bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geospatial characterization of immune cell distributions and dynamics across the microenvironment in clear cell renal cell carcinoma
Authors: Chakiryan Nicholas H , Kim Youngchul , Berglund Anders , Chang Andrew , Kimmel Gregory J , Hajiran Ali , Nguyen Jonathan , Moran-Segura Carlos , Saeed-Vafa Daryoush , Katende Esther N , Lopez-Blanco Neale , Chahoud Jad , Rappold Phillip , Spiess Philippe E , Fournier Michelle , Jeong Daniel , Wang Liang , Teer Jamie K , Dhillon Jasreman , Kuo Fengshen , Hakimi Abraham Ari , Altrock Philipp M , Mulé James J , Manley Brandon J 
Published: April 2023

IntroductionIn clear cell renal cell carcinoma (ccRCC), tumor-associated macrophage (TAM) induction of CD8+T cells into a terminally exhausted state has been implicated as a major mechanism of immunotherapy resistance, but a deeper biological understanding is necessary.MethodsPrimary ccRCC tumor samples were obtained from 97 patients between 2004 and 2018. Multiplex immunofluorescence using lymphoid and myeloid markers was performed in seven regions of interest per patient across three predefined zones, and geospatial analysis was performed using Ripley’s K analysis, a methodology adapted from ecology.ResultsClustering of CD163+M2 like TAMs into the stromal compartment at the tumor–stroma interface was associated with worse clinical stage (tumor/CD163+nK(75): stage I/II: 4.4 (IQR −0.5 to 5.1); stage III: 1.4 (IQR −0.3 to 3.5); stage IV: 0.6 (IQR −2.1 to 2.1); p=0.04 between stage I/II and stage IV), and worse overall survival (OS) and cancer-specific survival (CSS) (tumor/CD163+nK(75): median OS–hi=149 months, lo=86 months, false-discovery rate (FDR)-adj. Cox p<0.001; median CSS–hi=174 months, lo=85 months; FDR-adj. Cox p<0.001). An RNA-seq differential gene expression score was developed using this geospatial metric, and was externally validated in multiple independent cohorts of patients with ccRCC including: TCGA KIRC, and the IMmotion151, IMmotion150, and JAVELIN Renal 101 clinical trials. In addition, this CD163+ geospatial pattern was found to be associated with a higher TIM-3+ proportion of CD8+T cells, indicative of terminal exhaustion (tumor-core: 0.07 (IQR 0.04–0.14) vs 0.40 (IQR 0.15–0.66), p=0.05).ConclusionsGeospatial clustering of CD163+M2 like TAMs into the stromal compartment at the tumor–stromal interface was associated with poor clinical outcomes and CD8+T cell terminal exhaustion.
Chordoma recruits and polarizes tumor-associated macrophages via secreting CCL5 to promote malignant progression
Authors: Xu Jiuhui , Shi Qianyu , Lou Jingbing , Wang Boyang , Wang Wei , Niu Jianfang , Guo Lei , Chen Chenglong , Yu Yiyang , Huang Yi , Guo Wei , Lan Jianqiang , Zhu Yu , Ren Tingting , Tang Xiaodong 
Published: April 2023

BackgroundChordoma is an extremely rare, locally aggressive malignant bone tumor originating from undifferentiated embryonic remnants. There are no effective therapeutic strategies for chordoma. Herein, we aimed to explore cellular interactions within the chordoma immune microenvironment and provide new therapeutic targets.MethodsSpectrum flow cytometry and multiplex immunofluorescence (IF) staining were used to investigate the immune microenvironment of chordoma. Cell Counting Kit-8, Edu, clone formation, Transwell, and healing assays were used to validate tumor functions. Flow cytometry and Transwell assays were used to analyze macrophage phenotype and chemotaxis alterations. Immunohistochemistry, IF, western blot, PCR, and ELISA assays were used to analyze molecular expression. An organoid model and a xenograft mouse model were constructed to investigate the efficacy of maraviroc (MVC).ResultsThe chordoma immune microenvironment landscape was characterized, and we observed that chordoma exhibits a typical immune exclusion phenotype. However, macrophages infiltrating the tumor zone were also noted. Through functional assays, we demonstrated that chordoma-secreted CCL5 significantly promoted malignancy progression, macrophage recruitment, and M2 polarization. In turn, M2 macrophages markedly enhanced the proliferation, invasion, and migration viability of chordoma. CCL5 knockdown and MVC (CCL5/CCR5 inhibitor) treatment both significantly inhibited chordoma malignant progression and M2 macrophage polarization. We established chordoma patient-derived organoids, wherein MVC exhibited antitumor effects, especially in patient 4, with robust killing effect. MVC inhibits chordoma growth and lung metastasis in vivo.ConclusionsOur study implicates that the CCL5–CCR5 axis plays an important role in the malignant progression of chordoma and the regulation of macrophages, and that the CCL5–CCR5 axis is a potential therapeutic target in chordoma.
Gender differences in SLE: report from a cohort of 417 Caucasian patients
Authors: Trentin Francesca , Signorini Viola , Manca Maria Laura , Cascarano Giancarlo , Gualtieri Luca , Schilirò Davide , Valevich Anastasiya , Cardelli Chiara , Carli Linda , Elefante Elena , Ferro Francesco , Stagnaro Chiara , Zucchi Dina , Tani Chiara , Mosca Marta 
Published: April 2023

