bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for the systematic review of thePneumocystis jirovecii-associated pneumonia in non-HIV immunocompromised patients
Authors: Orozco-Ugarriza Mauricio Ernesto , Rodger-Cervantes Yuranis E. , Olivo-Martínez Yenifer 
Published: November 2023

AbstractIntroductionPneumocystis jiroveciipneumonia (PJP) is a well-known and frequent opportunistic infection in HIV patients. However, there has been an increase in the number of reports of PJP in other immunosuppressed patients with autoimmune inflammatory disorders or because of chemotherapy and high doses of steroids, especially when used in combination as part of immunosuppressive therapy.ObjectiveDespite the increasing importance of PJP in non-HIV patients, there is a lack of comprehensive and updated information on the epidemiology, pathogenesis, diagnosis, microbiology, treatments, and prophylaxis of this infection in this population. Therefore, the objective of this systematic review is to synthesize information on these aspects, from a perspective of evidence-based medicine.MethodsThe protocol is prepared following the preferred reporting items for systematic reviews and meta-analyses (PRISMA-P) guidelines. We will perform a systematic review from 2010 to 2022 in PubMed, Google Scholar, ScienceDirect, and Web of Science. In addition, manual searches will be carried out through related articles, and references to included articles. The main findings and clinical outcomes were extracted from all the eligible studies with a standardized instrument. Two authors will independently screen titles and abstracts, review full texts, and collect data. Disagreements will be resolved by discussion, and a third reviewer will decide if there is no consensus. We will synthesize the results using a narrative or a meta-analytic approach, depending on the heterogeneity of the studies.Expected resultsIt is expected that this systematic review will provide a comprehensive and up-to-date overview of the state-of-the-art of PJP in non-HIV patients. Furthermore, the study will highlight possible gaps in knowledge that should be addressed through new research.ConclusionsHere, we present the protocol for a systematic review which will consider all existing evidence from peer-reviewed publication sources relevant to the primary and secondary outcomes related to diagnosing and managing PJP in non-HIV patients.Systematic review registryThis study was registered at the International Prospective Registry for Systematic Reviews (PROSPERO registration number:CRD42023429112)
Hao-Fountain Syndrome: 32 novel patients reveal new insights into the clinical spectrum
Authors: Wimmer Moritz Claudius , Brennenstuhl Heiko , Hirsch Steffen , Dötsch Laura , Unser Samy , Caro Pilar , Schaaf Christian Patrick 
Published: November 2023

AbstractHao-Fountain syndrome (HAFOUS, OMIM: #616863) is a neurodevelopmental disorder caused by pathogenic variants in the geneUSP7coding for USP7, a protein involved in several crucial cellular homeostatic mechanisms and the recently described MUST complex. The phenotype of HAFOUS is insufficiently understood, yet there is a great need to better understand the spectrum of disease, genotype-phenotype correlations, and disease trajectories.We now present a larger cohort of 32 additional individuals and provide further clinical information about six previously reported individuals. A questionnaire-based study was performed to characterize the phenotype of Hao-Fountain syndrome more clearly, to highlight new traits, and to better distinguish the disease from related neurodevelopmental disorders. In addition to confirming previously described features, we report hyperphagia and increased body weight in a subset of individuals. HAFOUS patients present an increased rate of birth complications, congenital anomalies, and abnormal pain thresholds. Speech impairment emerges as a potential hallmark of Hao-Fountain syndrome. Cognitive testing reports reveal borderline intellectual functioning on average, although some individuals score in the range of intellectual disability.Finally, we created a syndrome-specific severity score. This score neither indicates a sex-nor age-specific difference of clinical severity, yet highlights a more severe outcome when amino acid changes colocalize to the catalytic domain of the USP7 protein.
Prediction of plant complex traits via integration of multi-omics data
Authors: Wang Peipei , Lehti-Shiu Melissa D. , Lotreck Serena , Abá Kenia Segura , Krysan Patrick J. , Shiu Shin-Han 
Published: November 2023

