bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Approach for Quantifying the Pharmacological Activity of T-Cell Engagers Utilizing In Vitro Time Course Experiments and Streamlined Data Analysis
Authors: Van De Vyver Arthur , Eigenmann Miro , Ovacik Meric , Pohl Christian , Herter Sylvia , Weinzierl Tina , Fauti Tanja , Klein Christian , Lehr Thorsten , Bacac Marina , Walz Antje-Christine 
Published: December 2021

AbstractCD3-bispecific antibodies are a new class of immunotherapeutic drugs against cancer. The pharmacological activity of CD3-bispecifics is typically assessed through in vitro assays of cancer cell lines co-cultured with human peripheral blood mononuclear cells (PBMCs). Assay results depend on experimental conditions such as incubation time and the effector-to-target cell ratio, which can hinder robust quantification of pharmacological activity. In order to overcome these limitations, we developed a new, holistic approach for quantification of the in vitro dose–response relationship. Our experimental design integrates a time-independent analysis of the dose–response across different time points as an alternative to the static, “snap-shot” analysis based on a single time point commonly used in dose–response assays. We show that the potency values derived from static
in vitro experiments depend on the incubation time, which leads to inconsistent results across multiple assays and compounds. We compared the potency values from the time-independent analysis with a model-based approach. We find comparably accurate potency estimates from the model-based and time-independent analyses and that the time-independent analysis provides a robust quantification of pharmacological activity. This approach may allow for an improved head-to-head comparison of different compounds and test systems and may prove useful for supporting first-in-human dose selection.
AMBRA1 promotes dsRNA- and virus-induced apoptosis through interacting with and stabilizing MAVS
Authors: Lin Yuxia , Huang Changbai , Gao Huixin , Li Xiaobo , Lin Quanshi , Zhou Shili , Huo Zhiting , Huang Yanxia , Liu Chao , Zhang Ping 
Published: December 2021

ABSTRACT
Apoptosis is an important cellular response to viral infection. In this study, we identified activating molecule in Beclin1-regulated autophagy protein 1 (AMBRA1) as a positive regulator of apoptosis triggered by double-stranded (ds)RNA. Depletion of AMBRA1 by gene editing significantly reduced dsRNA-induced apoptosis, which was largely restored by trans-complementation of AMBRA1. Mechanistically, AMBRA1 interacts with mitochondrial antiviral-signaling protein (MAVS), a key mitochondrial adaptor in the apoptosis pathway induced by dsRNA and viral infection. Further co-immunoprecipitation analysis demonstrated that the mitochondrial localization of MAVS was essential for their interaction. The impact of AMBRA1 on dsRNA-induced apoptosis relied on the presence of MAVS and caspase-8. AMBRA1 was involved in the stabilization of MAVS through preventing its dsRNA-induced proteasomal degradation. Consistently, AMBRA1 upregulated the apoptosis induced by Semliki Forest virus infection. Taken together, our work illustrated a role for AMBRA1 in virus-induced apoptosis through interacting with and stabilizing MAVS.
Non-Enzymatic Kinetic Resolution and Desymmetrization of α-Quaternary Carboxylic Acids via Chiral Bifunctional Sulfide-Catalyzed Bromolactonization
Authors: Okuno Ken , Hiraki Mana , Chan Bun , Shirakawa Seiji 
Published: December 2021

AbstractKinetic resolution of racemic carboxylic acids is a reliable method to enantioselectively prepare chiral carboxylic acids. Although efficient catalytic kinetic resolutions of chiral α-tertiary carboxylic acids have been reported, the kinetic resolution of α-quaternary carboxylic acids bearing an all-carbon quaternary stereocenter has remained a formidable challenge. Herein, we report a precious example of a kinetic resolution of α-quaternary carboxylic acids via a chiral bifunctional sulfide-catalyzed bromolactonization of alkynes. The ability of chiral sulfides to recognize α-quaternary carboxylic acids was evaluated via the catalytic enantioselective desymmetrizing bromolactonization of achiral α,α-dipropargyl carboxylic acids, which is a reaction that is related to target kinetic resolution. The optimum chiral sulfide was successfully applied to the efficient kinetic resolution of α-propargyl carboxylic acids that bear an all-carbon quaternary stereocenter.
Halide-Adducts of OsO4. Structure and Reactivity in Alcohol-Oxidation
Authors: Fujimoto Tomohiro , Hirata Yuka , Sugimoto Hideki , Miyanishi Mayuko , Shiota Yoshihito , Yoshizawa Kazunari , Itoh Shinobu 
Published: December 2021

