bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis of post-transplant lymphoproliferative disorders after solid organ and hematopoietic stem cell transplantation reveals differences in the tumor microenvironment
Authors: Overkamp Mathis , Granai Massimo , Bonzheim Irina , Steinhilber Julia , Schittenhelm Jens , Bethge Wolfgang , Quintanilla-Martinez Leticia , Fend Falko , Federmann Birgit 
Published: December 2020

AbstractPost-transplant lymphoproliferative disorders (PTLD) occur after solid organ transplantation (SOT) or hematopoietic stem cell transplantation (HCT) and are frequently associated with Epstein-Barr virus (EBV). Because of the complex immune setup in PTLD patients, the tumor microenvironment (TME) is of particular interest to understand PTLD pathogenesis and elucidate predictive factors and possible treatment options. We present a comparative study of clinicopathological features of 48 PTLD after HCT (n= 26) or SOT (n= 22), including non-destructive (n= 6), polymorphic (n= 23), and monomorphic (n= 18) PTLD and classic Hodgkin lymphoma (n= 1). EBV was positive in 35 cases (73%). A detailed examination of the TME with image analysis-based quantification in 22 cases revealed an inflammatory TME despite underlying immunosuppression and significant differences in its density and composition depending on type of transplant, PTLD subtypes, and EBV status. Tumor-associated macrophages (TAMs) expressing CD163 (p= 0.0022) and Mannose (p= 0.0016) were enriched in PTLD after HCT. Double stains also showed differences in macrophage polarization, with more frequent M1 polarization after HCT (p= 0.0321). Higher counts for TAMs (CD163 (p= 0.0008) and cMaf (p= 0.0035)) as well as in the T cell compartment (Granzyme B (p= 0.0028), CD8 (p= 0.01), and for PD-L1 (p= 0.0305)) were observed depending on EBV status. In conclusion, despite the presence of immunosuppression, PTLD predominantly contains an inflammatory TME characterized by mostly M1-polarized macrophages and cytotoxic T cells. Status post HCT, EBV positivity, and polymorphic subtype are associated with an actively inflamed TME, indicating a specific response of the immune system. Further studies need to elucidate prognostic significance and potential therapeutic implications of the TME in PTLD.
Immunotherapy and vaccination against infectious diseases
Authors: Ebbers Meinolf , Hemmer Christoph J. , Müller-Hilke Brigitte , Reisinger Emil C. 
Published: December 2020

SummaryDue to the overuse of antibiotics, infections, in particular those caused by multidrug-resistant bacteria, are becoming more and more frequent. Despite the worldwide introduction of antibiotic therapy, vaccines and constant improvements in hygiene, the burden of multidrug-resistant bacterial infections is increasing and is expected to rise in the future. The development of monoclonal therapeutic antibodies and specific immunomodulatory drugs represent new treatment options in the fight against infectious diseases. This article provides a brief overview of recent advances in immunomodulatory therapy and other strategies in the treatment of infectious disease.
Extracranial dose and the risk of radiation-induced malignancy after intracranial stereotactic radiosurgery: is it time to establish a therapeutic reference level?
Authors: Paddick Ian , Cameron A. , Dimitriadis A. 
Published: December 2020

Abstract
Background
To measure extracranial doses from Gamma Knife Perfexion (GKP) intracranial stereotactic radiosurgery (SRS) and model the risk of malignancy after SRS for different treatment platforms.

Methods
Doses were measured for 20 patients undergoing SRS on a GKP at distances of 18, 43 and 75 cm from the target, corresponding to the approximate positions of the thyroid, breast and gonads respectively. A literature review was conducted to collect comparative data from other radiosurgery platforms. All data was used to calculate the dose to body organs. The National Cancer Institute (NCI) RadRAT calculator was used to estimate excess lifetime cancer risk from this exposure. Five different age groups covering childhood and younger adults were modelled for both sexes.

