bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phosphorylation signal activates genome-wide transcriptional control by BfmR, the global regulator of Acinetobacter resistance and virulence
Authors: Raustad Nicole , Dai Yunfei , Iinishi Akira , Mohapatra Arpita , Soo Mark W , Hay Everett , Hernandez Gabrielle M , Geisinger Edward 
Published: January 2025

Abstract
The nosocomial pathogen Acinetobacter baumannii is a major threat to human health. The sensor kinase-response regulator system, BfmS-BfmR, is essential to multidrug resistance and virulence in the bacterium and represents a potential antimicrobial target. Important questions remain about how the system controls resistance and pathogenesis. Although BfmR knockout alters expression of &gt;1000 genes, its direct regulon is undefined. Moreover, how phosphorylation controls the regulator is unclear. Here, we address these problems by combining mutagenesis, ChIP-seq, and in vitro phosphorylation to study the functions of phospho-BfmR. We show that phosphorylation is required for BfmR-mediated gene regulation, antibiotic resistance, and sepsis development in vivo. Consistent with activating the protein, phosphorylation induces dimerization and target DNA affinity. Integrated analysis of genome-wide binding and transcriptional profiles of BfmR led to additional key findings: (1) Phosphorylation dramatically expands the number of genomic sites BfmR binds; (2) DNA recognition involves a direct repeat motif widespread across promoters; (3) BfmR directly regulates 303 genes as activator (e.g., capsule, peptidoglycan, and outer membrane biogenesis) or repressor (pilus biogenesis); (4) BfmR controls several non-coding sRNAs. These studies reveal the centrality of a phosphorylation signal in driving A. baumannii disease and disentangle the extensive pathogenic gene-regulatory network under its control.
Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer
Authors: Skoulidis Ferdinandos , Li Bob T , Hochmair Maximilian , Govindan Ramaswamy , Vincent Mark , van der Wekken Anthonie J , Reguart Aransay Noemi , O’Byrne Kenneth J , Girard Nicolas , Griesinger Frank , Nishio Makoto , Häfliger Simon , Lindsay Colin , Reinmuth Niels , Paulus Astrid , Papakotoulas Pavlos , Kim Sang-We , Ferreira Carlos Gil , Pasello Giulia , Duruisseaux Michael , Gennatas Spyridon , Dimou Anastasios , Mehta Bhakti , Kormany William , Nduka Chidozie , Sylvester Brooke E , Ardito-Abraham Christine , Wang Yang , de Langen Adrianus Johannes 
Published: January 2025

Abstract

Introduction
We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods
Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0. Adverse events were deemed sotorasib-related per investigator causality assessment.

Results
In the pooled population (n = 549), TRAEs were reported in 388 (70.7%) patients (grade 1: 124 [22.6%]; grade 2: 117 [21.3%]; grade ≥ 3: 147 [26.8%]). Gastrointestinal and hepatic TRAEs, including diarrhea (171 [31.1%]), nausea (80 [14.6%]), elevated alanine aminotransferase (ALT; 68 [12.4%]), and elevated aspartate aminotransferase (AST; 67 [12.2%]) were the most common (≥10%). Dose interruption and dose reduction of sotorasib resulted in the resolution of &gt;90% of diarrhea events; median time to resolution were 18.0 days and 22.0 days, respectively. Similar trends were observed for elevated ALT and AST events. Patients who stopped immunotherapy &lt;3 months before initiating sotorasib had a higher incidence of treatment-related hepatotoxicity (80/240 [33.3%]) than those who stopped immunotherapy ≥3 months before initiating sotorasib (26/188 [13.8%]). Treatment-related pneumonitis/interstitial lung disease (ILD) and corrected QT (QTc) prolongation were observed in 9 (1.6%) and 4 (0.7%) patients, respectively. Two (0.4%) patients died with TRAEs, 1 with ILD whose ultimate cause of death was disease progression, and the other with an unknown cause.

