bluuebunny/crossref_metadata_2025 huggingface dataset:
Network Meta‐Analysis Comparing the Outcomes of Treatments for Intermittent Claudication Tested in Randomized Controlled Trials
Authors: Thanigaimani Shivshankar , Phie James , Sharma Chinmay , Wong Shannon , Ibrahim Muhammad , Huynh Pacific , Moxon Joseph , Jones Rhondda , Golledge Jonathan
Published: June 2021

Background

No network meta‐analysis has considered the relative efficacy of cilostazol, home exercise therapy, supervised exercise therapy (SET), endovascular revascularization (ER), and ER plus SET (ER+SET) in improving maximum walking distance (MWD) over short‐ (<1 year), moderate‐ (1 to <2 years), and long‐term (≥2 years) follow‐up in people with intermittent claudication.

Methods and Results

A systematic literature search was performed to identify randomized controlled trials testing 1 or more of these 5 treatments according to Preferred Reporting Items for Systematic Review and Meta‐Analysis guidelines. The primary outcome was improvement in MWD assessed by a standardized treadmill test. Secondary outcomes were adverse events and health‐related quality of life. Network meta‐analysis was performed using the gemtc R statistical package. The Cochrane collaborative tool was used to assess risk of bias. Forty‐six trials involving 4256 patients were included. At short‐term follow‐up, home exercise therapy (mean difference [MD], 89.4 m; 95% credible interval [CrI], 20.9–157.7), SET (MD, 186.8 m; 95% CrI, 136.4–237.6), and ER+SET (MD, 326.3 m; 95% CrI, 222.6–430.6), but not ER (MD, 82.5 m; 95% CrI, −2.4 to 168.2) and cilostazol (MD, 71.1 m; 95% CrI, −24.6 to 167.9), significantly improved MWD (in meters) compared with controls. At moderate‐term follow‐up, SET (MD, 201.1; 95% CrI, 89.8–318.3) and ER+SET (MD, 368.5; 95% CrI, 195.3–546.9), but not home exercise therapy (MD, 99.4; 95% CrI, −174.0 to 374.9) or ER (MD, 84.2; 95% CrI, −35.3 to 206.4), significantly improved MWD (in meters) compared to controls. At long‐term follow‐up, none of the tested treatments significantly improved MWD compared to controls. Adverse events and quality of life were reported inconsistently and could not be meta‐analyzed. Risk of bias was low, moderate, and high in 4, 24, and 18 trials respectively.

Conclusions

This network meta‐analysis suggested that SET and ER+SET are effective at improving MWD over the moderate term (<2 year) but not beyond this. Durable treatments for intermittent claudication are needed.
Kawasaki Disease With Coronary Artery Lesions Detected at Initial Echocardiography
Authors: Ae Ryusuke , Maddox Ryan A. , Abrams Joseph Y. , Schonberger Lawrence B. , Nakamura Yosikazu , Kuwabara Masanari , Makino Nobuko , Kosami Koki , Matsubara Yuri , Matsubara Daisuke , Sasahara Teppei , Belay Ermias D.
Published: June 2021

Background

Detection of coronary artery lesions (CALs) at initial echocardiography can aid in diagnosing Kawasaki disease (KD) and inform primary adjunctive treatments. We aimed to characterize patients with KD with CALs detected at initial echocardiography.

Methods and Results

We analyzed data from the nationwide Japanese KD survey that contained information on 103 222 population‐based patients diagnosed with KD across Japan during 2011 to 2018. Patients with CALs detected at initial echocardiography were assessed by age, day of illness, and number of principal KD signs (≥3). Multivariable logistic regression analysis was performed to evaluate factors independently associated with CAL detection. Overall, 3707 (3.6%) patients had CALs detected at initial echocardiography. Patients aged <12 and ≥60 months were associated with CAL detection (adjusted odds ratio [95% CI], 1.28 [1.18‒1.39] and 1.32 [1.20‒1.45], respectively; reference, 12‒59 months). Patients with delayed hospital visits were increasingly at higher risk for CAL detection (days 7‒8, 1.84 [1.63‒2.08]; days 9–10, 4.30 [3.58–5.15]; and days ≥11, 9.12 [7.63‒10.90]; reference, days 1–4). Patients with 3 or 4 principal KD signs were independently associated with CAL detection (1.75 [1.63‒1.88]). These patients were significantly more likely to be aged <12 months but were not associated with delayed hospital visit. Younger patients visited at earlier days of illness.

Conclusions

Timely diagnosis could be beneficial for patients with KD. However, even when the hospital visit occurred early in the course of illness, patients with 3 or 4 principal KD signs, especially younger patients, were at higher risk of CAL detection at initial echocardiography.
Number and Replating Capacity of Endothelial Colony‐Forming Cells are Telomere Length Dependent: Implication for Human Atherogenesis
Authors: Toupance Simon , Simonici Stéphanie , Labat Carlos , Dumoulin Chloé , Lai Tsung‐Po , Lakomy Cécile , Regnault Véronique , Lacolley Patrick , Dignat George Françoise , Sabatier Florence , Aviv Abraham , Benetos Athanase , Gautier Sylvie , Watfa Ghassan , Louis Huguette , Folio Mélanie , Schmitt Margaux , Ayad Oualid , Didier Agnes , Vauthier Sandrine , François Nelly , Visvikis‐Siest Sophie , Stathopolou Maria G. , Kimura Masayuki , Rossi Pascal M. , Béranger Patricia , Malikov Serguei , Settembre Nicla , Hubert Jacques , Frimat Luc , Bertrand Baptiste , Boufi Mourad , Flecher Xavier , Sadoul Nicolas , Eschwege Pascal , Kessler Michèle , Tzanetakou Irene P. , Doulamis Ilias P. , Konstantopoulos Panagiotis , Tzani Aspasia , Korou Marilina , Gkogkos Anastasios , Perreas Konstantinos , Menenakos Evangelos , Samanidis Georgios , Vasiloglou‐Gkanis Michail , Kark Jeremy D. , Verhulst Simon
Published: June 2021

Background

Short leukocyte telomere length (TL) is associated with atherosclerotic cardiovascular disease. Endothelial repair plays a key role in the development of atherosclerosis. The objective was to examine associations between TL and proliferative dynamics of endothelial colony‐forming cells (ECFCs), which behave as progenitor cells displaying endothelial repair activity.

