bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO-101: Characterization of longitudinally collected fine needle aspiration biopsies of pancreatic ductal adenocarcinoma upon endoscopic ultrasound guided radiofrequency ablation
Authors: Desai Krisha , Lawrence Patrick Varun , Wadsworth Christopher , Mangal Nagina , Habib Nagy , Sadanandam Anguraj , Sodergren Mikael 
Published: November 2021

Abstract
Background: Most patients with pancreatic ductal adenocarcinoma (PDAC) are metastatic at presentation with dismal prognosis warranting improved systemic therapy options. Longitudinal sampling for assessment of treatment response poses a challenge for validating novel therapies. In this proof-of-principle study, we evaluate the role of endoscopic ultrasound (EUS)-guided serial fine-needle aspiration biopsies (FNABs) to study the mechanism of action of radiofrequency ablation (RFA). Methods: Patients with stage III inoperable PDAC with prior exposure to gemcitabine were selected into ARDEO (ethically approved Phase-II prospective clinical study of EUS-RFA). Post examination, targeted RF was delivered thrice and sequential FNABs of tumor were taken before and after treatment. Transcriptomic profiling of 6 FNABs from 2 patients was performed using a custom NanoString gene panel (144 genes) consisting of cancer and cancer-associated fibroblast (CAFs) subtypes along with immune changes. CAF culture was established from one FNAB and characterised by immunofluorescence and immunoblotting. Results: RFA treatments were well tolerated without any complications and both patients had stable disease immediately after EUS-RFA. Two-course RFA led to upregulation of CD1E gene (participates in antigen presentation) in both, patient 1 and 2 (4.5 and 3.9-fold) compared to baseline. Patient 1 showed increased expression of T cell genes (CD4 – 8.7-fold, CD8 – 35.7-fold), cytolytic function (6.4-fold) and inflammatory response (8-fold) post-RFA. Greater than 2-fold upregulation of CD274 (PDL1), IDO1, PDCD1 and TNFRSF18 (GITR) was observed post 2nd RFA in both the patients. Further, two-course RFA led to increased PDGFRa (4.5 and 9-fold) in both patients along with enrichment of pCAF subtypes B and C in patient 1 and subtypes A, B and D in patient 2. Immunofluorescence staining revealed expression of PDGFRa, aSMA, VIM, POSTN and MYH11 on patient2-derived CAFs post 1st RFA; validated by immunoblotting. Finally, RFA led to downregulation of classical PDA subtype in both patients. Conclusions: This feasibility study validates longitudinal sampling by EUS-FNABs as an appropriate research tool to study tumor microenvironmental changes associated with local pancreatic immunomodulatory techniques like RFA.
Citation Format: Krisha Desai, Patrick Varun Lawrence, Christopher Wadsworth, Nagina Mangal, Nagy Habib, Anguraj Sadanandam, Mikael Sodergren. Characterization of longitudinally collected fine needle aspiration biopsies of pancreatic ductal adenocarcinoma upon endoscopic ultrasound guided radiofrequency ablation [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-101.
Abstract PO-116: Deletion of Arginase 1 in myeloid cells alters the pancreatic cancer microenvironment
Authors: Menjivar Rosa E. , Nwosu Zeribe , Du Wenting , Donahue Katelyn , Espinoza Carlos , Velez-Delgado Ashley , Brown Kristee , Yan Wei , Halbrook Christopher , Zhang Yaqing , Lyssiotis Costas , Pasca di Magliano Marina 
Published: November 2021

