bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA014: Mass spectrometry and RNAseq based discovery of frameshift neoantigens and cryptic neoantigens from malignant peripheral nerve sheath tumors for prophylactic vaccines
Authors: Largaespada David A. 
Published: December 2022

Abstract
Neurofibromatosis type 1 (NF1) syndrome is an autosomal, dominant tumor predisposition syndrome caused by loss-of-function mutations of NF1 gene encoding neurofibromin. Loss of the non-mutant allele of NF1 in a rare Schwann cell or precursor leads to benign plexiform neurofibromas. The main cause of death among NF1 patients is the malignant peripheral nerve sheath tumor (MPNST), a highly aggressive soft tissue sarcoma that most likely develops from plexiform neurofibroma, in particular the so-called “atypical” plexiform neurofibroma. Approximately half of MPNSTs are NF1-associated, and NF1 patients have ~15% lifetime risk of developing this terrible cancer. NF1 patients could greatly benefit from prophylactic vaccination that would prevent the malignant transformation to MPNSTs. We hypothesize that malignant transformation leads to the expression of recurrent alternately processed transcripts, such as transcriptionally-induced chimeras, that could express neoantigens and be used as targets for prophylactic vaccines. Such transcripts can be translated to produce novel peptides downstream of frameshift mutations caused by coding exon read-through into introns, mis-splicing from a coding exon to a non-canonical splice acceptors or splice acceptors in other genes. In most cases, a premature termination codon (PTC) will be rapidly encountered by the ribosome translating such transcripts. Therefore, we furthermore hypothesize that these alternately processed transcripts can express what we call “cryptic” neoantigens when treated with drugs that suppress utilization of premature codons such as Ataluren or gentamicin. In such a way, we could administer a prophylactic vaccine and induce conditionally active immune response that would eliminate nascent tumors only when drug treatment is used. We have developed a PTC suppression read-through reporter which results in presentation of the SIINFEKL peptide on C57BL6/J tumor cells. We developed a bioinformatic algorithm that takes deep RNA-seq data and identifies candidate neoepitopes encoded by non-normally processed or mutant mRNAs called Identifying and Verifying Immunogenic Neoepitopes and Neojunctions (IVINN). We have also achieved successful purification of human HLA Class I complex using an anti-pan HLA antibody column, and bound peptides have been isolated and identified by liquid chromatography tandem mass spectrometry (LC-MS/MS). We plan to utilize these approaches for mouse model and human MPNST patient derived xenografts.
Citation Format: David A. Largaespada. Mass spectrometry and RNAseq based discovery of frameshift neoantigens and cryptic neoantigens from malignant peripheral nerve sheath tumors for prophylactic vaccines [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr IA014.
Abstract IA019: Clinical trials of GUCY2C (GCC) agonists for colorectal cancer prevention
Authors: Waldman Scott A. 
Published: December 2022

