bluuebunny/crossref_metadata_2025_split huggingface dataset:
FLGS-03. Fluorescein sodium-guided biopsy or resection in patients with contrast enhancing brainstem lesion in MRI
Authors: Lin Fuhua , Chen Zhenghe , Zhang Xiangheng , Mou Yonggao 
Published: November 2021

Abstract

BACKGROUND
It is challenging to resect or just biopsy the lesions in the brainstem, due to the essential function of the surfaces and limited space. Neuro-navigation is not always reliable and stereotatic biopsy is infrequently inconclusive due to small or inadequate samples. We want to share our experiences in the application of fluorescein sodium in surgery on patients with brainstem lesion which is contrast enhancing in MRI.

METHODS
Between January 2017 and June 2021, 5 patients with brainstem lesion underwent fluorescein sodium-guided surgery in neurosurgery department of Sun Yat-sen University Cancer Center. After injection of low dose of sodium fluorescein (3 mg/kg), the lesions with strong fluorescence staining were identified as the target area for biopsy or resection.

RESULTS
5 consecutive patients (aged 6–47 years) with brainstem lesions prospectively underwent fluorescein sodium-guided surgery. The lesions were located in pontine in 3 patients and in the medulla in 2 patients. Gross total resection was achieved in 2 patients, and partial resection in the other 3 patients. In all patients, a pathological diagnosis was obtained (4 gliomas and 1 metastasis from non-small cell lung carcinoma) without severe complications, including mild facial or abduct nerve palsy in 3 patients. And all the specimens with strong fluorescence staining sent for pathology were proved to be tumorous.

CONCLUSION
Fluorescein sodium-guided technique was helpful to locate the lesion in brainstem which was contrast-enhanced in MRI. It was effective and safe to figure out an ideal trajectory to avoid damage of the crucial structures and improve the diagnostic rate.
IOTG-02. Glioma Supra Marginal Incision Trial (G-SUMIT): a phase II pilot randomized control trial to assess the feasibility of “supra-marginal” surgical resection of malignant glioma
Authors: Lai Carolyn , Mansouri Alireza , Scales Damon , Perry James , Sahgal Arjun , Pirouzmand Farhad 
Published: November 2021

Abstract
High grade gliomas are the most common primary malignant brain tumor in adults having a median survival of only 13–16 months. This is despite the current standard of maximal safe surgical resection followed by fractionated radiotherapy and chemotherapy. Extending the tumor resection limit beyond the GAD-enhancing margin (i.e. supra-marginal resection) could in principle provide an added survival benefit as it has been shown that &gt;80% of post-operative tumor recurrence is within a 2cm region surrounding the original GAD-enhancing margin. However, this must be weighed against the risk of potential damage to functional brain tissue. In this phase II pilot randomized control trial (RCT), we aim to assess the feasibility of “supra-marginal” resection extending 1cm beyond the enhancing tumor in adults with radiographic evidence of GAD-enhancing intra-axial tumour consistent with high grade glioma in a safe anatomical location and a Karnofsky Performance Score &gt; 60. With six academic centres participating, we aim to enroll 72 patients over two years. Currently, four patients have already been enrolled in the first four months. Primary outcomes include evaluating the feasibility of performing a large-scale trial with regards to recruitment, allocation and outcome documentation as well as safety data. Secondary outcomes include determining if there is an increased survival benefit with supra-marginal resection and impact on quality of life. Our pilot RCT will test the feasibility of comparing standard gross total resection of GAD-enhancing tumour and supra-marginal resection to prepare for a larger definitive multicentre RCT.
Long-term contracts and the Unidroit PICC: towards a realistic regulation
Authors: Zuñiga Peralta Raul F 
Published: November 2021