Methods and Results

To isolate ECFCs, we performed a clonogenic assay on blood samples from 116 participants (aged 24–94 years) in the TELARTA (Telomere in Arterial Aging) cohort study. We detected no ECFC clones in 29 (group 1), clones with no replating capacity in other 29 (group 2), and clones with replating capacity in the additional 58 (group 3). Leukocyte TL was measured by Southern blotting and ECFCs (ECFC‐TL). Age‐ and sex‐adjusted leukocyte TL (mean±SEM) was the shortest in group 1 (6.51±0.13 kb), longer in group 2 (6.69±0.13 kb), and the longest in group 3 (6.78±0.09 kb) (
P
<0.05). In group 3, ECFC‐TL was associated with the number of detected clones (
P
<0.01). ECFC‐TL (7.98±0.13 kb) was longer than leukocyte TL (6.74±0.012 kb) (
P
<0.0001) and both parameters were strongly correlated (
r
=0.82;
P
<0.0001).

Conclusions

Individuals with longer telomeres display a higher number of self‐renewing ECFCs. Our results also indicate that leukocyte TL, as a proxy of TL dynamics in ECFCs, could be used as a surrogate marker of endothelial repair capacity in clinical and laboratory practice because of easy accessibility of leukocytes.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02176941.
Abstract 85: Drip ‘n Ship vs. Mothership for Endovascular Treatment: Modeling the Best Transportation Options for Optimal Outcomes in California and Alberta
Authors: Milne Matthew S , Hill Michael D , Nygren Anders , Qiu Chao , Kamal Noreen
Published: June 2021

Background:
There is uncertainty about how patients outside of endovascular-capable or Comprehensive Stroke Centers (CSC) access Endovascular treatment (EVT) for acute ischemic stroke. The role of the non-endovascular-capable Primary Stroke Centers (PSC) that can offer thrombolysis with alteplase but not EVT is unclear. A key question is whether average benefit is greater with early thrombolysis at the closest PSC before transportation to the CSC (Drip ‘n Ship), or with PSC by-pass and direct transport to the CSC (Mothership). Ideal transportation options for California, USA and Alberta, Canada were mapped based on the location of their CSCs and PSCs.

Methods:
For those who received both EVT and alteplase, probability models were developed from the ESCAPE trial’s decay curves for good outcome defined as mRS 0-2 at 90 days. To determine the benefits of alteplase alone, probability models were extracted from the Get-With-The-Guidelines decay curve. The onset to EMS arrival, time on scene, needle-to-door-out time at the PSC, door-to-needle-time (DNT) at the CSC, and door-to-reperfusion time were assumed constant at 30, 25, 20, 30, and 115 minutes, respectively. EMS transportation times were calculated using Google’s Distance Matrix API interfaced with MATLAB’s Mapping Toolbox to create maps demonstrating the transportation scenario resulting in the best outcomes. Six maps were generated for 30, 60, and 90 minute DNT’s at the PSC’s.

Results:
In the figure, green regions represent a greater probability of good outcome via Mothership, whereas red indicates that Drip ‘n Ship is best. Orange indicates that either option yields a similar outcome (+/- 2.5%). The color tint increases (becomes brighter) as the probability of good outcome decreases. Grey indicates areas with a sparse road network.

Conclusions:
The role of a PSC in close proximity to a CSC remains significant only when the PSC is able to achieve both a DNT of 30 minutes or less and a needle-to-door out time of 20 minutes.
Abstract TMP6: A Multi-center Study of Safety and Efficacy of Mechanical Thrombectomy for Acute Ischemic Stroke Patients with Emergent Large Vessel Occlusions Not Meeting Top Tier Evidence Criteria
Authors: Goyal Nitin , Tsivgoulis Georgios , Frei Donald , Turk Aquilla , Baxter Blaise , Froehler Michael , Mocco J , Vachhani Jay , Hoit Daniel , Bhole Rohini , Elijovich Lucas , Alexandrov Andrei V , Alexandrov Anne W , Arthur Adam S
Published: June 2021

Background:
Recent recommendations for mechanical thrombectomy (MT) of acute ischemic stroke (AIS) patients with emergent large-vessel occlusions (ELVO) appropriately award top tier evidence (TTE) to the same selective criteria that were employed in recent clinical trials. We sought to evaluate the safety and efficacy of MT in AIS patients with ELVO who fail TTE criteria in a prospective multi-center study.

Methods:
Data on consecutive AIS patients with ELVO who underwent mechanical thrombectomy were collected from 6 high-volume endovascular centers. Standard safety and efficacy outcomes were compared between patients meeting and failing TTE criteria.

