiple model architectures and a new ‘Binning-By-Gene’ normalization method. Comprehensive evaluation of our models clearly demonstrated that they significantly outperformed current state-of-the-art models3,12. This study improves our understanding of the capabilities of Transformer and self-supervised deep learning when applied to extensive expression data. Our methodological advancements offer crucial insights into refining these techniques. These innovations are set to significantly advance our understanding and exploration of biology.
Differentiating specific and non-specific protein-metabolite interactions using gradient open port probe electrospray ionization mass spectrometry
Authors: Tian Xiaobo , Hopfgartner Gérard
Published: March 2024

Native electrospray ionization mass spectrometry (ESI-MS) using nano ESI or desorption electrospray ionization (DESI) has been widely used to study interactions between macromolecules and ligands, usually protein-metabolite interactions (PMIs). In MS spectra the charge state distributions (CSD) of proteins differ between native and non-native conditions and based on this, we report a method that can differentiate specific protein-metabolite interactions from non-specific binding. Our approach is based on a 3D-printed open port probe electrospray system (gOPP-ESI) using mobile phase gradients (aqueous to methanol) for the ionization of protein/protein-metabolite complex. Notably, we found that a true protein-metabolite complex is more resistant to the denaturing effect of methanol compared to the free protein. This is corroborated by the observation that forming high charge states of protein-metabolite complexes requires higher proportions of methanol than free protein while, for non-specific complexes, there is no obvious difference in the CSD. Therefore, by comparing the changes in the CSD of free protein and protein-metabolite complex versus the increase of methanol, we can distinguish metabolites that specifically interact with the target protein. The approach is evaluated with well-characterized protein-ligand pairs, and we confirmed that cytidine phosphates,N, N′, N″-triacetylchitotriose, and fluvastatin are specific ligands for ribonuclease A, lysozyme, and beta-lactoglobulin respectively. However, cytidine-5’-triphosphate (CTP) interacts non-specifically with lysozyme and beta-lactoglobulin. We believe that after first-round native-MS assays to identify which metabolites cause mass shifts to the free protein, the gOPP-ESI-MS could be used as a quick second-round check to exclude non-specific binding and discover metabolites truly interacting with the protein of interest, reducing the number of candidates for subsequent validation experiments.

Abstract Figure
An Entrainment Oscillator Mechanism underlies Human Beat Matching Performance
Authors: Mondok Chloe , Wiener Martin
Published: March 2024

Humans possess an innate ability to effortlessly entrain to auditory rhythms, which previous theories have linked to the supplementary motor area (SMA). Yet, whether entrainment, as measured by electrophysiological (EEG) recordings reflects actual processing of rhythms or merely a reflection of their periodical nature, is unknown. Here we conducted tested human participants on a novel beat matching task, in which they listened to two simultaneous tempos and asked to modulate the rate of a variable tempo (1.67-2.34 Hz between trials) to match a constant target tempo (2 Hz). EEG recordings exhibited entrainment to both frequencies at frontocentral electrodes that shifted into alignment over the course of each trial Behaviorally, participants tended to anchor the matched tempo to the starting comparison frequency, such that they underestimated the tempo for slower initial conditions and overestimated for faster initial conditions; further, tempo judgments were shifted away from the variable tempo on the previous trial. A model of phase-coupled oscillators, in which both tempos were pulled towards one another, replicated both effects. This model further predicted that by strengthening the coupling strength of the constant tempo oscillator, both bias effects could be eliminated. To test this, a second group of subjects underwent transcranial alternating current stimulation (tACS) to the SMA phase-locked to the target tempo at 2 Hz. Consistent with model predictions, tACS attenuated both behavioral effects. Overall, these results provide causal support to the role of the SMA in entrainment during human beat matching.