bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing Mass Vaccination Programs with Queueing Theory and Spatial Optimization
Authors: Xie Sherrie , Rieders Maria , Changolkar Srisa , Bhattacharya Bhaswar B. , Diaz Elvis W. , Levy Michael Z. , Castillo-Neyra Ricardo 
Published: June 2024

ABSTRACTBackgroundMass vaccination is a cornerstone of public health emergency preparedness and response. However, injudicious placement of vaccination sites can lead to the formation of long waiting lines orqueues, which discourages individuals from waiting to be vaccinated and may thus jeopardize the achievement of public health targets. Queueing theory offers a framework for modeling queue formation at vaccination sites and its effect on vaccine uptake.MethodsWe developed an algorithm that integrates queueing theory within a spatial optimization framework to optimize the placement of mass vaccination sites. The algorithm was built and tested using data from a mass canine rabies vaccination campaign in Arequipa, Peru. We compared expected vaccination coverage and losses from queueing (i.e., attrition) for sites optimized with our queue-conscious algorithm to those obtained from a queue-naive version of the same algorithm.ResultsSites placed by the queue-conscious algorithm resulted in 9-19% less attrition and 1-2% higher vaccination coverage compared to sites placed by the queue-naïve algorithm. Compared to the queue-naïve algorithm, the queue-conscious algorithm favored placing more sites in densely populated areas to offset high arrival volumes, thereby reducing losses due to excessive queueing. These results were not sensitive to misspecification of queueing parameters or relaxation of the constant arrival rate assumption.ConclusionOne should consider losses from queueing to optimally place mass vaccination sites, even when empirically derived queueing parameters are not available. Due to the negative impacts of excessive wait times on participant satisfaction, reducing queueing attrition is also expected to yield downstream benefits and improve vaccination coverage in subsequent mass vaccination campaigns.
Style deflection is determined by the handedness of phyllotaxis and auxin-induced differential cell elongation in a species with mirror-image flowers
Authors: Robertson Caroline , Xue Haoran , Saltini Marco , Fairnie Alice L. M. , Lang Dirk , Kerstens Merijn H. L. , Willemsen Viola , Ingle Robert A. , Barrett Spencer C. H. , Deinum Eva E. , Illing Nicola , Lenhard Michael 
Published: June 2024

ABSTRACTMany animals and plants show left-right (LR) asymmetry. In some animal systems, handedness has a simple genetic basis, which has allowed identifying how handedness is determined at the molecular level, even if its functional relevance often remains unclear. Mirror-image flowers represent an example of LR asymmetry of clear functional significance, with the reciprocal placement of male and female organs in left- versus right-handed flowers promoting cross-pollination. Here, we use the South African geophyteCyanella albato study how handedness of its mirror-image flowers is determined and elaborated during development. Inflorescences ofC. albaproduce flowers with a largely consistent handedness. However, we find that this handedness has no simple genetic basis, and individual plants can switch their predominant handedness between years. Rather, it is the direction of the phyllotactic spiral that determines floral handedness. Cellular analysis combined with biophysical modelling demonstrates that style deflection is driven by increased cell expansion in the adaxial carpel facing the next oldest flower compared to the other adaxial carpel. The more expanding carpel shows transcriptional signatures of increased auxin signaling compared to the less expanding one, and auxin application to the latter can reverse the orientation of style deflection. We propose that a recently described inherent LR auxin asymmetry in the initiating organs of spiral phyllotaxis determines handedness inC. alba, representing a conserved non-genetic mechanism for creating a stable floral polymorphism. This mechanism links chirality across different levels of plant development and exploits a developmental constraint in a core patterning process to produce morphological variation of ecological relevance.
Effect of environmental conditions on seed germination and seedling growth in
Cuscuta campestris
Authors: Nagao Koki , Takahashi Taku , Yokoyama Ryusuke 
Published: June 2024

