bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Yeast RNAP I Transcription of Nucleosomal Templates In Vitro
Authors: Merkl Philipp E. , Schächner Christopher , Pilsl Michael , Schwank Katrin , Hergert Kristin , Längst Gernot , Milkereit Philipp , Griesenbeck Joachim , Tschochner Herbert 
Published: July 2022

AbstractNuclear eukaryotic RNA polymerases (RNAPs) transcribe a chromatin template in vivo. Since the basic unit of chromatin, the nucleosome, renders the DNA largely inaccessible, RNAPs have to overcome the nucleosomal barrier for efficient RNA synthesis. Gaining mechanistical insights in the transcription of chromatin templates will be essential to understand the complex process of eukaryotic gene expression. In this article we describe the use of defined in vitro transcription systems for comparative analysis of highly purified RNAPs I–III from S. cerevisiae (hereafter called yeast) transcribing in vitro reconstituted nucleosomal templates. We also provide a protocol to study promoter-dependent RNAP I transcription of purified native 35S ribosomal RNA (rRNA) gene chromatin.
Structural Studies of Eukaryotic RNA Polymerase I Using Cryo-Electron Microscopy
Authors: Pilsl Michael , Engel Christoph 
Published: July 2022

AbstractTechnical advances have pushed the resolution limit of single-particle cryo-electron microscopy (cryo-EM) throughout the past decade and made the technique accessible to a wide range of samples. Among them, multisubunit DNA-dependent RNA polymerases (Pols) are a prominent example. This review aims at briefly summarizing the architecture and structural adaptations of Pol I, highlighting the importance of cryo-electron microscopy in determining the structures of transcription complexes.
Physician-Assisted Suicide, Euthanasia, and Bioethics in Nazi and Contemporary Cinema
Authors: Rubenfeld Sheldon , Sulmasy Daniel P. 
Published: July 2022

AbstractToday, physician-assisted suicide and/or euthanasia are legal in several European countries, Canada, several jurisdictions in the United States and Australia, and may soon become legal in many more jurisdictions. While traditional Hippocratic and religious medical ethics have long opposed these practices, contemporary culture and politics have slowly weakened opposition to physician-assisted suicide and euthanasia. Our chapter examines how assisted suicide and euthanasia have been presented in cinema, one of the most powerful influences on culture, by Nazi propagandists during the German Third Reich and by Western filmmakers since the end of World War II.Almost all contemporary films about assisted suicide and euthanasia, including six winners of Academy Awards, promote these practices as didIch klage an(I Accuse) (1941), the best and archetypal Nazi feature film about euthanasia. The bioethical justifications of assisted suicide or euthanasia in bothIch klage anand contemporary films are strikingly similar: showing mercy; avoiding fear and/or disgust; equating loss of capability with loss of a reason to live; enabling self-determination and the right-to-die; conflating voluntary with involuntary and nonvoluntary euthanasia; and casting opposition as out-of-date traditionalism. Economics and eugenics, two powerful arguments for euthanasia during the Third Reich, are not highlighted inIch klage anand are only obliquely mentioned in contemporary cinema. One dramatic difference in the cinema of the two periods is the prominence of medical professionals inIch klage anand their conspicuous absence in contemporary films about assisted suicide and euthanasia. A discussion of the medical ethos of the two time periods reveals how cinema both reflects and influences the growing acceptance of assisted suicide and euthanasia.
From the Nuremberg “Doctors’ Trial” to the “Nuremberg Code”
Authors: Weindling Paul 
Published: July 2022

AbstractGuidelines on permissible clinical experiments were pronounced by the judges on August 19, 1947 at the close of the Nuremberg Medical Trial (NMT). Yet these guidelines were called the “Nuremberg Code” only starting in 1963, implying that only then were the guidelines invested with status as a fundamental bioethics document on proper research procedure. The aim of this chapter is to correct some misconceptions concerning the origins and implications of these guidelines. The first misconception is that the Code arose solely from courtroom proceedings. This misconception overlooks how during the post-war Allied liberation of Europe, victims of research and liberated prisoner doctors made a profound impression on Allied scientific intelligence officers. The second misconception is that the Code introduced the term “informed consent.” However, although the judges stressed the autonomy of the research subject and the obligation to inform subjects about potential risks, the term did not appear in the guidelines of 1947. The third misconception is that the Code was not widely known until 1963. Yet, the principles promulgated by the judges received extensive publicity even before the guideline’s official naming as the “Nuremberg Code.”
The Role of Professions in a State: The Effects of the Nazi Experience on Health Care Professionalism
Authors: Baker Robert , Wynia Matthew K. 
Published: July 2022