Abstract
The 2016 Unidroit Principles of International Commercial Contracts (PICC) were the first instrument that explicitly regulated long-term contracts in international commerce. Its main goal was to actualize uniform contract law for the emerging needs of international commerce. Despite this effort, scholars have briefly researched how uniform contract law instruments address international commerce as an economic reality or whether the PICC’s attempt is adequate. The gap in uniform contract law’s—particularly the PICC’s—literature on long-term contracts is odd compared to the completeness of economic literature on the matter. After revealing the pitfalls of the PICC’s regulation, demonstrating the convenience of a thorough review of the economics of long-term contracts, this article elaborates on the necessary character of the connection between uniform contract law and economics. It further reviews the economic research on the factors that prompt long-term contracting and the mechanisms that economic agents designed to address their needs. The overhaul reveals that two paradigmatic economic structures—competitive and cooperative—generally determine the design of long-term contracts. Finally, the article addresses the consequences of including the paradigmatic economic structures of long-term contracts in the PICC rules on contract interpretation and gap-filling.
Factors Associated With Increased Opioid Use During the COVID-19 Pandemic: A Prospective Study of Patients Enrolled in Opioid Agonist Treatment
Authors: Rosic Tea , Naji Leen , Sanger Nitika , Marsh David C. , Worster Andrew , Thabane Lehana , Samaan Zainab 
Published: November 2021

Objectives
The opioid use disorder (OUD) crisis in North America has become “an epidemic within a pandemic” in the context of the COVID-19 virus. We aimed to explore the association between the COVID-19 pandemic and changes in opioid use patterns among patients receiving treatment for OUD.

Methods
We used prospectively collected data from 456 patients attending 31 opioid agonist clinics across Ontario, Canada. All included participants underwent routine urine drug screens (UDSs) both before and after the onset of the COVID-19 pandemic. A paired sample t-test was used to compare the proportion of opioid-positive UDSs collected pre- and post-pandemic, and linear regression analysis was used to explore factors associated with this change.

Results
Participants had a mean age of 39.9 years (standard deviation = 10.9), 52%were male, and 81%were receivingmethadone treatment. The percentage of opioid-positive UDSs increased significantly during the pandemic, on average by 10.6% (95% confidence interval [CI] 8.17, 12.95, P < 0.001). Continued opioid use before the pandemic was associated with 9.43% increase, on average, in the percentage of opioid-positive UDSs during the pandemic (95% CI 3.79, 15.07). Self-reported past-month cocaine (adjusted betacoefficient 6.83, 95% CI 0.92, 12.73) and amphetamine (adjusted beta-coefficient 13.13, 95% CI 5.15, 21.1) use at study entry were also associated with increases in opioid-positive UDSs.

Conclusions
Increased opioid use is one measure of the negative impact the COVID-19 pandemic has had on individuals with OUD, an already marginalized population. Understanding factors associated with worse outcomes is essential to ensuring that treatment programs appropriately adapt to better serve this population during the pandemic.
Cost-effectiveness of colorectal cancer screening in Slovakia
Authors: Babela Robert , Orsagh Andrej , Ricova Jana , Lansdorp-Vogelaar Iris , Csanadi Marcell , De Koning Harry , Reckova Maria 
Published: November 2021

Background
Colorectal cancer (CRC) is an ideal disease for screening due to known and detectable precursor lesions and slow progression from benign adenoma to invasive cancer. The introduction of organized population-based screening programs reduces the burden of colorectal cancer and increases the quality of the screening process with a more favorable harm to benefit ratio compared to opportunistic screening.

Methods
The study used the microsimulation screening analysis-colon simulation model for the estimation of the effect of various factors on cancer incidence and mortality. The model simulated the Slovakian population from 2018 to 2050. Study includes the analysis of two screening strategies the fecal immunochemical test (FIT) every 2 years and annual FIT. Cost-effectiveness parameters were evaluated comparing each simulated screening scenario with no screening.

Results
Compared to no screening, the biennial FIT would detect 29 600 CRC cases and annual FIT 37 800 CRC cases. Mortality due to CRC showed benefits for both strategies with 17,38% reduction in biennial FIT and 24,67% reduction in annual FIT approach. Both screening programs were more costly as well as more effective compared to no screening. The ICER for biennial FIT strategy was 1776 EUR per 1 QALY and for the annual FIT 3991 EUR per 1 QALY.

Conclusions
In summary, this is the first cost-effectiveness analysis focusing on multiple national CRC screening strategies in Slovakia. Both strategies demonstrated cost-effectiveness compared to no screening. However, for optimal population-based programmatic screening strategy, the policymakers should also consider human resources availability, acceptability of screening test among the population or additional resources including the screening funding.
Revisiting the Performance of Firms Recognized for Creating a Healthy Culture
Authors: Payne Brian C. , Bredthauer Jeff S. 
Published: November 2021

Objective:
To augment several prior JOEM studies, which associated firms with recognized health and safety programs with outsized firm stock performance.

