bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypotheses on a tree: new error rates and testing strategies
Authors: Bogomolov Marina , Peterson Christine B , Benjamini Yoav , Sabatti Chiara 
Published: September 2020

SummaryWe introduce a multiple testing procedure that controls global error rates at multiple levels of resolution. Conceptually, we frame this problem as the selection of hypotheses that are organized hierarchically in a tree structure. We describe a fast algorithm and prove that it controls relevant error rates given certain assumptions on the dependence between the $p$-values. Through simulations, we demonstrate that the proposed procedure provides the desired guarantees under a range of dependency structures and that it has the potential to gain power over alternative methods. Finally, we apply the method to studies on the genetic regulation of gene expression across multiple tissues and on the relation between the gut microbiome and colorectal cancer.
Stage at Diagnosis and Survival of Colorectal Cancer With or Without Underlying Inflammatory Bowel Disease: A Population-based Study
Authors: Arhi Chanpreet , Askari Alan , Nachiappan Subramanian , Bottle Alex , Arebi Naila , Athanasiou Thanos , Ziprin Paul , Aylin Paul , Faiz Omar 
Published: September 2020

Abstract

Background
Inflammatory bowel disease [IBD] is a risk factor for colorectal cancer [CRC]. The aim of this study is to determine whether stage at diagnosis and survival differ between sporadic, ulcerative colitis [UC]- and Crohn’s disease [CD]-related CRC.

Methods
The English National Cancer Registry [NCIN], Hospital Episode Statistics [HES] and Office for National Statistics [ONS] datasets between 2000 and 2010 were linked, providing data on comorbidities, stage and date of death. A logistic regression model determined whether IBD was associated with an early [I/II] or late [III/IV] cancer. Cox regression analysis was used to examine survival differences between sporadic, UC- and CD-related cancers.

Results
A total of 234 009 patients with CRC were included, of whom 985 [0.4%] and 1922 [0.8%] had CD and UC, respectively. UC, but not CD, was associated with an earlier stage compared with sporadic cancers (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.79 to 0.98, p = 0.02). CD had a significantly worse survival compared with sporadic patients for stage II [HR = 1.71, CI 1.26 to 2.31 p &lt;0.005] and III [1.53, CI 1.20 to 1.96, p &lt;0.005] cancer. UC patients were associated with worse survival compared with the sporadic group for both stage III [1.38, CI 1.17 to 1.63, p &lt;0.0005] and IV [1.13, CI 1.01 to 1.28, p = 0.04] cancer. After excluding sporadic patients, UC was associated with improved survival compared with CD [0.62, CI 0.43 to 0.90, p = 0.01] for stage II cancer.

Conclusions
Patients with IBD are diagnosed at an earlier stage but tend to have a worse survival compared with sporadic cases of CRC, in particular for nodal disease [stage III].Specifically, patients with CD-related CRC appear to fare worst in terms of survival compared with both the sporadic and UC groups.
Wall shear stress in the thoracic aorta at rest and with dobutamine stress after arterial switch operation
Authors: van der Palen Roel L F , Juffermans Joe F , Kroft Lucia J M , Hazekamp Mark G , Lamb Hildo J , Blom Nico A , Roest Arno A W , Westenberg Jos J M 
Published: September 2020

Abstract

OBJECTIVES
Progressive root dilatation is an important complication in patients with transposition of the great arteries (TGA) after arterial switch operation (ASO) that may be caused by altered flow dynamics. Aortic wall shear stress (WSS) distribution at rest and under dobutamine stress (DS) conditions using 4D flow magnetic resonance imaging were investigated in relation to thoracic aorta geometry.

METHODS
4D flow magnetic resonance imaging was performed in 16 adolescent TGA patients after ASO (rest and DS condition) and in 10 healthy controls (rest). The primary outcome measure was the WSS distribution along the aortic segments and the WSS change with DS in TGA patients. Based on the results, we secondary zoomed in on factors [aortic geometry and left ventricular (LV) function parameters] that might relate to these WSS distribution differences. Aortic diameters, arch angle, LV function parameters (stroke volume, LV ejection fraction, cardiac output) and peak systolic aortic WSS were obtained.

