bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacogenomic panel testing provides insight and enhances medication management in persons living with HIV
Authors: Zeuli John D. , Rivera Christina G. , Wright Jessica A. , Kasten Mary J. , Mahmood Maryam , Ragan Ashley K. , Rizza Stacey A. , Temesgen Zelalem M. , Vergidis Paschalis , Wilson John W. , Cummins Nathan W. 
Published: May 2023

Objective:
Our study aimed to assess the impact of pharmacogenomic panel testing in persons living with HIV (PWH).

Design:
Prospective, observational intervention assessment

Methods:
One hundred PWH were provided a comprehensive pharmacogenomic panel during routine care visits within the HIV specialty clinic of a large academic medical center. The panel determined the presence of specific genetic variants that could predict response or toxicity to commonly prescribed antiretroviral therapy (ART) and non-ART medications. An HIV specialty pharmacist reviewed the results with participants and the care team. The pharmacist (1) recommended clinically actionable interventions based on the participants current drug therapy, (2) assessed for genetic explanations for prior medication failures, adverse effects, or intolerances, and (3) advised on potential future clinically actionable care interventions based on individual genetic phenotypes.

Results:
Ninety-six participants (median age 53y, 74% white, 84% male, 89% viral load <50 copies/ml) completed panel testing yielding 682 clinically relevant pharmacogenomic results (133 major, 549 mild-moderate). Ninety participants (89 on ART) completed follow-up visits with 65 (72%) receiving clinical recommendations based on current medication profiles. Of the 105 clinical recommendations, 70% advised additional monitoring for efficacy or toxicity, and 10% advised alteration of drug therapy. Panel results offered explanation for prior ART inefficacy in 1 participant and ART intolerance in 29%. Genetic explanation for non-ART toxicity was seen in 21% of participants, with genetic contributors to inefficacy of non-ART therapy identified in 39% of participants.

Conclusions:
Preliminary data in a small cohort of PWH demonstrates benefit of routine pharmacogenomic panel testing.
Striking allelic diversity despite structural homogeneity oface-1duplications inAnophelesmosquitoes
Authors: Claret Jean-Loup , Di-Liegro Marion , Namias Alice , Assogba Benoit , Makoundou Patrick , Koffi Alphonsine , Pennetier Cédric , Weill Mylène , Milesi Pascal , Labbé Pierrick 
Published: May 2023

AbstractA. gambiae s.l.has been the target of intense insecticide treatment since the mid-XXth century to try and control malaria, and a substitution in theace-1locus allowing resistance to organophosphate and carbamates insecticides has been rapidly selected for. Since then, several duplications of the ace-1 locus have been found in A. gambiae s.l. populations. They associate either several resistance copies (homogeneous duplications) or both resistance and susceptible copies (heterogeneous duplications). Heterogeneous duplications confer an intermediate trade-off between resistance in presence of insecticide and disadvantage in their absence. So far, and in striking contrast withC. pipiensmosquitoes, a single heterogeneous duplication had been describe in A. gambiae populations. We use an innovative approach, combining information from long and short read sequencing with Sanger sequencing to precisely identify and describe at least nine different heterogeneous duplications in A. gambiae. We further show that these alleles share the exact same structure than the previously identified heterogeneous and homogeneous duplications, namely 203-kb tandem amplifications with conserved breakpoints. Our study sheds a new light on the origin and maintenance of these alleles in A. gambiae populations, and pushes one step further the striking evolutionary convergence withC. pipiensmosquitoes.
Lipids of different phytoplankton groups differ in sensitivity to degradation: implications for carbon export
Authors: Godrijan Jelena , Pfannkuchen Daniela Marić , Djakovac Tamara , Frka Sanja , Gašparović Blaženka 
Published: May 2023

