bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystal entrainment from cool, low-silica rocks into hot, high-silica melts: diverse primary melt compositions at Taranaki volcano, New Zealand
Authors: D'Mello Nessa G. , Zellmer Georg F. , Kereszturi Gabor , Ubide Teresa , Procter Jonathan N. , Stewart Robert B.
Published: February 2023

The prevalence of antecrysts in arc volcanic rocks is widely accepted, yet the origin of their carrier melts remains debated. Crystal cargo in lava flows from Taranaki volcano, New Zealand, is dominated by plagioclase, clinopyroxene and amphibole. Except for some crystal rims, mineral phases are in disequilibrium with the melt they are entrained in. Major element chemistry reveals an almost complete compositional overlap between the crystals in the lava and those in xenoliths. The large volume fraction of crystals (35–55 vol%) exerts a strong control on whole-rock compositions, reducing silica by 5–11 wt% compared with the carrier melt. Yet there is no clear relationship between mineral proportion and bulk-rock compositions. Our data are inconsistent with extensive fractional crystallization, commonly invoked as a driver of magma evolution towards silica-rich compositions. Instead, high-temperature, aphyric carrier melts with varied compositions (55–68 wt% SiO
2
) entrain crystal cargo while ascending through colder, low-silica rocks. Thus, some parental melts at Taranaki volcano are significantly more silica-rich than arc basalts commonly invoked as primary magmas. Further, thermometric and hygrometric constraints preclude a deep crustal hot zone for the source of these melts, which we argue are of subcrustal origin.

Supplementary material:
Supplementary figures and databases are available at
https://doi.org/10.6084/m9.figshare.c.6406813
Robust Dimensionality Reduction via Low-rank Laplacian Graph Learning
Authors: Cai Mingjian , Shen Xiangjun , Abhadiomhen Stanley Ebhohimhen , Cai Yingfeng , Tian Sirui
Published: February 2023

Manifold learning is a widely used technique for dimensionality reduction as it can reveal the intrinsic geometric structure of data. However, its performance decreases drastically when data samples are contaminated by heavy noise or occlusions, which leads to unsatisfying data processing performance. We propose a novel robust dimensionality reduction method via low-rank Laplacian graph learning for classification and clustering tasks to solve the above problem. First, we construct a low-rank Laplacian graph by combining manifold learning and subspace learning. This graph can capture both global and local structural information of the data. And we introduce rank constraints for the Laplacian graph to make it more discriminative. Second, we put the learning of projection matrix and sample affinity graph into a unified framework. The projection matrix is embedded into a robust low-rank Laplacian graph so that the low-dimensional mapping of data can maintain the structural information in the graph well. Finally, we add a regularization term to the projection matrix to make it have the ability of both feature extraction and feature selection. Therefore, the proposed model can resist the interference of noise or data damage to learn the optimal projection to achieve better performance in dimensionality reduction through such a data dimensionality reduction joint framework. Comprehensive experiments on various benchmark datasets with varying degrees of occlusions or corruptions are carried out to evaluate the performance of the proposed method. Compared with the state-of-the-art dimensionality reduction methods in the literature, the experimental results are inspiring, showing our method’s effectiveness and robustness in classification and clustering, especially in object recognition scenarios with noise or occlusions.
Lung cancer-kidney cross talk induces kidney injury, interstitial fibrosis, and enhances cisplatin-induced nephrotoxicity
Authors: Orwick Andrew , Sears Sophia M. , Sharp Cierra N. , Doll Mark A. , Shah Parag P. , Beverly Levi J. , Siskind Leah J.
Published: February 2023

Patients with cancer have impaired kidney function and increased susceptibility to nephrotoxic agents. Cisplatin is a commonly used chemotherapeutic with nephrotoxicity as the dose-limiting side effect. Cisplatin nephrotoxicity is almost exclusively studied in mice without cancer. Our current preclinical models do not adequately represent the complexity of patients with cancer. This study demonstrates increased renal toxicity, injury, and fibrosis in mice with lung cancer, which is exacerbated with cisplatin treatment. These results highlight the necessity of using preclinical models that more accurately capture the altered physiology of patients with cancer treated with cisplatin.
Intrahospital supervised exercise training improves survival rate among hypertensive patients with COVID-19
Authors: Fernandez Francisco , Vazquez-Muñoz Manuel , Canals Andrea , Arce-Álvarez Alexis , Salazar-Ardiles Camila , Alvarez Cristian , Ramirez-Campillo Rodrigo , Millet Gregoire P. , Izquierdo Mikel , Andrade David C.
Published: February 2023

In the present study, we found that exercise training improves the survival rate in hypertensive patients with COVID-19 during their hospitalization period. Our results provide strong evidence for the therapeutic efficacy of exercise training as a feasible approach to improving the outcomes of patients with COVID-19 who suffer from hypertension during their hospitalization.
The multiple roles of salt-inducible kinases in regulating physiology
Authors: Jagannath Aarti , Taylor Lewis , Ru Yining , Wakaf Zeinab , Akpobaro Kayomavua , Vasudevan Sridhar , Foster Russell G.
Published: February 2023