RESULTS
TGA patients had significantly larger neoaortic root and smaller mid-ascending aorta (AAo) dimensions and aortic arch angle. At rest, patients had significantly higher WSS in the entire thoracic aorta, except for the dilated root. High WSS levels beyond the proximal AAo were associated with the diameter decrease from the root to the mid-AAo (correlation coefficient r = 0.54–0.59, P = 0.022–0.031), not associated with the aortic arch angle. During DS, WSS increased in all aortic segments (P &lt; 0.001), most pronounced in the AAo segments. The increase in LV ejection fraction, stroke volume and cardiac output as a result of DS showed a moderate linear relationship with the WSS increase in the distal AAo (correlation coefficient r = 0.54–0.57, P = 0.002–0.038).

CONCLUSIONS
Increased aortic WSS was observed in TGA patients after ASO, related to the ASO-specific geometry, which increased with DS. Stress-enhanced elevated WSS may play a role in neoaortic root dilatation and anterior aortic wall thinning of the distal AAo.
Draft genome sequences of concurrent Escherichia coli blood and fecal isolates from a patient with bacteremia and diarrhea belie BioFire-based detection of fecal enteropathogenic E. coli
Authors: Singh Pradip Kumar , Johnston Brian D , Johnson James R , Donnenberg Michael S 
Published: September 2020

ABSTRACT
The BioFire FilmArray® Gastrointestinal panel is a multiplex PCR assay widely used to determine the etiology of infectious gastroenteritis directly from stool specimens. Recently a positive BioFire result for fecal enteropathogenic Escherichia coli (EPEC) was reported by a clinical microbiology laboratory for an adult patient with diarrhea and bacteremia. Since EPEC infrequently infects adults and rarely causes bacteremia, we isolated fecal E. coli and characterized the patient's blood and fecal E. coli isolates. Draft genome sequencing using a combination of methods indicated that the blood and fecal strains are virtually identical, are from sequence type 963 (phylogroup D) and exhibit neither the virulence genes characteristic of EPEC and extraintestinal pathogenic E. coli (ExPEC) nor classic EPEC-associated phenotypes. These findings support a gut source for the patient's bacteremia but exclude EPEC as the causative organism, and suggest that results of multiplex PCR assays from complex samples can be misleading, and should be interpreted with caution when they are discordant with clinical information. BioProject accession numbers for strains MVAST5574 and MVAST5635 genomes are PRJNA611789 and PRJNA611804, respectively.
Multifaceted anti-colorectal tumor effect of digoxin on HCT8 and SW620 cells in vitro
Authors: Hou Yong-Qiang , Wang Ying-Ying , Wang Xing-Can , Liu Yao , Zhang Chun-Ze , Chen Zhe-Sheng , Zhang Zhe , Wang Wei , Kong De-Xin 
Published: September 2020

Abstract

Background
Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. Novel drugs for CRC therapy are urgently needed. Digoxin has been in clinical use for treatment of heart failure and atrial arrhythmias for many years. Fragmentary reports suggested that digoxin might have antitumor efficacy on CRC. Here, we aimed to investigate the antitumor effect of digoxin on human CRC cells and the underlying mechanism.

Methods
Cell viability was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and plate colony formation assay. The effects of digoxin on cell-cycle distribution and apoptosis were analysed by flow cytometry. The anti-metastatic effect on tumor cells was determined by wound-healing assay and transwell assay. Anti-angiogenic effect was examined by determining the inhibition against proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Mechanism study was performed by Western blot, enzyme-linked immunosorbent assay (ELISA), and gelatin-zymography assay.

Results
Digoxin potently inhibited cell proliferation, induced G1-phase and G2/M-phase arrest in colorectal-cancer HCT8 and SW620 cells, respectively. No obvious apoptosis was observed in the treated cells. Anti-metastatic activities were shown on HCT8 cells by inhibiting the migration and invasion. Meanwhile, the expression of MMP2, MMP9, and phosphorylated Integrinβ1 were decreased. Digoxin inhibited the proliferation, migration, and tube formation of HUVECs and reduced HIF1α expression and vascular endothelial growth factor A (VEGF-A) secretion in HCT8 cells, suggesting anti-angiogenic activity. Furthermore, digoxin significantly reversed ABCB1-mediated multidrug resistance on SW620/Ad300 cells.

