bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Ordovician ocean circulation: a modern synthesis based on data and models
Authors: Pohl Alexandre , Nardin Elise , Vandenbroucke Thijs R. A. , Donnadieu Yannick 
Published: October 2022

Abstract
Surface currents constitute an efficient transport agent for (larvae of) marine faunas, while the circulation of water masses in the ocean interior drives nutrient redistribution, ventilates the ocean and contributes to shaping surface biological productivity and the benthic redox landscape. Therefore, a robust understanding of ocean circulation, both shallow and deep, and of its response to climate change, is required to interpret palaeobiogeographic signals, biological productivity patterns and biodiversity trends. This is especially critical during periods of dynamic biological change, such as the Ordovician. Yet, oceanic circulation patterns leave no direct evidence in the geological record and can therefore be reconstructed solely based on indirect indicators, such as the distribution of faunas and geochemical proxies. General circulation models offer independent, physically robust insights onto the coupling between climate change and ocean circulation. Integrated approaches based on the assimilation of geological data in numerical models thus constitute a promising way forward. We here provide a literature review and updated synthesis of the current understanding of the Ordovician ocean circulation, based on data and models.
The Ordovician of Sardinia (Italy): from the ‘Sardic Phase’ to the end-Ordovician glaciation, palaeogeography and geodynamic context
Authors: Loi Alfredo , Cocco Fabrizio , Oggiano Giacomo , Funedda Antonio , Vidal Muriel , Ferretti Annalisa , Leone Francesco , Barca Sebastiano , Naitza Stefano , Ghienne Jean-François , Pillola Gian Luigi 
Published: October 2022

Abstract
This review illustrates the most important features of the Ordovician successions of the Sardinian basement. We focus on the stratigraphy and tectonic structures in the tectonic units of the External and Nappe zones of the Variscan basement. The Ordovician successions are characterized by unconformities related to tectonic events ascribed to the Sardic and Sarrabese phases. The different durations of the unconformity-related gaps in the External (17 myr) and Nappe (6 myr) zones, recent work on the trilobite fossil content, and the occurrence of a volcanic arc only in the Nappe Zone (Sarrabus and Gerrei units) highlight significant discrepancies suggesting that these domains did not share the same geodynamic setting and palaeogeographical position during the Ordovician. This implies they were amalgamated only in Variscan times. Whereas for the external and nappe zones the Ordovician features are clear, the high-grade metamorphic Inner Zone, where numerous Ordovician ortho- and para-gneiss occur, more detailed studies are needed to define a complete framework for the Ordovician evolution of Sardinia. The present revision of data for the best-preserved succession of Sardinian tectonic units suggests that at least two distinct terranes, which did not share the same Ordovician evolution, were only amalgamated during the Variscan Orogeny.
Lisaftoclax in Combination with Alrizomadlin Overcomes Venetoclax Resistance in Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia: Preclinical Studies
Authors: Zhai Yifan , Tang Qiuqiong , Fang Douglas D. , Deng Jing , Zhang Kaixiang , Wang Qixin , Yin Yan , Fu Chengcheng , Xue Sheng-Li , Li Na , Zhou Feng , Yang Dajun 
Published: October 2022

Abstract

Purpose:
Despite approval of B-cell lymphoma (BCL)-2 inhibitor venetoclax for certain hematologic malignancies, its broader clinical benefit is curtailed by resistance. Our study aimed to determine if treatment with novel anticancer agents targeting BCL-2 and mouse double minute 2 (MDM2) could overcome venetoclax resistance in preclinical models.

Experimental Design:
Venetoclax-sensitive and venetoclax-resistant acute myeloid leukemia (AML) and acute lymphoblastic leukemia cells and xenograft models were used to evaluate antitumor effects and underlying mechanisms associated with combined BCL-2 inhibitor lisaftoclax (APG-2575) and MDM2 inhibitor alrizomadlin (APG-115).

