bluuebunny/crossref_metadata_2025_split huggingface dataset:
GRP78 recognizes EV-F 3D protein and activates NF-κB to repress virus replication by interacting with CHUK/IKBKB
Authors: Chang Xiaoran , Guo Yidi , Zhang Qun , Zheng Xuebo , Cui Xuyuan , Hu Junying , Zhang Zhiyuan , Zhang Fan , Wang Xinping 
Published: May 2024

ABSTRACT

Enteroviruses are the causative agents associated with several human and animal diseases, posing a significant threat to human and animal health. As one of the host immune defense strategies, innate immunity plays a crucial role in defending against invading pathogens, where the host utilizes a variety of mechanisms to inhibit or eliminate the pathogen. Here, we report a new strategy for the host to repress enterovirus replication by the 78 kDa glucose-regulated protein (GRP78), also known as heat shock protein family A member 5 (HSPA5). The GRP78 recognizes the EV-encoded RNA-dependent RNA polymerases (RdRPs) 3D protein and interacts with the nuclear factor kappa B kinase complex (CHUK) and subunit beta gene (IKBKB) to facilitate the phosphorylation and nuclear translocation of NF-κB, which induces the production of inflammatory factors and leads to a broad inhibition of enterovirus replication. These findings demonstrate a new role of GRP78 in regulating host innate immunity in response to viral infection and provide new insights into the mechanism underlying enterovirus replication and NF-κB activation.

IMPORTANCE
GRP78 is known as a molecular chaperone for protein folding and plays a critical role in maintaining protein folding and participating in cell proliferation, cell survival, apoptosis, and metabolism. However, the functions of GRP78 to participate in enterovirus genome replication and innate immune responses are rarely documented. In this study, we explored the functions of the EV-3D-interacting protein GRP78 and found that GRP78 inhibits enterovirus replication by activating NF-κB through binding to EV-F 3D and interacting with the NF-κB signaling molecules CHUK/IKBKB. This is the first report that GRP78 interacts with CHUK/IKBKB to activate the NF-κB signaling pathway, which leads to the expression of the proinflammatory cytokines and inhibition of enterovirus replication. These results demonstrate a unique mechanism of virus replication regulation by GRP78 and provide insights into the prevention and treatment of viral infections.
Risk factors and patterns for progression of fellow-eye myopic traction maculopathy: a 3-year retrospective cohort study
Authors: Luo Nan , Long Kejun , Lian Ping , Huang Jieyong , Zhao Liyi , Alimu Subinuer , Liu Guang , Jin Ling , Wang Tong , Chen Chen , Huang Yanqiao , Zhao Xiujuan , Yu Xiling , Ding Xiaoyan , Huang Jingjing , Liu Bingqian , Chen Shida , Lu Lin 
Published: May 2024

Aims
To investigate the effect of preretinal tractional structures (PTS) and posterior scleral structures (PSS) on myopic traction maculopathy (MTM) progression.

Methods
This retrospective cohort study included 185 fellow highly myopic eyes of 185 participants who underwent surgery for MTM. PTS included epiretinal membrane, incomplete posterior vitreous detachment and their combination. PSS included posterior staphyloma and dome-shaped macula (DSM). The MTM stage was graded according to the Myopic Traction Maculopathy Staging System. Optical coherence tomography was used to identify MTM progression, defined as an upgrade of MTM. The Kaplan-Meier method with log-rank test was used to assess MTM progression over the 3-year follow-up period. Risk factors for progression were identified using Cox regression analysis.

Results

MTM progression was observed in 48 (25.9%) eyes. Three-year progression-free survival (PFS) rates for eyes with PTS, staphyloma and DSM were 53.7%, 58.2% and 90.7%, respectively. Eyes with PTS and staphyloma exhibited lower 3-year PFS rates than those without PTS or staphyloma (
P
log-rank test
=0.002 and <0.001), while eyes with DSM had a higher 3-year PFS rate than eyes without DSM (
P
log-rank test
=0.01). Multivariate Cox regression analysis showed that PTS (HR, 3.23; p<0.001) and staphyloma (HR, 7.91; p<0.001) were associated with MTM progression, whereas DSM (HR, 0.23; p=0.046) was a protective factor.