Abstract
Guanylyl cyclase C (GUCY2C), expressed on intestinal epithelial cells, is the receptor for heat-stable enterotoxins (STs) produced by diarrheagenic bacteria. Fluid secretion reflects ST activation of GUCY2C, which produces cyclic (c)GMP activating ion channels. Beyond toxins, GUCY2C binds uroguanylin in small intestine and guanylin in colorectum, which also stimulate secretion. This mechanism is the basis for the oral agonists linaclotide (ST analog) and plecanatide (uroguanylin analog) to treat constipation. Guanylin is the most commonly lost gene product, while GUCY2C expression is retained, in colorectal tumors. Eliminating GUCY2C promotes tumor formation, while oral GUCY2C agonists or transgenic guanylin reduce intestinal tumors, in mice. These data support a hypothesis in which loss of guanylin silencing GUCY2C is a key step in intestinal transformation which can be prevented by oral GUCY2C agonists. However, GUCY2C agonists are formulated for duodenal activity, without bioavailability in the colorectum. Here, we explored whether this pharmacokinetic (PK) barrier could be abrogated with high doses (HD) of linaclotide. Indeed, HD linaclotide induced a cGMP response in mucosal biopsies obtained by colonoscopy following oral polyethylene glycol (PEG) preparation. This cGMP response was validated by VASP phosphorylation and suppression of crypt proliferation. Similarly, HD linaclotide induced cGMP in colon biopsies obtained by sigmoidoscopy following oral PEG. However, HD linaclotide failed to induce cGMP in colon biopsies obtained by sigmoidoscopy i n the absence of oral PEG . Thus, oral PEG abrogated the PK barrier, delivering linaclotide to the colorectum. Unfortunately, dolcanatide, a proteolysis-resistant analog of plecanatide, also failed to overcome the colorectal PK barrier, although it produced duodenal secretion and diarrhea. Thus, guanylin loss silencing GUCY2C appears to be a key step in intestinal transformation. Preclinical models suggest that oral GUCY2C agonists stimulate GUCY2C signaling, opposing tumorigenesis. However, translation of these observations appears to be constrained by a PK barrier, reflecting agonists formulated for duodenal activity, without colorectal bioavailability. Exploiting GUCY2C for chemoprevention awaits agonists formulated for the colorectum. We are exploring the ability of GUCY2C agonists to activate cGMP in duodenum (within the PK barrier), as a prelude to trials in patients with FAP at risk for duodenal tumors.
Citation Format: Scott A. Waldman. Clinical trials of GUCY2C (GCC) agonists for colorectal cancer prevention [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr IA019.
Differential Expression of Inflammarafts in Macrophage Foam Cells and in Nonfoamy Macrophages in Atherosclerotic Lesions—Brief Report
Authors: Navia-Pelaez Juliana M. , Agatisa-Boyle Colin , Choi Soo-Ho , Sak Kim Yi , Li Shenglin , Alekseeva Elena , Weldy Kimberly , Miller Yury I. 
Published: December 2022

Background:
Reprogramming of monocytes and macrophage manifests in hyperinflammatory responses and chronification of inflammation in atherosclerosis. Recent studies focused on epigenetic, transcriptional, and metabolic alterations that characterize trained immunity. However, the underlying effector mechanisms driving the hyperinflammatory response of reprogrammed macrophages remain unclear. We hypothesized that the plasma membrane of atherosclerotic lesion macrophages undergoes reprogramming to maintain inflammarafts, enlarged lipid rafts (LR) serving as a platform for assembly of inflammatory receptor complexes.

Methods:

Single-cell suspensions from the aortae of Western diet–fed
Ldlr

−/−

mice were gated for BODIPY-high foamy and BODIPY-low nonfoamy F4/80 macrophages by flow cytometry. Inflammarafts were characterized by increased levels of LR, TLR4 (toll-like receptor-4) localization to LR, TLR4 dimers, and the proximity between TLR2, TLR1, and CD36. In a cellular model of trained immunity, LR, TLR4 dimers, and the inflammatory response were measured in bone marrow–derived macrophages subjected to a 24-hour treatment with LPS (lipopolysaccharide) or OxLDL (oxidized low-density lipoprotein), followed by a 6-day wash-out period.

Results:
Nonfoamy macrophages, which constituted ≈40% of macrophages in atherosclerotic lesions, expressed significantly higher levels of LR and TLR4 dimers, as well as proximity ligation signals for TLR4-LR, TLR2-CD36, and TLR2-TLR1 complexes, compared with foamy macrophages. These inflammaraft measures associated, to a different degree, with plasma cholesterol and inflammatory cytokines, as well as the size of the atherosclerotic lesions and necrotic cores. The bone marrow–derived macrophages trained with LPS simulated nonfoamy atherosclerotic lesion macrophages and continued to express inflammarafts and inflammatory genes for 6 days after LPS removal and displayed a hyperinflammatory response to Pam3CSK4, a TLR2/TLR1 agonist. OxLDL-exposed, lipid-laden macrophages did not express inflammarafts.

Conclusions:
Our data support the hypothesis that persistent inflammarafts in nonfoamy macrophages in atherosclerotic lesions serve as effectors of macrophage reprogramming into a hyperinflammatory phenotype.
Cardiac Adverse Events Associated With Chemo‐Radiation Versus Chemotherapy for Resectable Stage III Non‐Small‐Cell Lung Cancer: A Surveillance, Epidemiology and End Results‐Medicare Study
Authors: Herbach Emma , O'Rorke Michael A. , Carnahan Ryan M. , McDowell Bradley D. , Allen Bryan , Grumbach Isabella , London Barry , Smith Brian J. , Spitz Douglas R. , Seaman Aaron , Chrischilles Elizabeth A. 
Published: December 2022

Background
We compared cardiac outcomes for surgery‐eligible patients with stage III non‐small‐cell lung cancer treated adjuvantly or neoadjuvantly with chemotherapy versus chemo‐radiation therapy in the Surveillance, Epidemiology and End Results‐Medicare database.

