bluuebunny/crossref_metadata_2025 huggingface dataset:
The Nature of Testimony
Authors: Gerken Mikkel
Published: September 2022

Chapter 2 begins with a discussion of the nature of testimony as a speech act and an epistemic source. This discussion draws on foundational epistemological research such as the internalist/externalist debate and the reductionist/anti-reductionist debate. Here Gerken provides an epistemically externalist emphasis of the epistemic significance of the social environment. Chapter 2 also considers the senses in which testimony may and may not be said to transfer epistemic warrant from testifier to recipient. Specifically, Gerken criticizes various transmission principles and argues for a negative principle, Non-Inheritance of Scientific Justification, according to which the kind or degree of scientific justification that the testifier possesses is typically not transmitted to the recipient—even when the testimonial exchange is epistemically successful. Finally, Chapter 2 also includes a discussion of norms (objective benchmarks of assessment) and guidelines (concrete directives that scientific testifiers may follow).
The Significance of Scentific Testimony
Authors: Gerken Mikkel
Published: September 2022

Chapter 7 begins with arguments for two theses concerning intra-scientific testimony. The first thesis, Methodology, is the claim that the distinctive norms governing intra-scientific testimony are vital to the scientific methods of collaborative science. The second thesis, Parthood, is the claim that intra-scientific testimony is a vital part of collaborative science. Gerken then turns to arguments for two theses about public scientific testimony. The first thesis of this duo, Enterprise, has it that public scientific testimony is critical for the scientific enterprise in societies pursuing ideals of deliberative democracy. The second thesis, Democracy, is the claim that public scientific testimony is critical for societies pursuing ideals of deliberative democracy. In light of these two theses, the role of public scientific testimony in the societal division of cognitive labor is discussed. One result of this discussion is a novel norm for laypersons’ uptake of public scientific testimony.
Areal and diachronic trends in argument flagging across Slavic
Authors: Seržant Ilja A. , Wiemer Björn , Bužarovska Eleni , Ivanová Martina , Makartsev Maxim , Savić Stefan , Sitchinava Dmitri , Skwarska Karolína , Uhlik Mladen
Published: September 2022

This pilot study examines the variation in the flagging patterns across 10 modern Slavic languages—covering all three major Slavic branches: South, West, and East Slavic—and Old Church Slavic. Despite high homogeneity in this domain across Slavic, there are clear genealogical and areal trends that explain the distribution of different flagging patterns across Slavic. Thus, regarding transitivity prominence, an areal trend splitting Slavic languages into Northeast Slavic (Belarusian, Polish, Russian, Ukrainian) and Southwest Slavic (all other languages) was detected, the former group showing relatively low and the latter high transitivity prominence. The same split is also seen in the ratio of nominative marking of the subject(-like) arguments, albeit to a minor degree. Here too, Northeast Slavic languages have a lower ratio than the Southwest ones. Although the genealogical relations still largely determine similarities in argument flagging, language contact must have played an important role here as well.
Embracing the Unknown
Authors: Degenhardt Jane Hwang
Published: September 2022

Chapter 4 concludes the book’s trajectory—from the stage’s representation of fortune as a force that creates opportunity in the world to the theater’s own identifications with commercial fortune. It does so by focusing on the theater’s thematic and representational embrace of seafaring as a metaphor for theatrical risk and reward as well as a model for the cognitive and phenomenological experience of playgoing. Specifically, it considers the ways that Hamlet (1600) and Pericles (1608) employ dramaturgical strategies for representing long-distance sea travel. By locating Hamlet’s sea voyage off stage, Hamlet allows for a break from the patterns of possibility established through past actions of the play and enacts a shift from the realm of possibility to one of untold potentiality. Picking up on the sea’s unpredictability as a metaphor for commercial audiences, Pericles attempts to foster patient viewing practices by means of its dramaturgical strategies for representing the sea.
Tracking the Resilience of Hybridity
Authors: McBride Mark
Published: September 2022

Matthew Kramer is the preeminent contemporary proponent of the interest theory of rights—according to which rights function to protect the right-holder’s interests. Kramer’s meticulous articulation and refinement of that theory has involved countering alternative theories—in particular, most recently, third-way alternatives to both interest and will theories. Kramer has accepted certain of these alternatives are genuinely novel theories, and then sought to demonstrate their shortcomings. Gopal Sreenivasan’s hybrid theory of (claim-)rights is one such theory, and Kramer has delineated a putative counterexample against it, and indeed against hybrid theories in general. My aim in this chapter is to counter the counterexample on behalf of hybridity in general—I am a hybrid theorist, but of a different stripe from Sreenivasan. And it’s my contention that grappling with the counterexample serves as a useful expository aid to deeper articulation of hybridity. Hybridity’s resilience emerges therefrom.
Objectivity, Conventions, and the Possibility of Universal Error
Authors: Bix Brian H.
Published: September 2022

