bluuebunny/crossref_metadata_2025 huggingface dataset:
The complex relationship between disease resistance and yield in crops
Authors: Derbyshire Mark C. , Newman Toby E. , Thomas William J. W. , Batley Jacqueline , Edwards David
Published: May 2024

In plants, growth and defence are controlled by many molecular pathways that are antagonistic to one another. This results in a ‘growth‐defence trade‐off’, where plants temporarily reduce growth in response to pests or diseases. Due to this antagonism, genetic variants that improve resistance often reduce growth and vice versa. Therefore, in natural populations, the most disease resistant individuals are often the slowest growing. In crops, slow growth may translate into a yield penalty, but resistance is essential for protecting yield in the presence of disease. Therefore, plant breeders must balance these traits to ensure optimal yield potential and yield stability. In crops, both qualitative and quantitative disease resistance are often linked with genetic variants that cause yield penalties, but this is not always the case. Furthermore, both crop yield and disease resistance are complex traits influenced by many aspects of the plant's physiology, morphology and environment, and the relationship between the molecular growth‐defence trade‐off and disease resistance‐yield antagonism is not well‐understood. In this article, we highlight research from the last 2 years on the molecular mechanistic basis of the antagonism between defence and growth. We then discuss the interaction between disease resistance and crop yield from a breeding perspective, outlining the complexity and nuances of this relationship and where research can aid practical methods for simultaneous improvement of yield potential and disease resistance.
Effect of light‐induced changes in leaf anatomy on intercellular and cellular components of mesophyll resistance for CO2 in Fagus sylvatica
Authors: Janová J. , Kubásek J. , Grams T. E. E. , Zeisler‐Diehl V. , Schreiber L. , Šantrůček J.
Published: May 2024

Mesophyll resistance for CO2 diffusion (rm) is one of the main limitations for photosynthesis and plant growth. Breeding new varieties with lower rm requires knowledge of its distinct components.

We tested new method for estimating the relative drawdowns of CO2 concentration (c) across hypostomatous leaves of Fagus sylvatica. This technique yields values of the ratio of the internal CO2 concentrations at the adaxial and abaxial leaf side, cd/cb, the drawdown in the intercellular air space (IAS), and intracellular drawdown between IAS and chloroplast stroma, cc/cbd. The method is based on carbon isotope composition of leaf dry matter and epicuticular wax isolated from upper and lower leaf sides. We investigated leaves from tree‐canopy profile to analyse the effects of light and leaf anatomy on the drawdowns and partitioning of rm into its inter‐ (rIAS) and intracellular (rliq) components. Validity of the new method was tested by independent measurements of rm using conventional isotopic and gas exchange techniques.

73% of investigated leaves had adaxial epicuticular wax enriched in 13C compared to abaxial wax (by 0.50‰ on average), yielding 0.98 and 0.70 for average of cd/cb and cc/cbd, respectively. The rIAS to rliq proportion were 5.5:94.5% in sun‐exposed and 14.8:85.2% in shaded leaves. cc dropped to less than half of the atmospheric value in the sunlit and to about two‐thirds of it in shaded leaves.

This method shows that rIAS is minor but not negligible part of rm and reflects leaf anatomy traits, i.e. leaf mass per area and thickness.
A registered report of a two‐site study of variations of the flanker task: ERN experimental effects and data quality
Authors: Clayson Peter E. , Rocha Harold A. , McDonald Julia B. , Baldwin Scott A. , Larson Michael J.
Published: May 2024

Error‐related negativity is a widely used measure of error monitoring, and many projects are independently moving ERN recorded during a flanker task toward standardization, optimization, and eventual clinical application. However, each project uses a different version of the flanker task and tacitly assumes ERN is functionally equivalent across each version. The routine neglect of a rigorous test of this assumption undermines efforts to integrate ERN findings across tasks, optimize and standardize ERN assessment, and widely apply ERN in clinical trials. The purpose of this registered report was to determine whether ERN shows similar experimental effects (correct vs. error trials) and data quality (intraindividual variability) during three commonly used versions of a flanker task. ERN was recorded from 172 participants during three versions of a flanker task across two study sites. ERN scores showed numerical differences between tasks, raising questions about the comparability of ERN findings across studies and tasks. Although ERN scores from all three versions of the flanker task yielded high data quality and internal consistency, one version did outperform the other two in terms of the size of experimental effects and the data quality. Exploratory analyses of the error positivity (Pe) provided tentative support for the other two versions of the task over the paradigm that appeared optimal for ERN. The present study provides a roadmap for how to statistically compare psychometric characteristics of ERP scores across paradigms and gives preliminary recommendations for flanker tasks to use for ERN‐ and Pe‐focused studies.
Heterogeneous impacts of sudden stops of international capital flows on economic growth
Authors: Fan Xiaoyun , Wang Wei , Xu Zitong , Yang Haoxi
Published: May 2024

