bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causes of Death Following Nonmetastatic Colorectal Cancer Diagnosis in the U.S.: A Population-Based Analysis
Authors: Afifi Ahmed M. , Elmehrath Ahmed O. , Ruhban Inas A. , Saad Anas M. , Gad Mohamed M. , Al-Husseini Muneer J. , Bekaii-Saab Tanios , Sonbol Mohamad Bassam 
Published: June 2021

Abstract

Introduction
Because of the improved colorectal cancer (CRC) survival in the U.S., patients may live long enough after CRC diagnosis to the point where non–cancer-related comorbidities may considerably impact their overall survival. In this study, we perform a long-term analysis of causes of death (CODs) following nonmetastatic CRC with respect to different demographic and tumor-related criteria.

Materials and Methods
We gained access to the Surveillance, Epidemiology, and End Results data to review patients diagnosed with nonmetastatic CRC during 2000–2015. We calculated standardized mortality ratios (SMRs) for each COD following CRC. SMRs represented the change of risk of a specific COD following CRC diagnoses when compared with the risk in the general U.S. population.

Results
We reviewed 302,345 patients, of whom 112,008 died during the study period. More deaths (68.3%) occurred within 5 years following nonmetastatic CRC diagnosis, with 76,486 deaths. CRC was the most common COD (51.4%) within 5 years of diagnosis followed by heart disease (15.2%) and other cancers (8.4%). As time passed after diagnosis, the number of CRC deaths decreased, and other noncancer causes increased to the point that after 10 years only 10.4% of deaths were attributed to CRC, 15.3% were attributed to other cancers, and 34.2% were secondary to heart disease.

Conclusion
Following nonmetastatic CRC diagnosis, most deaths remain secondary to CRC. Other causes, including other cancers and cardiovascular disease, represent a significant number of deaths, especially in the 5 years following initial CRC diagnosis. Our findings help guide counseling patients with CRC regarding future health risks.

Implications for Practice
Most common causes of death following nonmetastatic colorectal cancer (CRC) are heart diseases, other cancers, chronic obstructive pulmonary disease, and cerebrovascular diseases. Physicians should counsel patients regarding survivorship with cancer screening and focus on prevention of noncancer deaths. These findings should be considered by physicians who give care for survivors of nonmetastatic CRC.
Recent Advances in Pathology: the 2021 Annual Review Issue of The Journal of Pathology
Authors: Herrington C Simon , Poulsom Richard , Koeppen Hartmut , Coates Philip J 
Published: June 2021

AbstractThe 2021 Annual Review Issue of The Journal of Pathology contains 14 invited reviews on current research areas of particular importance in pathology. The subjects included here reflect the broad range of interests covered by the journal, including both basic and applied research fields but always with the aim of improving our understanding of human disease. This year, our reviews encompass the huge impact of the COVID‐19 pandemic, the development and application of biomarkers for immune checkpoint inhibitors, recent advances in multiplexing antigen/nucleic acid detection in situ, the use of genomics to aid drug discovery, organoid methodologies in research, the microbiome in cancer, the role of macrophage‐stroma interactions in fibrosis, and TGF‐β as a driver of fibrosis in multiple pathologies. Other reviews revisit the p53 field and its lack of clinical impact to date, dissect the genetics of mitochondrial diseases, summarise the cells of origin and genetics of sarcomagenesis, provide new data on the role of TRIM28 in tumour predisposition, review our current understanding of cancer stem cell niches, and the function and regulation of p63. The reviews are authored by experts in their field from academia and industry, and provide comprehensive updates of the chosen areas, in which there has been considerable recent progress. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Solvent‐Free CO2 Fixation Reaction Catalyzed by MOFs Composites Containing Polycarboxylic Acid Ligands
Authors: Tang Yihan , Chen Wang , Liu Ruoxi , Wang Leyao , Pan Yating , Bi Ruimin , Feng Xuejun , He Mingyang , Chen Qun , Zhang Zhihui 
Published: June 2021