Conclusion
Both PTS and PSS play a critical role in the progression of MTM. Addressing these factors can aid in the management of MTM.
Priorities for health outcomes in glaucoma in an ethnically diverse UK cohort: an observational study
Authors: Safitri Atika , Konstantakopoulou Evgenia , Gazzard Gus , Hu Kuang 
Published: May 2024

ObjectivesTo assess whether patients from minority ethnic groups have different perceptions about the quality-of-life outcomes that matter most to them.DesignCross-sectional observational study.SettingHigh volume eye centres serving the most ethnically diverse region in the UK, recruiting from July 2021 to February 2022.Participants511 patients with primary open-angle glaucoma and the predisease state of ocular hypertension.Main outcome measuresThe main outcome was participants’ self-reported priorities for health outcomes.ResultsParticipants fell into one of four clusters with differing priorities for health outcomes, namely: (1) vision, (2) drop freedom, (3) intraocular pressure and (4) one-time treatment. Ethnicity was the strongest determinant of cluster membership after adjusting for potential confounders. Compared with white patients prioritising vision alone, the OR for black/black British patients was 7.31 (95% CI 3.43 to 15.57, p<0.001) for prioritising drop freedom; 5.95 (2.91 to 12.16, p<0.001) for intraocular pressure; and 2.99 (1.44 to 6.18, p=0.003) for one-time treatment. For Asian/Asian British patients, the OR was 3.17 (1.12 to 8.96, p=0.030) for prioritising intraocular pressure as highly as vision. Other ethnic minority groups also had higher ORs for prioritising health outcomes other than vision alone: 4.50 (1.03 to 19.63, p=0.045) for drop freedom and 5.37 (1.47 to 19.60, p=0.011) for intraocular pressure.ConclusionsEthnicity is strongly associated with differing perceptions about the health outcomes that matter. An individualised and ethnically inclusive approach is needed when selecting and evaluating treatments in clinical and research settings.
Efficacy and safety of pentosan polysulfate sodium in people with symptomatic knee osteoarthritis and dyslipidaemia: protocol of the MaRVeL trial
Authors: Siddiq Md Abu Bakar , Liu Xiaoqian , Fedorova Tatyana , Bracken Karen , Virk Sonika , Venkatesha Venkatesha , Farivar Abdolhay , Oo Win Min , Linklater James , Hill David Cullis , Hunter David J 
Published: May 2024

IntroductionKnee osteoarthritis (OA) is the most prevalent arthritis type and a leading cause of chronic mobility disability. While pain medications provide only symptomatic pain relief; growing evidence suggests pentosan polysulfate sodium (PPS) is chondroprotective and could have anti-inflammatory effects in knee OA. This study aims to explore the efficacy and safety of oral PPS in symptomatic knee OA with dyslipidaemia.Methods and analysisMaRVeL is a phase II, single-centre, parallel, superiority trial which will be conducted at Royal North Shore Hospital, Sydney, Australia. 92 participants (46 per arm) aged 40 and over with painful knee OA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) will be recruited from the community and randomly allocated to receive two cycles of either oral PPS or placebo for 5 weeks starting at baseline and week 11. Primary outcome will be the 16-week change in overall average knee pain severity measured using an 11-point Numeric Rating Scale. Main secondary outcomes include change in knee pain, patient global assessment, physical function, quality of life and other structural changes. A biostatistician blinded to allocation groups will perform the statistical analysis according to the intention-to-treat principle.Ethics and disseminationThe protocol has been approved by the NSLHD Human Research Ethics Committee (HREC) (2021/ETH00315). All participants will provide written informed consent online. Study results will be disseminated through conferences, social media and academic publications.Trial registration numbersAustralian New Zealand Clinical Trial Registry (ACTRN12621000654853); U1111-1265-3750.
Describing primary care patterns before and during the COVID-19 pandemic across Canada: a quasi-experimental pre–post design cohort study using national practice-based research network data
Authors: Hafid Shuaib , Freeman Karla , Aubrey-Bassler Kris , Queenan John , Drummond Neil , Lawson Jennifer , Vanstone Meredith , Nicholson Kathryn , Lussier Marie-Thérèse , Mangin Dee , Howard Michelle 
Published: May 2024

