bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sirpiglenastat (DRP-104) Induces Antitumor Efficacy through Direct, Broad Antagonism of Glutamine Metabolism and Stimulation of the Innate and Adaptive Immune Systems
Authors: Yokoyama Yumi , Estok Thomas M. , Wild Robert 
Published: August 2022

Abstract
Glutamine is a conditionally essential amino acid consumed by rapidly proliferating cancer cells, which deprives the same fuel from immune cells and contributes to tumor immune evasion. As such, the broad antagonism of glutamine in tumors and the tumor microenvironment may lead to direct antitumor activity and stimulation of antitumoral immune responses. DRP-104 (sirpiglenastat) was designed as a novel prodrug of the broad-acting glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON). DRP-104 is an inactive form that is preferentially converted to DON within tumors. Metabolomic profiling of tumors treated with DRP-104 revealed widespread changes indicative of the disruption of tumor anabolism and canonical cancer metabolism pathways; including altered glutamine metabolism while several immunosuppressive metabolites were decreased. Gene expression profiling revealed broad immunological modulation, confirmed by flow cytometry indicating that DRP-104 treatment resulted in substantial and broad changes in various immune cell infiltrates, such as increased TIL, T, NK, and NK T cells. Functionally, T cells became more proliferative and less exhausted; tumor-associated macrophages were polarized to the M1 phenotype; MDSCs and protumorigenic proteins were decreased in TME. Finally, DRP-104 demonstrated significant antitumor activity as a monotherapy, which was further enhanced in combination with checkpoint blockade therapies, leading to improved survival and long-term durable cures. In summary, DRP-104 broadly remodels the tumor microenvironment by inducing extensive tumor metabolism effects and enhancing the infiltration and function of multiple immune cells distinct from those obtained by checkpoint inhibitor therapy. This unique mechanism of action supports the ongoing clinical development of DRP-104 alone and in combination with checkpoint inhibitors.
BCL10 Mutants: Architects of Oncogenic Signaling Provide a Blueprint for Precision Medicine
Authors: Phelan James D. , Oellerich Thomas 
Published: August 2022

Summary:
BCL10, a key activator of NF-κB downstream of oncogenic B-cell receptor signaling, is mutated in nearly 40% of the BN2/C1 genetic subtype of diffuse large B-cell lymphoma, but how these mutations function to augment signaling and their relevance to targeted precision medicine agents remains unclear. In this issue of Cancer Discovery, Xia and colleagues demonstrate distinct mechanisms of oncogenic signaling regulation and therapeutic vulnerabilities among different recurrent BCL10 mutations.
See related article by Xia et al., p. 1922 (1).
Repeated Measures of Modified Rankin Scale Scores to Assess Functional Recovery From Stroke: AFFINITY Study Findings
Authors: Chye Alexander , Hackett Maree L. , Hankey Graeme J. , Lundström Erik , Almeida Osvaldo P. , Gommans John , Dennis Martin , Jan Stephen , Mead Gillian E. , Ford Andrew H. , Beer Christopher Etherton , Flicker Leon , Delcourt Candice , Billot Laurent , Anderson Craig S. , Stibrant Sunnerhagen Katharina , Yi Qilong , Bompoint Severine , Nguyen Thang Huy , Lung Thomas 
Published: August 2022

Background
Function after acute stroke using the modified Rankin Scale (mRS) is usually assessed at a point in time. The analytical implications of serial mRS measurements to evaluate functional recovery over time is not completely understood. We compare repeated‐measures and single‐measure analyses of the mRS from a randomized clinical trial.

Methods and Results
Serial mRS data from AFFINITY (Assessment of Fluoxetine in Stroke Recovery), a double‐blind placebo randomized clinical trial of fluoxetine following stroke (n=1280) were analyzed to identify demographic and clinical associations with functional recovery (reduction in mRS) over 12 months. Associations were identified using single‐measure (day 365) and repeated‐measures (days 28, 90, 180, and 365) partial proportional odds logistic regression. Ninety‐five percent of participants experienced a reduction in mRS after 12 months. Functional recovery was associated with age at stroke <70 years; no prestroke history of diabetes, coronary heart disease, or ischemic stroke; prestroke history of depression, a relationship partner, living with others, independence, or paid employment; no fluoxetine intervention; ischemic stroke (compared with hemorrhagic); stroke treatment in Vietnam (compared with Australia or New Zealand); longer time since current stroke; and lower baseline National Institutes of Health Stroke Scale & Patient Health Questionnaire‐9 scores. Direction of associations was largely concordant between single‐measure and repeated‐measures models. Association strength and variance was generally smaller in the repeated‐measures model compared with the single‐measure model.