AbstractMetal‐Organic Frameworks (MOFs) have been used to catalyze the conversion of CO2 to cyclic carbonates through cycloaddition reaction. A series of MOFs composites based on Cu‐BTC (H3BTC, 1,3,5‐Benzenetricarboxylic acid) were screened out by adjusting the ligands and loaded materials. Among them, Cu‐BTC@ZnFe2O4 achieved good yields in this reaction, and after several catalytic cycles, the yield also remained above 90 %. The larger the steric hindrance of epoxides used, the lower the yields of cycloaddition reaction. In addition, computational chemistry was used to explain this catalytic process. After adding the catalyst, the energy barrier of the initial step of the reaction was effectively reduced.
Radiographic and MRI characteristics of diffuse idiopathic skeletal hyperostosis in a cat presented with a painful chronic ambulatory paraparesis
Authors: Llanos Cesar , Rau Friederike , Uriarte Ane 
Published: June 2021

AbstractA 9‐year‐old, male neutered Maine Coon was presented with a several month chronic and progressive weakness in the pelvic limbs, difficulties jumping and increasing aggressiveness towards members of the family. A proprioceptive pelvic limb ataxia, ambulatory paraparesis with postural deficits in both pelvic limbs and severe spinal hyperaesthesia were observed during the neurological examination. Radiographs and magnetic resonance imaging (MRI) of the spine were compatible with diffuse idiopathic skeletal hyperostosis (DISH), chronic spinal cord compression and foraminal stenosis. Mild improvement of the general discomfort without neurological amelioration was seen following 5 months of conservative management. To the authors’ knowledge, this is the first case report describing the radiographic and MRI characteristics of DISH in a feline patient.
Reliability‐based topology optimization for offshore wind farm collection system
Authors: Pérez‐Rúa Juan‐Andrés , Lumbreras Sara , Ramos Andrés , Cutululis Nicolaos A. 
Published: June 2021

AbstractAn optimization framework for global optimization of the cable layout topology for offshore wind farm (OWF) is presented. The framework designs and compares closed‐loop and radial layouts for the collection system of OWFs. For the former, a two‐stage stochastic optimization program based on a mixed integer linear programming (MILP) model is developed, while for the latter, a hop‐indexed full binary model is used. The purpose of the framework is to provide a common base for assessing both designs economically, using the same underlying contingency treatment. A discrete Markov model is implemented for calculating the cable failure probability, useful for estimating the time under contingency for multiple power generation scenarios. The objective function supports simultaneous optimization of (i) initial investment (network topology and cable sizing), (ii) total electrical power loss costs and (iii) operation costs due to energy curtailment from cable failures. Constraints are added accounting for common engineering aspects. The applicability of the full method is demonstrated by tackling three differently sized real‐world OWFs. Results show that (i) the profitability of either topology type depends strongly on the project size and wind turbine rating. Closed loop may be a competitive solution for large‐scale projects where large amounts of energy are potentially curtailed. (ii) The stochastic model presents low tractability to tackle large‐scale instances, increasing the required computing time and memory resources. (iii) Strategies must be adopted in order to apply stochastic optimization for modern OWFs, intending analytically or numerically simplification of mathematical models.
Localization matters: nuclear-trapped Survivin sensitizes glioblastoma cells to temozolomide by elevating cellular senescence and impairing homologous recombination
Authors: Reich Thomas R. , Schwarzenbach Christian , Vilar Juliana Brandstetter , Unger Sven , Mühlhäusler Fabian , Nikolova Teodora , Poplawski Alicia , Baymaz H. Irem , Beli Petra , Christmann Markus , Tomicic Maja T. 
Published: June 2021