Abstract
Pancreatic ductal adenocarcinoma (PDA) is a deadly disease with a 5-year survival of only 10%. PDA is characterized by an abundant fibroinflammatory stroma that includes abundant fibroblasts and immune cells, mainly myeloid cells. Infiltrating myeloid cells express high levels of Arginase 1 (Arg1), an enzyme that metabolizes L-arginine. Conversely, CD8+ T cells are scarce in PDA, and when present have an overwhelmingly exhausted phenotype. Whether myeloid cell Arginase is a key driver of immune suppression in pancreatic cancer is unknown. Here, we tested the hypothesis that myeloid cells in the tumor microenvironment mediate immune suppression in PDA through expression of Arg1. To test this hypothesis, we used a combination of genetically engineered pancreatic cancer mouse models and pharmacological approaches. Using a FlpO- and Cre-based dual recombinase system, we have generated a mouse model that develops pancreatic cancer spontaneously because of oncogenic Kras expression in the epithelium, while at the same time lacking Arg1 expression in the myeloid cell compartment (Ptf1a-FlpO/+;KrasFrt-STOP-Frt-G12D/+;LysMCre;Arg1f/f). To complement the genetic model and inhibit the function of Arginase systemically, we used an Arginase inhibitor (CB-1158, Incyte, Inc.) alone and in combination with an immune checkpoint blockade (anti-PD1). Using these multiple approaches, we observed decrease progression to invasive disease in the genetic model, and sensitization to immune checkpoint treatment in the transplantation model. In both settings, changes in tumor growth were accompanied by an increase in CD8+ T cell infiltration and activation. These changes support the notion that myeloid Arg1 is mediator of immune suppression in PDA, and a potential therapeutic target.
Citation Format: Rosa E. Menjivar, Zeribe Nwosu, Wenting Du, Katelyn Donahue, Carlos Espinoza, Ashley Velez-Delgado, Kristee Brown, Wei Yan, Christopher Halbrook, Yaqing Zhang, Costas Lyssiotis, Marina Pasca di Magliano. Deletion of Arginase 1 in myeloid cells alters the pancreatic cancer microenvironment [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-116.
Abstract PO-127: A uPA/uPAR axis in both the tumor cell and stromal compartment drives PDAC disease progression
Authors: Yang Yi , Abrahams Sara R. , Kothari Aditi , Matada Harshi , Davey Keely , Wolberg Alisa S. , Flick Matthew J. 
Published: November 2021

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal solid tumor malignancy with a 5-year survival rate of 9%. In both patients and animal models of disease, PDAC is associated with robust coagulation system activity. Intriguingly, in addition to being a rich source of procoagulant factors, PDAC tumors highly express fibrinolytic system components. Supporting this concept, urokinase plasminogen activator (uPA) and uPA receptor (uPAR) expression positively correlates with reduced overall patient survival. Here, we tested the hypothesis that the expression and activity of plasminogen activation (PA) system components are functionally linked to PDAC tumor growth and disease progression. We generated C57Bl/6-derived KPC (i.e., KRasG12D, TRP53R172H) PDAC cell lines in which uPA and uPAR were knocked out using CRISPR-Cas9. We then analyzed orthotopic tumor growth and experimental metastasis in mice carrying null or functional mutations in uPA, uPAR, or plasminogen to evaluate the interplay of PA components derived from tumor cells and/or stromal cells in mediating PDAC progression. Although both KPC cell CRISPR variants retained procoagulant function, elimination of tumor cell uPA or uPAR yielded significantly smaller tumors when compared to Cas9 control tumor cells in wildtype mice. Similarly, the growth of WT KPC tumor cells in C57Bl/6 background uPA-KO or uPAR-KO mice also resulted in reduced tumor growth. To our surprise, the metastasis potential of WT KPC tumor cells in uPA-KO or uPAR-KO mice did not change when compared to wildtype mice. Regarding to the uPA/uPAR axis downstream effector plasminogen, the growth of WT KPC tumors in plasminogen-KO mice was also significantly reduced, but not to the same extent as when eliminating uPA or uPAR. In addition, eliminating plasminogen drastically reduced WT KPC tumor cells metastasis potential. In conclusion, our data suggest a mechanism whereby uPA functions through uPAR in both the tumor cell and stromal cell compartments to promote PDAC progression through plasminogen-dependent and -independent mechanisms.
Citation Format: Yi Yang, Sara R. Abrahams, Aditi Kothari, Harshi Matada, Keely Davey, Alisa S. Wolberg, Matthew J. Flick. A uPA/uPAR axis in both the tumor cell and stromal compartment drives PDAC disease progression [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-127.
Association of Race and Ethnicity and Anticoagulation in Patients With Atrial Fibrillation Dually Enrolled in Veterans Health Administration and Medicare: Effects of Medicare Part D on Prescribing Disparities
Authors: Essien Utibe R. , Kim Nadejda , Magnani Jared W. , Good Chester B. , Litam Terrence M.A. , Hausmann Leslie R.M. , Mor Maria K. , Gellad Walid F. , Fine Michael J. 
Published: November 2021

