bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic efficacy of antibody-drug conjugates targeting GD2-positive tumors
Authors: Kalinovsky Daniel V , Kibardin Alexey V , Kholodenko Irina V , Svirshchevskaya Elena V , Doronin Igor I , Konovalova Mariya V , Grechikhina Maria V , Rozov Fedor N , Larin Sergey S , Deyev Sergey M , Kholodenko Roman V 
Published: October 2022

BackgroundBoth ganglioside GD2-targeted immunotherapy and antibody-drug conjugates (ADCs) have demonstrated clinical success as solid tumor therapies in recent years, yet no research has been carried out to develop anti-GD2 ADCs against solid tumors. This is the first study to analyze cytotoxic activity of clinically relevant anti-GD2 ADCs in a wide panel of cell lines with varying GD2 expression and their effects in mouse models of GD2-positive solid cancer.MethodsAnti-GD2 ADCs were generated based on the GD2-specific antibody ch14.18 approved for the treatment of neuroblastoma and commonly used drugs monomethyl auristatin E (MMAE) or F (MMAF), conjugated via a cleavable linker by thiol-maleimide chemistry. The antibody was produced in a mammalian expression system, and its specific binding to GD2 was analyzed. Antigen-binding properties and biodistribution of the ADCs in mice were studied in comparison with the parent antibody. Cytotoxic effects of the ADCs were evaluated in a wide panel of GD2-positive and GD2-negative tumor cell lines of neuroblastoma, glioma, sarcoma, melanoma, and breast cancer. Their antitumor effects were studied in the B78-D14 melanoma and EL-4 lymphoma syngeneic mouse models.ResultsThe ch14.18-MMAE and ch14.18-MMAF ADCs retained antigen-binding properties of the parent antibody. Direct dependence of the cytotoxic effect on the level of GD2 expression was observed in cell lines of different origin for both ADCs, with IC50 below 1 nM for the cells with high GD2 expression and no cytotoxic effect for GD2-negative cells. Within the analyzed cell lines, ch14.18-MMAF was more effective in the cells overexpressing GD2, while ch14.18-MMAE had more prominent activity in the cells expressing low GD2 levels. The ADCs had a similar biodistribution profile in the B78-D14 melanoma model compared with the parent antibody, reaching 7.7% ID/g in the tumor at 48 hours postinjection. The average tumor size in groups treated with ch14.18-MMAE or ch14.18-MMAF was 2.6 times and 3.8 times smaller, respectively, compared with the control group. Antitumor effects of the anti-GD2 ADCs were also confirmed in the EL-4 lymphoma model.ConclusionThese findings validate the potential of ADCs targeting ganglioside GD2 in treating multiple GD2-expressing solid tumors.
Intratumoral immunotherapy using a TLR2/3 agonist, L-pampo, induces robust antitumor immune responses and enhances immune checkpoint blockade
Authors: Lee Won Suk , Kim Dong Sung , Kim Jeong Hun , Heo Yoonki , Yang Hannah , Go Eun-Jin , Kim Jin Hyoung , Lee Seung Joon , Ahn Byung Cheol , Yum Jung Sun , Chon Hong Jae , Kim Chan 
Published: October 2022