BackgroundSLE is an autoimmune disease that predominantly affects women. As most epidemiological and interventional studies are on populations with a clear female prevalence, the influence of gender in disease course, drug response and damage accrual is yet to be fully explored and comprehended.ObjectivesTo describe gender differences in disease course, comorbidities, use of medications and long-term outcomes of a large cohort of patients with SLE.MethodsRetrospective gender-based analysis of prospectively collected data from a monocentric cohort of Caucasian patients with SLE with at least 1 year of follow-up.Results417 patients were included, 51 men and 366 women. Men displayed a significantly higher median age at disease onset and diagnosis and a higher prevalence of late-onset SLE, serositis at disease onset, antiphospholipid syndrome (APS) and use of mycophenolate within the first year of disease. Women had a higher prevalence of haematological abnormalities, a higher cumulative exposure to azathioprine and higher cumulative dose of glucocorticoids at 5 years. Male patients had a shorter time to first damage item and a higher prevalence of damage at 1 and 5 years, but this association was no longer significant when late-onset patients were excluded. No differences were found in prevalence of childhood onset, delay between onset and diagnosis, time to renal involvement and histology, cumulative autoantibody positivity, number of flares and hospitalisations, median SLE Damage Index score, type of damage, age and time to first cardiovascular event, chronic kidney disease and death.ConclusionsIn our cohort, clinical manifestations and disease course were similar in male and female patients; however, male patients displayed higher prevalence of APS and early damage accrual probably due to the later disease onset. These data highlight the importance of an intensive follow-up, prevention and treatment of complications in this category of patients, especially in the first years of disease.
The European strategy for accelerator-based photon science
Authors: Abela R. , Biscari C. , Daillant J. , Dosch H. , Rivkin L. 
Published: April 2023

AbstractThe League of European Accelerator-based Photon Sources (LEAPS), comprising 19 large-scale user facilities in 10 member and associated states, has put forward for the first time a European strategy for a transformative way of cooperation, thereby mobilizing the members’ substantial expertise in photon science and technology, in infrastructure management and service to users and stakeholders. This European Strategy for Accelerator-based Photon Sources—ESAPS 2022—is a coherent pan-European plan addressing the future challenges and needs of the new era in research and innovation, designed to put Europe in a global leadership position in important future key technologies. In ESAPS2022, ambitious facility upgrades and technology development plans as well as a new strategic challenge-driven use of these facilities are discussed.
RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
Authors: Compadre Amanda J. , van Biljon Lillian N. , Valentine Mark C. , Llop-Guevara Alba , Graham Emily , Fashemi Bisiayo , Herencia-Ropero Andrea , Kotnik Emilee N. , Cooper Isaac , Harrington Shariska P. , Kuroki Lindsay M. , McCourt Carolyn K. , Hagemann Andrea R. , Thaker Premal H. , Mutch David G. , Powell Matthew A. , Sun Lulu , Mosammaparast Nima , Serra Violeta , Zhao Peinan , Lomonosova Elena , Khabele Dineo , Mullen Mary M. 
Published: April 2023

Abstract

Purpose:
To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples.

Experimental Design:
RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if &gt;10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated.

Results:
RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson r = 0.96, P = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (P &lt; 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; P &lt; 0.001) and to be platinum-sensitive (RR, ∞; P = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78–1.0; P &lt; 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; P &lt; 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33–0.85; P &lt; 0.001) and overall survival (HR, 0.43; 95% CI, 0.25–0.75; P = 0.003) than RAD51-High status.