Background:
Racial and ethnic disparities in anticoagulation exist in atrial fibrillation management in Medicare and the Veterans Health Administration, but the influence of dual Veterans Health Administration and Medicare enrollment is unclear. We compared anticoagulant initiation by race and ethnicity in dually enrolled patients and assessed the role of Medicare part D enrollment on anticoagulation disparities.

Methods:
We identified patients with incident atrial fibrillation (2014–2018) dually enrolled in Veterans Health Administration and Medicare. We assessed any anticoagulant initiation (warfarin or direct-acting oral anticoagulants [DOACs]) within 90 days of atrial fibrillation diagnosis and DOAC use among anticoagulant initiators. We modeled anticoagulant initiation, adjusting for patient, provider, and facility factors, including main effects for race and ethnicity and Medicare part D enrollment and an interaction term for these variables.

Results:

In 43 789 patients, 8.9% were Black, 3.6% Hispanic, and 87.5% White; 10.9% participated in Medicare part D. Overall, 29 680 (67.8%) patients initiated any anticoagulant, of whom 17 568 (59.2%) initiated DOACs. Lower proportions of Black (65.2%) than Hispanic (67.6%) or White (68.0%) patients initiated any anticoagulant (
P
=0.001) and, lower proportions of Black (56.3%) and Hispanic (55.9%) than White (59.6%) patients (
P
=0.001) initiated DOACs. Compared with White patients, Black patients had significantly lower initiation of any anticoagulant (adjusted odds ratio, 0.89 [95% CI, 0.82–0.97]). The adjusted odds ratios for DOAC initiation were significantly lower for Black (0.72 [95% CI, 0.65–0.81]) and Hispanic (0.84 [95% CI, 0.70–1.00]) than White patients. The interaction between race and ethnicity and Medicare part D enrollment was nonsignificant for any anticoagulant (
P
=0.99) and DOAC (
P
=0.27) therapies.

Conclusions:
In dually enrolled Veterans Health Administration and Medicare patients with atrial fibrillation, Black patients were less likely to initiate any anticoagulant, and Black and Hispanic patients were less likely to initiate DOACs. Medicare part D enrollment did not moderate the associations between race and ethnicity and anticoagulant therapies.
Intravenous Thrombolysis Before Mechanical Thrombectomy for Acute Ischemic Stroke: A Meta‐Analysis
Authors: Du Houwei , Lei Hanhan , Ambler Gareth , Fang Shuangfang , He Raoli , Yuan Qilin , Werring David J. , Liu Nan 
Published: November 2021

Background
Whether intravenous thrombolysis before mechanical thrombectomy provides additional benefit for functional outcome in acute ischemic stroke remains uncertain. We performed a meta‐analysis to compare the outcomes of direct mechanical thrombectomy (dMT) to mechanical thrombectomy with bridging using intravenous thrombolysis (bridging therapy [BT]) in patients with acute ischemic stroke.

