bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammation drives residual risk in chronic kidney disease: a CANTOS substudy
Authors: Ridker Paul M , Tuttle Katherine R , Perkovic Vlado , Libby Peter , MacFadyen Jean G 
Published: August 2022

Abstract

Aims
Hyperlipidaemia and inflammation jointly contribute to atherosclerotic disease. Yet, after the initiation of statin therapy, the relative contributions of these processes may differ in patient groups, such as those with and without impaired kidney function.

Methods and results
Among 9151 stable statin-treated post-myocardial infarction patients participating in the CANTOS trial, the contributions of residual cholesterol risk and residual inflammatory risk were evaluated as determinants of recurrent major adverse cardiovascular events (MACE) and total mortality, stratified by baseline estimated glomerular filtration rate (eGFR) above or below 60 mL/min/1.73 m2 using the race agnostic CKD-EPI 2021 formula (all participants had eGFR &gt; 30 mL/min/1.73 m2). Analyses of residual inflammatory risk focused on high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) while analyses of residual cholesterol risk focused on LDL-cholesterol (LDL-C) and non-HDL-cholesterol (non-HDL-C). Participants were followed for a period of up to 5 years (median 3.7 years). Median baseline levels of LDL-C and hsCRP were 81 mg/dL and 4.2 mg/L. Among participants with eGFR ≥ 60 mL/min/1.73 m2, increasing quartiles of plasma hsCRP, IL-6, LDL-C, and non-HDL-C all positively associated with risks of recurrent MACE [hazard ratios (HR) comparing the top to bottom quartile for hsCRP 1.45; for IL-6 2.48; for LDL-C 1.64; and for non-HDL-C 1.68] (all P &lt; 0.0001). By contrast, among those with eGFR &lt; 60 mL/min/1.73 m2, increasing quartiles of hsCRP and IL-6 significantly predicted recurrent MACE [HR comparing the top to bottom quartile for hsCRP 1.50 (P = 0.021); for IL-6 1.84 (P = 0.048)], whereas increasing quartiles of LDL-C and non-HDL-C did not [HR comparing the top to bottom quartile for LDL-C 1.04 (P = 0.80); for non-HDL-C 0.98 (P = 0.88)]. The predictive utility of hsCRP and IL-6 in the setting of eGFR &lt; 60 mL/min/1.73 m2 remained significant after adjustment for a wide range of potential confounding factors including age, sex, smoking status, blood pressure, body mass index, and diabetes. For the endpoint of total mortality, both hsCRP (HR 1.77, P = 0.0021) and IL-6 (HR 2.15, P = 0.015) were significant predictors among those with eGFR &lt; 60 mL/min/1.73 m2, whereas LDL-C (HR 0.91, P = 0.56) and non-HDL-C (HR 0.85, P = 0.31) were not. Similar effects were observed in analyses stratified by the albumin to creatinine ratio rather than eGFR.

Conclusion
Among atherosclerosis patients with impaired kidney function already aggressively treated with statin therapy, residual inflammatory risk plays a substantial role in determining the risk of recurrent cardiovascular events. These data have implications for risk stratification of individuals with chronic kidney disease and for the development of novel agents that target inflammatory processes in this high-risk group of patients.

Clinical Trial Registration
ClinicalTrials.gov: NCT01327846
Current practices and expectations to reduce environmental impact of electrophysiology catheters: results from an EHRA/LIRYC European physician survey
Authors: Boussuge-Roze Julie , Boveda Serge , Mahida Saagar , Anic Ante , Conte Giulio , Chun Julian K R , Marijon Eloi , Sacher Frederic , Jais Pierre 
Published: August 2022

