bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lysine-specific histone demethylase 1A (KDM1A/LSD1) inhibition attenuates DNA double-strand break repair and augments the efficacy of temozolomide in glioblastoma
Authors: Alejo Salvador , Palacios Bridgitte E , Venkata Prabhakar Pitta , He Yi , Li Wenjing , Johnson Jessica D , Chen Yihong , Jayamohan Sridharan , Pratap Uday P , Clarke Kyra , Zou Yi , Lv Yingli , Weldon Korri , Viswanadhapalli Suryavathi , Lai Zhao , Ye Zhenqing , Chen Yidong , Gilbert Andrea R , Suzuki Takayoshi , Tekmal Rajeshwar R , Zhao Weixing , Zheng Siyuan , Vadlamudi Ratna K , Brenner Andrew J , Sareddy Gangadhara R 
Published: January 2023

Abstract

Background
Efficient DNA repair in response to standard chemo and radiation therapies often contributes to glioblastoma (GBM) therapy resistance. Understanding the mechanisms of therapy resistance and identifying the drugs that enhance the therapeutic efficacy of standard therapies may extend the survival of GBM patients. In this study, we investigated the role of KDM1A/LSD1 in DNA double-strand break (DSB) repair and a combination of KDM1A inhibitor and temozolomide (TMZ) in vitro and in vivo using patient-derived glioma stem cells (GSCs).

Methods
Brain bioavailability of the KDM1A inhibitor (NCD38) was established using LS-MS/MS. The effect of a combination of KDM1A knockdown or inhibition with TMZ was studied using cell viability and self-renewal assays. Mechanistic studies were conducted using CUT&Tag-seq, RNA-seq, RT-qPCR, western blot, homologous recombination (HR) and non-homologous end joining (NHEJ) reporter, immunofluorescence, and comet assays. Orthotopic murine models were used to study efficacy in vivo.

Results
TCGA analysis showed KDM1A is highly expressed in TMZ-treated GBM patients. Knockdown or knockout or inhibition of KDM1A enhanced TMZ efficacy in reducing the viability and self-renewal of GSCs. Pharmacokinetic studies established that NCD38 readily crosses the blood-brain barrier. CUT&Tag-seq studies showed that KDM1A is enriched at the promoters of DNA repair genes and RNA-seq studies confirmed that KDM1A inhibition reduced their expression. Knockdown or inhibition of KDM1A attenuated HR and NHEJ-mediated DNA repair capacity and enhanced TMZ-mediated DNA damage. A combination of KDM1A knockdown or inhibition and TMZ treatment significantly enhanced the survival of tumor-bearing mice.

Conclusions
Our results provide evidence that KDM1A inhibition sensitizes GBM to TMZ via attenuation of DNA DSB repair pathways.
Collateral damage: a case report of vertebral artery dissection and stroke in the young with persistent primitive trigeminal artery
Authors: Caesar Kymmi S , Maharaj Dale A , Ramlakhansingh Anil , Sinanan Alexander , Ramsingh Richard 
Published: January 2023

ABSTRACTStroke in the young is an uncommon condition resulting in significant morbidity and as result trammels the integrity of healthcare systems [1]. We present an unusual case of a 37-year-old male presenting with neurologic signs of right parietal lobe infarction with evidence of vertebral artery dissection and persistent carotid-vertebrobasilar anastomosis as a conduit for thromboembolism.
Post thrombolytic alveolar hemorrhage: a case report
Authors: Mardenli Mahmoud , Ghabally Mike , Horo Barkhodan , Alkhatib Qais , Raee Malek 
Published: January 2023

ABSTRACT
Alveolar hemorrhage following thrombolytic agents administration is an extremely rare entity that has only been reported in twenty two patients in the medical literature. We herein report a case of a 60-year old male with an acute ST-elevation myocardial infarction who was treated with Streptokinase. Twelve hours after streptokinase adminstration, the patient developed severe hemoptysis and dyspnea and radiological studies were highly suggestive for acute alveolar hemorrhage. His past medical history is significant for severe chest trauma ten months prior to presentation. . Conservative therapy in addition to anti-coagulants withdrawal has led to gradual improvement in the next six days. We also discussed the aspects of our patient in comparison with published cases.
Poly-microbial Clostridium cadaveris bacteremia in an immune-compromised patient
Authors: Abarca Jorge , Awada Bassem , Itkin Boris , Milupi Manyando 
Published: January 2023