Results:
The combination exhibited synergistic antiproliferative and apoptogenic activities in TP53 wild-type AML cell lines in vitro. This synergy was further exemplified by deep antitumor responses and prolonged survival in AML cell line–derived and patient-derived xenograft models. Interestingly, the combination treatment resensitized (to apoptosis) venetoclax-resistant cellular and mouse models established via chronic drug exposure or genetically engineered with clinically relevant BCL-2 gene mutations. Synergistic effects in reducing cellular viability and proliferation were also demonstrated in primary samples of patients with venetoclax-resistant AML treated with lisaftoclax and alrizomadlin ex vivo. Mechanistically, alrizomadlin likely primes cancer cells to BCL-2 inhibition-induced cellular apoptosis by downregulating expression of antiapoptotic proteins myeloid cell leukemia-1 and BCL–extra-large and upregulating pro-death BCL-2–associated X protein.

Conclusions:
Lisaftoclax in combination with alrizomadlin overcomes venetoclax resistance mediated by various mechanisms, including BCL-2 mutations. In addition, we posit further, putative molecular mechanisms. Our data rationalize clinical development of this treatment combination in patients with diseases that are insensitive or resistant to venetoclax.
Pegylated Liposomal Doxorubicin Combined with Ifosfamide for Treating Advanced or Metastatic Soft-tissue Sarcoma: A Prospective, Single-arm Phase II Study
Authors: Liu Xin , Jiang Shiyu , Wang Huijie , Wu Xianghua , Yan Wangjun , Chen Yong , Xu Yu , Wang Chunmeng , Yao Weiqiang , Wang Jian , Yu Lin , Miao Jiashun , Chen Hao , Xia Jing , Huang Mengli , Zhang Xiaowei , Luo Zhiguo 
Published: October 2022

Abstract

Purpose:
This prospective single-arm phase II clinical trial aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) combined with ifosfamide (IFO) as the first-line treatment for patients with advanced or metastatic soft-tissue sarcoma (STS).

Patients and Methods:
Patients received PLD (30 mg/m2; day 1) in combination with IFO (1.8 g/m2; days 1–5) every 21 days until disease progression, unacceptable toxicities, patient death, or for up to six cycles. The primary endpoint was progression-free survival (PFS; NCT03268772).

Results:
Overall, 69 patients with chemotherapy-naïve advanced or metastatic STS were enrolled between May 2015 and November 2019. At a median follow-up of 47.2 months, the median PFS and overall survival (OS) were found to be 7.3 [95% confidence interval (CI): 5.7–8.9] and 20.6 (95% CI: 16.3–25.0) months, respectively. The response and disease control rates were 26.1% and 81.2%, respectively. Adverse events were manageable, and no grade 3–4 cardiotoxicities were observed. There was no significant change in left ventricular ejection fraction values between baseline and after treatment (P = 0.669). Exploratory biomarker analysis suggested NF1 single-nucleotide variant was associated with poor OS (P &lt; 0.0001) and PFS (P = 0.044). In addition, 2 patients with BRCA2 loss progressed in the initial 2 months and died within 10 months. Improved OS was observed in homologous recombination deficiency (HRD)-negative patients compared with their HRD-positive counterparts (P = 0.0056).

Conclusions:
Combination therapy comprising PLD and IFO is an effective and well-tolerated first-line treatment for patients with advanced or metastatic STS.
MED1 Regulates BMP/TGF-β in Endothelium: Implication for Pulmonary Hypertension
Authors: Wang Chen , Xing Yuanming , Zhang Jiao , He Ming , Dong Jianjie , Chen Shanshan , Wu Haoyu , Huang Hsi-Yuan , Chou Chih-Hung , Bai Liang , He Fangzhou , She Jianqing , Su Ailing , Wang Youhua , Thistlethwaite Patricia A. , Huang Hsien-Da , Yuan Jason X.-J. , Yuan Zu-Yi , Shyy John Y-J. 
Published: October 2022

Background:

Dysregulated BMP (bone morphogenetic protein) or TGF-β (transforming growth factor beta) signaling pathways are imperative in idiopathic and familial pulmonary arterial hypertension (PAH) as well as experimental pulmonary hypertension (PH) in rodent models. MED1 (mediator complex subunit 1) is a key transcriptional co-activator and KLF4 (Krüppel-like factor 4) is a master transcription factor in endothelium. However, MED1 and KLF4 epigenetic and transcriptional regulations of the BMP/TGF-β axes in pulmonary endothelium and their dysregulations leading to PAH remain elusive. We investigate the MED1/KLF4 co-regulation of the BMP/TGF-β axes in endothelium by studying the epigenetic regulation of BMPR2 (BMP receptor type II), ETS-related gene (
ERG
), and TGFBR2 (TGF-β receptor 2) and their involvement in the PH.

Methods:

High-throughput screening involving data from RNA-seq, MED1 ChIP-seq, H3K27ac ChIP-seq, ATAC-seq, and high-throughput chromosome conformation capture together with in silico computations were used to explore the epigenetic and transcriptional regulation of BMPR2, ERG, and TGFBR2 by MED1 and KLF4. In vitro experiments with cultured pulmonary arterial endothelial cells (ECs) and bulk assays were used to validate results from these in silico analyses. Lung tissue from patients with idiopathic PAH, animals with experimental PH, and mice with endothelial ablation of MED1 (EC-
MED1
−/−
) were used to study the PH-protective effect of MED1.

Results:

Levels of MED1 were decreased in lung tissue or pulmonary arterial endothelial cells from idiopathic PAH patients and rodent PH models. Mechanistically, MED1 acted synergistically with KLF4 to transactivate BMPR2, ERG, and TGFBR2 via chromatin remodeling and enhancer-promoter interactions. EC-
MED1
−/−
mice showed PH susceptibility. In contrast, MED1 overexpression mitigated the PH phenotype in rodents.

Conclusions:
A homeostatic regulation of BMPR2, ERG, and TGFBR2 in ECs by MED1 synergistic with KLF4 is essential for the normal function of the pulmonary endothelium. Dysregulation of MED1 and the resulting impairment of the BMP/TGF-β signaling is implicated in the disease progression of PAH in humans and PH in rodent models.
Intravenous Thrombolysis in Patients With Ischemic Stroke Aged ≥90 Years: A Cohort Study From the TRISP Collaboration
Authors: Altersberger Valerian L. , Rusche Norman , Martinez-Majander Nicolas , Hametner Christian , Scheitz Jan F. , Henon Hilde , Dell’Acqua Maria Luisa , Strambo Davide , Stolp Jeffrey , Heldner Mirjam R. , Grisendi Ilaria , Jovanovic Dejana R. , Bejot Yannick , Pezzini Alessandro , Leker Ronen R. , Kägi Georg , Wegener Susanne , Cereda Carlo W. , Lindgren Erik , Ntaios George , Piot Ines , Polymeris Alexandros A. , Lyrer Philippe A. , Räty Silja , Sibolt Gerli , Tiainen Marjaana , Heyse Miriam , Erdur Hebun , Kaaouana Olfa , Padjen Visnja , Zedde Marialuisa , Arnold Marcel , Nederkoorn Paul J. , Michel Patrik , Bigliardi Guido , Zini Andrea , Cordonnier Charlotte , Nolte Christian H. , Ringleb Peter A. , Curtze Sami , Engelter Stefan T. , Gensicke Henrik ,   for the Thrombolysis in Stroke Patients (TRISP) Collaborators
Published: October 2022

Background:
The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly.

Methods:
In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those <90 years using symptomatic intracranial hemorrhage (ECASS [European Cooperative Acute Stroke Study]-II criteria), death, and poor functional outcome in survivors (modified Rankin Scale score 3–5 for patients with prestroke modified Rankin Scale score ≤2 and modified Rankin Scale score 4–5 for patients prestroke modified Rankin Scale ≥3) at 3 months as outcomes. We calculated adjusted odds ratio with 95% CI using logistic regression models.