The essay explores whether it makes sense to say that every person or every legal official was wrong about some legal issue. It reviews discussions of the subject by Matthew Kramer, Connie Rosati, and Andrei Marmor, as well as an earlier article by the current author. The ultimate conclusion is that universal error probably is possible. As Kramer pointed out, officials can agree about the foundational rules or basic observations, but (all) get the applications or implications wrong. Also, everyone might previously have misunderstood the original intentions of the constitutional or legislative drafters, or the real meaning of equality or due process. However, the topic of universal error remains complex, because truth in law is complicated: because of the problem of legal authority and legal mistake, there are places where law appears not to be bivalent; also, legal truth is made problematic by law’s defeasibility.
Kramer and Inclusive Legal Positivism
Authors: Waluchow Wilfrid J.
Published: September 2022

Gerald Postema once claimed that, in responding to Dworkin’s critique of Hart’s theory of law, defenders of Inclusive Legal Positivism (ILP) “seemed to have lost contact with the original phenomena, problems, and the theoretical and practical motivations that gave them life.” As one of ILP’s most powerful champions, this indictment extends to Matthew Kramer, whose work includes one of the most robust, insightful defenses of ILP on offer, and whose monumental contributions to legal, political, and moral philosophy are the focus of this volume. The objective of this chapter is to blunt the force of Postema’s indictment of Kramer and his ILP allies, particularly in relation to their long-standing dispute with their Exclusive Legal Positivist (ELP) cousins. It does so by arguing that ILP provides a better, more enlightening account of the nature of law than ELP does. More specifically, it argues that (1) ILP better accounts for the conventional nature of law than ELP does; (2) ILP offers a conceptual map of legal practice that is more consonant than ELP with the self-understanding expressed in the norms and practices of many legal systems; and (3) ILP better accounts for the variety of ways in which law is capable of structuring our practical reasoning and, as a result, serving our moral interests. If the arguments of this chapter are right, then they will have provided what Postema finds missing—good reasons for thinking that Kramer’s subtle and insightful jurisprudential theory was not, in the end, pretty much a waste of time.
From Law’s Existence to Law’s Rule
Authors: Postema Gerald J.
Published: September 2022

Kramer accepts Lon Fuller’s eight standards articulate the core of the rule of law. These standards, he agrees, are internal to law and, taken together, they constitute a “morally cherishable” ideal. But, against Fuller, he insists that the respect in which they are internal to law is not the respect in which they speak the language of moral ideals. The two conceptions offer separable ways of articulating the significance of Fuller’s eight standards. These distinct accounts, Kramer argues, pivot on the shared assumption that individual legal subjects are rational, self-directing agents. Lawgivers acknowledge and assume for their purposes, that legal subjects are rational, self-directing agents, because law’s fundamental function is to guide behavior through addressing rules to them. And, from the liberal-democratic moral point of view, this feature of legal subjects is a fact of fundamental moral importance, demanding our respect. Building on Kramer’s analysis, this essay argues that, understood in a particular way, the pivotal assumption provides a reasonably solid bridge between these two conceptions. It argues, further, that (1) the Fuller-Kramer account of legality needs the notion of fidelity, which plays a crucial role in the realization of the rule of law, and (2) that Kramer’s plausible individualist account of the rule of law’s grounding value must be embedded in a broader notion of membership that makes room for dignity and equality understood as relational values.
Distinguishing Value-Neutrality from Value-Independence
Authors: Radoilska Lubomira
Published: September 2022

This chapter outlines a new disentangling strategy for moral epistemology. It builds on the fundamental distinction between value-neutrality and value-independence as two separate aspects of methodological austerity introduced by Matthew Kramer. This type of conceptual analysis is then applied to two major challenges in moral epistemology: globalized skepticism and debate fragmentation. Both challenges arise from collapsing the fact/value dichotomy. They can be addressed by comprehensive disentangling that runs along both dimensions—value-neutrality vs. value non-neutrality and value independence vs. value-dependence. The success of this strategy rests on two factors. The first is broadening the scope of disentangling to include theoretical-explanatory values on a par with distinctly ethical values. The second is differentiating between wider and narrower conceptualizations of what value-neutrality requires with respect to contested matters. The objective is to pre-empt unjust theorizing, a distinctive form of epistemic injustice that derives from the exclusive methodological focus on ethical evaluations at the expense of epistemic ones. When these methodological conditions are fulfilled, opponents should gain the confidence to treat each other as fellow inquirers engaged in the same project, that of reducing the scope of unhelpful disagreements.
Purgative Punishment and the Importance of Perspective
Authors: Duff R.A.
Published: September 2022