Results:
TTE criteria for MT were fulfilled in 349 (60%) cases (mean age 63±18 years; 47% men; median admission NIHSS-score

17 points, interquartile range 14-21), whereas 234 (40%) patients did not meet TTE criteria (mean age 62±19 years; 53% men; median admission NIHSS-score 16 points, interquartile range 9-21). (Table 1) The two most common reasons for failing TTE criteria were location of intracranial occlusion (n=144) and treatment window (n=108). In multivariate logistic regression models adjusting for potential confounders cases failing TTE criteria had similar safety (three-month mortality and symptomatic intracranial hemorrhage) and efficacy (three-month functional independence) outcomes with patients meeting TTE. Location of occlusion and proposed time-window according to TTE was also not related to any safety or efficacy outcome. (Table 2)

Conclusions:
Approximately 40% of AIS patients with ELVO offered MT do not fulfill TTE criteria for MT. Our multi-center experience indicates that MT may be offered to these patients with similar safety and efficacy to ELVO cases meeting TTE. Evidence-based medicine requires that health care providers understand published data and how those data might apply to a given patient’s treatment options. In a changing treatment environment this is a dynamic process.
Abstract 137: Vascular Smooth Muscle Cell MYPT1 Deficiency Induces Phenotype Switching and Disrupts Blood-Brain Barrier After Stroke
Authors: Fan Lizhen , Zhu Liwen , Meng Hailan , Xu Yun
Published: June 2021

Objectives:
Cerebral autoregulation and blood brain barrier (BBB) are often impaired in hypertensive and aging individuals, contributing to the development of stroke. Vascular smooth muscle cells (VSMC) play a vital role in cerebral blood flow control and maintenance of BBB. Ischemic injury triggers VSMC to switch into a detrimental phenotype in peripheral blood vessels, however, the pathological phenotype switching in cerebral VSMC and the impact of VSMC on BBB are not elucidated thoroughly in stroke with hypertension.

Methods:
Hypertensive mice with smooth muscle–specific deletion of MYPT1 (MYPT1
SMKO
mice) were generated. Middle cerebral artery occlusion (MCAO) was conducted in adult MYPT1
SMKO
mice and their wild-type (WT) mice for 60 min. Ischemic infarct volumes and neurological function were evaluated. Evens blue, immunofluorescence (IF), western blot (WB) and so on were performed to evaluate the permeability of BBB after stroke. The phenotype switching of VSMC was measured by WB, IF and quantitative real-time polymerase chain reaction (q-PCR) in oxygen glucose deprivation (OGD) and co-cultured in vitro models. Proteomic analysis was performed in cerebral capillaries. The q-PCR and WB were used for further validation.

Results:
It was found that the infarct volumes and neurological deficits were aggravated in MYPT1
SMKO
mice and the permeability of BBB was increased. The loss of pericyte cells and degradation of basement membrane of BBB were more severe in MYPT1
SMKO
mice. Furthermore, the protein expression of α-SMA in MYPT1
SMKO
mice after MCAO was reduced and the protein expression of Calponin and SM-22α was reduced. The ability of migration and proliferation in VSMC of MYPT1-knockout was altered after OGD. Proteomic analysis showed that the expression of protein associated with inflammation in VSMC of MYPT1
SMKO
mice was increased than that of WT mice, but the specific protein underlying the mechanism needs further verification.

Conclusions:
The damage of BBB was increased in MYPT1
SMKO
hypertensive mice. And there is a phenotype switching in cerebral VSMC after stroke in MYPT1
SMKO
hypertensive mice. The potential mechanism may involve the increasing expression of protein associated with inflammation in VSMC that needs further verification.
Abstract 25: Left Atrial Volume Index is Associated With Atrial Fibrillation and Recurrent Stroke in Embolic Stroke of Undetermined Source (ESUS)
Authors: Ho Jamie S , Sia Ching-Hui , Boi Yushan , Foo Anthia S , Dalakoti Mayank , Chan Mark Y , Ngiam Nicholas J , Chan Bernard P , Teoh Hock Luen , Sharma Vijay K , Kojodjojo Pipin , Seow Swee-Chong , Yeo Leonard L , Tan Benjamin Y
Published: June 2021

In ESUS, the relationship between atrial cardiopathy, occult AF and embolic stroke risk remains unclear. Studies suggest that left atrial volume index (LAVi) may be a better estimate of atrial cardiopathy than LA diameter. We explored LAVi as a marker of occult AF detection and ischemic stroke recurrence.

Methods:
From 2015-2017, consecutive ESUS patients diagnosed based on consensus criteria were studied. LAVi was measured using the Biplane Area-Length Method on TTE by trained cardiologists. Clinical outcomes measured were occult AF detection and ischemic stroke recurrence in a time-to-event analysis. Kaplan-Meier curves were constructed to compare outcomes in those with high versus low LAVi at optimized cut-off values.

Results:
199 consecutive ESUS patients were followed up for 2.2±1.0 years. 9 patients were excluded due to technically inadequate views. Increased LAVi was associated with AF detection (36.63mL/m
2
± 12.2 vs 26.93mL/m
2
± 9.6) and stroke recurrence (32.13mL/m
2
± 9.3 vs 27.23mL/m
2
± 10.1). On multivariate regression adjusting for age, sex, hypertension and diabetes mellitus, LAVI was independently associated with AF detection (OR 1.08, CI 95% 1.03-1.14; p=0.003) and stroke recurrence (OR 1.05, CI 95% 1.01-1.10; p=0.026). Kaplan-Meier curves showed significant differences in occult AF (log-rank 8.67, p=0.003) and stroke recurrence (log-rank 5.31, p=0.021) between high (>27.7ml/m
2
) and low LAVi (≤27.7ml/m
2
) groups.

Conclusion:
Increased LAVi in ESUS patients was associated with AF detection and stroke recurrence, suggesting that this may be a useful echocardiographic marker to identify high-risk patients who may potentially benefit from anticoagulation.
Abstract TP223: Carotid Web Quantification: Comparative Analysis Between 1-D, 2-D and 3-D Methods
Authors: Perry da Câmara Catarina , Nogueira Raul G , Alhamza Al-Bayati , Bouslama Mehdi , Pisani Leonardo , Mohammaden Mahmoud , Frankel Michael , Haussen Diogo C
Published: June 2021

Introduction:
Carotid webs (CaW) are now recognized as a cause of ischemic stroke specially in young patients. The thromboembolic potential appears related to the CaW morphology. We aim to evaluate the reliability of different measurements methods for the quantification of CaW size.

