bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of thermogenic adipose tissue in lipid metabolism and atherosclerotic cardiovascular disease: lessons from studies in mice and humans
Authors: Ying Zhixiong , Tramper Naomi , Zhou Enchen , Boon Mariëtte R , Rensen Patrick C N , Kooijman Sander
Published: August 2022

Brown adipocytes within brown adipose tissue (BAT) and beige adipocytes within white adipose tissue dissipate nutritional energy as heat. Studies in mice have shown that activation of thermogenesis in brown and beige adipocytes enhances the lipolytic processing of triglyceride-rich lipoproteins (TRLs) in plasma to supply these adipocytes with fatty acids for oxidation. This process results in formation of TRL remnants that are removed from the circulation through binding of apolipoprotein E (ApoE) on their surface to the LDL receptor (LDLR) on hepatocytes, followed by internalization. Concomitantly, lipolytic processing of circulating TRLs leads to generation of excess surface phospholipids that are transferred to nascent HDLs, increasing their capacity for reverse cholesterol transport. Activation of thermogenic adipocytes thus lowers circulating triglycerides and non-HDL-cholesterol, while it increases HDL-cholesterol. The combined effect is protection from atherosclerosis development, which becomes evident in humanized mouse models with an intact ApoE-LDLR clearance pathway only, and is additive to the effects of classical lipid-lowering drugs including statins and proprotein convertase subtilisin/kexin type 9 inhibitors. A large recent study revealed that the presence of metabolically active BAT in humans is associated with lower triglycerides, higher HDL-cholesterol and lower risk of cardiovascular diseases. This narrative review aims to provide leads for further exploration of thermogenic adipose tissue as a therapeutic target. To this end, we describe the latest knowledge on the role of BAT in lipoprotein metabolism and address, for example, the discovery of the β2-adrenergic receptor as the dominant adrenergic receptor in human thermogenic adipocytes.
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

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 > 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 < 0.0001). By contrast, among those with eGFR < 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 < 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 < 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

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

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

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 < 0.001) and AF burden (3.7 ± 1.9 vs. 9.3 ± 2.2%, P < 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 < 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 < 0.001]. The effect of pacing modalities was not pronounced in patients with VP < 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

Background and objectives

To clarify whether the presence or absence of fast walking and habitual physical activity are independently associated with the incidence of functional disability.

Methods

This 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.

Results

The 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 <75 years regardless of a physical activity habit.

Conclusion

In 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

Understanding 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

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

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 < 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

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

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

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

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.
False-negative and false-positive outcomes of computer-aided detection on brain metastasis: Secondary analysis of a multicenter, multireader study
Authors: Luo Xiao , Yang Yadi , Yin Shaohan , Li Hui , Zhang Weijing , Xu Guixiao , Fan Weixiong , Zheng Dechun , Li Jianpeng , Shen Dinggang , Gao Yaozong , Shao Ying , Ban Xiaohua , Li Jing , Lian Shanshan , Zhang Cheng , Ma Lidi , Lin Cuiping , Luo Yingwei , Zhou Fan , Wang Shiyuan , Sun Ying , Zhang Rong , Xie Chuanmiao
Published: August 2022

Background

Errors have seldom been evaluated in computer-aided detection on brain metastases. This study aimed to analyze false negatives (FNs) and false positives (FPs) generated by a brain metastasis detection system (BMDS) and by readers.

Methods

A deep learning-based BMDS was developed and prospectively validated in a multicenter, multireader study. Ad hoc secondary analysis was restricted to the prospective participants (148 with 1,066 brain metastases and 152 normal controls). Three trainees and 3 experienced radiologists read the MRI images without and with the BMDS. The number of FNs and FPs per patient, jackknife alternative free-response receiver operating characteristic figure of merit (FOM), and lesion features associated with FNs were analyzed for the BMDS and readers using binary logistic regression.

Results

The FNs, FPs, and the FOM of the stand-alone BMDS were 0.49, 0.38, and 0.97, respectively. Compared with independent reading, BMDS-assisted reading generated 79% fewer FNs (1.98 vs 0.42, P < .001); 41% more FPs (0.17 vs 0.24, P < .001) but 125% more FPs for trainees (P < .001); and higher FOM (0.87 vs 0.98, P < .001). Lesions with small size, greater number, irregular shape, lower signal intensity, and located on nonbrain surface were associated with FNs for readers. Small, irregular, and necrotic lesions were more frequently found in FNs for BMDS. The FPs mainly resulted from small blood vessels for the BMDS and the readers.

