bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testing of putative antiseizure medications in a preclinical Dravet syndrome zebrafish model
Authors: Whyte-Fagundes Paige A , Vance Anjelica , Carroll Aloe , Figueroa Francisco , Manukyan Catherine , Baraban Scott C 
Published: April 2024

Abstract
Dravet syndrome is a severe genetic epilepsy primarily caused by de novo mutations in a voltage-activated sodium channel gene (SCN1A). Patients face life-threatening seizures that are largely resistant to available anti-seizure medications. Preclinical Dravet syndrome animal models are a valuable tool to identify candidate anti-seizure medications for these patients. Among these, scn1lab mutant zebrafish, exhibiting spontaneous seizure-like activity, are particularly amenable to large-scale drug screening. Thus far, we have screened more than 3000 drug candidates in scn1lab zebrafish mutants, identifying valproate, stiripentol, and fenfluramine e.g. Food and Drug Administration-approved drugs, with clinical application in the Dravet syndrome population. Successful phenotypic screening in scn1lab mutant zebrafish is rigorous and consists of two stages: (i) a locomotion-based assay measuring high-velocity convulsive swim behaviour and (ii) an electrophysiology-based assay, using in vivo local field potential recordings, to quantify electrographic seizure-like events. Historically, nearly 90% of drug candidates fail during translation from preclinical models to the clinic. With such a high failure rate, it becomes necessary to address issues of replication and false positive identification. Leveraging our scn1lab zebrafish assays is one approach to address these problems. Here, we curated a list of nine anti-seizure drug candidates recently identified by other groups using preclinical Dravet syndrome models: 1-Ethyl-2-benzimidazolinone, AA43279, chlorzoxazone, donepezil, lisuride, mifepristone, pargyline, soticlestat and vorinostat. First-stage locomotion-based assays in scn1lab mutant zebrafish identified only 1-Ethyl-2-benzimidazolinone, chlorzoxazone and lisuride. However, second-stage local field potential recording assays did not show significant suppression of spontaneous electrographic seizure activity for any of the nine anti-seizure drug candidates. Surprisingly, soticlestat induced frank electrographic seizure-like discharges in wild-type control zebrafish. Taken together, our results failed to replicate clear anti-seizure efficacy for these drug candidates highlighting a necessity for strict scientific standards in preclinical identification of anti-seizure medications.
Artificial Wombs: Could They Deliver an Answer to the Problem of Frozen Embryos?
Authors: Gross Christopher 
Published: April 2024

Abstract
Catholic thinkers generally agree that artificial womb technology (AWT) would be permissible in cases of partial ectogenesis to assist severely premature infants, but there is substantially more debate concerning whether AWT could be used to save frozen embryos, which are the result of in vitro fertilization (IVF). In many cases, these embryos have been abandoned and left in a permanently cryogenic state, which is an affront to their human dignity. While AWT would allow people to adopt these embryos and give them an opportunity to develop, it gives rise to serious concerns over the possibility of scandal and the potential for cooperation in evil. Therefore, the author argues that even though AWT may one day represent a solution to this tragedy, it is currently not a morally licit answer, given the widespread use and approval of IVF in our culture.
What is a B chromosome? Early definitions revisited
Authors: Ferree Patrick M , Blagojević Jelena , Houben Andreas , Martins Cesar , Trifonov Vladimir A , Vujošević Mladen 
Published: April 2024

Abstract
Since the discovery of B chromosomes, multiple different definitions of these selfish genetic elements have been put forth. We reconsidered early definitions in light of recently published studies. While there are many characteristics that vary among different B chromosomes, such as their evolutionary origins, size, segregation behaviors, gene content, and function, there is one defining trait of all B chromosomes: they are nonessential for the organism. The points raised here may be useful for framing future B chromosome studies and help guide the categorization of new chromosomal elements that are uncovered in genomic studies.
An effective strategy for assembling the sex-limited chromosome
Authors: Wang Xiao-Bo , Lu Hong-Wei , Liu Qing-You , Li A-Lun , Zhou Hong-Ling , Zhang Yong , Zhu Tian-Qi , Ruan Jue 
Published: April 2024

Abstract

Background
Most currently available reference genomes lack the sequence map of sex-limited (such as Y and W) chromosomes, which results in incomplete assemblies that hinder further research on sex chromosomes. Recent advancements in long-read sequencing and population sequencing have provided the opportunity to assemble sex-limited chromosomes without the traditional complicated experimental efforts.