Methods:
Stock performance of CHAA and C. Everett Koop National Health Award winners are analyzed using standard asset-pricing, risk-adjusted modeling to compare them against benchmark stock portfolios.

Results:
While wellness programs are laudable, the firms did not universally outperform a market benchmark over extended periods when controlling for well-established measures of portfolio risk.

Conclusions:
Investors could have also expected to underperform the market based on the excess risk involved with these selected companies. Investors must recognize that adding these award-winning companies to their portfolios also increases the overall riskiness and volatility of their portfolios. The previously documented outsized returns could be the reward for bearing this additional risk.
JEL categories: G11, G51, J26, J32.
How Much Delay Matters? How Time to Treatment Impacts Overall Survival in Early Stage Lung Cancer
Authors: Tang Andrew , Ahmad Usman , Raja Siva , Bribriesco Alejandro C. , Sudarshan Monisha , Rappaport Jesse , Khorana Alok , Blackstone Eugene H. , Murthy Sudish C. , Raymond Daniel P. 
Published: November 2021

Objectives:
The aim of this study was to identify drivers of time from diagnosis to treatment (TTT) of surgically resected early stage non-small cell lung cancer (NSCLC) and determine the effect of TTT on post-resection survival.

Summary Background Data:
Large database studies that lack relevant comorbidity data have identified longer TTT asa driver of worse overall survival.

Methods:
From January 1, 2014 to April 1, 2018, 599 patients underwent lung resection for clinical stage I and II NSCLC. Random forest classification, regression, and survival were used to estimate likelihood of TTT = 0 (tissue diagnosis obtained at surgery), >0 (diagnosis obtained pre-resection), and effect of TTT on all-cause mortality.

Results:
Patients with TTT > 0 (n = 413) had median TTT of 42 days (25–75th percentile: 27-59 days). Patients with TTT = 0 (n = 186) had smaller tumors and higher percent predicted forced expiratory volume in 1 second (FEV1%). Patients with history of stroke, oncology consultation, invasive mediastinal staging, low and high extremes of FEV1% had longer TTT. Higher clinical stage, lack of preoperative stress test, anemia, older age, lower FEV1% and diffusion lung capacity, larger tumor size, and longer TTT were the most important predictors of all-cause mortality. One- and 5-year overall survival decreased when TTT was >50 days.

Conclusions:
Preoperative physiologic workup and multidisciplinary evaluation were the predominant drivers of longer TTT. Patients with TTT = 0have more favorable presentation and should be considered in TTT analyses for early stage lung cancer populations. The time needed to clinically stage and optimize patients for resection is not deleterious to overall survival until resection is performed after 50 days from diagnosis.
Nanoviricide’s platform technology based NV-CoV-2 polymer increases the half-life of Remdesivir in vivo
Authors: Chakraborty Ashok , Diwan Anil , Arora Vinod , Thakur Yogesh , Chiniga Vijetha , Tatake Jay , Holkar Preetam , Holkar Neelam , Pond Bethany 
Published: November 2021