ABSTRACT
Clostridium cadaveris (C. cadaveris), a strict anaerobic gram-positive rod, is rarely reported in clinical specimens. Since its detection in 1899, it has always been linked to the decay of dead bodies. C. cadaveris is considered non-pathogenic to humans, however infrequently it can cause severe infections including bacteremia. The latter was typically associated with gastro-intestinal pathologies. We report the first case of C. cadaveris invasive infection at Sultanate Oman. The source was most probably an infected decubitus ulcer.
A rare case of scleritis and multiple rheumatoid pulmonary nodules associated with seronegative rheumatoid arthritis
Authors: Sato Fumikazu , Yamano Takahiro , Manbo Yoshimi , Sakaguchi Kimikazu , Yamaguchi Kaori , Miyake Taito 
Published: January 2023

ABSTRACT
Seronegative rheumatoid arthritis (RA) is less likely to have extra-articular manifestations than seropositive RA. An 80-year-old man with polyarthritis was diagnosed with seronegative RA in which rheumatoid factors and anti-cyclic citrullinated peptides were not detected. He had multiple pulmonary nodules that diminished in size following treatment for RA, leading to the diagnosis of pulmonary rheumatoid nodules. During his treatment course, he developed scleritis, which could have resulted in blindness. As oral steroids did not improve his condition, topical steroid injections were administered, and his symptoms gradually improved. Here, we present a case of seronegative RA with an unusual combination of extra-articular manifestations: rheumatoid pulmonary nodules and scleritis.
Fairness
Authors: Barling Julian 
Published: January 2023

Abstract
One might question why a discussion about fairness is even necessary, but as Jerald Greenberg sadly reminded us, organizational fairness may be common sense but it is not common practice. This should be of huge concern for organizations and their members. Summarizing what is known about the effects of fairness and unfairness at work, no one has said it better than a group of noted epidemiologists: Being treated fairly, they claim, reminds us that we are valued, while unfair treatment can be “a source of oppression, deprivation and distress.” Just how important the experience of fairness or unfairness is evident from the vicarious experience of unfairness: even watching others being treated unfairly is enough to leave people feeling demoralized and wanting revenge.
Meaning
Authors: Barling Julian 
Published: January 2023

Abstract
While acknowledgment of the importance of belonging and growth needs is not new, appreciating the need for meaning at work is. We now know that finding meaning in your work is largely about helping others and is associated with favorable work attitudes, better work performance, and well-being. Of some concern, access to meaningful work seems to have declined since the turn of the century. And what does the opposite of meaningful work look like? We show that workaholism, doing boring work or dirty work, or feeling that you or your work are invisible are associated with negative work attitudes, work performance, and well-being. We pay special attention to how people engaged in dirty work—work that other people think is physically, socially, or morally disgusting, degrading, or distasteful—do what they can to find meaning in their work.
Questions
Authors: Rufai Sohaib R. 
Published: January 2023

Abstract
This paper covers the full range of core subjects tested in the FRCOphth Part 1 examination: optics, anatomy, physiology, pathology, pharmacology, genetics, investigations, and miscellaneous (biostatistics and evidence-based medicine). As well as ophthalmic subjects, this paper covers general physiology, general pathology, microbiology, biochemistry, and immunology. Several high-yield topics are covered. Ray diagrams are provided for the reflection of light by mirrors (convex and concave), Gullstrand’s schematic eye, and the reduced eye. An anatomical diagram displays the contents of the superior orbital fissure. The layers of the retina as seen on optical coherence tomography imaging are included, with a helpful mnemonic. Innervation and actions of the extraocular muscles are summarised in a table. The action potential is explained in a simple diagram. Histopathological slides displaying corneal dystrophies (lattice, macular, and granular) are included, with a helpful mnemonic. Electrodiagnostic tests are covered with useful figures. A flowchart for common statistical tests is provided.
Questions
Authors: Rufai Sohaib R. 
Published: January 2023

