bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I study of safety and immunogenicity of survivin long peptide vaccine (SurVaxM) in patients (pts) with metastatic neuroendocrine tumors (NETs).
Authors: Gupta Medhavi , Fenstermaker Robert Alan , Qiu Jing-Xin , Iyer Renuka V. 
Published: January 2021

TPS375 Background: Metastatic neuroendocrine tumors (NETs) have a poor prognosis and there are limited options after first-line treatment with somatostatin analogues (SSA)/chemotherapy. Therefore, new therapies are urgently needed. Survivin is an intracellular protein that alters cell division, function of cell death proteases and inhibits apoptosis. It is undetectable in adult cells and expressed in many tumors, making it an ideal target. SurVaxM is a 15 amino acid synthetic peptide vaccine. It stimulates antigen presentation via intracellular cell-surface target recognition and induces CD8+ & CD4+ T cells and IgG production. It was well tolerated in a phase I trial in recurrent glioma pts (Fenstermaker et al., Neurooncol; 2014). Prelim analysis from a phase II study in glioma patients (pts) showed its efficacy (Ahluwalia et al., Neurooncol; 2018). Targeting survivin in NETs is based on our work with tissue microarrays from gastroenteropancreatic (GEP) and lung NETs that showed that its expression correlated with a worse overall survival (Hanif et al., Oncotarget; 2020). We have an ongoing single-arm phase I trial evaluating the safety and immunogenicity of SurVaxM in metastatic NETs. Methods: Ten eligible pts with any grade metastatic GEP/lung origin NETs that are survivin positive by immunohistochemistry and have progression on SSA within the last 6 months on two CT scans >4 weeks apart per RECIST v1.1 are being enrolled. Pts receive a fixed dose of 500 mcg of SurVaxM in Montanide ISA 51 subcutaneously along with 100 mcg of GM-CSF q2 weeks X 4 doses. SSA is continued at the same dose as before. Pts free of progression and toxicity at 6 months get extra doses of SurVaxM q12 weeks, up to 1 year. Subjects are assessed continuously for safety per NCI CTCAEv5.0. Response assessment via CT scans per RECIST v1.1 q12 weeks. Primary objective is to assess safety of SurVaxM +/- SSA. Secondary objectives are to assess overall response rate, progression free survival, duration of response and vaccine immunological response (anti-survivin antibody titers and survivin-specific CD8 T-cell responses). Safety analysis is per Pocock stopping boundary with the assumption of true toxicity of 0.2 and unacceptable toxicity of 0.3 at a significance level of 0.05.To this date, eight patients were screened out of which five patients were enrolled. One patient did not meet the eligibility criterion due to negative survivin staining and the other two did not meet the RECIST v1.1 progression criterion. Of the five pts enrolled, two were of lung origin, two of GEP, and the remainder one of thymic origin. Three pts had high grade neuroendocrine carcinoma, one patient had atypical bronchial tumor and one with low-grade NET. Currently, two pts remain on the study. The enrollment is ongoing. The trial is funded by The Neuroendocrine Tumor Research Foundation.
A phase I dose escalation study of eryaspase in combination with modified FOLFIRINOX in locally advanced and metastatic pancreatic ductal adenocarcinoma.
Authors: Noel Marcus Smith , Philip Philip Agop , Tejani Mohamedtaki Abdulaziz , Marshall John , He Aiwu Ruth , Weinberg Benjamin Adam , Weiner Louis M. , Biswas-Baldwin Nigel , Hoke Frank , Youssoufian Hagop , El-Hariry Iman 
Published: January 2021

