bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Leukocyte-Rich and Leukocyte-Poor Platelet-Rich Plasma on Pressure Ulcer in a Rat Model
Authors: Yuan Ze , Wang Yanxue , Li Yudan , Lin Caina , Wang Shaoling , Wang Junchao , Ma Chao , Wu Shaoling
Published: January 2023

Pressure ulcer (PU) is a common type of chronic wound that is difficult to treat. Platelet-rich plasma (PRP) is rich in cytokines and growth factors, and it can be divided into two categories according to its leukocyte content: leukocyte-poor PRP (P-PRP) and leukocyte-rich PRP (L-PRP). PRP has been applied in a variety of wound treatments, due to its strong ability to promote repair. This study aims to investigate the therapeutic effects of PRP on PU and elucidate the role of leukocytes in the treatment process. Sprague-Dawley rats were used to establish PU models of ischemia–reperfusion injury by applying magnets externally. L-PRP, P-PRP, and saline were injected into the dermal wounds. Wound healing analysis and sampling were performed on days 3, 7, 11, and 15 after treatment. Histological examinations, real-time PCR, immunohistochemical examinations, and biomechanical assay were carried out on the wound samples. The PRP groups exhibited greater wound inflammatory response than the control group in the early stage but the response reduced rapidly as the wound healed. On days 7, 11, and 15, the PRP groups also yielded better wound healing rates and histological outcomes than the control group, with superior biomechanical properties observed on day 15. Among both PRP groups, the L-PRP group attained a higher wound healing rate than the P-PRP group on day 7, with greater significant early inflammatory responses, and more prominent angiogenesis. Therefore, PRP is proven to accelerate the healing of PU, with L-PRP being more effective in regulating inflammation and promoting angiogenesis than P-PRP.
Exploring Music Therapy Research in Preschool Settings that Include Children with Disabilities: A Scoping Review
Authors: Birch Joshua , Thompson Grace
Published: January 2023

With an increasing number of developed nations adopting elements of the social model of disability, early childhood intervention practice has evolved to place greater emphasis on an inclusive, ecological, and strength-based framework. Recent music therapy literature seems to align with this shift in policy and demonstrates how family-centered strategies can be promoted in homes. Although music therapy researchers have conducted studies in kindergartens and childcares, which are also fundamental naturalistic settings for children with disabilities, the overall breadth and nature of practice in these settings is unclear and has not been collated. This scoping review aims to identify the key characteristics of music therapy research in preschool settings that include children with disabilities, subsequently identifying key publication details, participants, therapeutic aims, outcome measures, study designs, preschool settings, delivery models, and choice of music therapy methods. A total of 19 peer-reviewed journal articles from 1988 to 2020 met inclusion and exclusion criteria, with more than half of the studies published during the last 15 years. Evaluation of these 19 studies reveals how funding policies and educational systems seem to inherently inform the application of music therapy research in early learning centers. Developmental perspectives and objectivist study designs underpin many of the included sources, with majority of the outcomes demonstrating music therapy’s positive impact upon a child’s development. Researchers outside of the United States should give greater focus to early childhood and collect data from preschools within their respective countries to broaden awareness on how music therapy can support children with disabilities in naturalistic settings.
Mutated FUS in familial amyotrophic lateral sclerosis involves multiple hnRNPs in the formation of neuronal cytoplasmic inclusions
Authors: Honda Hiroyuki , Yoshimura Motoi , Arahata Hajime , Yagita Kaoru , Sadashima Shoko , Hamasaki Hideomi , Shijo Masahiro , Koyama Sachiko , Noguchi Hideko , Sasagasako Naokazu
Published: January 2023

Fused in sarcoma (FUS), coded by FUS, is a heterogeneous nuclear ribonucleoprotein (hnRNP). FUS mutations are among the major mutations in familial amyotrophic lateral sclerosis (ALS-FUS: ALS6). The pathological hallmarks of ALS-FUS are FUS-positive neuronal cytoplasmic inclusions (NCI). We examined various hnRNPs in FUS NCIs in the hippocampus in ALS-FUS cases with different FUS mutations (Case 1, H517P; Case 2, R521C). We also examined TDP43-positive NCIs in sporadic ALS hippocampi. Immunohistochemistry was performed using primary antibodies against FUS, p-TDP43, TDP43, hnRNPA1, hnRNPD, PCBP1, PCBP2, and p62. Numerous FUS inclusions were found in the hippocampal granule and pyramidal cell layers. Double immunofluorescence revealed colocalization of FUS and p-TDP43, and FUS and PCBP2 (p-TDP43/FUS: 64.3%, PCBP2/FUS: 23.9%). Colocalization of FUS and PCBP1, however, was rare (PCBP1/FUS: 7.6%). In the hippocampi of patients with sporadic ALS, no colocalization was observed between TDP43-positive inclusions and other hnRNPs. This is the first study to show that FUS inclusions colocalize with other hnRNPs, such as TDP43, PCBP2, and PCBP1. These findings suggest that in ALS-FUS, FUS inclusions are the initiators, followed by alterations of multiple other hnRNPs, resulting in impaired RNA metabolism.
Mine Air Makes Free? Rural Liberty, Materiality, and Agency in Europe’s Long Thirteenth Century
Authors: Geltner G
Published: January 2023

