bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simple, reference-independent analyses help optimize hybrid assembly of microbial community metagenomes
Authors: Smith Garrett J. , van Alen Theo , van Kessel Maartje , Lücker Sebastian 
Published: September 2023

AbstractHybrid metagenomic assembly, leveraging both long- and short-read sequencing technologies, of microbial communities is becoming an increasingly accessible approach, yet its widespread application faces several challenges. High-quality references may not be available for assembly accuracy comparisons common for benchmarking, and certain aspects of hybrid assembly may require dataset-dependent, empirically-guided optimization rather than application of a uniform approach. In this study, several simple, reference-free characteristics – gene lengths and read recruitment – were analyzed as reliable proxies of assembly quality to guide hybrid assembly optimization. These characteristics were further explored in relation to reference-dependent genome- and gene-centric analyses that are common for microbial community metagenomic studies. Here, two laboratory-scale bioreactors were sequenced with short and long read platforms, and assembled with commonly used software packages. Following long read assembly, long read correction and short read polishing were iterated to resolve errors. Each iteration in this process was shown so have a substantial effect on gene- and genome-centric community composition. Simple, reference-free assembly characteristics, specifically changes in gene fragmentation and short read recruitment, explored throughout this process replicated patterns of more advanced analyses seen in published comparative studies, and therefore are suitable proxies for hybrid metagenome assembly accuracy to save computational resources. Hybrid metagenomic sequencing approaches will likely remain relevant due to the low costs of short read sequencing, therefore it is imperative that users are equipped to estimate assembly accuracy prior to downstream gene- and genome-centric analyses.
Mechanisms underneathXanthomonas citrisubsp.citripromoting ofAgrobacterium-mediated transient expression in citrus
Authors: Lamichhane Tirtha , Wang Nian 
Published: September 2023

AbstractAgrobacterium-mediated transient expression (TE) is an important tool in plant genetics study and biotechnology. Citrus is one of the top tree crops, butAgrobacterium-mediated TE remains problematic in citrus. Previous study has shown that pretreatment of citrus leaves withXanthomonas citrisubsp.citri(Xcc), which causes citrus canker in almost all citrus cultivars, significantly improves the TE efficacy. Here we have shown thatXccpromotesAgrobacterium-mediated TE via improvingAgrobacteriumgrowth, suppressing plant immune response, triggering cell division, and upregulating plant cell wall degrading enzymes. We demonstrate thatXccpromotesAgrobacterium-mediated TE via PthA and mutation ofpthA4abolishes the promoting effect ofXcc.PthA4 is known to trigger cell division of citrus. We have demonstrated the causative relationship between cell division andAgrobacterium-mediated TE using cell division inhibitor mimosine. Importantly, the differential effects of mimosine and colchicine onXccpromotingAgrobacterium-mediated TE indicate that S-phase is critical for agroinfiltration of citrus tissues. In addition, PthA4 is known to upregulate plant growth hormones auxin (IAA), gibberellin and cytokinin, as well as cell degrading enzymes (e.g., cellulase). Exogenous application of IAA, cytokinin, and cellulase but not gibberellin significantly improvedAgrobacterium-mediated TE in leaves of sweet orange, pummelo, Meiwa kumquat, lucky bamboo and rose mallow. Our study provides a mechanistic understanding regarding howXccpromotesAgrobacterium-mediated TE and identified two practical measures to improveAgrobacterium-mediated TE via pretreatment with plant hormones (i.e., auxin and cytokinin) and cellulase.
Protein expression profiles in brain organoids are more similar to those in human brain parenchyma than in mouse brain parenchyma
Authors: Wenzel Tyler J. , Mousseau Darrell D. 
Published: September 2023