TPS453 Background: FOLFIRINOX remains the standard of care for the first line treatment of patients with locally advanced and metastatic pancreatic adenocarcinoma, however the prognosis remains poor, thus novel treatment options are indicated. Eryaspase, asparaginase (ASNase) encapsulated in red blood cells (RBCs) is an investigational product under development. Following infusion, asparagine and glutamine are actively transported into RBCs where they are hydrolyzed by the encapsulated ASNase. A randomized phase IIb study in patients with advanced pancreatic cancer whose disease progressed following first-line treatment (NCT02195180) was previously conducted. Eryaspase in combination with gemcitabine monotherapy or FOLFOX combination therapy improved overall survival (OS) and progression free survival (PFS). The safety profile of eryaspase was acceptable. A second line pivotal randomized phase III trial (Trybeca-1) is currently enrolling (NCT03665441). We design this phase I study to determine the safety of mFOLFIRINOX combined with Eryaspase in the first line of treatment. Methods: Patients with locally or metastatic biopsy proven pancreatic adenocarcinoma will be treated with the combination of mFOLFIRINOX plus Eryaspase. This will be a standard 3+3 design with 4 possible doing levels. mFOLFIRINOX dosing will include 5-Fluorouracil 2400 mg/m2 over 46 hours, Oxaliplatin 85 mg/m2, Irinotecan 150 mg/m2 plus Eryaspase 75 Units/kg at dose level 0. Eryaspase will be dose escalated up to 100 Units/kg. The study will enroll at three academic centers. Key eligibility criteria include performance status 0 or 1; locally advanced or metastatic tumor disease; adequate organ function. The primary objective is to determine the maximum tolerated dose and safety of this novel combination. Key secondary objectives include objective response rate, progression-free survival, overall survival, pharmacokinetics, pharmacodynamics, and biomarker research. A data safety monitoring committee will review data every 3 months. Clinical trial information: 04292743.
A translational study to evaluate genomic markers and concordance with circulating-tumor DNA and circulating tumor cells to predict clinical outcomes in gastrointestinal and pancreatobiliary cancers: Valor trial.
Authors: Doi Ayako , Umemoto Kumiko , Oguri Tomoyo , Takeda Hiroyuki , Horie Yoshiki , Ogura Takashi , Mizukami Takuro , Izawa Naoki , Jung Sungmok , Kim Byung Chul , Sunakawa Yu 
Published: January 2021

TPS481 Background: Circulating tumor cells (CTCs) are cells that have shed into the vasculature or lymphatics from a primary tumor and are carried around the body in the blood circulation. The CTCs constitute seeds for the subsequent growth of additional tumors (metastases) in distant organs, a mechanism that is responsible for the vast majority of cancer-related deaths. Circulating-tumor DNA (ctDNA) includes DNA which derives from tumor necrosis or apoptosis; therefore, CTCs may potentially represent more precise tumor status compared to ctDNA. There have been few reports to assess the genomic concordance between ctDNA and CTCs in cancer patients. In addition, genomic analysis of ctDNA would find novel mechanism of resistance to anti-EGFR monoclonal antibody (mAb) in metastatic colorectal cancer (mCRC). RAS mutations in ctDNA are considered to be one of mechanism of resistance to anti-EGFR mAb in RAS wild-type mCRC. However, there is no data regarding CTCs when mCRC patients acquires resistance to anti-EGFR mAb. Methods: This translational study prospectively recruits patients with advanced/metastatic gastrointestinal and pancreatobiliary cancers (esophageal, gastric, pancreatic, biliary tract and colorectal cancers) who receive systemic chemotherapy in first- or second-line and mCRC with RAS wild-type tumors treated with anti-EGFR mAb in any lines, at St. Marianna University School of Medicine Hospital. We accumulate the clinical data regarding patients’ characteristics, treatment, and survival time. The primary objective is to evaluate genomic markers and concordance with ctDNA and CTCs in patients with advanced/metastatic gastrointestinal and pancreatobiliary cancers. Then, this study approaches to assess which biomarkers can predict clinical outcome more accurately. Secondary objectives include evaluating association between genomic status in ctDNA and clinical outcomes; association between genomic status in CTCs and clinical outcomes; comparing genomic change between ctDNA and CTCs in RAS wild-type mCRC patients treated with anti-EGFR mAb. Blood draw of total 10mL is performed for analyses of ctDNA and CTCs at 3 time points, pre-treatment of chemotherapy, 4 weeks after treatment start, and disease progression. Blood of 5mL is processed with CTCs enrichment using the CD-PRIME system (Clinomics Inc.) and remaining 5mL is used for the plasma preparation. Genomic alterations are measured using the customized cancer panel which allows the detection of mutations in 51 actionable genes. This study will enroll 70 patients with willing to undergo blood draws. Accrual is starting in May 2019. Clinical trial information: UMIN000036681.
Local translation in perisynaptic and perivascular astrocytic processes – a means to ensure astrocyte molecular and functional polarity?
Authors: Mazaré Noémie , Oudart Marc , Cohen-Salmon Martine 
Published: January 2021