ObjectiveThe objective was to analyse how the pandemic affected primary care access and comprehensiveness in chronic disease management by comparing primary care patterns before and during the early COVID-19 pandemic.DesignWe conducted a quasi-experimental pre–post design cohort study and reported indicators for the 21 months before and after the onset of the COVID-19 pandemic.SettingWe used electronic medical record data from primary care clinics enrolled in the Canadian Primary Care Sentinel Surveillance Network from 1 January 2018 to 31 December 2021.PopulationThe study population included patients (n=919 928) aged 18 years or older with at least one primary care contact from 12 March 2018 to 12 March 2020, in Canada.Outcome measuresThe study indicators included three indicators measuring access to primary care (encounters, blood pressure measurements and lab tests) and three for comprehensiveness (diagnoses, non-COVID-19 vaccines administered and referrals).Results67.3% of the cohort was aged ≥40 years, 56.4% were female and 53.5% were from Ontario, Canada. Fewer patients received an encounter during the pandemic (91.5% to 81.5%), while the median (IQR) number of encounters remained the same (5 (2–1)) for those with access. Fewer patients received a blood pressure measurement (47.9% to 31.8%), and patients received fewer measurements during the pandemic (2 (1–4) to 1 (0–2)).ConclusionsEncounters with primary care remained consistent during the pandemic, but in-person care, such as lab tests and blood pressure measurements, decreased. In-person care indicators followed temporally to national COVID-19 case counts during the pandemic.
Outcomes after reversed corneal graft rejection: a report from the European VISICORT project
Authors: Iselin Katja C , Hjortdal Jesper , Armitage W John , Tole Derek , Pleyer Uwe , Vabres Bertrand , Griffin Matthew D , Murphy Conor C 
Published: May 2024

ObjectiveThis study aims to describe the outcome of corneal grafts, both low risk and high risk, after successfully reversed immunological rejection.MethodsDatasets on reversed rejection episodes in penetrating and endothelial keratoplasties between 2014 and 2019 (n=876) were extracted from the Adverse Immune Signatures and their Prevention in Corneal Transplantation database, which contains the prospectively and consecutively collected corneal transplants from five European centres. Stratified by the preoperatively determined risk status for immunological rejection, the outcome parameters analysed included visual acuity, intraocular pressure, endothelial cell density and central corneal thickness before and after reversed rejection episodes.ResultsFourty-seven (52%) out of a total of 91 identified rejection episodes were successfully reversed and were available for analysis (23 penetrating and 24 endothelial keratoplasties). No statistically significant change was found for any of the parameters studied between the values before and the values 3 months after the rejection episode, irrespective of the preoperative risk status.ConclusionThe outcome of corneal grafts that survive immunological rejection may be clinically indistinguishable from the state before immunological rejection, irrespective of graft type and risk status. These findings support clinicians by providing information on prognosis after reversed rejection episodes and by giving patients realistic expectations regarding the outcome.
Intervention to increase colorectal cancer screening among emergency department patients: results from a randomised pilot study
Authors: Abar Beau , Park Chanjun Syd , Wood Nancy , Marino Danielle , Fiscella Kevin , Adler David 
Published: May 2024

BackgroundColorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Emergency departments (ED) represent a promising setting to address preventive health measures like CRC screening.ObjectivesThe current study adapted an existing cervical cancer screening intervention for use in catalysing CRC screening. We evaluated feasibility of identification, provided preliminary effect size estimates and documented participant acceptability.MethodsThis study was funded by the University of Rochester (ClinicalTrials.gov #NCT05004376). We enrolled ED patients, 45–75 years old, in the Greater Rochester, NY region into a randomised controlled pilot from January to May 2022. Patients were excluded if non-English speaking, lacking a cell phone or had a history of CRC, colorectal resection, inflammatory bowel disease or abdominal radiation. Participants were surveyed to determine adherence with recommended CRC screening guidelines. Patients found non-adherent were randomised to receive (1) recommendation for CRC screening only or (2) recommendation and a text-based intervention aimed at generating intention and motivation to get screened. Patients were blind to allocation at enrolment. The primary outcome was patient CRC screening or scheduling.Results1438 patients were approached, with 609 found ineligible, 576 declining participation and 253 enrolled. A randomised sample of 114 non-adherent patients were split evenly between the control and intervention arms. Among participants with follow-up data (ncontrol=38,nintervention=36), intervention participants had a 2%–3% higher rate of scheduling or receiving screening (7%–27% relative improvement). When using the complete sample (n=114) and conservatively assuming no screening for those lost to follow-up, differences in screening across arms were mildly decreased (0%–2% absolute difference). Acceptability of CRC intervention was high, and participants offered formative feedback.ConclusionThe piloted text message intervention through the ED shows potential promise for catalysing CRC screening. Subsequent replication in a fully powered trial is needed.
Risk of hypersensitivity pneumonitis and other interstitial lung diseases following organic dust exposure
Authors: Iversen Inge Brosbøl , Vestergaard Jesper Medom , Basinas Ioannis , Ohlander Johan , Peters Susan , Bendstrup Elisabeth , Bonde Jens Peter Ellekilde , Schlünssen Vivi , Rasmussen Finn , Stokholm Zara Ann , Andersen Michael Brun , Kromhout Hans , Kolstad Henrik Albert 
Published: May 2024