SummaryHuman brain organoids are emerging as relevant models for the study of human brain health and disease. However, it has not been shown whether human brain organoids exhibit a proteoform profile similar to the human brain. Herein, we demonstrate that unguided brain organoids exhibit minimal batch-to-batch variability in cell composition and metabolism when generated from induced pluripotent stem cells (iPSCs) derived from male-female siblings. We then show that profiles of select proteins in these brain organoids are more similar to autopsied human cortical and cerebellar profiles than to those in mouse cortical samples. Brain organoids derived from sibling iPSCs do not exhibit any sex differences in protein proportions. By benchmarking human brain organoid proteoforms against human parenchymal tissue, we establish the foundation for future studies that could investigate, for example, how well brain organoids can model any of the known sex-dependent differences in cellular function, including responses of drug-receptor interactions.HighlightsBrain organoids (BOs) display protein banding similar to human parenchymal lysatesProtein banding differs between mouse and human brain parenchyma lysatesSibling-derived BOs have similar cell composition and metabolism at day 90Sibling-derived BOs exhibit similar protein banding at day 90
Characterizing the blood stage antimalarial activity of pyronaridine in healthy volunteers experimentally infected withPlasmodium falciparum
Authors: Barber Bridget E. , Webster Rebecca , Potter Adam J. , Llewellyn Stacey , Sahai Nischal , Leelasena Indika , Mathison Susan , Kuritz Karsten , Flynn Julia , Chalon Stephan , Marrast Anne Claire , Gobeau Nathalie , Moehrle Joerg J. 
Published: September 2023

ABSTRACTAlthough pyronaridine has been used to successfully treat malaria for many years, its antimalarial activity in humans has not been completely characterized. This volunteer infection study aimed to determine the pharmacokinetic/pharmacodynamic (PK/PD) relationship of pyronaridine in healthy malaria naïve adults. Volunteers were inoculated withPlasmodium falciparum3D7-infected erythrocytes on day 0 and different single oral doses of pyronaridine were administered on day 8. Parasitemia, and concentrations of pyronaridine in whole blood were measured and standard safety assessments performed. Curative artemether-lumefantrine therapy was administered if parasite regrowth occurred, or on day 47±2. Outcomes were parasite clearance kinetics, PK and PK/PD parameters from modelling. Ten participants were inoculated and administered 360 mg (n=4), 540 mg (n=4), or 720 mg (n=1) pyronaridine. One participant was withdrawn without receiving pyronaridine. Time to maximum pyronaridine concentration after dosing was 1-2 hours and the elimination half-life was 8-9 days. A parasite clearance half-life of approximately 5 hours was calculated for all dose levels. Parasite regrowth occurred after dosing with 360 mg (4/4 participants) and 540 mg (2/4 participants). Key efficacy parameters of pyronaridine including the minimum inhibitory concentration (MIC: 5.5 ng/mL) and minimum parasiticidal concentration that leads to 90% of maximum effect (MPC90: 8 ng/mL) were derived from the final PK/PD model. Adverse events considered related to pyronaridine were predominantly mild to moderate gastrointestinal symptoms. There were no serious adverse events. Data obtained in this study will support the use of pyronaridine in new antimalarial combination therapies by informing partner drug selection and dosing considerations.
Leukocyte Telomere Length and Cardiac Structure and Function: A Mendelian Randomization Study
Authors: Salih Ahmed , Boscolo Galazzo Ilaria , Menegaz Gloria , Altmann André 
Published: September 2023

AbstractExisting research demonstrates association of shorter telomere length (TL) with increased risk of agerelated health outcomes including cardiovascular diseases. However, the direct causality of these relationships is not definitively established. Cardiovascular aging at an organ-level may be captured using image derived phenotypes (IDPs) of cardiac anatomy and function. In the current study, we use two-sample Mendelian Randomization (MR) to assess the causal link between TL and 54 cardiac magnetic resonance imaging (CMR) measures representing structure and function across the four cardiac chambers. Genetically predicted shorter TL was causally linked to smaller ventricular cavity sizes including left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), lower left ventricular mass (LVM) and pulmonary artery. The association with LVM (β= 0.217, PFDR= 0.016) remained significant after multiple testing adjustment, whilst other associations were attenuated. Our findings support a causal role for shorter TL and faster cardiac aging, with the most prominent relationship with LVM.
Cardiovascular Risks Among the Transgender Population in Rural United States: Spotlight on the Appalachian Region
Authors: Ezeh Ebubechukwu , Perdoncin Maddie , Ogbu Chukwuemeka , Akhigbe Esiemoghie , Al-Hiari Mohammed , Ramalingam Archana , Saunders Elizabeth , Mader Jason , Rodriguez Lozano Patricia F. 
Published: September 2023