Conclusions
Sotorasib has a well-characterized safety profile in patients with KRAS G12C-mutated advanced NSCLC, and key risks are manageable with dose modification.
Is it time to retire preoperative radiation for localized esophageal and gastro-esophageal adenocarcinoma?
Authors: Pabon Cindy M , Spieler Benjamin , Li Jenny J , Ajani Jaffer , Hosein Peter J , Blum Murphy Mariela 
Published: January 2025

Abstract
Whether preoperative chemoradiotherapy (CRT) or perioperative chemotherapy is superior for localized esophageal or gastro-esophageal junction (GEJ) cancers has been a topic of long-standing debate. For years, standard of care in the United States for localized esophageal or GEJ adenocarcinoma (EAC) has been physician’s choice between the 2 strategies. More recently, adjuvant immunotherapy has also been introduced into the treatment approach for those who received neoadjuvant CRT. While preoperative radiation remains an important option for patients with esophageal squamous cell carcinomas, the ESOPEC trial presented in 2024 suggested that perioperative chemotherapy is superior to preoperative CRT in EAC. In addition, the results of the TOPGEAR trial presented in 2024 showed that adding CRT to perioperative chemotherapy did not lead to improved outcomes. This has led to a shift in practice among oncologists. However, there are various complexities and factors to consider when interpreting these studies. In this review, we outline both trials and what their findings may mean for the future of preoperative CRT in EAC. Ultimately, until more data are available that incorporate novel agents such as immunotherapy, these studies indicate that we should defer the routine inclusion of radiation in preoperative treatment for EAC.
Levels of Description and Levels of Reality
Authors: List Christian 
Published: January 2025

Abstract
This expository chapter presents a general framework for representing levels and inter-level relations. The framework is intended to capture both epistemic and ontological notions of levels and to clarify the sense in which levels of explanation might or might not be related to a levelled ontology. The framework also allows us to study and compare different kinds of inter-level relations, especially supervenience and reduction but also grounding and mereological constitution. This, in turn, enables us to explore questions such as whether supervenience implies explanatory reducibility and whether there can be irreducible higher-level explanations or even “emergent” higher-level properties. The chapter finally discusses some further philosophical applications: to the free-will debate, the determinism-indeterminism distinction, indexicality and consciousness, and the relationship between positive and normative facts.
Antireductionism Has Outgrown Levels
Authors: Potochnik Angela 
Published: January 2025

Abstract
Positing levels of explanation has played an important role in philosophy of science. This facilitated the advocacy of antireductionism of explanations, which, at its most basic, is the idea that scientific explanations citing large (i.e., non-microphysical) entities will persist. The idea that explanations come in levels captures important features of explanatory practices, and it also does well at helping to define different positions one might take regarding explanatory reductionism or antireductionism. Yet the idea that explanations come in levels has also led philosophers astray. This systematically misconstrues the relationship different explanations bear to one another, suggests candidate explanations are less numerous than they in fact are, and occludes recognition of how the selection of explanations can vary across research projects. Antireductionists about explanation should move on from talk of levels. Or so this chapter will argue.
Messy but Real Levels in the Social Sciences
Authors: Kincaid Harold 
Published: January 2025

Abstract
This chapter surveys some issues about levels in the sciences as they surface in the social and behavioral sciences. However, it is hard to discuss issues in the social sciences without also discussing the issues about levels in science in general. Thus, the chapter proposes a general take on debates about levels that it calls naturalist and contextualist: naturalist in that conceptual metaphysics cannot trump science and contextualist in that the use and usefulness of level concepts means different things with different plausibility according to scientific context. The chapter argues that the levels concept is neither incoherent or always useful, that many objections to levels such as doubts about downward causation are anti-naturalist conceptual metaphysical approaches that should be rejected, and that levels cannot be replaced with concepts of mechanisms or scale. All this is tied down and expanded with discussions of some empirical social methodological and research areas. Section 1 sets up the general naturalist and contextualist framework, Section 2 applies these to general debates about levels, and Section 3 discusses in detail some social science research.
A Democracy of Laws
Authors: Townsen Hicks Michael 
Published: January 2025

