bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of nivolumab in Japanese patients with first recurrence of glioblastoma: an open-label, non-comparative study
Authors: Aoki Tomokazu , Kagawa Naoki , Sugiyama Kazuhiko , Wakabayashi Toshihiko , Arakawa Yoshiki , Yamaguchi Shigeru , Tanaka Shota , Ishikawa Eiichi , Muragaki Yoshihiro , Nagane Motoo , Nakada Mitsutoshi , Suehiro Satoshi , Hata Nobuhiro , Kuroda Junichiro , Narita Yoshitaka , Sonoda Yukihiko , Iwadate Yasuo , Natsumeda Manabu , Nakazato Yoichi , Minami Hironobu , Hirata Yuki , Hagihara Shunsuke , Nishikawa Ryo 
Published: September 2021

Abstract
Background
An open-label, non-comparative study assessed the efficacy and safety of nivolumab in Japanese patients with first recurrence glioblastoma.

Methods
Patients with first recurrence of histologically confirmed World Health Organization Grade IV glioma, after treatment with temozolomide and radiotherapy, received nivolumab 3 mg/kg every 2 weeks until confirmed disease progression (Response Assessment in Neuro-Oncology criteria) or toxicity. Primary endpoint was 1-year overall survival rate assessed by Bayesian approach. The prespecified efficacy criterion was that the Bayesian posterior probability threshold for exceeding the 1-year overall survival of bevacizumab (34.5%) from the Japanese phase 2 study (JO22506) would be 93%.

Results
Of the 50 enrolled patients, 44 (88.0%) had recurrent malignant glioma (glioblastoma, gliosarcoma), and of these, 26 (59.1%) had at least one measurable lesion at baseline. The Bayesian posterior mean 1-year overall survival (90% Bayesian credible intervals) with nivolumab was 54.4% (42.27–66.21), and the Bayesian posterior probability of exceeding the threshold of the 1-year overall survival rate of bevacizumab (34.5%) was 99.7%. Median (90% confidence interval) overall and progression-free survival was 13.1 (10.4–17.7) and 1.5 (1.4–1.5) months, respectively. One partial response was observed (objective response rate 1/26 evaluable patients [3.8%]). Treatment-related adverse event rates were 14.0% for Grade 3–4 and 2.0% for Grade 5; most adverse events resolved and were manageable.

Conclusions
The 1-year overall survival with nivolumab monotherapy in Japanese patients with glioblastoma met the prespecified efficacy criterion. The safety profile of nivolumab was consistent with that observed in other tumor types.

Clinical Trial Registration
JapicCTI-152967.
The Prevalence and Negative Impacts of Substance Use Disorders among People with HIV in the United States: A Real-Time Delphi Survey of Key Stakeholders
Authors: Garner Bryan R. , Gotham Heather J. , Knudsen Hannah K. , Zulkiewicz Brittany A. , Tueller Stephen J. , Berzofsky Marcus , Donohoe Tom , Martin Erika G. , Brown L. Lauren , Gordon Theodore 
Published: September 2021

AbstractAlthough HIV and substance use disorders (SUDs) constitute a health syndemic, no research to date has examined the perceived negative impacts of different SUDs for people with HIV (PWH). In May 2019, 643 stakeholders in the U.S., representing clients of AIDS service organizations (ASOs), ASO staff, and HIV/AIDS Planning Council members, participated in an innovative Stakeholder-Engaged Real-Time Delphi (SE-RTD) survey focused on the prevalence and individual-level negative impact of five SUDs for PWH. The SE-RTD method has advantages over conventional survey methods by efficiently sharing information, thereby reducing the likelihood that between-group differences are simply due to lack of information, knowledge, and/or understanding. The population-level negative impacts were calculated by weighting each SUD’s individual-level negative impact on indicators of the HIV Care Continuum and other important areas of life by the perceived prevalence of each SUD. Overall, we found these SUDs to have the greatest population-level negative impact scores (possible range 0–24): alcohol use disorder (population-level negative impact = 6.9; perceived prevalence = 41.9%), methamphetamine use disorder (population-level negative impact = 6.5; perceived prevalence = 3.2%), and opioid use disorder (population-level negative impact = 6.4; perceived prevalence = 34.6%). Beyond further demonstration of the need to better integrate SUD services within HIV settings, our findings may help inform how finite funding is allocated for addressing the HIV-SUD syndemic within the U.S. Based on our findings, such future efforts should prioritize the integration of evidence-based treatments that help address use disorders for alcohol, methamphetamine, and opioids.
Effective elastic properties of one-dimensional hexagonal quasicrystal composites
Authors: Li Shuang , Li Lianhe 
Published: September 2021