Conclusions:
RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials.
Abstract Number ‐ 3: Large and Giant Aneurysms Outcome in the Multicenter Prospective Core Lab Adjudicated SMART Coils Registry
Authors: Ashouri Yazan K , Spiotta Alejandro M , Park Min S , Bellon Richard J , Bohnstedt Bradley N , Yoo Albert J , Massad Abdallah , Pabon Boris , Zaidat Osama O 
Published: April 2023

Introduction
Endovascular coiling for intracerebral aneurysms has been evolving. Yet, large, and giant aneurysms (LAGA) remain a significant challenge for treatment and carry a high rate of morbidity and mortality. Previous studies have demonstrated 72–76% long‐term adequate occlusion and up to 34% retreatment rate in patients undergoing reconstructive treatment for LAGA.

Methods
The SMART registry, a prospective, multicenter outcome trial was used to identify patients with LAGA (Sac 10–24mm for large and ≥ 25mm for giant aneurysms) treated with the Penumbra SMART COIL® (SMART) system in the US and Canada. Patients’ characteristics and outcomes were then compared to patients with smaller aneurysms (SA) (Sac≤10mm). Primary effectiveness endpoint was aneurysm occlusion using Raymond‐Roy (RR) scale and safety endpoints included mortality and stroke outcomes. Fisher exact test and T‐test were used to compare categorical and continuous variables, respectively. P‐value < 0.05 was considered significant.

Results
A total of 131/903 (14.5%) patients had LAGA and 42 (32.1%) of those were ruptured. Patients with LAGA were older than SA (mean age: 61.9 vs 59.4, p = 0.04). Large aneurysms were mainly saccular in 75.6% of the cases (vs 87.7% of the ≤ 10 mm ones, p < 0.001). Fusiform LAGA were 8.4% (vs 1.4% of the ≤ 10 mm ones, p < 0.001). Furthermore, they are more likely to have wide neck (69.5% vs 59.7%, p = 0.042). They are less likely to have A‐Com aneurysm (10.7% vs 28%, p < 0.001), and more likely to have basilar tip aneurysms (3.1% vs 0.8%, p = 0.044) and cavernous aneurysms (4.6% vs 0.6%, p = 0.002) compared to patients with SA. Primary coiling was the main treatment modality for both SA and LAGA (43.3% vs 43.5%, respectively, p = 1.0). However, LAGA were more likely to be treated with flow diversion in addition to coiling (6.1% vs 1.0%, p < 0.001). Packing density was significantly lower in LAGA (mean (SD) = 21.2(13.1) vs 34.1(18.3), p < 0.001). Surprisingly, long‐term aneurysm RR occlusion Class I‐II on follow‐up imaging was 82.5% in LAGA vs 91.2% in SA, p = 0.016. Retreatment rates was 11.7% in LAGA vs 6.4% in SA, p = 0.063. mRS0‐2 score was 73.6% in LAGA vs 86.4% in SA, p = 0.007. All‐cause 1‐year mortality was 9.2% in LAGA vs 4.7% in SA, p = 0.054.

Conclusions
Despite challenges with treating Large and giant aneurysms, SMART coiling registry demonstrated high adequate aneurysm occlusion rate on follow‐up imaging, as well as a good independent functional outcome.
Abstract Number ‐ 8: HEMERA 1 CarboxyHEMoglobin OxygEn delivery for Revascularization in Acute Stroke: Phase 1 Clinical Trial
Authors: Linfante Italo , Hanel Ricardo , Reshi Rwoof , Clark Wayne M , Dabus Guilherme C , Lieberskind David , Nogueira Raul G 
Published: April 2023

Introduction
Despitehigh rates ofrecanalizationafter mechanical thrombectomy(MT),only 33–71% of patients achieve functional independence at 90 days.Experimental ischemia hashighlightedthe complexity of several pathophysiological events occurring at the level of the neurovascular unit and has revealed potential targets for neuroprotection. Apossible target is to increasebloodflow in the collateral circulationwhile delivering high levels of oxygen in the ischemic area.Hemoglobin based oxygen carriers (HBOC) as a transfusion media that can treat ischemic tissue have been investigatedfor a decade. More recently, a polyethylene glycol modifiedHBOCin the carboxy state (PP‐007)increases blood flow in the collateral circulationinrat modelsof middle cerebral artery occlusion (MCAO).PP‐007 may deliver more oxygen than Hb contained in RBCs because of increased diffusional surface area in plasma, and by facilitation of oxygen transport from RBC to endothelium.In addition,dilation ofcollateral circulationby diffusion of CO mayslow down infarct expansion andimprove the efficacy of reperfusion.