AbstractBackgroundGender diverse populations have disproportionately worse cardiovascular (CV) outcomes. However, the data on the prevalence of cardiovascular risk factors among the transgender population in rural Appalachia remains limited. The purpose of this study was to determine the prevalence of CV risk factors among the transgender population in rural Appalachia.MethodsThis retrospective case-control study from an Appalachian university teaching hospital clinic matched transgender individuals with controls from the same clinic. Logistic regression model was performed to determine the prevalence of CV risk factors among the transgender population in comparison to their cisgender counterparts.ResultsThe total number of transgender and cisgender individuals identified were 89 and 69, respectively. After adjusting for age and family history of atherosclerotic CV disease, transgender status remained independently associated with tobacco use (adjusted odds ratio [aOR] 6.64 [2.59-17.01]) and prediabetes/diabetes mellitus (aOR 3.98 [1.05-15.15]). Among the transgender population, there were increased odds of obesity (aOR 13.39 [3.30-54.30] and hyperlipidemia (aOR 3.46 [1.03-11.59]) in the transgender male group compared to the transgender female group. In another subgroup analysis, transgender individuals who underwent surgical and/or hormonal treatment had significantly higher odds of tobacco use (aOR 6.67 [2.80-15.98]), statin need (aOR 3.97 [1.14-13.81], and alcohol use (aOR 11.31 [1.34-95.53]). Increased statin use tends to be associated with normal LDL levels.ConclusionsIn rural Appalachia, transgender status is associated with disproportionately higher odds of tobacco use, elevated blood glucose and other CV risk factors.
Diagnostic Value of Carotid Ring Sign in Predicting Internal Carotid True Occlusion
Authors: Yi Tingyu , Sui Yi , Zheng Ding-huan , Ren Xinwen , Lin Xiao-hui , Wu Yan-min , Lin Ding-lai , Pan Zhi-nan , Zheng Xiu-fen , Hong Ganji , Wu Mei-hua , Zeng Lisan , Chen Wen-huo 
Published: September 2023

BACKGROUND AND PURPOSETo differentiate between pseudo-occlusion (PO) and true occlusion (TO) of internal carotid artery (ICA) is important in thrombectomy treatment planning for acute ischemic stroke (AIS) patients. Although delayed contrast filling has been differentiated carotid PO from TO, its application has been limited by the implementations of multiphasic computed tomography angiography (mCTA). In this study, we hypothesized that carotid ring sign, which is readily acquired from single-phasic CTA, can sufficiently differentiate carotid TO from PO.METHODSTwo hundred patients with non-visualization of the proximal ICA were included. Diagnosis of PO or TO of the cervical segment of ICA was made based on digital subtraction angiography. Diagnostic performances of carotid ring sign on arterial-phasic CTA and delayed contrast filling on mCTA were evaluated and compared.RESULTSOne-hundred-twelve patients had ICA PO and 88 had TO. Carotid ring sign was more common in TO patients (70.5% vs 6.3%, p<0.001), while delayed contrast filling was more common in PO (94.9% vs 7.7%, p<0.001). The sensitivity and specificity of carotid ring sign in diagnosing carotid TO was 0.70 and 0.94 respectively, while sensitivity and specificity of delayed contrast filling was 0.95 and 0.92 in judging carotid PO.CONCLUSIONSCarotid ring sign is a potent imaging marker in diagnosing ICA TO. Carotid ring sign could be complementary to delayed contrast filling sign in differentiating TO from PO, in particular in centers with only single-phasic CTA.
Factors associated with teenage pregnancies during the Covid-19 period in Pakwach district, Northern Uganda: a case-control study
Authors: Alunyo Jimmy Patrick , Mukunya David , Napyo Agnes , Matovu Joseph KB , Okia David , Wanume Benon , Okello Francis , Tuwa Ally Hassan , Wenani Daniel , Okibure Ambrose , Omara Godfrey , Olupot-Olupot Peter 
Published: September 2023

