bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract C077: Evidence for a tumoral temperature driven chemoresistance pathway in pancreatic cancer
Authors: de Laat Vincent , Topal Halit , Dehairs Jonas , Spotbeen Xander , Talebi Ali , Vanderhoydonc Frank , Ostyn Tessa , Roskams Tania , Topal Baki , Swinnen Johan 
Published: November 2022

Abstract
Tumor growth is inevitably accompanied by changes in the tumor-microenvironment to which cancer cells have to adapt in order to thrive. Alterations in metabolism and blood perfusion of solid tumors have been suggested to drive a spontaneous increase in tumoral temperature. However, it is currently unknown if this phenomenon affects cancer biology. We found increased temperature in human pancreatic ductal adenocarcinoma (PDAC) tumors. By mimicking this observation in PDAC cell lines, we found that cancer cells adapt to tumoral temperature by altering the cellular lipidome and accordingly evade ferroptosis, a lipid-dependent form of cell death. We found evidence that tumoral temperature-induced ferroptosis evasion depends on p38-MAPK deactivation and ultimately drives resistance to the chemotherapeutic drug gemcitabine. Collectively, our findings suggest a direct role for p38-dependend ferroptosis evasion in gemcitabine resistance, and we identify tumoral temperature as a pathophysiological driver of this process. Our discovery unveils temperature as an unexplored hallmark of the tumor-microenvironment.
Citation Format: Vincent de Laat, Halit Topal, Jonas Dehairs, Xander Spotbeen, Ali Talebi, Frank Vanderhoydonc, Tessa Ostyn, Tania Roskams, Baki Topal, Johan Swinnen. Evidence for a tumoral temperature driven chemoresistance pathway in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C077.
Abstract C082: Signaling pathways inducing tumoricidal phagocytosis in pancreatic cancer
Authors: Qiang Li , Liu Samantha , Ro Gabrielle , Ali Lestat , Lenehan Patrick , Hambizer Felix , Dougan Michael , Dougan Stephanie 
Published: November 2022

Abstract
Macrophages can be repolarized to promote tumor destruction, particularly by triggering tumoricidal phagocytosis of cancer cells. Despite the increasing interest in monoclonal antibody therapies targeting tumor antigens to drive cancer cell elimination via phagocidal macrophages, we still face tremendous challenges in developing adequate therapeutics due to lack of knowledge of the signaling pathways that induce phagocidal macrophages. Our previous work showed that cIAP1/2 antagonism and T cell derived cytokines promote anti-tumor immunity by reprogramming tumoricidal macrophages to phagocytose both live and dead tumor cells. Here we performed transcriptional analysis on both macrophages and tumor cells treated with cIAP1/2 antagonism or vehicle and identified candidate positive and negative regulators of phagocytosis. We are demonstrating how these receptors-ligand pairs on macrophages and tumor cells are induced and the mechanisms by which they effect tumor cell destruction. We also performed an in vitro CRISPR screen on tumor cells cocultured with macrophages, treated with cIAP1/2 antagonism or vehicle, recovered the DNA of phagocytosed tumor cells from within macrophages and compared to non-phagocytosed tumor cells to discover mediators of resistance or sensitivity to both baseline phagocytosis (efferocytosis) and cIAP1/2 antagonism induced phagocytosis.Our screen revealed a striking lack of dependence on MHC class I for tumors treated in vivo. Genes involved in phagocytosis resistance instead converged on regulation of the cytoskeleton and the tumor suppressor gene Stk11. This study will provide critical insights on tumoricidal macrophages, uncover the key pathways reprogramming these myeloid cells, and decipher the essential tumor-intrinsic pathways resulting in sensitivity and resistance to anti-tumor phagocytosis.
Citation Format: Li Qiang, Samantha Liu, Gabrielle Ro, Lestat Ali, Patrick Lenehan, Felix Hambizer, Michael Dougan, Stephanie Dougan. Signaling pathways inducing tumoricidal phagocytosis in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C082.
Abstract IA011: Precision oncology approaches in pancreatic cancer
Authors: Yeh Jen Jen 
Published: November 2022