Salt-inducible kinases (SIKs), which comprise a family of three homologous serine-threonine kinases, were first described for their role in sodium sensing but have since been shown to regulate multiple aspects of physiology. These kinases are activated or deactivated in response to extracellular signals that are cell surface receptor mediated and go on to phosphorylate multiple targets including the transcription cofactors CRTC1–3 and the class IIa histone deacetylases (HDACs). Thus, the SIK family conveys signals about the cellular environment to reprogram transcriptional and posttranscriptional processes in response. In this manner, SIKs have been shown to regulate metabolic responses to feeding/fasting, cell division and oncogenesis, inflammation, immune responses, and most recently, sleep and circadian rhythms. Sleep and circadian rhythms are master regulators of physiology and are exquisitely sensitive to regulation by environmental light and physiological signals such as the need for sleep. Salt-inducible kinases have been shown to be central to the molecular regulation of both these processes. Here, we summarize the molecular mechanisms by which SIKs control these different domains of physiology and highlight where there is mechanistic overlap with sleep/circadian rhythm control.
Deformation Characteristics and Control Mechanisms of Deep High‐Stress Large‐Span Roadways
Authors: Yang Bo , Chai Jing
Published: February 2023

Controlling the surrounding rock in soft rock roadways under deep high stress, strong rheology, and intensive mining is critical for the safety, efficiency, and economy of mine production. In this study, the mechanical properties, large deformation mechanism, and support countermeasures of surrounding rock in the high‐stress roadway in the Yuwu coal mine were systematically explored through laboratory tests, numerical calculations, and field measurements. It is shown that mudstone and sandstone are mainly composed of chlorite and kaolinite, respectively. Also, mudstone features elastoplasticity and experiences argillization and swelling in water. The mechanism of surrounding rock deformation in the high‐stress roadway in the Yuwu coal mine was determined. As the V‐shaped shear zone in the side corner expanded to the deep under high deviatoric stress, large‐scale tensile damage occurred in the shallow surrounding rock. Consequently, discontinuous stresses in deep and shallow parts induce the expansion and fracturing of the roadway. The deformation velocity and damage degree of surrounding rock rise exponentially under different stress release coefficients, so the reduced distance of the face roof under control and timely support is important for restricting the free surface. An idea of “timely and active reinforcing the side and strengthening the bottom” was proposed. This approach made the loads on all the support objects within the working range. The overall deformation of the surrounding rock was controlled within 350 mm, ensuring the long‐term stability of the roadway.
Deep Learning and Medical Image Processing Techniques for Diabetic Retinopathy: A Survey of Applications, Challenges, and Future Trends
Authors: Uppamma Posham , Bhattacharya Sweta
Published: February 2023

Diabetic retinopathy (DR) is a common eye retinal disease that is widely spread all over the world. It leads to the complete loss of vision based on the level of severity. It damages both retinal blood vessels and the eye’s microscopic interior layers. To avoid such issues, early detection of DR is essential in association with routine screening methods to discover mild causes in manual initiation. But these diagnostic procedures are extremely difficult and expensive. The unique contributions of the study include the following: first, providing detailed background of the DR disease and the traditional detection techniques. Second, the various imaging techniques and deep learning applications in DR are presented. Third, the different use cases and real‐life scenarios are explored relevant to DR detection wherein deep learning techniques have been implemented. The study finally highlights the potential research opportunities for researchers to explore and deliver effective performance results in diabetic retinopathy detection.
Comparative Study of Swelling Pressure in Expansive Soils considering Different Initial Water Contents and BOFS Stabilization
Authors: Keskin İnan , Salimi Mahdi , Ateyşen Eylem Özge , Kahraman Selman , Vakili Amir Hossein
Published: February 2023

In terms of geotechnical engineering, swelling soils are among the most important soil groups whose characteristics should be determined in detail before design studies. These types of soils cause significant damage to engineering structures. For this reason, it is expected that the swelling behavior of the soils will be known in advance to minimize the damage that may occur in the structures. Within the scope of this study, the swelling pressures of bentonite clay with 10 different water content were determined by keeping all conditions the same to reveal the effect of water content on soil swelling behavior. In this context, bentonite-type (montmorillonite content) clay, which has a very swelling property when it comes in contact with water, was used in the experiments. The fixed volume swelling pressure test method was used in the experiments and all samples were compressed at the same rate and placed in the swelling test device. In all samples left to swell with pure water, measurements were made for 10 days and the effects of swelling pressures on the initial water content were discussed. Thereafter, another swelling soil was stabilized using basic oxygen furnace slag (BOFS) during different curing times, and after performing the swelling pressure test, the results were compared with the findings obtained from different initial water contents. According to the results, while the swelling pressures increase in the regions close to optimum water content, significant decreases are observed in swelling pressure values in wetter and drier regions than in optimum water content. Finally, the results indicated that the application of BOFS, albeit small, after the proper curing time can significantly affect the swelling behavior of bentonite, even more than changing the initial water content.
Extraction Optimization, Preliminary Identification, and Bioactivities in Corn Silk
Authors: Li Ping , Ren Guangxi , Sun Yifan , Jiang Dan , Liu Chunsheng
Published: February 2023

