bluuebunny/crossref_metadata_2025 huggingface dataset:
Postchemotherapy immune status in infants with acute lymphoblastic leukemia: A report from the JPLSG MLL‐10 trial
Authors: Arakawa Yuki , Hasegawa Daisuke , Miyamura Takako , Ohshima Junjiro , Kimura Shunsuke , Imamura Toshihiko , Koga Yuhki , Yamamoto Shohei , Ogawa Atsushi , Shinoda Kunihiro , Eguchi Mariko , Hosoi Hajime , Imai Kohsuke , Koh Katsuyoshi , Tomizawa Daisuke
Published: July 2022

The MLL‐10 trial (UMIN000004801) modified a Children's Oncology Group (COG) AALL0631 therapy for infants with KMT2A‐rearranged acute lymphoblastic leukemia (ALL). In 2016, one registered case developed secondary immunodeficiency during maintenance therapy and eventually died due to cytomegalovirus infection. Around the same time, fatal secondary immunodeficiencies were reported in five infants with ALL in North America who had received COG‐based chemotherapy between 1996 and 2015. Given these cases, we decided to conduct a retrospective study on the postchemotherapy immune status of infants with ALL. A questionnaire collected data on posttreatment immune function, frequency of infections, and supportive care for the 34 infants in the MLL‐10 trial. Patients receiving allogeneic hematopoietic stem cell transplantation in first remission were excluded. Responses to the survey were obtained in 28 cases (85%). Most patients were immunocompetent after the completion of chemotherapy (median follow‐up duration from the day of chemotherapy completion was 431 days), except for the aforementioned case. There were seven patients with nonsevere viral infection, all of whom recovered. In conclusion, severe chemotherapy‐induced immunodeficiency in infants with ALL appears to be rare, but prospective data collection of immune function is necessary to clarify this finding.
Implementing the WHO Global Initiative for Childhood Cancer in Morocco: Survival study for the six indexed childhood cancers
Authors: Mechita Nada Bennani , Cherkaoui Siham , Abousselham Loubna , Benmiloud Sarra , Kili Amina , Kababri Maria El , Maani Khadija , Houdzi Jamila El , Benajiba Noufissa , Madani Abdellah , Bennani Maria , Belakhel Latefa , Bouffet Eric , Patte Catherine , Harif Mhamed , Youbi Mohammed , Hessissen Laila
Published: July 2022

Background

In 2018, the World Health Organization (WHO) launched the Global Initiative for Childhood Cancer (GICC). The goal is to achieve a global survival rate of at least 60% for all children with cancer by 2030. Morocco was designated as a pilot country for this initiative.

Procedure

This retrospective study included a cohort of children aged 0–15 years, with one of the six indexed cancers (acute lymphoblastic leukemia [ALL], Burkitt lymphoma [BL], Hodgkin lymphoma, retinoblastoma [RB], Wilms tumor or nephroblastoma, low‐grade glioma), diagnosed between January 1, 2017 and December 31, 2019 at the six Moroccan Pediatric Hematology and Oncology units. Patients were followed‐up until August 31, 2020. The Kaplan–Meier method was used to estimate survival rates, the log‐rank test for comparing survival curves, and the Cox model for identifying prognostic factors.

Results

Data on 878 patients were included in the study. The most frequently reported cancer type was ALL (n = 383, 43.6%), followed by Wilms tumor (n = 139, 15.8%) and BL (n = 133, 15%). Most patients were less than 5 years of age (n = 446, 50.9%) and the male/female ratio was 1.46. The 1, 2, and 3‐year overall survival rates were 80.1%, 73.6%, and 68.2%, respectively. In a multivariable Cox regression model, care center, cancer type, age group, and distance to the care center were statistically significantly associated to survival. Patients aged 10 years and older and patients living more than 100 km from the care center were more likely to die (respectively, HR = 1.39, p = .045 and HR = 1.44, p = .010).

Conclusion

The reported results represent the baseline for measuring the impact of GICC implementation in Morocco.
Heat‐shock protein 70—a hub gene—underwent adaptive evolution involved in whitefly‐wild tomato interaction
Authors: Tian Jiahui , Dewer Youssef , Qu Cheng , Li Fengqi , Luo Chen
Published: July 2022

BACKGROUND

The whitefly Bemisia tabaci causes severe damage to cultivated tomato plants, but actively avoids the wild tomato Solanum habrochaites. Moreover, the mortality of whitefly increases significantly after feeding with the wild tomato. However, additional experiments are warranted to more carefully elucidate the specific molecular elements underlying the interaction between whitefly and wild tomato.