Mines and miners began to proliferate in Europe from the late twelfth century on, in lockstep with the region’s accelerating economic integration and urbanization. Mining communities were often rural and remote, reflecting landlords’ capacity to attract workers through freedoms that echoed the era’s incentives for urban migration. If, according to the adage, “city air makes free,” so apparently did the mine. Yet the specific affordances of mines’ materiality, and the mobility regimes they fostered, shaped distinct social dynamics. These emerge in their complexity when mining ordinances—a new type of legal subgenre—are explored for their handling of matter and movement. Mining legislation attests that the composition of ores, the underground extension of seams, the quality of available tools, and the behavior of gas, water, and air across different topographies were salient factors over which elites had little control. The raw physical constraints on directing the flow of people and matter into, through, and out of mines thus created a network of subterranean agency that translated under certain conditions into exterranean power.
Progress on the antiferromagnetic topological insulator MnBi2Te4
Authors: Li Shuai , Liu Tianyu , Liu Chang , Wang Yayu , Lu Hai-Zhou , Xie X C
Published: January 2023

Topological materials, which feature robust surface and/or edge states, have now been a research focus in condensed matter physics. They represent a new class of materials exhibiting nontrivial topological phases, and provide a platform for exploring exotic transport phenomena, such as the quantum anomalous Hall effect and the quantum spin Hall effect. Recently, magnetic topological materials have attracted considerable interests due to the possibility to study the interplay between topological and magnetic orders. In particular, the quantum anomalous Hall and axion insulator phases can be realized in topological insulators with magnetic order. MnBi2Te4, as the first intrinsic antiferromagnetic topological insulator discovered, allows the examination of existing theoretical predictions; it has been extensively studied, and many new discoveries have been made. Here we review the progress made on MnBi2Te4 from both experimental and theoretical aspects. The bulk crystal and magnetic structures are surveyed first, followed by a review of theoretical calculations and experimental probes on the band structure and surface states, and a discussion of various exotic phases that can be realized in MnBi2Te4. The properties of MnBi2Te4 thin films and the corresponding transport studies are then reviewed, with an emphasis on the edge state transport. Possible future research directions in this field are also discussed.
New insights into the mucosal immune pathogenesis of IgA nephropathy from the perspective of COVID-19 vaccination
Authors: Ma Yaohui , Huang Yan , Xu Gaosi
Published: January 2023

Large-scale SARS-CoV-2 vaccination is one of the key strategies to curb the COVID-19 pandemic; however, there are increasing reports of IgA nephropathy following COVID-19 vaccination. The clinical manifestation, treatment and prognostic effects are different in IgAN patients who have had an onset after the first and second dose of vaccination, as well as new and recurrent IgAN patients. These conditions bring about a relatively important window for understanding the pathogenesis of IgAN. Gd-IgA1 is the core of the pathogenesis of IgAN. Most IgA is produced at mucosal sites; however, antigen-activated Toll-like receptor activation pathways expressed by antigen-presenting cells and B-cell homing receptors are different in the intestinal and respiratory mucosa, and the link between respiratory and intestinal mucosa is not well understood in the pathogenesis of IgAN. Budesonide treatment of IgAN is thought to inhibit the intestinal immune response by binding to glucocorticoid receptors in the intestinal mucosa or submucosa; however, it is unclear whether there is a therapeutic effect in respiratory mucosa-derived IgA nephropathy. The present review firstly described the relationship between the gut and respiratory mucosa, and the differences in antigen-presenting cell activation pathways and B-cell homing from the perspective of COVID-19 vaccines.
Discovery of novel Mamastroviruses in Bactrian camels and dromedaries reveals complex recombination history
Authors: Qureshi Muhammad I , Worthington Brian M , Liu Yongmei , Cheung William Y.-M , Su Shuo , Zheng Zuoyi , Li Lifeng , Lam Tommy T -Y , Guan Yi , Zhu Huachen
Published: January 2023

Virus emergence may occur through interspecies transmission and recombination of viruses coinfecting a host, with potential to pair novel and adaptive gene combinations. Camels are known to harbor diverse ribonucleic acid viruses with zoonotic and epizootic potential. Among them, astroviruses are of particular interest due to their cross-species transmission potential and endemicity in diverse host species, including humans. We conducted a molecular epidemiological survey of astroviruses in dromedaries from Saudi Arabia and Bactrian camels from Inner Mongolia, China. Herein, we deployed a hybrid sequencing approach coupling deep sequencing with rapid amplification of complementary deoxyribonucleic acid ends to characterize two novel Bactrian and eight dromedary camel astroviruses, including both partial and complete genomes. Our reported sequences expand the known diversity of dromedary camel astroviruses, highlighting potential recombination events among the astroviruses of camelids and other host species. In Bactrian camels, we detected partially conserved gene regions bearing resemblance to human astrovirus types 1, 4, and 8 although we were unable to recover complete reading frames from these samples. Continued surveillance of astroviruses in camelids, particularly Bactrian species and associated livestock, is highly recommended to identify patterns of cross-species transmission and to determine any epizootic threats and zoonotic risks posed to humans. Phylogenomic approaches are needed to investigate complex patterns of recombination among the astroviruses and to infer their evolutionary history across diverse host species.
Programmed intermittent bolus infusion vs. continuous infusion for erector spinae plane block in video-assisted thoracoscopic surgery
Authors: Taketa Yasuko , Takayanagi Yuki , Irisawa Yumi , Fujitani Taro
Published: January 2023

BACKGROUND

The optimal form of administration for erector spinae plane block has not been established.