For thousands of years, corn silk has been widely used as an antidiabetic, antioxidant, and antihyperlipidemic and for other effects, but there is a lack of studies that correlate the extracts of flavonoid composition with their biological activities. Thus, the objectives of this study were to optimize the conditions for extracting flavonoids, identify flavonoids, and correlate the flavonoid composition with the biological activities in corn silk. The response surface experiments showed that the highest flavonoid content was predicted at 45.321 min, 57.349°C, 26.089 mL/g, and 71.269%, respectively. The verification experiment results under these optimized conditions showed an ultrasonic time of 45 min, an ultrasonic temperature of 57°C, a liquid‐to‐material ratio of 26, and an ethanol volume fraction of 70%. No significant differences (the relative error is 4.378%) were observed between the theoretical and experimental TFC values, indicating that the developed models were accurate. Under these optimum extraction conditions, 20 major compounds were identified and quantified by UPLC‐LTQ/Orbitrap MS. Furthermore, these optimum ethanol extracts of corn silk are effective against Bacillus subtilis and hypoglycemic activity compared with the traditional heating reflux extraction method. Six corn silk components seem to be the main contributors to the inhibitory effect against Bacillus subtilis and hyperglycemia activities. These results are useful for the application of corn silk in the food or pharmaceutical industry.
Impact of Preoperative Quality of Life and Related Factors on the Development of Surgical Site Infections Following Primary Total Joint Arthroplasty: A Prospective Case-Control Study with a Five-Year Follow-Up
Authors: Iliopoulou-Kosmadaki Styliani , Hadjimichael Argyris C. , Kaspiris Angelos , Lianou Ioanna , Kalogridaki Marina , Trikoupis Ioannis , Touzopoulos Panagiotis , Velivasakis Emmanuel , Sperelakis Ioannis , Laskaratou Emmanouela Dionysia , Melissaridi Dimitra , Vasiliadis Elias , Kontakis Georgios , Papagelopoulos Panagiotis J. , Savvidou Olga D.
Published: February 2023

Introduction. As surgical site infections (SSIs) after joint arthroplasty contribute to increased morbidity and mortality, they require further surgical intervention, prolonged hospitalisation, and antimicrobial treatment. The aim of our study is to examine the association between preoperative quality of life (QoL) and other predictive factors on the development of SSIs after primary arthroplasty. Methods. This is a prospective study that enrolled 56 patients with hip and knee primary osteoarthritis who underwent joint replacement. Data were collected from January to March 2017, including patient demographic characteristics, comorbidities, laboratory results, and perioperative clinical data. The patients’ QoL was evaluated preoperatively by applying the knee injury and osteoarthritis outcome score (KOOS) and the hip disability and osteoarthritis outcome score (HOOS) for total knee replacement (TKR) and total hip replacement (THR), respectively. A 5-year follow-up was conducted to assess the clinical status of the patients. Results. 66.1% of patients underwent TKR, with 4.9 ± 1.2 days of hospitalisation, 16% of them required autologous blood transfusion, while 33.9% of patients were treated with THR, with 5.7 ± 1 days hospitalisation and 36.8 of them required this type of transfusion. 16 patients were diagnosed with SSIs, with the older of them (>65 years old) presenting lower probability (odds ratio: 0.13, 95% CI: 0.03–0.62) requiring treatment with additional antibiotics, while revision surgery was performed in 3 of these cases, following periprosthetic joint infection (PJI). Overall preoperative QoL was not statistically associated with SSIs, but low QoL scores were associated with higher rates of SSIs and increased levels of postoperative pain (

p

 = 0.009 < 0.05). Conclusions. The duration of each operation (>90 min), the length of hospitalisation (>4 days), and the presence of comorbidities including hypothyroidism and recurrent urinary tract infections were associated with a high risk for SSIs following arthroplasties. On the contrary, this study revealed no association between other comorbidities, including heart coronary disease, hypertension, and diabetes mellitus, with close monitoring of plasma glucose and SSIs. Moreover, the younger the patients, the more likely they were to require treatment with antibiotics. Overall, high QoL index scores were mainly accompanied by low rates of postoperative SSIs and pain.
Identification and Verification of Potential Biomarkers in Renal Ischemia‐Reperfusion Injury by Integrated Bioinformatic Analysis
Authors: Pan Ziwen , Yang Yuanyuan , Cao Rui , Qiu Yang , Li Shanglin , Zhao Yuanyuan , Chang Sheng , Chen Song , Chen Zhishui , Zhang Weijie , Zhao Daqiang
Published: February 2023

Background. Renal ischemia‐reperfusion injury (RIRI) plays an important role in the poor prognosis of patients with renal transplants. However, the potential targets and mechanism of IRI are still unclear. Method. Differential gene expression (DEG) analysis and weighted correlation network analysis (WGCNA) were performed on the GSE27274 dataset. Pathway enrichment analysis on the DEGs was performed. To identify the hub DEGs, we constructed a protein‐protein interaction (PPI) network. Finally, the hub genes were verified, and candidate drugs were screened from the DsigDB database. Results. A hundred DEGs and four hub genes (Atf3, Psmb6, Psmb8, and Psmb10) were screened out. Pathway enrichment analysis revealed that 100 DEGs were mainly enriched in apoptosis and the TNF signaling pathway. The four hub genes were verified in animal models and another dataset (GSE148420). Thereafter, a PPI network was used to identify the four hub genes (Atf3, Psmb6, Psmb8, and Psmb10). Finally, eight candidate drugs were identified as potential drugs. Conclusion. Three hub genes (Psmb6, Psmb8, and Psmb10) were associated with RIRI and could be potential novel biomarkers for RIRI.
Optimal Operation of Distributed Generations in Four-Wire Unbalanced Distribution Systems considering Different Models of Loads
Authors: Jin Xiuling , Moradi Zohre , Rashidi Rohollah
Published: February 2023