Results
Extracranial doses delivered during SRS with the GKP were a median 0.04%, 0.008% and 0.002% of prescription dose at 18 cm, 43 cm and 70 cm from the isocentre respectively. Comparison with the literature revealed that the extracranial dose was lowest from GKP, then linacs equipped with micro-multileaf collimators (mMLC), then linacs equipped with circular collimators (cones), and highest from Cyberknife (CK). Estimated lifetime risks of radiation-induced malignancy in the body for patients treated with SRS aged 5–45 years were 0.03–0.88%, 0.36–11%, 0.61–18% and 2.2–39% for GKP, mMLC, cones and CK respectively.

Conclusions
We have compared typical extracranial doses from different platforms and quantified the lifetime risk of radiation-induced malignancy. The risk varies with platform. This should be taken into account when treating children and young adults with SRS. The concept of a therapeutic reference level (TRL), similar to the diagnostic reference level (DRL) established in radiology, is proposed.
Maßnahmengesetzvorbereitungsgesetz und weitere Überlegungen zur Beschneidung des Umweltrechtsschutzes
Authors: Guckelberger Annette 
Published: December 2020

ZusammenfassungDer Beitrag beleuchtet die Bestrebungen zur Beschneidung des Umweltrechtsschutzes durch das Maßnahmengesetzvorbereitungsgesetz
sowie zu einer möglichen Rückkehr zur materiellen Präklusion vor dem Hintergrund des Unionsrechts
und der Aarhus-Konvention.
Identification of peat type and humification by laboratory VNIR/SWIR hyperspectral imaging of peat profiles with focus on fen-bog transition in aapa mires
Authors: Granlund L. , Keinänen M. , Tahvanainen T. 
Published: December 2020

AbstractAimsHyperspectral imaging (HSI) has high potential for analysing peat cores, but methodologies are deficient. We aimed for robust peat type classification and humification estimation. We also explored other factors affecting peat spectral properties.MethodsWe used two laboratory setups: VNIR (visible to near-infrared) and SWIR (shortwave infrared) for high resolution imaging of intact peat profiles with fen-bog transitions. Peat types were classified with support vector machines, indices were developed for von Post estimation, and K-means clustering was used to analyse stratigraphic patterns in peat quality. With separate experiments, we studied spectral effects of drying and oxidation.ResultsDespite major effects, oxidation and water content did not impede robust HSI classification. The accuracy betweenCarexpeat andSphagnumpeat in validation was 80% with VNIR and 81% with SWIR data. The spectral humification indices had accuracies of 82% with VNIR and 56%. Stratigraphic HSI patterns revealed that 36% of peat layer shifts were inclined by over 20 degrees. Spectral indices were used to extrapolate visualisations of element concentrations.ConclusionsHSI provided reliable information of basic peat quality and was useful in visual mapping, that can guide sampling for other analyses. HSI can manage large amounts of samples to widen the scope of detailed analysis beyond single profiles and it has wide potential in peat research beyond the exploratory scope of this paper. We were able to confirm the capacity of HSI to reveal shifts of peat quality, connected to ecosystem-scale change.
Advances in Knowledge of Androgens: How Intentional and Accidental Neurosteroid Changes Inform Us of Their Action and Role
Authors: Frye Cheryl A. , DaCosta Dan , Lembo Vincenzo F. , Walf Alicia A. 
Published: December 2020

AbstractPurpose of ReviewHere, we summarize current knowledge of androgens’ action gained over the recent years.Recent FindingsNeurosteroids are produced in the brain and peripheral nerves, independent of endocrine glands have been investigated for how they are regulated, and have actions via non-steroid receptor targets to mediate social, affective, and cognitive behavior and to protect the brain. Androgens’ organizing actions in the peri-natal period have effects throughout the lifetime that may be recapitulated later in life during critical periods and at times of challenge. Developmental changes in androgens occur during mid-childhood, adrenarche, puberty, adolescence, young adulthood, middle age, and andropause. Changes in androgens with a 5α-reductase inhibitor, such as finasteride, result in disruptions in organizational and activational functions of androgens that can be unremitting.SummaryNormal developmental or perturbation in androgens through other means can cause changes in androgen-sensitive phenotypes throughout the lifespan, in part through actions of neurosteroids.
Systems modelling to support the complex nature of healthcare services
Authors: Engelseth Per , White B. E. , Mundal Ingunn , Eines Trude Fløystad , Kritchanchai Duangpun 
Published: December 2020