RESULTS

Our results showed that S. habrochaites significantly increases the mortality of whitefly adults and decreases both their fertility and fecundity. In addition, the expression of stress‐response genes in whitefly after exposure to S. habrochaites was analyzed using RNA sequencing. Weighted gene co‐expression network analysis was conducted to identify the hub genes to determine their potential associations with the mortality of whitefly. These results suggested that the expression of heat‐shock protein (HSP), multicopper oxidase, and 2‐Oxo‐4‐hydroxy‐4‐carboxy‐5‐ureidoimidazoline (OHCU) decarboxylase genes were induced in whitefly. To validate the gene associations with whitefly mortality, a high‐throughput in vivo model system and RNAi‐based gene silencing were used. The results revealed that the RNAi‐mediated depletion of the HSP gene, which belongs to the HSP70 subfamily, increased the mortality of whitefly. Furthermore, the selection pressure analysis showed that a total of five amino acid sites of positive selection were identified, three of which were located in the nucleotide‐binding domain and the other two in the substrate‐binding domain.

CONCLUSIONS

This is the first report on the potential implication of HSPs in whitefly–wild plant interactions. This study could more precisely identify the molecular mechanisms of whitefly in response to wild tomatoes. © 2022 Society of Chemical Industry.
Cancer metabolism control by natural products: Pyruvate kinase M2 targeting therapeutics
Authors: El‐Far Ali H. , Al Jaouni Soad K. , Li Xiaotao , Fu Junjiang
Published: July 2022

Glycolysis is the primary source of energy for cancer growth and metastasis. The shift in metabolism from mitochondrial oxidative phosphorylation to aerobic glycolysis is called the Warburg effect. Cancer progression due to aerobic glycolysis is often associated with the activation of oncogenes or the loss of tumor suppressors. Therefore, inhibition of glycolysis is one of the effective strategies in cancer control. Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme overexpressed in breast, prostate, lung, colorectal, and liver cancers. Here, we discuss published studies regarding PKM2 inhibitors from natural products that are promising drug candidates for cancer therapy. We have highlighted the potential of natural PKM2 inhibitors for various cancer types. Moreover, we encourage researchers to evaluate the combinational effects between natural and synthetic PKM2 inhibitors. Also, further high‐quality studies are needed to firmly establish the clinical efficacy of natural products.
Bryodulcosigenin attenuates bleomycin‐induced pulmonary fibrosis via inhibiting AMPK‐mediated mesenchymal epithelial transition and oxidative stress
Authors: Ding Yue , Wang Lei , Liu Bei , Ren Guoqing , Okubo Ryosuke , Yu Jing , Zhang Chaofeng
Published: July 2022

Fibrosis is a pathological result of a dysfunctional repair response to tissue injury and occurs in several organs, including the lungs. Bryodulcosigenin (BDG) is a cucurbitane‐type triterpene isolated from Siratia grosvenori and has clear‐cut anti‐inflammatory effects, yet its benefit of pulmonary fibrosis (PF) remains unclear. In this study, we investigated the protective effects of BDG (10 mg/kg/day, for 14 days) against TGF‐β1‐stimulated mouse alveolar epithelial MLE‐12 cells and bleomycin (BLM)‐induced PF mice. In vitro experiments showed that BDG could inhibit epithelial‐mesenchymal transition (EMT) and oxidative stress. In vivo experiments indicated that BDG could ameliorate BLM‐induced PF in mice as evidenced by characteristic structural changes in histopathology, increased collagen deposition and reduced survival and weight of mice. The abnormal increased expressions of TGF‐β1, p‐Smad2/3, α‐SMA, COL‐I, and NOX4 and decreased expressions for Sirt1 and p‐AMPK were improved in BDG treatment. But these beneficial effects could be eliminated by co‐treatment with Compound C (CC, a selective AMPK inhibitor). Molecular docking technology also revealed the potential of BDG to activate AMPK. In summary, AMPK activation modulated by BDG not only ameliorated TGF‐β1/Smad2/3 signaling pathways but also partially mediated the suppression effects on EMT and oxidative stress, thus mediating the anti‐fibrotic effects.
A Markovian analytical approach to a repairable system under the mixed redundancy strategy with a repairman
Authors: Juybari Mohammad N. , Zeinal Hamadani Ali , Liu Baoliang
Published: July 2022