The distribution network is generally unbalanced due to the distribution of consumers in different phases and the different status of their energy consumption. Also, in recent years, the utilization of distributed generations (DGs) has flourished in the distribution network, thanks to their favorable operational and environmental benefits. Therefore, it is predicted that the optimal energy management of DGs in the unbalanced distribution network can improve the operation state of the network. Moreover, the consumer load model is generally a combination of constant impedance, constant current, and constant power conditions. Therefore, the current study focuses on the analysis of the operation of unbalanced four-wire distribution systems containing DGs, in which load models are also involved. An optimization structure is established to make the voltage deviation, power loss, neutral wire loss, and voltage unbalance minimized. Limitations of the problem include those related to the network and those concerning operating indices of the system like voltage magnitude and phase angle of buses, power flow through the distribution lines, constraints of operation of DGs, load model, and unbalanced conditions. The problem formed in this study is nonlinear and is solved using sequential quadratic programming (SQP) by implementing it in the GAMS simulation environment. To test the benefits of the introduced approach, a 13-bus distribution system has been adopted so that the optimal operation of DGs in the distribution network has been able to reduce the unbalanced situation of the network compared to the power flow studies. Also, this scheme has improved the operation of network, where energy losses and voltage drop have been reduced compared to power flow studies, and a smooth voltage profile has been extracted.
Phase I Study of the Liposomal Formulation of Eribulin (E7389-LF): Results from the Advanced Gastric Cancer Expansion Cohort
Authors: Shitara Kohei , Hirao Motohiro , Iwasa Satoru , Oshima Takashi , Komatsu Yoshito , Kawazoe Akihito , Sato Yasuyoshi , Hamakawa Takuya , Yonemori Kan , Machida Nozomu , Yuki Satoshi , Suzuki Takuya , Okumura Shiori , Takase Takao , Semba Taro , Zimmermann Bob , Teng Angela , Yamaguchi Kensei
Published: February 2023

Purpose:

In the dose-expansion part of this open-label, phase I study, we explored the efficacy and safety of E7389-LF (liposomal formulation of eribulin) in Japanese patients with advanced gastric cancer.

Patients and Methods:

Patients with advanced gastric cancer who had been previously treated with ≥2 lines of chemotherapy received E7389-LF 2.0 mg/m2 every 3 weeks (the previously determined maximum tolerated dose, the primary objective of Study 114). Secondary objectives included objective response rate (ORR), progression-free survival (PFS), and safety; exploratory objectives included disease control rate (DCR) and clinical benefit rate (CBR), as well as pharmacodynamic measurements of serum biomarkers.

Results:

As of June 24, 2021, 34 patients were enrolled and treated (10 from the original dose-expansion cohort, expanded to include 24 additional patients). Six patients had partial responses, for an ORR of 17.6% [95% confidence interval (CI), 6.8–34.5], and the median PFS was 3.7 months (95% CI, 2.7–4.8). The DCR was 79.4% (95% CI, 62.1–91.3), and the CBR was 32.4% (95% CI, 17.4–50.5). Overall, 32 patients (94.1%) experienced treatment-related adverse events, and 26 patients (76.5%) experienced grade ≥3 events, most commonly neutropenia (41.2%) and leukopenia (29.4%). Of the 8 endothelial cell/vasculature markers tested in this study, 7 were significantly increased among patients treated with E7389-LF; these changes were generally consistent regardless of best overall response.

Conclusions:

E7389-LF 2.0 mg/m2 every 3 weeks was tolerable and showed preliminary activity for the treatment of patients with gastric cancer.
Temporary Myopic Shift in a Patient with Multiple Parallel-Line Endotheliitis
Authors: Lee Jee Hye , Ahn Yongsun , Park Ji Min , Hwang Jehyung , Kang Min-Ji
Published: February 2023

Here, we report the case of a patient with multiple parallel-line endotheliitis with myopic shift, which has not been previously reported. A 36-year-old man visited our clinic with blurred vision in his left eye. A slit lamp examination revealed an interesting pattern of multiple parallel lines of keratic precipitates, along with subtle corneal edema. The spherical equivalents measured in the right and left eyes were −9.25 and −11.875 diopter, respectively, with the left eye showing more myopic progression. On specular microscopy, endothelial cell loss was found in the left eye. After administration of a weak topical steroid, keratic precipitates and corneal edema resolved completely within 2 days. The myopic shift in his left eye recovered to −10.0 diopters. Multiple parallel-line endotheliitis can be easily treated with a weak topical steroid in a short period. A temporary myopic shift may occur, which in this case resolved upon disease recovery. However, corneal endothelial cell loss is inevitable; therefore, careful monitoring is needed.
Developing an Actionable Taxonomy of Persistent Hypertension Using Electronic Health Records
Authors: Lu Yuan , Xinxin Du Cindy , Khidir Hazar , Caraballo César , Mahajan Shiwani , Spatz Erica S. , Curry Leslie A. , Krumholz Harlan M.
Published: February 2023

Background:

The digital transformation of medical data presents opportunities for novel approaches to manage patients with persistent hypertension. We sought to develop an actionable taxonomy of patients with persistent hypertension (defined as 5 or more consecutive measurements of blood pressure ≥160/100 mmHg over time) based on data from the electronic health records.

Methods:

This qualitative study was a content analysis of clinician notes in the electronic health records of patients in the Yale New Haven Health System. Eligible patients were 18 to 85 years and had blood pressure ≥160/100 mmHg at 5 or more consecutive outpatient visits between January 1, 2013 and October 31, 2018. A total of 1664 patients met criteria, of which 200 records were randomly selected for chart review. Through a systematic, inductive approach, we developed a rubric to abstract data from the electronic health records and then analyzed the abstracted data qualitatively using conventional content analysis until saturation was reached.

Results:

We reached saturation with 115 patients, who had a mean age of 66.0 (SD, 11.6) years; 54.8% were female; 52.2%, 30.4%, and 13.9% were White, Black, and Hispanic patients. We identified 3 content domains related to persistence of hypertension: (1) non-intensification of pharmacological treatment, defined as absence of antihypertensive treatment intensification in response to persistent severely elevated blood pressure; (2) non-implementation of prescribed treatment, defined as a documentation of provider recommending a specified treatment plan to address hypertension but treatment plan not being implemented; and (3) non-response to prescribed treatment, defined as clinician-acknowledged persistent hypertension despite documented effort to escalate existing pharmacologic agents and addition of additional pharmacologic agents with presumption of adherence.