Abstract
Philosophical views on the connection between the fundamental laws and the laws of the special sciences either emphasize the independence of the special sciences or emphasize their reduction to physics. Either option is problematic; philosophers emphasizing special scientific independence (who I here call ‘anarchists’) have trouble explaining inter-theoretic explanations. Meanwhile, philosophers emphasizing the reduction of the special sciences to physics have trouble explaining the counterfactual robustness of the higher-level laws. Here, I draw out these difficulties in detail. Then, I provide a version of the Humean Best-System Analysis of laws which balances the strengths of these two approaches. I call this the Democratic Best System, and conclude that it provides our best account of the metaphysics of special science lawhood.
Game-Mastering
Authors: von Moltke A.K. 
Published: January 2025

Abstract
Upstream platform dynamics can often be framed as a game-master–players relationship where suppliers are players and platforms are game-masters who organize the games, and sometimes also actively partake in them. ‘Game-mastering’ is therefore an inherent risk. Like role-playing game game-masters, powerful platforms have the ability and potential incentives to exploit their omniscient position to twink their own offers at the stage of inception and/or self-preference them later in time. Even when they forsake participation as players, game-mastering platforms may distort the value capture process by engaging in potentially harmful king-making. Can antitrust intervention be rationalized, then? From a consumer welfare perspective, the real issue is the need for rigour, which will often leave decision-makers caught between a rock and a hard place. Under the competitive process approach, ‘looking up’ becomes a more direct and more honest exercise. But formalizing the potential antitrust injury—ex ante unfairness—presents significant challenges.
Slavery, Abolition, and Islam
Authors: Bashir Haroon 
Published: January 2025

Abstract
Does the Qur’an promote the abolition of slavery? If so, why had the slave trade been allowed to operate across the Muslim world for over a millennium? And why had Muslim scholars not sought to eradicate slavery previously? These were the questions that Islamic abolitionist scholars explored as they sought to challenge the slavery throughout the nineteenth century. A mere two centuries ago, the slave trade was considered completely legitimate by scholars, philosophers, and jurists of all colours and creeds. The abolition of slavery remains a relatively new concept in human history. Scholars from all religious traditions have attempted to navigate the religious and ethical questions raised by the historical acceptance of slavery. This book tells the story of how scholars promoting abolition in the name of Islam transformed the debate regarding Islam and slavery. The book explores how abolitionism became the hegemonic position within contemporary Islamic thought and highlights the journey underpinning the current consensus. Abolitionist arguments were not simply accepted, with defenders of the slave trade using the weight of the historical tradition to emphasize the legitimacy of slavery. The strongly contested debates that ensued had huge ramifications for understandings of authority, tradition, and modernity within Islamic thought that are as present as they are past. In doing so, the book also explores broader themes regarding religious traditions, continuity, and transformation.
Sayyid Ahmad Khan and ‘Quranic Abolition’
Authors: Bashir Haroon 
Published: January 2025

Abstract
This chapter explores the birth and development of the ‘Quranic abolition’ thesis. Focusing on Sayyid Ahmad Khan and his Ibṭāl-e-Ghulāmī, Chapter 4 analyses Khan’s innovative arguments regarding the abolition of slavery being established at the time of Prophet Muḥammad. This chapter also assesses Khan’s interlocutors, and his disagreements with Orientalist scholars such as William Muir, whilst highlighting the reception of his ideas from scholars such as Abdullāh ‘Askarī and Saʻīd Akbarābādī, among others. Chapter 4 demonstrates how Khan’s arguments became popular and were promoted by influential reformist thinkers such as Cheragh Ali and Ghulām Aḥmad Parwez.
Muḥammad ‘Abduh, Rashīd Riḍā, and ‘Quranic Gradualism’
Authors: Bashir Haroon 
Published: January 2025