Findings
We introduce the first computational method, Sorting long Reads of Y or other sex-limited chromosome (SRY), which achieves improved assembly results compared to flow sorting. Specifically, SRY outperforms in the heterochromatic region and demonstrates comparable performance in other regions. Furthermore, SRY enhances the capabilities of the hybrid assembly software, resulting in improved continuity and accuracy.

Conclusions
Our method enables true complete genome assembly and facilitates downstream research of sex-limited chromosomes.
Enhanced bovine genome annotation through integration of transcriptomics and epi-transcriptomics datasets facilitates genomic biology
Authors: Beiki Hamid , Murdoch Brenda M , Park Carissa A , Kern Chandlar , Kontechy Denise , Becker Gabrielle , Rincon Gonzalo , Jiang Honglin , Zhou Huaijun , Thorne Jacob , Koltes James E , Michal Jennifer J , Davenport Kimberly , Rijnkels Monique , Ross Pablo J , Hu Rui , Corum Sarah , McKay Stephanie , Smith Timothy P L , Liu Wansheng , Ma Wenzhi , Zhang Xiaohui , Xu Xiaoqing , Han Xuelei , Jiang Zhihua , Hu Zhi-Liang , Reecy James M 
Published: April 2024

Abstract

Background
The accurate identification of the functional elements in the bovine genome is a fundamental requirement for high-quality analysis of data informing both genome biology and genomic selection. Functional annotation of the bovine genome was performed to identify a more complete catalog of transcript isoforms across bovine tissues.

Results
A total of 160,820 unique transcripts (50% protein coding) representing 34,882 unique genes (60% protein coding) were identified across tissues. Among them, 118,563 transcripts (73% of the total) were structurally validated by independent datasets (PacBio isoform sequencing data, Oxford Nanopore Technologies sequencing data, de novo assembled transcripts from RNA sequencing data) and comparison with Ensembl and NCBI gene sets. In addition, all transcripts were supported by extensive data from different technologies such as whole transcriptome termini site sequencing, RNA Annotation and Mapping of Promoters for the Analysis of Gene Expression, chromatin immunoprecipitation sequencing, and assay for transposase-accessible chromatin using sequencing. A large proportion of identified transcripts (69%) were unannotated, of which 86% were produced by annotated genes and 14% by unannotated genes. A median of two 5′ untranslated regions were expressed per gene. Around 50% of protein-coding genes in each tissue were bifunctional and transcribed both coding and noncoding isoforms. Furthermore, we identified 3,744 genes that functioned as noncoding genes in fetal tissues but as protein-coding genes in adult tissues. Our new bovine genome annotation extended more than 11,000 annotated gene borders compared to Ensembl or NCBI annotations. The resulting bovine transcriptome was integrated with publicly available quantitative trait loci data to study tissue–tissue interconnection involved in different traits and construct the first bovine trait similarity network.

Conclusions
These validated results show significant improvement over current bovine genome annotations.
Inhibition of RhoA Prevents Cryptococcus neoformans Capsule Glucuronoxylomannan-Stimulated Brain Endothelial Barrier Disruption
Authors: Munzen Melissa E , Mathew Cristian , Enriquez Vanessa , Minhas Amanjeet , Charles-Niño Claudia L , Saytoo Durvinand , Reguera-Gomez Marta , Dores Michael R , Martinez Luis R 
Published: April 2024

Abstract
Cryptococcus neoformans (Cn) is an opportunistic fungus that causes severe central nervous system (CNS) disease in immunocompromised individuals. Brain parenchyma invasion requires fungal traversal of the blood-brain barrier. In this study, we describe that Cn alters the brain endothelium by activating small GTPase RhoA, causing reorganization of the actin cytoskeleton and tight junction modulation to regulate endothelial barrier permeability. We confirm that the main fungal capsule polysaccharide glucuronoxylomannan is responsible for these alterations. We reveal a therapeutic benefit of RhoA inhibition by CCG-1423 in vivo. RhoA inhibition prolonged survival and reduced fungal burden in a murine model of disseminated cryptococcosis, supporting the therapeutic potential of targeting RhoA in the context of cryptococcal infection. We examine the complex virulence of Cn in establishing CNS disease, describing cellular components of the brain endothelium that may serve as molecular targets for future antifungal therapies to alleviate the burden of life-threatening cryptococcal CNS infection.
Abstract Spaces for Intervention in Libya and Nigeria
Authors: Malito Debora V , Dan Suleiman Muhammad 
Published: April 2024