AbstractHealthcare is a service commonly associated with lacking performance in relation to output and the economy of production. Contingency theory and complex systems thinking are approaches here combined to study the logistics of healthcare service flows. Contingency theory directs attention to networked interdependencies while complex systems thinking concerns process emergence and flexible resource use in supporting logistics. This hybrid form of analysis gives conceptual direction to information technology development and use to support the logistics of healthcare services. Three small examples of healthcare service as logistics processes in their as-is state are provided and analysed based on the developed analytical framework. These illustrate in detail what exemplifies complexity in this industry. Given the inherently complex nature of many types of healthcare services, this discussion concerns how to conceptually model information systems in healthcare services as a complex system. This chosen complexity-sensitive approach of service logistics constitutes a basis for information technology enabled healthcare service development sensitive to this type of service provision directing focus to the emergent features of healthcare service needs. It is also a basis for further investigation into this topic of information technology use to support the inherent logistical complexity of healthcare services.
The Risk of Generating Technical Debt Interest: A Case Study
Authors: Digkas Georgios , Ampatzoglou Apostolos , Chatzigeorgiou Alexander , Avgeriou Paris , Matei Oliviu , Heb Robert 
Published: December 2020

AbstractTechnical Debt (TD) interest refers to the extra maintenance costs incurred by the very existence of TD items in a system. The generation of TD interest can make or break a system: too little interest and the effect of TD is negligible; too much interest and the system becomes unsustainable. In this paper, we consider the generation of interest as a risk and present a metric to quantify this risk. Subsequently, we validate this metric in two ways. First, we explore whether the metric can be effectively used to prioritize TD remediation. Second, we investigate if adding new code reduces the risk of interest generation. The results of the study suggest that: (a) the proposed risk management metric is capable of efficiently prioritizing TD items; and (b) that the new code that is introduced in the system is usually less risky for producing interest, compared to legacy code.
Exploring the Relation Between Co-changes and Architectural Smells
Authors: Sas Darius , Avgeriou Paris , Kruizinga Ronald , Scheedler Ruben 
Published: December 2020

AbstractThe interplay between Maintainability and Reliability can be particularly complex and different kinds of trade-offs may arise when developers try to optimise for either one of these two qualities. To further understand how Maintainability and Reliability influence each other, we perform an empirical study using architectural smells and source code file co-changes as proxies for these two qualities, respectively. The study is designed using an exploratory multiple-case case study following well-know guidelines and using fourteen open source Java projects. Three different research questions are identified and investigated through statistical analysis. Co-changes are detected by using both a state-of-the-art algorithm and a novel approach. The three architectural smells selected are among the most important from the literature and are detected using open source tools. The results show that 50% of co-changes eventually end up taking part in an architectural smell. Moreover, statistical tests indicate that in 50% of the projects, files and packages taking part in smells are more likely to co-change than non-smelly files. Finally, co-changes were also found to appear before smells 90% of the times a smell and a co-change appear in the same file pair. Our findings show that Reliability is indirectly affected by low levels of Maintainability even at the architectural level. This is because low-quality components require more frequent changes by the developers, increasing chances to eventually introduce faults.
A novel method to rapidly calculate the urea clearance index and urea reduction rate based on parameters obtained during hemodialysis
Authors: Yang Yue , Chen Jia , Wang Wei , Zhang Yu‐Mei , Li Wen‐Ge 
Published: December 2020