Abstract
Interaction of osmium tetroxide (OsO4) with a series of halide ions (X− = I−, Br−, Cl−, and F−) is examined. Stable 1:1 adducts, [OsO4(X)]− (1X), are formed in the case of Br−, Cl−, and F−, whereas redox reaction takes place with I− to give [OsVIIO4]− and I•. The adduct formation constant (KfX) increases as the basicity of the halide ion increases (Br− &lt; Cl− &lt; F−). Upon the adduct formation, the symmetric (ν(Os=O)sym) and asymmetric (ν(Os=O)asym) Os=O stretching vibration energies are lowered as compared with those of OsO4. The X-ray crystallographic analyses of the halide adducts indicate that the structural distortion of the osmium center from tetrahedron to trigonal bipyramid becomes larger as the KfX value becomes larger. 1F shows much higher reactivity compared with 1Br and 1Cl in the oxidation of benzyl alcohol to benzaldehyde, even though 1F has a lower reduction potential compared to 1Br and 1Cl. Mechanistic details of the alcohol oxidation reaction are evaluated by kinetic studies including Hammett analysis and kinetic deuterium isotope effect as well as by DFT calculations.
Partial Completion as a Nonprofit Strategy
Authors: Zhang Can , Atasu Atalay , Ramachandran Karthik 
Published: December 2021

Problem definition: Faced with the challenge of serving beneficiaries with heterogeneous needs and under budget constraints, some nonprofit organizations (NPOs) have adopted an innovative solution: providing partially complete products or services to beneficiaries. We seek to understand what drives an NPO’s choice of partial completion as a design strategy and how it interacts with the level of variety offered in the NPO’s product or service portfolio. Academic/practical relevance: Although partial product or service provision has been observed in the nonprofit operations, there is limited understanding of when it is an appropriate strategy—a void that we seek to fill in this paper. Methodology: We synthesize the practices of two NPOs operating in different contexts to develop a stylized analytical model to study an NPO’s product/service completion and variety choices. Results: We identify when and to what extent partial completion is optimal for an NPO. We also characterize a budget allocation structure for an NPO between product/service variety and completion. Our analysis sheds light on how beneficiary characteristics (e.g., heterogeneity of their needs, capability to self-complete) and NPO objectives (e.g., total-benefit maximization versus fairness) affect the optimal levels of variety and completion. Managerial implications: We provide three key observations. (1) Partial completion is not a compromise solution to budget limitations but can be an optimal strategy for NPOs under a wide range of circumstances, even in the presence of ample resources. (2) Partial provision is particularly valuable when beneficiary needs are highly heterogeneous, or beneficiaries have high self-completion capabilities. A higher self-completion capability generally implies a lower optimal completion level; however, it may lead to either a higher or a lower optimal variety level. (3) Although providing incomplete products may appear to burden beneficiaries, a lower completion level can be optimal when fairness is factored into an NPO’s objective or when beneficiary capabilities are more heterogeneous. History: This paper has been accepted for the Manufacturing & Service Operations Management Special Section on Responsible Research in Operations Management. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2021.1031 .
Model Variasi Kalender pada Regresi Runtun Waktu untuk Peramalan Jumlah Pengunjung Grojogan Sewu
Authors: Zukhronah Etik , Sulandari Winita , Slamet Isnandar , Sugiyanto Sugiyanto , Susanto Irwan 
Published: December 2021

<p><strong>Abstract.</strong> Grojogan Sewu visitors experience a significant increase during school holidays, year-end holidays, and also Eid al-Fitr holidays. The determination of Eid Al-Fitr uses the Hijriyah calendar so that the occurrence of Eid al-Fitr will progress 10 days when viewed from the Gregorian calendar, this causes calendar variations. The objective of this paper is to apply a calendar variation model based on time series regression and SARIMA models for forecasting the number of visitors in Grojogan Sewu. The data are Grojogan Sewu visitors from January 2009 until December 2019. The results show that time series regression with calendar variation yields a better forecast compared to the SARIMA model. It can be seen from the value of root mean square error (<em>RMSE</em>) out-sample of time series regression with calendar variation is less than of SARIMA model.</p><p><strong>Keywords: </strong>Calendar variation, time series regression, SARIMA, Grojogan Sewu</p>
Being a transnational researcher and a mother amid the COVID-19 crisis
Authors: Tartari Morena 
Published: December 2021