AbstractThe future of life on Earth depends on how the ocean might change, as it plays an important role in mitigating the effects of global warming. The main role is played by phytoplankton. Not only are phytoplankton the base of the oceans’ food web, but they also play an important role in the biological carbon pump (BCP), the process of forming organic matter (OM) and transporting it to the deep sea, representing a sink of atmospheric CO2. Lipids are considered important vectors for carbon sequestration. A change in the phytoplankton community composition as a result of ocean warming is expected to affect the BCP. Many predictions indicate a dominance of small at the expense of large phytoplankton. To gain insight into interplay between the phytoplankton community structure, lipid production and degradation and adverse environmental conditions, we analyzed phytoplankton composition, POC and its lipid fraction in the northern Adriatic over a period from winter to summer at seven stations with a gradient of trophic conditions. We found that at high salinity and low nutrient content, where nanophytoplankton prevailed over diatoms, the newly fixed carbon is substantially directed toward the synthesis of lipids. Lipids produced by nanophytoplankton, coccolithophores and phytoflagellates, are more resistant to degradation than those produced by diatoms. This suggests a more successful lipid carbon sink of nanophytoplankton and thus a negative feedback on global warming. The difference in lipid degradability is discussed as a difference in the size of the cell phycosphere. We hypothesize that the lipids of nanophytoplankton are less degradable due to the small phycosphere with a poorer bacterial community and consequently a lower lipid degradation rate compared to diatoms. The chemical composition of the lipids of the different phytoplankton groups could have a different susceptibility to degradation, which could also contribute to the differences in lipid degradability.
High Resolution Acoustic Mapping of Gelatin-Based Soft Tissue Phantoms
Authors: Badawe Heba M. , Raad Petra , Khraiche Massoud L. 
Published: May 2023

AbstractBackgroundUtilizing spatially and temporally uniform tissue-mimicking phantoms for ultrasonic applications can facilitate the characterization of beam distortion and attenuation. The implementation of acoustic phantoms can enhance the efficacy of ultrasound therapy or imaging by providing guidance on optimal ultrasonic parameters, such as frequency and power. The efficacy of phantoms is heavily dependent on the accuracy and reliability of measurement techniques employed for assessing their acoustic properties.PurposeThe work aims to develop, build, and characterize, via high resolution acoustic mapping, Gelatin-Based ultrasound (US) soft tissue phantoms. To that effect, we built acoustic maps of the intensity distribution of US waves passing through the phantoms and studied the effect of gelatin concentrations and US frequency, duty cycle, and applied voltage on the acoustic intensity and focal region of the US waves. The methodology developed here offers well characterized and reproducible Gelatin-Based US phantoms for soft tissue (both acoustically and mechanically).MethodsWe developed gelatin-based phantoms, with conveniently adjustable parameters and measured, with high resolution, the acoustic attenuation of ultrasound waves when encountering the gelatin phantoms. This was done via a motorized acoustic system built for 3D-acoustic mapping of ultrasound waves. Mechanical assessment of the phantoms’ elasticity was carried out through unconfined compression tests. We characterized tissue mimicking phantoms with realistic acoustic properties and mechanical elasticity, emphasizing the effect of varying gelatin concentration on the ultrasound maximal intensity, thus causing acoustic attenuation throughout the acoustic profile. For validation, we used computational simulations to compare our data to predicted acoustical outcomes.ResultsOur results show high-resolution mapping of US waves in fluid with and without Gelatin-Based phantoms. We also confirm the impact of recipe and gelatin concentration on mechanical and acoustic characterization of phantoms. The density of the gelatin-based phantoms scales with the Young’s modulus. When characterizing the acoustic profiles of the different ultrasound transducers, the focal areas increased systematically as a function of increasing applied voltage and duty cycle yet decreased as a function of increased ultrasonic frequency.ConclusionsWe developed a Gelatin-Based US phantoms are a reliable and reproduce tool for examining the acoustic attenuations taking place as a function of increased tissue elasticity and stiffness. High resolution acoustic maps of the intensity distribution of US can provide essential information on the spatial changes in US wave intensity and focal point enabling a more in-depth examination of the effect of tissue on US waves.
Comparison of spontaneous recurrent seizures in rats following status epilepticus induced by organophosphate paraoxon, DFP, and sarin
Authors: Blair Robert E. , Hawkins Elisa , Lauren R. Pinchbeck , DeLorenzo Robert J. , Deshpande Laxmikant S. 
Published: May 2023