According to Kramer’s “Purgative Rationale,” capital punishment is sometimes morally obligatory, for those who commit “extravagant evils:” their continued existence constitutes an “affront to humanity;” any state that has jurisdiction over them ought therefore to execute them (after a fair criminal process that respects their dignity). I discuss key elements of this rationale, and argue that Kramer illuminates the importance of some unduly neglected aspects of very serious crimes and of our responses to them. However, his rationale fails to establish his conclusion. We must distinguish between first-, second-, and third-person perspectives on crimes and their perpetrators: between how a perpetrator can respond to his own crimes, and how others can respond to them; between a third-person account of what others may or must do to the perpetrator, and a second-person account of how we may or must communicate with him. I then argue that even if a perpetrator’s evil deeds could be so horrendous that they put him beyond repentance, so that his continued existence would be an “affront to humanity,” others lack the authority to make, and give practical effect to, such a judgment; that punishment should constitute an attempt to engage with the perpetrator in the second person—which makes the execution of someone who is (we think) beyond repentance problematic; and that we should anyway not accept Kramer’s account of what constitutes the affront to humanity, or of how it could be removed.
Up and Down with the Welfare State
Authors: Kumlin Staffan , Goerres Achim
Published: September 2022

Older research on the welfare state often promoted a reductionist view of elections, seeing these as instruments for aggregation of exogenous preferences rather than for deliberation and preference change. Thus, we know more about policy ‘preferences’ than about policy ‘agendas’, i.e. how salient issues are. By contrast, this chapter analyses changes over time in the salience of welfare state issues in election campaigns. The chapter draws on recent work using a ‘systemic’ approach to agenda-setting. We examine if welfare issues become more—or perhaps less—likely to dominate entire election campaigns over time as most welfare states have fallen deeper into the era of ‘permanent austerity’. Moreover, have we witnessed a gradual increase in attention (as welfare states have experienced gradually mounting pressure)? Or have we rather seen a ‘late and brief’ attention response? This is implied by theories of ‘punctuated equilibrium’ and ‘attention cycles’. Moreover, the chapter asks if welfare state debate is a ‘fair-weather sport’ that is mainly exercised in the absence of pressures and in contexts where blame can be easily shifted (such as in a massive economic crisis)? A final set of questions concern the ‘social/investment activation’ turn. Have such issues taken over attention from less popular policy responses such as retrenchment?
Democracy and Welfare State Change Revisited
Authors: Kumlin Staffan , Goerres Achim
Published: September 2022

The concluding chapter restates key results and analyses implications for the book’s two overarching research problems. What have we learned about the quality of representative democracy and the nature of welfare state change? The discussion is structured by the notions of democratic linkage and leadership. While the results are complex and partly positive, the chapter also highlights serious flaws in democratic linkage and leadership processes in changing mature welfare states. The book closes by discussing specific discrepancies between how leaders debate welfare state change and how citizens reason about it.
Policy Horizons
Authors: Calvert Julia
Published: September 2022

This chapter lays out the theoretical framework of the book. It theorizes the ways in which endogenous interests interact with exogenous pressures to shape infringement and reform preferences. It posits that programmatic beliefs—coherent sets of normative and causal frames which interlock to form a whole—impact state action under (and towards) investment treaty law. They do so in two ways: by defining the kinds of behaviour state actors view as appropriate in light of the conditions they face (the policy horizon); and by shaping the ways actors interpret their experiences under IIAs and in ISDS, which informs their understandings of the problems and solutions they face in investment treaty law. The implication is that two governments may respond differently to similar information and pressures where dominant belief systems vary. The chapter first discusses dominant theories of compliance and treaty reform as well as the various exogenous pressures governments face in maintaining and complying with their treaty commitments. The chapter then illustrates the role programmatic beliefs play in shaping whether IIAs lead to policy chill, policy alignment, or infringement. Finally, it addresses how programmatic beliefs guide political learning processes and how they ultimately shape reform preferences.
Constitution
Authors: James Simon P.
Published: September 2022

In many cases, value tracks meaning. In particular, when some natural entity has value for us on account of its meaning, and that meaning depends on some context, y, then the entity’s value for us will typically depend on y. More precisely, the entity will be of constitutive value—of value, that is, because it is part of, rather than a means to, y. This part–whole model of value sheds light on the case studies presented in Chapters 3 and 4. In each of those cases, some natural entity has value because it contributes (though not of course intentionally) to some meaningful whole which, in turn, qualifies as valuable by virtue of its links with human well-being. Take the example of the Saami’s reindeer. The reindeer play an important role in the Saami’s cultural identity. If, as seems likely, their having that identity contributes to their well-being, then, by the lights of the part–whole model, the reindeer have constitutive value for the Saami. This conception of constitutive value is then compared with three other kinds of value—namely, (1) value for us, (2) value all things considered, and (3) aesthetic value.
Beyond Value for Us
Authors: James Simon P.
Published: September 2022