Abstract
The healthcare sector accounts for nearly 5% of global greenhouse gas emissions (GHG) and is a significant contributor to complex waste. Reducing the environmental impact of technology-heavy medical fields such as cardiac electrophysiology (EP) is a priority. The aim of this survey was to investigate the practice and expectations in European centres on EP catheters environmental sustainability. A 24-item online questionnaire on EP catheters sustainability was disseminated by the EHRA Scientific Initiatives Committee in collaboration with the Lyric Institute. A total of 278 physicians from 42 centres were polled; 62% were motivated to reduce the environmental impact of EP procedures. It was reported that 50% of mapping catheters and 53% of ablation catheters are usually discarded to medical waste, and only 20% and 14% of mapping and ablation catheters re-used. Yet, re-use of catheters was the most commonly cited potential sustainability solution (60% and 57% of physicians for mapping and ablation catheters, respectively). The majority of 69% currently discarded packaging. Reduced (42%) and reusable (39%) packaging also featured prominently as potential sustainable solutions. Lack of engagement from host institutions was the most commonly cited barrier to sustainable practices (59%). Complexity of the process and challenges to behavioral change were other commonly cited barriers (48% and 47%, respectively). The most commonly cited solutions towards more sustainable practices were regulatory changes (31%), education (19%), and product after-use recommendations (19%). In conclusion, EP physicians demonstrate high motivation towards sustainable practices. However, significant engagement and behavioural change, at local institution, regulatory and industry level is required before sustainable practices can be embedded into routine care.
The association of coagulation and atrial fibrillation: a systematic review and meta-analysis
Authors: Tilly Martijn J , Geurts Sven , Pezzullo Angelo M , Bramer Wichor M , de Groot Natasja M S , Kavousi Maryam , de Maat Moniek P M 
Published: August 2022

Abstract

Aims
While atrial fibrillation (AF) is suggested to induce a prothrombotic state, increasing thrombotic risk, it is also hypothesized that coagulation underlies AF onset. However, conclusive evidence is lacking. With this systematic review and meta-analysis, we aimed to summarize and combine the evidence on the associations between coagulation factors with AF in both longitudinal and cross-sectional studies.

Methods and results
We systematically searched for longitudinal cohort and cross-sectional studies investigating AF and thrombosis. For longitudinal studies, pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. For cross-sectional studies, we determined pooled standardized mean differences (SMDs) and 95% CIs. A total of 17 longitudinal and 44 cross-sectional studies were included. In longitudinal studies, we found significant associations between fibrinogen (HR 1.05, 95% CI 1.00–1.10), plasminogen activator inhibitor 1 (PAI-1) (HR 1.06, 95% CI 1.00–1.12), and D-dimer (HR 1.10, 95% CI 1.02–1.19) and AF incidence. In cross-sectional studies, we found significantly increased levels of fibrinogen (SMD 0.47, 95% CI 0.20–0,74), von Willebrand factor (SMD 0.96, 95% CI 0.28–1.66), P-selectin (SMD 0.31, 95% CI 0.08–0.54), ß-thromboglobulin (SMD 0.82, 95% CI 0.61–1.04), Platelet Factor 4 (SMD 0.42, 95% CI 0.12–0.7), PAI-1 (1.73, 95% CI 0.26–3.19), and D-dimer (SMD 1.74, 95% CI 0.36–3.11) in AF patients, as opposed to controls.

Conclusion
These findings suggest that higher levels of coagulation factors are associated with prevalent and incident AF. These associations are most pronounced with prevalent AF in cross-sectional studies. Limited evidence from longitudinal studies suggests a prothrombotic state underlying AF development.
New-onset atrial fibrillation following left bundle branch area pacing vs. right ventricular pacing: a two-centre prospective cohort study
Authors: Zhu Haojie , Li Xiaofei , Wang Zhao , Liu Qian , Chu Bingqian , Yao Yan , Liu Zhimin , Xie Ruiqin , Fan Xiaohan 
Published: August 2022

Abstract

Aims
To investigate whether left bundle branch area pacing (LBBAP) can reduce the risk of new-onset atrial fibrillation (AF) compared with right ventricular pacing (RVP).

Methods and results
Patients with indications for dual-chamber pacemaker implant and no history of AF were prospectively enrolled if they underwent successful LBBAP or RVP. The primary endpoint was time to the first occurrence of AF detected by pacemaker programming or surface electrocardiogram. Follow-up at clinic visit was performed and multivariate Cox regression models were applied to evaluate the effect of LBBAP on new-onset AF. The final analysis included 527 patients (mean age 65.3 ± 12.6, male 47.3%), with 257 in the LBBAP and 270 in the RVP groups. During a mean follow-up of 11.1 months, LBBAP resulted in significantly lower incidence of new-onset AF (7.4 vs. 17.0%, P &lt; 0.001) and AF burden (3.7 ± 1.9 vs. 9.3 ± 2.2%, P &lt; 0.001) than RVP. After adjusting for confounding factors, LBBAP demonstrated a lower hazard ratio for new-onset AF compared with RVP {hazard ratio (HR) [95% confidence interval (CI)]: 0.278 (0.156, 0.496), P &lt; 0.001}. A significant interaction existed between pacing modalities and the percentage of ventricular pacing (VP%) (P for interaction = 0.020). In patients with VP ≥ 20%, LBBAP was associated with decreased risk of new-onset AF compared with RVP [HR (95% CI): 0.199 (0.105, 0.378), P &lt; 0.001]. The effect of pacing modalities was not pronounced in patients with VP &lt; 20% [HR (95% CI): 0.751 (0.309, 1.823), P = 0.316].