Abstract

The dodder,
Cuscuta
, is an obligate parasitic plant that cannot survive without a host plant and causes major damage to crop yields. To know its growth characteristics before parasitism, we examined the effect of various environmental conditions on seed germination and seedling growth in
Cuscuta campestris
. As for the effect of light on germination, far-red light was rather preferable to red light and the reversible response of the seeds to red and far-red light was confirmed, implicating a phytochrome-mediated signaling opposite to that in many seed plants. Among amino acids, aspartic acid and alanine had a promotive effect and histidine had an inhibitory effect on germination. We further found that, in addition to gibberellic acid, methyl jasmonate was stimulatory to germination and shoot elongation. While 2,4-D extended the viability of trichomes around the root cap, kinetin induced the formation of scale leaves on the shoot and calli at the base of the shoot and the root tip. RT-PCR experiments confirmed that expression of a putative
RbcS
gene for photosynthesis showed no response to light but that of a
Phytochrome A
homolog was increased in the dark. Our results indicate that some of the molecular mechanisms to respond to light and hormone signals are uniquely modified in dodder seedlings, providing a clue for understanding the survival strategy of parasitic plants.
Sup4h5-L19 activation tagging line partially restores root hair growth inp4h5mutant by introducing small transcriptomic changes inArabidopsis thaliana
Authors: Urzúa Lehuedé Tomás , Núñez-Lillo Gerardo , Salgado Salter Juan , Acha Romina , Ibeas Miguel Angel , Meneses Claudio , Estevez José M. 
Published: June 2024

AbstractAn specific group of 2-oxoglutarate (2OG) dioxygenases named as Prolyl 4-Hydroxylases (P4H) produce trans-4-hydroxyproline (Hyp/O) from peptidyl-proline, catalyzing proline hydroxylation of cell wall glycoproteins EXT, AGPs, and HRGPs in plant cells, a crucial modification forO-glycosylation. Out of the Arabidopsis thaliana 13 P4Hs, P4H5 regulate root hair cell elongation and T-DNA insertionalp4h5mutant has arrested cell elongation and shortened root hairs. P4H5 selectively hydroxylates EXT proline units indicating that EXT proline hydroxylation as an essential modification for root hair growth. In this work, we isolate an activation-tagging line called Sup4h5-L19/p4h5(p4h5-L19) that partially suppressed root hair phenotype in thep4h5mutant background. The T-DNA insertion site was mapped by Thermal Asymmetric Interlaced PCR (TAIL-PCR) followed by PCR product sequencing and the T-DNA is inserted at the beginning of the sixth exon of the AT3G17750 gene, an uncharacterized cytosolic kinase. By analyzing expression changes and mutants analysis in this loci, no clear direct effect was detected. By RNA-seq analysis, it become clear thatp4h5-L19 may largely reverse the genetic alterations caused by thep4h5mutant in Wt Col-0, particularly at 10°C where there is an increase in root hair growth, with a total of 14 genes that have been activated and 83 genes that have been suppressed due to the enhancer of the activation tagging L19 inp4h5L19 compared top4h5. Among these genes, 3 of them, Tonoplast Intrinsic Proteins (TIPs), were identified to be root hair specific (TIP1;1, TIP2;2, and TIP2;3) and the corresponding mutants for two of them (TIP1;1 and TIP2;3) showed reduced root hair growth response at low temperature. This study unmasked new components of the root hair growth response at low temperature that works independently of theO-glycosyated EXTs in the cell walls.
Single-nucleus multiomic analysis of Beckwith-Wiedemann syndrome liver reveals PPARA signaling enrichment and metabolic dysfunction
Authors: Nirgude Snehal , Tichy Elisia D. , Liu Zhengfeng , Pradieu Rose D. , Byrne Mariah , Gil De Gomez Luis , Mamou Brandon , Bernt Kathrin M. , Yang Wenli , MacFarland Suzanne , Xie Michael , Kalish Jennifer M. 
Published: June 2024