BackgroundToll-like receptors (TLRs) are critical innate immune sensors that elicit antitumor immune responses in cancer immunotherapy. Although a few TLR agonists have been approved for the treatment of patients with early-stage superficial cancers, their therapeutic efficacy is limited in patient with advanced invasive cancers. Here, we identified the therapeutic role of a TLR2/3 agonist, L-pampo (LP), which promotes antitumor immunity and enhances the immune checkpoint blockade.MethodsWe generated LP by combining a TLR2 agonist, Pam3CSK4, with a TLR3 agonist, Poly (I:C). Immune responses to stimulation with various TLR agonists were compared. Tumor-bearing mice were intratumorally treated with LP, and their tumor sizes were measured. The antitumor effects of LP treatment were determined using flow cytometry, multiplexed imaging, and NanoString nCounter immune profiling. The immunotherapeutic potential of LP in combination with α-programmed cell death protein-1 (PD-1) or α-cytotoxic T-lymphocytes-associated protein 4 (CTLA-4) was evaluated in syngeneic MC38 colon cancer and B16F10 melanoma.ResultsThe LP treatment induced a potent activation of T helper 1 (Th1) and 2 (Th2)-mediated immunity, tumor cell apoptosis, and immunogenic tumor cell death. Intratumoral LP treatment effectively inhibited tumor progression by activating tumor-specific T cell immunity. LP-induced immune responses were mediated by CD8+T cells and interferon-γ, but not by CD4+T cells and CD25+T cells. LP simultaneously activated TLR2 and TLR3 signaling, thereby extensively changing the immune-related gene signatures within the tumor microenvironment (TME). Moreover, intratumoral LP treatment led to systemic abscopal antitumor effects in non-injected distant tumors. Notably, LP treatment combined with ɑPD-1 and ɑCTLA-4 further enhanced the efficacy of monotherapy, resulting in complete tumor regression and prolonged overall survival. Furthermore, LP-based combination immunotherapy elicited durable antitumor immunity with tumor-specific immune memory in colon cancer and melanoma.ConclusionsOur study demonstrated that intratumoral LP treatment improves the innate and adaptive antitumor immunity within the TME and enhances the efficacy of αPD-1 and αCTLA-4 immune checkpoint blockade.
Outcomes of UK military personnel treated with ice cold water immersion for exertional heat stroke
Authors: Wood Felix , Roiz-de-Sa D , Pynn H , Smith J E , Bishop J , Hemingway R 
Published: October 2022

IntroductionDespite mitigation efforts, exertional heat stroke (EHS) is known to occur in military personnel during training and operations. It has significant potential to cause preventable morbidity and mortality. International consensus from sports medicine organisations supports treating EHS with early rapid cooling by immersing the casualty in cold water. However, evidence remains sparse and the practice is not yet widespread in the UK.MethodsFollowing changes to enable on-site ice cold water immersion (ICWI) at the Royal Marines Commando Training Centre, Lympstone, UK, we prospectively gathered data on 35 patients treated with ICWI over a 3-year period. These data included the incidence of adverse events (e.g. death, cardiac arrest or critical care admission) as the primary outcome. Basic anthropometric data, cooling rates achieved and biochemical and haematological test results on days 0–5 were also gathered and analysed.ResultsDespite being a cohort of patients in whom we might expect significant morbidity and mortality based on the severity of EHS at presentation, none experienced a serious adverse event. In this cohort with rapid initiation of effective cooling, biochemical derangement appeared less severe than that reported in previous studies. Higher body mass index (BMI) was associated with a lower cooling rate across a range of values previously reported as potentially of clinical significance.ConclusionsThis case series supports recent updates to UK military guidance that ICWI should be more widely adopted for the treatment of EHS. Clinicians should be aware of likely patterns of blood test abnormalities in the days following EHS. Further work should seek to establish the impact of lower rates of cooling and develop strategies to optimise cooling in patients with higher BMI.
Effect of upadacitinib on reducing pain in patients with active psoriatic arthritis or ankylosing spondylitis: post hoc analysis of three randomised clinical trials
Authors: McInnes Iain B , Ostor Andrew J K , Mease Philip J , Tillett William , Baraliakos Xenofon , de Vlam Kurt , Bessette Louis , Lippe Ralph , Maniccia Anna , Feng Dai , Gao Tianming , Zueger Patrick , Saffore Christopher , Kato Koji , Song In-Ho , Deodhar Atul 
Published: October 2022