OBJECTIVE

To compare the efficacy of programmed intermittent bolus infusion (PIB) and continuous infusion for erector spinae plane block.

DESIGN

A prospective, randomised, double-blind study.

SETTING

A single centre between June 2019 and March 2020.

PATIENTS

Included patients had an American Society of Anesthesiologists physical status 1 to 3 and were scheduled for video-assisted thoracic surgery.

INTERVENTIONS

Patients were randomised to receive continuous infusion (0.2% ropivacaine 8 ml h−1; Group C) or PIB (0.2% ropivacaine 8 ml every 2 h; Group P).

MAIN OUTCOME MEASURES

The primary outcome was the number of desensitised dermatomes in the midclavicular line, measured 21 h after first bolus injection.

RESULTS

Fifty patients were randomly assigned to each group; finally, the data of 24 and 25 patients in Group C and P, respectively, were analysed. The mean difference in the number of desensitised dermatomes in the midclavicular line at 5 and 21 h after the initial bolus administration was 1.0 [95% confidence interval (CI) 0.5 to 1.5] and 1.6 (95% CI 1.1 to 2.0), respectively, which was significantly higher in Group P than in Group C (P < 0.001). The median difference in rescue morphine consumption in the early postoperative period (0 to 24 h) was 4 (95% CI 1 to 8) mg, which was significantly lower in Group P (P = 0.035). No significant difference in the postoperative numerical rating scale score was found between the groups.

CONCLUSIONS

PIB for erector spinae plane block in video-assisted thoracic surgery resulted in a larger anaesthetised area and required a lower anaesthetic dose to maintain the analgesic effect. Therefore, it is more suitable for erector spinae plane block than continuous infusion.

TRIAL REGISTRATION

UMIN Clinical Trials Registry (UMIN-CTR, ID: UMIN000036574, Principal investigator: Taro Fujitani, 04/22/2019, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041671).
Adolescent and young adult cancers: unmet needs and closing the gaps
Authors: Berkman Amy M. , Mittal Nupur , Roth Michael E.
Published: January 2023

Purpose of review

There is a growing population of adolescent and young adult (AYA, ages 15–39 years) cancer patients and survivors, and the field of AYA oncology is rapidly evolving. Despite an increased focus on survival and quality of life for AYAs, gaps in knowledge remain. The current review focuses on what is known across several domains unique to AYA cancer care as well as areas of improvement and future directions in research and intervention.

Recent findings

Due to the developmental stages included in the AYA age range, a cancer diagnosis and treatment can affect relationships, education and employment, finances, and long-term health differently than diagnoses in younger or older populations. Recent studies that have focused on these unique aspects of AYA cancer care, including health-related quality of life (HRQoL), fertility, financial toxicity, barriers to clinical trial enrollment, genetic predisposition, and survivorship care are included in the current review.

Although studies have described many of the challenges faced by AYAs across the cancer continuum from diagnosis to survivorship, more work is needed, particularly in systematically measuring HRQoL, eliminating barriers to clinical trial enrollment, addressing financial toxicity, and increasing access to fertility preservation and high-quality survivorship care.
FDA regulatory considerations for the review of drugs intended to treat pediatric cancers and rare tumors
Authors: Bradford Diana , Singh Harpreet , Donoghue Martha
Published: January 2023

Purpose of review

We describe select recent FDA approvals in pediatric cancers and rare tumors, and the unique regulatory considerations raised by each application.

Recent findings

The approvals of naxitamab, selumetinib, selpercatinib, and crizotinib for pediatric and adolescent patients between April 2020 and January 2021 all represented first FDA approvals in their respective pediatric or adolescent populations. In addition, all represent approvals of targeted therapies administered in select patient populations, and were based on overall response rate (ORR) and duration of response (DOR) data in single-arm trials.

Recent approvals for the pediatric oncology indications have often, but not always, relied in part upon investigator-sponsored clinical trials. Early engagement with regulatory agencies to discuss drug development in rare populations is critical to obtain early agreement on trial design and streamline development. Although reliance on ORR and DOR data may be feasible to support an approval, the ability to rely on response rate depends on many factors, including the disease context, reliability of radiographic assessment, and the results of the trial. In some cases, a time-to-event endpoint may be most appropriate to assess clinical benefit; early consideration should be given to the feasibility of conducting of a randomized trial.
How the birth and death of shear layers determine confinement evolution: from the L → H transition to the density limit
Authors: Diamond Patrick H. , Singh Rameswar , Long Ting , Hong Rongjie , Ke Rui , Yan Zheng , Cao Mingyun , Tynan George R.
Published: January 2023

Electric field profile structure—especially its shear—is a natural order parameter for the edge plasma, and characterizes confinement regimes ranging from the H-mode (Wagner
et al.
1982
Phys. Rev. Lett.
49
, 1408–1412 (
doi:10.1103/PhysRevLett.49.1408
)) to the density limit (DL) (Greenwald
et al.
1988
Nucl. Fusion
28
, 2199–2207 (
doi:10.1088/0029-5515/28/12/009
)). The theoretical developments and lessons learned during 40 years of H-mode studies (Connor & Wilson 1999
Plasma Phys. Control. Fusion
42
, R1–R74 (
doi:10.1088/0741-3335/42/1/201
); Wagner 2007
Plasma Phys. Control. Fusion
49
, B1–B33 (
doi:10.1088/0741-3335/49/12b/s01
)) are applied to the shear layer collapse paradigm (Hong
et al.
2017
Nucl. Fusion
58
, 016041 (
doi:10.1088/1741-4326/aa9626
)) for the onset of DL phenomena. Results from recent experiments on edge shear layers and DL phenomenology are summarized and discussed in the light of L

