bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling charged-particle multiplicity distributions at LHC
Authors: Radi Amr 
Published: October 2020

With many applications in high-energy physics, Deep Learning or Deep Neural Network (DNN) has become noticeable and practical in recent years. In this article, a new technique is presented for modeling the charged particles multiplicity distribution [Formula: see text] of Proton-Proton [Formula: see text] collisions using an efficient DNN model. The charged particles multiplicity n, the total center of mass energy [Formula: see text], and the pseudorapidity [Formula: see text] used as input in DNN model and the desired output is [Formula: see text]. DNN was trained to build a function, which studies the relationship between [Formula: see text]. The DNN model showed a high degree of consistency in matching the data distributions. The DNN model is used to predict with [Formula: see text] not included in the training set. The expected [Formula: see text] had effectively merged the experimental data and the values expected indicate a strong agreement with Large Hadron Collider (LHC) for ATLAS measurement at [Formula: see text], 7 and 8 TeV.
Noninvasive Detection of Urothelial Carcinoma by Cost-effective Low-coverage Whole-genome Sequencing from Urine-Exfoliated Cell DNA
Authors: Zeng Shuxiong , Ying Yidie , Xing Naidong , Wang Baiyun , Qian Ziliang , Zhou Zunlin , Zhang Zhensheng , Xu Weidong , Wang Huiqing , Dai Lihe , Gao Li , Zhou Tie , Ji Jiatao , Xu Chuanliang 
Published: October 2020

Abstract

Purpose:
Urothelial carcinoma is a malignant cancer with frequent chromosomal aberrations. Here, we investigated the application of a cost-effective, low-coverage whole-genome sequencing technology in detecting all chromosomal aberrations.

Experimental Design:
Patients with urothelial carcinomas and nontumor controls were prospectively recruited in clinical trial NCT03998371. Urine-exfoliated cell DNA was analyzed by Illumina HiSeq XTen, followed by genotyping with a customized bioinformatics workflow named Urine Exfoliated Cells Copy Number Aberration Detector (UroCAD).

Results:
In the discovery phase, urine samples from 126 patients with urothelial carcinomas and 64 nontumor disease samples were analyzed. Frequent chromosome copy-number changes were found in patients with tumor as compared with nontumor controls. A novel diagnosis model, UroCAD, was built by incorporating all the autosomal chromosomal changes. The model reached performance of AUC = 0.92 (95% confidence interval, 89.4%–97.3%). At the optimal cutoff, |Z| ≥ 3.21, the sensitivity, specificity, and accuracy were 82.5%, 96.9%, and 89.0%, respectively. The prediction positivity was found correlated with tumor grade (P = 0.01). In the external validation cohort of 95 participants, the UroCAD assay identified urothelial carcinomas with an overall sensitivity of 80.4%, specificity of 94.9%, and AUC of 0.91. Meanwhile, UroCAD assay outperformed cytology tests with significantly improved sensitivity (80.4% vs. 33.9%; P &lt; 0.001) and comparable specificity (94.9% vs. 100%; P = 0.49).

Conclusions:
UroCAD could be a robust urothelial carcinoma diagnostic method with improved sensitivity and similar specificity as compared with cytology tests. It may be used as a noninvasive approach for diagnosis and recurrence surveillance in urothelial carcinoma prior to the use of cystoscopy, which would largely reduce the burden on patients.
Project Orbis: Global Collaborative Review Program
Authors: de Claro R. Angelo , Spillman Dianne , Hotaki Lauren Tesh , Shum Michael , Mouawad Laila Sofia , Santos Gustavo Mendes Lima , Robinson Kelly , Hunt Melissa , Healy Caroline , Chan Agnes , Looi Yee Hoo , Rodrigues Clare , Rohr Ulrich-Peter , Walther Chantal , Pazdur Richard 
Published: October 2020