AbstractThe formation of complex traits is the consequence of genotype and activities at multiple molecular levels. However, connecting genotypes and these activities to complex traits remains challenging. Here, we investigated whether integrating different omics data could improve trait prediction. We built prediction models using genomic, transcriptomic, and methylomic data from the Arabidopsis 1001 Genomes Project for six Arabidopsis traits, and found that transcriptome- and methylome-based models had performances comparable to those of genome-based models. However, when comparing models for flowering time prediction, we found that models built using different omics data identified different benchmark genes. Nine novel genes identified as important for flowering time from our models were experimentally validated as regulating flowering. In addition, we found that gene contributions to flowering time prediction are accession-dependent and that distinct genes contribute to trait prediction in different genetic backgrounds. Models integrating multi-omics data performed best and revealed known and novel gene interactions, extending knowledge about existing regulatory networks underlying flowering time determination. These results demonstrate the feasibility of revealing molecular mechanisms underlying complex traits through multi-omics data integration.
GCN2 mediates access to stored amino acids for somatic maintenance duringDrosophilaageing
Authors: Johnstone Joshua N. , Mirth Christen K. , Johnson Travis K. , Schittenhelm Ralf B. , Piper Matthew D.W. 
Published: November 2023

AbstractMany mechanistic theories of ageing argue that a progressive failure of somatic maintenance, the use of energy and resources to prevent and repair damage to the cell, underpins ageing. To sustain somatic maintenance an organism must acquire dozens of essential nutrients from the diet, including essential amino acids (EAAs), which are physiologically limiting for many animals. InDrosophila, adulthood deprivation of each individual EAA yields vastly different lifespan trajectories, and adulthood deprivation of one EAA, phenylalanine (Phe), has no associated lifespan cost; this is despite each EAA being strictly required for growth and reproduction. Moreover, survival under any EAA deprivation depends entirely on the conserved AA sensor GCN2, a component of the integrated stress response (ISR), suggesting that a novel ISR-mediated mechanism sustains lifelong somatic maintenance during EAA deprivation. Here we investigated this mechanism, finding that flies chronically deprived of dietary Phe continue to incorporate Phe into new proteins, and that challenging flies to increase the somatic requirement for Phe shortens lifespan under Phe deprivation. Further, we show that autophagy is required for full lifespan under Phe deprivation, and that activation of the ISR can partially rescue the shortened lifespan ofGCN2-nulls under Phe deprivation. We therefore propose a mechanism by which GCN2, via the ISR, activates autophagy during EAA deprivation, breaking down a larvally-acquired store of EAAs to support somatic maintenance. These data refine our understanding of the strategies by which flies sustain lifelong somatic maintenance, which determines length of life in response to changes in the nutritional environment.
Serotonin transporter-dependent histone serotonylation in placenta contributes to the neurodevelopmental transcriptome
Authors: Chan Jennifer C , Alenina Natalia , Cunningham Ashley M , Ramakrishnan Aarthi , Shen Li , Bader Michael , Maze Ian 
Published: November 2023

ABSTRACTBrain development requires appropriate regulation of serotonin (5-HT) signaling from distinct tissue sources across embryogenesis. At the maternal-fetal interface, the placenta is thought to be an important contributor of offspring brain 5-HT and is critical to overall fetal health. Yet, how placental 5-HT is acquired, and the mechanisms through which 5-HT influences placental functions, are not well understood. Recently, our group identified a novel epigenetic role for 5-HT, in which 5-HT can be added to histone proteins to regulate transcription, a process called H3 serotonylation. Here, we show that H3 serotonylation undergoes dynamic regulation during placental development, corresponding to gene expression changes that are known to influence key metabolic processes. Using transgenic mice, we demonstrate that placental H3 serotonylation largely depends on 5-HT uptake by the serotonin transporter (SERT/SLC6A4). SERT deletion robustly reduces enrichment of H3 serotonylation across the placental genome, and disrupts neurodevelopmental gene networks in early embryonic brain tissues. Thus, these findings suggest a novel role for H3 serotonylation in coordinating placental transcription at the intersection of maternal physiology and offspring brain development.
DNA Origami – Lipid Membrane Interactions Defined at Single-Molecular Resolution
Authors: Georgiou Elena , Cabello-Garcia Javier , Xing Yongzheng , Howorka Stefan 
Published: November 2023