The article focuses on the author’s experience as a transnational researcher during the early months of the COVID-19 outbreak (January–April 2020), and discusses the possibilities and impossibilities of the COVID-19 pandemic for mothers who are transnational researchers.
The sociological approach of institutional ethnography is utilised to analyse entries from the author’s diary, articles and videos from mass media, posts on social media, and institutional texts (for example, regulations, policies).
The disjunctures between the different versions of reality (the author’s experiential perspective versus the ruling perspectives of the various institutions that framed the author’s experience at different stages) are discussed from the author’s standpoint as an international researcher, a woman and a single mother.
Simultaneous imaging of sound propagations and spatial distribution of acoustic frequencies
Authors: Hashimoto Sota , Takase Yuki , Inoue Tomoyoshi , Nishio Kenzo , Xia Peng , Rajput Sudheesh K. , Matoba Osamu , Awatsuji Yasuhiro 
Published: December 2021

We propose a simultaneous imaging technique of both sound propagations and spatial distribution of acoustic frequencies. We experimentally demonstrated the proposed technique for the acoustic waves of frequencies 39,500 and 40,500 Hz, which have close sound pressure. The sounds were recorded at the framerate of 100,000 fps by parallel phase-shifting digital holography. To obtain the distribution of the acoustic frequencies, the short-time Fourier transform analysis was applied. The simultaneous imaging was carried out by assigning the frequencies and the pixel values of the phase-difference images to the components of HSL color space. The images obtained by the proposed technique represent the frequencies with the hue in addition to the sound propagations with the luminance. We succeeded in imaging the spatiotemporal evolution of the spatial frequencies of the sounds.
Psychological distress of patients with end-stage kidney disease undergoing dialysis during the 2019 coronavirus disease pandemic: A cross-sectional study in a University Hospital
Authors: Yu Jin Young , Kim Ji Sun , Hong Chae-Min , Lee Ka Young , Cho Nam-Jun , Park Samel , Gil Hyo-Wook , Lee Eun Young 
Published: December 2021

Introduction
Previous studies have revealed that the COVID-19 pandemic can cause psychological distress such as depression and anxiety. Patients with chronic kidney disease (CKD) might be more vulnerable to psychological distress due to the COVID-19 pandemic. Its impact could be different according to dialysis modality. The aim of this study was to investigate COVID-19-related psychological stress experienced by end-stage kidney disease (ESKD) patients and identify differences in concerns about COVID-19 between hemodialysis (HD) and peritoneal dialysis (PD) patients.

Methods
This cross-sectional study included 148 dialysis patients at Soonchunhyang University Cheonan Hospital from August 2020 to September 2020. These patients responded to a questionnaire covering mental health status and COVID-19 related concerns. Symptoms of depression, anxiety, stress, and insomnia were measured using a 9-item Patient Health Questionnaire (PHQ-9), a 7-item Generalized Anxiety Disorder (GAD-7) scale, a 22-item Impact of Event Scale-Revised (IES-R), and a 7-item Insomnia severity Index (ISI), respectively. Outcomes of HD and PD patients were compared by propensity score matching analysis.

Results
Dialysis patients reported psychological distress including symptoms of depression, anxiety, stress, and insomnia. HD patients showed higher scores for depression (p = 0.018), anxiety(p = 0.005), stress(p<0.001), and insomnia(p = 0.006) than the PD patients. After propensity score matching, HD was associated with depression(p = 0.0131), anxiety(p = 0.0143), and stress(p = 0.000415).