Conclusion
Left bundle branch area pacing demonstrated a reduced risk of new-onset AF compared with RVP. Patients with a high ventricular pacing burden might benefit from LBBAP.
Fast walking and physical activity are independent contributors to improved physical function
Authors: Shiozaki Haruka , Fujihara Kazuya , Yamada-Harada Mayuko , Yamamoto Masahiko , Mitsuma Yurie , Kitazawa Masaru , Yaguchi Yuta , Matsubayashi Yasuhiro , Iwanaga Midori , Yamada Takaho , Kodama Satoru , Sone Hirohito 
Published: August 2022

AbstractBackground and objectivesTo clarify whether the presence or absence of fast walking and habitual physical activity are independently associated with the incidence of functional disability.MethodsThis historical cohort study was comprised of 9,652 (4,412 men, mean age 65 years) individuals aged 39–98 years without functional disability at baseline. Functional disability was determined based on the Japanese long-term care insurance system, which specified requirements for assistance in the activities of daily living. The impact of fast walking and habitual physical activity on the incidence of functional disability was analysed by Cox proportional hazards models.ResultsThe follow-up period was a median of 3.7 years during which 165 patients were newly certified as having functional disability. In the multivariate analysis, baseline age in 5-year increments (hazard ratio 2.42 [95% confidence interval 2.18–2.69]), no habitual physical activity (1.56 [1.07–2.27]), and not fast walking (1.89 [1.32–2.69]) significantly increased the risk of functional disability after adjustment for covariates. The stratified analysis showed that compared with physical activity (+), the impact of physical activity (−) on the incidence of functional disability was observed in those aged ≥75 years regardless of fast walking (+). Fast walking (−) significantly increased the risk of disability compared with fast walking (+) in those aged &lt;75 years regardless of a physical activity habit.ConclusionIn Japanese, slow walking speed and lack of a physical activity habit were shown to be independent risk factors for incident functional disability, with their impact differing according to age.
Genomic-environmental associations in wild cranberry (Vaccinium macrocarponAit.)
Authors: Neyhart Jeffrey L , Kantar Michael B , Zalapa Juan , Vorsa Nicholi 
Published: August 2022

AbstractUnderstanding the genetic basis of local adaptation in natural plant populations, particularly crop wild relatives, may be highly useful for plant breeding. By characterizing genetic variation for adaptation to potentially stressful environmental conditions, breeders can make targeted use of crop wild relatives to develop cultivars for novel or changing environments. This is especially appealing for improving long-lived woody perennial crops such as the American cranberry (Vaccinium macrocarpon Ait.), the cultivation of which is challenged by biotic and abiotic stresses. In this study, we used environmental association analyses in a collection of 111 wild cranberry accessions to identify potentially adaptive genomic regions for a range of bioclimatic and soil conditions. We detected 126 significant associations between SNP marker loci and environmental variables describing temperature, precipitation, and soil attributes. Many of these markers tagged genes with functional annotations strongly suggesting a role in adaptation to biotic or abiotic conditions. Despite relatively low genetic variation in cranberry, our results suggest that local adaptation to divergent environments is indeed present, and the identification of potentially adaptive genetic variation may enable a selective use of this germplasm for breeding more stress-tolerant cultivars.
Understanding reasons for and strategic responses to administrative health data misreporting in an Indian state
Authors: Meghani Ankita , Rodríguez Daniela C , Peters David H , Bennett Sara 
Published: August 2022