ABSTRACTRigid DNA nanostructures that bind to floppy bilayer membranes are of fundamental interest as they replicate biological cytoskeletons for synthetic biology, biosensing, and biological research. Here, we establish principles underpinning the controlled interaction of DNA structures and lipid bilayers. As membrane anchors mediate interaction, more than 20 versions of a core DNA nanostructure are built each carrying up to five individual cholesterol anchors of different steric accessibility within the 3D geometry. The structures’ binding to membrane vesicles of tunable curvature is determined with ensemble methods and by single-molecule localization microscopy. This screen yields quantitative and unexpected insight on which steric anchor points cause efficient binding. Strikingly, defined nanostructures with a single molecular anchor discriminate effectively between vesicles of different nanoscale curvatures which may be exploited to discern diagnostically relevant membrane vesicles based on size. Furthermore, we reveal anchor-mediated bilayer interaction to be co-controlled by non-lipidated DNA regions and localized membrane curvatures stemming from heterogenous lipid composition, which modifies existing biophysical models. Our study extends DNA nanotechnology to control interactions with bilayer membranes and thereby facilitate the design of nanodevices for vesicle-based diagnostics, biosensing, and protocells.
Strong sequence dependence in RNA/DNA hybrid strand displacement kinetics
Authors: Smith Francesca G. , Goertz John P. , Stevens Molly M. , Ouldridge Thomas E. 
Published: November 2023

ABSTRACTStrand displacement reactions underlie dynamic nucleic acid nanotechnology. The kinetic and thermodynamic features of DNA-based displacement reactions are well understood and well predicted by current computational models. By contrast, understanding of RNA/DNA hybrid strand displacement kinetics is limited, restricting the design of increasingly complex RNA/DNA hybrid reaction networks with more tightly regulated dynamics. Given the importance of RNA as a diagnostic biomarker, and its critical role in intracellular processes, this shortfall is particularly limiting for the development of strand displacement-based therapeutics and diagnostics. Herein, we characterise 22 RNA/DNA hybrid strand displacement systems, systematically varying several common design parameters including toehold length and branch migration domain length. We observe the differences in stability between RNA-DNA hybrids and DNA-DNA duplexes have large effects on strand displacement rates, with rates for equivalent sequences differing by up to 3 orders of magnitude. Crucially, however, this effect is strongly sequence-dependent, with RNA invaders strongly favoured in a system with RNA strands of high purine content, and disfavoured in a system when the RNA strands have low purine content. These results lay the groundwork for more general design principles, allowing for creation ofde novoreaction networks with novel complexity while maintaining predictable reaction kinetics.
FeLIX is a restriction factor for mammalian retrovirus infection
Authors: Pramono Didik , Takeuchi Dai , Katsuki Masato , AbuEed Loai , Abdillah Dimas , Kimura Toru , Kawasaki Junna , Miyake Ariko , Nishigaki Kazuo 
Published: November 2023