Conclusion
Dialysis patients showed psychological distress during the COVID-19 pandemic period, with HD patients having more severe symptoms than PD patients.
Current practices of management of maternal and congenital Cytomegalovirus infection during pregnancy after a maternal primary infection occurring in first trimester of pregnancy: Systematic review
Authors: Périllaud-Dubois Claire , Belhadi Drifa , Laouénan Cédric , Mandelbrot Laurent , Picone Olivier , Vauloup-Fellous Christelle 
Published: December 2021

Introduction
Congenital CMV infection is the first worldwide cause of congenital viral infection but systematic screening of pregnant women and newborns for CMV is still debated in many countries.

Objectives
This systematic review aims to provide the state of the art on current practices concerning management of maternal and congenital CMV infection during pregnancy, after maternal primary infection (PI) in first trimester of pregnancy.

Data sources
Electronically searches on databases and hand searches in grey literature.

Study eligibility criteria and participants
Primary outcome was listing biological, imaging, and therapeutic management interventions in two distinct populations: population 1 are pregnant women with PI, before or without amniocentesis; population 2 are pregnant women with congenitally infected fetuses (after positive amniocentesis). Secondary outcome was pregnancy outcome in population 2.

Results
Out of 4,134 studies identified, a total of 31 studies were analyzed, with 3,325 pregnant women in population 1 and 1,021 pregnant women in population 2, from 7 countries (Belgium, France, Germany, Israel, Italy, Spain and USA). In population 1, ultrasound (US) examination frequency was 0.75/month, amniocentesis in 82% cases, maternal viremia in 14% and preventive treatment with hyperimmune globulins (HIG) or valaciclovir in respectively 14% and 4% women. In population 2, US examination frequency was 1.5/month, magnetic resonance imaging (MRI) in 44% cases at 32 weeks gestation (WG), fetal blood sampling (FBS) in 24% at 28 WG, and curative treatment with HIG or valaciclovir in respectively 9% and 8% patients.

Conclusions
This systematic review illustrates management of maternal and congenital CMV during pregnancy in published and non-published literature, in absence of international consensus.

Systematic review registration
PROSPERO CRD42019124342
Increase in cardioprotective SUR2A does not alter heart rate and heart rate regulation by physical activity and diurnal rhythm
Authors: Sudhir Rajni , Jaafar Nadim , Du Qingyou , Sukhodub Andriy , Jovanović Sofija , Kreouzi Magdalini , Jovanović Aleksandar 
Published: December 2021

Abstract

Objectives
SUR2A is an ABC protein serving as a regulatory subunit of ATP-sensitive (KATP) channels. An increase in SUR2A levels is cardioprotective and it is a potential therapeutic strategy against ischaemic heart disease, heart failure and other diseases. However, whether overexpression of this protein has any adverse effects is yet to be fully understood. Here, we examined the heart rate and the heart rate diurnal variation in mice overexpressing SUR2A (SUR2A+) and their littermate controls (WT) using ECG telemetry that was continuously recorded for 14 days (days 8–23 post-radiotransmitter implantation).

Methods
Using SigmaPlot 14.0 and Microsoft Excel, Area Under the Curve (AUC) for each parameter was calculated and plotted in a graph.

Results
Both WT and SUR2A+ mice were more physically active during nights and there were no significant differences between two phenotypes. Physical activity was associated with increased heart rate in both phenotypes, but there were no differences in heart rate between phenotypes irrespective of physical activity or time of the day. A diurnal heart rate variation was preserved in the SUR2A+ mice. As area under the curve (AUC) analysis has the potential to reveal differences that are invisible with other statistical methods, we compared AUC of heart rate in SUR2A+ and WT mice. This analysis did not yield anything different from traditional analysis.

Conclusions
We conclude that increased SUR2A levels are not associated with changes in physical activity, heart rate and/or circadian rhythm influence on the heart rate. This lack of adverse effects supports a notion that manipulation with SUR2A levels is a promising cardioprotective strategy.
Sign-Objects Among Neolithic Faunal Remains, Visible Symbols
Authors: Hachem Lamys 
Published: December 2021