ABSTRACT
Together with the compartmentalization of mRNAs in distal regions of the cytoplasm, local translation constitutes a prominent and evolutionarily conserved mechanism mediating cellular polarization and the regulation of protein delivery in space and time. The translational regulation of gene expression enables a rapid response to stimuli or to a change in the environment, since the use of pre-existing mRNAs can bypass time-consuming nuclear control mechanisms. In the brain, the translation of distally localized mRNAs has been mainly studied in neurons, whose cytoplasmic protrusions may be more than 1000 times longer than the diameter of the cell body. Importantly, alterations in local translation in neurons have been implicated in several neurological diseases. Astrocytes, the most abundant glial cells in the brain, are voluminous, highly ramified cells that project long processes to neurons and brain vessels, and dynamically regulate distal synaptic and vascular functions. Recent research has demonstrated the presence of local translation at these astrocytic interfaces that might regulate the functional compartmentalization of astrocytes. In this Review, we summarize our current knowledge about the localization and local translation of mRNAs in the distal perisynaptic and perivascular processes of astrocytes, and discuss their possible contribution to the molecular and functional polarity of astrocytes.
A Theoretical Procedure Based on Classical Electrostatics and Density Functional Theory for Screening Non-Square-Shaped Mixed-Valence Complexes for Logic Gates in Molecular Quantum-Dot Cellular Automata
Authors: Tokunaga Ken , Odate Fumiya , Asami Daiya , Tahara Keishiro , Sato Mitsunobu 
Published: January 2021

Abstract
Understanding the requisite geometry of molecules and peripheral components is an essential step in endowing molecules with logical functions in quantum-dot cellular automata. To respond to the real problem of structural distortion from the ideal square cell configuration, a practical procedure is presented that simplifies the molecular shapes for device design with features that combine aspects of classical electrostatics and density functional theory calculations. By applying this method to a library of biferrocenium dimers with a three-input junction, it was demonstrated in theory that a covalently bonded parallelogram dimer responds precisely to six different patterns of nanoscale electric fields and works correctly as a device cell in both AND and OR logic gates. The counterintuitive usefulness of the non-square-shape is rationalized by four ferrocene-based orbital orientations and a functional group arrangement, equalizing the disadvantageous energy asymmetry between the states 0 and 1. The present procedure was applied to quasi-square tetrametallic Ru complexes and it was found that these complexes do not work as logic gates. This procedure expands the range of existing candidate molecules from squares to parallelograms and facilitates screening for implementation.
New Idea for Narrowing an Energy Gap by Selective Perturbation of One Frontier Molecular Orbital
Authors: Tanaka Kazuo , Chujo Yoshiki 
Published: January 2021

Abstract
In this manuscript, we will illustrate a new idea for narrowing energy gaps between frontier molecular orbitals (FMOs) by selectively perturbing the levels of highest occupied molecular orbitals (HOMOs) and/or lowest unoccupied molecular orbitals (LUMOs). Initially, the basic concept of the isolated FMOs is explained by employing pentaazaphenalene (5AP) derivatives. It was found that electronic structures of the isolated LUMO of 5AP can be preserved even when incorporated into polymer chains if the connecting points are separated from the isolated LUMO. The mechanism and their unique electronic properties are summarized. Next, conversely, isolated HOMO and LUMO can be perturbed by conjugation effects independently. On the basis of this fact, near infrared (NIR)-absorbing molecules can be obtained by selectively elevating HOMO and lowering LUMO energy levels. We also mention strategies for enhancing luminescent properties of 5AP derivatives. Finally, we demonstrate that the isolated LUMO can be found in commodity luminescent dyes, such as boron dipyrromethene (BODIPY). By selectively lowering the LUMO energy level through the aza-substitution at the skeletal carbon where the isolated LUMO is distributed, NIR-emissive polymers can be obtained. Versatility of the isolated FMOs for obtaining optoelectronic organic materials is explained in this review.
Uma Análise Crítica Sobre Amor e Cuidado em Binswanger e Heidegger
Authors: Feijoo Ana Maria Lopez Calvo de , Accetta Marcello Furst de Freitas , Protasio Myriam Moreira , Costa Paulo Victor Rodrigues da , Silva Victor Portavales 
Published: January 2021