ABSTRACTEndogenous retroviruses (ERVs) are remnants of ancestral viral infections. Feline leukemia virus (FeLV) is an exogenous and endogenous retrovirus in domestic cats. It is classified into several subgroups (A, B, C, D, E, and T) based on viral receptor interference properties or receptor usage. ERV-derived molecules benefit animals, conferring resistance to infectious diseases. However, the soluble protein encoded by the defective envelope (env) gene of endogenous FeLV (enFeLV) functions as a co-factor in FeLV subgroup T infections. Thus, whether the gene emerged to facilitate viral infection is unclear. Based on the properties of ERV-derived molecules, we hypothesized that the defectiveenvgenes possess antiviral activity that would be advantageous to the host because FeLV subgroup B (FeLV-B), a recombinant virus derived from enFeLVenv, is restricted to viral transmission among domestic cats. When soluble truncated Env proteins from enFeLV were tested for their inhibitory effects against enFeLV and FeLV- B, they inhibited viral infection. Notably, this antiviral machinery was extended to infection with the Gibbon ape leukemia virus, Koala retrovirus-A, and Hervey pteropid gammaretrovirus. Although these viruses used feline phosphate transporter1 (fePit1) or fePit1 and phosphate transporter2 (fePit2) as receptors, the inhibitory mechanism involved competitive receptor binding in a fePit1-dependent manner. The shift of receptor usage may have occurred to avoid the inhibitory effect. Overall, these findings highlight the possible emergence of soluble truncated Env proteins from enFeLV as a restriction factor against retroviral infection, and might help in the control of retroviral spread for host immunity and antiviral defense.ImportanceRetroviruses are unique in using reverse transcriptase to convert RNA genomes into DNA, infecting germ cells, and transmitting to offspring. A large amount of ancient retroviral sequences are known as endogenous retroviruses (ERVs). Soluble Env protein derived from ERVs have been identified to function as a co-factor that assists in FeLV-T infection. However, herein, we show that the soluble Env protein exhibits antiviral activity and provides resistance to mammalian retrovirus infection through competitive receptor binding. In particular, this finding may explain why FeLV-B transmission is not observed among domestic cats. ERV-derived molecules can benefit animals in an evolutionary arm race, highlighting the double-edged sword nature of ERVs.
Rapid Adeno-Associated Virus Genome Quantification with Amplification-Free CRISPR-Cas12a
Authors: Hetzler Zach , Marinakos Stella M. , Lott Noah , Mohammad Noor , Lass-Napiorkowska Agnieszka , Kolbe Jenna , Turrentine Lauren , Fields Delaney , Overton Laurie , Marie Helena , Hucknall Angus , Rammo Oliver , George Henry , Wei Qingshan 
Published: November 2023

AbstractEfficient manufacturing of recombinant Adeno-Associated Viral (rAAV) vectors to meet rising clinical demand remains a major hurdle. One of the most significant challenges is the generation of large amounts of empty capsids without the therapeutic genome. There is no standardized analytical method to accurately quantify the viral genes, and subsequently the empty-to-full ratio, making the manufacturing challenges even more complex. We propose the use of CRISPR diagnostics (CRISPR-Dx) as a robust and rapid approach to determine AAV genome titers. We designed and developed the CRISPR-AAV Evaluation (CRAAVE) assay to maximize sensitivity, minimize time-to-result, and provide a potentially universal design for quantifying multiple transgene constructs encapsidated within different AAV serotypes. We also demonstrate an on-chip CRAAVE assay with lyophilized reagents to minimize end user assay input. The CRAAVE assay was able to detect AAV titers as low as 7e7 vg/mL with high precision (<3% error) in quantifying unknown AAV titers when compared with conventional quantitative PCR (qPCR) method. The assay only requires 30 minutes of assay time, shortening the analytical workflow drastically. Our results suggest CRISPR-Dx could be a promising tool for efficient rAAV genome titer quantification and has the potential to revolutionize biomanufacturing process analytical technology (PAT).Graphical Abstract
Factors influencing the outcomes of non-pharmacological interventions for managing fatigue across the lifespan of people living with musculoskeletal (MSK) conditions: a scoping review protocol
Authors: Fishpool Katie , Young George , Ciurtin Coziana , Cramp Fiona , Erhieyovwe Emmanuel , Farisogullari Bayram , Macfarlane Gary , Machado Pedro M. , Pearson Jen , Santos Eduardo , Dures Emma 
Published: November 2023