AbstractHow is the space for contemporary interventions constructed? This article deepens our understanding of counterterrorism as a dialectical form of intervention by highlighting the importance of unifying rationalities in the creation of “ungoverned spaces” as abstract spaces for intervention purposes. We combine dialectical and decolonial thinking to track how unifying rationalities in Nigeria and Libya are deployed across cognitive, normative, and operational constructs. The article examines how interventions are cognitively tied to coloniality of knowing, being, and power, which exploit identity, religion, or societal divisions to justify ungovernance and normalize state and foreign violence. The simultaneous and reciprocal globalization of local security concerns and localization of global security predicaments facilitates the formation of abstract spaces for counterterrorism purposes. Empirically, our analysis shows how portraying Libya and Nigeria as ungoverned creates a void of meaning, putting external actors in charge of restoring governance and protecting human security, modernity, and civility. Interveners in Libya contributed to normalizing a broader spectrum of violence, frequently internalized by competing actors through their normative tropes. In Nigeria, state and foreign interventionism and counterinsurgency have been responsible for the widespread use of violence against entire communities.
Yeast communities of a North American hybrid wine grape differ between organic and conventional vineyards
Authors: Bunbury-Blanchette Adele L , Fan Lihua , Kernaghan Gavin 
Published: April 2024

Abstract

Aims
To compare the species diversity and composition of indigenous yeast communities of hybrid grapes from conventionally and organically cultivated vineyards of an emerging cool-climate wine producing region.

Methods and Results
Illumina MiSeq sequences from L'Acadie blanc grape musts were processed and filtered to characterize indigenous yeast communities in organic and conventional vineyards of the Annapolis Valley wine region in Nova Scotia, Canada. While cultivation practice was not associated with yeast diversity or species richness, there was a strong effect on yeast community composition, with conventional vineyards characterized by higher proportions of Sporidiobolales and Filobasidium magnum, and organic vineyards supporting Filobasidium species other than F. magnum and higher proportions of Symmetrospora. There was also variation in yeast community composition among individual vineyards, and from year to year.

Conclusions
This is the first comprehensive assessment of yeasts associated with hybrid grapes grown using different cultivation practices in a North American cool climate wine region. Communities were dominated by basidiomycete yeasts and species composition of these yeasts differed significantly between vineyards employing organic and conventional cultivation practices. The role of basidiomycete yeasts in winemaking is not well understood, but some species may influence wine characteristics.
Navigating Scar Care: An Evaluation of Scar Treatment Patient Education Materials
Authors: Manasyan Artur , Ross Erin , Cannata Brigette , Malkoff Nicolas , Flores Elizabeth , Yenikomshian Haig A , Gillenwater T Justin 
Published: April 2024

AbstractWhile patient education materials (PEMs) across various specialties have been reported as being too difficult to read, the quality and understandability of PEMs related to scar management have not been assessed. In this study, we report the breadth of scar management interventions and readability of online PEMs authored by academic societies and university hospitals. Websites of academic medical societies and university hospitals with scar revision PEMs were assessed for relevance. PEM readability was assessed via Flesch Reading Ease, Flesch–Kincaid Grade Level, and Gunning-Fox Index scores. Understandability and actionability were evaluated using the Patient Education Material Assessment Tool (PEMAT). A total of 26 scar revision PEMs met the inclusion criteria. The most commonly mentioned scar management interventions were scar revision surgery (73%) and laser scar revision (70%), with minimal emphasis on noninvasive methods like scar massage or sun protection. Readability analysis yielded a mean Flesch reading level of 8.8. Overall, PEMAT understandability of online scar treatment PEMs was moderate, with a median of 76.0% (IQR 71.5%-80.5%). PEMs from all specialties and institution types were lacking in actionability, with median actionability of 40.8% (IQR 38.1%-60.0%). Online scar revision PEMs included a wide breadth of scar management interventions; however, the least costly interventions, such as sun protection and scar massage, were not commonly included. PEMs for scar management could be improved by simplifying language, including visual aids, and including checklists or specific steps, patients can take to take action on scar management interventions.
Breast Implant Imaging Surveillance Practice: Survey of Breast Imaging Radiologists in the Society of Breast Imaging
Authors: Moosavi Ali , Ha Jason , Papoutsis Brianna , Lehman Erik , Chetlen Alison , Choe Angela I 
Published: April 2024

Abstract

Objective
The objectives of this Society of Breast Imaging (SBI)-member survey study were to assess the current imaging patterns for evaluation of symptomatic and asymptomatic breast implant integrity, including modalities used and imaging intervals.