The mixed redundancy strategy is one of the most powerful techniques for improving system performance. This novel strategy has, however, been mostly studied in non‐repairable redundant systems, while the present study aims to study, for the first time, its application to a repairable system with a repairman in availability and maintainability perspectives. In this system, a repairman is responsible for providing the repair services. The intended system simultaneously benefits from the repairman's vacation concept following different policies, namely: vacation interruption and multiple vacations. Moreover, the system consists of two types of repairs, specifically: regular and working vacation repair. Also, successive vacation times are governed by the Markovian arrival process. Accordingly, the system is analyzed by modeling a vector‐valued Markov process and several performance measures are derived in both transient and stationary regimes following the matrix‐analytic procedure. Finally, the performance of the proposed approach is verified using numerical examples that involve a system with three repairable non‐identical components under the mixed strategy as well as a micro‐grid system with three parallel subsystems as a real‐life case study.
Ni‐Decorated Multi‐Walled Carbon Nanotubes for Electro‐Oxidation of Tri(ammonium) Phosphate as New Hydrogen Source Material
Authors: Barakat Nasser A. M. , Ahmed Enas , Farghali Ahmed Ali , Nassar Mamdouh M. , Tolba Gehan M. K. , Zaki Ayman H.
Published: July 2022

Hydrogen is considered the lifesaver against the highly expected depletion of the fossil fuels. Among the various hydrogen production processes, electro‐oxidation of hydrogen‐rich compounds (e. g. alcohols) is a promising technology due to simplicity and low cost. The cheap non‐precious materials can be exploited for hydrogen generation from alcohols electrolysis with small biases. However, the alcohols are either toxic and/or relatively expensive. Recently, hydrogen could be extracted from tri(ammonium) phosphate using Ni/C hetero‐catalytic reaction.[1,2] In the present study, electro‐oxidation of tri(ammonium) phosphate using Ni‐decorated carbon nanotubes is investigated. The utilized catalyst has been prepared by a simple one‐pot synthesis procedure; calcination of well mixed nickel acetate/carbon nanotubes composite under inert atmosphere at 850 °C. The results indicated that the prepared Ni‐decorated carbon nanotubes composite is an effective electro‐catalyst for tri(ammonium) phosphate oxidation when the nickel content is optimized; 1 wt% metal is the best composition. Moreover, chronoamperometry analysis results indicated that the electro‐oxidation reactions is independent on the nickel (oxy)hydroxide active layer, this creates a distinct advantage over alcohols. Workability of the inactive electrode is attributed to the reactivity of both of Ni(OH)2 and Ni(OOH) species toward tri(ammonium) phosphate electro‐oxidation process.
Multimodal Imaging Contrast Property of Nano Hybrid Fe3O4@Ag Fabricated by Seed‐Growth for Medicinal Diagnosis
Authors: Le The Tam , Nguyen Thi Ngoc Linh , Nguyen Hoa Du , Phan Thi Hong Tuyet , Pham Hong Nam , Le Duc Giang , Hoang Thanh Phong , Nguyen Thi Quynh Hoa , Le Trong Lu , Tran Lam Dai
Published: July 2022

Multimodal imaging, which integrates different imaging modalities, is emerging as a promising strategy to improve both preclinical and subclinical imaging. Computed tomography (CT) and magnetic resonance imaging (MRI) are among the imaging techniques widely used in clinical practice. These imaging modalities are used to diagnose and screen disease, each providing additional and different information about the patient and pathosis. In this research, we present the development of a model that combines a hybrid nanostructure, consisting of an iron oxide core and a silver‐shell nanoparticle for dual MRI/CT imaging. Fe3O4@Ag HNPs with core‐shell structure were fabricated by reducing Ag+ on the surface of Fe3O4 (NPs) nanoparticles by seed‐growth route in the thermal decomposition method. TEM images show that the synthesized nanoparticles have a uniform spherical shape and size, with an average diameter of 15.6 nm. The hybrid nanoparticles after functionalizing the surface with polyacrylic acid (PAA) became hydrophilic and dispersed well in water. The fluid of Fe3O4@Ag@PAA HNPs has high stability in water media with NaCl salt concentrations above 200 mM and a wide pH range from 4 to 11. The fluid Fe3O4@Ag@PAA has selective cytotoxicity with IC50 value 8.42 ug/ml for Hep‐G2 cell lines, and 40.3 ug/ml for normal Vero cell lines. The results of in‐vitro MRI/CT imaging showed that the value of transverse relaxation rate r2 was 138.6 mM−1s−1 and had good X‐ray attenuation ability. With these outstanding properties, the core‐shell structured nano hybrid fluid presented in this research has the potential as a candidate for multimodal bioimaging techniques in practical applications.
Geometrical influence on Hg determination in wet sediment using K‐shell fluorescence analysis
Authors: An Siwen , Krapohl David , González Charlotte , Rydblom Stefani , Norlin Börje , Thungström Göran
Published: July 2022