Methods:
This was a retrospective analysis of our CaW database (spanning September 2014 - July 2019). CT angiograms (CTA) were reviewed independently by two raters, blinded to the clinical information and laterality of the stroke/TIA. CaW were quantified with 1-D, 2-D and 3-D measurements (Figure) via Osirix software: 1-D was obtained with an oblique MIP with a perpendicular view of the CaW allowing the measurement of the base and the length of the CaW projection into the lumen; 2-D was defined by the area of the CaW delineated free-hand in the same view as the 1-D; 3-D was calculated with thin axial CTA cuts via volumetric analysis of free-hand delineated CaW limits.

Intraclass correlation coefficient was used to evaluate the inter-rater agreement and two sample t-test/ Mann Whitney U test to compare imaging characteristics between symptomatic and asymptomatic CaW. Patients with superimposed CaW thrombus and no repeat imaging were excluded.

Results:
Thirty-six patients with 46 CaW were included (33 symptomatic and 12 asymptomatic). Median age (IQR) was 49.5 (40.5-58.5) years, 77.8% were female and 77.1% were black. Inter-rater agreement was 0.961 (p<0.001) for 1-D, 0.933 (p<0.001) for 2-D and 0.936 (p<0.001) for 3-D measurements. Mean web length (1-D) was 3.1mm vs 2.5mm (p=0.01), while median area (2-D) was 5.8 vs 5.3mm
2
(p=0.35) and median volume (3-D) was 15.0 vs 10.8mm
3
(p=0.03) amongst symptomatic vs asymptomatic CaW, respectively.

Conclusion:
CaW size quantification (1-D, 2-D and 3-D) is highly reproducible. One dimensional measurement may be the method more strongly related to symptomatic vs asymptomatic status.
Abstract TP397: Modified Rankin Scores at 90-Days Post-Discharge
Authors: Sinogui Cynthia , Gregory Jeanette , Marion Tara , Mitchell Hillary , Keear Leslie , Moiseyenko Anna , DelaCruz Lloyd , Baumert Dalene , Girado Carolyn , Zrelak Pat , Hartman Jonathan
Published: June 2021

Background:
The modified Rankin Scale (mRS) is a validated tool used to assess a patient’s functional status. Comprehensive Stroke Centers are required to obtain mRS scores at 90-days for acute ischemic stroke patients who received intravenous alteplase and/or endovascular stroke treatment.

Purpose:
To develop and implement a sustained process for obtaining mRS scores 90-days post-hospitalization for all stroke patient types discharging from the acute hospital setting.

Methods:
A team of front-line nurses from various departments were trained on the mRS scoring tool. A smartphrase was developed to standardize documentation. CSTK-02 criteria were used and extended to all ischemic and hemorrhagic stroke discharges regardless of treatment or intervention received. A weekly call list was generated and provided. Calls were made to patients or caregivers between 8am and 7pm on weekdays, and occasionally on weekends, depending on the department making the calls. Three attempted calls were considered compliant. If a validation error occurred during screening, additional questions were asked based on the tool algorithm to resolve the error and ensure accuracy. Calls were rotated monthly by department.

Results:
Between May 2017 and May 2019, 1235 patients were discharged. A total of 297 patients were unable to be screened due to various reasons. 1115 patient contacts were attempted. Of those, 84% (938 patients) were screened. A retrospective breakdown of the mRS scores was stratified: 158 (17%) scored mRS of 0, 55 (6%) scored mRS of 1, 60 (6%) scored mRS of 2, 187 (20%) scored mRS of 3, 155 (17%) scored mRS of 4, 74 (8%) scored mRS of 5, and 249 (27%) scored mRS of 6.

Conclusion:
Having front-line nurses conduct 90-day post-discharge phone calls to obtain mRS scores appears to be an effective sustainable method in obtaining functional outcomes for all stroke types discharging from the acute hospital setting.
Abstract WMP101: Prediction of Clinical Outcome in Supratentorial Intracerebral Hemorrhage: Application of Baseline Ct Scan Radiomics Feature Extraction and Machine Learning Classifiers
Authors: Payabvash Seyedmehdi , Acosta Julian , Haider Stefan , Noche Rommell , Kirsch Elayna , Matouk Charles , Sansing Lauren H , Sheth Kevin N , Falcone Guido J
Published: June 2021

Aim:
Radiomics refers to automatic extraction of numerous quantitative features from medical images to supplement visual assessment. Machine-learning algorithms provide a suitable statistical methodology for devising predictive classifiers based on large radiomics datasets. We aimed to predict intracerebral hemorrhage (ICH) outcome by applying machine-learning classifiers to both clinical data and hematoma radiomics features.

Methods:
Patients enrolled in the Yale Longitudinal Study of ICH were included if they had (1) spontaneous supratentorial ICH, (2) baseline CT scan, (3) known admission Glasgow Coma Scale (GCS), and (4) 3-month modified Rankin Scale (mRS). A total of 1134 radiomics features related to the intensity, shape, texture, and waveform were extracted from manually segmented ICH lesions on baseline CT. Clinical variables were patients’ age, gender, GCS, presence of intraventricular hemorrhage, and thalamic ICH. We calculated the averaged receiver operating characteristics (ROC) area under curve (AUC) in outcome prediction among 100 repeats of 5-fold cross-validation (x500 iterations) for different combinations of feature selection and machine-learning algorithms.

Results:
A total of 119 ICH patients were included, of whom 60 had poor outcome (mRS ≥4). Among different combinations, lasso regression feature selection and partial least square (PLS) classification model yielded the highest accuracy in outcome prediction (Figure), with an averaged (95% confidence interval) ROC AUC of 0.86 (0.83 - 0.89) using clinical variables “only”, versus 0.92 (0.89 - 0.95) using combination of clinical variables and 54 radiomics features selected by lasso regression. Among radiomics features selected by lasso regression, ICH lesion flatness had the highest variable importance and was the only shape feature selected.