Conclusions

Despite the improvement in detection performance, attention should be paid to FPs and small lesions with lower enhancement for radiologists, especially for less-experienced radiologists.
Probable role of exosomes in the extension of fibrotic alterations from affected to normal cells in systemic sclerosis
Authors: Jimenez Sergio A , Piera-Velazquez Sonsoles
Published: August 2022

SSc is a systemic autoimmune disease of unknown etiology characterized by frequently progressive cutaneous and internal organ fibrosis causing severe disability, organ failure and high mortality. A remarkable feature of SSc is the extension of the fibrotic alterations to nonaffected tissues. The mechanisms involved in the extension of fibrosis have remained elusive. We propose that this process is mediated by exosome microvesicles released from SSc-affected cells that induce an activated profibrotic phenotype in normal or nonaffected cells. Exosomes are secreted microvesicles involved in an intercellular communication system. Exosomes can transfer their macromolecular content to distant target cells and induce paracrine effects in the recipient cells, changing their molecular pathways and gene expression. Confirmation of this hypothesis may identify the molecular mechanisms responsible for extension of the SSc fibrotic process from affected cells to nonaffected cells and may allow the development of novel therapeutic approaches for the disease.
Classifying the corporation: the role of naturalizing analogies in American corporate development, 1870–1930
Authors: Knight Carly R
Published: August 2022

Although the American corporation is now taken for granted as a private market actor, the corporation was once just as readily accepted as a quasi-public ‘creature of the state.’ This conceptual shift marks one of the most historically consequential instances of conceptual reclassification in American economic history. How was an understanding of the corporation as subordinate to the state replaced with an understanding of the corporation as prior to the state? In this article, I demonstrate that the symbolic privatization of the corporation was the joint product of both liberal and progressive legal theorizing. Further, I show that ‘naturalizing analogies’ are key to understanding this conceptual transformation. In tracing the legal theorization of the corporation, I show how the instability of naturalizing analogies, and their ability to entail associations beyond those intended by their proponents, played a role in corporate reclassification and are therefore critical to understanding the symbolic structure of corporate capitalism.
Post-COVID-19 neurologic syndrome
Authors: Luciew Joshua D. , Erickson Rodney A. , Kaufman Tara K.
Published: August 2022

COVID-19 quickly escalated to a global pandemic in 2020. As research on the topic continues, the medical community has found that this acute illness can cause a new chronic illness: postacute sequelae of SARS-CoV-2 (PASC). Some patients with PASC develop predominately neurologic sequelae (post-COVID-19 neurologic syndrome or PCNS). This article describes PASC and PCNS, their proposed pathogenicity and possible neurovirulence mechanisms, symptoms, and treatment recommendations.
Avascular Necrosis and Time to Surgery for Unstable Slipped Capital Femoral Epiphysis: A Systematic Review and Meta-analysis
Authors: Ibrahim Talal , Ball Matthew , Riaz Muhammad , Kenawey Mohamed
Published: August 2022

Background:

Avascular necrosis (AVN) is a well-known complication of unstable slipped capital femoral epiphysis (SCFE) and its cause is multifactorial. Higher AVN rates have been reported with surgery undertaken between 24 hours to 7 days from the onset of symptoms. The current evidence regarding time to surgery and AVN rate remains unclear. The aim of our study was to investigate the rate of AVN and time to surgery in unstable SCFE.

Methods:

A literature search of several databases was conducted. Eligibility criteria included all studies that reported AVN rates and time to surgery in unstable SCFE patients. We performed a meta-analysis using a random-effects model to pool the rate of AVN in unstable SCFE using different time to surgery subgroups (≤24 h, 24 h - 7 d and >7 d). Descriptive, quantitative and qualitative data were extracted.

Results:

Twelve studies matched our eligibility criteria. In total, there were 434 unstable SCFE of which 244 underwent closed reduction (CR). The pooled AVN rates were 24% [95% CI: 16%-35%] and 29% [95% CI: 16%-45%] for the total and CR groups, respectively. The highest AVN rates were with surgery between 24 hours to 7 days, 42% and 54% for the total and CR groups, respectively. The lowest rates of AVN were with time to surgery ≤24 hours (22% and 21% respectively) and >7 days (18% and 29% respectively). These differences were not statistically significant. There was significant subgroup heterogeneity which was highest in the 24 hours - 7 days subgroup and lowest in the >7 days subgroup.

Conclusions:

The cumulative evidence was not conclusive for an association between AVN rate and time to surgery. The overall AVN rates were lower in unstable SCFE patients who had surgery ≤24 hours and >7 days. However, treatment techniques were very variable and there was significant heterogeneity in the included studies. Multi-centre prospective studies are required with well-defined time to surgery outcomes.