Methods and Results

We performed a literature search in the PubMed, Excerpta Medica database, and Cochrane Central Register of Controlled Trials from January 1, 2003, to April 26, 2021. We included randomized clinical trials and observational studies that reported the 90‐day functional outcome in patients with acute ischemic stroke undergoing dMT compared with BT. The 12 included studies (3 randomized controlled trials and 9 observational studies) yielded 3924 participants (mean age, 68.0 years [SD, 13.1 years]; women, 44.2%; 1887 participants who received dMT and 2037 participants who received BT). A meta‐analysis of randomized controlled trial and observational data revealed similar 90‐day functional independence (odds ratio [OR], 1.04; 95% CI, 0.90–1.19), mortality (OR, 1.03; 95% CI, 0.78–1.36), and successful recanalization (OR, 0.93; 95% CI, 0.76–1.14) for patients treated with dMT or BT. Compared with those in the BT group, patients in the dMT group were less likely to experience symptomatic intracranial hemorrhage (OR, 0.68; 95% CI, 0.51–0.91;
P
=0.008) or any intracranial hemorrhage (OR, 0.71; 95% CI, 0.61–0.84;
P
<0.001).

Conclusions
In this meta‐analysis of patients with acute ischemic stroke, we found no significant differences in 90‐day functional outcome or mortality between dMT and BT, but a lower rate of symptomatic intracranial hemorrhage for dMT. These findings support the use of dMT without intravenous thrombolysis bridging therapy.

Registration

URL:
https://www.crd.york.ac.uk/prospero/
; Unique identifier: 42021234664.
Complex Effects of Telecouplings on Forest Dynamics: An Agent-Based Modeling Approach
Authors: Yang Hongbo , Ligmann-Zielinska Arika , Dou Yue , Chung Min Gon , Zhang Jindong , Liu Jianguo 
Published: November 2021

Abstract
Rural areas are increasingly subject to the effects of telecouplings (socioeconomic and environmental interactions over distances) whereby their human and natural dynamics are linked to socioeconomic and environmental drivers operating far away, such as the growing demand for labor and ecosystem services in cities. Although there have been many studies evaluating the effects of telecouplings, telecouplings in those studies were often investigated separately, and how telecouplings may interact and affect dynamics of rural coupled human and natural systems (CHANS) jointly was rarely evaluated. In this study, we developed an agent-based model and simulated the impacts of two globally common telecouplings, nature-based tourism and labor migration, on forest dynamics of a rural CHANS, China’s Wolong Nature Reserve (Wolong). Nature-based tourism and labor migration can facilitate forest recovery, and the predicted forest areas in Wolong in 2030 would be reduced by 26.2 km2 (6.8%) and 23.9 km2 (6.2%), respectively, without their effects. However, tourism development can significantly reduce the probability of local households to have member(s) outmigrate to work in cities and decrease the positive impact of labor migration on forest recovery. Our simulations show that the interaction between tourism and labor migration can reduce the potential forest recovery by 3.5 km2 (5.0%) in 2030. Our study highlights that interactions among different telecouplings can generate significant impacts on socioeconomic and environmental outcomes and should be jointly considered in the design, management, and evaluation of telecouplings for achieving sustainable development goals.

Significance Statement
Rural areas are increasingly connected with other places through telecouplings, such as tourism and labor migration. However, telecouplings’ effects were often evaluated separately, and their interaction remains poorly understood. In this study, we evaluated how two globally common telecouplings, tourism and labor migration, jointly affect forest dynamics in a demonstration site using an agent-based modeling approach. Although both tourism and labor migration can benefit forest conservation, we found that their interaction generates an antagonistic effect: households’ involvement in tourism activities reduces their probability to have members outmigrate to work in cities and significantly diminishes the beneficial impact of labor migration on forest recovery. Our study highlights the importance of considering interaction among telecouplings in the management of telecouplings for sustainability.
Comparing the Cognitive Functioning Effects of Aerobic and Pilates Exercises for Inactive Young Adults: A Randomized Controlled Trial
Authors: Kaya Begum Kara , Alpozgen Ayse Zengin 
Published: November 2021