Abstract
Advances in next generation sequencing and therapies have led to an explosion of possibilities for precision oncology in pancreatic cancer. The talk will focus on current and up and coming precision approaches for patients with pancreatic cancer.
Citation Format: Jen Jen Yeh. Precision oncology approaches in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr IA011.
Abstract IA018: ATP production in pancreas cancer and tumor infiltrating lymphocytes
Authors: Rabinowitz Joshua D. 
Published: November 2022

Abstract
Diet can influence both the microbiome and (at least in mice) the outcomes of pancreas cancer therapy. For example, ketogenic diet can synergize with either current standard of care therapy ( gemcitabine + nab-paclitaxel) or PI3K inhibition in mouse models of pancreas cancer. I will discuss our recent work exploring how diet interacts with the microbiome, and how such interactions may influence pancreas cancer chemotherapy response. A simple hypothesis for how diet influences microbiome composition is that certain microbes prefer certain nutrients, and diets high in those nutrients lead to outgrowth of those microbes. To enable testing of this hypothesis, we developed isotope-tracer strategies that directly measure the nutrient preferences of different members of the gut microbiome. I will describe this new technology and its application to support the above hypothesis. I will further describe experiments manipulating diet and/or microbiome to influence the response of pancreas cancer to PI3K inhibition. The longterm goal is to understand, at a biochemical level, the links between diet, microbiome, and the effectiveness of cancer therapy, and to develop translatable strategies for manipulating metabolism via diet to improve therapeutic outcomes.
Citation Format: Joshua D. Rabinowitz. ATP production in pancreas cancer and tumor infiltrating lymphocytes [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr IA018.
Abstract PR011: Proteomic profiling reveals subtype specific kinase expression in pancreatic cancer
Authors: Xu Yi , Morrison Ashley B. , Herrera Silvia G. , East Michael P. , Johnson Gary L. , Yeh Jen Jen 
Published: November 2022

Abstract
We have previously identified two tumor specific molecular subtypes in pancreatic ductal adenocarcinoma (PDAC), basal-like and classical. Although basal-like tumors are found in less than 20% of patients, patients with basal-like tumors have a worse prognosis and are largely resistant to FOLFIRINOX chemotherapy. To identify targetable basal-like subtype specific vulnerabilities in PDAC, we utilized Multiplexed kinase Inhibitor Beads and Mass Spectrometry (MIB-MS) to profile the kinome in patient derived xenograft (PDX) models that recapitulate the tumor subtypes found in patients. MIB-MS results show that kinase expression is significantly associated with molecular subtype. Notably, basal-like tumors show increased expression of receptor tyrosine kinases (RTKs) including EGFR, MET, and IGF1R and MAP kinase members MEK2 and BRAF indicating activation of the MAP kinase signaling cascade. These RTKs including EGFR are also differentially expressed in primary patient tumors suggesting the true efficacy of EGFR and other kinase inhibitors in basal-like tumors may have been masked by the larger proportion of patients (&gt;80%) with unresponsive classical tumors. Furthermore, inhibition of MAP kinase signaling with the MEK inhibitor trametinib results in kinome reprogramming exclusive to classical tumors. MIB-MS profiling reveals upregulation of TAOK3 and MEK3/6 indicating activation of p38 MAP kinase signaling as a classical subtype specific compensatory mechanism against MEK inhibition. Overall, these results present actionable basal-like subtype specific kinase targets by defining a novel subtype specific kinome in PDAC. Precision approaches in clinical trials are needed to determine if new and previously thought to be disappointing kinase inhibitors may be efficacious in patients with basal-like tumors.
Citation Format: Yi Xu, Ashley B. Morrison, Silvia G. Herrera, Michael P. East, Gary L. Johnson, Jen Jen Yeh. Proteomic profiling reveals subtype specific kinase expression in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr PR011.
Right Posterior Temporal Cortex Supports Integration of Phonetic and Talker Information
Authors: Luthra Sahil , Magnuson James S. , Myers Emily B. 
Published: November 2022