Abstract
In 2019, the FDA Oncology Center of Excellence launched Project Orbis, a global collaborative review program to facilitate faster patient access to innovative cancer therapies across multiple countries. Project Orbis aims for concurrent submission, review, and regulatory action for high-impact clinically significant marketing applications among the participating partner countries. Current Project Orbis partners (POP) include the regulatory health authorities (RHA) of Australia, Brazil, Canada, Singapore, and Switzerland. Project Orbis leverages the existing scientific and regulatory partnerships between the various RHA under mutual confidentiality agreements. While FDA serves as the primary coordinator for application selection and review, each country remains fully independent on their final regulatory decision. In the first year of Project Orbis (June 2019 to June 2020), a total of 60 oncology marketing applications were received, representing 16 unique projects, and resulting in 38 approvals. New molecular entities, also known as new active substances, comprised 28% of the received marketing applications. The median time gap between FDA and Orbis submission dates was 0.6 months with a range of −0.8 to 9.0 months. Across the program, the median time-to-approval was similar between FDA (4.2 months, range 0.9–6.9, N = 18) and the POP (4.4 months, range 1.7–6.8, N = 20). Participating countries have signified a strong commitment for continuation and growth of the program. Project Orbis expansion considerations include the addition of more countries and management of more complex applications.
Selective Tumor Cell Apoptosis and Tumor Regression in CDH17-Positive Colorectal Cancer Models using BI 905711, a Novel Liver-Sparing TRAILR2 Agonist
Authors: García-Martínez Juan Manuel , Wang Shirley , Weishaeupl Cordula , Wernitznig Andreas , Chetta Paolo , Pinto Catarina , Ho Jason , Dutcher Darrin , Gorman Philip N. , Kroe-Barrett Rachel , Rinnenthal Joerg , Giragossian Craig , Impagnatiello Maria Antonietta , Tirapu Iñigo , Hilberg Frank , Kraut Norbert , Pearson Mark , Kuenkele Klaus Peter 
Published: October 2020

Abstract

Activation of TRAILR2 has emerged as an important therapeutic concept in cancer treatment. TRAILR2 agonistic molecules have only had limited clinical success, to date, due either to lack of efficacy or hepatotoxicity. BI 905711 is a novel tetravalent bispecific antibody targeting both TRAILR2 and CDH17 and represents a novel liver-sparing TRAILR2 agonist specifically designed to overcome the disadvantages of previous strategies. Here, we show that BI 905711 effectively triggered apoptosis in a broad panel of CDH17-positive colorectal cancer tumor cells in vitro. Efficient induction of apoptosis was dependent on the presence of CDH17, as exemplified by the greater than 1,000-fold drop in potency in CDH17-negative cells. BI 905711 demonstrated single-agent tumor regressions in CDH17-positive colorectal cancer xenografts, an effect that was further enhanced upon combination with irinotecan. Antitumor efficacy correlated with induction of caspase activation, as measured in both the tumor and plasma. Effective tumor growth inhibition was further demonstrated across a series of different colorectal cancer PDX models. BI 905711 induced apoptosis in both a cis (same cell) as well as trans (adjacent cell) fashion, translating into significant antitumor activity even in xenograft models with heterogeneous CDH17 expression. In summary, we demonstrate that BI 905711 has potent and selective antitumor activity in CDH17-positive colorectal cancer models both in vitro and in vivo. The high prevalence of over 95% CDH17-positive tumors in patients with colorectal cancer, the molecule preclinical efficacy together with its potential for a favorable safety profile, support the ongoing BI 905711 phase I trial in colorectal cancer and additional CDH17-positive cancer types (NCT04137289).
Molecular Characterization of Appendiceal Goblet Cell Carcinoid
Authors: Arai Hiroyuki , Baca Yasmine , Battaglin Francesca , Kawanishi Natsuko , Wang Jingyuan , Soni Shivani , Zhang Wu , Millstein Joshua , Johnston Curtis , Goldberg Richard M. , Philip Philip A. , Seeber Andreas , Xiu Joanne , Hwang Jimmy J. , Shields Anthony F. , Marshall John L. , Korn W. Michael , Lenz Heinz-Josef 
Published: October 2020