Conclusion:
Addition of ICH lesion radiomics to clinical variables using machine-learning models can improve outcome prediction.
Abstract WP131: Is 3 Years Adequate for Tracking Completely Occluded Coiled Aneurysms?
Authors: Yeon Eung Koo
Published: June 2021

Objective:
To ascertain the long-term durability of coiled aneurysms completely occluded at 36 months during follow-up given the potential for delayed recanalization.

Methods:
As a retrospective review, we examined 299 patients with 339 aneurysms, all completely occluded at 36 months in follow-up images obtained between 2011 and 2013. Medical records and radiologic data acquired during extended monitoring (mean, 74.3±22.5 months) were retrieved, analyzing incidence (including average annual risk) and risk factors of delayed recanalization.

Results:
A total of five coiled aneurysms (1.5%) occluded completely at 36 months showed recanalization (0.46 % per aneurysm-year) during continued long-term surveillance (1081.9 aneurysm-years), two surfacing within 60 months and three developing thereafter. Four showed minor recanalization, with only one instance of major recanalization. The latter involved posterior communicating artery as an apparent
de novo
lesion, arising at the neck of a firmly coiled sac, and was unrelated to coil compaction or growth. Additional embolization was undertaken. In multivariate analysis, second embolization for recurred aneurysm (HR=22.088, p=0.003) independently correlated with delayed recanalization.

Conclusion:
Almost all coiled aneurysms (98.5%) showing complete occlusion at 36 months post-embolization proved to be stable in extended observation. Therefore, it is reasonable to suspend imaging surveillance of coiled aneurysms after 3 years in the absence of demonstrable recanalization. However, recurrent aneurysms were predisposed to delayed recanalization.
Abstract WP351: Strokophobia Among Neurology, Internal Medicine and Emergency Medicine Residents
Authors: El Jamal Sleiman , Belagaje Samir
Published: June 2021

Clinical care of acute stroke patients can be handled by multiple specialties yet the concept of “strokophobia”, or the fear of dealing with stroke patients has not been explored in the literature. We explore some of the roots of that fear in residents of the neurology, emergency medicine (EM) and internal medicine (IM) specialties. An anonymous survey was sent to neurology, IM and EM residents at two different academic institutions. The survey inquired about the respondent’s demographics, training, and the first time the had a strong discomfort dealing with stroke. More detailed questions followed regarding some of the common perceived misconceptions and reasons behind the fear of caring for stroke patients. The questionnaire also inquired about some available resources to mitigate that fear. Of the 47 respondents, 47% were male. 57% were in IM, 38% were in neurology, and 4% from EM. 23% were in their PGY1 of training, 30 % were PGY2, 32% PGY3, and 15% PGY4. Most residents (83%) had an inpatient component in their neurology clerkship. 66% report having some fear in dealing with stroke patients. 28% report the fear to originally stem from the clinical years of medical school and 28% during residency. 40% of residents agreed that more neuroanatomy teaching is needed and 36% did not think enough education was given in medical school. 11% did not have a neurology clerkship in their medical school, 4% did not have an opportunity to work with a neurologist in medical school. 25% of residents report having limited exposure to stroke patients. 23% of residents consult neurology out of fear of missing significant pathology, while 23% were not comfortable with their exam skills. 38 % residents blame excessive paperwork for the lack of education while 23% think it was witnessing some attendings uncomfortable with stroke patients. The high acuity of these patients would deter 30% of the residents from caring for them. 11% of residents shy away due to having to establish adequate time windows or asking for help. 72% agree that more hands-on teaching is needed while 38% state that more tutorial videos could be helpful. In this first-ever exploratory analysis of strokophobia, the results show that the phenomenon is prevalent and more education is needed in order to mitigate it amongst residents.
Scale and Complexity in Political Economy: A Question of Liberty
Authors: Root Hilton L. , Shaheen Joseph A. E. , Tanca Dersu E. , Vizzard James W.
Published: June 2021

An analysis of network interactions in complex systems presents a more plausible explanation for the development of states and societies and the origins of liberty than does the linear approach adopted by Acemoğlu and Robinson in The Narrow Corridor, which is based on a single dichotomy—state vs. society. A methodology that responds to complexity relies on a far more comprehensive understanding of endogenous mechanisms of social change, the importance of pathways for information, the effects of system scaling, and, more generally, the dynamic relationship between a system and its constitutive parts.
Morpho-phylogenetic evidence reveals Lasiodiplodia chiangraiensis sp. nov. (Botryosphaeriaceae) associated with woody hosts in northern Thailand
Authors: WU NA , DISSANAYAKE ASHA J. , CHETHANA K.W. THILINI , HYDE KEVIN D. , LIU JIAN-KUI
Published: June 2021

Lasiodiplodia species are commonly as endophytes, saprobes and pathogens in tropics and subtropics. During an investigation of Botryosphaeriaceae in Thailand, two Lasiodiplodia taxa were isolated. Morphological characteristics and phylogenetic analyses based on combined ITS, tef and tub2 sequence data support the establishment of a novel species, Lasiodiplodia chiangraiensis, isolated from woody hosts. Lasiodiplodia chiangraiensis is phylogenetically close to L. iraniensis and L. thailandica, but represents a distinct lineage. The new species could be distinguished from extant Lasiodiplodia species by its mature conidial dimensions. A detailed description and illustration are provided, as well as an updated phylogenetic tree (ITS, tef and tub2) including all species (with available molecular data) of Lasiodiplodia. In addition, the accepted genera in Botryosphaeriaceae based on recent studies are given.
New species of ischnoceran chewing lice (Phthiraptera: Philopteridae) from Chinese birds
Authors: GUSTAFSSON DANIEL R. , TIAN CHUNPO , ZOU FASHENG
Published: June 2021