Conclusions:

This study presents a novel actionable taxonomy for classifying patients with persistent hypertension by their contributing causes based on electronic health record data. These categories can be automated and linked to specific types of actions to address them.
Abstract 10: Determinants Of In-hospital Muscle Loss In Acute Ischemic Stroke - Results Of The Muscle Assessment In Stroke Study (MASS)
Authors: Gungor Ibrahim Levent , Arsava Ethem Murat , Topcuoglu Mehmet Akif ,   MASS Investigators
Published: February 2023

Background:
Recent literature, primarily based on chronic stroke patients, highlighted a change in the mass and composition of paretic and non-paretic skeletal muscles following stroke. The multi-center, prospective, and observational Muscle Assessment in Stroke Study (MASS; ClinicalTrials.gov ID: NCT03825419) was performed to evaluate the degree of muscle loss during the in-hospital acute stroke setting and determine factors contributing to this loss, especially from the perspective of protein/calorie intake.

Methods:
Acute dysphagic ischemic stroke patients admitted to neuro-intensive care units were evaluated by computed tomography on days 1 and 14 after admission to determine the cross-sectional muscle area (CSMA) at the level of the mid-humerus, mid-thigh, and third lumbar vertebra. The percentage change in CSMA and variables associated with this change were evaluated by univariate and multivariate analyses.

Results:
The study population was comprised of 107 patients [median (IQR) age:74 (63-82) years; 58 females]. There were significant reductions in CMSA in all the muscle groups analyzed; the most prominent change was observed in the arms (both: 14.2±10.7%; paretic: 17.7±11.6%; non-paretic: 10.1±12.5%), followed by the muscles in the legs (both: 12.4±8.7%; paretic: 12.9±9.9%; non-paretic: 12.0±9.3%) and L3-vertebra level (5.6±9.8%) (p<0.001 for all). The percent reduction in CSMA of the arms was associated with an unfavorable outcome (90-day mRS≥3) when adjusted for age and admission stroke severity [OR 1.13 (1.04-1.23) for each 1% reduction in CSMA; p=0.003]. The presence of a significant protein (≥0.4 g/kg/d) or calorie (≥5kcal/kg/d) gap between targeted or actual intake was related to a larger decrease in CSMA in all the anatomic regions evaluated (p≤0.05 for all). Other significant predictors of muscle loss included a history of diabetes mellitus, male sex, higher body mass index, in-hospital infections, and the necessity for invasive mechanical ventilation.

Conclusions:
There is a considerable degree of loss in the global muscle mass in acute ischemic stroke patients over a two-week period. Along several factors, falling significantly behind the daily protein or calorie targets was related to the decrease in muscle area.
Abstract 101: Direct Transfer To Angiosuite Versus Ct Scanner On Arrival To Endovascular Capable Centers; More Risks Or More Benefits
Authors: Saleem Sidra , Gharaibeh Khaled , Oliver Marion , Rao Rahul , Burgess Richard , Castonguay Alicia , Jumaa Mouhammad A , Zaidi Syed F
Published: February 2023

Background and Objectives:
Endovascular therapy (EVT) is standard treatment for large vessel occlusion strokes. To reduce inter-hospital times, most patients are usually transferred directly to the angio suite (DTAS) but some transfers are initially taken to the CT scanner (DTCT) to re-evaluate. The objective of our study is to compare outcomes in patients DTAS vs DTCT.

Methods:
This is retrospective study of LVO stroke from 2017 to 2021 transferred to our CSS from outside hospitals for mechanical thrombectomy (MT). Recruitment was done from the University of Toledo/Promedica stroke database and specific variables were included from chart review. Patients were divided into two cohorts, DTAS and DTCT. Results were calculated with SPSS software.

Results:
Total of 246 patients were transferred from an outside hospital for MT, 55.6% patients were DTAS vs 44.3% patients to DTCT. There was no significant difference between basic demographics. In both groups, most common vessels involved were M1 (38.4% vs 39.4%), followed by M2 (25.4% vs 29.4%) then ICA terminus (19.6% vs 16.5%). DTAS had significant shorter door to puncture time (35 vs 62 mins, p=0.03), onset to recanalization time (346 vs 583 mins, p=0.012) and onset to groin puncture (329 vs 557 mins, p<0.01). There was no statistically significant difference in puncture to recanalization between two groups (35.6 vs 22.8, p=0.05). Successful MT (mTICI ≥2b) was more in DTAS vs DTCT (91.9% vs 86.9%, p=0.02). At discharge, DTAS group had more decrement in NIHSS, compared to presentation and discharge (Δ13, NIHSS 18.1 to 5) compared to DTCT group (Δ9, NIHSS 16 to 7). Both groups had statistically non-significant rates of functional dependence at discharge (mRS 0-2, 18% vs 13%, p=0.23), at 90 days (mRS 0-2, 35% vs 36%) and mortality at 90 days (34% vs 36%, p=0.56). Rate of complications in DTAS vs DTCT, hemorrhagic transformation (29.1% vs 23.9%, p=0.23) and intracranial hemorrhage (5.2% vs 8.3%, p=0.54) was not significant.