Results:

Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratio
adjusted
1.14 [0.83–1.57]) did not differ significantly between both groups. However, the probability of death (odds ratio
adjusted
3.77 [3.14–4.53]) and poor functional outcome (odds ratio
adjusted
2.63 [2.13–3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar.

Conclusions:
The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.
Network Meta-Analysis of Non-Conventional Therapies for Improving Upper Limb Motor Impairment Poststroke
Authors: Saikaley Marcus , Pauli Griffin , Sun Hao , Serra Julisa Rodriguez , Iruthayarajah Jerome , Teasell Robert 
Published: October 2022

Background:
Network meta-analysis is a method that can estimate relative efficacy between treatments that may not have been compared directly within the literature. The purpose of this study is to present a network meta-analysis of non-conventional interventions to improve upper extremity motor impairment after stroke.

Methods:
A literature search was conducted in 5 databases from their inception until April 1, 2021. Terms were used to narrow down articles related to stroke, the upper extremity, and interventional therapies. Randomized controlled trials written in English were eligible if; 50% poststroke patients; ≥18 years old; applied an intervention for the upper extremity, and/or used the Fugl-Meyer upper extremity scale as an outcome measure; the intervention had ≥3 randomized controlled trials with comparisons against a conventional care group; conventional care groups were dose matched for therapy time. A Bayesian network meta-analysis approach was taken to estimate mean difference (MD) and 95% CI.

Results:
One hundred seventy-six randomized controlled trials containing 6781 participants examining 20 non-conventional interventions were identified for inclusion within the final model. Eight of the identified interventions proved significantly better than conventional care, with modified constraint induced movement therapy (MD, 6.7 [95% CI, 4.3–8.9]), high frequency repetitive transcranial magnetic stimulation (MD, 5.4 [95% CI, 1.9–8.9]), mental imagery (MD, 5.4 [95% CI, 1.8–8.9]), bilateral arm training (MD, 5.2 [95% CI, 2.2–8.1]), and intermittent theta-burst stimulation (MD, 5.1 [95% CI, 0.62–9.5]) occupying the top 5 spots according to the surface under the cumulative ranking curve.

Conclusions:
Overall, it would seem that modified constraint induced movement therapy has the greatest probability of being the most effective intervention, with high-frequency repetitive transcranial magnetic stimulation, mental imagery, and bilateral arm training all having similar probabilities of occupying the next spot in the rankings. We think this analysis can provide a guide for where future resources and clinical trials should be directed, and where a clinician may begin when considering alternative therapeutic interventions.
Taking the Warp for the Weft: Gendered Anger in the Lienüzhuan
Authors: Curry Alba , Raphals Lisa 
Published: October 2022

Abstract
The emotion of anger has received overall negative treatment in recent moral philosophy. This article explores the gendered representations of anger in the Lienüzhuan 《列女傳》 of Liu Xiang 劉向 (77–6 BCE). It begins with a brief account of the semantic field of anger and its representation in the Lienüzhuan, focusing on three important patterns. Perhaps most important is the didactic role of anger; and how female teachers use it (or avoid it) in instructing male sons, husbands and rulers. Second is the treatment of women’s distinct strategies for addressing the effects of being the object of the anger of others. The third is the representation of female anger in accounts of female vice. The representations of anger in the LNZ provides an important alternative to views of anger as motivated by the desire for payback and status. The LNZ, like other pre-Qin texts, understands anger very differently, and focuses on other-regarding anger, based on perceptions of wrongdoing and injustice.
Recovering Ontology in Anglo-American Interpretations of Hermeneutics: Chung-ying Cheng and Hans-Georg Gadamer
Authors: Fuyarchuk Andrew 
Published: October 2022

Abstract
Whereas a selective yet representative sample of Anglo-American scholarship undermines its own intentions to explain Gadamer’s language-ontology and theory of time by confusing the ground of beings with beings, Cheng and Gadamer explain how a transformation in human existence allows for a temporalization of Being in time that incorporates the subjectivity of the human subject. This argument draws on the dual structure of their cosmogenic worldview in the source and origins of their traditions (Lao Zi/Heraclitus) and has implications for Cheng’s organistic model of causality: It depends on mechanical causation to understand things in themselves.
Service and Reciprocity: Confucian Political Authority
Authors: Hong Cheng 
Published: October 2022

