bluuebunny/crossref_metadata_2025_split huggingface dataset:
KLF2 Mediates the Suppressive Effect of Laminar Flow on Vascular Calcification by Inhibiting Endothelial BMP/SMAD1/5 Signaling
Authors: Huang Juan , Pu Yujie , Zhang Hongsong , Xie Liping , He Lei , Zhang Cheng-Lin , Cheng Chak Kwong , Huo Yingsong , Wan Song , Chen Shaoliang , Huang Yuhong , Lau Chi Wai , Wang Li , Xia Yin , Huang Yu , Luo Jiang-Yun 
Published: June 2021

Rationale:
Vascular calcification in arterial intima is closely associated with atherosclerosis. Endothelial cells (ECs) sense blood flow and respond to the mechanical cues generated by different flow patterns. Laminar flow induces an anti-atherosclerotic EC phenotype whereas disturbed flow exerts an atheroprone effect. However, the contribution of blood flow to calcification in atherosclerotic arteries remains to be evaluated.

Objective:
We aim to investigate whether blood flow plays a determinant role in the distribution of vascular calcification and the underlying mechanisms involved.

Methods and Results:

Computed tomography angiography analysis of human coronary arteries (n=48) shows that calcification preferentially develops at flow perturbated sites. Similar phenomenon was observed in calcified human aortic valves and mouse arteries. Nonuniform shear stress produced in Y-shaped slide simulating live conditions in branched arteries promotes calcification in human umbilical vein ECs. The expression of KLF2 (Krüppel-like factor 2), a transcription factor inducible by laminar flow, is reduced in ECs of calcified human aortic valves and in endothelial calcification model, suggesting that KLF2 downregulation is likely involved in intimal calcification. Indeed,
KLF2
silencing induces endothelial-to-mesenchymal transition and accelerates osteoinduction in both human aortic ECs and human umbilical vein ECs. EC-specific KLF2 knockdown promotes whereas AAV9 (adeno-associated virus serotype 9)-mediated EC-KLF2 overexpression ameliorates vascular calcification in
ApoE
−/−
mice. Global mRNA profiling in human umbilical vein ECs reveals that KLF2 inhibits the BMP (bone morphogenetic proteins)/SMAD1/5 pathway which is critical in vascular calcification. Furthermore, KLF2 mediates laminar flow-induced inhibition of the BMP/SMAD1/5 pathway. By contrast, disturbed flow-induced activation of BMP/SMAD1/5 pathway is suppressed by KLF2 overexpression. Mechanistically, KLF2 binds to the promoters of
BMP4
,
BMPER
, and
SMAD1
to directly regulate their expression in ECs.

Conclusions:
Vascular calcification prefers to occur at branched or bifurcated areas of vasculature. Laminar flow inhibits vascular calcification through KLF2-mediated inhibition of endothelial BMP/SMAD1/5 signaling. Targeting KLF2 may represent a novel therapeutic approach against vascular calcification.
Association of Meal and Snack Patterns With Mortality of All‐Cause, Cardiovascular Disease, and Cancer: The US National Health and Nutrition Examination Survey, 2003 to 2014
Authors: Wei Wei , Jiang Wenbo , Huang Jiaxin , Xu Jiaxu , Wang Xuanyang , Jiang Xitao , Wang Yu , Li Guili , Sun Changhao , Li Ying , Han Tianshu 
Published: June 2021

Background
Although accumulating evidence has demonstrated that consumption time of energy and macronutrients plays an important role in maintaining health, the association between consumption time of different foods and cardiovascular disease, cancer, and all‐cause mortalities is still largely unknown.