Abstract
Goblet cell carcinoid (GCC) is a distinct subtype of appendiceal neoplasm that exhibits unique clinical and pathologic features. We aimed to reveal the molecular profiles of GCC compared with other appendiceal tumors, such as adenocarcinomas and neuroendocrine tumors. A total of 495 appendiceal tumor samples (53 GCCs, 428 adenocarcinomas, and 14 neuroendocrine tumors) were tested with next-generation sequencing (NGS) on a 592-gene panel and IHC. Microsatellite instability (MSI)/mismatch repair (MMR) status was tested with a combination of NGS, IHC, and fragment analyses. Tumor mutational burden (TMB) was evaluated by NGS, and PD-L1 expression was tested by IHC (SP142). The most prevalent mutated genes within GCCs were TP53 (24.0%), ARID1A (15.4%), SMAD4 (9.4%), and KRAS (7.5%). Pathway-specific alterations were dominantly observed in cell cycle, MAPK, epigenetic, and TGFβ signaling pathways. GCCs as compared with adenocarcinomas exhibited significantly lower mutation rates in KRAS, GNAS, and APC, and significantly higher mutation rates in CDH1, CHEK2, CDC73, ERCC2, and FGFR2. GCCs as compared with neuroendocrine tumors showed significantly lower mutation rates in KRAS, APC, BRCA2, and FANCA. In GCCs, MSI high/MMR deficient, TMB high (≥17 mutations/Mb), and PD-L1 expression were seen in 0.0%, 0.0%, and 2.0% of tumors, respectively. No significant differences were observed in any immunotherapy-related markers examined when compared with adenocarcinomas and neuroendocrine tumors. In conclusion, GCCs had considerably distinct mutational profiles compared with appendiceal adenocarcinomas and neuroendocrine tumors. Understanding these molecular characteristics may be critical for the development of novel and more effective treatment strategies for GCC.
PCBP2Posttranscriptional Modifications Induce Breast Cancer Progression via Upregulation of UFD1 and NT5E
Authors: Wang Xiaonan , Guo Qianying , Wang Hao , Yuan Xiaodong , Wang Bijun , Lobie Peter E. , Zhu Tao , Tan Sheng , Wu Zhengsheng 
Published: October 2020

AbstractIt is commonly accepted that cellular protein levels are primarily determined by mRNA levels. However, discordance between protein and mRNA expression has been implicated in many pathologic conditions including oncogenesis. The mechanisms involved in this discordance are complicated and far from understood. In this study, it was observed that the expression levels of poly(C) binding protein 2 (PCBP2) mRNA and protein were diametric in breast normal and cancer cell lines, paraffin-embedded and fresh tissue specimens, consistent with data from The Cancer Genome Atlas and the Clinical Proteomic Tumor Analysis Consortium. Moreover, PCBP2 protein expression was significantly associated with disease progression and poor outcome in patients with breast cancer. Depletion of PCBP2 protein inhibited cell proliferation, colony formation, migration, invasion, and in vivo tumor growth and metastasis. Forced expression of PCBP2 exhibited the opposite effect. Mechanistically, it was demonstrated that PCBP2 3′ untranslated region (3′UTR) was subject to alternative splicing and polyadenylation (APA) in breast cancer tissues and cell lines. Non-full-length 3′UTR PCBP2 transcripts yielded more protein than the full-length 3′UTR transcripts and enhanced the oncogenic and metastatic capacities of human breast cancer cells. Furthermore, UFD1 and NT5E were identified as genes downstream of PCBP2. PCBP2 promoted oncogenicity of breast cancer cells via upregulation of the expression of UFD1 and NT5E by direct binding to their 3′UTR-B portions.Implications:Findings demonstrate that APA of PCBP2 3′UTR contributes to its increased expression with subsequent promotion of breast cancer progression by regulating UFD1 and NT5E.Visual Overview:http://mcr.aacrjournals.org/content/molcanres/19/1/86/F1.large.jpg.
Left Ventricular Unloading Is Associated With Lower Mortality in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation
Authors: Schrage Benedikt , Becher Peter Moritz , Bernhardt Alexander , Bezerra Hiram , Blankenberg Stefan , Brunner Stefan , Colson Pascal , Cudemus Deseda Gaston , Dabboura Salim , Eckner Dennis , Eden Matthias , Eitel Ingo , Frank Derk , Frey Norbert , Funamoto Masaki , Goßling Alina , Graf Tobias , Hagl Christian , Kirchhof Paulus , Kupka Danny , Landmesser Ulf , Lipinski Jerry , Lopes Mathew , Majunke Nicolas , Maniuc Octavian , McGrath Daniel , Möbius-Winkler Sven , Morrow David A. , Mourad Marc , Noel Curt , Nordbeck Peter , Orban Martin , Pappalardo Federico , Patel Sandeep M. , Pauschinger Matthias , Pazzanese Vittorio , Reichenspurner Hermann , Sandri Marcus , Schulze P. Christian , H.G. Schwinger Robert , Sinning Jan-Malte , Aksoy Adem , Skurk Carsten , Szczanowicz Lukasz , Thiele Holger , Tietz Franziska , Varshney Anubodh , Wechsler Lukas , Westermann Dirk 
Published: October 2020

Background:
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to treat cardiogenic shock. However, VA-ECMO might hamper myocardial recovery. The Impella unloads the left ventricle. This study aimed to evaluate whether left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO was associated with lower mortality.

Methods:
Data from 686 consecutive patients with cardiogenic shock treated with VA-ECMO with or without left ventricular unloading using an Impella at 16 tertiary care centers in 4 countries were collected. The association between left ventricular unloading and 30-day mortality was assessed by Cox regression models in a 1:1 propensity score–matched cohort.