Conclusions
Repeated‐measures may improve trial precision in identifying trial associations and effects. Further repeated‐measures stroke analyses are required to prove methodological value.

Registration

URL: http://
www.anzctr.org.au
; Unique identifier: ACTRN12611000774921.
Risk of Sudden Death in a General Unbiased Epidemiological Cohort of Sarcoidosis
Authors: Chahal C. Anwar A. , Brady Peter A. , Cooper Leslie T. , Lin Grace , Somers Virend K. , Crowson Cynthia S. , Matteson Eric L. , Ungprasert Patompong 
Published: August 2022

Background
Sarcoidosis is an inflammatory, noncaseating, granulomatous disorder of unknown cause that can affect any body system and is associated with cardiovascular disease including sudden cardiac death (SCD). Cardiac involvement in sarcoidosis is associated with higher risk of SCD, but the SCD risk in the general sarcoidosis population is unknown. We aimed to determine the risk of SCD in people with sarcoidosis versus the matched general population.

Methods and Results
A population‐based cohort of sarcoidosis and age‐ and sex‐matched comparators from January 1, 1976 to December 31, 2013 was used; presence of other comorbidities in the comparator group was not an exclusion criterion. Mortality, including time, place, and cause of death were measured and manually adjudicated for SCD events. Incidence rates are reported per 100 000 person‐years, and Cox models were used for group comparisons. Of the 345 incident cases of sarcoidosis (171 men; 50%) there were 58 reported deaths; 10 were definite/probable SCD versus 57 all‐cause and 9 SCDs in comparators. Median follow‐up was 12.9 years (interquartile range, 6.0–23.4 years) . Incidence rate of SCD in sarcoidosis was 192 (95% CI, 92–352) versus 155 (95% CI, 71–294) in comparators (hazard ratio [HR], 1.28 (95% CI, 0.52–3.17). Nocturnal deaths were more frequent in sarcoidosis 57 (95% CI, 12–168) versus 17 (95% CI, 0.4–95) (HR, 3.76 [95% CI, 0.39–36.47]). No significant differences were detected between the groups by sex, age, calendar year of diagnosis, or disease duration.

Conclusions
In a population‐based cohort of patients with sarcoidosis, the risk for SCD compared with matched comparators was not increased. There were more nocturnal deaths among patients with sarcoidosis, yet this was statistically insignificant.
Divided Loyalties: The Elector Palatine and Charles I, 1638–1649
Authors: Pert Thomas 
Published: August 2022

Abstract
In August 1644, the eldest nephew of Charles I landed in England and publicly declared his support for parliament. Charles Louis, the exiled Elector of the Palatinate, has been accused by successive generations of scholars of either harboring ambitions for his uncle’s throne, or having a long-standing friendship with leading parliamentarians which made his eventual allegiance an inevitability. However, such interpretations ignore the influence of short-term developments in the British Isles and on the continent on the actions of this impoverished and exiled prince, who was dependent on English financial and diplomatic support and faced the very real risk of being permanently excluded from his ancestral lands and titles. This article therefore provides a valuable insight into how political and financial necessities could clash with the perceived obligations of dynastic loyalty between ruling elites in early modern Europe.
(Meta) Grotian Moment: International Organizations and the Rapid Formation of Customary International Law
Authors: Gasbarri Lorenzo 
Published: August 2022

Abstract
In this paper, I first discuss the concept of ‘Grotian Moment’ in the context of the capacity of international organizations to contribute to the formation and identification of customary international law. Afterward, I apply three levels to discuss the time element of the formation of custom. At the micro-level of the institutional practice, the time required to form a customary norm may depend on whether each form of practice is directed to the institutional or to the international dimension. At the level of the organ, I reflect on the difference played by the presence or absence of member States in the institutional organ that adopts the practice relevant for custom formation. At the macro-level of the characteristics of the organization, I distinguish between so-called supranational and functional organizations. In general, I exclude the relevance of speaking in terms of a ‘Moment’ that produces a paradigm shift, and I stress the continuous change to which international law is subject.
Grotian Moments in the Law of Self-Determination: Law, Rhetoric, and Reality
Authors: Sparks Tom 
Published: August 2022