Abstract
The misreporting of administrative health data creates an inequitable distribution of scarce health resources and weakens transparency and accountability within health systems. In the mid-2010s, an Indian state introduced a district ranking system to monitor the monthly performance of health programmes alongside a set of data quality initiatives. However, questions remain about the role of data manipulation in compromising the accuracy of data available for decision-making. We used qualitative approaches to examine the opportunities, pressures and rationalization of potential data manipulation. Using purposive sampling, we interviewed 48 district-level respondents from high-, middle- and low-ranked districts and 35 division- and state-level officials, all of whom had data-related or programme monitoring responsibilities. Additionally, we observed 14 district-level meetings where administrative data were reviewed. District respondents reported that the quality of administrative data was sometimes compromised to achieve top district rankings. The pressure to exaggerate progress was a symptom of the broader system for assessing health performance that was often viewed as punitive and where district- and state-level superiors were viewed as having limited ability to ensure accountability for data quality. However, district respondents described being held accountable for results despite lacking the adequate capacity to deliver on them. Many rationalized data manipulation to cope with high pressures, to safeguard their jobs and, in some cases, for personal financial gain. Moreover, because data manipulation was viewed as a socially acceptable practice, ethical arguments against it were less effective. Potential entry points to mitigate data manipulation include (1) changing the incentive structures to place equal emphasis on the quality of data informing the performance data (e.g. district rankings), (2) strengthening checks and balances to reinforce the integrity of data-related processes within districts and (3) implementing policies to make data manipulation an unacceptable anomaly rather than a norm.
Complement factor B is critical for sub-RPE deposit accumulation in a model of Doyne honeycomb retinal dystrophy with features of age-related macular degeneration
Authors: Crowley Maura A , Garland Donita L , Sellner Holger , Banks Angela , Fan Lin , Rejtar Tomas , Buchanan Natasha , Delgado Omar , Xu Yong Yao , Jose Sandra , Adams Christopher M , Mogi Muneto , Wang Karen , Bigelow Chad E , Poor Stephen , Anderson Karen , Jaffee Bruce D , Prasanna Ganesh , Grosskreutz Cynthia , Fernandez-Godino Rosario , Pierce Eric A , Dryja Thaddeus P , Liao Sha-Mei 
Published: August 2022

Abstract
EFEMP1 R345W is a dominant mutation causing Doyne honeycomb retinal dystrophy/malattia leventinese (DHRD/ML), a rare blinding disease with clinical pathology similar to age-related macular degeneration (AMD). Aged Efemp1 R345W/R345W knock-in mice (Efemp1ki/ki) develop microscopic deposits on the basal side of retinal pigment epithelial cells (RPE), an early feature in DHRD/ML and AMD. Here, we assessed the role of alternative complement pathway component factor B (FB) in the formation of these deposits. RNA-seq analysis of the posterior eyecups revealed increased unfolded protein response, decreased mitochondrial function in the neural retina (by 3 months of age) and increased inflammatory pathways in both neural retina and posterior eyecups (at 17 months of age) of Efemp1ki/ki mice compared with wild-type littermate controls. Proteomics analysis of eye lysates confirmed similar dysregulated pathways as detected by RNA-seq. Complement activation was increased in aged Efemp1ki/ki eyes with an approximately 2-fold elevation of complement breakdown products iC3b and Ba (P &lt; 0.05). Deletion of the Cfb gene in female Efemp1ki/ki mice partially normalized the above dysregulated biological pathway changes and oral dosing of a small molecule FB inhibitor from 10 to 12 months of age reduced sub-RPE deposits by 65% (P = 0.029). In contrast, male Efemp1ki/ki mice had fewer sub-RPE deposits than age-matched females, no elevation of ocular complement activation and no effect of FB inhibition on sub-RPE deposits. The effects of FB deletion or inhibition on Efemp1ki/ki mice supports systemic inhibition of the alternative complement pathway as a potential treatment of dry AMD and DHRD/ML.
A new method for identifying and delineating spatial agglomerations with application to venture-backed startups
Authors: Egan Edward J , Brander James A 
Published: August 2022

Abstract
This article advances a new approach using hierarchical cluster analysis (HCA) for identifying and delineating spatial agglomerations and applies it to venture-backed startups. HCA identifies nested clusters at varying aggregation levels. We describe two methods for selecting a particular aggregation level and the associated agglomerations. The ‘elbow method’ relies entirely on geographic information. Our preferred method, the ‘regression method’, uses geographic information and venture capital investment data and identifies finer agglomerations, often the size of a small neighborhood. We use heat maps to illustrate how agglomerations evolve and we describe how our methods can help assess agglomeration support policies.
Hydroxysafflor yellow B induces apoptosis via mitochondrial pathway in human gastric cancer cells
Authors: Wang Dan , Wang Shasha , Liu Wenjing , Li Minjing , Zheng Qiusheng , Li Defang 
Published: August 2022

Abstract

Objectives
Hydroxysafflor yellow B (HSYB) is extracted from the petals of the safflower, a Chinese medicine. Relevant research results have demonstrated that HSYA can suppress the abnormal tumour cell proliferation and induce cell apoptosis. However, the properties of HSYB have rarely been reported, especially its antitumour effects on gastric cancer (GC).