→

H transition physics. The theory of shear layer collapse is then developed. We demonstrate that shear layer physics captures both the well known current (Greenwald) scaling of the DL (Greenwald 2002
Plasma Phys. Control. Fusion
44
, R27–R53 (
doi:10.1088/0741-3335/44/8/201
); Greenwald
et al.
2014
Phys. Plasmas
21
, 110501 (
doi:10.1063/1.4901920
)), as well as the emerging power scaling (Zanca, Sattin, JET Contributors 2019
Nucl. Fusion
59
, 126011 (
doi:10.1088/1741-4326/ab3b31
)). The derivation of the power scaling theory exploits an existing model, originally developed for the L

→

H transition (Diamond, Liang, Carreras, Terry 1994
Phys. Rev. Lett.
72
, 2565–2568 (
doi:10.1103/PhysRevLett.72.2565
); Kim & Diamond 2003
Phys. Rev. Lett.
90
, 185006 (
doi:10.1103/PhysRevLett.90.185006
)). We describe the enhanced particle transport events that occur following shear layer collapse. Open problems and future directions are discussed.

This article is part of a discussion meeting issue ‘H-mode transition and pedestal studies in fusion plasmas’.
H-mode transition in the TJ-II stellarator plasmas
Authors: Estrada Teresa , Hidalgo Carlos
Published: January 2023

Since the first H-mode transitions were observed in TJ-II plasmas in 2008, an extensive experimental effort has been done aiming at better physics understanding of confinement transitions. In this article, an overview of the main findings related to the L-H transition in TJ-II is presented including how the radial electric field is driven, what are the possible mechanisms for turbulence suppression and what are the related temporal and spatial scales that can impact the transition. The trigger of the L-H transition in TJ-II plasmas is found to be more correlated with the development of fluctuating

E
×
B

flows than with steady-state

E
r

effects, pointing to the role played by zonal flows in mediating the transition. Experimental evidence supporting the predator–prey relationship between turbulence and flows as the basis for the L-H transition, found for the first time in TJ-II, reinforces this conclusion. Besides, the reduction in the turbulent transport at the transition is detected at the barrier region but also in a wider radial range with weak or even zero

E
×
B

flow shear, which points to other mechanisms beyond the turbulence suppression by local sheared flows.

This article is part of a discussion meeting issue ‘H-mode transition and pedestal studies in fusion plasmas’.
Turbulence characteristics and flow dynamics impacts on the H-mode transition in favourable magnetic geometry with lower power threshold
Authors: Yan Z. , McKee G. R. , Schmitz L. , Gohil P. , Haskey S. ,   DIII-D team
Published: January 2023

The L-H transition power threshold (
P
LH
) in favourable magnetic geometry (ion ∇
B
drift pointing towards X-point) is much lower than in the unfavourable magnetic geometry (ion ∇
B
drift pointing away from X-point) on multiple tokamaks. In a systematic experiment on DIII-D, the ion ∇
B
drift direction was changed continuously from the unfavourable to favourable configuration during plasma discharges. During such process, the input neutral beam power was kept constant at a value that was above
P
LH
for favourable configuration, but lower than
P
LH
for unfavourable configuration. Toroidal field and plasma current were also kept constant and there was little change in the edge electron density
n

e

and electron temperature

T
e

profiles. The density fluctuation amplitude was reduced approaching the transition, while a large increase of turbulence Reynolds stress and flow shear were simultaneously observed. The turbulence decorrelation rate was found to increase as the ion ∇
B
drift direction was moving towards the favourable configuration, but the flow shear also increased and exceeded the turbulence decorrelation rate. These measurements demonstrate an important correlation between turbulence and turbulence-driven flow and a lowering of
P
LH
, provide insights into the underlyingphysics behind the hidden parameters and inform a more complete physics-based model of the L-H transition power threshold.

This article is part of a discussion meeting issue 'H-mode transition and pedestal studies in fusion plasmas'.
Botrytis cinereasmall RNAs are associated with tomato AGO1 and silence tomato defense-related target genes supporting cross-kingdom RNAi
Authors: He Baoye , Cai Qiang , Weiberg Arne , Li Wei , Cheng An-Po , Ouyang Shouqiang , Borkovich Katherine , Stajich Jason , Abreu-Goodger Cei , Jin Hailing
Published: January 2023

