bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brief Report: Group-Based Trajectory Modeling to Determine Long-Term HIV Viral Load Trends Among Children With HIV in Kenya
Authors: Neary Jillian , Njuguna Irene , Wagner Anjuli D. , Richardson Barbra A. , Chebet Daisy , Langat Agnes , Ngugi Evelyn , Benki-Nugent Sarah , Moraa Hellen , Hawes Stephen E. , Overbaugh Julie , Slyker Jennifer A. , Lehman Dara A. , Wamalwa Dalton , John-Stewart Grace 
Published: April 2024

Background:
Identifying determinants of longitudinal HIV viral load (VL) trajectories using group-based trajectory modeling (GBTM) can inform clinical strategies and mechanisms of nonadherence among children.

Methods:
Children under 12 months old who were newly diagnosed with HIV were enrolled in the Optimizing Pediatric HIV therapy cohort (NCT00428116) from 2007 to 2010. Children initiated antiretroviral therapy at enrollment, and VL was assessed every 3 months for 24 months post–antiretroviral therapy and every 6 months thereafter up to 8 years old. VL trajectory groups were defined using GBTM. Fisher's exact and Kruskal–Wallis tests were used to determine the correlates of each trajectory group compared with the sustained-low VL group.

Results:
Five VL trajectory groups were identified among 89 children with 522 VL visits from 6 to 24 months: sustained-low (63% of children), sustained-very-high (16%), sustained-high (9%), low-to-high (7%), and high-with-periods-of-low (6%). Children in the sustained-high group were more frequently on a first-line protease inhibitor (PI)-based regimen (63% vs 38%; P = 0.03) and had younger caregivers (median: 22 vs 28 years; P = 0.02). Among 54 children with 560 VL visits followed from 48 to 96 months, 5 trajectory groups were identified: sustained-low (74%), mid-range (4%), periods-of-low (7%), high-to-low (7%), and sustained-high (7%). Those in the high-to-low group had younger caregivers (21 vs 29 years; P = 0.01).

Conclusions:
GBTM identified unique VL patterns among children with unsuppressed VL. Caregiver and regimen-related characteristics were associated with patterns of nonsuppression. Younger caregivers may benefit from tailored counseling to help them support child antiretroviral therapy adherence. Palatable regimens are necessary for viral suppression among children with HIV.
Non-apoptotic role of EGL-1 in exopher production and neuronal health inCaenorhabditis elegans
Authors: Wu Zheng , Cardona Eric A. , Pierce Jonathan T. 
Published: April 2024

AbstractWhile traditionally studied for their pro-apoptotic functions, recent research suggests BH3-only proteins also have non-apoptotic roles. Here, we find that EGL-1, the BH3-only protein inCaenorhabditis elegans, promotes the cell-autonomous production of exophers in adult neurons. Exophers are large, micron-scale vesicles that are ejected from the cell and contain cellular components such as mitochondria. EGL-1 facilitates exopher production potentially through regulation of mitochondrial dynamics. Moreover, an endogenous, low level of EGL-1 expression appears to benefit dendritic health. Our findings provide insights into the mechanistic role of BH3-only protein in mitochondrial dynamics, downstream exopher production, and ultimately neuronal health.Significance statementBH3-only proteins were known for their function in inducing cell death. Their presence in healthy adult neurons, however, suggests additional roles. Our study focused on the BH3-only protein EGL-1 in the nematodeCaenorhabditis elegans, where its apoptotic role was discovered. We reveal a new role in cell-autonomously promoting exopher production – a process where neurons extrude large vesicles containing potentially harmful cell contents. EGL-1 appears to promote this by regulating mitochondrial dynamics. We also report that low levels of EGL-1 benefit neuronal health and function. These findings expand our understanding of BH3-only proteins, mitochondrial dynamics, and exopher production in neurons and provide insights for neurodegenerative diseases.
A factorial randomised controlled trial to examine the potential effect of a text-message based intervention on reducing adolescent susceptibility to e-cigarette use: A study protocol
Authors: Barnes Courtney , Turon Heidi , McCrabb Sam , Mantach Stephanie , Janssen Lisa , Duffy Megan , Groombridge Daniel , Hodder Rebecca Kate , Meharg David , Robinson Elly , Bialek Caitlin , Wallace Seaneen , Leigh Lucy , Wolfenden Luke 
Published: April 2024