O presente artigo tem como objetivo refletir, por meio de um estudo teórico, acerca do existencial cuidado (Sorge) no pensamento de Martin Heidegger e amor (Liebe) em Ludwig Binswanger. O texto retoma os principais aspectos da forma como ambos compreendem a noção de cuidado e amor, desdobrando criticamente o impasse gerado a partir daí. Demonstra-se que o cerne da querela se dá no modo como Binswanger compreende e interpreta o ser-no-mundo (In-der-Welt-sein) heideggeriano, ligando-o à noção de ser-para-além-do-mundo (Über-die-Welt-hinaus-sein). O psiquiatra suíço procede desse modo na medida em que julga ter identificado um limite e uma carência do elemento eternidade no modo como Heidegger desenvolve sua ontologia fundamental. Com tal apontamento, Binswanger elege a tonalidade do amor como fundamento de toda relação, que faz dessa experiência de infinito sua forma de ser. No bojo de tal apontamento se encontra o desenvolvimento da Daseinsanálise como o desdobramento – a princípio psiquiátrico – de uma relação clínica pautada pelo amor como meio do acesso fundamental ao outro e como elemento que promove a cura. O artigo conclui que tal indicação binswangeriana recai sutilmente em elementos instrumentais e produtivistas, uma vez que Binswanger reproduz elementos da técnica justamente lá onde tais elementos deveriam permanecer inoperantes.
Partial Glossectomy as an adjunct to Orthodontic Treatment of Anterior Open Bite Associated with Macroglossia: A Case Report
Authors: Mittal Tarun K , Achal Kulraj , Taylor James T , Kindelan Jay D 
Published: January 2021

Orthodontic treatment of an anterior open bite is one of the most challenging malocclusions to treat, especially with respect to post-treatment stability. Complete diagnosis and targeted treatment is required for successful post treatment stability. In instances where macroglossia is the primary aetiology, partial glossectomy will greatly improve post treatment stability. The following case report describes a patient with severe anterior open bite and bimaxillary protrusion secondary to macroglossia. Treatment was successfully performed with partial glossectomy and straight wire orthodontics. Post-treatment relapse was minimal. CPD/Clinical Relevance: This article describes a review of the aetiology of anterior open bite and documents one possible treatment option, when the main aetiology of the malocclusion is of soft tissue origin
Traumatic Iatrogenic Complications Associated with Orthodontic Treatments: A Systematic Review
Authors: Manouchehri Shaadi , Haddad Ali Rezaei , Shakib Kaveh 
Published: January 2021

Adverse outcomes of orthodontic treatment have been reported in the literature, yet there are currently no systematic reviews on the subject. We undertook a comprehensive review of the literature using the Medline and Ovid electronic databases, complemented by manual searching. The occurrence of unforeseen iatrogenic traumatic complications due to orthodontic treatment was used as the primary outcome. Traumatic iatrogenic complications associated with orthodontic treatment are infrequent. The most common complication reported is ingestion of orthodontic components. In the majority of the cases, management of the offending agent resulted in complete recovery without further complaint. The exception to this is ocular injury sustained as a result of improper use of or accidental injuries related to orthodontic headgear. These injuries are potentially devastating for the patient.CPD/Clinical Relevance: Orthodontic treatment is carried out routinely and it is important to be aware of the unexpected complications that can occur during treatment and their consequences.
Endogenous Tongue Thrust – Myth?
Authors: Lam Yung , Shelton Andrew , Sandler Jonathan 
Published: January 2021