This paper empirically examines the heterogeneous impacts of sudden stops in international capital flows on economic growth. We identified 24 sudden stop episodes since 1990 and employed a counterfactual method with cross‐economy panel data to evaluate the impact of each episode on economic growth. The results indicate that 14 sudden stop episodes triggered significant economic decline, with varying magnitudes; 9 episodes were accompanied by insignificant economic downturn, and 1 episode was followed by economic growth. We further utilize the treatment effect derived from the counterfactual analysis to investigate the causes of these heterogeneous impacts of sudden stops on economic growth. Results obtained from the panel data model suggest that external debt, financial development, and real investment return are the main driving forces contributing to the observed heterogeneity.
Sirolimus is effective and safe in childhood relapsed‐refractory autoimmune cytopenias: A multicentre study
Authors: Acar Sultan Okur , Tahta Neryal , Al Işık Odaman , Erdem Melek , Gözmen Salih , Karapınar Tuba Hilkay , Kılınç Burcu , Celkan Tiraje , Kirkiz Serap , Koçak Ülker , Ören Hale , Yıldırım Ayşen Türedi , Arslantaş Esra , Ayhan Aylin Canbolat , Oymak Yeşim
Published: May 2024

Autoimmune cytopenias are a heterogeneous group of disorders characterized by immune‐mediated destruction of haematopoietic cell lines. Effective and well‐tolerated treatment options for relapsed‐refractory immune cytopenias are limited. In this study, the aim was to evaluate the efficacy and safety of sirolimus in this disease group within the paediatric age group. The study enrolled patients in the paediatric age group who used sirolimus with a diagnosis of immune cytopenia between December 2010 and December 2020, followed at six centres in Turkey. Of the 17 patients, five (29.4%) were treated for autoimmune haemolytic anaemia (AIHA), six (35.2%) for immune thrombocytopenic purpura (ITP) and six (35.2%) for Evans syndrome (ES). The mean response time was 2.7 months (range, 0–9 months). Complete response (CR) and partial response (PR) were obtained in 13 of 17 patients (76.4%) and nonresponse (NR) in four patients (23.5%). Among the 13 patients who achieved CR, three of them were NR in the follow‐up and two of them had remission with low‐dose steroid and sirolimus. Thus, overall response rate (ORR) was achieved in 12 of 17 patients (70.5%). In conclusion, sirolimus may be an effective and safe option in paediatric patients with relapsed‐refractory immune cytopenia.
Cox processes driven by transformed Gaussian processes on linear networks—A review and new contributions
Authors: Møller Jesper , Rasmussen Jakob G.
Published: May 2024

There is a lack of point process models on linear networks. For an arbitrary linear network, we consider new models for a Cox process with an isotropic pair correlation function obtained in various ways by transforming an isotropic Gaussian process which is used for driving the random intensity function of the Cox process. In particular, we introduce three model classes given by log Gaussian, interrupted, and permanental Cox processes on linear networks, and consider for the first time statistical procedures and applications for parametric families of such models. Moreover, we construct new simulation algorithms for Gaussian processes on linear networks and discuss whether the geodesic metric or the resistance metric should be used for the kind of Cox processes studied in this paper.
Importancia de la función simbólica para la adquisición de la lectura
Authors: González Moreno Claudia Ximena , Solovieva Yulia
Published: May 2024

Se presenta el proceso de evolución de la función simbólica desde la edad preescolar(con el juego de roles sociales)hasta la edad escolar(con la introducción del aprendizaje formal de la lectura).Se parte de la relación entre la función simbólica y el proceso lector, y luego se analizan sus implicaciones en el desarrollo infantil. Se concluye que entre más se fomente la expresión de ideas verbales de un texto en grupo de manera dialogada, se alcanzan mejores niveles de representaciones simbólicas, y por consiguiente se progresa en la comprensión lectora en el niño, porque se generan actualizaciones y transformaciones de la información.
Face the (unamplified) music: Key findings for musicians
Authors: Dance S. , Zepidou G.
Published: May 2024

Music is complex. There are risks to hearing health associated with playing due to excessive sound exposure. Face the Music is an on-going cross-sectional project to assess the risks to unamplified classical musicians. Key findings over the first fifteen years are presented based on the research undertaken with a leading conservatoire on more than 5000 classical music students. The work covers hearing health surveillance, education and awareness, sound exposure, and new technology. The future of the research programme is discussed along with opportunities in objective hearing health assessment and new acoustic solutions. A lot has changed in fifteen years, but the research was driven by a change in United Kingdom legislation. It is hoped that the research results can inform future regulation.
LINC08148 promotes the caveola-mediated endocytosis of Zika virus through upregulating transcription of Src
Authors: Huo Zhiting , Zhu Xuanfeng , Peng Qinyu , Chen Cancan , Yang Xiaoyi , Huang Changbai , Xiang Yincheng , Tian Qingju , Liu Jingyu , Liu Chao , Zhang Ping
Published: May 2024

Long non-coding RNAs (lncRNAs) represent a new group of host factors involved in viral infection. Current study identified an intergenic lncRNA, LINC08148, as a proviral factor of Zika virus (ZIKV) and Dengue virus 2 (DENV2). Knockout (KO) or silencing of LINC08148 decreases the replication of ZIKV and DENV2. LINC08148 mainly acts at the endocytosis step of ZIKV but at a later stage of DENV2. RNA-seq analysis reveals that LINC08148 knockout downregulates the transcription levels of five endocytosis-related genes including
AP2B1
,
CHMP4C
,
DNM1
,
FCHO1
, and
Src
. Among them, loss of Src significantly decreases the uptake of ZIKV.
Trans
-complementation of Src in the LINC08148
KO
cells largely restores the caveola-mediated endocytosis of ZIKV, indicating that the proviral effect of LINC08148 is exerted through Src. Finally, LINC08148 upregulates the
Src
transcription through associating with its transcription factor SP1. This work establishes an essential role of LINC08148 in the ZIKV entry, underscoring a significance of lncRNAs in the viral infection.