Methods and Results

Patients were age 66+, had stage IIIA/B resectable non‐small‐cell lung cancer diagnosed between 2007 and 2015, and received adjuvant or neoadjuvant chemotherapy or chemo‐radiation within 121 days of diagnosis. Patients having chemo‐radiation and chemotherapy only were propensity‐score matched and followed from day 121 to first cardiac outcome, noncardiac death, radiation initiation by patients who received chemotherapy only, fee‐for‐service enrollment interruption, or December 31, 2016. Cause‐specific hazard ratios (HRs) and competing risks subdistribution HRs were estimated. The primary outcome was the first of these severe cardiac events: acute myocardial infarction, other hospitalized ischemic heart disease, hospitalized heart failure, percutaneous coronary intervention/coronary artery bypass graft, cardiac death, or urgent/inpatient care for pericardial disease, conduction abnormality, valve disorder, or ischemic heart disease. With median follow‐up of 13 months, 70 of 682 patients who received chemo‐radiation (10.26%) and 43 of 682 matched patients who received chemotherapy only (6.30%) developed a severe cardiac event (
P
=0.008) with median time to first event 5.45 months. Chemo‐radiation increased the rate of severe cardiac events (cause‐specific HR: 1.62 [95% CI, 1.11–2.37] and subdistribution HR: 1.41 [95% CI, 0.97–2.04]). Cancer severity appeared greater among patients who received chemo‐radiation (noncardiac death cause‐specific HR, 2.53 [95% CI, 1.93–3.33] and subdistribution HR, 2.52 [95% CI, 1.90–3.33]).

Conclusions
Adding radiation therapy to chemotherapy is associated with an increased risk of severe cardiac events among patients with resectable stage III non‐small‐cell lung cancer for whom survival benefit of radiation therapy is unclear.
Sonic Piety in Early New England
Authors: Russo Francis 
Published: December 2022

Abstract
This article reinterprets New England's 1720s Singing Controversy as a sensory event that altered the nature of puritan sonic piety in early New England. Far from a parochial peculiarity in the history of American music, the 1720s singing reforms were part of broader challenges to a previous way of knowing-an epistemology, or, in this context, an “acoustemology.”
Keeping up with the Catholics: Protestant Evangelism in the Late 17th Century
Authors: Diller Lisa Clark 
Published: December 2022

Abstract
James II’s reign opened up space for Catholic mission activity within England. Priests, both foreign and English-born, set up public worship services that were open for visitors to attend. A wave of pamphlets explaining the Roman Catholic faith rolled over the country, and converts were encouraged to publish their stories of leaving Protestantism. Schools were opened, apparently attended by both Catholics and Protestants. And the important pastoral work of invigorating English Catholics, educating them and encouraging them in piety, began. Devout Protestants immediately recognized the efficacy of these missions and admired how quickly they worked. Beginning in the reign of James, they argued that they should also be doing such missional work. This paper looks at what Catholics prioritized in their work in England under James II, and how English Protestants referenced those examples in their own work after 1688.
Transculturality, Otherness and the Antimonies of Transnational Mobility in Jamal Mahjoub’s Travelling with Djinns
Authors: Ezema Nnaemeka 
Published: December 2022

Abstract
The continuous transnational mobility facilitated by various elements of globalisation, evidently, enhances transcultural consciousness. Despite the increasing interest in transnational mobility among critics, its effect on the different perceptions of new identity formation in Mahjoub’s Travelling with Djinns has not got the deserved critical attention. Using Achille Mbembe’s perspectives in On the Postcolony, the paper attempts to critically engage the transcultural sensibility of the characters and otherness that occur in their relationships and how all these affect their sense of belonging. Estranged from their supposed indigenous cultural affiliation, the characters are also unable to get integrated into the mainstream western culture. In the text, it is clear that while transnational mobility continues to influence new identity formation, the characters are still perceived with stereotypical indexicalities. Mahjoub’s text depicts the contested place of identity by juxtaposing transculturality and otherness, portraying their effects on the person, the family and the postcolonial state.
Pour une redéfinition de la notion de “retour”
Authors: Godin Marie , Nsengiyumva Jean-Luc , Demart Sarah 
Published: December 2022