So far, the discussion has focused on nature’s value for us—that is, the value it has by virtue of the contributions it makes to human well-being. Readers towards the dark green pole of the environmental spectrum may dismiss this focus on human well-being as unacceptably anthropocentric. But to highlight nature’s constitutive value for us is not to deny that it can have other kinds of value. And in fact there are reasons to think that some natural entities have constitutive value because of the meanings they have for certain non-human animals. Besides, whether or not meaning-apprehension is a distinctively human capacity, some such entities certainly can have instrumental value for animals, as berries have value for bears or aspen twigs value for beavers. In addition to this, there are reasons to think that some natural entities are valuable for their own sakes, and not simply for the sake of other things, such as those human or non-human beings to whose well-being they contribute. There are reasons, that is, to think that some natural entities have intrinsic value. The relations between nature’s intrinsic values and its constitutive values are explored by means of a tenth case study, Dugong hunting.
Blood and Demons
Authors: Zellentin Holger M.
Published: September 2022

Using the double prohibition of murder, on the one hand, and the consumption of animal blood and of improperly slaughtered animals, on the other, as first case study, the first chapter introduces the laws given to Noah and his offspring in Genesis 9. It argues that these laws, legally as well as narratively, form the background also of the laws given to the non-Israelite residents of the Holy Land, the gerim, in Leviticus 17. The chapter further considers the entirety of the gerim laws in Leviticus 17–26 and argues that these laws underlie not only the Decree of the Apostles but also the rabbinic Noahide Laws, following different exegetical hermeneutics. This allows for a triangulation of the exegetical background of both legal narratives, and equally highlights two key differences between the stricter Christian and the more lenient rabbinic tradition of gentile law. The chapter then traces the prohibition of idol meat, blood, and carrion throughout late antique Christianity and up to the Qur’an. It argues that the gentile purity laws defined in the Decree of the Apostles, though partially softened or even dismissed by a small minority of Church Fathers since the fourth century, remained part of mainstream Christianity throughout late antiquity and were universally appreciated as well as repeatedly connected to Leviticus 17. The chapter concludes with a consideration of the Qur’an’s food laws, arguing that the Qur’an dismisses pagan Arabian food laws and instead takes the appreciative and especially the expansive Christian tradition of gentile food laws as its point of departure, all the while expanding some of its regulations and prohibitions pertaining to impurity and introducing dispensations for specific circumstances.
Purity and Punishment in the Qur’an
Authors: Zellentin Holger M.
Published: September 2022

In lieu of a conclusion, this chapter will synthesize this study’s findings from the point of view of their implications for the interrelated subjects of purity and this-worldly punishment, which we will consider in three steps. First, we will briefly consider some of the Qur’an’s notions of purity and impurity, along with the adjacent issue of sacredness. Establishing the Islamic Scripture’s concepts of purity and of the holy will allow for a broader comparison of similar notions in the Hebrew Bible and in various streams within the Jewish and Christian traditions. Second, we will revisit Christian and especially rabbinic takes on the biblical concept of “impurity of the land”—which proved essential for the biblical concept of prohibited impurity—in order to probe their relevance for understanding the respective qur’anic notion of “corruption in the land.” Third, a comparative consideration of the few qur’anic passages that delineate modes of this-worldly punishment will allow for a comparison of qur’anic with biblical, Jewish, as well as especially late Roman Christian modes of punishment, leading us to a concluding assessment of the role that prohibited impurity plays in the various penal codes.
An Outlook
Authors: Zellentin Holger M.
Published: September 2022

The Outlook offers a very brief restatement of key findings and then considers which questions this volume raised, and how they may be addressed in future scholarship. Issues include the role of Middle Eastern law more broadly and Arabian legal culture more specifically; questions of orality and of translations of the Bible; the relationship of the Qur’an with specific types of Judaism and Christianity; the importance of epigraphy and of traditional Islamic sources for the study of the Qur’an and of pre-Islamic Arabia; the value of the insights of the later Islamic jurists for the understanding of the Qur’an; and the relationship of Islamic jurisprudence with ancient Arabian as well as with Jewish, Christian, especially Byzantine, and plausibly Aksumite law.
Disentangling Neanderthal-Modern Human Interactions in Western Europe
Authors: Gravina Brad , d’Errico Francesco , Bachellerie Frçncois
Published: September 2022

This chapter highlights methodological challenges for an understanding of acculturation and creolization in early prehistory. The authors note that this is especially evident in situations such as the Châtelperronian where there is little chronological definition. In reference to the Châtelperronian, it is recognized as remarkable how such a restricted spectrum of evidence proves to be so incredibly agile, producing such outwardly conflicting and occasionally paradoxical models. It is also noted that concepts such as acculturation and creolization flounder when confronted with the period’s temporal resolution and lack of direct evidence for individual and group-level interactions. The authors recognize that the satisfactory furtherance of this research depends upon a thorough archaeological and taphonomic analysis of key sites.
Economic Environment
Authors: Verhagen Hendrik L. E.
Published: September 2022