AbstractBeckwith-Wiedemann Syndrome (BWS) is an epigenetic overgrowth syndrome caused by methylation changes in the human 11p15 chromosomal locus. Patients with BWS exhibit tissue overgrowth, as well as an increased risk of childhood neoplasms in the liver and kidney. To understand the impact of these 11p15 changes, specifically in the liver, we performed single-nucleus RNA sequencing (snRNA-seq) and single-nucleus assay for transposase-accessible chromatin with sequencing (snATAC-seq) to generate paired, cell-type-specific transcriptional and chromatin accessibility profiles of both BWS-liver and nonBWS-liver nontumorous tissue. Our integrated RNA+ATACseq multiomic approach uncovered hepatocyte-specific enrichment and activation of the peroxisome proliferator-activated receptor α (PPARA) – a liver metabolic regulator. To confirm our findings, we utilized a BWS-induced pluripotent stem cell (iPSC) model, where cells were differentiated into hepatocytes. Our data demonstrates the dysregulation of lipid metabolism in BWS-liver, which coincided with observed upregulation of PPARA during hepatocyte differentiation. BWS liver cells exhibited decreased neutral lipids and increased fatty acid β-oxidation, relative to controls. We also observed increased reactive oxygen species (ROS) byproducts in the form of peroxidated lipids in BWS hepatocytes, which coincided with increased oxidative DNA damage. This study proposes a putative mechanism for overgrowth and cancer predisposition in BWS liver due to perturbed metabolism.
Receptor tyrosine kinase inhibition leads to regression of acral melanoma by targeting the tumor microenvironment
Authors: Smith Eric A. , Belote Rachel L. , Cruz Nelly M. , Moustafa Tarek E. , Becker Carly A. , Jiang Amanda , Alizada Shukran , Chan Tsz Yin , Seasor Tori A. , Balatico Michael , Cortes-Sanchez Emilio , Lum David H. , Hyngstrom John R. , Zeng Hanlin , Deacon Dekker C. , Grossmann Allie H. , White Richard M. , Zangle Thomas A. , Judson-Torres Robert L. 
Published: June 2024

ABSTRACTAcral melanoma (AM) is an aggressive melanoma variant that arises from palmar, plantar, and nail unit melanocytes. Compared to non-acral cutaneous melanoma (CM), AM is biologically distinct, has an equal incidence across genetic ancestries, typically presents in advanced stage disease, is less responsive to therapy, and has an overall worse prognosis. Independent analysis of published genomic and transcriptomic sequencing identified that receptor tyrosine kinase (RTK) ligands and adapter proteins are frequently amplified, translocated, and/or overexpressed in AM. To target these unique genetic changes, a zebrafish acral melanoma model was exposed to a panel of narrow and broad spectrum multi-RTK inhibitors, revealing that dual FGFR/VEGFR inhibitors decrease acral-analogous melanocyte proliferation and migration. The potent pan-FGFR/VEGFR inhibitor, Lenvatinib, uniformly induces tumor regression in AM patient-derived xenograft (PDX) tumors but only slows tumor growth in CM models. Unlike other multi-RTK inhibitors, Lenvatinib is not directly cytotoxic to dissociated AM PDX tumor cells and instead disrupts tumor architecture and vascular networks. Considering the great difficulty in establishing AM cell culture lines, these findings suggest that AM may be more sensitive to microenvironment perturbations than CM. In conclusion, dual FGFR/VEGFR inhibition may be a viable therapeutic strategy that targets the unique biology of AM.
Transformer-based modeling of Clonal Selection and Expression Dynamics (TraCSED) reveals resistance signatures in breast cancer
Authors: Maulding Nathan , Zou Jun , Zhou Wei , Metcalfe Ciara , Stuart Josh , Ye Xin , Hafner Marc 
Published: June 2024