AbstractBackgroundTeenage pregnancy rates have globally decreased over the years, but remain high, especially in low- and middle-income countries (LMICs). Among girls aged 15-19, teenage pregnancy remains the leading cause of death and a significant barrier to education and productivity. Its prevalence underscores concern about the sexual and reproductive health of youth. However, limited data exist regarding factors contributing to its rise during the COVID-19 pandemic in Uganda. This study explores the factors associated with teenage pregnancy in Pakwach district during this period.MethodsWe conducted a matched case-control study, enrolling 362 teenage girls aged 10-19 years, divided into two groups: 181 pregnant teenagers and 181 not pregnant teenagers. We collected exposure data from both groups using questionnaires to evaluate factors associated with teenage pregnancy. The study period covered March 2020 to January 2021, coinciding with lockdown measures.ResultsDuring the COVID-19 lockdown, teenage pregnancies were only associated with having exclusively female peers (AOR 3.0, 95% CI: 0.1-104.4). Conversely, having a Radio/TV at home (AOR 0.2, 95% CI: 0.1-0.6), age at first sexual encounter (AOR 0.1, 95% CI: 0.03-0.9), considering teenage pregnancy as sexual abuse (AOR 0.1, 95% CI: 0.02-0.4), feeling comfortable asking questions during consultations (AOR 0.5, 95% CI: 0.2-1.3), and ensuring sufficient privacy during consultations were protective against teenage pregnancy.ConclusionThe factors contributing to increased teenage pregnancies during the COVID-19 pandemic were consistent with long-standing contextual factors associated with teenage pregnancy. The lockdown environment may have slightly exacerbated these factors, but no direct association was observed. Only having female peers was linked to teenage pregnancy during the lockdown. Conversely, having access to a radio/TV at home and other healthcare system-related factors offered protection. Therefore, interventions should prioritize providing comprehensive information on the risks of teenage pregnancy during any lockdown scenario.
The HOMEODOMAIN-Like protein HDL mediates chromatin organization and rewires leaf epidermal patterning
Authors: Ali Ansar , Kuan Chi , Hung Fu-Yu , Chen Tsai-Chen , Lee Hui-Chun , Yang Shao-Li , Feng Yun-Ru , Wu Keqiang , Ho Chin-Min Kimmy 
Published: September 2023

AbstractTheArabidopsisleaf epidermis is comprised of trichomes, pavement cells, and stomata, originating from versatile precursor cells capable of dividing or differentiating to create unique epidermal patterns. The mechanism governing these transitions and the maintenance of cell heterogeneity remains unclear. In this study, we identified a novelhomeodomain-like superfamily protein, HDL, localized in chromocenters and playing a role in chromatin organization. HDL interacts withhistonedeacetylase 6 (HDA6) and methyltransferases, indicating its function in modulating chromatin accessibility. Inhdlmutants, we observed moderately increased chromatin accessibility in the promoter region of protein-coding genes, along with reduced stomatal density and elevated trichome numbers on leaf surfaces. Corresponding to these phenotypes, stomatal-related gene expression decreased, while a transcriptional reporter forGLABRA2, a trichome initiation gene, exhibited higher and more variable expression levels. These findings highlight how HDL-mediated chromatin organization influences epidermal cell fate by modulating gene expression and enhancing cell heterogeneity within the leaf epidermis.One Sentence SummaryA homeodomain-like protein functions with histone modifiers to regulate chromatin and influence cell fate decisions.
Proximal immune-epithelial progenitor interactions drive chronic tissue sequelae post COVID-19
Authors: Narasimhan Harish , Cheon In Su , Qian Wei , Hu Sheng’en , Parimon Tanyalak , Li Chaofan , Goplen Nick , Wu Yue , Wei Xiaoqin , Son Young Min , Fink Elizabeth , Santos Gislane , Tang Jinyi , Yao Changfu , Muehling Lyndsey , Canderan Glenda , Kadl Alexandra , Cannon Abigail , Young Samuel , Hannan Riley , Bingham Grace , Arish Mohammed , Chaudhari Arka Sen , Sturek Jeffrey , Pramoonjago Patcharin , Shim Yun Michael , Woodfolk Judith , Zang Chongzhi , Chen Peter , Sun Jie 
Published: September 2023