Cross-kingdom or cross-species RNA interference (RNAi) is broadly present in many interacting systems between microbes/parasites and their plant and animal hosts. A recent study by Qinet al. (2022) performed correlation analysis using global sRNA- and mRNA-deep sequencing data of culturedB. cinereaandB. cinerea-infected tomato leaves and claimed that cross-kingdom RNAi may not occur inB. cinerea–tomato interaction (Qinet al., 2022). Here, we use experimental evidence and additional bioinformatics analysis of the datasets produced by Qinet al. (2022) to identify the key reasons why a discrepancy between the conclusion of Qin et al. 2022 and previously published findings occurred. We also provided additional experimental evidence to support the presence of cross-kingdom RNAi between tomato andB. cinerea. We believe it is important to clarify the basic concept and mechanism of cross-kingdom/cross-species sRNA trafficking and illustrate proper bioinformatics analyses in this regard for all the scientists and researchers in this field.
Replacing continuous stimulation of one set of electrodes with successive stimulation of multiple sets of electrodes can improve the focality of transcranial temporal interference stimulation (tTIS), especially the focality of stimulation towards deep brain regions: A simulation study
Authors: Li Yixuan , Zhang Wei
Published: January 2023

Withdrawal statement

The authors have withdrawn their manuscript because they suspect that there may have been an issue with the data collection process, despite the fact that their proposal is original and beneficial. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Regionalized protein localization domains in the zebrafish hair cell kinocilium
Authors: Erickson Timothy , Biggers William Paul , Williams Kevin , Butland Shyanne E. , Venuto Alexandra
Published: January 2023

Sensory hair cells are the receptors for auditory, vestibular, and lateral line sensory organs in vertebrates. These cells are distinguished by “hair”-like projections from their apical surface collectively known as the hair bundle. Along with the staircase arrangement of actin-filled stereocilia, the hair bundle features a single, non-motile, true cilium called the kinocilium. The kinocilium plays important roles in bundle development and the mechanics of sensory detection. To understand more about kinocilial development and structure, we performed a transcriptomic analysis of zebrafish hair cells looking for cilia-associated genes that have yet to be characterized in hair cells. Here, we focus on three such genes -ankef1a,odf3l2a, andsaxo2- because the human or mouse orthologs are either associated with sensorineural hearing loss or are located near uncharacterized deafness loci. We made transgenic fish that express fluorescently tagged versions of their proteins, demonstrating their localization to the kinocilia of zebrafish hair cells. Furthermore, we find that Ankef1a, Odf3l2a, and Saxo2 exhibit distinct localization patterns along the length of the kinocilium and within the cell body. Lastly, we report a novel overexpression phenotype for Saxo2. Overall, these results suggest that the hair cell kinocilium is regionalized along its proximal-distal axis and set the groundwork to understand more about the roles of these kinocilial proteins in hair cells.
RGT: a toolbox for the integrative analysis of high throughput regulatory genomics data
Authors: Li Zhijian , Kuo Chao-Chung , Ticconi Fabio , Shaigan Mina , Gusmao Eduardo Gade , Allhoff Manuel , Manolov Martin , Zenke Martin , Costa Ivan G.
Published: January 2023

Background

Massive amounts of data are produced by combining next-generation sequencing (NGS) with complex biochemistry techniques to characterize regulatory genomics profiles, such as protein-DNA interaction and chromatin accessibility. Interpretation of such high-throughput data typically requires different computation methods. However, existing tools are usually developed for a specific task, which makes it challenging to analyze the data in an integrative manner.

Results

We here describe the Regulatory Genomics Toolbox (RGT), a computational library for the integrative analysis of regulatory genomics data. RGT provides different functionalities to handle genomic signals and regions. Based on that, we developed several tools to perform distinct downstream analyses, including the prediction of transcription factor binding sites using ATAC-seq data, identification of differential peaks from ChIP-seq data, and detection of triple helix mediated RNA and DNA interactions, visualization, and finding an association between distinct regulatory factors.

Conclusion

We present here RGT; a framework to facilitate the customization of computational methods to analyze genomic data for specific regulatory genomics problems. RGT is a comprehensive and flexible Python package for analyzing high throughput regulatory genomics data and is available at:https://github.com/CostaLab/reg-gen. The documentation is available at:https://reg-gen.readthedocs.io
OptoCRISPRi-HD: engineering a green-light activated CRISPRi system with high dynamic range
Authors: Chen Ke-Ning , Ma Bin-Guang
Published: January 2023

The ability to modulate gene expression is crucial for studying gene function and programming cell behaviors. Combining the reliability of CRISPRi and the precision of optogenetics, the opto-CRISPRi technique is emerging as an advanced tool for live-cell gene regulation. Since previous versions of opto-CRISPRi often exhibit a no more than 10 folds’ dynamic range due to the leakage activity, they are not suitable for targets that are sensitive to such leakage or critical for cell growth. Here, we describe a green-light activated CRISPRi system with high dynamic range (40-fold) and the flexibility of changing targets inEscherichia coli. Our optoCRISPRi-HD system can efficiently repress essential genes, non-essential genes or inhibit the initiation of DNA replication. Providing a regulative system with high resolution over space-time and extensive targets, our study would facilitate further researches involving complex gene networks, metabolic flux redirection or bioprinting.
Order of events in a developing genetic code
Authors: Yarus Michael
Published: January 2023

Preexisting partial genetic codes can fuse to evolve toward the Standard Genetic Code (SGC). Code fusion provides a path of least selection, generating a code precursor that resembles the SGC, consequently evolving quickly. Optimal evolution requires wobble coding delayed until late in primordial codon assignment, because early wobble specifically retards evolution of complete and accurate codes. Given delayed wobble, the SGC can emerge after a modest selection for more proficient encoding.
The online metacognitive control of decisions
Authors: Bénon Juliette , Lee Douglas , Hopper William , Verdeil Morgan , Pessiglione Mathias , Vinckier Fabien , Bouret Sebastien , Rouault Marion , Lebouc Raphael , Pezzulo Giovanni , Schreiweis Christiane , Burguière Eric , Daunizeau Jean
Published: January 2023