ABSTRACTIntroductionAdolescent e-cigarette use, globally and within Australia, has increased in recent years. In response, public health agencies have called for the development of education and communication programmes targeting adolescents. Despite such recommendations, few rigorous evaluations of such interventions currently exist. The main objective of this study is to examine the potential effect of a text-message intervention targeting parents and adolescents on adolescent susceptibility to e-cigarette use (e.g. intentions towards using e-cigarettes). Secondary objectives are to: (1) examine the effect of the intervention on adolescent e-cigarette and combustible tobacco use; and (2) examine the acceptability of the intervention.Methods and analysisA randomised controlled trial employing a 2x2 factorial design will be conducted with parent-adolescent dyads (aged 12-15 years). Dyads will be randomly allocated to one of four arms: Arm 1 - a text-message intervention delivered to adolescents only; Arm 2 – a text- message intervention delivered to the parents of adolescents only; Arm 3 – a text-message intervention delivered to both the parents and adolescents; and Arm 4 - an information only control, consisting of an e-cigarette factsheet provided to parents only. Participant recruitment commenced in April 2023 with the aim to recruit 120 parent-adolescent dyads. Data collection to assess study outcomes will occur at baseline, 6-, 12- and 24-months post the commencement of the intervention. The primary endpoint will be 6-month follow-up. The primary outcome will be adolescent susceptibility to e-cigarette use, assessed using validated items. Analyses of trial outcomes will be undertaken under an intention-to-treat framework, with all participants included in the analysis in the group they were allocated.Ethics and disseminationEthics approval has been obtained from the University of Newcastle Human Research Ethics Committee (H-2022-0340). Findings will be disseminated in peer-reviewed journals and at conferences.Trial registrationProspectively registered with Australia New Zealand Clinical Trials Registry (ACTRN12623000079640).STRENGTHS AND LIMITATIONSThis study will employ a rigorous factorial randomised controlled trial design to test the effectiveness of a text-message based intervention;This study will contribute to the limited existing evidence base, with no randomised controlled trials aiming to prevent adolescent e-cigarette use currently published yet several underway;Selection bias may occur if adolescents who are highly susceptible to e-cigarette use refuse to participate in the study.
Contrasting dynamics of two incursions of low pathogenicity avian influenza virus into Australia
Authors: Wille Michelle , Broz Ivano , Cherrington Tanya , Crawley Allison , Farrugia Blaine , Ford Mark , Frost Melinda , Grimsey Joanne , Kirkland Peter D. , Latimore Shaylie , Lynch Stacey E. , Martin Sue , Matereke Cornelius , Mee Peter T. , Neave Matthew J. , O’Dea Mark , Read Andrew J. , O’Riley Kim , Stevens Vittoria , Thayaparan Sivapiragasam , Zufan Sara , de Gouvea Pedroso Silvia Ban , Grillo Victoria , Breed Andrew C. , Barr Ian G. , Holmes Edward C. , Klaassen Marcel , Wong Frank Y. K. 
Published: April 2024

AbstractThe current panzootic of high pathogenicity avian influenza virus H5N1 demonstrates how viral incursions can have major ramifications for wildlife and domestic animals. Herein, we describe the recent incursion into Australia of two low pathogenicity avian influenza virus subtypes, H4 and H10, that exhibited contrasting evolutionary dynamics. Viruses detected from national surveillance and disease investigations between 2020-2022 revealed 27 genomes, 24 of which have at least one segment more closely related to Eurasian or North American avian influenza lineages than those already circulating in Australia. Phylogenetic analysis revealed that H4 viruses circulating in shorebirds represent a recent incursion from Asia that is distinct from those circulating concurrently in Australian waterfowl. Analysis of the internal segments further demonstrates exclusive, persistent circulation in shorebirds. This contrasts with H10, where a novel lineage has emerged in wild waterfowl, poultry and captive birds across Australia, and has likely replaced previously circulating H10 lineages through competitive exclusion. Elucidating different dynamics for avian influenza incursions supports effective disease risk identification and communication that better informs disease preparedness and response.
Quinoxaline-Based Anti-Schistosomal Compounds Have Potent Anti-Malarial Activity
Authors: Rawat Mukul , Padalino Gilda , Yeo Tomas , Brancale Andrea , Fidock David A. , Hoffmann Karl F. , Lee Marcus C. S. 
Published: April 2024