Aerobic exercises (AE) have been found to have short-term positive effects on certain aspects of cognitive functioning. Pilates exercises (PE) may have similar benefits. In this randomized controlled study, we compared the effectiveness of PE and AE on participants’ cognitive functions. We randomly assigned 52 physically inactive young adult volunteers into either a PE group ( Mage = 20.85, SD = 2.11 years; 18 females and 8 males) or an AE group ( Mage = 19.88, SD = 0.91 years; 18 females and 8 males). In both groups, participants engaged in a moderately intense exercise program three days a week for four weeks. We tested participants on cognitive measures of selective attention and inhibitory control (Stroop test), verbal fluency (verbal fluency tests (letter and category); VFTs), and speed of movement (Nelson’s Speed of Movement Test; NSMT). There were no group differences on the Stroop and the VFTs ( p>0.05). However, there was a significant pre- to post-exercise difference for participants in both groups with a medium-large effect size (ES) on Stroop sections 1, 3, 4, and 5, respectively (PE: p < 0.001, ES = 0.58, p = 0.001, ES = 0.54, p < 0.001, ES = 0.88, p = 0.001, ES = 0.60; AE: p < 0.001, ES = 0.70, p < 0.001, ES = 0.89, p < 0.001, ES = 0.86, p = 0.006, ES = 0.65). There was a large effect size pre- to post-exercise detected for VFT sections labeled letter (PE: p < 0.001, ES = 1.45; AE: p < 0.001, ES = 1.11), and category (PE: p < 0.001, ES = 1.11; AE: p < 0.001, ES = 0.83), and there was a large ES for NSMT in the PE group ( p < 0.001, ES = 1.07). Both PE and AE may lead to short-term improvements in selective attention, verbal fluency, and executive control in inactive young adults, and PE may benefit speed of movement.
A Comparison of Clinical Outcomes of Endovascular Repair Versus Open Surgery for Ruptured Descending Thoracic Aorta
Authors: Xie Xinsheng , Shu Xiaolong , Zhang Wei , Guo Daqiao , Zhang Wayne W. , Wang Lixin , Fu Weiguo 
Published: November 2021

Objective: The comparisons between thoracic endovascular aortic repair for ruptured thoracic aorta (TEVAR) and open surgery (OS) have not been well documented, although both procedures have been widely utilized. We performed a systematic review and meta-analysis to investigate the effectiveness and safety between TEVAR and OS in the repair of ruptured descending thoracic aorta. Methods: PubMed, Embase, and Cochrane Library databases were searched to find relevant studies to assess TEVAR and OS outcomes. The comparative parameters were perioperative mortality (30 day/in-hospital), 1 year mortality, paraplegia or paraparesis, renal insufficiency, stroke, pulmonary embolism, re-intervention rate, pulmonary complications, and cardiac complications. A fixed-effects model was applied to calculate the odds ratio (OR) with a 95% confidence interval (CI) on pooled outcomes from different studies. Results: Eighteen observational trials involving 2088 patients were evaluated (TEVAR=560; OS=1528). Meta-analysis showed that TEVAR in repairing the ruptured descending thoracic aorta was associated with lower perioperative mortality (OR=0.47; 95% CI: 0.34–0.66; p<0.01), 1 year mortality (OR=0.46; 95% CI: 0.29–0.75; p<0.01), renal insufficiency incidence (OR=0.56; 95% CI: 0.33–0.93; p=0.03), and pulmonary complications (OR=0.69; 95% CI: 0.52–0.92; p=0.01) when compared with OS. There was no significant difference between TEVAR and OS in terms of paraplegia, stroke, pulmonary embolism, cardiac complications, and early re-intervention rates. However, the late re-intervention rate was higher in the TEVAR group than that in the OS group. Conclusions: When repairing the ruptured descending thoracic aorta, TEVAR may be performed rapidly and safely. TEVAR is associated with lower rates of perioperative morbidity and early postoperative complications than OS.
Comparison of two simple stitches and modified Mason-Allen suture for medial meniscus posterior root tear based on the progression of meniscal posterior extrusion: A retrospective cohort study
Authors: Kintaka Keisuke , Furumatsu Takayuki , Okazaki Yuki , Masuda Shin , Hiranaka Takaaki , Kodama Yuya , Kamatsuki Yusuke , Ozaki Toshifumi 
Published: November 2021