Methods
A 12-question survey assessing the frequency of imaging modalities used to evaluate implant integrity, approximate number of breast implant integrity studies requested per month, intervals of integrity studies, and referring provider and radiology practice characteristics was distributed to members of the SBI.

Results
The survey response rate was 7.6% (143/1890). Of responding radiologists, 54.2% (77/142) were in private, 29.6% (42/142) in academic, and 16.2% (23/142) in hybrid practice. Among respondents, the most common initial examination for evaluating implant integrity was MRI without contrast at 53.1% (76/143), followed by handheld US at 46.9% (67/143). Of respondents using US, 67.4% (91/135) also evaluated the breast tissue for abnormalities. Among respondents, 34.1% (46/135) reported being very confident or confident in US for diagnosing implant rupture. There was a range of reported intervals for performing implant integrity studies: 39.1% (43/110) every 2-3 years, 26.4% (29/110) every 4-5 years, 15.5% (17/110) every 6-10 years, and 19.1% (21/110) every 10 years.

Conclusion
For assessment of implant integrity, the majority of respondents (53.2%, 76/143) reported MRI as initial imaging test. US is less costly, but the minority of respondents (34.1%, 46/135) had confidence in US performance. Also, the minority of respondents (39.1%, 43/110) performed implant integrity evaluations every 2-3 years per the FDA recommendations for asymptomatic surveillance.
Evidence for 3-hydroxyhexan-2-one as a shared pheromone component for 12 South American species of cerambycid beetles
Authors: Silva Weliton D , Hanks Lawrence M , Bento José Mauricio S , Zou Yunfan , Millar Jocelyn G 
Published: April 2024

Abstract
3-Hydroxyhexan-2-one (3-C6-ketol) has emerged as the most conserved pheromone structure within the beetle family Cerambycidae. In this study, we report the sex-specific production of this compound by males of 12 species of South American cerambycid beetles. Males of Chrysoprasis chalybea Redtenbacher and Mallosoma zonatum (Sahlberg) (Tribe Dichophyiini), and Ambonus lippus (Germar), Eurysthea hirta (Kirby), Pantonyssus nigriceps Bates, Stizocera plicicollis (Germar), and Stizocera tristis (Guérin-Méneville) (Elaphidiini) produced 3R-C6-ketol as a single component, whereas males of Neoclytus pusillus (Laporte & Gory) (Clytini), Aglaoschema concolor (Gounelle), Orthostoma abdominale (Gyllenhal) (Compsocerini), Dorcacerus barbatus (Olivier), and Retrachydes thoracicus thoracicus (Olivier) (Trachyderini) produced 3R-C6-ketol, along with lesser amounts of other compounds. In field trials testing 8 known cerambycid pheromone compounds, C. chalybea, E. hirta, and R. t. thoracicus were attracted in significant numbers to traps baited with 3-C6-ketol. A second field experiment provided support for the strategy of using the attraction of cerambycid species to test lures as a method of providing leads to their likely pheromone components. Because both sexes are attracted to these aggregation-sex pheromones, live beetles can be obtained from baited traps to verify they produce the compound(s) to which they were attracted, that is, that the compounds are indeed pheromone components.
Comparison of the effect of tea shoots during different seasons in Arma chinensis (Hemiptera: Pentatomidae) reared on Ectropis grisescens (Lepidoptera: Geometridae) pupae
Authors: Liu Qi , Chen Li-Lin , Wang Lin-Lin , Sun Yue , Lai Yu-Ying , Long Na-Dang , Shi Yi-Han , Quan Li-Fei , Feng Wan-Qiu , Liang Gui-Mei , Zhao Jia-Lin , Zhou Zi-Qin 
Published: April 2024