Methods
SGC-7901 and BGC-823 cells were treated with different concentrations of HSYB. Cell proliferation inhibition rate was detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation detection. The changes in morphology of cells was observed by Hoechst 33258 staining. Cell apoptosis was evaluated by Annexin V-FITC/PI (fluoresceinisothiocyanate/propidium iodide) double staining. JC-1 was used to detect the level of mitochondrial membrane potential (MMP). The protein levels of cleaved-caspase-3, cleaved-caspase-9, APAF-1, cytoplasmic cytochrome C, BAX and BCL-2 were examined by western blot.

Key findings
HSYB significantly suppressed the proliferation of SGC-7901 and BGC-823 cells. Hoechst 33258 staining assay showed that HSYB treatment triggered apoptotic morphology and the apoptotic rates were significantly increased after being treated with HSYB and the mitochondrial membrane potential was gradually decreased in human GC cells. In addition, Western blot analysis revealed that the levels of cleaved-caspase-3 and cleaved-caspase-9 were remarkably increased in HSYB-treated BGC-823 and SGC-7901 cells. And, the levels of apoptotic protease activating factor-1 (APAF-1) and cytoplasmic cytochrome C were remarkably up-regulated in HSYB-treated cells. At the same time, HSYB could up-regulate the level of BAX and down-regulate the level of BCL-2.

Conclusions
Our data suggest that HSYB could induce GC cell apoptosis via the mitochondrial pathway.
‘The Name of God Has Priority’: ‘God’ and The Apophatic Element in Vladimir Nabokov’s Pale Fire
Authors: Eklund Erik 
Published: August 2022

Abstract
However one might interpret Vladimir Nabokov’s self-styled ‘utter indifference’ to religion, mysticism, and theology, his 1962 metafictional masterpiece, Pale Fire, betrays a measured though nonetheless peculiar engagement with theological ideas and sources. Focusing on the novel’s theological centre—Charles Kinbote’s note to line 549 of John Shade’s poem (‘While snubbing gods, including the big G’), which records Kinbote’s conversation with Shade on 23 June 1959 about religion and God—this article uncovers Pale Fire’s direct engagement with core tenets of the apophatic theologies of St Augustine and St Thomas Aquinas, and argues, moreover, that this works to highlight the analogy which the novel seeks to express between theological and literary discourse.
Cryptococcus neoformans can utilize ferritin as an iron source
Authors: Song Moonyong , Thak Eun Jung , Kang Hyun Ah , Kronstad James W , Jung Won Hee 
Published: August 2022

Abstract

Ferritin, a major iron storage protein in vertebrates, supplies iron upon iron deficiency. Ferritin is also found extracellularly, and acts as an iron carrier and a contributor to the immune response to invading microbes. Some microbial pathogens take advantage of ferritin as an iron source upon infection. However, no information is currently available on whether the human fungal pathogen Cryptococcus neoformans can acquire iron from ferritin. Here, we found that C. neoformans grew well in the presence of ferritin as a sole iron source. We showed that the binding of ferritin to the surface of C. neoformans is necessary and that acidification may contribute to ferritin-iron utilization by the fungus. Our data also revealed that the high-affinity reductive iron uptake system in C. neoformans is required for ferritin-iron acquisition. Furthermore, phagocytosis of C. neoformans by macrophages led to increased intracellular ferritin levels, suggesting that iron is sequestered by ferritin in infected macrophages. The increase in intracellular ferritin levels was reversed upon infection with a C. neoformans mutant deficient in the high-affinity reductive iron uptake system, indicating that this system plays a major role in iron acquisition in the phagocytosed C. neoformans in macrophages.

Lay Summary
Cryptococcus neoformans is an opportunistic fungal pathogen causing life-threatening pulmonary disease and cryptococcal meningitis, mainly in immunocompromised patients. In this study, we found that C. neoformans can use ferritin, a major iron storage protein in vertebrates, as a sole iron source.