Abstract
This paper covers the full range of core subjects tested in the FRCOphth Part 1 examination: optics, anatomy, physiology, pathology, pharmacology, genetics, investigations, and miscellaneous (biostatistics and evidence-based medicine). As well as ophthalmic subjects, this paper covers general physiology, general pathology, microbiology, biochemistry, and immunology. Several high-yield topics are covered. Biological inheritance is explained using pedigree charts showing autosomal dominant and autosomal recessive inheritance and a helpful pedigree chart key is provided, covering essential terms. Basic orbital anatomy is displayed on neuroimaging. The box and whisker plot is explained in a helpful diagram.
Solutions
Authors: Rufai Sohaib R. 
Published: January 2023

Abstract
This paper covers the full range of core subjects tested in the FRCOphth Part 1 examination: optics, anatomy, physiology, pathology, pharmacology, genetics, investigations, and miscellaneous (biostatistics and evidence-based medicine). As well as ophthalmic subjects, this paper covers general physiology, general pathology, microbiology, biochemistry, and immunology. Several high-yield topics are covered. Ray diagrams are provided for the reflection of light by mirrors (convex and concave), Gullstrand’s schematic eye, and the reduced eye. An anatomical diagram displays the contents of the superior orbital fissure. The layers of the retina as seen on optical coherence tomography imaging are included, with a helpful mnemonic. Innervation and actions of the extraocular muscles are summarised in a table. The action potential is explained in a simple diagram. Histopathological slides displaying corneal dystrophies (lattice, macular, and granular) are included, with a helpful mnemonic. Electrodiagnostic tests are covered with useful figures. A flowchart for common statistical tests is provided
Solutions
Authors: Rufai Sohaib R. 
Published: January 2023

Abstract
This paper covers the full range of core subjects tested in the FRCOphth Part 1 examination: optics, anatomy, physiology, pathology, pharmacology, genetics, investigations, and miscellaneous (biostatistics and evidence-based medicine). As well as ophthalmic subjects, this paper covers general physiology, general pathology, microbiology, biochemistry, and immunology. Several high-yield topics are covered. Biological inheritance is explained using pedigree charts showing autosomal dominant and autosomal recessive inheritance and a helpful pedigree chart key is provided, covering essential terms. Basic orbital anatomy is displayed on neuroimaging. The box and whisker plot is explained in a helpful diagram
Strict Liability in the Four Tort Systems
Authors: Cappelletti Marco 
Published: January 2023

Abstract
Part 2 presents the four substantive laws and sets out the contexts of strict liability which can be identified in each of them. This will provide the necessary background for the comparative discussion of legal reasoning in Part 3, where the various arguments are discussed in relation to the specific contexts of liability for which they are invoked. More in detail, Part 2 explains how strict liability is understood in each of the four systems studied and it illustrates contexts of strict liability such as the vicarious liability of employers and parents, liability of public authorities, liability for defective products, the French and the Italian liabilities for the deeds of things, the English rule in Rylands v Fletcher, and the US liability for abnormally dangerous activities. Overall, Part 2 shows that strict liability is understood in loosely similar ways across the four laws and that, while strict liability features in all the four legal systems, it does so in different ways and to conspicuously differing extents across them.
Accident Avoidance
Authors: Cappelletti Marco 
Published: January 2023

Abstract
This section explores accident avoidance as a justification put forward to explain or support the imposition of strict liability in the four legal systems studied. First, the section explains how this argument works by identifying the ways in which strict liability may promote the avoidance of accidents more effectively than liability based on fault. Secondly, it unravels the patterns of use that characterize this argument in the four legal systems, while also assessing its justificatory significance and paying attention to the contexts of liability in relation to which this argument is invoked. The section shows that accident avoidance represents a widespread and important argument in the US and Italian legal reasoning on strict liability, while it is of more limited significance in the French and English contexts. There are various reasons for these differences, and they mainly relate to the way in which tort law and its functions are perceived as well as to the role that the economic analysis of law plays in the four legal systems studied.
Loss Spreading
Authors: Cappelletti Marco 
Published: January 2023