Level of Evidence:

Level III/IV.
An Anatomic Study of the Proximal Tibial Epiphysis With Relevance to Percutaneous Epiphysiodesis Using Transphyseal Screws (PETS)
Authors: Do Michael T. , McCarthy Conor F. , Cooperman Daniel R. , Liu Raymond W.
Published: August 2022

Background:

Percutaneous epiphysiodesis using transphyseal screws (PETS) is a common procedure to correct lower extremity limb-length discrepancies in the pediatric population. A potential complication of this procedure is development of tibial valgus deformity, which may occur secondary to decreased screw purchase in the thinner medial proximal tibial epiphysis. The thickness of the proximal tibial epiphysis has not yet been well quantified, which was the aim of this study.

Methods:

Three-dimensional surface scans of 32 cadaveric proximal tibial epiphyses in specimens aged 3 to 17 years old were obtained and computer modeling software was utilized to measure the thickness of the proximal tibial epiphysis at 20 standardized potential screw insertion points according to a generated 5×4 map.

Results:

When normalized to the total width of the proximal tibial epiphysis, the lateral side is thicker compared with the medial side. The positions with the greatest thickness are located at the midline in the sagittal plane and 33% of the total physeal width away from the medial and lateral edges in the coronal plane (0.265 and 0.261 normalized thickness, respectively). The proximal tibial epiphysis is particularly thin 25% from the medial edge (normalized thickness range: 0.196 to 0.221). Multiple regression analysis revealed a significant relationship between increasing age and female sex with thinner normalized medial and lateral heights.

Conclusions:

During PETS, areas for greater screw purchase are located centrally in the sagittal plane and 33% of the total width away from the medial and lateral edges of the proximal tibial epiphysis in the coronal plane. Caution should be taken when inserting screws in the medial 25% of the proximal tibial epiphysis as it is thinner relative to the lateral edge, particularly in females.

Clinical Relevance:

This study provides quantitative, anatomic data on the thickness of the proximal tibial epiphysis, which can direct screw placement during PETS for correcting limb-length discrepancies. These data may help lessen the risk of developing tibial valgus deformity although future clinical studies are necessary to fully evaluate this possibility.
Semispinalis Cervicis Sarcopenia is Associated With Worsening Cervical Sagittal Balance and Junctional Alignment Following Posterior Cervical Fusion for Myelopathy
Authors: Pinter Zachariah W. , Salmons Harold I. , Townsley Sarah , Omar Adan , Michalopoulos Giorgos , Freedman Brett A. , Currier Bradford L. , Elder Benjamin D. , Nassr Ahmad N. , Bydon Mohamad , Fogelson Jeremy , Sebastian Arjun S.
Published: August 2022

Study Design:

This was a retrospective cohort study.

Objective:

The present study is the first to investigate whether cervical paraspinal sarcopenia is associated with cervicothoracic sagittal alignment parameters after posterior cervical fusion (PCF).

Summary of Background Data:

Few studies have investigated the association between sarcopenia and postoperative outcomes after cervical spine surgery.

Methods:

We retrospectively reviewed patients undergoing PCF from C2–T2 at a single institution between the years 2017–2020. Two independent reviewers utilized axial cuts of T2-weighted magnetic resonance imaging sequences to perform Goutallier classification of the bilateral semispinalis cervicis (SSC) muscles. Cervical sagittal alignment parameters were compared between subgroups based upon severity of SSC sarcopenia.

Results:

We identified 61 patients for inclusion in this study, including 19 patients with mild SSC sarcopenia and 42 patients with moderate or severe SSC sarcopenia. The moderate-severe sarcopenia subgroup demonstrated a significantly larger change in C2–C7 sagittal vertical axis (+6.8 mm) from the 3-month to 1-year postoperative follow-up in comparison to the mild sarcopenia subgroup (−2.0 mm; P=0.02). The subgroup of patients with moderate-severe sarcopenia also demonstrated an increase in T1–T4 kyphosis (10.9–14.2, P=0.007), T1 slope (28.2–32.4, P=0.003), and C2 slope (24.1–27.3, P=0.05) from 3-month to 1-year postoperatively and a significant decrease in C1-occiput distance (6.3–4.1, P=0.002) during this same interval.