Methods and Results

A noninstitutionalized household population of the US 21 503 participants from National Health and Nutrition Examination Survey was included. Meal patterns and snack patterns throughout a whole day were measured using 24‐hour dietary recall. Principal component analysis was performed to establish dietary patterns. Cox proportional hazards models were used to evaluate the association between dietary patterns across meals and cardiovascular disease (CVD), cancer, and all‐cause mortalities. During the 149 875 person‐years of follow‐up, 2192 deaths including 676 deaths because of CVD and 476 because of cancer were documented. After adjusting for potential confounders, participants consuming fruit‐lunch had lower mortality risks of all‐cause (hazard ratio [HR], 0.82; 95% CI, 0.72–0.92) and CVD (HR, 0.66; 95% CI, 0.49–0.87); whereas participants who consumed Western‐lunch were more likely to die because of CVD (HR, 1.44; 95% CI, 1.10–1.89). Participants who consumed vegetable‐dinner had lower mortality risks of all‐cause, CVD, and cancer (HR
all‐cause
, 0.69; 95% CI, 0.60–0.78; HR
CVD
, 0.77; 95% CI, 0.61–0.95; HR
cancer
, 0.63; 95% CI, 0.48–0.83). For the snack patterns, participants who consumed fruit‐snack after breakfast had lower mortality risks of all‐cause and cancer (HR
all‐cause
, 0.78; 95% CI, 0.66–0.93; HR
cancer
, 0.55; 95% CI, 0.39–0.78), and participants who consumed dairy‐snack after dinner had lower risks of all‐cause and CVD mortalities (HR
all‐cause
, 0.82; 95% CI, 0.72–0.94; HR
CVD
, 0.67; 95% CI, 0.52–0.87). Participants who consumed a starchy‐snack after main meals had greater mortality risks of all‐cause (HR
after‐breakfast
, 1.50; 95% CI, 1.24–1.82; HR
after‐lunch
, 1.52; 95% CI, 1.27–1.81; HR
after‐dinner
, 1.50; 95% CI, 1.25–1.80) and CVD (HR
after‐breakfast
, 1.55; 95% CI, 1.08–2.24; HR
after‐lunch
, 1.44; 95% CI, 1.03–2.02; HR
after‐dinner
, 1.57; 95% CI, 1.10–2.23).

Conclusions
Fruit‐snack after breakfast, fruit‐lunch, vegetable‐dinner, and dairy‐snack after dinner was associated with lower mortality risks of CVD, cancer, and all‐cause; whereas Western‐lunch and starchy‐snack after main meals had greater CVD and all‐cause mortalities.
The Use of Design in Business Strategy: What's Beneath the
Surface?
Authors: Monteiro Guilherme Fowler A. 
Published: June 2021

Abstract
For a growing number of managers, a good strategy is supposedly one that is planned by heterogeneous groups in a design studio and one that manifests itself through a creative flash that can only be expressed in colorful Post-it notes. However, what does this mean exactly? Starting from this fundamental question, this article sketches the broad contours of a more theoretically grounded dialogue between the fields of design and strategy. The article highlights the examination of strategy problems as design problems, the role of paradoxes in strategy thinking, and the nature of design as a strategic meta-capability.
A Commander’s Motivations and Geographical Remoteness under Command Responsibility: An Analysis of Controversial Issues of the Bemba Appeal Judgment
Authors: Colorio Matteo 
Published: June 2021

Abstract
The Bemba Appeal Judgment undermines confident prospects that the International Criminal Court could make a greater use of charges alleging command responsibility. This judgment introduces serious uncertainties in the law on command responsibility, in particular by reflecting long-lasting disputes concerning this doctrine on the ‘all necessary and reasonable measures’ element under Article 28 of the Rome Statute. The Bemba Appeal Judgment, indeed, includes a controversial evaluation of the relevance of a commander’s motivations in taking measures and of her geographical remoteness from the crime scene. This Article analyses these issues through the lenses of International Humanitarian Law and of fundamental principles of International Criminal Law, in particular the principle of legality and the principle of individual culpability.
Stratospheric Mountain Waves Trailing across Northern Europe
Authors: Dörnbrack Andreas 
Published: June 2021