ABSTRACTThe human pathogensPlasmodiumandSchistosomaare each responsible for over 200 million infections annually, being particularly problematic in low- and middle-income countries. There is a pressing need for new drug targets for these diseases, driven by emergence of drug-resistance inPlasmodiumand the overall dearth of new drug targets forSchistosoma. Here, we explored the opportunity for pathogen-hopping by evaluating a series of quinoxaline-based anti-schistosomal compounds for activity againstP. falciparum. We identified compounds with low nanomolar potency against 3D7 and multidrug-resistant strains. Evolution of resistance using a mutatorP. falciparumline revealed a low propensity for resistance. Only one of the series, compound 22, yielded resistance mutations, including point mutations in a non-essential putative hydrolasepfqrp1,as well as copy-number amplification of a phospholipid-translocating ATPase,pfatp2, a potential target. Notably, independently generated CRISPR-edited mutants inpfqrp1also showed resistance to compound 22 and a related analogue. Moreover, previous lines withpfatp2copy-number variations were similarly less susceptible to challenge with the new compounds. Finally, we examined whether the predicted hydrolase activity of PfQRP1 underlies its mechanism of resistance, showing that both mutation of the putative catalytic triad and a more severe loss of function mutation elicited resistance. Collectively, we describe a compound series with potent activity against two important pathogens and their potential target inP. falciparum.
Revolutionizing Postoperative Ileus Monitoring: Exploring GRU-D’s Real-Time Capabilities and Cross-Hospital Transferability
Authors: Ruan Xiaoyang , Fu Sunyang , Jia Heling , Mathis Kellie L. , Thiels Cornelius A. , Wilson Patrick M. , Storlie Curtis B. , Liu Hongfang 
Published: April 2024

BackgroundPostoperative ileus (POI) after colorectal surgery leads to increased morbidity, costs, and hospital stays. Identifying POI risk for early intervention is important for improving surgical outcomes especially given the increasing trend towards early discharge after surgery. While existing studies have assessed POI risk with regression models, the role of deep learning’s remains unexplored.MethodsWe assessed the performance and transferability (brutal force/instance/parameter transfer) of Gated Recurrent Unit with Decay (GRU-D), a longitudinal deep learning architecture, for real-time risk assessment of POI among 7,349 colorectal surgeries performed across three hospital sites operated by Mayo Clinic with two electronic health records (EHR) systems. The results were compared with atemporal models on a panel of benchmark metrics.ResultsGRU-D exhibits robust transferability across different EHR systems and hospital sites, showing enhanced performance by integrating new measurements, even amid the extreme sparsity of real-world longitudinal data. On average, for labs, vitals, and assisted living status, 72.2%, 26.9%, and 49.3% respectively lack measurements within 24 hours after surgery. Over the follow-up period with 4-hour intervals, 98.7%, 84%, and 95.8% of data points are missing, respectively. A maximum of 5% decrease in AUROC was observed in brutal-force transfer between different EHR systems with non-overlapping surgery date frames. Multi-source instance transfer witnessed the best performance, with a maximum of 2.6% improvement in AUROC over local learning. The significant benefit, however, lies in the reduction of variance (a maximum of 86% decrease). The GRU-D model’s performance mainly depends on the prediction task’s difficulty, especially the case prevalence rate. Whereas the impact of training data and transfer strategy is less crucial, underscoring the challenge of effectively leveraging transfer learning for rare outcomes. While atemporal Logit models show notably superior performance at certain pre-surgical points, their performance fluctuate significantly and generally underperform GRU-D in post-surgical hours.ConclusionGRU-D demonstrated robust transferability across EHR systems and hospital sites with highly sparse real-world EHR data. Further research on built-in explainability for meaningful intervention would be highly valuable for its integration into clinical practice.
Macrophage-derived developmental endothelial locus 1 (DEL-1) expression promotes an immunoprotective phenotype in experimental visceral leishmaniasis
Authors: Lukaszonek Jakub , Brown Najmeeyah , Zenga Jessie , Myburgh Elmarie , Hewitson James P. , Hajishengalis George , Chavakis Triantafyllos , Kaye Paul M. , Kourtzelis Ioannis 
Published: April 2024