Conclusions:

In a uniform cohort of patients undergoing PCF from C2–T2, SSC sarcopenia was associated with worsening cervicothoracic alignment from 3-month to 1-year postoperatively.
Axial Neck-Shoulder Pain After Posterior Correction and Fusion for Adolescent Idiopathic Scoliosis With Structural Thoracic Curve
Authors: Watanabe Kei , Ohashi Masayuki , Tashi Hideki , Shibuya Yohei , Makino Tatsuo , Hasegawa Kazuhiro , Hirano Toru
Published: August 2022

Study Design:

A retrospective cohort study using prospectively collected data.

Objectives:

To investigate the incidence and impact of fusion to the upper thoracic spine on neck-shoulder symptoms after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS).

Summary of Background Data:

Axial neck-shoulder pain is established as a sequela of posterior cervical spine surgery and is mainly caused by the dissection of extensor muscles in the cervical and upper thoracic spine.

Materials and Methods:

Sixty-three female patients with AIS who underwent PSF using segmental pedicle screw constructs for structural main thoracic curve with a minimum 2-year follow-up were included. Axial neck-shoulder pain was assessed using the visual analog scale and cervical spine function domain score of the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire. The patients were divided into 2 groups, a higher group (underwent fusion up to T3 or above, n=27) and a lower group (underwent fusion up to T4 or below, n=36), and radiologic and clinical outcomes were compared.

Results:

The incidence of axial neck-shoulder pain (visual analog scale ≥30) preoperatively and at the 2-year follow-up was 29 and 40%, respectively. The pain and mental health domains of the Scoliosis Research Society-22 and cervical spine function domain of the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire were correlated with the severity of axial neck pain. In the comparison of clinical outcomes between the 2 groups, the pain domain score of the Scoliosis Research Society-22 in the lower group was significantly better than that in the higher group at the 2-year follow-up (P<0.05). Other parameters showed no significant differences preoperatively or at the 2-year follow-up.

Conclusion:

Female patients with AIS had a relatively high incidence of axial neck-shoulder pain after PSF, which affected their health-related quality of life. Both groups showed similar clinical outcomes, and the cranial fusion level did not affect axial neck-shoulder pain and cervical spine function.

Level of Evidence:

Level 3.
Advancing Curriculum Development and Design in Health Professions Education: A Health Equity and Inclusion Framework for Education Programs
Authors: Agic Branka , Fruitman Howard , Maharaj Asha , Taylor Jessica , Ashraf Aamna , Henderson Joanna , Ronda Natalia , McKenzie Kwame , Soklaridis Sophie , Sockalingam Sanjeev
Published: August 2022

The COVID-19 pandemic has exacerbated pre-existing health inequities in vulnerable and marginalized patient populations. Continuing professional development (CPD) can be a critical driver of change to improve quality of care, health inequities, and system change. In order for CPD to address these disparities in care for patient populations most affected in the health care system, CPD programs must first address issues of equity and inclusion in their education development and delivery. Despite the need for equitable and inclusive CPD programs, there remains a paucity of tools and frameworks available in the literature to guide CPD and broader education providers on how best to develop and deliver equitable and inclusive education programs. In this article, we describe the development and application of a Health Equity and Inclusion (HEI) Framework for education and training grounded in the Analyze, Design, Develop, Implement, and Evaluate model for instructional design. Using a case example, specifically a hospital-wide trauma-informed de-escalation for safety program, we demonstrate how the HEI Framework can be applied practically to CPD programs to support equity and inclusion in the planning, development, implementation, and evaluation phases of education program delivery. The case example illustrates how the HEI Framework can be used by CPD providers to respect learner diversity, improve accessibility for all learners, foster inclusion, and address biases and stereotypes. We suggest that the HEI Framework can serve as an educational resource for CPD providers and health professions educators aiming to create equitable and inclusive CPD programs.
General anaesthesia for nonobstetric surgery during pregnancy
Authors: Bleeser Tom , Vally Janine C. , Van de Velde Marc , Rex Steffen , Devroe Sarah
Published: August 2022