Abstract
Though the right hemisphere has been implicated in talker processing, it is thought to play a minimal role in phonetic processing, at least relative to the left hemisphere. Recent evidence suggests that the right posterior temporal cortex may support learning of phonetic variation associated with a specific talker. In the current study, listeners heard a male talker and a female talker, one of whom produced an ambiguous fricative in /s/-biased lexical contexts (e.g., epi?ode) and one who produced it in /∫/-biased contexts (e.g., friend?ip). Listeners in a behavioral experiment (Experiment 1) showed evidence of lexically guided perceptual learning, categorizing ambiguous fricatives in line with their previous experience. Listeners in an fMRI experiment (Experiment 2) showed differential phonetic categorization as a function of talker, allowing for an investigation of the neural basis of talker-specific phonetic processing, though they did not exhibit perceptual learning (likely due to characteristics of our in-scanner headphones). Searchlight analyses revealed that the patterns of activation in the right superior temporal sulcus (STS) contained information about who was talking and what phoneme they produced. We take this as evidence that talker information and phonetic information are integrated in the right STS. Functional connectivity analyses suggested that the process of conditioning phonetic identity on talker information depends on the coordinated activity of a left-lateralized phonetic processing system and a right-lateralized talker processing system. Overall, these results clarify the mechanisms through which the right hemisphere supports talker-specific phonetic processing.
Indicators of research quality, quantity, openness, and responsibility in institutional review, promotion, and tenure policies across seven countries
Authors: Pontika Nancy , Klebel Thomas , Correia Antonia , Metzler Hannah , Knoth Petr , Ross-Hellauer Tony 
Published: November 2022

Abstract
The need to reform research assessment processes related to career advancement at research institutions has become increasingly recognized in recent years, especially to better foster open and responsible research practices. Current assessment criteria are believed to focus too heavily on inappropriate criteria related to productivity and quantity as opposed to quality, collaborative open research practices, and the socioeconomic impact of research. Evidence of the extent of these issues is urgently needed to inform actions for reform, however. We analyze current practices as revealed by documentation on institutional review, promotion, and tenure (RPT) processes in seven countries (Austria, Brazil, Germany, India, Portugal, the United Kingdom and the United States). Through systematic coding and analysis of 143 RPT policy documents from 107 institutions for the prevalence of 17 criteria (including those related to qualitative or quantitative assessment of research, service to the institution or profession, and open and responsible research practices), we compare assessment practices across a range of international institutions to significantly broaden this evidence base. Although the prevalence of indicators varies considerably between countries, overall we find that currently open and responsible research practices are minimally rewarded and problematic practices of quantification continue to dominate.
When standard network measures fail to rank journals: A theoretical and empirical analysis
Authors: Vaccario Giacomo , Verginer Luca 
Published: November 2022

Abstract
Journal rankings are widely used and are often based on citation data in combination with a network approach. We argue that some of these network-based rankings can produce misleading results. From a theoretical point of view, we show that the standard network modeling approach of citation data at the journal level (i.e., the projection of paper citations onto journals) introduces fictitious relations among journals. To overcome this problem, we propose a citation path approach, and empirically show that rankings based on the network and the citation path approach are very different. Specifically we use MEDLINE, the largest open-access bibliometric data set, listing 24,135 journals, 26,759,399 papers, and 323,356,788 citations. We focus on PageRank, an established and well-known network metric. Based on our theoretical and empirical analysis, we highlight the limitations of standard network metrics and propose a method to overcome them.
Remoteness and socioeconomic status reduce access to specialist mental health care across Australia
Authors: Amos Andrew , Coleman Mathew , Spring Walsh Breeanna , Gardiner Fergus W 
Published: November 2022