AbstractBackgroundThe efficacy of hemodialysis (HD) is closely associated with patient survival time and quality of life. The classical method (CLM) to calculate the urea clearance index (Kt/V) and urea reduction rate (URR) requires multiple blood tests. A novel method that may be used as a noninvasive alternative to CLM is required.MethodsBased on the urea kinetic model, a new method, named the “assessment method” (ASM), was established to calculate blood urea nitrogen after HD, based on parameters obtained during HD. The consistency of the Kt/V and URR values between the ASM and CLM was evaluated in 41 patients from the China–Japan Friendship Hospital between September 2017 and December 2018.ResultsForty‐one patients (24 males and 17 females; mean age, 55.7 ± 14.2 years) undergoing regular HD in our hospital were randomly selected for this study. The blood flow rate was 244.5 ± 19.6 mL/min and the dialysate flow rate was 500 mL/min. We obtained Kt/V (CLM = 1.40 ± 0.06, ASM = 1.37 ± 0.07) and URR (CLM = 68.6 ± 6.4%, ASM = 67.7 ± 7.2%) values. Paired t‐test indicated no significant differences between the ASM‐ and CLM‐derived values. The intraclass correlation coefficients were 0.907 and 0.916 for Kt/V and URR, respectively. Similarly, Bland–Altman plots suggested good concordance between the 2 methods.ConclusionsThe Kt/V and URR values calculated using the ASM and CLM were in significant agreement, and both can be used to effectively assess the adequacy of HD in patients undergoing maintenance HD. The ASM is an effective, rapid, inexpensive, and noninvasive alternative to the CLM for obtaining Kt/V and URR values. The ASM has good potential for clinical application, particularly for patients in areas of low socioeconomic status.
Gerrymandering and Compactness: Implementation Flexibility and Abuse
Authors: Barnes Richard , Solomon Justin 
Published: December 2020

AbstractPolitical districts may be drawn to favor one group or political party over another, or gerrymandered. A number of measurements have been suggested as ways to detect and prevent such behavior. These measures give concrete axes along which districts and districting plans can be compared. However, measurement values are affected by both noise and the compounding effects of seemingly innocuous implementation decisions. Such issues will arise for any measure. As a case study demonstrating the effect, we show that commonly used measures of geometric compactness for district boundaries are affected by several factors irrelevant to fairness or compliance with civil rights law. We further show that an adversary could manipulate measurements to affect the assessment of a given plan. This instability complicates using these measurements as legislative or judicial standards to counteract unfair redistricting practices. This paper accompanies the release of packages in C++, Python, and R that correctly, efficiently, and reproducibly calculate a variety of compactness scores.
Transferrin receptor (TFRC) is essential for meiotic progression during mouse spermatogenesis
Authors: Gao Tingting , Lin Meng , Wu Yangyang , Li Kai , Liu Chenchen , Zhou Quan , Shen Cong , Zheng Bo , Huang Xiaoyan 
Published: December 2020

SummaryMeiosis is a highly conserved process, and is responsible for the production of haploid gametes and generation of genetic diversity. We previously identified the transferrin receptor (TFRC) in the proteome profile of mice neonatal testes, indicating the involvement of the TFRC in meiosis. However, the exact molecular role of the TFRC in meiosis remains unclear. In this study, we aimed to determine the function of the TFRC in neonatal testicular development by TFRC knockdown using the testis culture platform. Our results showed high TFRC expression in 2-week testes, corresponding to the first meiotic division. Targeting TFRC using morpholino oligonucleotides resulted in clear spermatocyte apoptosis. In addition, we used the chromosomal spread technique to show that a deficiency of TFRC caused the accumulation of leptotene and zygotene spermatocytes, and a decrease of pachytene spermatocytes, indicating early meiotic arrest. Moreover, the chromosomes of TFRC-deficient pachytene spermatocytes displayed sustained γH2AX association, as well as SYCP1/SYCP3 dissociation beyond the sex body. Therefore, our results demonstrated that the TFRC is essential for the progression of spermatocyte meiosis, particularly for DNA double-stranded break repair and chromosomal synapsis.
The map of cognitive processes in boredom: multiple mediation models
Authors: Milea Ion , Cardoş Roxana A.I. , David Daniel 
Published: December 2020