Methods
HEMERA 1 is a phase 1 safety clinical trialof PP‐007 in patient with acute ischemic strokewith LVO (ClinicalTrials.gov NCT04677777). Inclusion criteria are patients with Intracranial ICA and/or MCA‐M1 or M2 occlusion,baseline NIHSS ≥ 6, Baseline ASPECTS score ≥ 5 on NCCT and/or Core Volumes <70mL + Mismatch > 50mL on CT perfusion (CTP), time fromlast seen well to start ofPP‐007infusion ≤ 24 hours,pre‐MorbidmRS< 2, and ineligibility for intravenous thrombolysis. The trial plans to enroll approximately 16–20 subjectswith3:1 randomizationtoPP‐007 (320 mg/kg with 30 min bolus + 2‐hour infusion) plus MT versus MT alone.

Results
Tenpatients have been enrolled so far.Mean age was 76.1 (STD±11.6), ASPECT score = 7.8 (±1.8), NIHSS at baseline = 17.3 (±5.6),TICI 2b or c in 7, TICI 3 in 3. Seven patients were randomized PP‐007 and received the complete infusion. Two patients were randomized to standard of care (MT only) and1was randomized to PP‐007 but not treated.Three patients had elevation of Partial Prothrombin Time (PTT) after the PP‐007 infusion that however had no clinical consequences.

Conclusions
HEMERA 1 isphase 1 clinical trialcurrently enrolling patients.No safety concerns were identified so far.
Abstract Number ‐ 17: Robot‐assisted transcranial Doppler versus transthoracic echocardiography for right to left shunt detection: Final Results
Authors: Rubin Mark N , Shah Ruchir , Devlin Thomas , Youn Teddy S , Waters Michael , Volpi John J , Stayman Aaron , Douville Colleen , Lowenkopf Ted , Tsivgoulis Georgios , Alexandrov Andrei V 
Published: April 2023

Introduction
Right to left shunt (RLS), including patent foramen ovale (PFO), is a recognized risk factor for stroke. RLS/PFO diagnosis is made by transthoracic echocardiography (TTE) which is insensitive, transesophageal echocardiography (TEE) which is invasive, and transcranial Doppler (TCD) which is noninvasive and accurate but scarce.

Methods
We conducted a multi‐center device clinical trial of robot‐assisted TCD (raTCD) versus TTE for RLS diagnosis in patients who presented with an event suspicious for embolic cerebrovascular ischemia. raTCD was performed with standard TCD bubble study technique. TTE bubble study was performed to local standards. The primary outcome was rate of RLS detection by raTCD versus TTE.

Results
133 patients were enrolled (intention to treat, ITT) and 126 subjects had complete data. In the ITT cohort, mean age was 60 +/‐ 15 years, 46% were women, and 92% of qualifying events were diagnosed as ischemic stroke. raTCD was positive for RLS in 82 subjects (64%) and TTE was positive in 26 (20%) [absolute difference 43.4% (95% CI 34.3%‐52.5%), p < 0.001]. On prespecified secondary analysis, large RLS was detected by raTCD in 35 subjects (28%) vs 13 (10%) by TTE [absolute difference 17.5% (95% CI 10.1%‐24.8%), p < 0.001]. There were no serious adverse events.

Conclusions
raTCD was safe and 3 times more likely to diagnose RLS than TTE. TTE completely missed or underdiagnosed two thirds of large shunts diagnosed by raTCD. The raTCD device, used by health professionals with no prior TCD training, may allow providers to achieve the known sensitivity of TCD for RLS and PFO detection without the need for an experienced operator. TCD is the superior screen for RLS compared to TTE.
Abstract Number ‐ 31: No Mercy on Stroke Campaign: The Use of Pop Culture Icons to Raise Stroke Awareness
Authors: Dammavalam Vikalpa 
Published: April 2023

Introduction
About 24–46% of acute ischemic strokes are due to large vessel occlusions1, however only a small fraction2,3 of thrombectomy eligible patients undergo emergent clot retrieval. Despite advances in thrombolytics and endovascular interventions, many patients are not candidates for emergent therapies due to delay in patient presentation, prehospital delay, triage delay and limited access to care. No Mercy on Stroke (NMOS) campaign aims to raise public stroke awareness by increasing social media footprint. Thereby enabling the general population with tools for earlier symptom detection, seeking rapid medical attention and fighting for legislature to improve prehospital networks.