ABSTRACTThe long-term physiological consequences of SARS-CoV-2, termed Post-Acute Sequelae of COVID-19 (PASC), are rapidly evolving into a major public health concern. The underlying cellular and molecular etiology remain poorly defined but growing evidence links PASC to abnormal immune responses and/or poor organ recovery post-infection. Yet, the precise mechanisms driving non-resolving inflammation and impaired tissue repair in the context of PASC remain unclear. With insights from three independent clinical cohorts of PASC patients with abnormal lung function and/or viral infection-mediated pulmonary fibrosis, we established a clinically relevant mouse model of post-viral lung sequelae to investigate the pathophysiology of respiratory PASC. By employing a combination of spatial transcriptomics and imaging, we identified dysregulated proximal interactions between immune cells and epithelial progenitors unique to the fibroproliferation in respiratory PASC but not acute COVID-19 or idiopathic pulmonary fibrosis (IPF). Specifically, we found a central role for lung-resident CD8+T cell-macrophage interactions in maintaining Krt8hitransitional and ectopic Krt5+basal cell progenitors, thus impairing alveolar regeneration and driving fibrotic sequelae after acute viral pneumonia. Mechanistically, CD8+T cell derived IFN-γ and TNF stimulated lung macrophages to chronically release IL-1β, resulting in the abnormal accumulation of dysplastic epithelial progenitors and fibrosis. Notably, therapeutic neutralization of IFN-γ and TNF, or IL-1β after the resolution of acute infection resulted in markedly improved alveolar regeneration and restoration of pulmonary function. Together, our findings implicate a dysregulated immune-epithelial progenitor niche in driving respiratory PASC. Moreover, in contrast to other approaches requiring early intervention, we highlight therapeutic strategies to rescue fibrotic disease in the aftermath of respiratory viral infections, addressing the current unmet need in the clinical management of PASC and post-viral disease.
Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic
Authors: Crits-Christoph Alexander , Levy Joshua I. , Pekar Jonathan E. , Goldstein Stephen A. , Singh Reema , Hensel Zach , Gangavarapu Karthik , Rogers Matthew B. , Moshiri Niema , Garry Robert F. , Holmes Edward C. , Koopmans Marion P. G. , Lemey Philippe , Popescu Saskia , Rambaut Andrew , Robertson David L. , Suchard Marc A. , Wertheim Joel O. , Rasmussen Angela L. , Andersen Kristian G. , Worobey Michael , Débarre Florence 
Published: September 2023

AbstractZoonotic spillovers of viruses have occurred through the animal trade worldwide. The start of the COVID-19 pandemic was traced epidemiologically to the Huanan Wholesale Seafood Market, the site with the most reported wildlife vendors in the city of Wuhan, China. Here, we analyze publicly available qPCR and sequencing data from environmental samples collected in the Huanan market in early 2020. We demonstrate that the SARS-CoV-2 genetic diversity linked to this market is consistent with market emergence, and find increased SARS-CoV-2 positivity near and within a particular wildlife stall. We identify wildlife DNA in all SARS-CoV-2 positive samples from this stall. This includes species such as civets, bamboo rats, porcupines, hedgehogs, and one species, raccoon dogs, known to be capable of SARS-CoV-2 transmission. We also detect other animal viruses that infect raccoon dogs, civets, and bamboo rats. Combining metagenomic and phylogenetic approaches, we recover genotypes of market animals and compare them to those from other markets. This analysis provides the genetic basis for a short list of potential intermediate hosts of SARS-CoV-2 to prioritize for retrospective serological testing and viral sampling.
Temporal Generative Models for Learning Heterogeneous Group Dynamics of Ecological Momentary Data
Authors: Kim Soohyun , Kim Young-geun , Wang Yuanjia 
Published: September 2023

SummaryOne of the goals of precision psychiatry is to characterize mental disorders in an individualized manner, taking into account the underlying dynamic processes. Recent advances in mobile technologies have enabled the collection of Ecological Momentary Assessments (EMAs) that capture multiple responses in real-time at high frequency. However, EMA data is often multi-dimensional, correlated, and hierarchical. Mixed-effects models are commonly used but may require restrictive assumptions about the fixed and random effects and the correlation structure. The Recurrent Temporal Restricted Boltzmann Machine (RTRBM) is a generative neural network that can be used to model temporal data, but most existing RTRBM approaches do not account for the potential heterogeneity of group dynamics within a population based on available covariates. In this paper, we propose a new temporal generative model, the Heterogeneous-Dynamics Restricted Boltzmann Machine (HDRBM), to learn the heterogeneous group dynamics and demonstrate the effectiveness of this approach on simulated and real-world EMA data sets. We show that by incorporating covariates, HDRBM can improve accuracy and interpretability, explore the underlying drivers of the group dynamics of participants, and serve as a generative model for EMA studies.