AbstractPlanetary waves disturbed the hitherto stable Arctic stratospheric polar vortex in the middle of January 2016 in such a way that unique tropospheric and stratospheric flow conditions for vertically and horizontally propagating mountain waves developed. Coexisting strong low-level westerly winds across almost all European mountain ranges plus the almost zonally aligned polar-front jet created these favorable conditions for deeply propagating gravity waves. Furthermore, the northward displacement of the polar night jet resulted in a widespread coverage of stratospheric mountain waves trailing across Northern Europe. This paper describes the particular meteorological setting by analyzing the tropospheric and stratospheric flows based on the ERA5 data. The potential of the flow for exciting internal gravity waves from nonorographic sources is evaluated across all altitudes by considering various indices to indicate flow imbalances as δ, Ro, Roζ, Ro⊥, and ΔNBE. The analyzed gravity waves are described and characterized. The main finding of this case study is the exceptionally vast extension of the mountain waves trailing to high latitudes originating from the flow across the mountainous sources that are located at about 45°N. The magnitudes of the simulated stratospheric temperature perturbations attain values larger than 10 K and are comparable to values as documented by recent case studies of large-amplitude mountain waves over South America. The zonal means of the resolved and parameterized stratospheric wave drag during the mountain wave event peak at −4.5 and −32.2 m s−1 day−1, respectively.
Abundant Cold Anticyclonic Eddies and Warm Cyclonic Eddies in the Global Ocean
Authors: Ni Qinbiao , Zhai Xiaoming , Jiang Xuemin , Chen Dake 
Published: June 2021

AbstractMesoscale eddies are ubiquitous features of the global ocean circulation and play a key role in transporting ocean properties and modulating air–sea exchanges. Anticyclonic and cyclonic eddies are traditionally thought to be associated with anomalous warm and cold surface waters, respectively. Using satellite altimeter and microwave data, here we show that surface cold-core anticyclonic eddies (CAEs) and warm-core cyclonic eddies (WCEs) are surprisingly abundant in the global ocean—about 20% of the eddies inferred from altimeter data are CAEs and WCEs. Composite analysis using Argo float profiles reveals that the cold cores of CAEs and warm cores of WCEs are generally confined in the upper 50 m. Interestingly, CAEs and WCEs alter air–sea momentum and heat fluxes and modulate mixed layer depth and surface chlorophyll concentration in a way markedly different from the traditional warm-core anticyclonic and cold-core cyclonic eddies. Given their abundance, CAEs and WCEs need to be properly accounted for when assessing and parameterizing the role of ocean eddies in Earth’s climate system.
Does Medical School Geography and Ranking Influence Residency Match in Otolaryngology?
Authors: Goshtasbi Khodayar , Tsutsumi Kotaro , Merna Catherine , Kuan Edward C. , Haidar Yarah M. , Tjoa Tjoson 
Published: June 2021

Objective: To elucidate the associations between geographic locations, rankings, and size/funding of medical schools and residency programs among the current otolaryngology residents. Methods: This retrospective cross-sectional study queried otolaryngology residency program websites for relevant publicly accessible information. Location was categorized as Midwest, Northeast, South, and West. Ranking was according to Doximity (residency) and US News and World Report (medical school). Medical school and residency programs were labeled large if they had >704 students or >15 residents, respectively. Results: A total of 1413 residents from 98 (89%) otolaryngology residency programs were included. Residents attending their home medical schools (18%) were equally distributed among regions ( P = .845). Residents who attended medical schools in the same US regions (54%) were more likely from top-25 ( P = .001) or private ( P < .001) medical schools. Southern residents were most likely (64%) and Western residents were least likely (39%) from regional medical schools ( P < .001), while residents from Midwest and Northeast had similar rates (54%-55%). The percentage of Midwest residents coming from regional medical schools has decreased from the 2013 to 2014 residency cycle ( P = .037). Completing undergraduate school, medical school, and residency in the same region (38%) was also highest in the South (45%) and lowest in the West (25%) ( P < .001). Residents at top-ranked residency programs were more likely from top-ranked ( P < .001), large ( P = .025), and private ( P = .018) medical schools. Conclusion: There exist significant associations between otolaryngology residents’ medical school location, ranking, size, and funding source and their residency destination. More than half of the current otolaryngology residents attended medical school in the same geographic region, and about one-fifth have attended medical school and residency at the same institution. Future studies are warranted to evaluate how these results change as the match process evolves in the future. Level of Evidence: N/A.
Dysphagia Severity and Outcomes Following Iatrogenic High Vagal Nerve Injury
Authors: Miles Ethan R. , Krishna Priya D. , Inman Jared C. , Lee Steve C. , Walker Paul C. , Simental Alfred A. , Crawley Brianna K. 
Published: June 2021