AbstractThe explicit expression of Eshelby tensors for one-dimensional (1D) hexagonal quasicrystal composites is presented by using Green’s function method. The closed forms of Eshelby tensors in the special cases of spheroid, elliptic cylinder, ribbon-like, penny-shaped, and rod-shaped inclusions embedded in 1D hexagonal quasicrystal matrices are given. As an application of Eshelby tensors, the analytical expressions for the effective properties of the 1D hexagonal quasicrystal composites are derived based on the Mori-Tanaka method. The effects of the volume fraction of the inclusion on the elastic properties of the composite materials are discussed.
Construction of a rAAV-SaCas9 system expressing eGFP and its application to improve muscle mass
Authors: Weng Shaoting , Zhao Yitian , Yu Changhong , Wang Xiaofan , Xiao Xuehan , Han Liqiang , Zhang Kunpeng , Wang Jiang , Yang Guoyu 
Published: September 2021

AbstractAn ideal rAAV gene editing system not only effectively edits genes at specific site, but also prevents the spread of the virus from occurring off-target or carcinogenic risks. This is important for gene editing research at specific site in vivo. We report a single rAAV containing SaCas9 and guide RNAs under the control of subtle EF1a and tRNA promoters. The capacity of rAAV was compressed, and the editing efficiency was similar to that of the classical Cas9 system in vitro and in vivo. And we inserted the sequence of the green fluorescent protein eGFP into rAAV. The number of cells infected with the rAAV and the region in which the rAAV spreads were known by the fluorescent expression of eGFP in cells. In addition, we demonstrated that myostatin gene in the thigh muscles of C57BL/10 mice was knocked out by the rAAV9-SaCas9 system to make muscle mass increased obviously. The protein eGFP into rAAV has significant implications for our indirect analysis of the editing efficiency of SaCas9 in the genome of the target tissue and reduces the harm caused by off-target editing and prevents other tissue mutations. The rAAV system has substantial potential in improving muscle mass and preventing muscle atrophy.
Biomarkers in Child and Adolescent Depression
Authors: Zwolińska Weronika , Dmitrzak-Węglarz Monika , Słopień Agnieszka 
Published: September 2021

AbstractDespite the significant prevalence of Major Depressive Disorder in the pediatric population, the pathophysiology of this condition remains unclear, and the treatment outcomes poor. Investigating tools that might aid in diagnosing and treating early-onset depression seems essential in improving the prognosis of the future disease course. Recent studies have focused on searching for biomarkers that constitute biochemical indicators of MDD susceptibility, diagnosis, or treatment outcome. In comparison to increasing evidence of possible biomarkers in adult depression, the studies investigating this subject in the youth population are lacking. This narrative review aims to summarize research on molecular and biochemical biomarkers in child and adolescent depression in order to advocate future directions in the research on this subject. More studies on depression involving the youth population seem vital to comprehend the natural course of the disease and identify features that may underlie commonly observed differences in treatment outcomes between adults and children.
Improved interval methods for solving circle packing problems in the unit square
Authors: Markót Mihály Csaba 
Published: September 2021

AbstractIn this work computer-assisted optimality proofs are given for the problems of finding the densest packings of 31, 32, and 33 non-overlapping equal circles in a square. In a study of 2005, a fully interval arithmetic based global optimization method was introduced for the problem class, solving the cases 28, 29, 30. Until now, these were the largest problem instances solved on a computer. Using the techniques of that paper, the estimated solution time for the next three cases would have been 3–6 CPU months. In the present paper this former method is improved in both its local and global search phases. We discuss a new interval-based polygon representation of the core local method for eliminating suboptimal regions, which has a simpler implementation, easier proof of correctness, and faster behaviour than the former one. Furthermore, a modified strategy is presented for the global phase of the search, including improved symmetry filtering and tile pattern matching. With the new method the cases $$n=31,32,33$$

n
=
31
,
32
,
33

have been solved in 26, 61, and 13 CPU hours, giving high precision enclosures for all global optimizers and the optimum value. After eliminating the hardware and compiler improvements since the former study, the new proof technique became roughly about 40–100 times faster than the previous one. In addition, the new implementation is suitable for solving the next few circle packing instances with similar computational effort.
The impact of mergers in higher education on micro-level processes – a literature review
Authors: Wollscheid Sabine , Røsdal Trude 
Published: September 2021