AbstractThe identification of tissue-derived homeostatic molecules regulating immune plasticity is essential for understanding the role of macrophages in immune responses to intra-phagosomal pathogens. Developmental endothelial locus-1 (DEL-1) is a functionally versatile homeostatic factor capable of inhibiting the onset of inflammation and promoting inflammation resolution, but its role in the response to intracellular infections has not been previously addressed.Leishmania, causative agents of the neglected tropical disease leishmaniasis, are intra-phagosomal parasites that establish a replicative niche within macrophages.Here, using a well-established murine model of visceral infection withLeishmania donovani, we establish DEL-1 as a novel regulator of immunity to this infection. Parasite burden was significantly higher in B6.Edil3-/-(Del1-KO) compared to wild type B6 mice, as determined by whole body IVIS imaging, largely as a result of increased liver parasite load. However, lack of DEL-1 enhanced hepatomegaly and enhanced granulomatous inflammation. Conversely, parasite burden and the formation of large granulomas was reduced in mice overexpressing DEL-1 in macrophages but not in endothelial cells. Our findings reveal a hitherto unknown role of DEL-1 in the immune response toL. donovaniinfection and may represent a novel approach to mitigate immunopathology.
Single-nucleus RNA/ATAC-seq in early-stage HCM models predicts SWI/SNF-activation in mutant-myocytes, and allele-specific differences in fibroblasts
Authors: Thottakara Tilo , Padmanabhan Arun , Tanriverdi Talha , Thambidurai Tharika , Diaz-RG Jose A. , Amonkar Sanika R. , Olgin Jeffrey E. , Long Carlin S. , Abraham M. Roselle 
Published: April 2024

ABSTRACTHypertrophic cardiomyopathy (HCM) is associated with phenotypic variability. To gain insights into transcriptional regulation of cardiac phenotype, single-nucleus linked RNA-/ATAC-seq was performed in 5-week-old control mouse-hearts (WT) and two HCM-models (R92W-TnT, R403Q-MyHC) that exhibit differences in heart size/function and fibrosis; mutant data was compared to WT. Analysis of 23,304 nuclei from mutant hearts, and 17,669 nuclei from WT, revealed similar dysregulation of gene expression, activation of AP-1 TFs (FOS, JUN) and the SWI/SNF complex in both mutant ventricular-myocytes. In contrast, marked differences were observed between mutants, for gene expression/TF enrichment, in fibroblasts, macrophages, endothelial cells. Cellchat predicted activation of pro-hypertrophic IGF-signaling in both mutant ventricular-myocytes, and profibrotic TGFβ-signaling only in mutant-TnT fibroblasts. In summary, our bioinformatics analyses suggest that activation of IGF-signaling, AP-1 TFs and the SWI/SNF chromatin remodeler complex promotes myocyte hypertrophy in early-stage HCM. Selective activation of TGFβ-signaling in mutant-TnT fibroblasts contributes to genotype-specific differences in cardiac fibrosis.
Horizontally acquired HosA transcription factor bound with 4-hydroxy-benzoic acid exhibits unique tug-of-water dynamics
Authors: Goswami Arpita , Ullah Samee , Brito José A. 
Published: April 2024

AbstractPathogenicEscherichia coli(E. coli) causes serious illnesses in humans aided by several multiple antibiotic resistance regulator (MarR) transcription factors. Among these proteins, HosA provides support to these organisms by executing crucial roles in functions ranging from flagella motility to organic compound metabolism. The crystal structure of HosA from enteropathogenicE. coliis elucidated in this study along with conformational changes orchestrated by different amino acids due to para-hydroxy benzoic acid (PHB) binding in the hinge region. Structural analysis and extensive molecular dynamics simulation reveal role of a dynamic water molecule as a bridging entity in PHB bound structure which is not shown for any MarR structure yet. Also, it is shown that the HosA gene is transferred horizontally fromShigellato pathogenicE. coli, having 97.6% sequence similarity with an uncharacterized transcription factor fromShigella dysenteriae Sd197. This study may be promising to address several unanswered questions for the functioning of MarR transcription factors from infectiousE. coliand design inhibitors to combat these pathogens.
Dual CRALBP isoforms unveiled: iPSC-derived retinal modelling and AAV2/5-RLBP1 gene transfer raise considerations for effective therapy
Authors: Damodar Krishna , Dubois Gregor , Guillou Laurent , Mamaeva Daria , Pequignot Marie , Erkilic Nejla , Sanjurjo-Soriano Carla , Boukhaddaoui Hassan , Bernex Florence , Bocquet Béatrice , Vialaret Jerome , Arsenijevic Yvan , Redmond T. Michael , Hirtz Christopher , Meunier Isabelle , Brabet Philippe , Kalatzis Vasiliki 
Published: April 2024