Objective: To examine severity of dysphagia and outcomes following iatrogenic high vagal nerve injury. Methods: Retrospective chart review of all patients with iatrogenic high vagal nerve injury that were seen at a tertiary referral center from 2012 to 2020. Results: Of 1304 patients who met criteria for initial screening, 18 met all inclusion criteria. All 18 required intervention to address postoperative dysphagia. Eleven required enteral feeding tubes with 7 eventually able to advance to exclusively per oral diets. Fourteen underwent vocal fold injection and 6 underwent laryngeal framework surgery. Sixteen pursued swallowing therapy with speech language pathology. Patients lost a mean of 8.6 kg of weight in the 6 months following the injury. Swallowing function on the Functional Outcome Swallowing Scale (FOSS) and Functional Oral Intake Scale (FOIS) was 4.4 and 2.4 respectively immediately following the injury and improved to 1.9 and 5.3 at the last follow-up. No patients had complete return of normal swallowing function at last follow up. Conclusion: Iatrogenic high vagal injury causes significant lasting dysphagia which improves with intervention but does not completely resolve. Interventions such as vocal fold injection, medialization laryngoplasty, cricopharyngeal myotomy, or swallowing therapy may be required to reestablish safe swallowing in these patients.
Coverage and Timing of Influenza Vaccination Among Privately Insured Pregnant Women in the United States, 2010-2018
Authors: Hong Kai , Lindley Megan C. , Zhou Fangjun 
Published: June 2021

Objective Pregnant women are at increased risk of serious complications from influenza and are recommended to receive an influenza vaccination during pregnancy. The objective of this study was to assess trends, timing patterns, and associated factors of influenza vaccination among pregnant women. Methods We used 2010-2018 MarketScan data on 1 286 749 pregnant women aged 15-49 who were privately insured to examine trends and timing patterns of influenza vaccination coverage. We examined descriptive statistics and identified factors associated with vaccination uptake by using multivariate log-binomial and Cox proportional hazard models. Results In-plan influenza vaccination coverage before delivery increased from 22.0% during the 2010-2011 influenza season to 33.2% during the 2017-2018 influenza season. About two-thirds of vaccinated women received the vaccine in September or October during each influenza season. For women who delivered in September through May, influenza vaccination coverage increased rapidly at the beginning of influenza season and flattened after October. For women who delivered in June through August, influenza vaccination coverage increased gradually until February and flattened thereafter. Most vaccinated women who delivered before January received the vaccine in the third trimester. Increased likelihood of being vaccinated was associated with age 31-40, living in a metropolitan statistical area, living outside the South, enrollment in a consumer-driven or high-deductible health plan, being spouses or dependents of policy holders, and delivery in November through January. Conclusions Despite increases during the past several years, vaccination uptake is still suboptimal, particularly after October. Health care provider education on timing of vaccination and recommendations throughout influenza seasons are needed to improve influenza vaccination coverage among pregnant women.
Increased number of deaths within 24 h of admission during a period of social restriction related to the COVID-19 pandemic: A retrospective service evaluation in a metropolitan palliative care unit
Authors: Everitt Rachel , Robinson Neil , Marco David , Weil Jennifer , Bryan Tamsin 
Published: June 2021

Background: COVID-19 has led to implementation of wide-ranging social restriction measures with consequent impact on health care utilisation in many domains. There is little published data on the experience of palliative care services catering to a population with low case numbers of COVID-19. Aim: This study aimed to consider the impact of COVID-19 on utilisation of inpatient palliative care in the context of low community transmission, and low numbers of cases in hospital. Design: A retrospective service evaluation examining differences in number of admissions, diagnoses, number of deaths and time from admission to death, across three discrete 8-week time periods spanning the early COVID-19 pandemic. Setting/participants: All admissions ( n = 194) to a metropolitan tertiary hospital inpatient palliative care unit in Melbourne during the study period. Results: An initial 16.9% fall in admissions was followed by a return to baseline admission numbers, with a 46.7% increase in number of deaths compared to baseline. The number of deaths within 24 h rose from 10.8% to 37.3% ( p < 0.01). The number of patients with non-malignant diagnoses increased from 32.4% to 52%, and those with non-malignant diagnoses were more likely to die rapidly ( p < 0.01). There were no patients with COVID-19 infection. Conclusion: Increased numbers of deaths within 24 h of admission occurred on the palliative care unit despite low COVID-19 case numbers in the wider community, and in the setting of widespread social restriction measures. More research is needed examining the health-related consequences of such restrictions for individuals not infected with COVID-19.
The impact of digital health interventions on the psychological outcomes of patients and families receiving paediatric palliative care: A systematic review and narrative synthesis
Authors: Archer Stephanie , Cheung Natalie H.Y. , Williams Ivor , Darzi Ara 
Published: June 2021