This chapter discusses the economic environment of the law of real security, in particular in the context of secured lending. Agriculture was the most important sector of the Roman economy and it was precisely this sector of the economic environment that initially triggered important developments in the law of real security. From circa 250 bc onwards there was a shift in agriculture towards commercialization and specialization, as well as a substantial increase in trade, commerce, and credit. In the late Republic and Principate, ‘irritations’ produced by the financial sector became significant stimuli for the evolution of the Roman law of real security. This chapter will look at the role of bankers and elite financiers in the Roman credit markets. It will review various forms of credit, as well as categories of capital goods serving as collateral. Finally, it will discuss the significance of real security for the (urban and rural) rental markets.
Origins
Authors: Verhagen Hendrik L. E.
Published: September 2022

In this chapter, the origins of pignus and its remedies in the Republic will be discussed. The pledges we encounter in Cato’s De agricultura are ancestors of the tenant’s pledge of invecta et illata and are early and important examples of transactional practices with formative effect. In the first century bc, for the first time in the history of Roman law specific legal remedies were developed for pignus: the interdictum Salvianum and the interdictum de migrando. Not long after the introduction of these interdicts, the actio Serviana was included in the praetor’s edict, perhaps originally exclusively for tenant’s pledges. In republican law a second form of real security was already originated: fiducia cum creditore. This chapter will also review the origin and early evolution of this form of real security and examine its historical and structural relationships with pignus.
From Special to General Pledge
Authors: Verhagen Hendrik L. E.
Published: September 2022

In the second half of the second century ad a pledge originated which extended to all the assets which were from time to time part of the debtor’s patrimony. For centuries the general pledge has given rise to two questions: what was its object and what were its legal consequences? This chapter will first look at generic pledges as ancestors of the general pledge. The origin of the general pledge, via the intermediate stage of the so-called cetera bona pledge, will then be charted. The remaining sections of this chapter will review the legal consequences of the general pledge. It will appear that the Roman general pledge can be regarded as a ‘floating’ charge, which covered all the assets which were from time to time in the debtor’s patrimony and which allowed the debtor to dispose of these assets free from pledge.
Adaptedness of Pignus and Hypotheca
Authors: Verhagen Hendrik L. E.
Published: September 2022

The central questions of this chapter are: was the Roman law of real security adapted to its economic environment, and did it contribute to economic growth? The findings of law and economics on the role of the law of secured credit in modern economies are to be applied to Roman law. It will appear that classical Roman law had all but one (public title registries) of the features of effective collateral laws identified in economic analyses of modern law. The negative effects of the Romans’ failure to set up a public register for ownership and security interests in the western part of the empire, may have been neutralized by contractual practices and social norms for a long time. This makes it plausible that for most of the Principate, the Roman law of real security was capable of facilitating credit in a similar manner as its descendants do in modern economies and did contribute to growth of the Roman economy.
Anther development—The long road to making pollen
Authors: Marchant D Blaine , Walbot Virginia
Published: September 2022

Anthers express the most genes of any plant organ, and their development involves sequential redifferentiation of many cell types to perform distinctive roles from inception through pollen dispersal. Agricultural yield and plant breeding depend on understanding and consequently manipulating anthers, a compelling motivation for basic plant biology research to contribute. After stamen initiation, two theca form at the tip, and each forms an adaxial and abaxial lobe composed of pluripotent Layer 1-derived and Layer 2-derived cells. After signal perception or self-organization, germinal cells are specified from Layer 2-derived cells, and these secrete a protein ligand that triggers somatic differentiation of their neighbors. Historically, recovery of male-sterile mutants has been the starting point for studying anther biology. Many genes and some genetic pathways have well-defined functions in orchestrating subsequent cell fate and differentiation events. Today, new tools are providing more detailed information; for example, the developmental trajectory of germinal cells illustrates the power of single cell RNA-seq to dissect the complex journey of one cell type. We highlight ambiguities and gaps in available data to encourage attention on important unresolved issues.
Confronting Commercial Sexual Exploitation of Children in Comprehensive Sex Education
Authors: Wickline Mihkaila Maurine
Published: September 2022

An argument for applying an antiracist lens.
Multispecies Probiotic Can Prevent Antibiotic-Associated Diarrhea in Children
Authors: Rosenberg Karen
Published: September 2022

According to this study:

Although a multispecies probiotic didn't reduce the risk of antibiotic-associated diarrhea in children when the most stringent definition of the condition was used, it did, however, have a beneficial effect on the overall risk of diarrhea during and seven days after antibiotic treatment.