To quickly identify maritime sites polluted by heavy metal contaminants, reductions in the size of instrumentation have made it possible to bring an X‐ray fluorescence (XRF) analyzer into the field and in direct contact with various samples. The choice of source‐sample‐detector geometry plays an important role in minimizing the Compton scattering noise and achieving a better signal‐to‐noise ratio (SNR) in XRF measurement conditions, especially for analysis of wet sediments. This paper presents the influence of geometrical factors on a prototype, designed for in situ XRF analysis of mercury (Hg) in wet sediments using a 57Co excitation source and an X‐ray spectrometer. The unique XRF penetrometer prototype has been constructed and tested for maritime wet sediment. The influence on detection efficiency and SNR of various geometrical arrangements have been investigated using the combination of Monte Carlo simulations and laboratory experiments. Instrument calibration was performed for Hg analysis by means of prepared wet sediments with the XRF prototype. The presented results show that it is possible to detect Hg by K‐shell emission, thus enabling XRF analysis for underwater sediments. Consequently, the XRF prototype has the potential to be applied as an environmental screening tool for analysis of polluted sediments with relatively high concentrations (e.g., >2880 ppm for Hg), which would benefit in situ monitoring of maritime pollution caused by heavy metals.
The Palearctic blackfly Simulium equinum (Diptera: Simuliidae) as a biting pest of captive nyala antelopes (Tragelaphus angasii)
Authors: Ebmer David , Balfanz Folko , Voracek Thomas , Hering‐Hagenbeck Stephan , Pichler‐Scheder Christian , Walochnik Julia , Kniha Edwin
Published: July 2022

Blackflies (Diptera: Simuliidae) are cosmopolitan nuisance pests of great economic importance as well as vectors of many pathogens. After reports of massive blackfly biting of captive nyala antelopes in the Vienna Zoo, Austria, this study aimed to identify the species causing multiple skin lesions on the antelope hosts. The Palearctic species Simulium equinum, belonging to the medically and veterinary important Wilhelmia subgenus, was identified as the most likely causative agent. Barcoding and maximum likelihood analysis supported morphological species identification and highlighted the complex phylogeny of the subgenus Wilhelmia. Our study gives first evidence of the multi‐host feeding blackfly S. equinum in the Vienna Zoo, thereby raising the question whether other hosts could also be bitten on a regular basis. The preliminary results urge for further analysis of blackfly breeding sites as well as the clarification of the host spectrum to assess the medical and veterinary importance of blackflies in the Zoo.
A Comparative Perspective on Ribosome Biogenesis: Unity and Diversity Across the Tree of Life
Authors: Jüttner Michael , Ferreira-Cerca Sébastien
Published: July 2022

Ribosomes are universally conserved ribonucleoprotein complexes involved in the decoding of the genetic information contained in messenger RNAs into proteins. Accordingly, ribosome biogenesis is a fundamental cellular process required for functional ribosome homeostasis and to preserve satisfactory gene expression capability.

Although the ribosome is universally conserved, its biogenesis shows an intriguing degree of variability across the tree of life. These differences also raise yet unresolved questions. Among them are (a) what are, if existing, the remaining ancestral common principles of ribosome biogenesis; (b) what are the molecular impacts of the evolution history and how did they contribute to (re)shape the ribosome biogenesis pathway across the tree of life; (c) what is the extent of functional divergence and/or convergence (functional mimicry), and in the latter case (if existing) what is the molecular basis; (d) considering the universal ribosome conservation, what is the capability of functional plasticity and cellular adaptation of the ribosome biogenesis pathway?

In this review, we provide a brief overview of ribosome biogenesis across the tree of life and try to illustrate some potential and/or emerging answers to these unresolved questions.
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

Nuclear 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

Technical 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

Today, 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

Guidelines 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

This 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

Low-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

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

Die 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

A 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

Increasing 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

Purpose

We aimed to report the clinical and immunological characteristics of variant type X91+chronic granulomatous disease (CGD) in a Chinese cohort.

Methods

The 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.

Results

Patients 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.