Background: Digital health interventions are becoming increasingly important and may be particularly relevant for paediatric palliative care. In line with the aims of palliative care, digital health interventions should aim to maintain, if not improve, psychological wellbeing. However, the extent to which the psychological outcomes of digital health interventions are assessed is currently unknown. Aim: To identify and synthesise the literature exploring the impact of all digital health interventions on the psychological outcomes of patients and families receiving paediatric palliative care. Design: Systematic review and narrative synthesis. Data sources: MEDLINE, EMBASE, Health Management Information Consortium, PsycINFO, Cumulative Index to Nursing and Allied Health Literature and the Midwives Information & Resource Service were searched on the 27th July 2020, in addition to the first five pages of Google Scholar. To be included in the review, papers must have contained: quantitative or qualitative data on psychosocial outcomes, data from patients aged 0–18 receiving palliative care or their families, a digital health intervention, and been written in English. Results: Three studies were included in the review. All looked at the psychological impact of telehealth interventions. Papers demonstrated fair or good quality reporting but had small sample sizes and varied designs. Conclusions: Despite the design and development of digital health interventions that span the technological landscape, little research has assessed their psychosocial impact in the paediatric palliative care community. Whilst the evidence base around the role of these interventions continues to grow, their impact on children and their families must not be overlooked.
Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model
Authors: Cattaneo Giorgio FM , Herrmann Andrea M , Eiden Sebastian A , Wieser Manuela , Kellner Elias , Doostkam Soroush , Süß Patrick , Kiefer Selina , Fauth Lisa , Maurer Christoph J , Wolfertz Julia , Nitzsche Björn , Büchert Michael , Jost Tobias , Ihorst Gabriele , Haberstroh Jörg , Mülling Christoph , Strecker Christoph , Niesen Wolf-Dirk , Shah Mukesch J , Urbach Horst , Boltze Johannes , Meckel Stephan 
Published: June 2021

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model. Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes. Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups. Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.
Correlation between matrix metalloproteinase-2 polymorphisms and first and recurrent atherosclerotic ischemic stroke events: a case–control study
Authors: Li Ying , Ouyang Qing-rong , Li Juan , Chen Xiao-rong , Li Lin-lin , Xu Lei , Yu Ming 
Published: June 2021

Objective To determine the associations between matrix metalloproteinase-2 (MMP-2, encoded by the MMP2 gene) 1306C/T and 735C/T polymorphisms and first and recurrent ischemic stroke in a Chinese population. Methods Patients with first and recurrent ischemic stroke were included. Serum MMP-2 was measured, and MMP2 1306C/T and 735C/T polymorphisms were detected. The associations between MMP2 1306C/T and 735C/T polymorphisms and first and recurrent ischemic stroke were analyzed. Results Serum MMP-2 in patients with first and recurrent ischemic stroke was significantly higher compared with controls, and patients with recurrent ischemic stroke had higher MMP-2 than those with first ischemic stroke. The frequency of the CC genotype and C allele of MMP2 735C/T was highest in patients with recurrent ischemic stroke, followed by patients with first ischemic stroke, and controls. Conversely, the genotype and allele of MMP2 1306C/T did not significantly differ between groups. The CC genotype of MMP2 735C/T was independently associated with first and recurrent ischemic stroke (odds ratios = 1.45 and 1.64, respectively), as was the C allele of MMP2 735C/T (odds ratios = 1.68 and 1.77, respectively). Conclusions The CC genotype and C allele of MMP2 735C/T were associated with first and recurrent ischemic stroke in a Chinese population.