AbstractInherited retinal diseases (IRDs) are clinically and genetically heterogeneous disorders characterised by progressive vision loss. Over 270 causative genes have been identified and variants within the same gene can give rise to clinically distinct disorders. Human induced pluripotent stem cells (iPSCs) have revolutionised disease modelling, by allowing pathophysiological and therapeutic studies in the patient and tissue context. The IRD geneRLBP1encodes CRALBP, an actor of the rod and cone visual cycles in the retinal pigment epithelium (RPE) and Müller cells, respectively. Variants inRLBP1lead to three clinical subtypes: Bothnia dystrophy, Retinitis punctata albescens and Newfoundland rod-cone dystrophy. We modelledRLBP1-IRD subtypes by patient-specific iPSC-derived RPE and identified pertinent therapeutic read-outs. We developed an AAV2/5-mediated gene replacement strategy and provided a proof-of-concept in theex vivohuman models that was validated in anin vivo Rlbp1−/−murine model. Most importantly, we identified a previously unsuspected smaller CRALBP isoform that is naturally and differentially expressed in both human and murine retina. The new isoform arises from an alternative methionine initiation site and plays a role in the visual cycle. This work provides novel insights into CRALBP expression andRLBP1-associated pathophysiology and raises important considerations for successful gene supplementation therapy.
Expanding the genome information onBacillalesfor biosynthetic gene cluster discovery
Authors: Song Lijie , Dyrbye Nielsen Lasse Johan , Xu Xinming , Mohite Omkar Satyavan , Nuhamunada Matin , Xu Zhihui , Murphy Rob , Bodawatta Kasun , Poulsen Michael , Abdulla Mohamed Hatha , Sonnenschein Eva C. , Weber Tilmann , Kovács Ákos T. 
Published: April 2024

AbstractThis study showcases 121 new genomes of spore-formingBacillalesfrom strains collected globally from a variety of habitats, assembled using Oxford Nanopore long-read and MGI short-read sequences.Bacilliare renowned for their capacity to produce diverse secondary metabolites with use in agriculture, biotechnology, and medicine. These secondary metabolites are encoded within biosynthetic gene clusters (smBGCs). smBGCs have significant research interest due to their potential for the discovery of new bioactivate compounds. Our dataset includes 62 complete genomes, 2 at chromosome level, and 57 at contig level, covering a genomic size range from 3.50 Mb to 7.15 Mb. Phylotaxonomic analysis revealed that these genomes span 16 genera, with 69 of them belonging toBacillus. A total of 1,176 predicted BGCs were identified byin silicogenome mining. We anticipate that the open-access data presented here will expand the reported genomic information of spore-formingBacillalesand facilitate a deeper understanding of the genetic basis ofBacillales’ potential for secondary metabolite production.
Characterizing losses in InAs two-dimensional electron gas-based gatemon qubits
Authors: Strickland William M. , Baker Lukas J. , Lee Jaewoo , Dindial Krishna , Elfeky Bassel Heiba , Strohbeen Patrick J. , Hatefipour Mehdi , Yu Peng , Levy Ido , Issokson Jacob , Manucharyan Vladimir E. , Shabani Javad 
Published: April 2024

The tunneling of Cooper pairs across a Josephson junction (JJ) allows for the nonlinear inductance necessary to construct superconducting qubits, amplifiers, and various other quantum circuits. An alternative approach using hybrid superconductor-semiconductor JJs can enable superconducting qubit architectures with all electric control. Here we present continuous-wave and time-domain characterization of gatemon qubits and coplanar waveguide resonators based on an InAs two-dimensional electron gas. We show that the qubit undergoes a vacuum Rabi splitting with a readout cavity, and we drive coherent Rabi oscillations between the qubit ground and first excited states. We measure qubit relaxation times to be T1= 100 ns over a 1.5 GHz tunable band. We detail the loss mechanisms present in these materials through a systematic study of the quality factors of coplanar waveguide resonators. While various loss mechanisms are present in III-V gatemon circuits, we detail future directions in enhancing the relaxation times of qubit devices on this platform.

Published by the American Physical Society
2024