AbstractOrganophosphate (OP) compounds are highly toxic and include household, industrial, agricultural, and chemical warfare nerve agents (CWNA). OP exposure inhibits acetylcholinesterase enzyme, causing cholinergic overstimulation that can evolve into status epilepticus (SE) and produce lethality. Furthermore, OP-SE survival is associated with mood and memory dysfunction and spontaneous recurrent seizures (SRS). Here we assessed hippocampal pathology and chronic SRS following SE induced by OP agents in rats. Male Sprague-Dawley rats were injected with 1.5x LD50of various OP agents, followed by atropine and 2-PAM. At 1-h post-OP-SE onset, midazolam was administered to control SE. Approximately 6 months following OP-SE, SRS were evaluated using continuous video-EEG monitoring. Histopathology was conducted using Hematoxylin and Eosin (H&E), while silver sulfide (Timm) staining was utilized to assess Mossy Fiber Sprouting (MFS). Over 60% of OP-SE surviving rats developed SRS with varying seizure frequencies, durations, and Racine severity scores. H&E staining revealed a significant hippocampal neuronal loss, while Timm staining revealed extensive MFS within the inner molecular region of the dentate gyrus of SRS-expressing OP-SE rats. This study demonstrates that OP-SE is associated with hippocampal neuronal loss, extensive MFS, and SRS, all hallmarks of chronic epilepsy.
Advancing multi-day ex vivo kidney perfusion using spatially resolved metabolomics
Authors: de Haan Marlon J.A. , Witjas Franca M.R. , de Graaf Annemarie M.A. , Jacobs Marleen E. , Sánchez-López Elena , Kostidis Sarantos , Giera Martin , Maanaoui Mehdi , Hubert Thomas , Kerr-Conte Julie , Pattou François , de Vries Dorottya K. , Kers Jesper , Alwayn Ian P.J. , van Kooten Cees , Heijs Bram P.A.M. , Wang Gangqi , Engelse Marten A. , Rabelink Ton J. 
Published: May 2023

ABSTRACTThe ability to preserve metabolically active kidneys ex vivo for multiple days may permit reconditioning, repair and regeneration of deceased donor kidneys. However, the kidneys high metabolic demand limits its functional preservation. Current approaches focus on normothermic machine perfusion (NMP) at 37°C or hypothermic machine perfusion (HMP) at 4-8°C. At normothermia, kidneys are metabolically active butex vivopreservation is limited to hours. During hypothermia kidneys can be preserved up to 24 hours but are metabolically inactive and suffer cold-induced injury. Therefore, we revisited sub normothermic perfusion (at 25°C) as an alternative approach to preserve human kidneys in a metabolically active state for extended periods of time.In a custom-made platform that includes a cell-free perfusate enriched with TCA cycle fuels, urine recirculation, and continuous hemofiltration we perfused discarded human kidneys up to 8 days. Using spatially resolved single cell resolution isotope tracing we demonstrate active metabolism in all the different renal cell types over this period. However, beyond 4 days cell composition of nephron segments assessed with spatial lipidomics changed substantially and injury markers such as NGAL and LDH increased in the perfusate. Up to 4 days, perfused human discarded donor kidneys maintained metabolic fluxes, functional parameters and allow for reperfusion using a porcine auto transplantation model. These data underpin that extended multi-day metabolic preservation of human kidneys is achievable using a sub normothermic perfusion platform.
Chromatin and Gene Regulatory Dynamics of Optic Nerve Invasion in Retinoblastoma at Single-Cell Resolution
Authors: Zhao Yihan , Liu Peng , Hu Lei , Ke Mingxi , Min Nan , Zeng Zehua , Du Hongwu 
Published: May 2023