Résumé
La question du retour des migrants africains installés en Europe est loin d’être neuve avec des travaux qui se focalisent essentiellement sur les aspirations au retour et les processus de sa concrétisation. Aussi pertinent qu’il puisse être, ce focus repose sur une approche limitée, du fait du privilège accordé à la spatialité du phénomène, ce qui trahit une conception normative héritée des politiques d’immigration et de développement. Soumettre notre compréhension du retour à une catégorie qui est indissociable du management des flux migratoires, ne permet pas de penser de manière adéquate le retour comme déplacement spatial, mais aussi politique, culturel, identitaire, devant être resitué dans l’histoire longue de cet espace afro-européen. Ce changement d’échelle temporelle suppose un changement de régime épistémologique que nous souhaitons explorer à partir du point de vue des personnes d’ascendance congolaise et rwandaise nées et, ou socialisées en Belgique.
Energy-efficient manufacturing of multifunctional vascularized composites
Authors: Centellas Polette , Garg Mayank , Chen Zhuoting , Zhang Xiang , Parikh Nil , Geubelle Philippe , Sottos Nancy 
Published: December 2022

The retention and transport of different fluids inside synthetic microvascular fiber-reinforced polymer (FRP) composites enable environmentally adaptive functions, including thermal regulation, self-healing, and electromagnetic modulation. However, manufacturing of vascularized components involves an energy- and time-intensive multistep process to cure the host matrix (several hours at elevated temperature) and then evacuate the embedded sacrificial template (12–24 h at 200°C under vacuum). Here, we demonstrate rapid (minutes), energy-efficient, and scalable fabrication of vascularized FRP composites at room temperature using the exothermic frontal polymerization of a dicyclopentadiene host matrix. The chemical energy released during frontal curing of the host resin facilitates the endothermic depolymerization of an embedded sacrificial thermoplastic to create structures with high-fidelity microchannels, reducing the thermal energy for fabrication by nearly four orders of magnitude compared to previous methods. The presence of fiber reinforcement in this tandem curing and vascularization strategy presents several challenges related to successful frontal curing and microchannel formation. Increasing the volume fraction of fiber reinforcement ( Vf) decreases the volume of the host resin matrix, generating less energy for sustaining the curing and vascularization processes. Heat retention for several minutes after completion of frontal curing using thermally insulating tooling is crucial for obtaining clear microchannels in composite specimens with Vf = 60%. Simulation of the vascularization process confirms the slower depolymerization of the sacrificial templates in high- Vf composites. A nominal decrease in channel circularity also occurs with an increase in the compaction pressure required for high Vf of composite panels. We leverage this rapid manufacturing strategy to fabricate hybrid composites with vascular networks that span the bulk of the composite and a surface coating for potential self-healing applications.
Neurological manifestations of COVID-19: a retrospective observational study based on 1060 patients with a narrative review
Authors: Negro Alberto , Tortora Mario , Gemini Laura , de Falco Arturo , Somma Francesco , d’Agostino Vincenzo 
Published: December 2022