Abstract
Self-determination is one of international law’s most reviled and yet most important principles. The legal development of self-determination – or specific forms thereof – as a customary norm of international law has been shaped and spurred by key moments. These include the American and French declarations of 1776 and 1789, the conclusion of the UN Charter, and the General Assembly’s resolution 1514 (xv) in 1960. This article analyses whether, in characterising the effect of such moments, the label ‘Grotian’ moment adds meaningfully to the analysis. It concludes that the example of self-determination suggests that the ‘Grotian’ moment concept is not meaningfully illuminating; tending either to reduce to a slight of hand in favour of the so-called ‘Great Powers’, or alternatively to pathologise developments that would be amenable to standard forms of customary legal analysis.
Ancient Geographers and Modern Travelogues in the Early Seventeenth Century. The Difference between Hugo Grotius’s Bewys van den waren Godsdienst (1622) and De veritate religionis christianae (1627–40)
Authors: Bergjan Silke-Petra 
Published: August 2022

Abstract
The Bewys van den waren Godsdienst and De veritate religionis Christianae originated against the background of Grotius’s familiarity with classical literature. To understand the innovative impact of these writings, the historical method applied must be considered. Grotius did not rely on authorities, but was compiling historical witnesses for the three religions. The availability and visibility of the witness reports are regularly referred to in the text. Thus, history and classical historians enter the picture. Interestingly, this cannot be separated from the debate about the methods to be used in geography, a matter that gains importance as the difference between Bewys and De veritate is nowhere as visible as in the geographical references. The generous sprinkling of place names from different continents contributes to the poem’s factual character. The place names in the Bewys derive from the Dutch sea trade and can be found in the travel reports of the time. This is elucidated by two examples: the island Waygat in the Artic, and the coast of Mina in the Gulf of Guinea. In De veritate, however, all such references are removed. In their stead appear examples from ancient topography, to be annotated in the 1640 edition with ample quotations from Pliny, Strabo, Josephus and others.
Searching for Meaning: Inaccurate Interpretations and Deceitful Predictions in Dream Narratives of the Qing
Authors: Lucas Aude 
Published: August 2022

Abstract
This paper explores cases of inaccurate interpretations or deceitful dream predictions in early and mid-Qing xiaoshuo and biji – Chinese leisure literature of short stories and anecdotes. While most dream narratives from this body of literature drew on the oneiromantic tradition and featured dream omens that get realized, some anecdotes playfully recounted tales of misunderstood dreams or deceptive oneiric forecasts. Such cases reveal a disillusioned stance of Qing authors toward the classical discourse on oneiromancy and a playful use of the usual rhetoric of how dreams were supposed to convey the truth. Through them, one may perceive an intention of Qing authors to reassess the conventional discourse on dreams and find a new way of writing about dreams with other concerns than divination.
This paper reminds how the signifiers of a dream may mean different things to each dreamer or each person that interprets a dream, revealing how dream omens and interpretations are subject to individual understanding. This article is divided into two main parts. The first part is devoted to wrong interpretations of dreams, either because the following events are happier than what the person interpreting the dream expected, or because the realization of the omens turns out more disappointing than predicted. The second part deals with dream predictions that are evidently deceptive. These dishonest forecasts may be granted to dreamers by manipulative beings, or more surprisingly, by forces that are harder to understand. In the latter case, those who are tricked by what seems to be fate itself are left at a loss, looking in vain for the meaning of their dreams.
The Christian Attitude to Hippomancy in Twelfth-Century Szczecin and the Desacralization of the Sacred Horse
Authors: Dragnea Mihai 
Published: August 2022