The authors point out that the cause of diarrhea may not be relevant so long as the preventive intervention is effective.
More Than Fluff and Buff
Authors: Hynes Millie R.
Published: September 2022

Massage therapy with older patients can be healing and rewarding work.
Anesthesiologists and the Other Pandemic: Tobacco Use
Authors: Warner David O.
Published: September 2022

Tobacco use will kill a projected 1 billion people in the 21st century in one of the deadliest pandemics in history. Tobacco use disorder is a disease with a natural history, pathophysiology, and effective treatment options. Anesthesiologists can play a unique role in fighting this pandemic, providing both immediate (reduction in perioperative risk) and long-term (reduction in tobacco-related diseases) benefits to their patients who are its victims. Receiving surgery is one of the most powerful stimuli to quit tobacco. Tobacco treatments that combine counseling and pharmacotherapy (e.g., nicotine replacement therapy) can further increase quit rates and reduce risk of morbidity such as pulmonary and wound-related complications. The perioperative setting provides a great opportunity to implement multimodal perianesthesia tobacco treatment, which combines multiple evidence-based tactics to implement the four core components of consistent ascertainment and documentation of tobacco use, advice to quit, access to pharmacotherapy, and referral to counseling resources.
A novel platform for the production of autologous human antibodies
Authors: Hatzidaki Eleana , Apostolou Panagiotis , Ntanovasilis Dimitrios Athanasios , Papasotiriou Ioannis
Published: September 2022

At Research Genetic Cancer Centre, we have developed a novel method for the production of human monoclonal antibodies against a specific antigen of our choice (c-met) using isolated human blood cells. By mimicking nature, dendritic, CD4 and CD19 cells from healthy volunteers were driven towards Th2 immunity. Cell activation was succeeded by a cytokine cocktail, and IgG production was promoted by IgG class switching factors. IgG secretion was determined using both enzyme linked immunosorbent assay (ELISA) and Western blot as well as immunoglobulin heavy chain gamma polypeptide gene expression. Secreted antibody was further purified by affinity column chromatography against c-met peptide. Anti-c-met activity was determined using the purified antibody as primary antibody for c-met detection by ELISA, Western blot and flow cytometry. Finally, anti-c-met antibody efficiency was determined by MCF-7 viability assay. Plasma cell formation and IgG secretion took place after 6 days of culture. Plasma cells produced anti-c-met IgG antibody that significantly decreased MCF-7 breast cancer cell proliferation. To our knowledge, this is the first platform of its kind, generating fully human antibodies-on-demand using patient’s own cells, bringing personalized, targeted therapy for cancer one step closer.
Ceramide synthase 6 antisense RNA 1 contributes to the progression of breast cancer by sponging miR-16-5p to upregulate ubiquitin-conjugating enzyme E2C
Authors: Pan Wu , Chen Ke-Jun , Huang You-Cheng
Published: September 2022

Breast cancer (BC) is the most dangerous female mortality all over the world, described by unavoidable spread and metastaticity of BC cells. Increasing evidences verified that lncRNA play a major role in the tumorgenesis and development of BC cell. The purpose of this study is to investigate the roles of lncRNA ceramide synthase 6 antisense RNA 1 (CERS6-AS1) and ubiquitin-conjugating enzyme E2C (UBE2C) in BC and explore the regulatory association among miR-16-5p, CERS6-AS1, and UBE2C in BC. The CERS6-AS1 and UBE2C expression levels were determined by real time quantitative PCR in cell lines and tissues of BC. The function of CERS6-AS1 and UBE2C in the apoptosis, proliferation, and migration was confirmed by cell counting kit-8, Transwell, and flowcytometry tests. We performed tumor xenograft assay to validate the roles of CERS6-AS1 in vivo. The expression of UBE2C proteins was evaluated by Western Blot analysis. Moreover, the relationship among UBE2C, CERS6-AS1, and miR-16-5p was verified by luciferase report assay. It was found that CERS6-AS1 and UBE2C were meaningfully upregulated in BC, and knockdown of both CERS6-AS1 and UBE2C inhibited the BC cell proliferation and migration, whereas induced apoptosis. Mechanistically, CERS6-AS1 could facilitate BC progression by sponging miR-16-5p for upregulation of the UBE2C expression. The CERS6-AS1/miR-16-5p/UBE2C axis might be a prospective therapeutic target in the BC treatment by sponging miR-16-5p to upregulate UBE2C, which might contribute to the development of BC.
Circ_0002111 modulates the growth process of papillary thyroid carcinoma cells by targeting the miR-363-3p/HMGB1 axis
Authors: Zhang Zhijian , Mo Yanping , Wu Lixuan , Wang Xiaolong , Liao Guansheng , Tan Wenzhi , Li Dexiang
Published: September 2022