Conclusion
Our findings suggest that digoxin has the potential to be applied as an antitumor drug via inhibiting proliferation and metastasis as well as reversing the ABCB1-mediated multidrug resistance of colorectal cancer.
Taking Investors’ Rights Seriously: The Achmea and CETA Rulings of the European Court of Justice do not Bar Intra-EU Investment Arbitration
Authors: Reuter Alexander 
Published: September 2020

Abstract
In its 2018 Achmea ruling, the European Court of Justice (ECJ) found intra-European Union (EU) investment arbitration incompatible with EU law, and in its 2019 opinion on the proposed Canada–EU Trade Agreement (CETA), the ECJ has set out requirements for the recognition by the EU of investor–State arbitration at large. On the other hand, in the last few years a great many tribunals (under both International Centre for the Settlement of Investment Disputes (ICSID) and non-ICSID regimes) have dealt with intra-EU investment arbitrations, most of them under the Energy Charter Treaty (ECT). None of these tribunals found the proceedings to be incompatible with EU law.
The reason for this discrepancy is that the tribunals deal with investors’ rights, while the ECJ, in contrast, is concerned with intra-EU governance issues. However, individual rights are not alien to EU law. Against that background, this note is based on the established finding that investment treaties bestow private investors with individual rights under public international law. These rights need to be taken seriously: as third parties, investors can, under both public international law and EU law, draw upon these rights, irrespective of the internal EU governance rules with which the ECJ was concerned. Hence, this note2 is not meant to be a further contribution to the voluminous debate on the internal EU governance rules drawn upon by the ECJ. In contrast, it is based on the binding effect on the EU of the investors’ individual rights. Furthermore, it shows that the ECJ’s rulings do not have an adverse precedent effect on the pursuit of investors’ rights and that, in addition, the ECT meets the criteria under which the ECJ has assessed EU compatibility of investment arbitration. Last but not least, the denial by EU institutions of investors' rights under the ECT may, in itself, constitute an infringement of the ECT.
Engaging ethnic minority communities through performance and arts: health education in Cambodian forest villages
Authors: Callery James J , Sanann Nou , Tripura Rupam , Buntau Thoek , Peto Thomas J , Kunthea Pich , Pell Christopher , Soviet Ung , Nguon Chea , Lek Dysoley , Cheah Phaik Yeong 
Published: September 2020

Abstract

Background
In Siem Pang, northeastern Cambodia, malaria transmission persists in remote forested areas populated by ethnic minorities. Engaging affected communities in health education campaigns is challenging due to language, access and literacy constraints. During 2018, a newly established medical research station conducted a health education programme in local villages harnessing traditional songs, arts and crafts, along with theatre, comedy and health talks and quizzes. Health education topics were proposed by community leaders and focused on maternal and child health and malaria. This article describes a process evaluation of these activities, the community's response and whether this was an appropriate form of health education in this context.

Methods
In-depth interviews were conducted with community members, leaders and performers. Interviews were audio-recorded, transcribed and translated to English for thematic analysis.

Results
In total, 65 interviews were conducted; 20 of these were follow-up interviews with respondents interviewed prior to the performances. Respondents were able to recall the key health messages about malaria, antenatal care and infant vaccination. They also showed good awareness of malaria transmission and prevention and described how they enjoyed the events and appreciated the efforts of the project team.

Conclusions
In isolated communities in Cambodia, a health education programme harnessing performance and arts engaged the whole community and its messages were readily recalled and prompted reflection.
Diminished Consciousness in a Woman Following an Unsuspected Scopolamine Overdose
Authors: Barceló Bernardino , Gomila Isabel , de-Castro-Ríos Ana , Perez-Barcena Jon , Jimenez Carmen , Lendoiro Elena , Elorza Miguel Ángel 
Published: September 2020

Abstract
Scopolamine is used clinically, but it is also used as a recreational drug and as an incapacitating drug, in sexual crimes and robberies. In this paper, the authors report the case of a woman with a diminished consciousness following an unsuspected overdose with scopolamine and review published articles on scopolamine poisoning that included concentrations in biological samples. Scopolamine was identified in the patient’s serum and urine samples collected 1 h post-admission to intensive care unit at concentrations of 8.4 ng/mL and 62,560 ng/mL (169,539 ng/mg creatinine), respectively. In non-fatal cases, the median [interquartile range] of serum scopolamine levels was 1.9 [2.1] ng/mL. The serum concentration found in our case would explain the abrupt clinical presentation suffered by the patient. Scopolamine in urine could be detected up to 48 h after admission. This report illustrates that broad toxicology screening, including scopolamine, should be considered when patients with diminished consciousness are attended after ruling out infection or cerebrovascular disease. This can play an important role in identifying this potentially life-threatening etiology.
The Impact of Different System Call Representations on Intrusion Detection
Authors: Wunderlich Sarah , Ring Markus , Landes Dieter , Hotho Andreas 
Published: September 2020