ABSTRACTIntroductionFatigue is an important and distressing symptom for many people living with chronic musculoskeletal (MSK) conditions. Many non-pharmacological interventions have been investigated in recent years and some have been demonstrated to be effective in reducing fatigue and fatigue impact, however there is limited guidance for clinicians to follow regarding the most appropriate management options. The objective of this scoping review is to understand and map the extent of evidence in relation to the impact of non-pharmacological interventions on MSK condition-related fatigue across the lifespan.Methods and analysisThis scoping review will include evidence relating to people of all ages living with chronic MSK conditions who have been offered a non-pharmacological intervention with either the intention or effect of reducing fatigue and its impact. Databases including AMED, PsycINFO, CINAHLPlus, MEDLINE, EMBASE and Scopus will be searched for peer reviewed primary research studies published after 1stJanuary 2007 in English language. These findings will be used to identify factors associated with successful interventions and to map gaps in knowledge.Ethics and disseminationEthical approval was not required for this review. Findings will be disseminated by journal publication, conference presentation and by communicating with relevant healthcare and charity organisations.Article SummaryStrengths and limitations of this study-Patient and Public Involvement and Engagement (PPIE) workshops at key time points will ensure that the protocol, review findings and subsequent discussion are relevant to stakeholders and reflect lived experience of MSK-fatigue-All studies will be reviewed, and data extraction checked by a minimum of two researchers-The effectiveness of specific interventions and methodological quality of included studies is not covered in this scoping review-Only evidence available in English will be reviewed
Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR-Cas9 RNP
Authors: Chen Kai , Han Hesong , Zhao Sheng , Xu Bryant , Yin Boyan , Trinidad Marena , Burgstone Benjamin W. , Murthy Niren , Doudna Jennifer A. 
Published: November 2023

AbstractLipid nanoparticle (LNP) delivery of CRISPR ribonucleoproteins (RNPs) has the potential to enable high-efficiencyin vivogenome editing with low toxicity and an easily manufactured technology, if RNP efficacy can be maintained during LNP production. In this study, we engineered a thermostable Cas9 fromGeobacillus stearothermophilus(GeoCas9) using directed evolution to generate iGeoCas9 evolved variants capable of robust genome editing of cells and organs. iGeoCas9s were significantly better at editing cells than wild-type GeoCas9, with genome editing levels >100X greater than those induced by the native GeoCas9 enzyme. Furthermore, iGeoCas9 RNP:LNP complexes edited a variety of cell lines and induced homology-directed repair (HDR) in cells receiving co-delivered single-stranded DNA (ssDNA) templates. Using tissue-selective LNP formulations, we observed genome editing of 35‒56% efficiency in the liver or lungs of mice that received intravenous injections of iGeoCas9 RNP:LNPs. In particular, iGeoCas9 complexed to acid-degradable LNPs edited lung tissuein vivowith an average of 35% efficiency, a significant improvement over editing efficiencies observed previously using viral or non-viral delivery strategies. These results show that thermostable Cas9 RNP:LNP complexes are a powerful alternative to mRNA:LNP delivery vehicles, expanding the therapeutic potential of genome editing.
Vicarious abusive supervision among restaurant frontline employees: the role of employee industry tenure
Authors: Li Mengxuan , Wang Xingyu , Paşamehmetoğlu Aysin 
Published: November 2023

Purpose
Vicarious abusive supervision (VAS) has recently garnered the attention of hospitality researchers. VAS is prevalent in hospitality work settings characterized by long production chains and open operating environments. Based on the conservation of resources (CORs) theory, this study aims to examine how VAS influences hospitality employees’ work behaviours (i.e. supervisor-directed deviance, silence and helping behaviour) via affective rumination, with the moderating role of industry tenure as an individual contingency on the relationship between VAS and affective rumination.

Design/methodology/approach
The data were gathered from 233 restaurant frontline employees and their supervisors in Turkey. The authors tested the proposed model using partial least squares method through SmartPLS 3.

Findings
The results reveal that VAS triggers affective rumination, which, in turn, is positively related to supervisor-directed deviance and silence, and negatively related to helping behaviour. Moreover, industry tenure, as a buffer resource, significantly moderates the relationship between VAS and affective rumination.

Practical implications
To reduce the occurrence of VAS and mitigate its negative effects, managers should establish a work environment that embraces understanding and respect, pay attention to how they communicate with employees, implement appropriate interventions when VAS occurs and conduct stress management training and improve employees’ emotion regulation skills in ways that correspond to the employees’ industry experience.

Originality/value
This study advances research on VAS by offering insight into how VAS impacts employees’ work behaviours via the underlying mechanism of affective rumination through a COR lens. The findings also shed light on the salient buffering effect of industry tenure as an individual contingency.