Anterior open bite cases are very challenging to manage due to the high relapse potential associated with this feature of malocclusion. It is helpful if the aetiology is established before embarking on treatment to ensure that the appropriate treatment modalities are carried out. Determining whether the aetiology of an anterior open bite is caused by an ‘endogenous tongue thrust’ is extremely difficult. In particular, differentiating between an adaptive and endogenous tongue thrust can be extremely challenging. The case study presented explores the clinical considerations when diagnosing and treating anterior open bites.CPD/Clinical Relevance: This report raises the question: is it possible to diagnose an endogenous tongue thrust?
Cementless knee arthroplasty: a review of recent performance
Authors: Asokan Ajay , Plastow Ricci , Kayani Babar , Radhakrishnan Ganan T. , Magan Ahmed A. , Haddad Fares S. 
Published: January 2021

Cementless knee arthroplasty has seen a recent resurgence in popularity due to conceptual advantages, including improved osseointegration providing biological fixation, increased surgical efficiency, and reduced systemic complications associated with cement impaction and wear from cement debris. Increasingly younger and higher demand patients are requiring knee arthroplasty, and as such, there is optimism cementless fixation may improve implant survivorship and functional outcomes. Compared to cemented implants, the National Joint Registry (NJR) currently reports higher revision rates in cementless total knee arthroplasty (TKA), but lower in unicompartmental knee arthroplasty (UKA). However, recent studies are beginning to show excellent outcomes with cementless implants, particularly with UKA which has shown superior performance to cemented varieties. Cementless TKA has yet to show long-term benefit, and currently performs equivalently to cemented in short- to medium-term cohort studies. However, with novel concepts including 3D-printed coatings, robotic-assisted surgery, radiostereometric analysis, and kinematic or functional knee alignment principles, it is hoped they may help improve the outcomes of cementless TKA in the long-term. In addition, though cementless implant costs remain higher due to novel implant coatings, it is speculated cost-effectiveness can be achieved through greater surgical efficiency and potential reduction in revision costs. There is paucity of level one data on long-term outcomes between fixation methods and the cost-effectiveness of modern cementless knee arthroplasty. This review explores recent literature on cementless knee arthroplasty, with regards to clinical outcomes, implant survivorship, complications, and cost-effectiveness; providing a concise update to assist clinicians on implant choice. Cite this article: Bone Jt Open 2021;2(1):48–57.
Burden of disease and productivity impact of Streptococcus suis infection in Thailand
Authors: Rayanakorn Ajaree , Ademi Zanfina , Liew Danny , Lee Learn-Han 
Published: January 2021

BackgroundStreptoccocus suis (S.suis)infection is a neglected zoonosis disease in humans mainly affects men of working age. We estimated the health and economic burden ofS.suisinfection in Thailand in terms of years of life lost, quality-adjusted life years (QALYs) lost, and productivity-adjusted life years (PALYs) lost which is a novel measure that adjusts years of life lived for productivity loss attributable to disease.MethodsA decision-analytic Markov model was developed to simulate the impact ofS.suisinfection and its major complications: death, meningitis and infective endocarditis among Thai people in 2019 with starting age of 51 years. Transition probabilities, and inputs pertaining to costs, utilities and productivity impairment associated with long-term complications were derived from published sources. A lifetime time horizon with follow-up until death or age 100 years was adopted. The simulation was repeated assuming that the cohort had not been infected withS.suis. The differences between the two set of model outputs in years of life, QALYs, and PALYs lived reflected the impactof S.suisinfection. An annual discount rate of 3% was applied to both costs and outcomes. One-way sensitivity analyses and Monte Carlo simulation modeling technique using 10,000 iterations were performed to assess the impact of uncertainty in the model.Key resultsThis cohort incurred 769 (95% uncertainty interval [UI]: 695 to 841) years of life lost (14% of predicted years of life lived if infection had not occurred), 826 (95% UI: 588 to 1,098) QALYs lost (21%) and 793 (95%UI: 717 to 867) PALYs (15%) lost. These equated to an average of 2.46 years of life, 2.64 QALYs and 2.54 PALYs lost per person. The loss in PALYs was associated with a loss of 346 (95% UI: 240 to 461) million Thai baht (US$11.3 million) in GDP, which equated to 1.1 million Thai baht (US$ 36,033) lost per person.ConclusionsS.suisinfection imposes a significant economic burden both in terms of health and productivity. Further research to investigate the effectiveness of public health awareness programs and disease control interventions should be mandated to provide a clearer picture for decision making in public health strategies and resource allocations.