Abstract
Among the “idolatrous” Pomeranians, the horse was considered a sacred animal that was kept in a major temple and used by priests in the exercise of their spiritual power. In order to diminish the influence of the Pomeranian priesthood upon the upper and lower classes, the German clergy sometimes desacralized the sacred horse. This study will analyze the missionaries’ tactic to reduce the faith of the Pomeranians in ancient superstitions such as divination and thus convince them to accept baptism voluntarily and not to organize raids against Christians. The analysis will provide a much deeper insight into the beliefs of the Slavic communities on the Baltic Sea in the ecclesiastical circles of the twelfth century. It will show that the horse was a key tool in Pomeranian society used in divination to decide about the most relevant public matters, including military campaigns.
Impacts of Stratospheric Polar Vortex Shift on the East Asian Trough
Authors: Zhang Chongyang , Zhang Jiankai , Xu Mian , Zhao Siyi , Xia Xufan 
Published: August 2022

Abstract
Impacts of stratospheric polar vortex shift on the wintertime East Asian trough (EAT) on intraseasonal time scales are investigated using a reanalysis dataset and a climate model. The result based on composite analysis shows that the shift of the stratospheric polar vortex toward eastern Siberia (ES-shift event) is associated with higher geopotential height at 500 hPa than normal over East Asia, corresponding to the weakened EAT. Furthermore, the simulated EAT is also weakened when nudging the stratospheric state toward that during the ES-shift events. This study further found that there is no significant difference in the stratospheric polar vortex intensity between the ES-shift events and nonshift events, implying that the polar vortex strength change may have little influence on the possible connection between the polar vortex shift and the EAT change. The underlying mechanisms are listed as follows: First, the positive potential vorticity (PV) anomalies in the lower stratosphere associated with ES-shift events could explain approximately 40% of the local westerly anomalies in the upper troposphere to the north of East Asia via PV conservation, leading to the rise of the geopotential height over East Asia and the weakening of the EAT. Second, the shift of stratospheric polar vortex could modulate the synoptic-scale Rossby wave activity in the upper troposphere, favorable for the southward propagation of synoptic-scale waves and divergence of extended Eliassen-Palm flux in the upper troposphere. Finally, the transient wave feedback could enhance the tropospheric westerly anomalies in the north of East Asia and induce positive height anomalies to its south, further weakening the EAT. Our results revealed that the stratospheric polar vortex shift leads the EAT intensity variation by around 2–5 days, implying that the stratospheric polar vortex shift could be applicable to the prediction of the EAT intensity.
Teachers’ awareness and perceptions of Health Education Nutrition Programmes in Greece: A qualitative study
Authors: Koutsaki Maria , Saltaouras Georgios , Diamantopoulou Eryfili , Dardavessis Theodoros , Androutsos Odysseas 
Published: August 2022

Objective: The aim of this study was to evaluate primary and secondary school teachers’ attitudes and perceptions regarding the usefulness and effectiveness of Health Education Nutrition Programmes (HENPs) in Greece. Design: Qualitative study using semi-structured interviews. Method: In total, 18 teachers (7 men, 11 women), aged 36–55 years, working in primary ( n = 8) and secondary education ( n = 10) were recruited via purposive sampling from three counties in Greece and were interviewed via through an online platform. Thematic analysis was used to interpret the data. Results: Four main themes were identified: teachers’ awareness of HENPs; the role of the external environment in shaping students’ dietary habits; the value of experiential learning; and barriers and facilitators to the implementation of HENPs. Most teachers considered HENPs important and effective in improving children’s eating habits through experiential learning; however, training and support were very limited. The family has a crucial role in shaping children’s eating habits, which highlights the need for collaboration between school and family. The main barriers for the implementation of HENPs were lack of time and resources. Conclusions and implications: Teachers perceive HENPs as effective tools to improve children’s dietary behaviour. However, they need support/training from experts to deliver them successfully at school. Expert guidance to train the teachers and family involvement are needed to increase the effectiveness of the HENPs used in Greek primary and secondary schools.
Analysis of postoperative radiotherapy for non-metastatic head and neck adenoid cystic carcinoma based on SEER data
Authors: Du Yan , Zeng Yong 
Published: August 2022