AbstractSo far, there are seven coronaviruses identified that infect humans and only 4 of them belong to the beta family of coronavirus (HCoV-HKU1, SARS-CoV-2, MERS-CoV and SARS-CoV). SARS family are known to cause severe respiratory disease in humans. In fact, SARS-CoV-2 infection caused a pandemic COVID-19 disease with high morbidity and mortality. Remdesivir (RDV) is the only antiviral drug so far approved for COVID-19 therapy by the FDA. However, the efficacy of RDV in vivo is limited due to its low stability in presence of plasma. This is the report of analysis of the non-clinical pharmacology study of NV-CoV-2 (Polymer) and NV-CoV-2-R (Polymer encapsulated Remdesivir) in both infected and uninfected rats with SARS-CoV-2.Detection and quantification of NV-CoV-2-R in plasma samples was done by MS-HPLC chromatography analyses of precipitated plasma samples from rat subjects.NV-CoV-2-R show RDV peak in MS-HPLC chromatography, whereas only NV-CoV-2 does not show any RDV-Peak, as expected.NV-CoV-2 polymer encapsulation protects RDV in vivo from plasma-mediated catabolism.Body weight measurements of the normal (uninfected) rats after administration of the test materials (NV-CoV-2, and NV-CoV-2-R) show no toxic effects on them.Our platform technology based NV-387-encapsulated-RDV (NV-CoV-2-R) drug has a dual effect on coronaviruses. First, NV-CoV-2 itself as an antiviral regimen. Secondly, RDV is protected from plasma-mediated degradation in transit, rendering altogether the safest and an efficient regimen against COVID-19.
Human Cytomegalovirus modifies placental small extracellular vesicle secretion and composition towards a proviral phenotype to enhance infection of fetal recipient cells
Authors: Bergamelli Mathilde , Martin Hélène , Aubert Yann , Mansuy Jean-Michel , Marcellin Marlène , Burlet-Schiltz Odile , Hurbain Ilse , Raposo Graça , Izopet Jacques , Fournier Thierry , Benchoua Alexandra , Bénard Mélinda , Groussolles Marion , Cartron Géraldine , le Gac Yann Tanguy , Moinard Nathalie , D’Angelo Gisela , Malnou Cécile E. 
Published: November 2021

AbstractAlthough placental small extracellular vesicles (sEVs) are extensively studied in the context of pregnancy, little is known about their role during human cytomegalovirus (hCMV) congenital infection, especially at the beginning of pregnancy. In this study, we examined the consequences of hCMV infection on sEVs production, composition and function using an immortalized human cytotrophoblast cell line derived from first trimester placenta. By combining complementary approaches of biochemistry, electron microscopy and quantitative proteomic analysis, we showed that hCMV infection increases the yield of sEVs produced by cytotrophoblasts and modifies their protein content towards a proviral phenotype. We further demonstrate that sEVs secreted by hCMV-infected cytotrophoblasts potentiate infection in naive recipient cells of fetal origin, including human neural stem cells. Importantly, these functional consequences are also observed with sEVs prepared from either anex vivomodel of infected histocultures from early placenta or from the amniotic fluid of patients naturally infected by hCMV at the beginning of pregnancy. Based on these findings, we propose that placental sEVs could be key actors favoring viral dissemination to the fetal brain during hCMV congenital infection.Significance StatementHuman cytomegalovirus (hCMV) infection is a major issue during pregnancy, affecting 1% of births in western countries. Despite extensive research, the pathophysiology of this congenital infection remains unclear. Recently, increasing evidence point to the key role of placental small extracellular vesicles (sEVs) in materno-fetal communication during pregnancy. Here, we examined the impact of hCMV infection on the protein composition and function of placental sEVs. We observe that hCMV infection leads to major changes in placental sEV protein content. Functional studies show the ability of sEVs produced by placental infected cells to facilitate further infection of naive recipient fetal cells, notably human neural stem cells. Our study demonstrates that placental sEVs are key players of hCMV pathophysiology during congenital infection.
TWIST1 methylation by SETD6 selectively antagonizes LINC-PINT expression in Glioblastoma multiforme
Authors: Admoni-Elisha Lee , Feldman Michal , Elbaz Tzofit , Chopra Anand , Shapira Guy , Fry Christopher J , Shomron Noam , Biggar Kyle , Levy Dan 
Published: November 2021

AbstractGlioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor among adults, which is characterized by high invasion, migration and proliferation abilities. One important process that contributes to the invasiveness of GBM is the epithelial to mesenchymal transition (EMT). EMT is regulated by a set of defined transcription factors which tightly regulate this process, among them is the basic helix-loop-helix family member, TWIST1. Here we show that TWIST1 is methylated on lysine-33 at chromatin by SETD6, a methyltransferase with expression levels correlating with poor survival in GBM patients. RNA-seq analysis in U251 GBM cells suggested that both SETD6 and TWIST1 regulate cell adhesion and migration processes. We further show that TWIST1 methylation attenuates the expression of the long-non-coding RNA, LINC-PINT, thereby suppressing EMT in GBM. Mechanistically, TWIST1 methylation represses the transcription of LINC-PINT by increasing the occupancy of EZH2 and the catalysis of the repressive H3K27me3 mark at the LINC-PINT locus. Under un-methylated conditions, TWIST1 dissociates from the LINC-PINT locus, allowing the expression of LINC-PINT which leads to increased cell adhesion and decreased cell migration. Together, our findings unravel a new mechanistic dimension for selective expression of LINC-PINT mediated by TWIST1 methylation.
Modulation of hippocampal network oscillation by PICK1-dependent cell surface expression of mGlu3 receptors
Authors: Tuduri Pola , Bouquier Nathalie , Girard Benoit , Moutin Enora , Thouaye Maxime , Perroy Julie , Bertaso Federica , Ster Jeanne 
Published: November 2021