Abstract
This section explores loss spreading as a justification put forward to explain or support the imposition of strict liability in the four legal systems studied. First, the section presents the core idea behind this argument and its several internal variations (insurance spreading (comprising insurability and actual insurance coverage), enterprise spreading, taxation spreading, and burden–benefit proportionality). Secondly, the section unravels the patterns of use that characterize all these variations in the four legal systems, it assesses their justificatory significance, and it pays attention to the contexts of liability in relation to which the arguments are invoked. The section shows that the patterns of use and significance of arguments based on the spreading of losses present marked variations across the four systems studied, and explains why this is so. In particular, it is suggested that these differences are linked to the ways in which the debate on the functions of tort law has unfolded, with two key elements here. First, the degree to which the four legal systems are committed to the idea that tort law should be concerned only with considerations of interpersonal justice, to the exclusion of broader, collective concerns. Secondly, and relatedly, the extent to which values such as social solidarity and burden–benefit proportionality or goals such as the protection of victims or the minimization of the costs of accidents influence decisions as to the allocation of losses.
Victim Protection
Authors: Cappelletti Marco 
Published: January 2023

Abstract
This section explores the victim protection argument as put forward to justify the imposition of strict liability in the four legal systems studied. First, the section presents the idea behind this argument. Secondly, it unravels the patterns of use that characterize it in the four legal systems, while also assessing its justificatory significance and paying attention to the contexts of liability in relation to which it is invoked. The section shows that the victim protection argument is particularly significant in France, where there is a compensation ideology driving the reasoning in tort. In Italy and the United States the argument is also significant, though not as much as in France, with criticisms being levelled at it and attention being paid to other functions of strict liability as well. Finally, in England the patterns of use of the argument are the same as in the other three legal systems, but victim protection is invoked far less frequently and it is met with broad and explicit criticism.
Introduction
Authors: Borlik Todd Andrew 
Published: January 2023

Abstract
The book opens with an overview of Shakespearean ecoriticism and its overinvestment in green worlds. It argues that the Jacobean Shakespeare takes a greater interest in the prismatic wilds of Great Britain under the influence of his patron, the Scottish hunter-king James I. Synthesizing recent scholarship on Shakespeare as a court dramatist, the introduction contends that his late tragedies and romances grapple with the thorny environmental politics of the Stuart court. These plays often simulate a monarch’s-eye view of the natural world, applauding King James’s concerns about sustainability, overpopulation, and species loss. Yet they also reveal how fiercely the Crown’s dream of absolute dominion over Britain was contested. Sharing these scruples, Shakespeare appropriates and recoils from the poetics of Jacobean absolutism to dramatize the limitations imposed on the rule of both monarchs and mankind by the unruliness of the more-than-human environment.
Staging Darkness at Whitehall and Blackfriars
Authors: Borlik Todd Andrew 
Published: January 2023

Abstract
The final chapter spotlights the role of the theatre industry as a driver of human nocturnalization in Stuart Britain. As a court dramatist, Shakespeare was directly involved in the late-night revels of the Stuart court, but remained ambivalent about the court masque and its enactment both on-stage and off of the state’s vanquishing of darkness through artificial illumination. The chapter juxtaposes the nocturnal carnivalesque in plays like Antony and Cleopatra and Timon of Athens with tragic anti-masques of night-induced disability in Macbeth and King Lear that expose the flattering of James as an all-seeing, sun-like monarch. The chapter then links these divergent responses to the respective lighting levels in the hyper-illuminated Whitehall and the more dimly lit Blackfriars. Detecting an ugly correlation between nyctophobia and racism, the chapter gauges whether Shakespearean drama reinforces prejudice against other races, species, and abilities, or might instil a salutary acceptance of darkness and difference.
Conclusion
Authors: Borlik Todd Andrew 
Published: January 2023