Five new species of chewing lice (Phthiraptera: Ischnocera) are described and illustrated from Chinese birds, as follows: Cuculicola calyptocamptus new species ex Hierococcyx sparverioides (Vigors, 1832) (Cuculiformes), Goniocotes kristinae new species ex Lophura swinhoii (Gould, 1863) (Galliformes), Goniocotes rolandi new species ex Crossoptilon harmani Elwes, 1881 (Galliformes), Rallicola (Rallicola) tibetana new species ex Zapornia bicolor Walden, 1872 (Gruiformes), and Resartor elugeus new species ex Alcippe fratercula yunnanensis Harington, 1913 (Passeriformes).
Molecular Mechanism of circRAPGEF5 in Regulating the Molecular Axis of microRNA-4712-5p/Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Epsilon Affecting Cellular Proliferation and Apoptosis in Mammary Cancer
Authors: Chen Tao , Sun Shengrong
Published: June 2021

To understand the molecular mechanism of circRAPGEF5, its effect on the proliferation and apoptosis of mammary cancer cells, and its regulatory effect on the molecular axis of miRNA-4712-5p/YWHAE. qRT-PCR and Western blot were used to test circRAPGEF5, miRNA-4712-5p, and YWHAE expression
in mammary cancer and paracancerous tissues. The human mammary cancer cell, MDA-MB-231, was cultured in vitro, and pcDNA-NC, pcDNA-circRAPGEF5, anti-miRNA-NC, anti-miRNA-4712-5p, pcDNA-circRAPGEF5, and miRNA-NC, pcDNA-circRAPGEF5 were transfected into MDA-MB-231 cells with miRNA-4712-5p
mimics. qRT-PCR and Western blot were employed to detect circRAPGEF5, miRNA-4712-5p, and YWHAE expression in cells. The CCK-8 methodand plate clone formation experiment were conducted to test cellular proliferation ability. Flow cytometry was performed to detect apoptosis rate. Dual luciferase
reporter assays were used to test the targeting association between circRAPGEF5 and miRNA-4712-5p, and the targeting association between miRNA-4712-5p and YWHAE. Western blot was utilized to detect Bcl-2, Bax, and Cleared Caspase-3 protein expression. In comparison with paracancerous tissues,
circRAPGEF5 and YWHAE expression levels in mammary cancer tissues were significantly reduced (P < 0.05), and miRNA-4712-5p expression levels were significantly increased (P < 0.05). Transfection of pcDNA-circRAPGEF5 or trans-anti-miRNA-4712-5p could reduce the optical density
(OD) value, Bcl-2 protein level and clonal formation number to a significant extent (P < 0.05), and it increases Bax and Cleaved Caspase-3 apoptosis rate and protein levels (P < 0.05). Dual luciferase reporter assays confirmed that there was target binding between circRAPGEF5
and miRNA-4712-5p and between miRNA-4712-5p and YWHAE. Co-transfection of pcDNA-circRAP GEF5 and miRNA-4712-5p could greatly reduce transfection of pcDNA-circRAP GEF5 and its effect on the proliferation and apoptosis of MDA-MB-231 cells. Overexpression of circRAPGEF5 can inhibit the proliferation
of mammary cancer cells and induce apoptosis by regulating the molecular axis of miRNA-4712-5p/YWHAE.
MiR-579-3p Protects Intestinal Mucosal Epithelial Cells from Hypoxia-Reoxygenation Injury by Targeting Cyclin-Dependent Kinase Inhibitor 1B
Authors: Guo Yuxiu , Ding Juan , Yan Wenjuan
Published: June 2021

Intestinal ischemia/reperfusion (I/R) injury is a common tissue and organ injury during surgery. This study explores miR-579-3p’s effect on the hypoxia-reoxygenation injury of intestinal mucosal epithelial cells via cyclin-dependent kinase inhibitor 1B (CDKN1B). Fetal human
cells (FHC) cells, which are human normal colorectal mucosal epithelial cells, were cultured in vitro to establish a hypoxia-reoxygenation (H/R) cell model. Nano-based qRT-PCR and Western blot detected miR-579-3p and CDKN1B expressions in HCCLM3 cells treated with H/R. CCK-8
method and flow cytometry measured miR-579-3p and CDKN1B expressions on cell activity and death after H/R treatment. Dual-Luciferase reporter experiment and Western blot analyzed the relationship between miR-579-3p and CDKN1B. After the FHC cells were treated with H/R, miR-579-3p
expression was decreased, whereas CDKN1B expression was increased (P < 0.05). FHC cells’ activity was decreased, and its apoptosis rate was upregulated; also, TNF-α and IL-6 protein levels were significantly enhanced (P < 0.05). Nevertheless, the
activity of FHC cells treated with H/R after miR-579-3p overexpression was significantly increased, while the apoptosis rate was upregulation, and TNF-α level, IL-6 levels were reduced (P < 0.05). The effect of inhibiting CDKN1B expression was the same as that
of overexpression miR-579-3p. After CDKN1B overexpression, the H/R-treated FHC cells’ viability was reduced, while the apoptosis rate was elevated, and TNF-α and IL-6 levels were elevated (P < 0.05). Compared to miR-579-3p overexpression, FHC cell activity
in treated with H/R after the overexpression of miR-579-3p+CDKN1B was reduced. At the same time, the apoptosis rate and the level of TNF-α and IL-6 protein were elevated (P < 0.05). In summary, MiR-579-3p’s targeting of CDKN1B protects FHC cells from
H/R injury by alleviating H/R-induced apoptosis and inflammation.
Long Non-Coding RNA GATA3-AS1 Promotes 5-Fluorouracil Resistance of Ovarian Cancer via Mediating miR-6771-3p/SOX4 Target Axis
Authors: Hao Yafei , Li Changzhou , Zhao Teng , Liu Hansheng
Published: June 2021