Difficult decisions typically involve mental effort, which scales with the deployment of cognitive (e.g., mnesic, attentional) resources engaged in processing decision-relevant information. But how does the brain regulate mental effort? A possibility is that the brain optimizes a resource allocation problem, whereby the amount of invested resources balances its expected cost (i.e. effort) and benefit. Our working assumption is that subjective decision confidence serves as the benefit term of the resource allocation problem, hence the “metacognitive” nature of decision control. Here, we present a computational model for theonline metacognitive control of decisionsor oMCD. Formally, oMCD is a Markov Decision Process that optimally solves the ensuing resource allocation problem under agnostic assumptions about the inner workings of the underlying decision system. We demonstrate how this makes oMCD a quasi-optimal control policy for a broad class of decision processes, including -but not limited to-progressive attribute integration. We disclose oMCD’s main properties (in terms of choice, confidence and response time), and show that they reproduce most established empirical results in the field of value-based decision making. Finally, we discuss the possible connections between oMCD and most prominent neurocognitive theories about decision control and mental effort regulation.
Innovation subsidies and entrepreneurial activity in an emerging market
Authors: Wang Chun-Hsien
Published: January 2023

Purpose

This study aims to find that entrepreneurial activities can spur entrepreneurial firms' superior performance, but this effect is contingent on the different levels of government innovation subsidies. Extending the institutional perspective explanation and entrepreneurship perspective explanation, this study examines how a firm's entrepreneurial orientation (EO) affects its superior performance when it receives innovation subsidies.

Design/methodology/approach

Entrepreneurial firms in China, an emerging economy, are taken as the context for empirical evidence. A large-scale questionnaire survey is used for firm data collection. Ordinary least squares (OLS) regression is employed to test the hypothesized model using a sample of 287 entrepreneurial firms.

Findings

The results show a curvilinear, inverse U-shaped moderating effect in the relationship between EO and firm performance. This relationship is strongest at intermediate levels of innovation subsidies but is comparatively weaker when innovation subsidies are low or high.

Originality/value

The study contributes to entrepreneurship research by examining the nonlinear moderating effect of innovation subsidies on entrepreneurial firms' performance. The study also contributes to entrepreneurship theory by elaborating on the innovation subsidy scheme and how it facilitates the development of entrepreneurial activity.
Nurturing mental health and well-being using ordinary farms
Authors: Deegan Deirdre , Fingleton Emma , McEvoy Joseph James , Quigley Kate
Published: January 2023

Purpose

This practice piece aims to review an occupational therapy led pilot programme – social farming as an intervention option in an adult community mental health setting in Ireland. It will also reflect on the practical implications of delivering the natural surroundings based programme through the COVID-19 pandemic and plans for the future development of such programmes in adult mental health services.

Design/methodology/approach

The Occupational Circumstances Assessment Interview Rating Scale (OCAIRS) was used to measure occupational participation (Forsyth, 2005). This was administered with participants’ pre and post their participation in the 10-week programme. An internal questionnaire was developed to further capture both the participant and farmer experiences of the social farming programme.

Findings

Whilst improvements were noted in a number of OCAIRS domains, it was difficult to identify small changes over a short period of time. The main domains of change were habits, roles, interests and personal causation. The success of the social farming placements was also reflected in the internal questionnaire. The pilot programme has resulted in the further development of the social farming programme and securing of funding for placements for five years.

Originality/value

It would be beneficial to consider other standardised assessments that assess quality of life and occupation for future placements. It is also beneficial to consider practical implications in delivering a social farming programme, particularly to those with barriers to transport. It is hoped this paper will contribute to the growing knowledge of social farming as a meaningful therapeutic intervention in mental health occupational therapy practice.
The role of teachers’ views and attitudes in the academic achievement of Roma students
Authors: Fehérvári Anikó
Published: January 2023

Purpose

Inclusive education of Roma students is a priority goal of the European Union. However, synthesising analyses reveal precious little progress scored in this area. This study aims to explore the factors that have affect Roma students’ academic achievement, specifically, whether the views of their teachers have an impact on the performance besides individual and family background factors.

Design/methodology/approach

A large-sample questionnaire-based research study was conducted in the 2019/2020 academic year involving 4,674 seventh-grade students and 2,656 teachers from 194 Hungarian schools. On a self-admission basis, 374 of the students were Roma.

Findings

In the schools examined, the performance of Roma students is poorer, their commitment to learning is weaker, yet they have a higher opinion of their school and their teachers than their non-Roma peers. The involvement of majority students in extracurricular private tutoring, particularly foreign language learning, is greater. Roma students’ academic achievement is mainly affected by individual background factors, in particular by their school history.