AbstractTo clarify whether differential compartmentalization of Survivin impacts temozolomide (TMZ)-triggered end points, we established a well-defined glioblastoma cell model in vitro (LN229 and A172) and in vivo, distinguishing between its nuclear and cytoplasmic localization. Expression of nuclear export sequence (NES)-mutated Survivin (SurvNESmut-GFP) led to impaired colony formation upon TMZ. This was not due to enhanced cell death but rather due to increased senescence. Nuclear-trapped Survivin reduced homologous recombination (HR)-mediated double-strand break (DSB) repair, as evaluated by γH2AX foci formation and qPCR-based HR assay leading to pronounced induction of chromosome aberrations. Opposite, clones, expressing free-shuttling cytoplasmic but not nuclear-trapped Survivin, could repair TMZ-induced DSBs and evaded senescence. Mass spectrometry-based interactomics revealed, however, no direct interaction of Survivin with any of the repair factors. The improved TMZ-triggered HR activity in Surv-GFP was associated with enhanced mRNA and stabilized RAD51 protein expression, opposite to diminished RAD51 expression in SurvNESmut cells. Notably, cytoplasmic Survivin could significantly compensate for the viability under RAD51 knockdown. Differential Survivin localization also resulted in distinctive TMZ-triggered transcriptional pathways, associated with senescence and chromosome instability as shown by global transcriptome analysis. Orthotopic LN229 xenografts, expressing SurvNESmut exhibited diminished growth and increased DNA damage upon TMZ, as manifested by PCNA and γH2AX foci expression, respectively, in brain tissue sections. Consequently, those mice lived longer. Although tumors of high-grade glioma patients expressed majorly nuclear Survivin, they exhibited rarely NES mutations which did not correlate with survival. Based on our in vitro and xenograft data, Survivin nuclear trapping would facilitate glioma response to TMZ.
Splicing and editing of ionotropic glutamate receptors: a comprehensive analysis based on human RNA-Seq data
Authors: Herbrechter Robin , Hube Nadine , Buchholz Raoul , Reiner Andreas 
Published: June 2021

AbstractIonotropic glutamate receptors (iGluRs) play key roles for signaling in the central nervous system. Alternative splicing and RNA editing are well-known mechanisms to increase iGluR diversity and to provide context-dependent regulation. Earlier work on isoform identification has focused on the analysis of cloned transcripts, mostly from rodents. We here set out to obtain a systematic overview of iGluR splicing and editing in human brain based on RNA-Seq data. Using data from two large-scale transcriptome studies, we established a workflow for the de novo identification and quantification of alternative splice and editing events. We detected all canonical iGluR splice junctions, assessed the abundance of alternative events described in the literature, and identified new splice events in AMPA, kainate, delta, and NMDA receptor subunits. Notable events include an abundant transcript encoding the GluA4 amino-terminal domain, GluA4-ATD, a novel C-terminal GluD1 (delta receptor 1) isoform, GluD1-b, and potentially new GluK4 and GluN2C isoforms. C-terminal GluN1 splicing may be controlled by inclusion of a cassette exon, which shows preference for one of the two acceptor sites in the last exon. Moreover, we identified alternative untranslated regions (UTRs) and species-specific differences in splicing. In contrast, editing in exonic iGluR regions appears to be mostly limited to ten previously described sites, two of which result in silent amino acid changes. Coupling of proximal editing/editing and editing/splice events occurs to variable degree. Overall, this analysis provides the first inventory of alternative splicing and editing in human brain iGluRs and provides the impetus for further transcriptome-based and functional investigations.
Definition und Behandlung der A.-mesenterica-superior-Revaskularisations- und -Dissektions-assoziierten Diarrhö (SMARD-Syndrom) in Deutschland
Authors: Téoule Patrick , Tombers Katharina , Rahbari Mohammad , Sandra-Petrescu Flavius , Keese Michael , Rahbari Nuh N. , Reißfelder Christoph , Rückert Felix 
Published: June 2021

Zusammenfassung
Hintergrund
Die A. mesenterica superior (AMS) wird im Rahmen von Pankreasresektionen (PR) und mesenterialen Gefäßeingriffen (MG) freigelegt und disseziert. Eine dadurch entstandene Schädigung des umliegenden ex- und intrinsischen vegetativen Nervenplexus kann zu einer passageren oder therapierefraktären Diarrhö führen.

Fragestellung
Die vorliegende Studie soll einen Überblick über den derzeitigen Stellenwert der AMS-Revaskularisations- und -Dissektions-assoziierten Diarrhö („superior mesenteric artery revascularisation and dissection-associated diarrhea“[SMARD]-Syndrom) in Deutschland geben.

Material und Methoden
Nach selektiver Literaturrecherche (SLR) mit der Fragestellung, ob und wie häufig eine postoperativ neu aufgetretene Diarrhö nach PR und MG vorkommt, wurde eine Onlineumfrage versendet.