AbstractThis paper reviews three competing ways of organizing health care delivery—professionalism, consumerism and statism—and explores how Germany’s exclusively statist model facilitated the ascendency of an alternative Nazi medical ethics predicated on eugenic conceptions of national “race hygiene.” The primary obligation of health care personnel became using their skills and knowledge to achieve the aims of the Nazi state, which justified forcible eugenic sterilization programs, and then the killing of children and adults with mental or physical disabilities and, eventually, the medicalized mass murder of other groups seen to pose a genetic threat to the health of the state, such as homosexuals, Jews, and Roma. The evolving international response to these medical crimes would come to affect medical professional approaches to virtually every issue in contemporary Bioethics, from abortion to xenotransplantation. In the early post-war years, news of German health care professionals’ participation in these actions shocked fellow health care professionals. Many denied these accounts, some defended German researchers, others dismissed the Germans’ justifications of their actions as madness parading as medicine or medical ethics. Ultimately, however, reformers seeking to remedy or prevent actions reminiscent of Nazi medicine created the foundational documents of modern health care professional ethics and the new field of Bioethics. These are the Nuremberg Code, the Declaration of Geneva, and the Belmont Report. In firmly rejecting Nazi medical ethics, these documents emphasize the rights of autonomous individuals, with health professionals serving as their agents, thus cementing modern ideals of health care professionalism.
Quantitation of methotrexate polyglutamates in human whole blood, erythrocytes and leukocytes collected via venepuncture and volumetric absorptive micro-sampling: a green LC–MS/MS-based method
Authors: Daraghmeh Dala N. , Moghaddami Mahin , Bobrovskaya Larisa , Proudman Susanna M. , Wiese Michael D. 
Published: July 2022

AbstractLow-dose methotrexate (MTX) plays a key role in treatment of rheumatoid arthritis. However, not all patients respond satisfactorily, and no therapeutic drug monitoring has been implemented in clinical practice, despite the fact that MTX therapy has now been available for decades. Analysis of individual intracellular MTX metabolites among rheumatoid arthritis (RA) patients is hampered by the low intracellular concentrations of MTX-PGs which require a highly sensitive method to quantify. Here, we present a rapid and highly sensitive LC (HILIC) MS/MS method with LLOQ 0.1 nM, 0.8 nmol/L for each metabolite of MTX-PG1-5 and MTX-PG6-7 respectively. Over a linear range of 0.1–100 nM, 0.8–100 nmol/L for each metabolite of MTX-PG1-5 and MTX-PG6-7, respectively, the inter- and intra- accuracy and precision were within 15% of the nominal value for all MTX metabolites. The presented assay was used to assess and compare MTX metabolite concentrations extracted from four different matrices: red blood cells, plasma, peripheral blood mononuclear cells, and whole blood that have been collected either using traditional venepuncture or volumetric absorptive micro-sampling (VAMS) sampling techniques. The presented method not only improves analyte coverage and sensitivity as compared to other published methods; it also improves the greenness.
Graphical abstract
Accurate staging of non-metastatic colon cancer with CT: the importance of training and practice for experienced radiologists and analysis of incorrectly staged cases
Authors: van de Weerd S. , Hong E. , van den Berg I. , Wijlemans J. W. , van Vooren J. , Prins M. W. , Wessels F. J. , Heeres B. C. , Roberti S. , Nederend J. , van Krieken J. H. J. M. , Roodhart J. M. L. , Beets-Tan R. G. H. , Medema J. P. 
Published: July 2022

Abstract
Purpose
To investigate whether locoregional staging of colon cancer by experienced radiologists can be improved by training and feedback to minimize the risk of over-staging into the context of patient selection for neoadjuvant therapy and to identify potential pitfalls of CT staging by characterizing pathologic traits of tumors that remain challenging for radiologists.

