bluuebunny/crossref_metadata_2025 huggingface dataset:
Remedies Aplenty
Authors: Sarkar Natasha
Published: March 2024

The chapter highlights two very different ways of treating patients, namely, indigenous medicine and Western biomedicine, and examines various perceptions of illness and the disease itself. At the time of the third plague pandemic, medicine had advanced to a considerable extent, and the chapter looks at the efficacy of and response to Yersin’s serum, Lustig’s serum, and Haffkine’s vaccine. It also discusses details of the general treatment that was provided to patients. Haffkine’s development of the plague vaccine and its reception receives much-needed attention as do other efforts at combating plague within the realm of Ayurveda. Attempts by Ayurvedic revivalists to regenerate their own system of medical practice by negotiating between tradition and modernity are also addressed. The accounts of popular medicine and even a plague goddess are revealing of the fascinating, intriguing, and even absurd non-biomedical alternatives that the masses took refuge in.
Not All Reproduction Involves Sex
Authors: Teather Kevin
Published: March 2024

Reproduction was asexual for almost half the time that life existed on Earth. The first way organisms made copies of themselves was probably by splitting or fission, resulting in two identical cells. In some cases today, a bud grown from the parent forms a new individual, while in others, regeneration through fragmentation can result in multiple individuals. Spores refer to sexually or asexually produced reproductive stages often designed to withstand harsh conditions. Finally, plants exhibit an impressive array of ways to propagate, many not requiring any other individual. Variability in prokaryotes, needed for natural selection to operate, is produced by mutation and incorporating the genetic material of others through transformation, transduction, and conjugation. Parthenogenetic females have offspring that are often (but not always) identical to themselves, without any genetic material supplied by males. While parthenogenesis is a form of asexual reproduction, these species descend from sexual reproducers with whom they may share more characteristics.
The Road to Sexual Reproduction
Authors: Teather Kevin
Published: March 2024

Living organisms are divided into two superkingdoms: the prokaryotes and eukaryotes. Prokaryotes consist of eubacteria and archaebacteria, are single-celled, and breed asexually. All other organisms comprise eukaryotes. These are larger, more complex, often multicellular, and, with some exceptions, reproduce sexually. About two billion years ago, eukaryotes evolved from prokaryotes by incorporating oxygen-using eubacteria into anaerobic archaeans. This development was accompanied by increased oxidative metabolism using the newly acquired bacteria, or mitochondria. The mitochondrial genome interacts with the nuclear genome to provide the proteins necessary for energy production. While using oxygen is more efficient when producing energy for the cell, it also results in extensive DNA damage by releasing free oxygen radicals. Meiosis is an integral part of sexual reproduction and is present in nearly all organisms that reproduce sexually. It likely evolved during the transition between the prokaryotes and eukaryotes. Of significant importance, crossing-over during an early stage of meiosis provided the capacity to repair DNA and resulted in increased levels of variability in progeny. Both of these factors may be important in the evolution of sex.
Two Sexes
Authors: Teather Kevin
Published: March 2024

Males and females of a particular species may differ in many ways. Such differences may include hormone levels, genotypes, and various anatomical and physiological characteristics. However, the only consistent difference across all species having two sexes is gamete size; females have larger, stationary eggs, while males have smaller, mobile sperm or pollen. Models suggest that having two sizes of gametes, especially when the larger is stationary and sends out signals, has been selected because the ability to find each other is high. Although a few species remain isogamous (having gametes of the same size), even these have differences between mating types that permit recognition. In addition, a few species have more than one mating type, potentially increasing the encounter rate of a mating partner. These conditions are, however, rare. While the ability to produce male and female gametes is most often found in different individuals, hermaphrodites can contain both types of sex cells within one body. Regardless, self-fertilization is uncommon. After male and female gametes come together, they undergo a series of physiological processes, enabling them to recognize one another and ultimately combine their genetic material.
The Epistemology of Desire and the Problem of Nihilism
Authors: Hazlett Allan
Published: March 2024