AbstractAmidst increased research on mergers in higher education, studies addressing micro level processes are scarce and fragmented across disciplines: our aim is to systematically review existing studies, providing implications for research and practice. We grouped 21 studies from different countries under four themes: academic identity and self-image; cultural integration; staff reaction; teaching and research. Timing, status of institutions and staff, and disciplinary cultures apparently affect post-merger micro-level processes. Policy reforms might indirectly address micro-level processes following a merger, for example in a change of academic identities. Few studies investigated the impact of mergers on teaching and research activities. Studying merger consequences for academic core activities is complex, requiring a longer perspective involving students, staff and quantitative indicators. Longitudinal design in further studies might investigate changes from different angles and for different staff groups and students, exploring country differences in micro-level processes, applying a comparative design. Despite limitations, our review might inform the planning of merger processes regarding reactions at micro level.
Effects of Gentiopicroside on activation of NLRP3 inflammasome in acute gouty arthritis mice induced by MSU
Authors: He Menglin , Hu Cheng , Chen Meijuan , Gao Qian , Li Liqiu , Tian Weiqian 
Published: September 2021

AbstractAcute gouty arthritis is a self-limiting inflammatory disease resulting from the deposition of monosodium urate (MSU) crystals. It has been shown that Gentiopicroside (GPS) possesses anti-inflammatory and analgesic functions. The aim of this study was to parse out whether GPS has an effect on acute gouty arthritis. We established an acute gouty arthritis model by the injection of MSU into the paw, and found that GPS relieves MSU-induced mechanical, thermal hyperalgesia, and paw swelling. Furthermore, GPS down-regulated the release of pro-inflammatory cytokines in paw tissues, including IL-1β, IL-6, IL-18, and TNF-α. The results of H&E staining and MPO activity measurement showed that GPS inhibits neutrophil infiltration. And the over-expressions of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and Caspase-1 induced by MSU were inhibited by treatment with GPS. These results revealed that GPS can treat acute gouty arthritis based on anti-inflammatory and analgesic properties in vivo, which might be ascribed to the inhibition on NLRP3 inflammasome. Furthermore, we performed in vitro study to confirm the results of in vivo study. Consistently, the results proved that GPS could inhibit the activation of NLRP3 inflammasome in RAW264.7 macrophages stimulated by LPS-MSU. In conclusion, this study provides an experimental basis for the application of GPS and expands the potential value of GPS in the therapy of acute gouty arthritis.
Lernen und Lehren mit digitalen Medien: Eine Standortbestimmung
Authors: Scheiter Katharina 
Published: September 2021

ZusammenfassungIm Beitrag wird der Stand der Forschung zum Einsatz digitaler Medien im Bildungskontext vor dem Hintergrund zweier Forschungsperspektiven beschrieben. Die erste, schon länger vertretene Forschungsperspektive beschäftigt sich mit dem Lernen mit digitalen Medien. Untersucht werden hier vor allem Lernprozesse und -ergebnisse in Abhängigkeit von Medienmerkmalen und individuellen Eigenschaften der Lernenden. Diese Forschungstradition hat zahlreiche Erkenntnisse hervorgebracht. Allerdings wird die Frage nach einer lernwirksamen Integration digitaler Medien in den Unterricht hier nicht berücksichtigt. Hier greift die zweite, jüngere Forschungsperspektive zum Lehren mit digitalen Medien, in welchem das Unterrichten mit digitalen Medien und dafür notwendige professionelle Kompetenzen von Lehrpersonen adressiert werden. Im Beitrag wird abschließend dafür plädiert, beide Perspektiven stärker miteinander zu kombinieren, insbesondere da diese relevante Gemeinsamkeiten in ihren Grundannahmen aufweisen. So werden in beiden Perspektiven digitale Medien weniger anhand von Oberflächenmerkmalen, sondern vielmehr bezüglich ihrer Funktionen für die Förderung von Lern- und Lehrprozessen analysiert.
Establishment of Down’s syndrome periodontal ligament cells by transfection with SV40T-Ag and hTERT
Authors: Asakawa Takeyoshi , Yamada Atsushi , Kugino Masumi , Hasegawa Tomokazu , Yoshimura Kentaro , Sasa Kiyohito , Kinoshita Mitsuhiro , Nitta Masakazu , Nagata Karin , Sugiyama Tomomi , Kamijo Ryutaro , Funatsu Takahiro 
Published: September 2021