Objective The postoperative role of adjuvant radiotherapy in non-metastatic head and neck adenoid cystic carcinoma (ACC) remains controversial. We analyzed adjuvant radiotherapy’s effect on surgical patient survival. Methods Patients diagnosed with ACC from 2004 to 2015 in the Surveillance, Epidemiology, and End Results database were analyzed. The overall survival (OS) and disease-specific survival (DSS) of patients after adjuvant radiotherapy were assessed using the Kaplan–Meier and multivariate Cox methods. Propensity score matching (PSM) was performed to adjust confounders between patients with or without adjuvant radiotherapy; a forest plot was generated by subgroup analysis. Results The study included 742 patients. In the PSM cohort, adjuvant radiotherapy did not improve OS or DSS. Radiotherapy was not a protective factor for OS or DSS in the univariate and multivariate Cox proportional hazard models. In the subgroup analysis, postoperative radiotherapy improved the OS of female and N1-stage patients and those with oropharyngeal tumors or over 79 years and the DSS of N1-stage patients. Conclusions Postoperative radiotherapy showed different benefits in ACC patients, and postoperative radiotherapy recommendations should be individualized. Female and N1-stage ACC patients and those with oropharyngeal tumors or patients over 79 years without distant metastases postoperatively could benefit from adjuvant radiotherapy.
Risk Factors Associated With Opioid/Benzodiazepine Iatrogenic Withdrawal Syndrome in COVID-19 Acute Respiratory Distress Syndrome
Authors: Maffei Melissa Vu , Laehn Spencer , Bianchini Monica , Kim Andy 
Published: August 2022

Background Mechanically ventilated COVID-19 acute respiratory distress syndrome (ARDS) patients often receive deeper sedation and analgesia to maintain respiratory compliance and minimize staff exposure, which incurs greater risk of iatrogenic withdrawal syndrome (IWS) and has been associated with worse patient outcomes. Objective: To identify potential risk factors and differences in patient outcomes associated with the development of IWS in COVID-19 ARDS patients. Methods: Retrospective analysis of ventilated COVID-19 ARDS intensive care unit (ICU) patients who received continuous intravenous (IV) analgesia and sedation for ≥5 days from March 2020–May 2021. Patients were classified as IWS and non-IWS based on receipt of scheduled oral sedative/analgesic regimens after cessation of IV therapy. Risk factors were assessed in univariate analyses and multivariable modeling. Results: A total of 115 patients were included. The final multivariable model showed: (1) each additional day of IV opioid therapy was associated with an 8% increase in odds of IWS (95% CI, 1.02-1.14), (2) among sedatives, receipt of lorazepam was associated with 3 times higher odds of IWS (95% CI 1.12-8.15), and (3) each 1-point increase in Simplified Acute Physiology Score (SAPS) II was associated with a 4% reduction in odds of IWS (95% CI 0.93-0.999). Conclusion: Prolonged and high dose exposures to IV opioids and benzodiazepines should be limited when possible. Additional prospective studies are needed to identify modifiable risk factors to prevent IWS.
Determination of epoxy resin usability for mass production of reinforced laminated veneer lumber
Authors: Çiftçi Seymen , Ciritcioglu Hasan Hüseyin , As Nusret , Tankut Nurgül 
Published: August 2022

This study is part of a comprehensive study on the industrial production of reinforced laminated wood composites. The main aim of the study is to determine the production parameters of reinforced laminated wood composite board under an optimal production cycle time under temperature and pressure, using epoxy resin cured at room temperature for 24 h. For this purpose, 1.2 mm thick Samsun Poplar (Populus Deltoides I-77/51) veneer layers, three different pressing cycle times (15, 20, and 25 min), three different temperatures (100°C, 120°C, and 140°C), and three different amounts of adhesive (100, 150, and 200 g/m²) were used also 200 g/m² density twill woven glass–carbon fiber fabric was used as the reinforcement layer. In order to determine the production quality of reinforced laminated wood composite boards, the adhesion strength between the reinforcement layer and the wood veneer layer was determined according to TS EN 3969 314-1. Considering the adhesion strengths in terms of production parameters, the best results were observed at 100°C press temperature, 20 min press cycle time, 200 g/m² adhesive amount, and the use of glass fiber woven fabrics for reinforcement. Under these conditions, the best adhesion strength was found to be 4.17 N/mm². When the samples were examined, it was seen that almost all of the failures occurred as a result of the fracture in the wood layer. This indicates that sufficient adhesion can be achieved between the reinforcement layer and the wood layer.