AbstractRetinoblastoma is a rare and aggressive form of eye cancer that arises from the retina’s photoreceptor precursor cells. Yet, the mechanism of cancer evolution in optic invasion and the identification of molecularly defined tumor-propagating cells has not been reported. Using single-cell RNA and ATAC sequencing, we uncovered a propagating cell named STER after invasion of the optic nerve. We also report on the dynamic processes of photoreceptor degeneration and optic nerve injury in the retina and identify potential regulatory elements and transcription factors involved. STER cells mediate optic nerve destruction and retinal degeneration during the proliferation and migration of retinoblastoma. Finally, we develop drug sensitivity testing algorithms for malignant clusters, providing potential therapeutic targets and drug predictions for retinoblastoma invasion.
Development of genomic markers associated to production traits in lumpfish (Cyclopterus lumpus)
Authors: Gutierrez Alejandro P. , Selly Sarah-Louise Counter , Taggart John B. , Kokkinias Panagiotis , Cavrois-Rogacki Thomas , Fernandez Eduardo Jimenez , Migaud Herve , Lein Ingrid , Davie Andrew , Bekaert Michaël 
Published: May 2023

ABSTRACTCleaner fish species have gained great importance in the control of sea lice, among them, lumpfish (Cyclopterus lumpus) has become one of the most popular. Lumpfish life cycle has been closed, and hatchery reproduction is now possible, however, current production is reliant on wild caught broodstock to meet the increasing demand. Selective breeding practices are called to play an important role in the successful breeding of most aquaculture species, including lumpfish.In this study we analysed a lumpfish population for the identification of genomic markers linked to production traits. Sequencing of RAD libraries allowed us to identify, 7,193 informative markers within the sampled individuals. Genome wide association analysis for sex, weight, condition factor and standard length was performed. One single major QTL region was identified for sex determination, while nine QTL regions were detected for weight, and three QTL regions for standard length.A total of 177 SNP markers of interest (from QTL regions) and 399 top FstSNP markers were combined in a low-density panel, useful to obtain relevant genetic information from lumpfish populations. Moreover, a robust combined subset of 29 SNP markers (10 associated to sex, 14 to weight and 18 to standard length) provided over 90% accuracy in predicting the animal’s phenotype. Overall, our findings provide significant insights into the genetic control of important traits in lumpfish and deliver important genomic resources that will facilitate the establishment of selective breeding programs in lumpfish.
Analysis of the heterogeneity and complexity of murine extraorbital lacrimal gland via single-cell RNA sequencing
Authors: Zou Sen , Jiao Xinwei , Huang Shenzhen , Liu Jiangman , Si Hongli , Qi Di , Pei Xiaoting , Lu Dingli , Wang Yimian , Li Zhijie 
Published: May 2023

ABSTRACTPurposeThe lacrimal gland is essential for maintaining ocular surface health and avoiding external damage by secreting the aqueous layer of the tear film. However, a healthy lacrimal gland’s inventory of cell types and heterogeneity remains understudied.MethodsHere, 10X genome-based single-cell RNA sequencing was used to generate an unbiased classification of cellular diversity in the extraorbital lacrimal gland (ELG) of C57BL/6J mice. From 48,077 high-quality cells, an atlas of cell heterogeneity was produced, and cell types were defined by classic marker genes. The possible functions of these cells and the pseudotime trajectories for certain cell populations were analyzed through bioinformatics. In addition, a preliminary analysis of the cell-cell communication network in ELG was performed.ResultsOver 41 subclasses of cells were identified, including 9 kinds of glandular epithelial cells, 7 kinds of fibroblasts, 10 kinds of myeloid-derived immune cells, at least 10 kinds of lymphoid-derived immune cells, 3 kinds of vascular-associated cell subsets, and 2 kinds of Schwann cells. Analysis of cell–cell communication networks revealed that innate lymphoid cells were closely associated with other cells.ConclusionsThis study provides the first comprehensive transcriptome atlas and related database of mouse ELG. This resource can aid in a deeper understanding of lacrimal gland biology and pathophysiology of its related diseases.
EASTR: Correcting systematic alignment errors in multi-exon genes
Authors: Shinder Ida , Hu Richard , Ji Hyun Joo , Chao Kuan-Hao , Pertea Mihaela 
Published: May 2023