IMPORTANCE

Long non-coding RNAs (lncRNAs), like proteins, participate in viral infection. However, functions of most lncRNAs remain unknown. In this study, we performed a functional screen based on microarray data and identified a new proviral lncRNA, LINC08148. Then, we uncovered that LINC08148 is involved in the caveola-mediated endocytosis of ZIKV, rather than the classical clathrin-mediated endocytosis. Mechanistically, LINC08148 upregulates the transcription of Src, an initiator of caveola-mediated endocytosis, through binding to its transcription factor SP1. This study identifies a new lncRNA involved in the ZIKV infection, suggesting lncRNAs and cellular proteins are closely linked and cooperate to regulate viral infection.
Whole-genome sequencing of
Paenibacillus phoenicis
isolated from the Phoenix Mars Lander spacecraft assembly facility
Authors: Garcia Andrew , Rivera Romar , Simpson Anna C. , Singh Nitin K. , Green Stefan , Venkateswaran Kasthuri
Published: May 2024

The genome of
Paenibacillus phoenicis,
a spore-forming bacterium isolated from the spacecraft assembly facility of the Phoenix mission, was generated via hybrid assembly by merging short and long reads. Examining this genome may shed light on strategies to minimize the risk of contaminating extraterrestrial environments with Earth-based microorganisms.
Short-term dietary fiber interventions produce consistent gut microbiome responses across studies
Authors: Rodriguez Cynthia I. , Isobe Kazuo , Martiny Jennifer B. H.
Published: May 2024

The composition of the human gut microbiome varies tremendously among individuals, making the effects of dietary or treatment interventions difficult to detect and characterize. The consumption of fiber is important for gut health, yet the specific effects of increased fiber intake on the gut microbiome vary across studies. The variation in study outcomes might be due to inter-individual (or inter-population) variation or to the details of the interventions including the types of fiber, length of study, size of cohort, and molecular approaches. Thus, to identify generally (on average) consistent fiber-induced responses in the gut microbiome of healthy individuals, we re-analyzed 16S rRNA sequencing data from 21 dietary fiber interventions from 12 human studies, which included 2,564 fecal samples from 538 subjects across all interventions. Short-term increases in dietary fiber consumption resulted in highly consistent gut bacterial community responses across studies. Increased fiber consumption explained an average of 1.5% of compositional variation (vs 82% of variation attributed to the individual), reduced alpha-diversity, and resulted in phylogenetically conserved responses in relative abundances among bacterial taxa. Additionally, we identified bacterial clades, at approximately the genus level, that were highly consistent in their response (on average, increasing or decreasing in their relative abundance) to dietary fiber interventions across the studies.

IMPORTANCE

Our study is an example of the power of synthesizing and reanalyzing 16S rRNA microbiome data from many intervention studies. Despite high inter-individual variation of the composition of the human gut microbiome, dietary fiber interventions cause a consistent response both in the degree of change and the particular taxa that respond to increased fiber.
Relationship between Respiration Rate and Body Weight in Arctic Copepods at Subzero Temperature
Authors: Arashkevich E. G. , Drits A. V. , Pasternak A. F. , Frenkel S. E. , Karmanov V. A.
Published: May 2024

The dependence of the respiration rate (R) on an animal’s weight (W) is described by the equation R = aW  
b
, where the exponential coefficient b is usually taken equal to 3/4. However, several authors have indicated that the value of coefficient b may vary with temperature changes, as well as during ontogeny. In Arctic seas, copepods spend most of their lives at temperatures below or close to zero. Meanwhile, there are very few respiration rate measurements at temperature ≤ 0°C, which does not allow us to estimate the value of coefficient b at subzero temperature. The study was carried out on three cruises of the R/V Akademik Mstislav Keldysh in the Siberian Arctic seas in 2018–2020. Copepods caught from the sea were adapted to the experimental temperature and placed in tightly capped vials filled with filtered seawater for 24 h. The oxygen concentration was measured with a fiber-optic oxygen probe. The results of 120 respiration rate measurements and 111 body carbon measurements in five species of copepods at a temperature of –1.5°C are presented. The obtained relationship between body carbon content (W) and prosome length (L) is described by the equation W = 6.982L
3.221, and the dependence of respiration on body weight is described by the equation R = 0.077W  0.753. No effect of subzero temperature on coefficient b was revealed. The parameters of regression R(W) did not change with the ontogenetic development of Calanus glacialis.
Tactics of Fish Behavior in the Water Flow during Starvation
Authors: Pavlov D. S. , Parshina V. Yu. , Kostin V. V.
Published: May 2024

Individual movement parameters for the zebrafish Danio rerio and the Prussian carp Carassius gibelio during starvation for 12 days have been determined in an experimental hydrodynamic installation circular tank. The fishes represent two tactics of behavioral responses on starvation. The tactics of unidirectional responses have been manifested in the movement of individuals in one direction relative to the water flow on days 2–5 of starvation. The tactics of multidirectional responses have been manifested on days 10–12 of starvation as movements in different directions relative to the water flow. The population advantages of such behavioral tactics of fish response to an unfavorable factor are considered.
Assessing the impact of obesity interventions in the early years: a systematic review of UK-based studies
Authors: Michalopoulou Semina , Sifaki Maria , Packer Jessica , Lanigan Julie , Stansfield Claire , Viner Russell M , Russell Simon
Published: May 2024

Objectives

Childhood obesity rates in the UK are high. The early years of childhood are critical for establishing healthy behaviours and offer interventional opportunities. We aimed to identify studies evaluating the impact of UK-based obesity interventions in early childhood.