Nonobstetric surgery may be required in up to 1% of pregnancies. Most common procedures are urgent abdominal surgeries requiring general anaesthesia. Maintaining normal maternal physiology during anaesthesia is vital. Left lateral tilt position prevents aortocaval compression and preserves normal venous return. Preparation for a difficult airway is required in all obstetric patients due to the known anatomical and physiological changes. Aspiration prophylaxis and a rapid sequence induction are traditionally recommended to avoid the (probably overestimated) risk of aspiration. Although the minimum alveolar concentration (MAC) of volatile anaesthetic agents is reduced by 30 to 40%, awareness occurs more frequently in the obstetric population. Maternal outcomes from surgery are comparable with those of nonpregnant women, but increased incidences of foetal loss, preterm delivery, low birth weight and caesarean section have been reported. Although animal studies have observed impaired foetal brain development after antenatal exposure to anaesthesia, the translational value of these studies remain controversial. Clinical evidence is nearly absent. Withholding urgent/essential procedures is certainly more threatening than proceeding with the surgery. To increase the safety of mother and foetus, nonurgent or nonessential procedures should be postponed until after delivery, and if procedures cannot wait, locoregional anaesthesia should be used if possible. Where general anaesthesia cannot be avoided, the duration of exposure should be kept to a minimum. This narrative review summarises the literature of the past 20 years concerning the anaesthetic management and outcomes of nonobstetric surgery under general anaesthesia during pregnancy.
“No One Should Feel Like They're Unsafe”
Authors: Romano Evalynn Fae T. , Baquero Barbara , Hicks Olivia , Gardner Victoria A. , Shannon KL , Hoerster Katherine D.
Published: August 2022

Mobility is an often overlooked social determinant of health that broadly affects people of color's health. This study aimed to examine personal and community mobility challenges and opportunities among youth of color and partner to advance equitable community mobility. We conducted a community-based participatory research photovoice study using mobility justice principles from November 2020 to May 2021 with 10 youth of color from South Seattle, Washington. We conducted thematic content analysis of verbatim transcripts. Youth recommended infrastructure changes and free transit to facilitate safe, accessible mobility. Youth reported feeling vulnerable riding public transit alongside people experiencing mental health issues, while recognizing the dangers police can bring to people with mental health challenges and/or communities of color. They emphasized the importance of youth voice and intergenerational community discussions to inform policy making. We coorganized an online forum with youth to exchange ideas for advancing equitable mobility with their community and city leaders. Youth expressed feeling empowered and deepening dedication to mobility justice. Leaders should implement policy and infrastructure changes to enhance equitable mobility by incorporating youth and mobility justice principles in decision-making processes, pay youth for their time, employ facilitators of color, and offer technology support.
Risk Factors for GDM in Subsequent Pregnancy Among Women Without GDM History in China: A Multicenter Retrospective Study
Authors: Song Geng , Wei Yumei , Juan Juan , Su Rina , Yan Jianying , Xiao Mei , Zhao Xianlan , Zhang Meihua , Ma Yuyan , Liu Haiwei , Sun Jingxia , Hu Kejia , Yang Huixia
Published: August 2022

Objective

This study aimed to determine the likelihood of gestational diabetes mellitus (GDM) in subsequent pregnancy among women without GDM history and to identify risk factors for GDM in subsequent pregnancy.

Methods

This retrospective cohort study involved participants who delivered twice in same hospital of 18 research centers when delivered the second baby from January 2018 to December 2018. Finally 6204 women were enrolled and 5180 women without GDM history were analyzed further. Women were categorized as non-GDM or GDM based on the blood glucose values of the subsequent pregnancy, and the characteristics and GDM risk of these groups were compared. A univariate analysis of potential risk factors was performed using the Chi-squared test and/or t-test for qualitative or quantitative variables, respectively. Associations with P values <0.1 were chosen to be included in the multivariate binary logistic regression model.

Results

In primary analysis of 6204 women, the incidence of GDM in subsequent pregnancy is 48.9% (490/1002) in women with GDM history and 16.1% (835/5202) in women without GDM history. In a further analysis for 5180 women without GDM at index pregnancy, compared with the non-GDM group, the GDM group had a significantly higher age, prepregnancy body mass index, and blood glucose value at each oral glucose tolerance test (OGTT) timepoint (fasting, 1h and 2h) during the index and subsequent pregnancies, as well as higher weight retention during the interval between the two pregnancies (P<0.001). Age above 35years in subsequent pregnancy (odds ratio (OR)=1.540, 95% confidence interval (CI) = 1.257–1.886, P<0.001), macrosomia in index pregnancy (OR=1.749, 95% CI=1.277–2.395, P<0.001), OGTT blood glucose values in index pregnancy (fasting, OR=2.487, 95% CI=1.883–3.285, P<0.001; 1h, OR=1.142, 95% CI=1.051–1.241, P<0.001; 2h, OR=1.290, 95% CI=1.162–1.432, P<0.001) and weight retention (OR=1.052, 95% CI=1.035–1.068, P<0.001) were independent risk factors for GDM in subsequent pregnancy.

Conclusion

For women without GDM history, GDM risk factors including age, macrosomia history, OGTT value, and weight retention, these can be evaluated before a subsequent pregnancy. Early warning and interventions are needed for women at high risk.