Background In the past two decades, three coronavirus epidemics have been reported. Coronavirus disease 2019 (COVID-19) is caused by a severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). In most patients, the disease is characterized by interstitial pneumonia, but features can affect other organs. Purpose To document the radiological features of the patients and to perform a narrative review of the literature. Material and Methods We conducted a retrospective, single-center study on 1060 consecutive hospitalized patients with COVID-19 at our institution. According to the inclusion criteria, we selected patients to be studied in more radiological detail. All images were obtained as per standard of care protocols. We performed a statistic analysis to describe radiological features. We then presented a systematic review of the main and conventional neuroimaging findings in COVID-19. Results Of 1060 patients hospitalized for COVID-19 disease, 15% (159) met the eligibility criteria. Of these, 16 (10%) did not undergo radiological examinations for various reasons, while 143 (90%) were examined. Of these 143 patients, 48 (33.6%) had positive neuroimaging. We found that the most frequent pathology was acute ischemic stroke (n=16, 33.3%). Much less frequent were Guillain–Barre syndrome (n=9, 18.8%), cerebral venous thrombosis (n=7, 14.6%), encephalitis or myelitis (n=6, 12.5%), intracranial hemorrhage and posterior hemorrhagic encephalopathy syndrome (n=4, 8.3%), exacerbation of multiple sclerosis (n=4, 8.3%), and Miller–Fisher syndrome (n=2, 4.2%). Conclusion Our data are coherent with the published literature. Knowledge of these patterns will make clinicians consider COVID-19 infection when unexplained neurological findings are encountered.
Disruptions in Primary Care among People with Schizophrenia in Ontario, Canada, During the COVID-19 Pandemic
Authors: Stephenson Ellen , Yusuf Abban , Gronsbell Jessica , Tu Karen , Melamed Osnat , Mitiku Tezeta , Selby Peter , O’Neill Braden 
Published: December 2022

Objective To investigate how primary care access, intensity and quality of care changed among patients living with schizophrenia before and after the onset of the COVID-19 pandemic in Ontario, Canada. Methods This cohort study was performed using primary care electronic medical record data from the University of Toronto Practice-Based Research Network (UTOPIAN), a network of > 500 family physicians in Ontario, Canada. Data were collected during primary care visits from 2643 patients living with schizophrenia. Rates of primary care health service use (in-person and virtual visits with family physicians) and key preventive health indices indicated in antipsychotic monitoring (blood pressure readings, hemoglobin A1c, cholesterol and complete blood cell count [CBC] tests) were measured and compared in the 12 months before and after onset of the COVID-19 pandemic. Results Access to in-person care dropped with the onset of the COVID-19 pandemic. During the first year of the pandemic only 39.5% of patients with schizophrenia had at least one in-person visit compared to 81.0% the year prior. There was a corresponding increase in virtual visits such that 78.0% of patients had a primary care appointment virtually during the pandemic period. Patients prescribed injectable antipsychotics were more likely to continue having more frequent in-person appointments during the pandemic than patients prescribed only oral or no antipsychotic medications. The proportion of patients who did not have recommended tests increased from 41.0% to 72.4% for blood pressure readings, from 48.9% to 60.2% for hemoglobin A1c, from 57.0% to 67.8% for LDL cholesterol and 45.0% to 56.0% for CBC tests during the pandemic. Conclusions There were substantial decreases in preventive care after the onset of the pandemic, although primary care access was largely maintained through virtual care. Addressing these deficiencies will be essential to promoting health equity and reducing the risk of poor health outcomes.
On the acoustic emission characteristics of airfoils with different trailing edge configurations
Authors: Jha Shailesh Kumar , Narayanan S. 
Published: December 2022

The present study experimentally and numerically investigates the flow past flat plates and NACA0012 airfoils with the different trailing edge (i.e., blunt, sharp, and rounded) and both end-rounded configurations on the far-field acoustic emissions and complex flow phenomena to determine the best edge geometry for low noise. The studies are conducted for various jet speeds of 20, 30, and 40 m/s (chordwise Reynolds numbers of 1.812 × 105, 2.72 ×105, and 3.62 ×105). It is observed that all the edge-modified flat plates show the highest directivity at an emission angle of 60° for all jet velocities studied. The comparison of power directivities between realistic and flat plate airfoils reveals that the realistic airfoils radiate lower acoustic emissions as compared to flat plate airfoils, albeit they show a common feature of downstream directivity. In general, the far-field acoustic emissions of both end-rounded plates are observed to be lower as compared to blunt, sharp, and rounded trailing edge geometries. The leading edge modification is also observed to reduce airfoil self-noise. The likely reason for the lower far-field acoustic emissions provided by both end-rounded trailing edged foils is due to the modification in the boundary layer characteristics owing to the presence of smooth flow around the rounded leading edge as well as reduced vortex strength as compared to the other foil geometries. Thus, the present study demonstrates that passive modifications of leading edge profiles are essential along with trailing edge for achieving lower acoustic emissions and higher noise reductions.