Previous studies have suggested that circular RNAs (circRNAs) are engaged in the progression of papillary thyroid carcinoma (PTC). However, the mechanism of circ_0002111 in PTC is still unclear. In this study, quantitative real-time PCR was carried out to measure the expressions of circ_0002111, microRNAs (miRNAs) and high-mobility group box 1 (HMGB1). Immunohistochemistry assay and western blot were applied for the determination of protein levels. The assays of 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide and thymidine analog 5-ethynyl-2’-deoxyuridine were deployed to assess PTC cell viability and proliferation, respectively. Besides, the capacities of cell apoptosis, invasion and angiogenesis were determined by flow cytometry, transwell and tube formation assays, respectively. Moreover, the interaction between miR-363-3p and circ_0002111 or HMGB1 was confirmed using a dual-luciferase reporter assay. Lastly, we established a xenograft model for the examination of the function of circ_0002111 in vivo. It was found that the expression of circ_0002111 was enhanced in PTC tissues and cells. Silencing circ_0002111 apparently retarded the viability, proliferation, invasion and tube formation, as well as expedited the apoptosis of PTC cells. Besides, circ_0002111 knockdown impeded the growth of the tumor in vivo. For mechanism analysis, circ_0002111 adjusted the expression of HMGB1 by sponge adsorption of miR-363-3p. Moreover, miR-363-3p inhibitor regained the influence of cellular malignant phenotype caused by circ_0002111 knockdown. Additionally, miR-363-3p overexpression impacted the cell functions by targeting HMGB1 in PTC. Thus, silencing circ_0002111 constrained the progression of PTC by the miR-363-3p/HMGB1 axis, which perhaps provided a novel idea of the therapeutic in PTC.
Exome sequencing in a Swedish family with PMS2 mutation with varying penetrance of colorectal cancer: investigating the presence of genetic risk modifiers in colorectal cancer risk
Authors: Bryant Patrick , Walton Bernstedt Sophie , Thutkawkorapin Jessada , Backman Ann-Sofie , Lindblom Annika , Lagerstedt-Robinson Kristina
Published: September 2022

Objective

Lynch syndrome is caused by germline mutations in the mismatch repair (MMR) genes, such as the PMS2 gene, and is characterised by a familial accumulation of colorectal cancer. The penetrance of cancer in PMS2 carriers is still not fully elucidated as a colorectal cancer risk has been shown to vary between PMS2 carriers, suggesting the presence of risk modifiers.

Methods

Whole exome sequencing was performed in a Swedish family carrying a PMS2 missense mutation [c.2113G>A, p.(Glu705Lys)]. Thirteen genetic sequence variants were further selected and analysed in a case-control study (724 cases and 711 controls).

Results

The most interesting variant was an 18 bp deletion in gene BAG1. BAG1 has been linked to colorectal tumour progression with poor prognosis and is thought to promote colorectal tumour cell survival through increased NF-κB activity.

Conclusions

We conclude the genetic architecture behind the incomplete penetrance of PMS2 is complicated and must be assessed in a genome wide manner using large families and multifactorial analysis.
Approaches to Estimating Clearance Rates for Human Papillomavirus Groupings: A Systematic Review and Real Data Examples
Authors: Wijstma Eline S. , Jongen Vita W. , Alberts Catharina J. , de Melker Hester E. , Hoes Joske , Schim van der Loeff Maarten F.
Published: September 2022

Introduction:

Approaches to estimating clearance rates, an important metric of human papillomavirus (HPV) clearance, for HPV groupings differ between studies. We aimed to identify the approaches used in the literature for estimating grouped HPV clearance rates. We investigated whether these approaches resulted in different estimations, using data from existing studies.

Methods:

In this systematic review, we included articles that reported clearance rates of HPV groupings. We identified approaches to data in the HAVANA cohort, comprising adolescent girls, and the H2M cohort, comprising men who have sex with men. We estimated clearance rates for six HPV groupings (bivalent-, quadrivalent- and nonavalent vaccine-related, and low-risk, high-risk, and any HPV).

Results:

From 26 articles, we identified 54 theoretically possible approaches to estimating clearance rates. These approaches varied regarding definitions of clearance events and person–time, and prevalence or incidence of infections included in the analysis. Applying the nine most-used approaches to the HAVANA (n = 1,394) and H2M (n = 745) cohorts demonstrated strong variation in clearance rate estimates depending on the approach used. For example, for grouped high-risk HPV in the H2M cohort, clearance rates ranged from 52.4 to 120.0 clearances/1000 person–months. Clearance rates also varied in the HAVANA cohort, but differences were less pronounced, ranging from 24.1 to 57.7 clearances/1000 person–months.

Conclusions:

Varied approaches from the literature for estimating clearance rates of HPV groupings yielded different clearance rate estimates in our data examples. Estimates also varied between study populations. We advise clear reporting of methodology and urge caution in comparing clearance rates between studies.
Community Mitigation Strategies, Mobility, and COVID-19 Incidence Across Three Waves in the United States in 2020
Authors: Ledesma Jorge R. , Zou Lin , Chrysanthopoulou Stavroula A. , Giovenco Danielle , Khanna Aditya S. , Lurie Mark N.
Published: September 2022

Background:

Summarizing the impact of community-based mitigation strategies and mobility on COVID-19 infections throughout the pandemic is critical for informing responses and future infectious disease outbreaks. Here, we employed time-series analyses to empirically investigate the relationships between mitigation strategies and mobility on COVID-19 incident cases across US states during the first three waves of infections.

Methods:

We linked data on daily COVID-19 incidence by US state from March to December 2020 with the stringency index, a well-known index capturing the strictness of mitigation strategies, and the trip ratio, which measures the ratio of the number of trips taken per day compared with the same day in 2019. We utilized multilevel models to determine the relative impacts of policy stringency and the trip ratio on COVID-19 cumulative incidence and the effective reproduction number. We stratified analyses by three waves of infections.