Ergebnisse
Die SLR (n = 4) bestätigte, dass eine postoperativ neu aufgetretene Diarrhö eine häufige Komplikation nach Präparation zur Revaskularisation (RV) bzw. Dissektion (DIS) der AMS ist (Inzidenz ca. 62 %). Therapierefraktäre Verläufe sind selten 14 %. 54 von 159 Zentren beteiligten sich an der Umfrage. 63 % gaben an, eine AMS-RV/-DIS im Rahmen von PR oder MG durchzuführen. Der Durchschnitt an PR pro Zentrum lag 2018 bei 47 und bei 49 im Jahr 2019. Fünf MG erfolgten durchschnittlich in beiden Jahren pro Zentrum. Drei Patienten litten durchschnittlich am SMARD-Syndrom.

Diskussion
Diese Umfrage erfasst erstmals den derzeitigen Stellenwert des SMARD-Syndroms in Deutschland. Bisher fehlen Empfehlungen zur Therapie einer solchen Diarrhö. Die Ergebnisse zeigen, dass zunächst eine symptomatische Therapie erfolgen sollte. Aufgrund der Komplexität der Pathophysiologie sind kausale Therapieansätze bislang nicht entwickelt.
Integration of Formal Proof into Unified Assurance Cases with Isabelle/SACM
Authors: Foster Simon , Nemouchi Yakoub , Gleirscher Mario , Wei Ran , Kelly Tim 
Published: June 2021

Abstract
Assurance cases are often required to certify critical systems. The use of formal methods in assurance can improve automation, increase confidence, and overcome errant reasoning. However, assurance cases can never be fully formalised, as the use of formal methods is contingent on models that are validated by informal processes. Consequently, assurance techniques should support both formal and informal artifacts, with explicated inferential links between them. In this paper, we contribute a formal machine-checked interactive language, called Isabelle/SACM, supporting the computer-assisted construction of assurance cases compliant with the OMG Structured Assurance Case Meta-Model. The use of Isabelle/SACM guarantees well-formedness, consistency, and traceability of assurance cases, and allows a tight integration of formal and informal evidence of various provenance. In particular, Isabelle brings a diverse range of automated verification techniques that can provide evidence. To validate our approach, we present a substantial case study based on the Tokeneer secure entry system benchmark. We embed its functional specification into Isabelle, verify its security requirements, and form a modular security case in Isabelle/SACM that combines the heterogeneous artifacts. We thus show that Isabelle is a suitable platform for critical systems assurance.
Autologous semitendinosus tendon graft could function as a meniscal transplant
Authors: Rönnblad Erik , Rotzius Pierre , Eriksson Karl 
Published: June 2021

Abstract
Purpose
Meniscectomy results in poor knee function and increased risk for osteoarthritis. Meniscal allograft transplantation is not widely used due to costs and availability. The semitendinosus tendon (ST) has the potential to remodel and revascularize in an intraarticular environment, such as ACL reconstruction. The objective for this pilot study was to investigate whether the ST graft could function as a meniscal transplant.

Methods
The ST was doubled and sutured with running sutures and pull-out sutures in each end. Bone tunnels were used for root anchorage and the graft was sutured with allinside, inside-out and outside-in technique. The pull-out sutures were fixed over a button. Partial weight bearing was allowed with limited range of motion in a brace for the first 6 weeks. Evaluation was assessed using clinical examination, radiology and patient reported outcome.

Results
A total of seven patients have been included between January 2018 and June 2020. Six medial transplants and one lateral transplant were performed. Mean age was 29 years. Four patients had completed the 12-month follow-up. Improvements were noted for IKDC Global Score, KOOS pain subscale and Lysholm. MRI indicated that the transplant become more wedge-like with visible roots and minor protrusion.