Design

Systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data sources

Nine databases were searched in March 2023. Eligibility criteria: We included UK-based obesity intervention studies delivered to children aged 6 months to 5 years that had diet and/or physical activity components and reported anthropometric outcomes. The primary outcome of interest was z-score Body Mass Index (zBMI) change (within and between subjects). Studies evaluating the effects of breastfeeding interventions were not included as obesity prevention interventions, given that best-practice formula feeding is also likely to encourage healthy growth. The publication date for studies was limited to the previous 12 years (2011–23), as earlier reviews found few evaluations of interventions in the UK.

Data extraction and synthesis

The reviewers worked independently using standardised approach to search, screen and code the included studies. Risk of bias was assessed using Cochrane tools (ROB 2 or ROBINS-I).

Results

Six trials (five studies) were identified, including two randomised controlled trials (RCT), one cluster randomised trial (CRT), two feasibility CRTs and one impact assessment. The total number of participants was 566. Three trials focused on disadvantaged families and two included high-risk children categorised as having overweight or obesity. Compared with baseline, five interventions reported reductions in zBMI, three of which were statistically significant (p<0.05). Compared with control, five interventions showed zBMI reductions, one of which was significant. Only two trials were followed up beyond 12 months. All studies were found to have a high risk of bias. Meta-analysis was not possible due to the heterogeneity of studies.

Conclusion

UK evidence was limited but some interventions showed promising results in promoting healthy growth. As part of a programme of policies, interventions in the early years may have an important role in reducing the risk of childhood obesity.

PROSPERO registration number

CRD42021290676
Exploring community participation in vectorborne disease control in Southeast Asia: a scoping review protocol
Authors: Naserrudin Nurul Athirah , Adhikari Bipin , Culleton Richard , Hod Rozita , Saffree Jeffree Mohammad , Ahmed Kamruddin , Hassan Mohd Rohaizat
Published: May 2024

Introduction

Vector borne diseases (VBDs) present significant public health challenges in Southeast Asia (SEA), and the increasing number of cases threatens vulnerable communities. Inadequate vector control and management have been linked to the spread of VBDs. To address these issues, community participation has been proposed as a promising approach to enhance health programmes and control of VBDs. This article outlines a protocol for a scoping review of the published literature on community-participation approaches to control VBDs in the SEA region. The primary research question is ‘How does community participation complement the control of VBDs in SEA?’ This review aims to provide an overview of various approaches and identify barriers and facilitators to effective implementation.

Methods and analysis

The research questions will guide the scoping review. In stage 1, peer-reviewed publications from PubMed, Web of Science and Scopus will be searched using predefined search terms related to community-based approaches and VBDs in the SEA region, English, Indonesian and Malay published between 2012 and 2022. In stage 2, the references from relevant articles will be screened for eligibility. In stage 3, eligible articles will be charted in Microsoft Excel to facilitate the review process, and studies will be characterised based on the investigated diseases; this review will also highlight the methodological context of these studies. In stage 4, a thematic analysis will be conducted to derive meaningful findings from the dataset relevant to the research inquiry, followed by writing the results in stage 5. This scoping review aims to be the first to explore community participation in VBD control in the SEA population, providing valuable insights for future research and stakeholders involved in disease control.

Ethics and dissemination

This scoping review does not require ethical approval because the methodology synthesises information from available articles. This review is planned for dissemination in academic journals, conference presentations and shared with stakeholders as part of knowledge sharing among those involved in VBD control.
Association between non-registration of chronic kidney disease and mortality and cardiovascular outcome: a time-to-event analysis of retrospective primary care data
Authors: Van den Wyngaert Ine , Mamouris Pavlos , Ali Endale Alemayehu , Vaes Bert , Van Pottelbergh Gijs
Published: May 2024

Objective

Patients with impaired kidney function and increased albuminuria are at risk of developing cardiovascular disease (CVD). Previous research has revealed that a substantial proportion of patients with chronic kidney disease (CKD) do not get a registered diagnosis in the electronic health record of the general practitioner. The aim of this study was to investigate the association between non-registration of CKD and all-cause mortality and cardiovascular outcome.

Design and setting

A retrospective study in primary care.

Methods

The analyses were carried out in the INTEGO database, a general practice-based morbidity registration network in Flanders, Belgium. The study used INTEGO data from the year 2018 for all patients ≥18 years old, including 10 551 patients. To assess the risk of mortality and CVD, a time-to-event analysis was performed. Cox proportional hazard model was used to evaluate the association between non-registration and incidence of all-cause mortality and cardiovascular events with mortality as a competing risk. Subgroup analyses were performed for estimated glomerular filtration rate stages (3A, 3B, 4 and 5). Multiple imputation was done following the methodology of Mamouriset al.