Abstract
In this study, we compared the growth, development, and fecundity of Arma chinensis (Fallou) reared on pupae of the geometrid Ectropis grisescens Warren fed on tea shoots during different seasons of the year. The raw data on life history were analyzed using the age–stage, 2-sex life table. When reared on spring or winter geometrid pupae, the duration of the immature stage of A. chinensis was significantly longer than in those produced during the summer or autumn. The survival rate of immature A. chinensis reared on autumn geometrid pupae was significantly lower compared to other treatments. Reproductive diapause was observed in adult A. chinensis reared on winter geometrid pupae. The adult preoviposition period (APOP), total preoviposition period (TPOP), and total longevity were significantly longer in A. chinensis reared on winter pupae than in the other treatments. The fecundity of A. chinensis reared on spring geometrid pupae was significantly lower than in the other treatments. The higher intrinsic rate of increase of the A. chinensis reared on summer pupae (r = 0.0966 day-1) and autumn pupae (r = 0.0983 day-1) resulted in higher fecundity, shorter immature duration, and shorter TPOP compared to the winter and spring populations. These findings can be utilized to enhance and sustain biological control of E. grisescens in tea plantations.
A population-based study of COVID-19 mortality risk in US cancer patients
Authors: Mani Kyle A , Wu Xue , Spratt Daniel E , Wang Ming , Zaorsky Nicholas G 
Published: April 2024

Abstract

Background
In this study, we provide the largest analysis to date of a US-based cancer cohort to characterize death from COVID-19.

Methods
A total of 4 020 669 patients across 15 subtypes living with cancer in 2020 and included in the National Cancer Institute’s Surveillance, Epidemiology, and End Results database were abstracted. We investigated prognostic factors for death due to COVID-19 using a Cox proportional hazards model and calculated hazard ratios (HRs). Standardized mortality ratios were calculated using observed mortality counts from Surveillance, Epidemiology, and End Results and expected mortality based on US mortality rates.

Results
A total of 291 323 patients died, with 14 821 (5.1%) deaths attributed to COVID-19 infection. The COVID-19 disease-specific mortality rate was 11.81/10 000-persons years, and the standardized mortality ratio of COVID-19 was 2.30 (95% confidence interval [CI] = 2.26 to 2.34; P &lt; .0001). COVID-19 ranked as the second leading cause of death following ischemic heart disease (5.2%) among 26 noncancer causes of death. Patients who are older (80 years and older vs 49 years and younger: HR = 21.47, 95% CI = 19.34 to 23.83), male (vs female: HR = 1.46, 95% CI = 1.40 to 1.51), unmarried (vs married: HR = 1.47, 95% CI = 1.42 to 1.53), and Hispanic or non-Hispanic African American (vs non-Hispanic White: HR = 2.04, 95% CI = 1.94 to 2.14 and HR = 2.03, 95% CI = 1.94 to 2.14, respectively) were at greatest risk of COVID-19 mortality.

Conclusions
We observed that people living with cancer are at 2 times greater risk of dying from COVID-19 compared with the general US population. This work may be used by physicians and public health officials in the creation of survivorship programs that mitigate the risk of COVID-19 mortality.
Historical review: The golden age of the Golgi method in human neuropathology
Authors: Ferrer Isidro 
Published: April 2024

Abstract
Golgi methods were used to study human neuropathology in the 1970s, 1980s, and 1990s of the last century. Although a relatively small number of laboratories applied these methods, their impact was crucial by increasing knowledge about: (1) the morphology, orientation, and localization of neurons in human cerebral and cerebellar malformations and ganglionic tumors, and (2) the presence of abnormal structures including large and thin spines (spine dysgenesis) in several disorders linked to mental retardation, focal enlargements of the axon hillock and dendrites (meganeurites) in neuronal storage diseases, growth cone-like appendages in Alzheimer disease, as well as abnormal structures in other dementias. Although there were initial concerns about their reliability, reduced dendritic branches and dendritic spines were identified as common alterations in mental retardation, dementia, and other pathological conditions. Similar observations in appropriate experimental models have supported many abnormalities that were first identified using Golgi methods in human material. Moreover, electron microscopy, immunohistochemistry, fluorescent tracers, and combined methods have proven the accuracy of pioneering observations uniquely visualized as 3D images of fully stained individual neurons. Although Golgi methods had their golden age many years ago, these methods may still be useful complementary tools in human neuropathology.