Results:

Every five-point increase in the stringency index was associated with 2.89% (95% confidence interval = 1.52, 4.26%) and 5.01% (3.02, 6.95%) reductions in COVID-19 incidence for the first and third waves, respectively. Reducing the number of trips taken by 50% compared with the same time in 2019 was associated with a 16.2% (−0.07, 35.2%) decline in COVID-19 incidence at the state level during the second wave and 19.3% (2.30, 39.0%) during the third wave.

Conclusions:

Mitigation strategies and reductions in mobility are associated with marked health gains through the reduction of COVID-19 infections, but we estimate variable impacts depending on policy stringency and levels of adherence.
Tarsal Ectropion Repair With Modified Bick Eyelid Tightening and Inverting Sutures
Authors: Wang Diane , Deng Wenyu , Shinder Roman
Published: September 2022

Purpose:

The authors report on a 10-year experience of correcting tarsal ectropion using a combined method of modified Bick eyelid tightening (MBLT) and inverting sutures.

Methods:

Retrospective, interventional case series of consecutive patients with tarsal ectropion who underwent MBLT and inverting sutures by a single surgeon (RS) between July 2010 and July 2020. Thirty-four patients, 24 of whom were female, with a mean age of 81.6 years (range 59–92) were included. Eight patients had bilateral disease. All procedures were performed under local anesthesia in an office setting. Treatment success was defined by eyelid position, symptoms, and need for reoperation.

Results:

Thirty-one patients (91%) had a successful outcome. Three patients (9%) had satisfactory results with improved symptoms and mild residual ectropion, for which further surgery was not required. No patients had poor results. The mean follow-up time was 4.5 months (range 3–11 months). The inverting sutures were well tolerated in all cases and none had to be removed due to ocular surface discomfort. There were no visible scars from the inverting sutures in any patient at postoperative month 3.

Conclusions:

A combination of eyelid tightening using MBLT and inverting sutures is a simple and effective treatment for lower eyelid tarsal ectropion with minimal tissue dissection.
Implantable Electronic Cardiovascular Device Complications Related to Electrocautery During Ophthalmology Surgery: A Systematic Review
Authors: Tauber Jenna , Tingley Jennifer P. , Barmettler Anne
Published: September 2022

Purpose:

Implantable electronic cardiovascular device such as cardiac pacemakers and implantable defibrillators are common life-saving devices. Device-related complications can arise when undergoing surgical interventions with electrosurgical tools due to electromagnetic interference, based on electrocautery type, implantable electronic cardiovascular device type, electrocautery location, and a number of other factors. The risk of device-related complications due to electrocautery in oculoplastic surgery has not been established. This systematic literature review assesses prevalence, risk factors, and outcomes of electrocautery-related device complications in oculoplastic surgery.

Methods:

Systematic literature review followed Preferred Reporting Items for Systematic and Meta-Analysis guidelines and used the search terms “pacemaker,” “implantable cardioverter defibrillator,” “electrocautery,” “cautery,” and “electrosurgery” through June 2022. Inclusion criteria were full-text articles, discussing ocular, oculoplastic, or other facial surgery. Exclusion criteria were non-English language or surgery focused on other parts of the body. Full-text manuscripts of identified articles were reviewed and relevant data were extracted.

Results:

Twelve studies met inclusion criteria. Two studies were level I and II evidence, while 10 studies were level III or IV. There were no reports of electromagnetic interference with bipolar cautery use. With monopolar cautery use, cases of electromagnetic interference were reported, but without related significant morbidity or mortality. Safety recommendations to minimize electrical flow through the implantable electronic cardiovascular device are described.

Conclusions:

There were no reports of implantable electronic cardiovascular device–related complications from bipolar or thermocautery use in ophthalmic or oculoplastic surgeries. Monopolar have been associated with electromagnetic interference, but additional preoperative and perioperative measures can be taken to mitigate this risk.
Obesity Classification of the Body Mass Index Does Not Predict Participation Restrictions at Work
Authors: Arnold Christopher , Linden Michael , Warnke Max Holger
Published: September 2022

Objective

The objective was to explore the differences of the three body mass index (BMI) obesity classes regarding sociodemographic data, medical and psychological well-being, but especially participation restrictions at work.

Methods

A specialist in psychosomatic medicine reported on the health and occupational status of 190 patients (BMI >30), who were treated as inpatients in a psychosomatic rehabilitation unit.

Results

Significant increases in severity or work limitations were found for higher BMI groups concerning metabolic, cardiologic, and orthopedic comorbidity. There were no differences regarding indicators of occupational participation. Independent of the obesity status, about three quarters were seen as fit for work.

Conclusions

The initial hypothesis is rejected, as no difference concerning objective parameters of work participation were found between the BMI classes. The data suggest that BMI class I to BMI class III do not allow predictions of the ability to work.