Objective Estimate impact of socioeconomic factors and remoteness from tertiary hospital on incidence/duration of Australian mental health admissions. Methods Retrospective analysis of incidence/duration of public mental health unit admissions (2018–19). Covariates included Indigenous population, potentially preventable hospitalisations (PPH) and socioeconomic disadvantage. Results Regional distance from hospital was correlated with socioeconomic disadvantage ( ρ: p < 0.01). Population identifying as Aboriginal or Torres Strait Islander was associated with distance from hospital, socioeconomic disadvantage and PPH ( ρ: p < 0.01). Bed days per capita was explained ( R2adj: 0.48) by distance and socioeconomic disadvantage ( p < 0.0001). A 1% increase in distance from hospital was associated with a 0.37% decrease in per capita bed days. Admission rate per capita across Queensland and WA was explained ( R2adj: 0.36) by distance, education/occupation and state ( p < 0.05). Across Queensland and WA a 1% increase in distance from hospital was associated with a 0.05% decreased incidence of admission. Conclusions Rural Australians face high mental illness burden, socioeconomic disadvantage and limited service provision. Overcoming the additional disadvantages of reduced likelihood of admission to and reduced time in hospital with increasing distance from hospital will require increased outreach proportional to remoteness.
Multicenter investigation of technical and clinical outcomes after thrombectomy for Proximal Medium Vessel Occlusion (pMeVO) by frontline technique
Authors: Grossberg Jonathan A , Chalhoub Reda M , Al Kasab Sami , Pullmann Dominika , Jabbour Pascal , Psychogios Marios , Starke Robert M , Arthur Adam S , Fargen Kyle M , De Leacy Reade , Kan Peter , Dumont Travis , Rai Ansaar , Crosa Roberto J , Naamani Kareem E , Maier Ilko , Goyal Nitin , Wolfe Stacey Quintero , Michael Cawley C , Mocco J , Hafeez Muhammad , Howard Brian M , Dimisko Laurie , Saad Hassan , Ogilvy Christopher S , Webster Crowley R , Mascitelli Justin , Fragata Isabel , Levitt Michael , Spiotta Alejandro M , Alawieh Ali M ,   on behalf of the STAR Collaborators
Published: November 2022

Background Endovascular thrombectomy(EVT) is the standard of care for large vessel occlusion(LVO) stroke. Data on technical and clinical outcome in proximal medium vessel occlusions(pMeVOs) comparing frontline techniques remain limited. Methods We report an international multicenter retrospective study of patients undergoing EVT for stroke at 32 centers between 2015–2021. Patients were divided into LVOs(ICA/M1/Vertebrobasilar) or pMeVOs(M2/A1/P1) and categorized by thrombectomy technique. Primary outcome was 90-day good functional outcome(mRS ≤ 2). Multivariate logistic regressions were used to evaluate the impact of technical variables on clinical outcomes. Propensity score matching was used to compare outcome in patients with pMeVO treated with aspiration versus stent-retriever. Results In the cohort of 5977 LVO and 1287 pMeVO patients, pMeVO did not independently predict good-outcome(p  =  0.55). In pMeVO patients, successful recanalization irrespective of frontline technique(aOR = 3.2,p < 0.05), procedure time ≤ 1-h(aOR = 2.2,p < 0.05), and thrombectomy attempts ≤ 4(aOR =  2.8,p < 0.05) were independent predictors of good-outcomes. In a propensity-matched cohort of aspiration versus stent-retriever pMeVO patients, there was no difference in good-outcomes. The rates of hemorrhage were higher(9%vs.4%,p < 0.01) and procedure time longer(51-min vs. 33-min,p < 0.01) with stent-retriever, while the number of attempts was higher with aspiration(2.5vs.2,p < 0.01). Rates of hemorrhage and good-outcome showed an exponential relationship to procedural metrics, and were more dependent on time in the aspiration group compared to attempts in the stent-retriever group. Conclusions Clinical outcomes following EVT for pMeVO are comparable to those in LVOs. The golden hour or 3-pass rules in LVO thrombectomy still apply to pMeVO thrombectomy. Different techniques may exhibit different futility metrics; SR thrombectomy was more influenced by attempts whereas aspiration was more dependent on procedure time.
Catastrophic antiphospholipid syndrome after pregnancy complicated by hemolysis, elevated liver enzymes and low platelets syndrome
Authors: Saini Aashna , Wilkie Gianna , Dumont Tina 
Published: November 2022