Results

Mortality was higher in patients with non-registered CKD compared with patients with registered CKD (HR 1.29, 95% CI 1.19 to 1.41). Non-registration of CKD was not associated with an increased risk for the development of CVD (HR 0.92, 95% CI 0.77 to 1.11).

Conclusion

An association between non-registration and all-cause mortality was identified, although no such association was apparent for CVD.
Analgesia for the treatment of acute pancreatitis: a protocol for a systematic review and network meta-analysis
Authors: Subramani Sriya S , Berg Alaina C , Kral Lee A , Murad Mohammad Hassan , Smith Abigail , Phillips Anna Evans , Yadav Dhiraj , Uc Aliye , Imdad Aamer
Published: May 2024

Introduction

Gastrointestinal hospitalisations in the USA cause over US$130 billion in expenditures, and acute pancreatitis is a leading cause of these hospitalisations. Adequate pain control is one of the primary treatment goals for acute pancreatitis. Though opioids are commonly used for analgesia in these patients, there have been concerns about short-term and long-term side effects of using opioids. Recently, non-opioid medications have been studied to treat pain in patients with acute pancreatitis. This systematic review and network meta-analysis aims to assess the comparative efficacy of analgesic medication for non-severe, acute pancreatitis.

Methods and analysis

We will search multiple electronic databases for randomised controlled trials that study pain management in patients with non-severe, acute pancreatitis. The intervention will be any analgesic for acute pancreatitis in the hospital setting. The comparison group will be patients who received a placebo or other active interventions for pain management. The primary outcomes of interest include pain scores and the need for supplementary analgesia. The secondary outcomes will be serious adverse events, local complications, progression to severe pancreatitis, transfer to the intensive care unit, length of hospitalisation, time to start enteral feeds, 30-day all-cause mortality and Quality of Life Scale scores. If sufficient homogeneity exists among included studies, the findings will be pooled using a traditional pairwise and network meta-analysis. The risk of bias in randomised control trials will be evaluated using the Cochrane Risk of Bias Tool 2.0. The Grading of Recommendations, Assessment, Development, and Evaluation approach will be used to report the certainty of evidence.

Ethics and dissemination

This systematic review will not involve direct contact with human subjects. The findings of this review will be published in a peer-reviewed journal. They will give healthcare providers a better awareness of the optimal analgesic medication for pain treatment in non-severe, acute pancreatitis.
Theory and evidence-base for a digital platform for the delivery of language tests during awake craniotomy and collaborative brain mapping
Authors: Veljanoski Damjan , Ng Xin Yi , Hill Ciaran Scott , Jamjoom Aimun A B
Published: May 2024

Objectives

Build the theoretical and evidence-base for a digital platform (map-OR) which delivers intraoperative language tests during awake craniotomy and facilitates collaborative sharing of brain mapping data.

Design

Mixed methodology study including two scoping reviews, international survey, synthesis of development guiding principles and a risk assessment using failure modes and effects analysis.

Setting

The two scoping reviews examined the literature published in the English language. International survey was completed by members of awake craniotomy teams from 14 countries.

Main outcome measures

Scoping review 1: number of technologies described for language mapping during awake craniotomy. Scoping review 2: barriers and facilitators to adopting novel technology in surgery. International survey: degree of language mapping technology penetration into clinical practice.

Results

A total of 12 research articles describing 6 technologies were included. The technologies required a range of hardware components including portable devices, virtual reality headsets and large integrated multiscreen stacks. The facilitators and barriers of technology adoption in surgery were extracted from 11 studies and mapped onto the 4 Unified Theory of Acceptance and Use of Technology constructs. A total of 37 awake craniotomy teams from 14 countries completed the survey. Of the responses, 20 (54.1%) delivered their language tests digitally, 10 (27.0%) delivered tests using cards and 7 (18.9%) used a combination of both. The most commonly used devices were tablet computers (67.7%; n=21) and the most common software used was Microsoft PowerPoint (60.6%; n=20). Four key risks for the proposed digital platform were identified, the highest risk being a software and internet connectivity failure during surgery.

Conclusions

This work represents a rigorous and structured approach to the development of a digital platform for standardized intraoperative language testing during awake craniotomy and for collaborative sharing of brain mapping data.

Trial registration number

Scoping review protocol registrations in OSF registries (scoping review 1: osf.io/su9xm; scoping review 2: osf.io/x4wsc).
Targeting squalene epoxidase restores anti-PD-1 efficacy in metabolic dysfunction-associated steatohepatitis-induced hepatocellular carcinoma
Authors: Wen Jun , Zhang Xiang , Wong Chi Chun , Zhang Yating , Pan Yasi , Zhou Yunfei , Cheung Alvin Ho-Kwan , Liu Yali , Ji Fenfen , Kang Xing , Liu Dabin , Yu Jun
Published: May 2024

Objective

Squalene epoxidase (SQLE) promotes metabolic dysfunction-associated steatohepatitis-associated hepatocellular carcinoma (MASH-HCC), but its role in modulating the tumour immune microenvironment in MASH-HCC remains unclear.