Abstract
Confucian political authority is often assumed illegitimate and it is regarded as meritocratic rather than democratic. However, I disagree with such an assumption, because from my perspective, Confucian political authority actually has a potential legitimacy which may contribute to establishing a responsive and harmonious state. Doing so, I argue that, since Confucian political authority is derived from the idea of “service” and “reciprocity,” it therefore advocates non-coercive moral persuasion and reciprocal obligations. In the following discussion, I will point out that certain modern democratic theories on political authority, such as those concerning “general acceptability,” “consent,” “autonomy,” and “paternalism,” are inadequate to refute the legitimacy of Confucian political authority. Accordingly, I will propose that our contemplation over whether Confucian political authority is legitimate or not ought to be furthermore widened and deepened.
ʿAli al-Aʿlā and the Early History of Horufism
Authors: Arslan Hüseyin Ongan 
Published: October 2022

Abstract
This article examines the life and activities of ʿAli al-Aʿlā (d. 1419/822), the principal successor of the founder of Horufism, Fazlollāh Astarābādi (d. 1394/796), and early Horufi history. Widely known as “Khalifatollāh (Vice-gerent of God)” in Horufi literature, the prolific ʿAli al-Aʿlā compiled five Persian books in the first two decades of the fifteenth century, namely the Korsi-nāma, Towhid-nāma, Qeyāmat-nāma, Ferāq-nāma, and Mahshar-nāma. By principally working on ʿAli al-Aʿlā’s corpus, I construct his biography, as well as explore Fazlollāh’s life and his Horufi doctrine. By critically engaging with the modern scholarship on Horufism, I discuss the crisis among Horufis following the execution of Fazlollāh, their political positioning among different political entities in western Asia, e.g., the Timurids and Qara Qoyunlus, and Horufi missionary activities in Syria, Anatolia, and the Ottoman Balkans in the first decades of the fifteenth century. By doing so, I attempt to add another dimension to the existing Horufi literature.
A Prince in the Body of a Parrot (Cuckoo)
Authors: Kapišovská Veronika 
Published: October 2022

Abstract
The eighteenth-century Tibetan narrative The Tale of Moon Cuckoo and its subsequent adaptation as a Mongolian traditional opera was performed from the nineteenth century up to the early twentieth. The story is based on the motif of a prince who is tricked into entering the body of a cuckoo; later on, he is not able to regain his human form, stolen by his evil-minded companion. The narrative, along with its Mongolian-language versions and operatic adaptation, is a vivid example of Tibet-Mongolian literary transmission. The underlying motif of the tale is also closely linked to the so-called frame narratives of Indian origin concerning King Vikramāditya; the popularity of these narratives was very widespread in Central and Inner Asia in times past. This paper describes some of the literary contacts concerning the narrative and motifs of The Tale of Moon Cuckoo in Central and Inner Asia and beyond, with a view as well to cross-genre considerations.
Ciceronian Skeptical Fideism in the Octavius of Minucius Felix
Authors: Ribeiro Brian 
Published: October 2022

Abstract
The dialogue Octavius by Minucius Felix is a point of reception in the legacy of Ciceronian skeptical fideism, and as such it deserves its place in the history of skeptical fideism. Drawing on his Ciceronian model, Minucius depicts a skeptical fideist—Caecilius—struggling to hold on to his religious traditions in the face of the challenges posed by the new religion of Christianity. But Minucius himself is a convert to the new religion and writes in its defense. And this authorial intent distorts the skeptical fideism which Minucius found in Cicero’s De natura deorum by adding credulous and/or dogmatic elements that are ill-fitted to skeptical fideism but well-suited to his authorial intention of answering all available objections to Christianity in the hopes of winning converts.