ObjectiveEvaluate the effect of upadacitinib on pain outcomes in patients with active psoriatic arthritis (PsA) or ankylosing spondylitis (AS) across 3 randomised trials (SELECT-PsA 1 and 2 for PsA; SELECT-AXIS 1 for AS).MethodsPatients were randomised to upadacitinib 15 mg once daily or placebo (all 3 studies), or adalimumab 40 mg every other week (SELECT-PsA 1 only). Pain outcomes included proportion of patients achieving ≥30%, ≥50% and ≥70% reduction from baseline in patient global assessment of pain and other end points.ResultsA higher proportion of patients receiving upadacitinib versus placebo achieved ≥30%, ≥50% and ≥70% reduction in pain end points as early as week 2; these improvements with upadacitinib were generally sustained or increased through year 1 (PsA 1/2 studies: 64%/48%, 58%/42% and 38%/22%, respectively; SELECT-AXIS 1 study: 76%, 72% and 54%). Results were similar with adalimumab in PsA 1 (59%, 49% and 32%). Patients who switched from placebo to upadacitinib 15 mg were able to reach a similar level of improvement as the continuous upadacitinib groups by year 1 (PsA 1/2 studies: 46%–60%, 35%–49% and 15%–34%; AS study: 83%, 72% and 46%). Results were similar with other pain end points.ConclusionRapid and sustained improvements in pain outcomes across several end points were consistently shown with upadacitinib over 1 year in patients with active PsA or AS who had either inadequate response to prior non-biologic or biologic disease-modifying antirheumatic drugs (PsA studies) or were biologic-naïve with inadequate response to non-steroidal anti-inflammatory drugs (AS study).
Right Ventricular Maladaptation to Pressure Overload in Fischer Rats Is Associated With Profound Deficiency in Adenylate Kinase 1 and Impaired Ventricular Energetics
Authors: Zelt Jason G.E. , Cadete Virgilio , Deng Yupu , Godoy Rafael , Cuillerier Alexanne , Rowe Katelynn , Abdul-Ghani Mohammad , Megeney Lynn , Burelle Yan , Giulivi Antonio , Stewart Alexandre F.R. , Provencher Steeve , Breuils-Bonnet Sandra , Bonnet Sébastien , deKemp Robert , Beanlands Rob , Mielniczuk Lisa M. , Stewart Duncan J. 
Published: October 2022

Background:
We explored the mechanism of maladaptive right ventricular (RV) remodeling in Fischer compared with Sprague-Dawley (SD) rats exposed to pressure overload.

Methods:

Pulmonary hypertension was induced by injection of the VEGFR antagonist, SU5416, followed by a 3-week exposure to hypoxia (Sugen chronic hypoxia). In vivo oxidative metabolism was assessed by RV/left ventricle ratio of [
11
C]acetate positron emission tomography clearance (kmono). Unbiased, global transcriptional and proteomic profiling was performed in Fischer and SD rats at baseline and after Sugen chronic hypoxia.

Results:

All Fischer rats succumbed to RV failure by 5 weeks, whereas SD rats showed preserved RV function and 88% survival beyond 9 weeks (
P
<0.0001). Fischer rats exhibited increased oxidative metabolism at 4 weeks (
P
<0.05) and impaired RV efficiency compared with SD (work metabolic index: 52±10 versus 91±27 mmHg·mL/cm
2
, respectively;
P
<0.05), but no differences in mitochondrial complex activity. AK1 (adenylate kinase 1) was among the top 10 differentially expressed genes between Fischer and SD rats, with markedly lower RV expression in Fischer rats (FC: 3.36,
P
<0.05), confirmed by proteomic analysis and validated by Western blotting (>10-fold reduction,
P
<0.001). While whole-genome sequencing failed to reveal any coding region mutations in Fischer rats, there was a unique variant in a highly conserved upstream flanking region likely involved in the regulation of AK1 expression.

Conclusions:
Therefore, Fischer rats exhibit profound AK1 deficiency and inefficient cardiac energetics likely related to reduced adenosine triphosphate shuttling from the mitochondria to the contractile fibers. This represents a novel mechanism for RV failure in response to chronic increases in afterload.
A New Transcription and Assessment of 4Q9 (4QGenesisj)
Authors: Tigchelaar Eibert 
Published: October 2022

Abstract
This article presents a new transcription of 4Q9 on the basis of the new photographs and the identification of four more fragments. The irregular hand and the scribal errors indicate that the scribe was not very skilled. Orthographically and morphologically the text is very close to the Samaritan Pentateuch.
One new species of Comesoma Bastian, 1865 (Nematoda: Araeolaimida: Comesomatidae) and redescription with molecular characterisation of Sphaerolaimus callisto Zograf, Pavlyuk, Trebukhova & Nguyen, 2020 (Nematoda: Monhysterida: Sphaerolaimidae) from the South China Sea
Authors: Fu Sujing , Cai Lizhe , Leduc Daniel , Lin Heshan 
Published: October 2022