AbstractUnderstanding transcriptional heterogeneity in cancer cells and its implication for treatment response is critical to identify how resistance occurs and may be targeted. Such heterogeneity can be captured byin vitrostudies through clonal barcoding methods. We present TraCSED (Transformer-based modeling of Clonal Selection and Expression Dynamics), a dynamic deep learning approach for modeling clonal selection. Using single-cell gene expression and the fitness of barcoded clones, TraCSED identifies interpretable gene programs and the timepoints at which they are associated with clonal selection. When applied to cells treated with either giredestrant, an estrogen receptor (ER) antagonist and degrader, or palbociclib, a CDK4/6 inhibitor, time-dependent resistance pathways are revealed. For example, ER activity is associated with positive selection around day four under palbociclib treatment and this adaptive response can be suppressed by combining the drugs. Yet, in the combination treatment, one clone still emerged. Clustering based on partial least squares regression found that high baseline expression of both SNHG25 and SNCG genes was the primary marker of positive selection to co-treatment and thus potentially associated with innate resistance – an aspect that traditional differential analysis methods missed. In conclusion, TraCSED enables associating pathways with phenotypes in a time-dependent manner from scRNA-seq data.
High orientation and low delayed recall in the standardisation of the Spanish version of the Montreal Cognitive Assessment (MoCA) in elders of Peru
Authors: Bulgarelli Lucia , Gyr Emilia , Villanueva Jose , Mejía Koni , Mejía Claudia , Paredes Renato , Blumen Sheyla 
Published: June 2024

AbstractINTRODUCTIONThe elderly in Peru face healthcare barriers in detecting cognitive impairment and dementia due to a lack of validated tools. The Montreal Cognitive Assessment (MoCA) effectively detects early dementia, assessing visuo-spatial function, executive function, naming, memory, attention, language, abstraction, and orientation.METHODSThis study aims to standardise the Spanish version of the MoCA for the elderly in Lima. The test was administered to 338 elders from three institutions: Municipality of San Miguel District, San José Obrero Polyclinic, and EDMECON. Regression-based normed scores were computed, adjusted for age and education.RESULTSOur results show high orientation scores and low delayed recall, highlighting cognitive strengths and weaknesses in our sample. Age and education significantly influenced cognitive performance, with education as the strongest predictor.DISCUSSIONThis study offers normative data for the Peruvian elderly, aiding the clinical use of MoCA in Peru. We discuss appropriate cut-off points and cultural sensitivity in the Peruvian context.
An international study to investigate and optimise the safety of discontinuing valproate in young men and women with epilepsy: protocol
Authors: Mbizvo Gashirai K. , Martin Glen P. , Sperrin Matthew , Bonnett Laura J. , Schofield Pieta , Buchan Iain , Lip Gregory Y.H. , Marson Anthony G. 
Published: June 2024

AbstractValproate is the most effective treatment for idiopathic generalised epilepsy. Currently, its use is restricted in women of childbearing potential owing to high teratogenicity. Recent evidence extended this risk to men’s offspring, prompting recommendations to restrict use in everybody aged <55 years.This study will evaluate mortality and morbidity risks associated with valproate withdrawal by emulating a hypothetical randomised-controlled trial (called a “target trial”) using retrospective observational data. The data will be drawn from ∼250m mainly US patients in the TriNetX repository and ∼60m UK patients in Clinical Practice Research Datalink (CPRD). These will be scanned for individuals aged 16–54 years with epilepsy and on valproate who either continued, switched to lamotrigine or levetiracetam, or discontinued valproate between 2015–2018, creating four groups. Randomisation to these groups will be emulated by baseline confounder adjustment using g-methods. Mortality and morbidity outcomes will be assessed and compared between groups over five years, employing time-to-first-event and recurrent events analyses. A causal prediction model will be developed from these data to aid in predicting the safest alternative antiseizure medications.Together, these findings will optimise informed decision-making about valproate withdrawal and alternative treatment selection, providing immediate and vital information for patients, clinicians and regulators.
Mindfulness-Based Cognitive Therapy for Treatment-Resistant Depression: A protocol for a systematic review and meta-analysis
Authors: F Rodrigues Michele , Junkes Larissa , C Appolinario Jose , E Nardi Antonio 
Published: June 2024