Results:

Left ventricular unloading was used in 337 of the 686 patients (49%). After matching, 255 patients with left ventricular unloading were compared with 255 patients without left ventricular unloading. In the matched cohort, left ventricular unloading was associated with lower 30-day mortality (hazard ratio, 0.79 [95% CI, 0.63–0.98];
P
=0.03) without differences in various subgroups. Complications occurred more frequently in patients with left ventricular unloading: severe bleeding in 98 (38.4%) versus 45 (17.9%), access site–related ischemia in 55 (21.6%) versus 31 (12.3%), abdominal compartment in 23 (9.4%) versus 9 (3.7%), and renal replacement therapy in 148 (58.5%) versus 99 (39.1%).

Conclusions:
In this international, multicenter cohort study, left ventricular unloading was associated with lower mortality in patients with cardiogenic shock treated with VA-ECMO, despite higher complication rates. These findings support use of left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO and call for further validation, ideally in a randomized, controlled trial.
Expanding Stroke Preparedness to Vulnerable Populations: A Music Video for the Deaf Community
Authors: Springer Mellanie V. , Corches Casey L. , McCracklin Bernadette , Scott Melecia , Robles Maria Cielito , Skolarus Lesli E. 
Published: October 2020

Background
Acute stroke treatments reduce disability after stroke, but eligibility for these treatments depends on rapid hospital arrival after symptom onset. Stroke preparedness interventions teach stroke symptoms and the importance of calling 911, thereby increasing patient eligibility for stroke treatments. Stroke preparedness interventions for the Deaf community are lacking. We sought to adapt a stroke preparedness music video, which was initially created for the hearing, for the Deaf community.

Methods and Results
We used a community‐engaged approach, partnering with members of the Deaf community, to adapt the video over 4 months. Adaptation involved assessing the comprehensibility and appropriateness of the video and interpreting the song lyrics into American Sign Language.

Conclusions
We collaborated with the Deaf community to create a stroke preparedness video for the Deaf. Future research will involve refining the video and testing its efficacy to increase stroke symptom recognition and intent to call 911.
Utility of gas inlet pressure monitoring in extracorporeal membrane oxygenation
Authors: Nakamura Yuki , Nakakita Takafumi , Yamamoto Kazuhiko , Kamada Aki , Iguchi Shinichi , Umimoto Koichi 
Published: October 2020

Purpose: Purpose: Condensation that clogs the hollow fibers of the oxygenation and accumulation of plasma leaks reduces oxygenated lung capacity. In this study, artificial We evaluated whether monitoring changes in lung gas inlet pressure was a way to predict these complications. Methods: Changes in gas inlet pressure and oxygenation capacity of three different prostheses (BIOCUBE6000, EXCELUNG PRIME, and Capiox-LX) Evaluated the relationship. When simulating plasma leakage using BIOCUBE6000, sodium dodecyl sulfate (SDS) (1%, 0.1%, A solution of 0.01%, and RO water) reduced surface tension. During 120 minutes of circulation, changes in gas inlet pressure and leakage from the membrane into the gas flow path The amount of fluid was measured. Results: There was a significant negative correlation between the gas inlet pressure changes and the oxygenation capacity of all three oxygenators (BIOCUBE6000: R2 = 0.957, EXCELUNG PRIME: R2 = 0.946, Capiox-LX: R2 = 0.878). After 120 min of SDS solution circulation using the BIOCUBE6000, both the gas inlet pressure and the volume of fluid leaking from the membrane into the gas flow path increased in proportion to the SDS solution concentration: RO water (0.56 ± 0.11 mmHg and 16.67 mL ± 0.94 mL), 0.01% SDS (0.98 ± 0.11 mmHg and 23.3 ± 0.47 mL,) 0.1% SDS (1.64 ± 0.21 mmHg and 29.0 ± 1.63 mL), and 1%SDS (14.3 ± 0.27 mmHg and 36.7 ± 0.47 mL) (n = 3). Conclusion: This study confirmed that monitoring the gas inlet pressure changes of an oxygenator during ECMO is clinically useful.
Thinking Out-of-the-Box: A Non-Standard Application of Standard Pulse-Oximetry and Standard Near-Infrared Spectroscopy in a COVID-19 Patient
Authors: Schober Patrick , Lust Erik J. , Heunks Leo M. A. , Schwarte Lothar A. 
Published: October 2020