Ovarian cancer (OC) ranks as the 5th highest cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) exert significant effects on chemotherapy resistance. The effects of lncRNA GATA3-AS1 on the 5-Fluorouracil (5-FU) resistance in ovarian carcinoma were explored in the
current study. The results showed that GATA3-AS1 was highly expressed in OC tissues and 5-FU resistant OC cells. Moreover, GATA3-AS1 knockdown reduced 50% inhibitory concentration (IC50) of 5-Fluorouracil and promoted cell apoptosis, while GATA3-AS1-overexpression showed the opposite effect.
In vivo experiment and murine xenograft assay indicated GATA3-AS1 knockdown inhibited neoplasm growth, promoted cell apoptosis, and altered the expression level of apoptosis-associated proteins. GATA3-AS1 promoted SOX4 expression, a well-known transcription factor regulating apoptosis,
via targeting miR-6771-3p. In summary, our findings suggested GATA3-AS1 was associated with OC 5-Fluorouracil viaregulating miR-6771-3p/SOX4, providing novel insights into OC chemoresistance.
Nano Gold-Related PCR in Detection of MiR-145 and Its Correlation with Th1/Th2 in Premature Rupture of Fetal Membranes
Authors: Wang Hongyou , Chen Mei , Zhou Jianbo , Wang Yongfang , Zhang Lei
Published: June 2021

This study aimed to study miR-145’s correlation with Th1/Th2 in premature rupture of fetal membranes (pPROM) with nanogold-related PCR. Sixty pregnant women with pPROM between January 2019 to December 2019 were selected as the treatment group, and another sixty healthy pregnant
women at the stage were chosen as the control group. Blood samples were collected for the quantification of miR-145 and the Th1/Th2 ratio. The result showed that nanoPCR could detect miR-145 with higher sensitivity and specificity. Then, nanoPCR detected a decreased miR-145 in pPROM pregnant
women. Immunofluorescence staining and flow cytometry data presented a higher Th1/Th2 ratio in pPROM pregnant women. Western blotting showed the Th1/Th2 ratio increased significantly in pPROM pregnant women; also, the IFN-γ and IL-2 secreted by Th1 increased at the same time.
On the other hand, the IL-4 and IL-6 secreted by Th2 were reduced, consistent with the change in Th2’s pattern in number reduction. A significant negative correlation was shown between Th1, Th1/Th2, and miR-145, and a positive correlation was shown between Th2 and miR-145. In conclusion,
we propose thatin pPROM pregnant women, the decrease in miR-145 induces Th1 proliferation and Th2 reduction, causing relative cytokines to change and the immune system to lose imbalance. As more infections occur, and pPROM occurred as a result of fetal membrane fragility.
Study on the Effects of miR-490-3p on the Malignant Biological Behavior of Lung Tumor Cell A549 and Its Molecular Mechanism
Authors: Li Yuxiao , Hou Wei
Published: June 2021

The objective of this research was to prove whether miR-490-3p regulated the propagation, migration, and invasion of lung tumor cells using targeting sequence similarity as family 83F (FAM83F). The gene expression of miR-490-3p and FAM83F of human embryonic lung fibroblasts (HELF) and
lung cancer cells (A549, H1299, 95D) were analyzed using real-time quantitative reverse transcription-polymerase chain reaction PCR (RT-qPCR) and western blot. Analysis of the targeted relationship of miR-490-3P with FAM83F was performed through double luciferase reporting assays with the
addition of western blotting. The impacts of miR-490-3p and FAM83F gene expression were tested by cell counting kits (CCK-8), a scraping healing test, and a transwell test on the proliferation activity, scratch healing rate, and the numbers of migrating and invading A549 cells. Impacts of
miR-490-3P and FAM83F expressions on the phosphorylated protein kinase B’ (p-AKT) expression were tested with western blotting. miR-490-3P gene expressions in A549 were observably less expressed compared to that of HELF cells, but the mRNA and protein expressions of FAM83F were observably
greater than those in HELF (P < 0.05), which indicates that miR-490-3p-bound FAM83F regulates the expression of FAM83F immediately and negatively. After up-regulating miR-490-3p expression or down-regulating FAM83F expression, the proliferation activity, rate of wound-healing, the
numbers of migrating and invading cells, and p-AKT protein expression of A549 cells were observably reduced (P < 0.05). Compared to upregulation of miR-490-3p, the propagation activity, wound-healing rate, numbers of migrating and invading cells, and expression of the P-Akt protein
of A549 cells were significantly decreased after the upregulation of miR-490-3p and FAM83F (P < 0.05). MiR-490-3p observably inhibited migration and invasion in lung cancer cells with negatively regulating expression of FAM83F, and the mechanisms might be relevant to restraining
the AKT pathway.
Poriaic Acid Affecting Epithelial-Mesenchymal Transition and Apoptosis of A549/DDP Cells via Glycogen Synthesis Kinase-3β/Snail Signaling Pathway
Authors: Li Gengyao , Liu Bin , Xu Weiwei , Li Dongmei , Ji Wei
Published: June 2021

Background:The paper explored the mechanism of Poriaic acid-containing serum interfering with EMT and apoptosis of A549/DDP cells. The aim is to find experimental evidence of Poriaic acid intervening cisplatin resistance in lung cancer, searching for effective targets, and to explore the mechanism of cisplatin resistance in lung cancer.Material and methods:Immunochemistry and western blotting were employed to detect the effects of Poriaic acid-containing serum on the expressions of p-GSK-3β(ser9), Snail protein and mRNA in GSK-3β/Snail signaling pathway, and the effects of Poriaic acid-containing serum on the expressions of EMT markers and related apop-totic factors.Results:The results of immunoblotting and immunocytochemistry rendered that the expressions of p-GSK-3β(ser9), Snail protein and mRNA decreased in the administration group as contrast to the blank group. As to the effect of Poriaic acid-containing serum on EMT markers, the immunoblotting results showed that the E-cadherin protein and mRNA expressions increased while the expressions of N-cadherin protein and mRNA decreased. Poriaic acid-containing serum can up-regulate the expressions of P53, Bax protein and mRNA, and down-regulate the expressions of Bcl-2 protein and mRNA.Conclusion:Poriaic acid-containing serum can affect EMT and apoptosis of A549/DDP cells by interfering with GSK-3β/Snail signaling pathway.
The dejudicialization of religious freedom?
Authors: Mayrl Damon , Venny Dahlia
Published: June 2021