Purpose: Medial meniscus (MM) posterior root (PR) tear leads to severe MM posterior extrusion (PE), resulting in rapid knee cartilage degeneration. MMPR repairs are recommended to reduce MMPE, especially during knee flexion. However, the difference in MMPE between different repair techniques remains unknown. This study aimed to investigate preoperative and postoperative MMPE following several pullout repair techniques. We hypothesized that a technique using two simple stitches (TSS) would be more useful than FasT-Fix-dependent modified Mason-Allen suture (F-MMA) to prevent the progression of MMPE in knee extension. Methods: This retrospective study included 35 patients who underwent MMPR repair. To compare MMPE, patients were divided into two groups according to the use of F-MMA while grasping the posterior capsule and TSS without grasping it. Open magnetic resonance imaging was performed at 10° and 90° knee flexion preoperatively, and at 3 and 12 months postoperatively, and the MMPE of both groups was evaluated. Results: A significant difference was observed between preoperative and 3-month postoperative MMPE at 90° knee flexion in both groups ( p < .01). A significant difference was observed in 3- and 12-month postoperative MMPE at 10° knee flexion between both groups ( p = .04/.02), whereas no significant difference in the preoperative MMPE at 10° knee flexion was observed between them ( p = .45). Conclusions: Both repairs were found to be useful to reduce MMPE in knee flexion. Further, F-MMA repair increased MMPE in knee extension, unlike TSS repair. These findings suggest that TSS might have more advantages for load distribution when standing or walking.
Rate of Incidental Parathyroidectomy in a Pediatric Population
Authors: Sahyouni Grace , Osterbauer Beth , Park Soyun , Paik Connie , Austin Juliana , Gomez Gabriel , Kwon Daniel 
Published: November 2021

ObjectiveIncidental parathyroidectomy is a relatively common occurrence in thyroid surgery, which may lead to hypoparathyroidism and postoperative hypocalcemia, but it is not well studied in children. The objectives of this study were to determine the rate of incidental parathyroidectomy, identify potential risk factors, and investigate postoperative complications in children undergoing thyroidectomy.Study DesignRetrospective cohort study.SettingPatients who underwent thyroidectomy over a 10‐year period at a tertiary children’s hospital.MethodsPathology reports were reviewed to determine incidental parathyroid gland tissue. Additional data collected included patient demographics, type of procedure, underlying thyroid pathology, as well as immediate and long‐term postoperative clinical outcomes.ResultsOf 209 patients, 65 (31%) had incidental parathyroidectomy. Several variables were associated with incidental parathyroidectomy on univariable analysis. However, in the final multivariable model, only thyroidectomy with lymph node dissection was associated with increased odds of having incidental parathyroidectomy (odds ratio, 3.3; P =. 04; 95% CI, 1.1‐9.8). After a median follow up of 1 year, a significantly higher percentage of patients with incidental parathyroidectomy had evidence of long‐term hypoparathyroidism (9/62 [15%] vs 3/144 [2%], P =. 001).ConclusionIncidental parathyroidectomy was relatively common in our pediatric thyroidectomy population, which may be a result of several anatomic, clinical, and surgeon‐related factors. Close attention to parathyroid preservation with meticulous surgical technique is the most practical method of preventing long‐term hypoparathyroidism and hypocalcemia.