AbstractAccurate alignment of transcribed RNA to reference genomes is a critical step in the analysis of gene expression, which in turn has broad applications in biomedical research and in the basic sciences. We have discovered that widely used splice-aware aligners, such as STAR and HISAT2, can introduce erroneous spliced alignments between repeated sequences, leading to the inclusion of falsely spliced transcripts in RNA-seq experiments. In some cases, the “phantom” introns resulting from these errors have made their way into widely-used genome annotation databases. To address this issue, we have developed EASTR (Emending Alignments of Spliced Transcript Reads), a novel software tool that can detect and remove falsely spliced alignments or transcripts from alignment and annotation files. EASTR improves the accuracy of spliced alignments across diverse species, including human, maize, andArabidopsis thaliana, by detecting sequence similarity between intron-flanking regions. We demonstrate that applying EASTR before transcript assembly substantially reduces false positive introns, exons, and transcripts, improving the overall accuracy of assembled transcripts. Additionally, we show that EASTR’s application to reference annotation databases can detect and correct likely cases of mis-annotated transcripts.
Mutational scanning pinpoints distinct binding sites of key ATGL regulators in lipolysis
Authors: Kohlmayr Johanna M. , Grabner Gernot F. , Nusser Anna , Höll Anna , Halwachs Bettina , Jany-Luig Evelyne , Engelke Hanna , Zimmermann Robert , Stelzl Ulrich 
Published: May 2023

AbstractATGL is the key enzyme in intracellular lipolysis playing a critical role in metabolic and cardiovascular diseases. ATGL is tightly regulated through a known set of protein-protein interaction partners with activating or inhibiting functions in control of lipolysis. However, the binding mode and protein interaction sites of ATGL and its partners are unknown. Using deep mutational protein interaction perturbation scanning we generated comprehensive profiles of single amino acid variants effecting the interactions of ATGL with its regulatory partners: CGI-58, G0S2, PLIN1, PLIN5 and CIDEC. Twenty-three ATGL variants gave a specific interaction perturbation pattern when validated in co-immunoprecipitation experiments in mammalian cells. We identified and characterized eleven, highly selective ATGL “switch” mutations which affect the interaction of one of the five partners without affecting the others. Switch mutations thus provided distinct interaction determinants for ATGL’s key regulatory proteins at an amino acid resolution. When tested for triglyceride hydrolase activityin vitroand lipolysis in cells, the activity patterns of the ATGL switch variants traced to their protein interaction profile. In the context of structural data, the integration of variant binding and activity profiles provided important insights into lipolysis regulation and the impact of mutations in human disease.
Paternal CHH methylation potentiates stress responses against Pseudomonas syringae in Arabidopsis progenies
Authors: Li Yongping , Liu Tianjia , Leung Even Yee Man , Zhao Xusheng , Zhu Guopeng , Ng Danny W-K 
Published: May 2023

AbstractSystemic acquired resistance (SAR) is an induced immune mechanism in plants, involving epigenetic regulation by chromatin remodeling and DNA methylation, which can be inherited to progeny following stress exposure. Intersexual epigenetic conflict sometimes leads to unequal expression of maternal and paternal alleles in offspring, resulting in parent-of-origin effects of inheritance. To better understand the parental contributions of epialleles in plant defense, isogenicArabidopsisparental lines were mock-treated (M) andPseudomonas syringae(Pst)-treated (P) for reciprocal crosses to produce F1 progenies (MP, PM). Together with their self-fertilized F1 descendants (MM, PP), the genome-wide inherited DNA methylation and transcriptomic changes againstPstwere analyzed. F1 descendants shared widespread DNA methylation and transcriptional changes at transposable elements (TEs) and genes. The confrontation of epigenomes triggers the reprogramming of DNA methylation in reciprocal crosses, resulting in transgressive segregation that also shows the parental effect ofPsttreatment. Compared to PM, the MP (Pst-primed paternal genome) was found to contributes to CHH hypermethylation, which is associated with processes in plant-pathogen interaction, including carbohydrate metabolism, glutathione metabolism and stronger translation process, which potentially contribute to improved disease resistance in MP in response toPstchallenge. Our data suggested a parent-of-origin effect of defense priming that contributes differently toward improved defense response in progenies.