Abstract
This chapter assesses the development of the ‘Quranic gradualism’ thesis promoted by Muḥammad ‘Abduh and Rashīd Riḍā. ‘Abduh has been described as one of the most important reformist voices of his time, and Riḍā was his most famous student. Working primarily from the Manār, it explores the attempt to reconcile Islam with abolition as presented originally by Egyptian reformists. This chapter highlights the refutations lodged against ‘Abduh and Riḍā from scholars such as Ḥussain al-Jisr and Yūsuf al-Nabahānī. It also explores how the ideas of ‘Abduh were popularized by the likes of Sayyid Quṭb and Ibn ‘Āshūr, some of the most prominent Muslim thinkers of the twentieth century.
What is the Islamic Position on Abolition? Hermeneutical Paradigms and Interpretive Communities
Authors: Bashir Haroon 
Published: January 2025

Abstract
All readings of the Qur’ān are ultimately mediated by the interlocutor. That is to say, the interpreter’s preferences, contexts, and hermeneutical paradigms ultimately shape the manner by which scripture is engaged. To fully account for interpretive differences regarding the issue of slavery, then, it becomes necessary to explore the question of hermeneutics. This chapter assesses the divergent interpretations of slavery and abolition, exploring why scholars are approaching the same subject matter and producing different readings. Focusing on hermeneutical paradigms, Chapter 6 provides overarching analysis regarding differing reading formations and interpretive communities. Using Stanley Fish’s model of interpretive communities, it explores how authority is constructed and enacted within differing reading formations.
The Transformation of the Politics of Ethics from Kınalızade to Birgivi
Authors: Tezcan Baki 
Published: January 2025

Abstract
Birgivi’s (d. 1573) The Muhammadan Path in Arabic and Kınalızade’s (d. 1572) The Sublime Ethics in Turkish are two Ottoman classics that enjoyed a very wide degree of circulation since the sixteenth century. Ethics is at the heart of both works. Whereas Kınalızade engages the Greco-Islamic tradition of practical philosophy through the Persian works of Tusi (d. 1274) and Davvani (d. 1502), Birgivi is most directly engaged with al-Ghazali (d. 1111). Since practical philosophy comprises ethics, as well as economics (in the ancient sense of household management) and politics, the connections between the moral and political worlds of Kınalızade and, thus, the political assumptions that inform his moral world are not difficult to uncover. While Birgivi is ostensibly less engaged with political power, this chapter suggests that there are important political (and epistemological) assumptions on which his moral world is built and that these assumptions are, arguably, more adoptable to modernity.
“Where There Is Love, Justice Is Not Needed”
Authors: Gürbüzel Aslıhan 
Published: January 2025

Abstract
This chapter analyzes Ottoman conceptions of public order and civic community through the twin concepts of justice and love. In ethical thought, justice sustained a frame against oppression, thus ensuring a stable and conflict-free society. While indispensable for the safety of citizens, a society governed merely via justice was tyrannical. It was another cardinal social virtue, namely friendship, that elevated the polity to a virtuous social union. Through the argument that it was incumbent upon a virtuous polity to enable the flourishing of friendship, ethicists framed the rights of civic communities. Chief among these rights was a degree of protection from the public authority’s invasion of their private sphere. Love and justice framed Ottoman discussions about public order and civic community, respectively. Explicating the concepts of love and justice also drives home the eclecticism of Ottoman ethical writing; rather than forming a framework that applied to all social gatherings, ethicists articulated different normative frames for different social groups. As a result, ethicists developed a rich taxonomy of types of friendship, namely types of civic community.
A Gendered History of Honor in the Ottoman Legal Praxis
Authors: Tuğ Başak 
Published: January 2025