Methods
Society of Vascular and Interventional Neurology (SVIN) launched NMOS campaign just prior to World Stroke Day (WSD) on October 25th, 2021 via Twitter. Pop culture icon and martialist Martin Kove launched the campaign as Sensei Kreese from the movie Cobra Kai in a video encouraging viewers to “strike fast and strike hard” when treating stroke. SVIN and Kove urged followers to spread the fight against stroke by sharing karate poses with hashtag #NoMercyOnStroke. Metrics such as social media reach, impact, location and others were extracted via Tweepsmap and Tweetbinder from October 25th, 2021 to August 20th, 2022.

Results
#NoMercyOnStroke was tweeted 716 times by 211 contributors4 across 19 countries and 77 cities5 for a potential reach of 374,200 people and potential impact of 2,051,908 people4. Tweet breakdown consisted of 126 original tweets and 590 retweets4. Engagements were primarily likes recorded at 2437, and followed by 97 replies and 55 quotes. Activity timeline was highest during week of WSD and accounted for majority exposure, however, there was another small peak in activity one month later. Top 3 countries involved were USA, Canada and India although USA accounted for 90.4% of all activity. Other countries include Mexico, Colombia, Spain, Egypt, Croatia, UK, Saudi Arabia, Kenya, Libya, Vietnam, Italy, Cuba, France, Peru, Chile and Venezuela5. Top associated hash tags were #worldstrokeday, #WSD and #alz0212465.

Conclusions
Use of pop culture icon as an advocate for stroke awareness greatly increased reach and impression of the NMOS campaign by touching nearly two million followers. Compared to raw data across three social media platforms for a similar campaign by Mission Thrombectomy called #BEFASTChallenge, #NoMercyOnStroke had exponentially more engagement with almost double the original posts and triple the retweets. Still, activity was concentrated around initial launch with minimal tail in the activity timeline. The overall impact of such campaigns on the end‐goal of decreasing the ratio of eligible thrombectomies to number of thrombectomies performed is yet to be uncovered. However, it is clear that larger campaigns involving celebrity influencers and community outreach are imperative to keeping the momentum of raising stroke awareness.
Abstract Number ‐ 35: Maximum Euclidean Deflection‐A Novel Metric For Safety Of Neurovascular Devices
Authors: Desai Shashvat M , Catapano Joshua , Majmundar Neil , Ducruet Andrew , Jadhav Ashutosh P 
Published: April 2023

Introduction
Endovascular thrombectomy (EVT) devices are evolving rapidly to improve safety and efficacy of EVT‐mediated recanalization of large vessel occlusion strokes, and to access medium and distal vessel occlusions. To enable effective comparative analyses, there is a need to develop an objective in‐vitro safety metric for new EVT devices.

Methods
We utilized three FDA‐approved stent‐retrievers (4 mm diameter; variable lengths) currently available in the United States and deployed them in an in‐vitro ischemic stroke bench model (Sim Agility, Mentice Inc., Sweden). The stent‐retrievers were deployed in the M1 segment of the middle cerebral artery of the model using a system comprised of an 0.014 inch guide wire and 0.021 inch microcatheter. After unsheathing in the M1 segment, in the absence of a blood clot, the microcatheter was withdrawn back into the petrous internal carotid artery, and the whole system was withdrawn as a rate of 5 mm per second. Maximum deflection of the terminal internal carotid was measured in 3 axes using a specialized camera set‐up.

Results
A total of 3 passes were performed for each stent‐retriever (stent A, stent B, and stent C). Maximum deflection of the terminal internal carotid artery (from resting position to largest displacement during stent‐retrieval withdrawal) was measured in 3 planes and the values were as follows (Table).Maximum Euclidean Deflection (MED) ranged from 6.1 to 9.1 mm. Deflection varied based on 3 stent‐retriever designs and the plane of measurement. Figure demonstrates deflections as seen in Stent A.

Conclusions
Withdrawing an unsheathed stent‐retriever from the middle cerebral artery leads to significant deflection of the internal carotid artery terminus in an in‐vitro stroke model. The degree of deflection is variable in different planes and varies based on stent‐retriever design. Further studies are required to examine the predictors and impact of the deflection.