Originality/value

The findings suggest that although the role of the school and pedagogical views is important, they are not predominant factors determining Roma students’ performance. The explanatory power of individual characteristics is stronger than that of school factors. The comparison between Roma and non-Roma students also shows that cooperation between different sectors (education, social and health) would be essential within and outside school in terms of home learning conditions, digital access and student well-being.
How does particulate air pollution affect barrier functions and inflammatory activity of lung vascular endothelium?
Authors: Olesiejuk Krzysztof , Chałubiński Maciej
Published: January 2023

Both particulate matter and gaseous components of air pollution have already been shown to increase cardiovascular mortality in numerous studies. It is, however, important to note that on their way to the bloodstream the polluting agents pass the lung barrier. Inside the alveoli, particles of approximately 0.4–1 μm are most efficiently deposited and commonly undergo phagocytosis by lung macrophages. Not only the soluble agents, but also particles fine enough to leave the alveoli enter the bloodstream in this finite part of the endothelium, reaching thus higher concentrations in close proximity of the alveoli and endothelium. Additionally, deposits of particulate matter linger in direct proximity of the endothelial cells and may induce inflammation, immune responses, and influence endothelial barrier dysfunction thus increasing PM bioavailability in positive feedback. The presented discussion provides an overview of possible components of indoor PM and how endothelium is thus influenced, with emphasis on lung vascular endothelium and clinical perspectives.
The Fontan immunophenotype and post‐transplant outcomes in children: A multi‐institutional study
Authors: Mantell Benjamin S. , Azeka Estela , Cantor Ryan S. , Carlo Waldemar F. , Chrisant Maryanne , Dykes John C. , Hoffman Timothy M. , Kirklin James K. , Koehl Devin , L'Ecuyer Thomas J. , McAllister Jennie M. , Prada‐Ruiz Adriana C. , Richmond Marc E.
Published: January 2023

Background

Patients after Fontan palliation represent a growing pediatric population requiring heart transplant (HTx) and often have lymphopenia (L) and/or hypogammaglobinemia that may be exacerbated by protein‐losing enteropathy (PLE, P). The post‐HTx effects of this altered immune phenotype are not well studied.

Methods

In this study of the Pediatric Heart Transplant Society Registry, 106 Fontan patients who underwent HTx between 2005 and 2018 were analyzed. The impact of lymphopenia and PLE on graft survival, infection, rejection, and malignancy was analyzed at 1 and 5 years post‐HTx.

Results

The following combinations of lymphopenia and PLE were noted: +L+P, n = 37; +L−P, n = 23; −L+P, n = 10; and −L−P, n = 36. Graft survival between the groups was similar within the first year after transplant (+L+P: 86%, +L−P: 86%, −L+P: 87%, −L−P: 89%, p = .9). Freedom from first infection post‐HTx was greatest among −L−P patients compared to patients with either PLE, lymphopenia, or both; with a 22.1% infection incidence in the −L−P group and 41.4% in all others. These patients had a significantly lower infection rate in the first year after HTx (+L+P: 1.03, +L−P: 1, −L+P: 1.3, −L−P: 0.3 infections/year, p < .001) and were similar to a non‐single ventricle CHD control group (0.4 infections/year). Neither freedom from rejection nor freedom from malignancy 1 and 5 years post‐HTx, differed among the groups.

Conclusions

Fontan patients with altered immunophenotype, with lymphopenia and/or PLE, are at increased risk of infection post‐HTx, although have similar early survival and freedom from rejection and malignancy. These data may encourage alternative immunosuppression strategies and enhanced monitoring for this growing subset of patients.
Long‐term mortality in pediatric solid organ recipients—A nationwide study
Authors: Salonen Rebekka , Jahnukainen Timo , Nikkilä Atte , Endén Kira
Published: January 2023

Background

The present study aimed at investigating long‐term mortality of patients who underwent solid organ transplantation during childhood and at identifying their causes of death.

Methods

A cohort of 233 pediatric solid organ transplant recipients who had a kidney, liver, or heart transplantation between 1982 and 2015 in Finland were studied. Year of birth‐, sex‐, and hometown‐matched controls (n = 1157) were identified using the Population Register Center registry. The Causes of Death Registry was utilized to identify the causes of death.

Results

Among the transplant recipients, there were 60 (25.8%) deaths (median follow‐up 18.0 years, interquartile range of 11.0–23.0 years). Transplant recipients' risk of death was nearly 130‐fold higher than that of the controls (95% CI 51.9–1784.6). The 20‐year survival rates for kidney, liver, and heart recipients were 86.1% (95% CI 79.9%–92.3%), 58.5% (95% CI 46.2%–74.1%), and 61.4% (95% CI 48.1%–78.4%), respectively. The most common causes of death were cardiovascular diseases (23%), infections (22%), and malignancies (17%). There were no significant differences in survival based on sex or transplantation era.

Conclusion

The late mortality is still significantly higher among pediatric solid organ recipients in comparison with controls. Cardiovascular complications, infections, and cancers are the main causes of late mortality for all studied transplant groups. These findings emphasize the cruciality of careful monitoring of pediatric transplant recipients in order to reduce long‐term mortality.
Localised chronic fibrosing vasculitis versus erythema elevatum diutinum
Authors: Tabata Mika M , Lin William M , Goldstein Jay , Quinn Timothy R , Chen Steven T
Published: January 2023