Abstract
This chapter studies honor in the Ottoman legal praxis, particularly concerning the new Tanzimat penal codes of the nineteenth century. It mainly focuses on the 1858 Penal Code as the first criminal code that codified honor extensively in a comprehensive section devoted to various sexual offenses. It argues that the centralizing state of the Tanzimat expanded its control over the private sphere of its subjects. The state claimed to assert itself as the supreme arbiter of morality by entrusting women’s sexuality to its male subjects to control. Nevertheless, this gendered construction of morality based on honor has undermined its claims of creating a novel universal citizenship/subjecthood. This study also argues that the 1858 Penal Code was part of global codification movements in which the Napoleonic Code Pénal has been adapted according to local needs. Thus, it reveals how the section on sexual offenses and public outrage in the Code Pénal and the French gendered norms have been translated and adapted to the Ottoman moral codes of family and patriarchal honor with the introduction of ırz.
Pavagan E (Enough!)
Authors: Bilal Melissa 
Published: January 2025

Abstract
This chapter focuses on Armenian feminist writer and activist Zabel Yesayan’s “Pavagan E (Enough!)” published in 1922 in Vienna’s Arek (Sun) monthly. A piece of creative non-fiction or autobiographical fiction on the First Balkan War, “Pavagan E” lends itself to a discussion of Yesayan’s standpoint with regard to peace, justice, and people’s right to self-defense. The chapter offers a reading of the text in light of its author’s political activism and other writings and contextualizes it as a fundamental work in the history of Ottoman political thought. Reclaiming “Pavagan E”s place in historiography requires addressing the silences imposed in Turkey on the Ottoman Armenian intellectual legacy that the text documents along with the lived experiences it refers to. It also opens up the possibility for a critical reflection on its relevance for today.
Securing Resilient Peace
Authors: Njeru Shastry , Masiya Tyanai 
Published: January 2025

Abstract
The African Union Transitional Justice Framework (AUTJF) is conceptualized to ‘end violent conflicts and repressive rule, and nurture sustainable development, social justice, human and peoples’ rights, democratic rule, and good governance, consolidate peace, reconciliation and justice in Africa, and prevent impunity’. However, instead of consolidating the peace dividend after many years of violent conflict, many African countries leap back into conflict. Though institutions such as the African Union (AU) and the Intergovernmental Authority on Development advocate for hybrid courts, this chapter argues that the complexity and plurality of such conflicts around the continent need more than court hybridity. The Western neo-liberal peacebuilding and transitional justice models, from which most elements of hybridity are borrowed, are inadequate. They are narrow; focus on retributive outcomes; and have logics of inclusion and exclusion. They are prone to instrumentalization, misappropriation, or co-option by more powerful national or international actors against the interests of local justice and security. This affects the resilience of peace outcomes in most of the cases. However, the vaunted traditional approaches cannot be successful alone because they lack universality of application across ethnic groups. This chapter advocates for strategic localized polyvalence responses to address the ever-challenging situations besetting the countries in conflict time and again. In Africa, these are the layers of local actors starting from the least powerful person to the AU. Through this model, this chapter not only considers dominant discourses, but also the operant, dormant, challenged, and even the strongly negated views within the transitional justice field.
Victim Participation in Hybrid International(ized) Tribunals
Authors: Ambach Philipp 
Published: January 2025

Abstract
The International Criminal Court (ICC) pioneered a set of new victim-centred features in its normative framework that are unprecedented by the ICC’s predecessors. All internationalized ad hoc criminal courts and tribunals established subsequent to the ICC’s creation include legal regimes on victim participation and, to some degree, reparations. It would thus appear that such a victim participation/reparations component has become a core feature of any modern international criminal justice mechanism. Yet such victim participation and reparations regimes are not without their challenges. These range from capacity/budgetary constraints to the general question of meaningfulness and impact on victims and affected communities. While the ICC promises to be well equipped to face these problems due to its permanent nature and rather secure capacity and funding, this appears less likely in some respects for regional ad hoc solutions exercising international criminal justice. A number of key challenges can be identified which may be decisive over the success or failure of meaningful victim participation in criminal proceedings and reparations at the end of the criminal process. Future lawmakers may want to consider how comprehensive a victim regime they want to introduce into future hybrid courts to avoid setting it up for failure.