Methods
Forty-five cases of stage I-III colon cancer were included in this retrospective study. Five experienced radiologists evaluated the CTs; 5 baseline scans followed by 4 sequential batches of 10 scans. All radiologists were trained after baseline scoring and 2 radiologists received feedback. The learning curve, diagnostic performance, reader confidence, and reading time were evaluated with pathologic staging as reference. Pathology reports and H&E slides of challenging cases were reviewed to identify potential pitfalls.

Results
Diagnostic performance in distinguishing T1-2 vs. T3-4 improved significantly after training and with increasing number of reviewed cases. Inaccurate staging was more frequently related to under-staging rather than over-staging. Risk of over-staging was minimized to 7% in batch 3–4. N-staging remained unreliable with an overall accuracy of 61%. Pathologic review identified two tumor characteristics causing under-staging for T-stage in 5/7 cases: (1) very limited invasive part beyond the muscularis propria and (2) mucinous composition of the invading part.

Conclusion
The high accuracy and specificity of T-staging reached in our study indicate that sufficient training and practice of experienced radiologists can ensure high validity for CT staging in colon cancer to safely use neoadjuvant therapy without significant risk of over-treatment, while N-staging remained unreliable.
Klagemöglichkeiten im Zusammenhang mit der Lärmaktionsplanung?
Authors: Altehenger Ronja 
Published: July 2022

ZusammenfassungDie rechtlichen Probleme mit der Lärmaktionsplanung sind bisher noch nicht zu den Gerichten durchgedrungen.
Diese lehnten bisher in jedem Versuch bereits die Klagebefugnis von Individualklägern wie Umweltvereinigungen
ab. Das Urteil des BVerwG vom 29.11.2019 hat diese Tradition fortgesetzt, allerdings zwischen der Zeilen
angedeutet, dass die Betrachtung für anerkannte Umweltvereinigungen nach UmwRG anders sein könnte.
Dieser Beitrag beschäftigt sich mit der Frage, ob für anerkannte Umweltvereinigungen seit der
Änderung des UmwRG 2017 die Klage gegen Lärmaktionspläne denkbar ist.
Impact of Psychotherapy for Children and Adolescents with Anxiety Disorders on Global and Domain-Specific Functioning: A Systematic Review and Meta-analysis
Authors: Dickson Sophie J. , Kuhnert Rebecca-Lee , Lavell Cassie H. , Rapee Ronald M. 
Published: July 2022

AbstractA substantial empirical base supports the use of psychotherapy to alleviate anxiety symptoms and diagnoses in children and adolescents. However, focusing only on symptom or diagnostic reduction provides an incomplete picture of clinically meaningful efficacy given that anxiety disorders in this age group are integrally associated with problems in functioning. A systematic review and meta-analysis (N studies = 40, N participants = 3094) evaluating the impacts of psychotherapy for anxiety was conducted on the following outcomes: global functioning, social functioning, academic functioning, and school attendance. Randomised controlled trials with a passive control condition, a child and/or adolescent sample (7–17 years) with a primary anxiety diagnosis, and receiving anxiety-focused psychotherapy were eligible for inclusion if they reported suitable outcome data. Results from the meta-analysis indicated that from pre- to post-treatment, psychotherapy led to significant improvements in global functioning according to clinician (d = 1.55), parent (d = 0.67), and child (d = 0.31) reports and on social functioning according to parent (d = 0.51), but not child (d = 0.31) reports. The qualitative review provided preliminary support psychotherapy’s efficacy in increasing family functioning and school attendance, but not so much in enhancing academic performance. These results indicate that psychotherapy improves daily functioning in anxious children and adolescents. The study also highlighted the limited attention paid to measures of functioning in the empirical literature on treatment of childhood anxiety.Trial Registry: This study is registered with PROSPERO under the identification number CRD42021246565.
Capturing and incorporating expert knowledge into machine learning models for quality prediction in manufacturing
Authors: Link Patrick , Poursanidis Miltiadis , Schmid Jochen , Zache Rebekka , von Kurnatowski Martin , Teicher Uwe , Ihlenfeldt Steffen 
Published: July 2022