Summary
One new Comesoma Bastian, 1865 species and one known Sphaerolaimus species are described from the intertidal areas of a sand beach and mangrove wetland, respectively, in Beihai City, P.R. China (South China Sea) using morphological and molecular data. Comesoma sinica n. sp. is characterised by body length 2366-2925 μm, long cephalic setae 24-32 μm, cuticle without lateral differentiation, spiral amphids with 2.5 turns, bent spicules and 3.5-4.3 cloacal body diam. long, gubernaculum parallel with spicules, and males with 20 minute precloacal supplements in the form of small pores. Molecular analyses of 18S rDNA and 28S rDNA indicate that Comesoma sinica n. sp. is closely related to other Comesomatidae genera. Sphaerolaimus callisto Zograf, Pavlyuk, Trebukhova & Nguyen, 2020, which was originally described from an estuary of northern Vietnam, the South China Sea, is characterised by long spicules and vulva situated far posterior to mid-body (82% of body length from anterior extremity), and is recorded from mangrove wetlands in Beihai City. In addition, as Sphaerolaimus longispiculatus Yang, Liu & Guo, 2021 is highly similar to S. callisto in morphology, these two species should be synonymised. Phylogenetic analyses of 18S rDNA show that S. callisto is closely related to other species of Sphaerolaimus.
On the Colonial History of the Ideas of God(s) in Africa
Authors: Lunkwitz Diana 
Published: October 2022

Abstract
This contribution examines contested ideas of god(s) as held by Protestant missionaries and the German explorer Hugo Zöller in the early colonial period of Cameroon and in neighbouring West African countries in the 1880s. While many present studies on African Traditional Religion(s) tend to perpetuate an understanding of religion around one supreme god, Zöller’s reports included discontinuities and open questions. An intertextual reading approach is used to question historical and translation barriers and analyse the ideas of god(s) in reception history, including through the report of a later mission director and a handbook of religion. It becomes apparent that all the analysed historical material assumed one supreme god or one origin of religion, albeit according to the different interests of each foreign writer’s point of view. A decolonising reading that focuses on the foreigner’s idea of god(s) in the local people’s view then offers interesting insights into the perception and interpretation of the exploitative trade with ‘products’ from Cameroon linked to the coloniser’s own religion. That shift in perspective animadverts on the entire colonising trade system. This contribution thus proposes a decolonial historiography of religion in Africa in order to extend the critical investigation of reception history and perspectives.
Rescuing Ottoman History from the Turks
Authors: Eldem Edhem 
Published: October 2022

Abstract
History in Turkey has always been the prey of political and ideological pressures emanating from the state and government. For decades, most of this political ‘monitoring’ was dominated by the Kemalist view of history, which often bypassed or marginalized the Ottoman past. However, the last three decades or so have witnessed a gradual but radical shift, and Ottoman history has made a comeback, to the point of warranting the use of the term ‘neo-Ottomanist’ to describe governmental policies under the Justice and Development Party (akp). This qualitative change has been further enhanced by a quantitative one, concerning an unprecedented echoing of the new government- and state-sponsored grand narrative by the media and popular culture, leading to a serious and threatening siege of the discipline from non-academic circles. The time has come for the discipline to reflect on this phenomenon and evaluate its dangers and damages.
The ‘Turkish-Type’ Presidential System: an Imperial Civilisational Restoration?
Authors: Moudouros Nikos 
Published: October 2022

Abstract
This article analyses the ideological background on which the Justice and Development Party’s (akp) policy rested for the adoption of the presidential system in Turkey. It examines the presidential system as an akp claim aiming at the resolution of Turkey’s ‘basic historical contradiction’ through the effort to restore the Ottoman imperial legacy. In the same context, the analysis extends to the ideological content of ‘New Turkey’, which focuses on the adoption of a ‘Turkish-type’ presidential system. At this level the importance of the identification of a powerful state with the centralisation of executive power is emphasised as a natural result of the restoration of the Ottoman imperial legacy. Finally, the article presents specific problematic aspects arising from the social and ideological polarisation accompanying the transition of Turkey to the presidential system.
Aspects of Populism and Nostalgia in the akp’s Turkey
Authors: Theodorou Michalis 
Published: October 2022

Abstract
As a consequence of a long series of domestic and international political, economic and social developments that resulted in the rise of political Islam in Turkey, the Justice and Development Party (akp) came to power in 2002. Since then, it has been the dominant party in the country, developing a political narrative and a public discourse that have many attributes of modern populism. In line with its strategy to consolidate its power, the akp espouses a populist public discourse that is distinctive and multifaceted. One of its most important manifestations is the mobilization of the population through neo-Ottoman nostalgia, in a context of politicization of emotion to connect with the broader masses.
Historical Novel as a Propaganda Tool: Reviving the Ottoman Past in Fiction
Authors: Yıkık Ahmet 
Published: October 2022