Despite a recent trend toward the judicialization of religious freedom (JRF), both historical experience and theoretical considerations suggest ‘dejudicialization’ is likely at some point. Yet, dejudicialization has provoked a little comment, and even less theorization, among social scientists studying religious freedom. This article conceptualizes the dejudicialization of religious freedom (DRF) in institutionalist terms, examines the structural forces that have facilitated JRF, and considers whether and how they may be waning in recent years. We argue conditions favorable toward dejudicialization in general, and DRF more specifically, are already emerging; highlight recent developments consistent with such a turn; and develop a typology of the forms that DRF may take.
Differences in social participation of older adults across European welfare regimes: Fourteen years of SHARE data collection
Authors: Lakomý Martin
Published: June 2021

Social participation amongst older adults is considered generally beneficial and is supported by active ageing policies in Europe. However, efforts to increase the quality of life and enhance the ageing experience may have the unintended consequence of increasing later life inequalities. This study uses six waves from SHARE to illustrate how social participation develops over time and how it is structured by education, financial situation and health status in the context of five European welfare regimes. The level of participation slightly increases over time for the population 55+, whilst the inequalities in access to these activities and their outcomes remain stable. Therefore, support of these activities does not strengthen or reduce inequalities amongst older adults – it may rather legitimise the inequalities in its emphasis on individual responsibilities. These findings suggest that the active ageing approach needs to become more context-sensitive or replaced by other social policy approaches.
Factors related to spiritual well-being in the last days of life in three East Asian countries: An international multicenter prospective cohort study
Authors: Hiratsuka Yusuke , Suh Sang-Yeon , Kim Sun-Hyun , Cheng Shao-Yi , Yoon Seok-Joon , Koh Su-Jin , Park Shin Ae , Seo Ji-Yeon , Kwon Jung Hye , Park Jeanno , Park Youngmin , Hwang Sun Wook , Lee Eon Sook , Ahn Hong-Yup , Hui David , Chen Ping-Jen , Yamaguchi Takashi , Morita Tatsuya , Tsuneto Satoru , Mori Masanori , Inoue Akira ,   and the EASED Investigators
Published: June 2021

Background:

Some factors associated with spiritual well-being in dying patients have previously been reported. However, there has been no cross-cultural study comparing factors related to spiritual well-being. The current investigation may shed light on this under-investigated area through a comparison of diverse factors.

Aim:

We aimed to (1) examine factors associated with spiritual well-being in the last days and (2) compare those factors across three East Asian countries.

Design:

This is an international multicenter prospective cohort study.

Setting/participants:

Newly admitted inpatients with far advanced cancer in palliative care units in Japan, Korea and Taiwan were enrolled. Each patient was classified into one of two groups based on spiritual well-being score in the last days of life. Univariate and multivariate analyses were performed to identify the factors related to better spiritual well-being score in each country.

Results:

A total of 1761 patients treated at 37 palliative care units from January 2017 to September 2018 were analyzed. Seven variables were significant in Japan, three in Korea, and five in Taiwan. “Good death scale [acceptance],” “fatigue” and “expressed wish for hastened death” were unique in Japan. “Visit from a pastoral care worker within 48 h of death” was unique in Korea. “Patient’s preferences for place of death,” “dyspnea” and “continuous deep sedation” were unique in Taiwan.

Conclusions:

This study found novel factors related to spiritual well-being in the last days of life, several of which differed according to country. Recognition of factors associated with spiritual well-being can improve the quality of palliative care.
Traffic Trumps All: Examining the Effect of Traffic Impact Analyses on Urban Housing
Authors: Ding Hao , Taylor Brian D.
Published: June 2021

Traffic impact analysis (TIA), which estimates the nearby traffic effects of proposed land development, tends to bias against higher density developments in urban areas where traffic is often heavy and travel alternatives plentiful. This has important implications for housing supply and affordability, suburban sprawl, and private vehicle dependence. We examine the understudied implications of TIA on housing by drawing on empirical evidence from distinct bodies of research in the transportation and land use planning literatures to describe the mechanisms through which TIA may affect housing markets. We conclude that TIAs likely have negative effects on both urban housing production and affordability.
Psychedelic psychodrama: Raising and expanding consciousness in Jane Arden’s The Other Side of the Underneath (1973)
Authors: Satchell-Baeza Sophia
Published: June 2021

Jane Arden’s debut feature film The Other Side of the Underneath (1973) is an adaptation of the radical feminist play A New Communion for Freaks, Prophets and Witches (1971). In both the play and the later film, the all-female cast re-enact personal and archetypal situations using autobiographical material, which was collectively gathered from group therapy sessions led by the director. Psychedelic drugs were also consumed during the group therapy sessions. In this article, I will situate Arden’s distinct approach to performance in the film within the framework of psychodrama, focusing specifically on the role that psychedelic drugs play in unleashing performers’ repressed feelings of trauma, rage, and desire; these emotions are harnessed into a dynamic mode of performance that amplifies the cathartic possibilities of women’s speech. The film’s heady brew of radical feminist politics, group therapy, and countercultural self-actualisation is both challenging and contentious. I argue that Arden’s pursuit of consciousness liberation through psychodrama and psychedelics—in other words, through ‘raising’ and ‘expanding’ consciousness—is best understood as a concerted attempt to align countercultural and radical feminist tactics for unravelling repressive forms of social conditioning.