Design

We established hepatocyte-specificSqletransgenic (tg) and knockout mice, which were subjected to a choline-deficient high-fat diet plus diethylnitrosamine to induce MASH-HCC. SQLE function was also determined in orthotopic and humanised mice. Immune landscape alterations of MASH-HCC mediated by SQLE were profiled by single-cell RNA sequencing and flow cytometry.

Results

Hepatocyte-specificSqletg mice exhibited a marked increase in MASH-HCC burden compared with wild-type littermates, together with decreased tumour-infiltrating functional IFN-γ+and Granzyme B+CD8+T cells while enriching Arg-1+myeloid-derived suppressor cells (MDSCs). Conversely, hepatocyte-specificSqleknockout suppressed tumour growth with increased cytotoxic CD8+T cells and reduced Arg-1+MDSCs, inferring that SQLE promotes immunosuppression in MASH-HCC. Mechanistically, SQLE-driven cholesterol accumulation in tumour microenvironment underlies its effect on CD8+T cells and MDSCs. SQLE and its metabolite, cholesterol, impaired CD8+T cell activity by inducing mitochondrial dysfunction. Cholesterol depletion in vitro abolished the effect of SQLE-overexpressing MASH-HCC cell supernatant on CD8+T cell suppression and MDSC activation, whereas cholesterol supplementation had contrasting functions on CD8+T cells and MDSCs treated with SQLE-knockout supernatant. Targeting SQLE with genetic ablation or pharmacological inhibitor, terbinafine, rescued the efficacy of anti-PD-1 treatment in MASH-HCC models.

Conclusion

SQLE induces an impaired antitumour response in MASH-HCC via attenuating CD8+T cell function and augmenting immunosuppressive MDSCs. SQLE is a promising target in boosting anti-PD-1 immunotherapy for MASH-HCC.
Genetics of inherited peripheral neuropathies and the next frontier: looking backwards to progress forwards
Authors: Parmar Jevin M , Laing Nigel G , Kennerson Marina L , Ravenscroft Gianina
Published: May 2024

Inherited peripheral neuropathies (IPNs) encompass a clinically and genetically heterogeneous group of disorders causing length-dependent degeneration of peripheral autonomic, motor and/or sensory nerves. Despite gold-standard diagnostic testing for pathogenic variants in over 100 known associated genes, many patients with IPN remain genetically unsolved. Providing patients with a diagnosis is critical for reducing their ‘diagnostic odyssey’, improving clinical care, and for informed genetic counselling. The last decade of massively parallel sequencing technologies has seen a rapid increase in the number of newly described IPN-associated gene variants contributing to IPN pathogenesis. However, the scarcity of additional families and functional data supporting variants in potential novel genes is prolonging patient diagnostic uncertainty and contributing to the missing heritability of IPNs. We review the last decade of IPN disease gene discovery to highlight novel genes, structural variation and short tandem repeat expansions contributing to IPN pathogenesis. From the lessons learnt, we provide our vision for IPN research as we anticipate the future, providing examples of emerging technologies, resources and tools that we propose that will expedite the genetic diagnosis of unsolved IPN families.
Health impact of “reduced yield” cigarettes: a critical assessment of the epidemiological evidence
Authors: Thun Michael J , Burns David M
Published: May 2024

Cigarettes with lower machine measured “tar” and nicotine yields have been marketed as “safer” than high tar products over the last four decades, but there is conflicting evidence about the impact of these products on the disease burden caused by smoking. This paper critically examines the epidemiological evidence relevant to the health consequences of “reduced yield” cigarettes. Some epidemiological studies have found attenuated risk of lung cancer but not other diseases, among people who smoke “reduced yield” cigarettes compared to smokers of unfiltered, high yield products. These studies probably overestimate the magnitude of any association with lung cancer by over adjusting for the number of cigarettes smoked per day (one aspect of compensatory smoking), and by not fully considering other differences between smokers of “high yield” and “low yield” cigarettes. Selected cohort studies in the USA and UK show that lung cancer risk continued to increase among older smokers from the 1950s to the 1980s, despite the widespread adoption of lower yield cigarettes. The change to filter tip products did not prevent a progressive increase in lung cancer risk among male smokers who began smoking during and after the second world war compared to the first world war era smokers. National trends in vital statistics data show declining lung cancer death rates in young adults, especially males, in many countries, but the extent to which this is attributable to “reduced yield” cigarettes remains unclear. No studies have adequately assessed whether health claims used to market “reduced yield” cigarettes delay cessation among smokers who might otherwise quit, or increase initiation among non-smokers. There is no convincing evidence that past changes in cigarette design have resulted in an important health benefit to either smokers or the whole population. Tobacco control policies should not allow changes in cigarette design to subvert or distract from interventions proven to reduce the prevalence, intensity, and duration of smoking.
Tobacco use by Massachusetts public college students: long term effect of the Massachusetts Tobacco Control Program
Authors: Rigotti N A , Regan S , Majchrzak N E , Knight J R , Wechsler H
Published: May 2024

Objective:To assess tobacco use among Massachusetts public college students and compare students who attended high school in Massachusetts and were exposed to the Massachusetts Tobacco Control Program (MTCP) with students who attended high school outside Massachusetts and were unexposed to the programme.