AbstractBackground:Trait boredom is associated with several internalizing and externalizing problems. Addressing existing research gaps in the field, the present study investigated the map of cognitive processes for boredom, based on the rational emotive behaviour therapy model (REBT).Aims:The general aim of the study was to investigate the organization of irrational and rational evaluative cognitions related to boredom, and the association between boredom and depression symptoms and state/trait anxiety.Methods:The 233 participants (84% women) completed online scales of evaluative cognitions, trait boredom, trait/state anxiety and depression. Multiple mediation models via the SPSS extension PROCESS were employed.Results:The REBT psychopathology and psychological health models were partially confirmed, as the evaluative primary cognitions predicted positively and significantly the secondary ones in both cases. Low frustration tolerance (LFT) and global evaluations (GE), and frustration tolerance (FT), respectively, had significant effects. We found a positive significant association between boredom proneness and the negative dysfunctional emotions investigated.Conclusions:Both results offer further support for the hierarchy of cognitions and the distinction between the level of irrationality and rationality in REBT. This is the first attempt to assess a cognitive map of boredom, underlining the importance of (L)FT in relation to boredom. The significance of GE in boredom suggests that people might see themselves responsible, or even blame themselves, others or life itself while bored. The associations of boredom with anxiety and depression are relevant, as its role in those contexts is not yet fully understood.
Combined Modeling of US Fluvial, Pluvial, and Coastal Flood Hazard Under Current and Future Climates
Authors: Bates Paul D. , Quinn Niall , Sampson Christopher , Smith Andrew , Wing Oliver , Sosa Jeison , Savage James , Olcese Gaia , Neal Jeff , Schumann Guy , Giustarini Laura , Coxon Gemma , Porter Jeremy R. , Amodeo Mike F. , Chu Ziyan , Lewis‐Gruss Sharai , Freeman Neil B. , Houser Trevor , Delgado Michael , Hamidi Ali , Bolliger Ian , E. McCusker Kelly , Emanuel Kerry , Ferreira Celso M. , Khalid Arslaan , Haigh Ivan D. , Couasnon Anaïs , E. Kopp Robert , Hsiang Solomon , Krajewski Witold F. 
Published: December 2020

AbstractThis study reports a new and significantly enhanced analysis of US flood hazard at 30 m spatial resolution. Specific improvements include updated hydrography data, new methods to determine channel depth, more rigorous flood frequency analysis, output downscaling to property tract level, and inclusion of the impact of local interventions in the flooding system. For the first time, we consider pluvial, fluvial, and coastal flood hazards within the same framework and provide projections for both current (rather than historic average) conditions and for future time periods centered on 2035 and 2050 under the RCP4.5 emissions pathway. Validation against high‐quality local models and the entire catalog of FEMA 1% annual probability flood maps yielded Critical Success Index values in the range 0.69–0.82. Significant improvements over a previous pluvial/fluvial model version are shown for high‐frequency events and coastal zones, along with minor improvements in areas where model performance was already good. The result is the first comprehensive and consistent national‐scale analysis of flood hazard for the conterminous US for both current and future conditions. Even though we consider a stabilization emissions scenario and a near‐future time horizon, we project clear patterns of changing flood hazard (3σ changes in 100 years inundated area of −3.8 to +16% at 1° scale), that are significant when considered as a proportion of the land area where human use is possible or in terms of the currently protected land area where the standard of flood defense protection may become compromised by this time.
Genetic architecture of host proteins involved in SARS-CoV-2 infection
Authors: Pietzner Maik , Wheeler Eleanor , Carrasco-Zanini Julia , Raffler Johannes , Kerrison Nicola D. , Oerton Erin , Auyeung Victoria P. W. , Luan Jian’an , Finan Chris , Casas Juan P. , Ostroff Rachel , Williams Steve A. , Kastenmüller Gabi , Ralser Markus , Gamazon Eric R. , Wareham Nicholas J. , Hingorani Aroon D. , Langenberg Claudia 
Published: December 2020

AbstractUnderstanding the genetic architecture of host proteins interacting with SARS-CoV-2 or mediating the maladaptive host response to COVID-19 can help to identify new or repurpose existing drugs targeting those proteins. We present a genetic discovery study of 179 such host proteins among 10,708 individuals using an aptamer-based technique. We identify 220 host DNA sequence variants acting in cis (MAF 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links and evidence that putative viral interaction partners such as MARK3 affect immune response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and detailed interrogation of results is facilitated through an interactive webserver (https://omicscience.org/apps/covidpgwas/).