AbstractDown’s syndrome is one of the most common human congenital genetic diseases and affected patients have increased risk of periodontal disease. To examine involvement of the disease with periodontal disease development, we established immortalized periodontal ligament cells obtained from a Down’s syndrome patient by use of SV40T-Ag and hTERT gene transfection. Expressions of SV40T-Ag and hTERT were observed in periodontal ligament cell-derived immortalized cells established from healthy (STPDL) and Down’s syndrome patient (STPDLDS) samples. Primary cultured periodontal ligament cells obtained from a healthy subject (pPDL) had a limited number of population doublings (< 40), while STPDL and STPDLDS cells continued to grow with more than 80 population doublings. Primary cultured periodontal ligament cells obtained from the patient showed a chromosome pattern characteristic of Down’s syndrome with trisomy 21, whereas STPDLDS samples showed a large number of abnormal chromosomes in those results. Gene expression analysis revealed that expression of DSCR-1 in STPDLDS is greater than that in STPDL. These results suggest that the newly established STPDLDS cell line may be a useful tool for study of periodontal disease in Down’s syndrome patients.
Anticancer Properties and Mechanism of Action of Oblongifolin C, Guttiferone K and Related Polyprenylated Acylphloroglucinols
Authors: Bailly Christian , Vergoten Gérard 
Published: September 2021

AbstractPolyprenylated acylphloroglucinols represent an important class of natural products found in many plants. Among them, the two related products oblongifolin C (Ob-C) and guttiferone K (Gt-K) isolated from Garcinia species (notably from edible fruits), have attracted attention due to their marked anticancer properties. The two compounds only differ by the nature of the C-6 side chain, prenyl (Gt-K) or geranyl (Ob-C) on the phloroglucinol core. Their origin, method of extraction and biological properties are presented here, with a focus on the targets and pathways implicated in their anticancer activities. Both compounds markedly reduce cancer cell proliferation in vitro, as well as tumor growth and metastasis in vivo. They are both potent inducer of tumor cell apoptosis, and regulation of autophagy flux is a hallmark of their mode of action. The distinct mechanism leading to autophagosome accumulation in cells and the implicated molecular targets are discussed. The specific role of the chaperone protein HSPA8, known to interact with Ob-C, is addressed. Molecular models of Gt-K and Ob-C bound to HSPA8 provide a structural basis to their common HSPA8-binding recognition capacity. The review shed light on the mechanism of action of these compounds, to encourage their studies and potential development.
Vermessung und Vermittlung der Krise in den frühen Lageberichten zur Corona-Pandemie: ein deutsch-französischer Vergleich
Authors: Koch Christian , Thörle Britta 
Published: September 2021

ZusammenfassungMit Ankunft des Coronavirus in Europa im Frühjahr 2020 beginnen in Deutschland und Frankreich relativ zeitgleich Lageberichte durch die staatlichen Gesundheitsinstitutionen – das Robert Koch-Institut und die Direction générale de la santé. Diese mündlich gehaltenen Expertenvorträge dienen sowohl zur Beschreibung der aktuellen Verbreitung des Virus als auch zur Begründung der zu ergreifenden Maßnahmen. Untersucht wird in diesem Artikel eine Reihe von Lageberichten beider Länder im Hinblick auf Ähnlichkeiten und Unterschiede auf sprachlicher Ebene. Neben den verschiedenen kommunikativen Handlungen des Beschreibens und Interpretierens der Sachlage, des Argumentierens für Maßnahmen sowie des Empfehlens und Anordnens von Handlungen wird die neu entstehende Lexik zur Bezeichnung des Virus und der Masken genauer betrachtet. Die Gegenüberstellung von deutschen und französischen Textauszügen zeigt, dass die beiden parallel, aber voneinander unabhängig stattfindenden Veranstaltungen zahlreiche Ähnlichkeiten aufweisen. Unterschiede, die gezeigt werden können, betreffen im Bereich der Maßnahmen und Appelle die divergierende politische Funktion der beiden Einrichtungen mit einer stärker beratenden Rolle des Robert Koch-Instituts gegenüber der Direction générale de la santé als Teil des Gesundheitsministeriums und damit als dem stärkeren politischen Entscheidungsträger.
360° Videos for Immersive Mental Health Interventions: a Systematic Review
Authors: Ionescu Alina , Van Daele Tom , Rizzo Albert , Blair Carolyn , Best Paul 
Published: September 2021