Design:Analysis of the 1999 Massachusetts College Alcohol Survey.

Setting:Four year public colleges and universities in Massachusetts (n = 11).

Subjects:1252 randomly selected students (response rate 56%).

Main outcome measures:Self report of current (past 30 day), past year, and lifetime use of cigarettes, cigars, and smokeless tobacco.

Results:One third of students had used a tobacco product in the past month and 46.4% had used tobacco in the past year. Cigarettes accounted for most of this tobacco use. Total tobacco use was higher among males than females but cigarette smoking did not differ by sex. Tobacco use was lower among athletes and higher among students who used alcohol or marijuana. Current tobacco use was lower among public college students who had attended high school in Massachusetts compared with those who attended high school in another state (31.5%v42.6%, p = 0.006). This difference persisted after adjustment for age, sex, race, parental education, and students' college residence (adjusted odds ratio (OR) 0.67, 95% confidence interval (CI) 0.46 to 0.97, p = 0.034).

Conclusion:Tobacco use is common among Massachusetts public college students. Students who were exposed to the MTCP during high school are less likely to use tobacco than their peers who were not exposed to this programme. The MTCP may have reduced tobacco use among this group of young adults.
Economic effect of restaurant smoking restrictions on restaurant business in Massachusetts, 1992 to 1998
Authors: Bartosch W J , Pope G C
Published: May 2024

Objective:To determine if restaurant business declines or improves after the implementation of restrictive restaurant smoking policies.

Design:Analysis used a pre/post-quasi-experimental design that compared town meals tax receipts before and after the imposition of highly restrictive restaurant smoking policies in adopting versus non-adopting communities. The effect of restaurant smoking policies was estimated using a fixed effects regression model, entering a panel of 84 months of data for the 239 towns in the study. A separate model estimated the effect of restaurant smoking policies on establishments that served alcohol.

Main outcome measure:Change in the trend in meals tax revenue (adjusted for population) following the implementation of highly restrictive restaurant smoking policies.

Results:The local adoption of restrictive restaurant smoking policies did not lead to a measurable deviation from the strong positive trend in revenue between 1992 and 1998 that restaurants in Massachusetts experienced. Controlling for other less restrictive restaurant smoking policies did not change this finding. Similar results were found for only those establishments that served alcoholic beverages.

Conclusions:Highly restrictive restaurant smoking policies do not have a significant effect on a community's level of meal receipts, indicating that claims of community wide restaurant business decline under such policies are unwarranted.
A longitudinal study of externally visible cigarette advertising on retail storefronts in Massachusetts before and after the Master Settlement Agreement
Authors: Celebucki C C , Diskin K
Published: May 2024

Objectives:To assess the effect of the Master Settlement Agreement (MSA) on the amount of cigarette advertisements visible from outside of over-the-counter tobacco retailers, for five specific premium brands and an “all other” category, for five types of establishments, and in three areas (windows/doors, building/other detached areas, and sidewalks); to assess the relation of total exterior retail cigarette advertising to illegal sales to youth.

Methods:Observations were conducted on the number of cigarette advertisements visible from outside tobacco retail establishments in a paired convenience sample (n = 556) in Massachusetts before and after the MSA. Archival databases containing information on merchant compliance with age related sales laws during the time period were used to assess the relation of total cigarette advertising with sales to underage youth. Paired samplettests assessed planned comparisons pre- to post-MSA; Spearman's ρ tested associations for dichotomous variables.

Results:Significant post-ban increases were observed in the prevalence of exterior cigarette advertising on gas (petrol) stations and gas mini/marts (gasoline retailers) buildings, windows, and doors. Significant declines were observed on windows of liquor stores. Winston advertising declined overall, while advertisements of the “all other” brand category increased. Correlations between advertising and illegal sales, while modest, were significant.

Conclusions:These pre- to post-MSA increases suggest the tobacco industry may be shifting expenditures selectively from billboard advertising to retailer exteriors more favoured by youth. Greater amount of cigarette advertising visible from outside over-the-counter tobacco retailers is associated with greater cigarette sales to minors.
Testing the weak cosmic censorship conjecture in short haired black holes
Authors: Zhao Min , Tang Meirong , Xu Zhaoyi
Published: May 2024

The weak cosmic censorship conjecture is a hypothesis about the nature of event horizons and singularities during the formation of black holes. It posits that singularities are always enveloped by the event horizons of black holes, thereby preventing naked singularities from affecting the causal structure of spacetime. In this paper, we study the effect of rotating short haired black holes on the weak cosmic censorship conjecture. Discussion of whether the event horizons of a rotating short haired black hole is disrupted by studying incident neutral test particles and scalar fields. In the context of short haired black holes, when incident neutral test particles are considered for extreme and near extreme cases, our research results indicate that neutral test particles can destroy the event horizons of short haired black holes, violating the weak cosmic censorship conjecture. In the case of scalar field incidence in short haired black holes, for extreme situations, when the incident wave modes fall within the range of $$\frac{1}{2\kappa M+\frac{\beta }{M\kappa }}<\frac{\omega }{m}<\frac{1}{2M\kappa + \frac{\beta }{M\kappa }-\frac{1}{2\kappa }},$$