BackgroundOrganic dust is associated with hypersensitivity pneumonitis, and associations with other types of interstitial lung disease (ILD) have been suggested. We examined the association between occupational organic dust exposure and hypersensitivity pneumonitis and other ILDs in a cohort study.MethodsThe study population included all residents of Denmark born in 1956 or later with at least 1 year of gainful employment since 1976. Incident cases of hypersensitivity pneumonitis and other ILDs were identified in the Danish National Patient Register 1994–2015. Job exposure matrices were used to assign individual annual levels of exposure to organic dust, endotoxin and wood dust from 1976 to 2015. We analysed exposure-response relations by different exposure metrics using a discrete-time hazard model.ResultsFor organic dust, we observed increasing risk with increasing cumulative exposure with incidence rate ratios (IRR) per 10 unit-years of 1.19 (95% CI 1.12 to 1.27) for hypersensitivity pneumonitis and 1.04 (95% CI 1.02 to 1.06) for other ILDs. We found increasing risk with increasing cumulative endotoxin exposure for hypersensitivity pneumonitis and other ILDs with IRRs per 5000 endotoxin units/m3-years of 1.55 (95% CI 1.38 to 1.73) and 1.09 (95% CI 1.00 to 1.19), respectively. For both exposures, risk also increased with increasing duration of exposure and recent exposure. No increased risks were observed for wood dust exposure.ConclusionExposure-response relations were observed between organic dust and endotoxin exposure and hypersensitivity pneumonitis and other ILDs, with lower risk estimates for the latter. The findings indicate that organic dust should be considered a possible cause of any ILD.Trial registration numberj.no.: 1-16-02-196-17
No influence of steady-state postural changes on cerebrovascular compliance in humans
Authors: Kells Alicia M. , Moir M. Erin , Coombs Geoff B. , D'Souza Andrew W. , Klassen Stephen A. , Al-Khazraji Baraa K. , Shoemaker J. Kevin 
Published: May 2024

The aim of this study was to determine the effect of posture changes on vascular compliance in intracranial (brain) versus extracranial vascular beds (forearm). Eighteen young adults (nine females) performed a supine-to-seated-to-standing protocol involving 5 min of rest in each position. Continuous blood pressure, middle cerebral artery (MCA) blood velocity, and brachial artery blood velocity were recorded at each posture. Three to five consecutive steady-state cardiac cycles at each posture were analyzed by a four-element lumped parameter modified Windkessel model to calculate vascular compliance. Mean arterial pressure (MAP) increased from supine to seated (76(9) vs. 81(12) mmHg; P = 0.006) and from supine to standing (76(9) vs. 82(13) mmHg; P = 0.034). Mean blood flow was greater in the MCA relative to the forearm (forearm: 40(5) mL·min−1, MCA: 224(17) mL·min−1; main effect P < 0.001). Conversely, vascular resistance (forearm: 3.25(0.50) mmHg−1·mL·min−1, brain: 0.36(0.04) mmHg−1·mL·min−1; main effect P < 0.001) and compliance (forearm: 0.010(0.001) mL·min−1·mmHg−1, brain: 0.005(0.001) mL·min−1·mmHg−1; main effect P = 0.001) were greater in the forearm compared to the brain. Significant main effects of posture were observed with decreasing values in upright positions for mean blood flow ( P = 0.001) in both vascular beds, but not for resistance ( P = 0.163) or compliance ( P = 0.385). There were no significant interaction effects between vascular bed and posture for mean flow ( P = 0.057), resistance ( P = 0.258), or compliance ( P = 0.329). This study provides evidence that under steady-state conditions, posture does not affect cerebrovascular compliance.
Yield of yellow cooking onions is not affected by added phosphorous fertilizer in muck soils with high soil test phosphorus in Ontario
Authors: McDonald Mary Ruth , Speranzini Donna , Kessel Christoph , O'Halloran Ivan , Audette Yuki , Nemeth Deanna 
Published: May 2024