Conclusion
Our study concluded that DTAS has better reperfusion rates, time matrices and decrement of NIHSS compared to DTCT. Functional outcomes at discharge, 90 days and mortality at 90 days was not significantly difference between two groups.
Abstract 105: Sex Differences In The Response To Global Cerebral Hypo-Perfusion In A Mouse Model Of Cerebral Amyloid Angiopathy
Authors: Khan Romeesa , Guzman Gary , Maniskas Michael E , ChunFeng Tan , Li Jun , McCullough Louise D
Published: February 2023

Cerebral amyloid angiopathy (CAA) is a disease of small and medium-sized vessels, characterized by amyloid deposition. The incidence of CAA increases with age and evidence reveals worsened cognition in females compared to males. Cerebral hypoperfusion, or a decrease in cerebral blood flow (CBF), changes the integrity of the blood brain barrier and contributes to microhemorrhages, cerebral atrophy, and white matter loss. However, the link between vascular amyloid deposition and hypoperfusion remains understudied. We induced global cerebral hypoperfusion with bilateral carotid artery stenosis (BCAS) in CAA mice of both sexes and examined cognitive deficits, white matter loss, and cerebral gliosis. We
hypothesize
that chronic cerebral hypoperfusion will accelerate cognitive decline in CAA, increase white matter damage, and induce gliotic changes in the brain.Using a mouse model of CAA (Tg-SwDI), male and female mice (3 months of age) were randomized to either BCAS (n=15) or sham (n=11) surgery using 0.18mm coils to induce global cerebral hypoperfusion. Cognitive (Y-maze (YM), NORT, Water Maze (WM)) and motor function (Open Field (OF)) testing was performed by a blinded investigator prior to surgery (baseline) and at regular intervals until tissue harvest 6 months post-BCAS (PB). The brain and brainstem were harvested for immunohistochemical (IHC) analysis (Kluver-Barrera (KB), Iba-1, GFAP, Myelin Basic Protein (MBP)).Sex-specific changes in spatial memory (YM) and learning (NORT/WM) were present in BCAS mice. Female BCAS mice displayed greater deficits in cognition (NORT) at 3 (p=.0028), 4 (YM, p=.0007), and 5-months PB (NORT, p=.0149). Male BCAS mice demonstrated similar cognitive deficits, but at a later timepoint of 5 months PB (NORT, p=.0007). Both female and male BCAS mice had poorer cognition (WM) and motor function (OF, p=.0011/.0055) 6 months PB. IHC demonstrated increased demyelination (MBP) (p=.0038) and atrophy (KB) in the anterior corpus collosum (p=.0447) and significant gliosis (p=.0230).This study shows that chronic global hypoperfusion accelerates cognitive deficits in a CAA model, an effect that is accelerated in female mice. BCAS led to gliotic changes and demyelination associated with white matter damage in the brain.
Abstract 107: Potentiating GPR68 Function With Ogerin Protects Against Ischemic Brain Injury In Mice
Authors: Wang Tao , Jonchhe Sarun , Zha Xiangming
Published: February 2023

Introduction:
Ischemic stroke leads to prolonged reduction in brain pH. We previously found that G-protein coupled receptor 68 (GPR68), a proton-sensitive GPCR, mediates a neuroprotective pathway in brain ischemia. To investigate translational potential of GPR68 targeting, we examine here the effect of Ogerin, a positive allosteric modulator of GPR68, on ischemic brain injury.

Methods:
Using organotypic cortical slices, we examined the effect of Ogerin on signaling. Next, we induced oxygen-glucose deprivation (OGD) in slices and analyzed delayed neuronal injury at 24 hr with propidium iodide (PI) staining. Further, we performed transient middle cerebral artery occlusion (tMCAO) in WT and GPR68 knockout mice, treated them with vehicle or Ogerin, and analyzed brain infarct with TTC staining. We then assessed the effect of Ogerin on cerebral blood flow using Laser Speckle Imaging. Lastly, we performed immunostaining to determine the effect of Ogerin on neuroinflammation.

Results:
Ogerin induced phosphorylation of protein kinase C substrates in wild-type but not GPR68-/- slices. Ogerin (10 μM) reduced PI intake in OGD-treated slices, suggesting a reduced neuronal injury. Following tMCAO, intraperitoneal injection of Ogerin had no significant effect on brain infarct size. In contrast, Ogerin through intracerebroventricular injection (i.c.v) (0.25 mg/kg) significantly reduced brain infarct in WT (18.5 ± 11.8% (Ogerin) vs. 37.7 ± 7.2% (vehicle); p = 0.0043) but had no significant effect in GPR68-/- mice. Intravenous (i.v.) delivery of Ogerin at 3 & 1 mg/kg, but not at 0.3 mg/kg, significantly reduced brain infarct in WT. Moreover, delayed i.v delivery of Ogerin (1 mg/kg) at both 3 hours and 6 hours after reperfusion significantly reduced brain infarct. We further replicated the experiment in female mice, focusing on the metestrus stage. Ogerin through i.v (1 mg/kg) also reduced brain infarct in female mice. In parallel with the reduced brain infarct, Ogerin-treated mice exhibited a balanced (ipsilateral: contralateral) cerebral blood perfusion at 24 hour, and a reduced inflammatory response in microglia/macrophages.

Conclusion:
These data suggest that GPR68 potentiation with Ogerin is a promising neuroprotective reagent in brain ischemia.
Abstract 109: Regional Cerebral Hypoperfusion In Patients Recovered From Mild COVID-19
Authors: Sen Souvik , Newman-Norlund Roger , Riccardi Nicholas , Newman-Norlund Sarah , Sayers Sara , Wilson Sarah , Busby Natalie , Nemati Samaneh , Rorden Christopher , Fridriksson Julius
Published: February 2023

Background:
Cerebral hypoperfusion have been described in both severe and mild forms of symptomatic coronavirus disease 2019 (COVID-19) infection. The purpose of this study was to investigate global and regional gray matter (GM) and white matter (WM) cerebral blood flow (CBF) in asymptomatic COVID-19 infection patients compared with age-gender-race matched controls.