AbstractIncreasing digitalization enables the use of machine learning (ML) methods for analyzing and optimizing manufacturing processes. A main application of ML is the construction of quality prediction models, which can be used, among other things, for documentation purposes, as assistance systems for process operators, or for adaptive process control. The quality of such ML models typically strongly depends on the amount and the quality of data used for training. In manufacturing, the size of available datasets before start of production (SOP) is often limited. In contrast to data, expert knowledge commonly is available in manufacturing. Therefore, this study introduces a general methodology for building quality prediction models with ML methods on small datasets by integrating shape expert knowledge, that is, prior knowledge about the shape of the input–output relationship to be learned. The proposed methodology is applied to a brushing process with 125 data points for predicting the surface roughness as a function of five process variables. As opposed to conventional ML methods for small datasets, the proposed methodology produces prediction models that strictly comply with all the expert knowledge specified by the involved process specialists. In particular, the direct involvement of process experts in the training of the models leads to a very clear interpretation and, by extension, to a high acceptance of the models. While working out the shape knowledge requires some iterations in general, another clear merit of the proposed methodology is that, in contrast to most conventional ML, it involves no time-consuming and often heuristic hyperparameter tuning or model selection step.
Variant Type X91+ Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort
Authors: Sun Bijun , Zhu Zeyu , Hui Xiaoying , Sun Jinqiao , Wang Wenjie , Ying Wenjing , Zhou Qinhua , Yao Haili , Hou Jia , Wang Xiaochuan 
Published: July 2022

AbstractPurposeWe aimed to report the clinical and immunological characteristics of variant type X91+chronic granulomatous disease (CGD) in a Chinese cohort.MethodsThe clinical manifestations and immunological phenotypes of patients with X91+CGD were collected. A dihydrorhodamine (DHR) analysis was performed to evaluate neutrophil function. Gp91phoxprotein expression was determined using extracellular staining with the monoclonal antibody (mAb) 7D5 and flow cytometry.ResultsPatients with X91+CGD accounted for 8% (7/85) of all patients with CGD. The median age of onset in the seven patients with X91+CGD was 4 months. Six patients received the BCG vaccine, and 50% (3/6) had probable BCG infections.Mycobacterium tuberculosisinfection was prominent. The most common sites of infection were the lung (6/7), lymph nodes (5/7), and soft tissue (3/7). Two patients experienced recurrent oral ulcers. The stimulation index (SI) of the patients with X91+CGD ranged widely from 1.9 to 67.3. The difference in the SI among the three groups of patients (X91+CGD, X91−CGD, and X910CGD) was statistically significant (P = 0.0071). The three groups showed no significant differences in onset age, diagnosis age, or severe infection frequency.CYBBmutations associated with X91+CGD were commonly located in the second transmembrane or intracellular regions. Three novel X91+CGD–related mutations (c.1462–2 A > T, c.1243C > T, and c.925G > A) were identified.ConclusionsVariant type X91+CGD may result in varied clinical manifestations. Moreover, the laboratory findings might indicate a moderate neutrophil SI. We should deepen our understanding of variant X91+CGD to prevent missed diagnoses.
Kindergarteners Use Cross-Situational Statistics to Infer the Meaning of Grammatical Elements
Authors: Spit Sybren , Andringa Sible , Rispens Judith , Aboh Enoch O. 
Published: July 2022

AbstractMany studies demonstrate that detecting statistical regularities in linguistic input plays a key role in language acquisition. Yet, it is unclear to what extent statistical learning is involved in more naturalistic settings, when young children have to acquire meaningful grammatical elements. In the present study, we address these points, by investigating whether statistical learning is involved in acquiring a morpho-syntactic structure from input that resembles natural languages more closely. We exposed 50 kindergarteners (M = 5 years, 5 months) to a miniature language in which they had to learn a grammatical marker that expressed number, and which could only be acquired on the basis of the distributional properties in the input. Half of the children performed an attention check during the experiment. Results show that young children are able to learn this meaning. We found no clear evidence that facilitating attention to the input increases learning performance.
Moving to the rhythm of spring: a case study of the rhythmic structure of dance
Authors: Charnavel Isabelle 
Published: July 2022