Abstract
From the nineteenth century to the present day, a considerable number of Turkish novels have been published which either incorporate facts from Ottoman history directly into their plots, or rely on that history to form the background of the action. These novels play a significant role in the formation of Turkish national consciousness. The scope of this article is to analyse the historical novels İtiraf (Confession) and Her Yerde Kan Var (There is blood everywhere), which were written during the reign of the Justice and Development Party (akp). The article uses a sociology of literature approach to examine the two books’ depiction of the Ottoman Empire—their ‘Ottoman image’.
Imperial Genealogies and Ottoman Nobility in Republican Turkey: Reassessing the Distinction Between Public and Private Archives
Authors: Bouquet Olivier 
Published: October 2022

Abstract
As Grand Vizier from 1782 to 1785, Halil Hamid Pasha established a pious foundation (vakıf) in 1783. Administered by his descendants, the foundation gave impetus to various forms of family genealogy in the last two centuries. Celal Bükey and his son Erol Bükey administered the foundation (tevliyet) from 1973 to 1981 and from 1992 to 2002 respectively. Using their personal documents, the article studies the way father and son handled the various symbolic materials they had inherited from their predecessors in order to transform an ancien régime lineage into a republican dynasty organized through new family memorial references. Underlining the extent to which family archives need to be addressed as a cumulative process of preserving documents as deeds that legally guarantee ownership, the article also reassesses the line usually drawn by scholars between private papers and public archives.
Patrons, Painters, Women In Distress: The Changing Fortunes of Nevʿizade Atayi and Üskübi Mehmed Efendi in Early Eighteenth-Century Istanbul
Authors: Artan Tülay 
Published: October 2022

Abstract
Images of Ottoman women in verse and manuscript painting that have long been interpreted as realistic representations of their everyday life stand in stark contrast with how women are represented, addressed, and pigeonholed in religious books of conduct. While no distinction is made between the elite and commoners in these depictions of pleasurable outdoor activities, the regular, routine roles that the women played in the family and society disappear from sight. In light of a rare but well-known court scene showing women in public space and at a real trial of 1582, appended in all illustrated copies of Nevʿizade Atayi’s Ḫamse, I discuss the specifics of the legal opinion with which Pir Mehmed Efendi was associated, and how the trial was recollected in Istanbul’s literate circles after more than a century. Whether the production of the five illustrated Ḫamses in the first quarter of the eighteenth century was a concerted effort on the part of a specific group of artists, both Istanbulites and Inner Asians, is discussed in the second part of the article.
The Kutubiyya Mosque of Marrakesh Revisited
Authors: Almagro Antonio , Jiménez Alfonso 
Published: October 2022

Abstract
The aim of this article is to present a new survey of the Kutubiyya Mosque in Marrakesh (Morocco) produced between 2015 and 2018 using photogrammetric techniques. This work intends to close a surprising gap in the available information for one of the most important monuments of Western Islamic architecture. We also present our preliminary observations, formed during the course of producing these drawings. Although a building such as this mosque—with one part in use and therefore maintained regularly and another part heavily restored as a ruin—is difficult to investigate archaeologically, an analysis of the chronology and the construction process is proffered. We reject the prevalent theory that there were two subsequent mosques, with the newer one serving as a substitute for the older building. Instead, by presenting new dates and arguments, we propose that the Kutubiyya represents a single mosque built in two phases, the first part of which later fell into ruin.
Recognition for Good Europeans: On Axel Honneth’s Recognition
Authors: Kretz David 
Published: October 2022

Abstract
Axel Honneth’s Recognition tells a history of the concept of recognition along national lines. This response argues that a focus on transnational cross-pollination would be preferable on the grounds of historical accuracy, philosophical fecundity, and political cosmopolitanism. It would recognize its existent protagonists as the good Europeans they actually were and bring in others now relegated to the margins. It would lay the groundwork for a creative integration of national traditions, beyond the subsumption of French and British under German models. It would facilitate a theoretical dialogue with traditions beyond the Old Continent. I suggest that Hobbes could be a starting point for such a historical narrative, pointing to the importance of social recognition for his political theory (via Oakeshott), but also to traces of an incipient notion of moral-political recognition closer to the post-Kantian paradigm that Honneth champions.