Methods:
Cases with mild COVID-19 infection and age-gender-race matched healthy controls, were drawn from the ABC@UofSC data repository. Demographics, risk factors and data from the Montreal Cognitive Assessment (MOCA score) were collected within a week of magnetic resonance imaging (MRI) perfusion image acquisition using pseudo-continuous arterial spin labeling. Mean CBF values for GM, WM and whole brain were calculated by averaging CBF values of standard space normalized CBF image values falling within GM and WM masks. Whole-brain, region of interest (ROI) based analyses were used to create standardized cerebral blood flow maps and further explore differences between the two groups.

Results:
Twenty-eight cases with prior mild COVID-19 infection were compared with 28 age-, gender-, race-matched controls. The MOCA score was similar between cases and controls. Whole-brain CBF (46.7±5.6 vs. 49.3±3.7, p=0.05), GM-specific CBF (64.2±8.9 vs. 67.6±6.0, p=0.10), and WM-specific CBF (29.3±2.6 vs. 31.0±1.6, p=0.03) were noted to be lower in COVID-19 cases as compared to controls. Further analysis identified several brain regions with lower CBF than the CONTROL group colors representing Z-scores shown in the figure. Predictive models based on these data predicted COVID-19 group membership with a high degree of accuracy (85.2%) suggesting CBF patterns as a key imaging marker of mild infection.

Conclusion:
In this study, lower white matter CBF, as well as widespread regional CBF changes identified using quantitative MRI, were found in patients recovered from mild to moderate COVID-19 infection.
Abstract 11: Identifiable Patterns Of Noninvasive Cerebral Oximetry During Endovascular Therapy For Acute Ischemic Stroke Are Associated With Neurological Deterioration
Authors: Olexa Madelynne , Begunova Yelyzaveta , Bartolome David , Peng Teng J , Sheth Kevin N , Matouk Charles , Petersen Nils H
Published: February 2023

Background:
Cerebral near-infrared spectroscopy (NIRS) is a useful tool to monitor real-time cerebral oxygenation levels. However, the mechanisms through which varying oxygenation levels during endovascular thrombectomy (EVT) affect functional outcomes remain to be determined. In this study, we categorized NIRS trends into descriptive “fingerprints” and examined the relationship between these fingerprints and neurological worsening.

Methods:
We enrolled patients that presented to Yale New Haven Hospital with large vessel occlusion acute ischemic stroke and underwent EVT. NIRS was implemented into the standard operating procedure. Time stamps of defined events (medication administration, recanalization, etc.) were synchronized with corresponding NIRS values. We inspected NIRS curves from arrival to angio-suite to time of recanalization. Neurological deterioration was defined as an increase of 4 points or more on the National Institutes of Health Stroke Scale (NIHSS).

Results:
Forty-eight patients (mean age 72 ± 13, mean NIHSS 14) were analyzed. Five “fingerprints” were observed in the affected hemisphere: sustained decreases, downward rSO2 peaks, no change, upward rSO2 peaks, and sustained increases (Fig. 1), which were assigned nominal values of -2, -1, 0, 1, and 2, respectively. After adjusting for age and admission NIHSS, sustained decreases and downward rSO2 peaks were independently associated with neurological deterioration (P = 0.0076, Fig. 2).

Conclusions:
Identifiable NIRS “fingerprints” of downward rSO2 peaks and sustained decreases in the affected hemisphere during EVT are associated with neurological deterioration. Further distillation of identifiable intraprocedural NIRS trends in real time could provide guidance for anesthesia and hemodynamic management during EVT to optimize patient outcomes after stroke.
Abstract 114: Changes In Quantitative Susceptibility Mapping On Magnetic Resonance Imaging During Prospective Follow-Up Of Cavernous Angiomas With Symptomatic Hemorrhage In Trial Readiness Project
Authors: Hage Stephanie F , Stadnik Agnieszka , Lee Justine , Flemming Kelly D , Kim Helen , Torbey Michel T , Huang Judy , Mendoza-Puccini Carolina , Koenig James I , Thompson Richard E , Carroll Timothy J , Girard Romuald , Shenkar Robert , Hanley Daniel F , Awad Issam A
Published: February 2023

Background:
Quantitative susceptibility mapping (QSM) is a measure of iron content, and ≥6% increase in QSM has been correlated with new hemorrhage in previously stable cavernous angiomas. Longitudinal changes in QSM are not known in cavernous angiomas with symptomatic hemorrhage (CASH) with high rates of rebleeding and are the targets of novel pharmacotherapies. In a prospective multisite Trial Readiness project (clinicaltrials.gov NCT03652181), QSM is longitudinally assessed.

Methods:
Trial eligible subjects with CASH in the prior year and not undergoing lesion resection or radiation, were enrolled. Mean QSM of CASH lesion was acquired at baseline and at 1 and 2 year planned follow-ups. Relative change in mean lesional QSM during each follow-up year was assessed, and any symptomatic hemorrhage (SH), asymptomatic changes (AC; defined as subclinical bleed or growth) in the lesion during the same epoch.