Excess phosphorus (P) loading has been identified as an important cause of poor water quality in Lake Simcoe. A small (∼4%) but important source of P is the marshland that was developed for agriculture in and near the Holland Marsh. Applying the optimum rate of P fertilizer is an economical and environmentally friendly approach to crop management. In Ontario, P fertilizer recommendations are made based on the Olsen P soil test that is accredited by the Ontario Ministry of Agriculture, Food and Rural Affairs (OMAFRA). The current study was a response to concern about high application rates of P fertilizer and grower and industry suggestions that the recommended rates for P were too low. The marketable yield of yellow cooking onions was assessed in relation to different rates of P fertilizer in high organic matter (muck) soils. Organic matter ranged from 38% to 86%. Small- (6 site-years) and large-scale (21 site-years) field trials were conducted in the Holland Marsh area from 2009 to 2011 on muck soils that varied in pre-plant P (17–312 mg L−1). The study demonstrated that there was more plant-available P in the soil than was required for optimum yield in most fields; thus, P fertilizer applications had no effect on marketable yield of the onions. These results supported the OMAFRA P recommendations for onion production on muck soils, especially for soil test P levels over 61 mg L−1 where a response to applied P is rated as “low, rare, or no response”.
A review of arsenic speciation in freshwater fish: perspectives on monitoring approaches and analytical methods
Authors: Lepage Adam T. , Laird Brian , Skinner Kelly , Gunn John M. , Lescord Gretchen L. 
Published: May 2024

Arsenic accumulation in fish poses concerns for subsistence and recreational fishers worldwide. However, the toxicity of arsenic to consumers strongly depends on the chemical forms, or species, present. Risk assessments often rely on total arsenic concentrations ([As]), adjusting for assumed small percentages of the most harmful inorganic species. While studies on arsenic speciation in marine fish are widespread, and commonly report less toxic arsenobetaine (AsB) as the dominant form, fewer studies have been conducted on freshwater fish, where arsenic speciation may be more variable. To assess these findings, we conducted a systematic literature review on arsenic speciation in freshwater fish using Covidence© review management software. From over 1100 screened studies, 41 were selected for inclusion based on predefined criteria. These studies reported highly variable arsenic speciation patterns in freshwater fish, calling into question the assumption that AsB is the dominant form present. Sites with suspected or known arsenic contamination issues were prominent, with >50% of data reviewed originating from a contaminated river or lake, but the effect of contamination on arsenic speciation was variable. Although AsB and other organic forms typically dominated, some studies (6/41; 15%) identified fish with elevated concentrations of inorganic arsenic (>1 mg/kg dry wt.), most often corresponding to over 20% of total arsenic. Furthermore, arsenic speciation results accounted for a highly variable proportion of total [As] in fish, often less than 50%. Assuming 20% inorganic arsenic appears to be a poor approximation that cannot be applied to all fish. Based on this considerable variability, we recommend the direct measurement of arsenic species whenever possible, especially when total [As] is elevated above relevant guidelines for the most toxic species (e.g., 0.1–2 mg/kg inorganic arsenic wet wt.). We also recommend that future works communicate their results in more detail, including complete description of quality assurance and control protocols, to improve the potential for future meta-analyses. Additional work is needed to characterize arsenic speciation in freshwater fish and assess the toxicity of various arsenic species to accurately evaluate the environmental and human health risks associated with arsenic in fish.
A Mean Field to Capture Asynchronous Irregular Dynamics of Conductance-Based Networks of Adaptive Quadratic Integrate-and-Fire Neuron Models
Authors: Alexandersen Christoffer G. , Duprat Chloé , Ezzati Aitakin , Houzelstein Pierre , Ledoux Ambre , Liu Yuhong , Saghir Sandra , Destexhe Alain , Tesler Federico , Depannemaecker Damien 
Published: May 2024

Abstract
Mean-field models are a class of models used in computational neuroscience to study the behavior of large populations of neurons. These models are based on the idea of representing the activity of a large number of neurons as the average behavior of mean-field variables. This abstraction allows the study of large-scale neural dynamics in a computationally efficient and mathematically tractable manner. One of these methods, based on a semianalytical approach, has previously been applied to different types of single-neuron models, but never to models based on a quadratic form. In this work, we adapted this method to quadratic integrate-and-fire neuron models with adaptation and conductance-based synaptic interactions. We validated the mean-field model by comparing it to the spiking network model. This mean-field model should be useful to model large-scale activity based on quadratic neurons interacting with conductance-based synapses.