Purpose: Purpose of this report is to describe the feasibility of lingual pulse oximetry and lingual near-infrared spectroscopy (NIRS) in a COVID-19 patient to assess lingual tissue viability after several days of mechanical ventilation in the prone position. Materials & Methods: In a COVID-19 ICU-patient, the tongue became grotesquely swollen, hardened and protruding from the oral cavity after 20 h of mechanical ventilation uninterrupted in the prone position. To assess the doubtful viability of the tongue, pulse-oximetric hemoglobin O2-saturation (SpO2; Nellcor, OxiMax MAX-NI, Covidien, MA, USA) and NIRS-based, regional tissue O2-saturation measurements (rSO2; SenSmart, Nonin, MN, USA) were performed at the tongue. Results: At the tongue, regular pulse-oximetric waveforms with a pulse-oximetric hemoglobin O2-saturation (SpO2) of 88% were recorded, i.e. only slightly lower than the SpO2 reading at the extremities at that time (90%). Lingual NIRS-based rSO2 measurements yielded stable tissue rSO2-values of 76-78%, i.e. values expected also in other adequately perfused and oxygenated (muscle-) tissues. Conclusion: Despite the alarming, clinical finding of a grotesquely swollen, rubber-hard tongue and clinical concerns on the adequacy of the tongue perfusion and oxygenation, our measurements of both arterial pulsatility (SpO2) and NIRS-based tissue oxygenation (rSO2) suggested adequate perfusion and oxygenation of the tongue, rendering non-vitality of the tongue, e.g. by lingual venous thrombosis, unlikely. To our knowledge, this is the first clinical report of lingual rSO2 measurement.
Associations Among Maternal Adiposity, Insulin, and Adipokines in Circulation and Human Milk
Authors: Schneider-Worthington Camille R. , Bahorski Jessica S. , Fields David A. , Gower Barbara A. , Fernández José R. , Chandler-Laney Paula C. 
Published: October 2020

Background Insulin, leptin, and adiponectin regulate energy balance and may influence infant growth via their presence in human milk. Maternal body mass index has been associated with human milk insulin, leptin, and adiponectin concentrations, but results are inconsistent. Maternal serum hormone concentrations and fat mass may better characterize human phenotype and be more appropriate predictors of human milk insulin, leptin, and adiponectin. Research aim To examine the associations of human milk insulin, leptin, and adiponectin with their concentrations in maternal circulation and with maternal fat mass. Methods Insulin, leptin, and adiponectin were measured in serum and human milk at 1 month postpartum in 25 women. Total body fat mass and fat-free mass were measured using bioelectrical impedance analysis. Linear regression modeling was used to examine associations of serum hormone concentrations or fat mass with human milk insulin, leptin, and adiponectin after adjusting for covariates. Results Serum insulin ( p = .007), leptin ( p < .001), and adiponectin ( p < .001) were each associated with their respective concentrations in human milk. Fat mass was positively associated with insulin ( p = .005) and leptin ( p < .001), but not with adiponectin ( p = .65), in human milk. Conclusions Human milk insulin, leptin, and adiponectin were positively associated with their concentrations in serum, and human milk insulin and leptin were associated with maternal fat mass. Future research is needed to elucidate the role of human milk hormones in infant energy balance and growth.
Municipal strategies and meeting minutes’ descriptions of the promotion of children’s mental health: a document analysis
Authors: Savolainen Outi , Turunen Hannele , Sormunen Marjorita 
Published: October 2020

Aims: Little is known about how municipal strategies, programmes and plans pay attention to the promotion of children’s mental health and whether it is discussed and reported in the municipal councils, boards and committees. The purpose of this study was to examine how municipalities in one Finnish region promote mental health, with a focus on the promotion of children’s mental health. Methods: Document analysis was used as a research method. Documents were selected for a one-year period (2018) from three municipalities of the North Savo region. Analysed documents ( n=269) were municipal strategies, programmes and plans, as well as meeting minutes of municipal councils, boards and committees. Eight domains of the structural indicators of mental health were used as an analysis frame. Results: In total, 1169 mentions related to the structural indicators of mental health were found in the documents. In strategies, programmes and plans, parenting-related mentions were found most often. Regarding the minutes, the issues discussed and reported about the wellbeing of children focused on practical issues, such as the construction of day care buildings. Conclusions: Document analysis indicated that mental health promotion involved mostly the society and environment and not as much the age and setting. There was a lack of mentions regarding preschool experiences and family support/childcare and the promotion of mental health through schools and education, especially in the meeting minutes of municipal councils, boards and committees.