Results:
Paired QSM assessments were completed to date in 99 CASH lesions (67 year 1, and 32 year 2) and are reported herein. Four SH and 6 ACs occurred during 1
st
follow-up year, and 3 SH during 2
nd
year. QSM increased in 54 lesion-years, decreased in 44, and remained stable in 1. The % lesional QSM change in year 1 was significantly higher than that observed in year 2 (mean +9.33, SD 37.52 vs. +5.20; SD= 24.86; p=0.05; Spearman correlation ρ -0.36). CAs with clinical SH or AC had a significantly higher % QSM change than lesions without (mean +28.03, SD 17.77 vs. +4.97, SD= 34.75; p=0.0014). All 13 lesions with SH/AC demonstrated a QSM increase ≥6% while 31 of 86 (36%) lesions with no clinical events had a ≥6% QSM increase.

Conclusion:
QSM change of ≥6% is present in every CASH lesion manifesting a new SH or AC (100% specificity), and is more common than clinical events (3.4X higher sensitivity). The biomarker can hence be used as a more sensitive categorical outcome than SH or AC in clinical trials of novel therapies aimed at bleeding in CASH lesions. Effect of an intervention on % QSM change may also be proposed as a time-averaged difference between 2 arms using a repeated measures analysis implemented as an unadjusted linear mixed model. These results are the basis of application for certification by the U.S F.D.A. of QSM as a monitoring biomarker of drug effect in CASH.
Abstract 115: Periventricular But Not Subcortical White Matter Lesions Are Associated With Adult Moyamoya Disease
Authors: Yang Wookjin , Kang Dong-wan , Lee Eung-Joon , Jeong Han-Yeong , Kim Jeong-Min , Lee Seung-Hoon , Jung Keun-hwa
Published: February 2023

Introduction:
White matter hyperintensities (WMH) are reportedly increased in moyamoya disease (MMD); however, their clinical importance is not well-established owing to their pathophysiological heterogeneity by distribution. This study aimed to evaluate the burden and pattern of WMH and its clinical implications in the MMD trajectory.

Methods:
Adult MMD patients without significant structural lesions were 1:1 propensity score-matched with healthy controls for sex and vascular risk factors. The total, periventricular, and subcortical WMH volumes were segmented and quantified fully automatically. WMH volumes were detrended by age and compared between the two groups. MMD severity based on Suzuki stage and future ischemic events were assessed for their association with WMH volumes.

Results:
A total of 190 pairs of patients with MMD and controls were analyzed. MMD significantly correlated with increased total (B, 0.086; standard error [SE], 0.027; p=0.002) and periventricular WMH volumes (B, 0.079; SE, 0.025; p=0.002). In the MMD subgroup, advanced MMD had an independent positive association with the total (B, 0.124; SE, 0.034; p<0.001) and periventricular WMH volumes (B, 0.116; SE, 0.030; p<0.001). Periventricular WMH volume was associated with future ischemic events (adjusted hazard ratio [aHR], 4.96; 95% confidence intervals [CIs], 1.21-20.25) in medically followed-up MMD patients. However, no demonstrable association was found between subcortical WMH volume and MMD (B, 0.007; SE, 0.007; p=0.35), MMD severity (B, 0.010; SE, 0.011; p=0.37), or future ischemic events (aHR, 14.15; 95% CIs, 0.20-1022.96).

Conclusions:
Periventricular WMH, but not subcortical WMH, may represent the main pathophysiology of MMD. Periventricular WMH may be used as a marker for ischemic vulnerability in patients with MMD.
Abstract 12: Higher Blood Pressure Trajectories After Endovascular Thrombectomy Are Associated With Cerebral Edema Development
Authors: Begunova Yelyzaveta , Bartolome David , Olexa Madelynne , Kumar Atul , Chen Yasheng , Peng Teng J. , Ortega-Gutierrez Santiago , Sheth Kevin N , Dhar Rajat , Petersen Nils H
Published: February 2023

Introduction:
High blood pressure after endovascular thrombectomy (EVT) can cause cerebral hyperemia and disrupt the blood-brain barrier. However, its role in cerebral edema development is incompletely understood. In this study, we examined the relationship between post-EVT systolic blood pressure (SBP) trajectories and cerebral edema.

Methods:
We prospectively enrolled patients with large-vessel occlusion stroke who underwent EVT. Cerebrospinal fluid (CSF) volume was measured using a deep-learning algorithm on CT images at baseline, 24 hours, and 72 hours after stroke. The ratio of CSF volumes between hemispheres was calculated. Automated segmentation of infarct regions on follow-up scans was used to measure net water uptake (NWU), the ratio of density within infarcted tissue relative to the mirrored contralateral region. Latent variable mixture modeling (LVMM) divided patients into SBP trajectory groups during the first 72 hours post-EVT (Fig. 1A). Measures of edema (change in CSF ratio, NWU) were compared between groups.

Results:
One hundred patients (mean age 70 ± 16, mean NIHSS 15) were analyzed. Edema was assessed by a gradual increase in NWU (20.5, 27.0) at 24 and 72 hours, respectively, and by a reduction in CSF ratio (0.95, 0.78, 0.68) in the affected hemisphere at baseline, 24 hours, and 72 hours, respectively. LVMM identified five SBP trajectories. Higher SBP trajectories were associated with higher NWU (Fig. 1B) but not lower CSF ratio at 24 hours (p<0.001 and p=0.343, respectively). After adjusting for age, admission NIHSS, and TICI score, the moderate-to-high and high-to-moderate trajectory groups were independently associated with higher NWU (aOR 11.40, 95% CI 2.14-20.66) and (aOR 10.97, 95% CI 0.12-21.82), relative to the low and moderate groups.

Conclusions:
Higher SBP trajectories are associated with an increase in NWU post-EVT. NWU is a promising radiographic biomarker for measuring cerebral edema during the early phase after stroke.