AbstractVirtual reality is increasingly recognized as a powerful method for clinical interventions in the mental health field, but has yet to achieve mainstream adoption in routine mental healthcare settings. A similar, yet slightly different technology, immersive 360° videos might have the potential to cover this gap, by requiring both lower costs and less technical skills to construct and operate such virtual environments. This systematic review therefore aims to identify, evaluate, and summarize mental health interventions using immersive 360° videos to support an understanding of their implementation in daily clinical practice. The quality of the 14 selected studies was evaluated using a critical appraisal tool, addressing populations with clinical levels of psychopathological symptoms, somatic conditions associated with psychological implications, and other at-risk groups. Immersive 360° videos successfully increased users’ feelings of presence, given their realistic features, and therefore yielded positive outcomes in clinical interventions where presence is considered as an essential precondition. Because the technical skills required to create immersive 360° video footage are fairly limited, most of the interventions using this approach have been created by mental health researchers or clinicians themselves. Immersive 360° videos are still in an early phase of implementation as a tool for clinical interventions for mental health, resulting in high heterogeneity in focus, procedures, and research designs. An important next step for making use of this technology may therefore involve the creation of standardized procedures, as a means to increase the quality of research and evidence-based interventions.
Der Antisemitismus der Anderen: Für eine differenzierte Betrachtung antisemitischer Einstellungen unter Muslim:innen in Deutschland
Authors: Öztürk Cemal , Pickel Gert 
Published: September 2021

ZusammenfassungBereits seit einigen Jahren schwelt eine Diskussion über einen neuen Antisemitismus. Im Fokus dieser Debatten finden sich immer häufiger Einwanderer:innen, vor allem aber Muslim:innen wieder. Als Folge kam der Begriff eines islamisierten Antisemitismus auf. Schnell wurden diese Diskussionen zu einem Politikum. Rechtsextreme Akteure wie die Alternative für Deutschland griffen die Hinweise auf Antisemitismus unter Muslim:innen auf und instrumentalisierten diese für ihre antimuslimische Agenda. Diese Instrumentalisierung wiederum macht es Menschen, die sich gegen antimuslimische Diskriminierung einsetzen, schwer, die Existenz eines muslimischen Antisemitismus anzuerkennen. Anhand unterschiedlichen empirischen Materials untersucht dieser Beitrag die Prävalenz antisemitischer Ressentiments unter Muslim:innen und wie diese mit der Persistenz von Antisemitismus in der deutschen Gesellschaft zusammenhängen. Die Ergebnisse zeigen, dass traditionelle Formen des Antisemitismus und insbesondere israelbezogener Antisemitismus unter Muslim:innen besonders akzentuiert ausfällt. Der Antisemitismus, in muslimischen Submilieus, stellt neben dem ethnonationalen, rechtsextremen Antisemitismus eine Bedrohung für Jud:innen in Deutschland dar. Der Antisemitismus unter Muslim:innen stützt sich sowohl auf Narrative, die aus ihren Herkunftsländern stammen, sowie auf religiöse Quellen. Allerdings ist der Antisemitismus unter Muslim:innen in Deutschland geringer ausgeprägt als in den meisten Gesellschaften der islamischen Welt. Darüber hinaus sind schuldverleugnende Artikulationen von Antisemitismus nach wie vor ein Markenzeichen der autochthonen Bevölkerung und rechter politischer Milieus. Antisemitismus in Deutschland bedarf daher eines differenzierteren Verständnisses, als es noch vor wenigen Jahren notwendig erschien.