AbstractmGlu3 receptors control the sleep/wake architecture which plays a role in the glutamatergic pathophysiology of schizophrenia. Interestingly, mGlu3 receptors expression is decreased in the brain of schizophrenic patients. However, little is known about the molecular mechanisms regulating mGlu3 receptors at the cell membrane. Subcellular receptor localization is strongly dependent on proteinprotein interactions. Here we show that mGlu3 interacts with PICK1 and that their binding is important for receptor surface expression and function. Disruption of their interaction via an mGlu3 C-terminal mimicking peptide or an inhibitor of the PDZ domain of PICK1 altered the functional expression of mGlu3 receptors. Consequently, we investigated whether disruption of the mGlu3-PICK1 interaction affects hippocampal theta oscillations in vitro and in vivo. We found a decreased frequency of theta oscillations in organotypic hippocampal slices, similar to what previously observed in mGlu3 −/− mice. In addition, hippocampal theta power was reduced during REM sleep, NREM sleep and wake states after intra-ventricular administration of the mGlu3 C-terminal mimicking peptide. Targeting the mGlu3-PICK1 complex could thus be relevant to the pathophysiology of schizophrenia.
A Sequence-Ready BAC Clone Contig of a 2.2-Mb Segment of Human Chromosome 1q24
Authors: Vollrath Douglas , Jaramillo-Babb Virna L. 
Published: November 2021

Human chromosomal region 1q24 encodes two cloned disease genes and lies within large genetic inclusion intervals for several disease genes that have yet to be identified. We have constructed a single bacterial artificial chromosome (BAC) clone contig that spans over 2 Mb of 1q24 and consists of 78 clones connected by 100 STSs. The average density of mapped STSs is one of the highest described for a multimegabase region of the human genome. The contig was efficiently constructed by generating STSs from clone ends, followed by library walking. Distance information was added by determining the insert sizes of all clones, and expressed sequence tags (ESTs) and genes were incorporated to create a partial transcript map of the region, providing candidate genes for local disease loci. The gene order and content of the region provide insight into ancient duplication events that have occurred on proximal 1q. The stage is now set for further elucidation of this interesting region through large-scale sequencing.[The sequence data described in this paper have been submitted to GenBank under accession nos. G42259–G42312 and G42330–G42335.]
Functional Genomics in Caenorhabditis elegans: An Approach Involving Comparisons of Sequences from Related Nematodes
Authors: Thacker Colin , Marra Marco A. , Jones Alana , Baillie David L. , Rose Ann M. 
Published: November 2021

Comparative genomic analysis was used to investigate the gene structure of the bli-4 locus from two relatedCaenorhabditis species, C. elegans and C. briggsae. In C. elegans, bli-4 is a complex gene encoding a member of the kex2/subtilisin-like family of proprotein convertases. Genomic sequence comparisons coupled with RT–PCR analysis identified five additional coding exons that had not been identified previously using standard recombinant DNA techniques. The C. briggsae gene was able to rescue both viable blistered and developmentally arrested mutants of C. elegans bli-4, demonstrating functional conservation. In addition, deletion analysis of conserved sequences outside of coding regions, combined with phenotypic rescue experiments, identified regulatory elements that alter the expression of the bli-4 gene. These results demonstrate the utility of genomic sequence comparisons of homologous genes in related species as an effective tool with which to dissect the functional information of complex genes.[The sequence for cosmid K0410 is available at GenBank (accession no. AFO 39719); fosmids G06P23 and G25K01 are available as online supplementary material atwww.genome.org.]