AbstractThe specific goal of the article is to investigate the principles governing the perception of rhythmic structure in dance and music—taken separately and together—on the basis of a case study. I take as a starting point Lerdahl and Jackendoff’s (A generative theory of tonal music. MIT Press, 1983) conception of musical rhythm as the interaction between grouping and meter, and I examine to what extent it can apply to dance. Then, I explore how the rhythmical structures of music and dance interact in a single event. I conclude that dance and music perception largely share the same abstract system, and the differences in the properties of their structure derives from the different (visual vs. auditory) modalities in which they are perceived; their modality difference also affects the perceived structure resulting from their combination in dance-music events. The exploration is guided by a detailed examination of the opening of Stravinsky’s Augurs of Spring (1913) as choreographed by Nijinsky (1913), Béjart (1970) and Bausch (1975). By comparing these minimal pairs of dance-music events, I adapt the formal methodology of linguistics to other cognitive systems. The general goal of the article is to shed further light on the organizational principles of mental representations by comparing several cognitive systems in order to distinguish between general cognitive properties and modality-specific or domain-specific properties.
Anti-inflammatory effects of extracellular vesicles from Morchella on LPS-stimulated RAW264.7 cells via the ROS-mediated p38 MAPK signaling pathway
Authors: Chen Qi , Che Chengchuan , Yang Shanshan , Ding Pingping , Si Meiru , Yang Ge 
Published: July 2022

AbstractMorchella is a kind of important edible and medicinal fungi, which is rich in polysaccharides, enzymes, fatty acids, amino acids and other active components. Extracellular vesicles (EVs) have a typical membrane structure, and the vesicles contain some specific lipids, miRNAs and proteins, and their can deliver the contents to different cells to change their functions. The present study investigated whether Morchella produce extracellular vesicles and its anti-inflammatory effect on lipopolysaccharide (LPS)-induced RAW246.7 macrophages. The experimental results showed that Morchella produced extracellular vesicles and significantly reduced the production of nitric oxide (NO) and reactive oxygen species (ROS) in a model of LPS-induced inflammation. In addition, the expression of inflammatory factor-related genes such as inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) showed dose-dependent inhibition. Morchella extracellular vesicles also can inhibit the inflammatory response induced by LPS by inhibiting the production of ROS and reducing the phosphorylation levels of the p38 MAPK signaling pathway. These results indicate that the Morchella extracellular vesicles can be used as a potential anti-inflammatory substance in the treatment of inflammatory diseases.
Phenomenology, abduction, and argument: avoiding an ostrich epistemology
Authors: Reynolds Jack 
Published: July 2022

AbstractPhenomenology has been described as a “non-argumentocentric” way of doing philosophy, reflecting that the philosophical focus is on generating adequate descriptions of experience. But it should not be described as an argument-free zone, regardless of whether this is intended as a descriptive claim about the work of the “usual suspects” or a normative claim about how phenomenology ought to be properly practiced. If phenomenology is always at least partly in the business of arguments, then it is worth giving further attention to the role and form of phenomenological argumentation, how it interacts with its more strictly descriptive component, and the status of phenomenological claims regarding conditions for various kinds of experience. I contend that different versions of phenomenological reasoning encroach upon argument forms that are commonly thought to be antithetical to phenomenology, notably abductive reasoning, understood in terms of its role in both hypothesis generation and in terms of justification. This paper identifies two main steps to making this case. The first step takes seriously the consequences of the intrinsically dialectical aspect of phenomenology in intersection with other modes of philosophy, the natural attitude, and non-philosophy. The second step focuses on transcendental reflection and arguments about the conditions/structures they contain. Together, these two steps aim to rescue phenomenology from the objection that it has an “ostrich epistemology” with regard to the ostensible purity of description, the intuition of essences, or the “conditions” ascertained through transcendental reflection.