Conclusions

Variant 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

Many 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

The 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

Morchella 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

Phenomenology 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.
What Works for Whom in School-Based Anti-bullying Interventions? An Individual Participant Data Meta-analysis
Authors: Hensums Maud , de Mooij Brechtje , Kuijper Steven C. ,   BIRC: the anti-Bullying Interventions Research Consortium, Cross Donna , DeSmet Ann , Garandeau Claire F. , Joronen Katja , Leadbeater Bonnie , Menesini Ersilia , Palladino Benedetta Emanuela , Salmivalli Christina , Solomontos-Kountouri Olga , Veenstra René , Fekkes Minne , Overbeek Geertjan
Published: July 2022

The prevalence of bullying worldwide is high (UNESCO, 2018). Over the past decades, many anti-bullying interventions have been developed to remediate this problem. However, we lack insight into for whom these interventions work and what individual intervention components drive the total intervention effects. We conducted a large-scale individual participant data (IPD) meta-analysis using data from 39,793 children and adolescents aged five to 20 years (Mage = 12.58, SD = 2.34) who had participated in quasi-experimental or randomized controlled trials of school-based anti-bullying interventions (i.e., 10 studies testing nine interventions). Multilevel logistic regression analyses showed that anti-bullying interventions significantly reduced self-reported victimization (d =  − 0.14) and bullying perpetration (d =  − 0.07). Anti-bullying interventions more strongly reduced bullying perpetration in younger participants (i.e., under age 12) and victimization for youth who were more heavily victimized before the intervention. We did not find evidence to show that the inclusion of specific intervention components was related to higher overall intervention effects, except for an iatrogenic effect of non-punitive disciplinary methods–which was strongest for girls. Exploratory analyses suggested that school assemblies and playground supervision may have harmful effects for some, increasing bullying perpetration in youth who already bullied frequently at baseline. In conclusion, school-based anti-bullying interventions are generally effective and work especially well for younger children and youth who are most heavily victimized. Further tailoring of interventions may be necessary to more effectively meet the needs and strengths of specific subgroups of children and adolescents.
Promoting University Students’ Engagement in Intercultural Group Work: The Importance of Expectancy, Value, and Cost
Authors: Poort Irene , Jansen Ellen , Hofman Adriaan
Published: July 2022

Intercultural group work (IGW) is a valuable learning strategy to enhance deep learning and prepare university students to participate in a globalized world, so more insight is needed into what motivates students to engage actively in IGW. Using an expectancy–value theory framework, this study investigates the extent to which the different components of this theory (i.e., self-efficacy, perceived benefit, and perceived cost) relate to each other and contribute to student engagement in IGW. Responses to a questionnaire, gathered from 846 bachelor’s students from six universities in the Netherlands and Canada, reveal that strong self-efficacy for IGW, high perceived benefit of IGW, and low perceived cost of IGW correlate. In structural equation modeling analyses, self-efficacy and emotional cost emerge as important predictors of behavioral and cognitive engagement; intercultural benefit is critical for cognitive engagement. As a prerequisite of cognitive engagement, behavioral engagement also mediates the effects of self-efficacy, costs, and benefits. Therefore, developing students’ self-efficacy, increasing perceived benefits of IGW, and decreasing perceived costs of IGW can promote student engagement and deeper learning. Universities thus should prepare students for IGW and provide support and feedback during group work process. Based on the results, we theorize about the relationships among the components of the expectancy–value theory.
Gastrointestinal parasites in red-legged partridges (Alectoris rufa) hunted in Spain: a warning to game managers
Authors: Arcenillas-Hernández Irene , Martínez-Carrasco Carlos , Tizzani Paolo , Berriatua Eduardo , del Rocío Ruiz de Ybáñez María
Published: July 2022

Red-legged partridge (Alectoris rufa) populations are currently declining in the Iberian Peninsula, mainly due to habitat degradation and hunting pressure. In addition, the release of farm-reared partridges may introduce pathogens, including parasites, to wild populations. The presence of digestive parasites in red-legged partridges hunted in fifteen Spanish provinces was studied. Fecal samples and gastrointestinal tracts were collected, analyzed, and the morphometric identification of parasites was carried out.Eimeriaspp. oocysts, nematode, cestode and trematode eggs were observed in fecal samples. Adult nematodes (Ascaridia galli,Ascaridia compar,Heterakis gallinarum,Heterakis tenuicauda,Trichostrongylus tenuis, Subuluraspp.,Cyrneaspp. andAonchotheca caudinflata), tapeworms (Raillietina tetragona, R. echinobothrida, R. micracantha,Rhabdometra nigropunctata,andChoanotaenia infundibulum), and trematodes (Brachylaimaspp.,Brachylecithumspp.,Dicrocoeliumspp.) were identified in the gastrointestinal tracts. Significant statistical differences were found among climatic regions in the prevalence and intensity ofEimeriaspp. infection, median intensity and the prevalence of indirect life cycle helminths, with Southern areas always showing higher infection values. The study provides information of the health status of red-legged partridges in Spain, highlighting the risk associated with the release of farm-reared partridges for restocking purposes. This should be taken into account to improve management strategies for the long-term conservation of the species.