Abstract
Over the years, artificial neural networks have been applied successfully in many areas including IT security. Yet, neural networks can only process continuous input data. This is particularly challenging for security-related, non-continuous data like system calls of an operating system. This work focuses on five different options to preprocess sequences of system calls so that they can be processed by neural networks. These input options are based on one-hot encodings and learning word2vec, GloVe or fastText representations of system calls. As an additional option, we analyse if mapping system calls to their respective kernel modules is an adequate generalization step for (i) replacing system calls or (ii) enhancing system call data with additional information regarding their context. When performing such preprocessing steps it is important to ensure that no relevant information is lost during the process. The overall objective of system call analysis in the context of IT security is to categorize a sequence of them as benign or malicious behavior. Therefore, this scenario is used to evaluate different system call representations in a classification task. Results indicate that a broader range of attacks can be detected when enriching system call representations with corresponding kernel module information. Prior learning of embeddings does not achieve significant improvements. This work is an extension of the work by Wunderlich et al. [1] published in Advances in Intelligent Systems and Computing (AISC, volume 951).
Failure Types and Related Factors of Spinopelvic Fixation After Long Construct Fusion for Adult Spinal Deformity
Authors: Park Se-Jun , Park Jin-Sung , Nam Yunjin , Yum Tae-Hoon , Choi Youn-Taek , Lee Chong-Suh 
Published: September 2020

Abstract

BACKGROUND
Rigid internal fixation of the spine is an essential part of adult spinal deformity (ASD) surgery. Despite the use of pelvic fixation and anterior column support, spinopelvic fixation failure (SPFF) still remains an issue. Few studies have evaluated the types of such failure or its related factors.

OBJECTIVE
To classify the types of SPFF and investigate its risk factors, including the fusion status at L5-S1 on CT scan.

METHODS
The study cohort consisted of ninety-eight ASD patients who underwent more than 4-level fusions to the sacrum with interbody fusion at L5-S1. Patients with SPFF were divided into the two groups: above-S1 and below-S1 failure groups. The patient, surgical, and radiographic variables in each group were compared to those of the no-failure group. The L5-S1 fusion status was assessed using 2-yr computed tomography (CT) scan. Univariate and multivariate analyses were performed to determine the risk factors for each failure group.

RESULTS
The mean age was 68.5 yr. Follow-up duration was 55.7 mo. The SPFF developed in 46 (46.9%) patients at 32.7 mo postoperatively. There were 15 patients in the above-S1 failure group and 31 patients in the below-S1 failure group. Multivariate analysis revealed that nonunion at L5-S1 was a single risk factor for above-S1 failure. In contrast, the risk factors for below-S1 failure included a greater number of fused segments and postoperative less thoracic kyphosis.

CONCLUSION
SPFF develops in different patterns with different risk factors. Above-S1 SPFF was associated with nonunion at L5-S1, while below-S1 SPFF was associated with mechanical stress.
Endovascular Selective Intra-Arterial Infusion of Mesenchymal Stem Cells Loaded With Delta-24 in a Canine Model
Authors: Srinivasan Visish M , Gumin Joy , Camstra Kevin M , Collins Dalis E , Chen Melissa M , Shpall Elizabeth J , Parker Kerrigan Brittany C , Johnson Jeremiah N , Chen Stephen R , Fueyo Juan , Gomez-Manzano Cande , Lang Frederick F , Kan Peter 
Published: September 2020

Abstract

BACKGROUND
Delta-24-RGD, an oncolytic adenovirus, shows promise against glioblastoma. To enhance virus delivery, we recently demonstrated that human bone marrow-derived mesenchymal stem cells loaded with Delta-24-RGD (hMSC-D24) can eradicate glioblastomas in mouse models. There are no studies examining the safety of endovascular selective intra-arterial (ESIA) infusions of MSC-D24 in large animals simulating human clinical situations.

OBJECTIVE
To perform canine preclinical studies testing the feasibility and safety of delivering increasing doses of hMSCs-D24 via ESIA infusions.