A woman in her 70s was referred for a painless plaque on the shin, present for 2 years and progressing in thickness. Examination revealed a large erythematous to violaceous indurated plaque with cobblestone appearance. Biopsy revealed an inflammatory infiltrate of neutrophils with scattered histiocytes, lymphocytes, eosinophils and plasma cells interspersed with areas of lamellar fibrosis and focal areas of vascular damage, suggestive of a localised chronic fibrosing vasculitis of the skin. Localised chronic fibrosing vasculitis is a rare dermatosis, typically presenting as ulcerated violet-red nodules, which can appear histologically similar to erythema elevatum diutinum (EED), which typically presents as red-brown annular plaques. EED may have a predominance of neutrophils and granulomas, while chronic fibrosing vasculitis may have a sparse infiltrate of mixed inflammatory cells without granulomas. While dapsone is a first-line treatment for EED, there are no formal guidelines on the treatment of localised chronic fibrosing vasculitis. Given the neutrophils in this sample and similarities with EED, this patient was treated with oral dapsone, resulting in plaque improvement.
Pneumothorax in patients with COPD and emphysema receiving home chronic non-invasive ventilation: is it the emphysema phenotype or ventilator setting?
Authors: Sloots Joanne M , Duiverman Marieke L
Published: January 2023

We describe three patients with chronic obstructive pulmonary disease (COPD) and emphysema who developed a pneumothorax while receiving chronic home non-invasive ventilation (NIV). These cases raise the question whether the high alveolar pressures given by NIV may have contributed to the development of their pneumothorax by barotrauma. Pneumothorax in patients with COPD receiving NIV is uncommon, the pressures in our patients with COPD who developed pneumothorax were not extremely high and time to development of pneumothorax was relatively long after the initiation of NIV. Further, in our patients, the CT scan showed paraseptal emphysema, a known risk factor for pneumothorax. This suggests that COPD/emphysema phenotype is probably a more important factor for indicating pneumothorax risk than ventilator settings. Better phenotyping of patients with COPD in whom benefits of NIV can be expected at minimal risk of serious side-effects is needed to inform our patients properly and bring the field of chronic NIV in COPD forward.
Fibrinolytic therapy in patients with COVID-19 and ARDS: protocol for a systematic review and meta-analysis
Authors: Savioli Felicio , Ribeiro dos Santos Lucas , Duarte Marcio Luis , Feitosa do Carmo Andreia Cristina , Gois Aecio , Nakano Luis , Da Silva Ramos Fernando Jose , Pastore Laerte , Costa Eduardo Leite Vieira
Published: January 2023

Introduction

In COVID-19-related acute respiratory distress syndrome (ARDS), the clot play a role in gas exchange abnormalities. Fibrinolytic therapy can improve alveolar ventilation by restoring blood flow. In this systematic review and meta-analysis protocol, we aim to assess the safety and efficacy of fibrinolytic therapy in such a population.

Methods

We will perform a systematic search in MEDLINE, EMBASE, Cochrane CENTRAL and LILACS databases without language restrictions for relevant randomised controlled trials (RCTs) and quasi-RCTs. Two review authors will independently perform data extraction and quality assessments of data from included studies. In case of divergence, a third author will be contacted. The Cochrane handbook will be used for guidance. If the results are not appropriate for a meta-analysis, a descriptive analysis will be performed.

Discussion

This systematic review and meta-analysis protocol will provide current evidence about the safety and efficacy of fibrinolytic therapy in patients with COVID-19 and ARDS. These findings will provide if fibrinolytic therapy might be an option for a desperate clinical setting, where all medical efforts have been used.

PROSPERO registration number

PROSPERO CRD42020187482.

Ethics and dissemination

Ethics committee approval is not necessary. We intend to update the public registry, report any protocol amendments and publish the results in a widely accessible journal.
Evaluation of the England Community Pharmacy Quality Scheme (2018–2019 and 2019–2020) in reducing harm from NSAIDs in older patients
Authors: Parekh Sejal , Livingstone Carina , Jani Yogini H
Published: January 2023

Introduction

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic and anti-inflammatory action, but the gastrointestinal (GI) adverse effects are a known cause of preventable harm. A medication safety audit was incentivised for community pharmacies in England in 2 successive years as part of the Pharmacy Quality Scheme (PQS) to address GI safety of NSAIDs.

Aims

To evaluate community pharmacy’s contributions to NSAID safety and determine any change between audit 1 (2018–2019) and audit 2 (2019–2020).

Method

Patients aged 65 years or over prescribed an NSAID were included in both audits. The audit tool assessed compliance with national standards relating to co-prescribed gastroprotection, referrals to the prescriber and patient advice on long-term NSAID use and effects, with responses submitted via an online portal. Descriptive analyses were performed to explore differences between the years and tested for significance using Χ2tests. Qualitative data were analysed using an inductive thematic approach.

Key findings

Data from 91 252 patients in audit 1 and 73 992 in audit 2 were analysed. More patients were prescribed gastroprotection in audit 2 (85.0%) than audit 1 (80.7%, p<0.001). More patients without gastroprotection in audit 2 had a current or recent referral (67.5%) than in audit 1 (58.8%, p<0.001). Verbal or other communications between pharmacists and patients about their NSAID medication were reported more frequently in audit 2 (76.0% vs 63.5%, p<0.001).

Conclusion

During two audits, community pharmacists in England reported referring more than 15 000 patients at risk of preventable harm from NSAIDs to prescribers for review. The audits demonstrated significant potential for year-on-year improvement in GI safety for a large cohort of older patients prescribed NSAIDs. This evaluation provides evidence of how the PQS can effectively address a specific aspect of medicines safety and the place of community pharmacy more broadly in improving medicines safety.