Most people have wondered whether anything really matters, some have temporarily thought that nothing really matters, and some philosophers have defended the view that nothing really matters. However, if someone thinks that nothing matters—if they are a “nihilist about value”—then it seems that it is irrational for them to care about anything. It seems that nihilism about value mandates total indifference. However, it is not irrational to care about something that you believe does not matter. Defending this conclusion requires an examination of the nature of desire. It is argued that goodness is the accuracy condition for desire, in the same way that truth is the accuracy condition for belief; that desires, like beliefs, can amount to knowledge; and that that desires, like beliefs, can be irrational. Despite these similarities between desire and belief, and even though it is obviously irrational to believe something that you believe is not true, it is not irrational to desire something you believe is not good. This reveals that nihilism about value does not mandate total indifference. It also shows that nihilism about value can coherently be combined with the anti-Humean view that desire is a species of evaluation.
Empirical Imagination in Perception and Experience
Authors: Matherne Samantha
Published: March 2024

This chapter’s aim is to clarify Kant’s account of the empirical contribution that imagination makes in perception and experience. It situates this contribution in an interpretation of Kant’s theory of experience as involving three stages: the sense stage that involves sensing, the imagination stage that involves perceiving, and the understanding stage that involves judging. Part of the chapter is devoted to an analysis of the imagination stage and Kant’s claim that imagination is a ‘necessary ingredient of perception’, and the other part to a discussion of how the imagination stage relates to the sense and understanding stages. It makes the case that, on Kant’s view, whereas the sensing involved in the sense stage does not depend on concepts, the perceiving at issue in the imagination stage does. However, the chapter also proposes that the role that concepts play in perception differs from the role that they play in the judging required for the understanding stage of experience.
Between the Lines
Authors: Bennett Michael Y
Published: March 2024

To investigate theatre and its in-between spaces, Between the Lines: A Philosophy of Theatre introduces some basic ideas about coherence and correspondence and, much more prominently, conversations surrounding subsumption and distinctness to better describe theatre as an art form. Instead of limiting the concept and use of subsumption to suggest that constituent parts are subsumed within a distinct whole (as is done in philosophical semantics, from where subsumption comes), in this book, the concept is broadened to claim that many of the properties of a theatrical character and/or a theatrical world are subsumed within the text. Unlike how fiction has a narrator that generally describes the properties of literary characters, theatre (particularly for the theatregoer) is largely devoid of distinct properties attributed to theatrical characters. Outside of the fact that character x says “_______” and does _______, with its corresponding properties being, character x has the properties of being-the-speaker-of-“_______” and being-the-doer-of-_______, there are little-to-no specified properties regarding theatrical characters and/or theatrical worlds. In thinking about the conceptual empty spaces of theatre, this book investigates three main topics: (1) theatre as an art form, (2) the properties of theatrical characters and theatrical worlds (i.e., distinct properties, subsumed properties, and truthful properties), and (3) the difference between truth and truthfulness in the theatre. Ultimately, this book aims to offer the first (contemporary) systematic account of theatre—thinking about theatre metaphysically, epistemologically, and ethically (the last, only in terms of value).
Gas Exchange Rates and Sucrose Concentrations Affect Development in Microstumps of Eucalyptus urophylla Grown In Vitro
Authors: Miranda Natane A , Xavier Aloisio , de Moura Luciana C , Otoni Wagner C
Published: March 2024

Micropropagation enables the efficient clonal propagation of plants, bringing advantages to the Eucalyptus plantlet process. Herein, the influence of gas exchange rates and sucrose concentrations on the development of microstumps of a Eucalyptus urophylla S. T. Blake clone for microcutting production was evaluated. The microstumps were cultured under three gas exchange systems using caps with membrane, caps without membrane or a combination of the above, and also supplemented with 0, 7, 15 and 30 g L-1 sucrose. Gas exchange and sucrose supplementation affected the development of microstumps in vitro and the survival of microcuttings ex vitro. Lower sucrose concentrations were necessary under higher gas exchange rate conditions to improve the development and production of microstumps. Higher survival rates of ex vitro microcuttings were also observed under higher gas exchange rate. Sucrose is important in the initial plant development, but it can be reduced after the culture is established, depending on the gas exchange rate used. Thus, our findings show that reducing sucrose and increasing the gas exchange rates are efficient strategies for establishing microstumps of the Eucalyptus urophylla clone maintained under an in vitro condition.