AbstractBackgroundMajor Depressive Disorder is a global health issue that affects more than 300 million people worldwide, which is about 4.4% of the global population. Treatment usually consists of a combination of antidepressant medication and therapy. However, approximately 30% of individuals with Major Depressive Disorder experience a Treatment-Resistant Depression (a failure to respond to at least two antidepressants used in a regular dosage and time interval). Our research aims to investigate how effective Mindfulness-Based Cognitive Therapy is for individuals with Treatment-Resistant Depression.Materials and MethodsWe will conduct a thorough search for publications in MEDLINE, Embase, PsycINFO, Web of Science databases, and ClinicalTrials.gov. Additionally, we will manually review the reference lists of the included studies to find any other potentially relevant studies. There will be no restrictions on language or publication date. The quality of the included studies will be assessed independently using the Jadad scale (Oxford quality scoring system). To assess the certainty of the evidence, we will use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. This study aims to determine the effectiveness and tolerability of Mindfulness-Based Cognitive Therapy as an intervention for Treatment-Resistant Depression.Ethics and disseminationEthical approval is not necessary because individual patient data is not being collected. Our objective is to publish the systematic review in an open-access medical journal once the review process is completed.Prospero registration IDCRD42023411978. Registered on April 07, 2023.
Unveiling the gap of heart failure: a DATASUS study
Authors: Batista Vivian Cardoso , Vitorasso Renato Lima , Nogueira-Pileggi Vicky , Picoli Renato Mantelli , Bilevicius Elizabeth 
Published: June 2024

AbstractHeart failure (HF) decompensation is the main cause of hospitalizations in developed countries. In Brazil, it represents the third general cause. Aiming to analyze the treatment journey for different types of HF in Brazil, the present study seeks to define a flowchart and clinical rationale that covers the procedures (and their respective frequency) in patients with HF in the Brazilian Unified Health System (SUS) included in DATASUS database. By doing so, the final objectives were: a) To identify potential patients with HF to present an estimate of the underreporting of the disease in the country; b) To describe the estimated mortality of potential patients with HF in Brazil. We used data from DATASUS, which encompasses information from the Brazilian Unified Health System (SUS). Specifically, we utilized the SUS-SIM (Mortality Information System) and SUS-SIA (Ambulatory Information System). Results: According to the data, we had a potential missing of patients with HF of 54,000 patients per year at diagnosis and 200,000 deaths that could lead to HF (both sexes). Considering the sensitivity analysis when there was a 20% underestimation in the number of potential HF cases, the underestimation rate of cases diagnosed with HF was 12%. We also found that when there was an underestimation of 40% in potential cases of death due to HF, there was an average underestimation of 41% in cases of death diagnosed as HF. the results highlight the importance of accurate diagnosis and a comprehensive approach to identifying potential cases of HF to improve the recording and management of this condition. Underestimation of these cases may have significant implications for public health and clinical management of HF emphasizing the need for strategies to increase early detection and adequate case recording. The next steps would be how much this underestimation impacts the public health in Brazil, particularly in terms of financial resources.
Refining the Allostatic Self-Efficacy Theory of Fatigue and Depression Using Causal Inference
Authors: Hess Alexander J. , von Werder Dina , Harrison Olivia K. , Heinzle Jakob , Stephan Klaas Enno 
Published: June 2024

ABSTRACTAllostatic self-efficacy (ASE) represents a computational theory of fatigue and depression. In brief, it postulates that (i) fatigue is a feeling state triggered by a metacognitive diagnosis of loss of control over bodily states (persistently elevated interoceptive surprise); and that (ii) generalisation of low self-efficacy beliefs beyond bodily control induces depression. Here, we convert ASE theory into a structural causal model (SCM). This allows for identification of empirically testable hypotheses regarding casual relationships between variables of interest. We use conditional independence tests on questionnaire data from healthy volunteers (N=60) to identify contradictions to the proposed SCM. Moreover, we estimate two causal effects proposed by ASE theory using three different methods.Our analyses suggest that, in healthy volunteers, the data are not fully compatible with the proposed SCM. We therefore refine the SCM and present an updated version for future research. Second, we confirm the predicted negative average causal effect from metacognition of allostatic control to fatigue across all three different methods of estimation. Our study represents an initial attempt to refine and formalise ASE theory using methods from causal inference. Our results confirm key predictions from the ASE theory but also suggest revisions which require empirical verification in future studies.