1

2
κ
M
+

β

M
κ

<

ω
m

<

1

2
M
κ
+

β

M
κ

-

1

2
κ

,

the results indicate that the event horizons of rotating short haired black holes is disrupted. For near extreme cases, the presence of hair allows for the disruption of the event horizons of rotating short haired black holes, as indicated by our results. Therefore, these conclusions are intriguing and will provide new insights for us to further understand the weak cosmic censorship conjecture and explore the properties of short haired black holes.
Notes on time entanglement and pseudo-entropy
Authors: Narayan K. , Saini Hitesh K.
Published: May 2024

Following arXiv:2210.12963 [hep-th], we investigate aspects of the time evolution operator regarded as a density operator and associated entanglement-like structures in various quantum systems. These involve timelike separations and generically lead to complex-valued entropy, although there are interesting real subfamilies. There are many parallels and close relations with reduced transition matrices and pseudo-entropy, which we discuss and clarify. For instance, a related quantity involves the time evolution operator along with a projection onto some initial state, which amounts to analysing pseudo-entropy for the initial state and its time-evolved final state.
Accretion of matter by a charged dilaton black hole
Authors: Jia Yinan , He Tong-Yu , Wang Wen-Qian , Han Zhan-Wen , Yang Rong-Jia
Published: May 2024

Considering accretion onto a charged dilaton black hole, the fundamental equations governing accretion, general analytic expressions for critical points, critical velocity, critical speed of sound, and ultimately the mass accretion rate are obtained. A new constraint on the dilation parameter coming from string theory is found and the case for polytropic gas is delved into a detailed discussion. It is found that the dialtion and the adiabatic index of accreted material have deep effects on the accretion process.
Observational tests of 4D double field theory
Authors: Li Shunrui , Liu Yang
Published: May 2024

Although General Relativity (GR) is a very successful theory of gravity, it cannot explain every observational phenomenon. People have tried many kinds of modified gravity theory to explain these phenomena which GR cannot explain very well, such as string theory. In recent years Double Field Theory (DFT) has been an exciting research area in string theory. The most general, spherically symmetric, asymptotically flat, static vacuum solution to $$D=4$$

D
=
4

double field theory has been derived by S.M. Ko, J.H. Park and M. Suh. In this article, we calculate the minor corrections to the three predictions in GR: optical deflation, planet precession and gravitational redshift. These three predictions should be able to tested by observations and find the discrepancies between GR and DFT in the future.
Mean flow generated by asymmetric periodic excitation in an annular channel
Authors: Borcia Ion Dan , Bestehorn Michael , Borcia Rodica , Schön Franz-Theo , Harlander Uwe , Richter Sebastian
Published: May 2024

Surface waves of a shallow liquid layer confined in an annular channel of length $${{\tilde{L}}}$$

L
~

are generated by periodic acceleration of the channel along its azimuthal direction. We show that if the oscillations are anharmonic, e.g., having the form of a saw tooth, a mean mass flow is generated and even the mean speed over one period is zero. The flow is studied both experimentally and numerically. In the experiment, the velocity field and surface deflection are derived from the frames of videos recorded with a Go-Pro Hero 4 camera with custom rectilinear lens. We show resonance curves of the mean square of the water surface deflection and of the averaged mass flow. Both curves show almost coinciding maxima for multiples of the fundamental resonance frequency $${{\tilde{f}}}_r=\tilde{c}_0/(2{{\tilde{L}}}),$$

f
~

r

=

c
~

0

/

(
2

L
~

)

,

where $${{\tilde{c}}}_0$$

c
~

0

is the shallow water wave velocity. The measurements are confirmed by numerical solutions of an integrated boundary layer model including inertia and dissipation.
Streaming Algorithms with Few State Changes
Authors: Jayaram Rajesh , Woodruff David P. , Zhou Samson
Published: May 2024

In this paper, we study streaming algorithms that minimize the number of changes made to their internal state (i.e., memory contents). While the design of streaming algorithms typically focuses on minimizing space and update time, these metrics fail to capture the asymmetric costs, inherent in modern hardware and database systems, of reading versus writing to memory. In fact, most streaming algorithms write to their memory on every update, which is undesirable when writing is significantly more expensive than reading. This raises the question of whether streaming algorithms with small space and number of memory writes are possible.

We first demonstrate that, for the fundamental F
p
moment estimation problem with p ≥ 1, any streaming algorithm that achieves a constant factor approximation must make Ω(n
1-1/p
) internal state changes, regardless of how much space it uses. Perhaps surprisingly, we show that this lower bound can be matched by an algorithm which also has near-optimal space complexity. Specifically, we give a (1+ε)-approximation algorithm for F
p
moment estimation that use a near-optimal ~O
ε
(n
1-1/p
) number of state changes, while simultaneously achieving near-optimal space, i.e., for p∈[1,2), our algorithm uses poly(log n,1/ε) bits of space for, while for p>2, the algorithm uses ~O
ε
(n
1-1/p
) space. We similarly design streaming algorithms that are simultaneously near-optimal in both space complexity and the number of state changes for the heavy-hitters problem, sparse support recovery, and entropy estimation. Our results demonstrate that an optimal number of state changes can be achieved without sacrificing space complexity.