AbstractThe purpose of this article is to present an inventory of certain faunal remains from Linearbandkeramic (LBK) settlements in the Paris Basin (Ile-de-France, Hauts-de-France and Champagne) that seem to belong to a particular category, that of “sign-objects,” in other words, tangible evidence intended to be shown and directly interpretable by an observer belonging to the society which produced them. Based on three categories of archaeological contexts, a ceremonial enclosure, settlements and graves, we will attempt to highlight the species that were important to Neolithic society. Two of them, the domestic cattle and the aurochs, are particularly involved in the deposits through the exhibition of their bones or their horn cores. Sheep and roe deer are also involved through, for example, transformed bones such as perforated tibias or sharpened roe deer antlers. The results of the analysis were integrated into an archaeological model previously developed to approach the social structure of the Neolithic society.
Legacy in the Making – A Knowledge Infrastructural Perspective on Systems for Archeological Information Sharing
Authors: Börjesson Lisa 
Published: December 2021

AbstractArcheological research depends on a complex infrastructure of information systems and services built on different funding models. The information systems enable innovative approaches and progress in information making, but each system also organizes information by means of the system design, the structures, and relations established and the terminologies promoted. This article adopts a knowledge infrastructural perspective on systems used for information sharing in archeology. The purpose is first to expand the perspective on the systems for research information sharing in archeology and second to discuss the potential impact of the knowledge infrastructure on disciplinary knowledge-making, the shaping of archeological information, and legacy data. Based on an analysis of qualitative interviews (N= 31) with archeologists from Europe and the United States, the results show that the interviewees use sharing solutions developed within the archeology discipline as well as general information sharing systems. One important task for further research is to better understand how archeologists choose information sharing systems and how their choices impact what information they share. Also, information sharing for specific topics or with specific coverage appears to be developed with project funding outside of the more established sharing institutions. A key question for the infrastructural sustainability is how to support the inclusion of innovative sharing solutions in institutionalized sharing environments. The results emphasize the need for further studies of how information systems shape archeological legacy in the making, which in turn will support data literacy awareness and training.
Chalcogenative spirocyclization of N-aryl propiolamides with diselenides/disulfides promoted by Selectfluor
Authors: Yuan Jin-Wei , Huang Guang-Chao , Wang Li-Li , Wang Xin-Yuan , Yang Liang-Ru , Zhang Shou-Ren , Mao Pu , Xiao Yong-Mei , Qu Ling-Bo 
Published: December 2021

Abstract
A practical and efficient synthetic route to construct a variety of 3-arylselenenyl/3-arylthio spiro[4.5]trienones was developed using Selectfluor reagent as a mild oxidant. This reaction proceeds via a sequence of electrophilic cation addition, spirocyclization and dearomatization, then offers an approach to introduce Se/S-centered cation into the C–C triple bonds. The utility of this protocol were justified by the excellent compatibility of a wide range of functional groups, good yields and scalability under mild reaction conditions.
Drug-Induced Hyperglycemia as a Potential Contributor to Translational Failure of Uncompetitive NMDA Receptor Antagonists
Authors: Wang Eric Yuhsiang , Lai Ted Weita 
Published: December 2021

AbstractHyperglycemia is a comorbidity in 60–80% of stroke patients; nevertheless, neuroprotective drugs like NMDA receptor (NMDAR) antagonists are typically assessed in normoglycemic animals at the preclinical stage before they are approved to enter clinical trials. Interestingly, as a possible explanation for the translational failure of NMDAR antagonists, it was recently reported that stroke occurring during nighttime causes smaller infarctions in rodents and therefore has a smaller window for neuroprotection. To investigate why stroke occurring during different circadian phases confers a difference in severity, we reanalyzed the published source data and found that some mice that were used in the daytime have higher blood glucose than mice that were used in the nighttime. We then repeated the experiments but found no difference in blood glucose concentration or infarct volume regardless of the circadian phase during which stroke occurs. On the other hand, induction of hyperglycemia by glucose injection reproducibly increased stroke severity. Moreover, although hyperglycemia increases infarction volume, which presumably would provide a larger window for neuroprotection, uncompetitive NMDAR antagonists were unexpectedly found to exacerbate stroke outcome by worsening hyperglycemia. Taken together, our new data and reanalysis of the published source data suggested that blood glucose during stroke, rather than the circadian phase during which stroke occurs, affects the size of the ischemic infarction; moreover, we have revealed drug-induced hyperglycemia as a potential reason for the translational failure of uncompetitive NMDAR antagonists. Future trials for this class of neuroprotective drugs should monitor patients’ blood glucose at enrollment and exclude hyperglycemic patients.