Background Antiphospholipid syndrome (APLS) is rarely complicated by catastrophic antiphospholipid syndrome (CAPS). Peripartum CAPS is rarer still and can masquerade as other obstetric disorders. A high degree of suspicion is critical for early diagnosis and specific management given the significant morbidity and mortality associated with this disorder. Case We report a case of a 27-year-old at 22 week's gestation with a history of APLS found to have severe hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, resulting in termination of pregnancy. Further workup revealed the diagnosis of CAPS followed by prompt treatment with triple therapy leading to clinical improvement. Conclusion CAPS should be considered within the differential in an obstetric patient with a history of APLS who has evidence of multiorgan involvement with macro- or microvascular thrombosis. Although this may mimic alternative disorders, prompt diagnosis is imperative for appropriate therapy and reduction in maternal morbidity and mortality.
3D Analysis of the Hindfoot Following Total Ankle Replacement for Varus Ankle Osteoarthritis
Authors: Kvarda Peter , Siegler Lena , Horn-Lang Tamar , Susdorf Roman , Ruiz Roxa , Hintermann Beat 
Published: November 2022

Category: Hindfoot; Ankle; Ankle Arthritis Introduction/Purpose: In advanced stages of varus ankle osteoarthritis (OA) progressive destabilization of the peritalar structures is common. Total ankle replacement (TAR) is a viable treatment option although data, particularly on changes in the subtalar joint position following TAR, is scarce. Therefore, we evaluated the subtalar joint using semi-automated measurements based on weightbearing cone-beam CT scans (WBCT) before and after TAR. Methods: 14 patients (15 ankles) who received TAR without additional bony procedures for varus ankle OA were analyzed using semi-automated measurements of the hindfoot based on pre-and postoperative WBCT. Pain on visual analog scale (VAS) and American Orthopedic Foot and Ankle Society Hindfoot Score (AOFAS) were assessed. Results: Five of 6 measurements showed a significant improvement including sagittal and axial talocalcaneal angle, talar horizontal inclination angle, hindfoot angle, and talar tilt. Conclusion: Besides ankle joint realignment, TAR for varus ankle OA without additional bony procedures achieved significant correction of the subtalar joint based on WBCT.
Midfoot Joint Arthrodesis using Compression Plate with Lag Screw Augmenting with Highly Porous β- Tricalcium Phosphate (β-TCP) and Bone Marrow Aspirate Concentrate (BMAC)
Authors: Lee Wonyong , MacDonald Justin , Prat Dan , Chao Wen , Farber Daniel C. , Wapner Keith L. 
Published: November 2022

Category: Midfoot/Forefoot Introduction/Purpose: There is still a controversy regarding the most optimal fixation instruments and bone graft materials for midfoot joint arthrodesis. We present the results of midfoot joint arthrodesis using compression plate highly porous β-tricalcium phosphate (β-TCP) and bone marrow aspirate concentrate (BMAC). Methods: We performed a retrospective review of patients undergoing midfoot joint arthrodesis using compression plate with lag screw augmenting with highly porous β - tricalcium phosphate (β - TCP) and bone marrow aspirate concentrate (BMAC) from January 2014 to May 2019. The radiographic bony union rate was investigated. Postoperative complications and reoperations were also noted. A total of 36 patients (37 feet) including 75 joints were available in this study. Results: A high bony union rate was achieved as of 97.3% in 73 out of 75 joints. Nonunion was seen in two patients including two joints: one for 1st TMT joint and the other for medial NC joint. There was no delayed union in this study. Time to radiographic union was 10.5 +- 1.9 (range, 7-15) weeks. A total of five postoperative complications were noted. All of them were related to hardware irritation, and all five patients underwent removal of hardware procedure. There was no major complication such as infection during the follow-up period. Of the two nonunion patients, only one with medial NC joint nonunion underwent a revision arthrodesis surgery. Conclusion: Based on our results, the fixation construct of compression plate with lag screw augmenting with highly porous β - tricalcium phosphate (β - TCP) and bone marrow aspirate concentrate (BMAC) is safe and effective for midfoot joint arthrodesis with an excellent union rate and a low complication rate.