Conclusions
Even though this is primarily a technical report the follow-up data indicate that the transplant survives and adapts in shape and capabilities to an original meniscus. There were no adverse events and the patients seem to improve in terms of pain and quality of life.
Cognitive capabilities for the CAAI in cyber-physical production systems
Authors: Strohschein Jan , Fischbach Andreas , Bunte Andreas , Faeskorn-Woyke Heide , Moriz Natalia , Bartz-Beielstein Thomas 
Published: June 2021

AbstractThis paper presents the cognitive module of the Cognitive Architecture for Artificial Intelligence (CAAI) in cyber-physical production systems (CPPS). The goal of this architecture is to reduce the implementation effort of artificial intelligence (AI) algorithms in CPPS. Declarative user goals and the provided algorithm-knowledge base allow the dynamic pipeline orchestration and configuration. A big data platform (BDP) instantiates the pipelines and monitors the CPPS performance for further evaluation through the cognitive module. Thus, the cognitive module is able to select feasible and robust configurations for process pipelines in varying use cases. Furthermore, it automatically adapts the models and algorithms based on model quality and resource consumption. The cognitive module also instantiates additional pipelines to evaluate algorithms from different classes on test functions. CAAI relies on well-defined interfaces to enable the integration of additional modules and reduce implementation effort. Finally, an implementation based on Docker, Kubernetes, and Kafka for the virtualization and orchestration of the individual modules and as messaging technology for module communication is used to evaluate a real-world use case.
Second-generation antipsychotic use during pregnancy and risk of congenital malformations
Authors: Ellfolk Maria , Leinonen Maarit K. , Gissler Mika , Kiuru-Kuhlefelt Sonja , Saastamoinen Leena , Malm Heli 
Published: June 2021

Abstract
Purpose

To study if second-generation antipsychotic (S-GA) use during the first trimester of pregnancy is associated with an increased risk of major congenital malformations (MCM).

Methods
A population-based birth cohort study using national register data extracted from the Drugs and Pregnancy database in Finland, years 1996–2017. The sampling frame included 1,273,987 pregnant women. We included singleton pregnancies ending in live or stillbirth or termination of pregnancy due to severe malformation. Pregnancies with exposure to known teratogens were excluded. Women were categorized into three groups: exposed to S-GAs (n = 3478), exposed to first-generation antipsychotics (F-GAs) (n = 1030), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 22,540). We excluded genetic conditions and compared the prevalence of MCMs in S-GA users to the two comparison groups using multiple logistic regression models.

Results
Use of S-GAs during early pregnancy was not associated with an increased risk of overall MCMs compared to unexposed (adjusted odds ratio, OR 0.92; 95% CI 0.72–1.19) or to F-GA users (OR 0.82; 95% CI 0.56–1.20). Of individual S-GAs, olanzapine use was associated with an increased risk of overall MCMs (OR 2.12; 95% CI 1.19–3.76), and specifically, an increased risk of musculoskeletal malformations (OR 3.71; 95% CI 1.35–10.1) when compared to unexposed, while comparisons to F-GA users did not show significant results.

Conclusions
Olanzapine use is associated with an increased risk of major congenital malformations and specifically, musculoskeletal malformations. Use during pregnancy should be restricted to situations where no safer alternatives exist.
Application of experimental data to model local fouling resistances
Authors: Schlüter Florian , Augustin Wolfgang , Scholl Stephan 
Published: June 2021

AbstractFouling is a problem that varies in space and time, but a fouling situation is commonly quantified using the integral thermal fouling resistance based on the integral heat balance and an area-averaged heat transfer assessment. However, current modeling does not take into consideration the local differences, such as constrictions, that can affect the integral fluid dynamic behavior. This work shows experimental and analytical results of local investigations of a fouled counterflow double-pipe heat exchanger. The determined local parameters are used to calculate different local fouling resistances as part of a holistic modeling approach with the aim of modeling and linking local and integral fouling resistances as well as the thermal and the mass based approaches. Therefore, mass based parameters are utilized to recalculate the obtained local thermal fouling resistances as a way to account for the heat transfer increases caused by local surface roughness and/or local constrictions. The aim of this procedure is to explain and eliminate apparent negative fouling resistances on a local basis. The local thermal fouling resistances are determined by measuring the local temperatures and then used for quantification of the local overall heat transfer coefficients. Modeling of the local mass based fouling resistances requires knowledge of the density and thermal conductivity of the local material, as well as the local layer thickness and/or the local fouling mass. The local thermal fouling resistances are recalculated using the local friction coefficients and local flow velocities resulting from local constrictions. All experimental and theoretical approaches are merged into the model presented here for the determination of local fouling resistances.