METHODS
ESIA infusions of hMSC-D24 were performed in the cerebral circulation of 10 normal canines in the target vessels (internal carotid artery [ICA]/P1) via transfemoral approach using commercially available microcatheters. Increasing concentrations of hMSC-D24 or particles (as a positive control) were injected into 1 hemisphere; saline (negative control) was infused contralaterally. Toxicity (particularly embolic stroke) was assessed on postinfusion angiography, diffusion-weighted magnetic resonance imaging, clinical exam, and necropsy.

RESULTS
ESIA injections were performed in the ICA (n = 7) or P1 (n = 3). In 2 animals injected with particles (positive control), strokes were detected by all assays. Of 6 canines injected with hMSC-D24 through the anterior circulation, escalating dose from 2 × 106 cells/20 mL to 1 × 108 cells/10 mL resulted in no strokes. Two animals had ischemic and hemorrhagic strokes after posterior cerebral artery catheterization. A survival experiment of 2 subjects resulted in no complications detected for 24-h before euthanization.

CONCLUSION
This novel study simulating ESIA infusion demonstrates that MSCs-D24 can be infused safely at least up to doses of 1 × 108 cells/10 mL (107 cells/ml) in the canine anterior circulation using commercially available microcatheters. These findings support a clinical trial of ESIA infusion of hMSCs-D24.
“An Outlet to the Western Sea”: Puget Sound, Terraqueous Mobility, and Northern Pacific Railroad’s Pursuit of Trade with Asia, 1864–1892
Authors: Fraga Sean 
Published: September 2020

Abstract
The Northern Pacific Railroad saw Puget Sound harbors as environments uniquely suited to connect the North American interior with the Pacific Ocean and enable U.S. trade with East Asia. But in building the physical infrastructure to link transcontinental trains with transpacific ships, Northern Pacific significantly altered Commencement Bay’s shoreline and displaced Puyallups from their traditional territory. The articles uses a terraqueous perspective, emphasizing movement between terrestrial and aqueous environments, to demonstrate how U.S. pursuit of transpacific trade shaped the North American West.
Revision Surgery for Adjacent Segment Degeneration After Fusion for Lumbar Spondylolisthesis
Authors: Duan Ping-Guo , Mummaneni Praveen V. , Berven Sigurd H. , Mayer Rory , Ruan Hui-Bing , Chang Chih-Chang , Chou Dean 
Published: September 2020

Study Design.
Retrospective study.

Objective.
The aim of this study was to investigate whether there is an association between revision surgery rates for adjacent segment degeneration (ASD) and Roussouly type after L4-5 transforaminal lumbar interbody fusion (TLIF) for spondylolisthesis.

Summary of Background Data.
Revision surgery for ASD is known to occur after spinal fusion; however, it is unclear whether rates of ASD are associated with certain Roussouly types.

Methods.
Patients who underwent L4-5 TLIF for spondylolisthesis at the University of California San Francisco from January 2006 to December 2016 with minimum 2-year follow-up were retrospectively analyzed by Roussouly type. Revision surgery for ASD was noted and correlated by Roussouly type. Spinopelvic parameters were also measured for correlation. A value of P < 0.05 was significant.

Results.
There were 174 patients who met inclusion criteria, (59 males and 115 females). The average age was 62.3 (25–80) years. A total of 132 patients had grade I spondylolisthesis, and 42 had grade II. Mean follow-up was 45.2 months (24–497). A total of 22 patients (12.6%) underwent revision surgery for ASD after L4-5 TLIF. When classified by Roussouly type, revision surgery rates for ASD were: 1, 14.3%; 2, 22.6%; 3, 4.9%; and 4, 15.6% (P = 0.013). Type 3 spines with normal PI-LL (8.85° ± 6.83°) had the lowest revision surgery rate (4.9%), and type 2 spines with PI-LL mismatch (11.06° ± 8.81°) had the highest revision surgery rate (22.6%), a four-fold difference (P = 0.013). The PI-LL mismatch did not change significantly in each type postoperatively (P > 0.05).

Conclusion.
We found that there may be a correlation between Roussouly type and revision surgery for ASD after L4-5 TLIF for spondylolisthesis, with type 2 spines having the highest rate. Spinopelvic parameters may also correlate with revision surgery for ASD after L4-5 TLIF.

Level of Evidence: 4