Abstract
The conclusion reviews Lewis and Maslin’s claim that the Anthropocene commenced in 1610, and considers whether the developments in cultural and environmental history documented in this book make this something more than a coincidence. It argues that Jacobean absolutism’s polarizing rhetoric gave rise to corresponding notion of the sovereignty of the people in the early Anthropocene, but that Shakespearean drama is highly sceptical of both royal absolutism and the cosmic narcissism of mere mortals. Shakespeare’s clinical dissection of the ideological trifecta of god/king/man makes his late plays a valuable resource for exposing humanity’s eco-hubris as ecological tyranny. The book concludes by encouraging readers to find ways to teach and perform Shakespearean tragedies as ritual abdications of species tyranny and his tragicomedies as fables of resilience and radical hope.
An Equality-sensitive Approach to Delivering Socio-economic Rights during Crises
Authors: Miyandazi Victoria 
Published: January 2023

Abstract
This chapter discusses how the dire situation of vulnerable groups in Kenya is exacerbated in times of crises, such as the Covid-19 pandemic. Loss of employment, food shortages, and the high cost of living, coupled with the lack of equality-sensitive interventions by the government, have led to a rise in the number of Kenyans living in absolute poverty. This is despite the fact that Kenya’s 2010 Constitution contains multiple provisions on the protection of the socio-economic rights of vulnerable groups, with Article 20(5)(b) going even further to require the prioritization of the needs of vulnerable groups when implementing the socio-economic rights in Article 43 of the Constitution, to ensure their widest possible enjoyment. The chapter argues that, as much as Kenya’s laws provide the necessary legal framework and impetus for applying equality-sensitive approaches to delivering socio-economic rights and to avoid reinforcing inequality in times of crisis, they are not implemented by those in charge. The challenge, therefore, is the lack of application of actual laws in practice to facilitate the implementation of socio-economic rights to address the adverse effects of crises and their aftermath. In the final analysis, the chapter emphasizes that the needs of the most vulnerable in society should be prioritized when the state is implementing initiatives to respond to crises. This is what is constitutionally mandated in Kenya. To achieve this may mean the enactment of laws to best tackle contempt of court orders and blatant disregard of the law.
A First Look at Strategic Thinking
Authors: Arterton F. Christopher 
Published: January 2023

Abstract
For those working in public life, the overused term “strategy” can lead to vagueness in thinking and sloppiness and confusion in performance. Political managers need a precise term that defines their struggle to enact public policies that will implement their vision for a better world. Four different arenas of reflection will serve to renew the reader’s ability to think strategically: the science of military conflicts, strategic planning, persuasive communications, and dynamic interpersonal interaction. As an instrumental concept, “strategy” is more precisely applied to thinking than to actions. Strategy is then a means—a plan of action—to achieve one’s objective or vision despite aggressive opposition.
Real Women
Authors: McKinney Jennifer 
Published: January 2023

Abstract
This chapter addresses the primary roles for women in the context Mark Driscoll’s hypermasculine theology. Within their “homeward domain,” women were expected to be exemplary wives, mothers, and lovers. To be successful in these roles, women were told to resist being conformed to the broader culture’s feminist ideology. By rejecting feminist ideology and choosing to learn in submission, women could strive to be “Proverbs 31 women,” the epitome of successful wives and mothers. Women also needed to learn to be generous lovers to their husbands. While the roles of women were often embraced by members of Mars Hill Church, adhering to these roles could be problematic.
Conclusion
Authors: McKinney Jennifer 
Published: January 2023

Abstract
This chapter links the rise in hypermasculine theology with the rise in Christian nationalism and evangelical support for Donald Trump in the 2016 and 2020 presidential elections. Hypermasculine theology and Christian nationalism both seek to return American families to patriarchal gender norms. Both movements are a reaction against feminism. Mark Driscoll’s hypermasculine theology was abetted by the New Calvinism, a movement within evangelical Christianity to reassert hierarchical gender roles, to put men into power—in the home and throughout American institutions, including politics. The growth of megachurches has also intensified the power and visibility of these theologies and evangelicals’ political power.