Study Implications: Photoautotrophic micropropagation can promote significant growth of Eucalyptus, and in this system, environmental factors need to be adequately controlled. This study has revealed efficient combinations of sucrose concentrations and gas exchange systems that promote greater in vitro production and greater ex vitro survival of microcuttings. Plants grown under higher gas exchange conditions show better acclimatization with higher survival rate during the ex vitro stage and require lower sucrose concentration during in vitro cultivation. This approach is useful in enhancing micropropagation techniques and indicates its potential application for scaling up large culture vessels to aseptic culture rooms for closed microcutting production systems.
Piloting a Community-Based, Culturally Adapted Health Promotion Program for Children with Autism Spectrum Disorder and Developmental Disabilities in First-Generation Korean Immigrant Families
Authors: Son Esther , Alford Sabretta
Published: March 2024

Children with autism spectrum disorder and developmental disabilities (ASD/DD) face barriers to participation in health promotion programs due to the lack of available and/or affordable programs and trained staff at recreation centers. Children with ASD/DD in Korean immigrant families are one of the most underserved minority groups due to language, racial/ethnic discrimination, and stigma and shame within their own ethnic community. However, little research is available on development, implementation, and evaluation of a culturally adapted community health promotion program in this population. The purpose of this study is to assess effectiveness of a pilot program for children with ASD/DD from first-generation Korean immigrant families. The pilot study used a quantitative, quasiexperimental design (one-group design with pre- and posttest) following a seven-week health promotion program. We recruited 15 children with ASD/DD, ages nine through 16, from first-generation Korean immigrant families. The findings of the study suggest that the pilot program was effective in gaining nutrition knowledge and increasing physical involvement among participants. Given the fact that Asian immigrants are a fast-growing population and that nearly 75 percent of them were born abroad, development and evaluation of a community-based, culturally adapted health promotion program is urgently needed.
Pushed to Breaking Point? The Prohibition of ‘Constructive’ or ‘Disguised’ Refoulement under International Law
Authors: Rodenhäuser Tilman
Published: March 2024

The cornerstone of international refugee law is the principle of non-refoulement, which protects refugees, asylum seekers, and other persons with protection needs from being returned against their will to a place where they risk facing persecution or other fundamental rights violations. A person who is protected against refoulement may, however, return voluntarily. Determining when such returns are truly voluntary is an issue increasingly at the heart of discussions about the lawfulness of returns, including recently in the Lake Chad Basin, East Africa, the Middle East, Southeast Asia, Europe, and Australia.

Today, there does not appear to be a generally agreed legal standard to determine when a return is truly voluntary. Likewise, international law does not define a clear line at which State action to ‘incentivize’ or ‘induce’ returns amounts to refoulement or an unlawful expulsion. However, recent publications by international law expert bodies and ensuing debate among States have provided some indications as to where international law stands on the issue and the direction in which it might develop. Thus, this article first examines the interplay between voluntary returns and the principle of non-refoulement. Secondly, it analyses recent positions taken by the International Law Commission and the United Nations Committee against Torture concerning legal limits on the measures that States may take to incentivize or induce returns. Thirdly, the article considers certain measures taken by States to incentivize or induce the ‘voluntary’ return of a person and indicates when such measures may amount to acts of coercion or force in violation of international law.
The impact of elective surgery postponement during COVID-19 on emergency bellwether procedures in a large tertiary centre in Singapore
Authors: Chan Sze Ling , Zhang Alwin Yaoxian , Lam Sean Shao Wei , Rao Vijaya , Kanagalingam Devendra , Tan Hiang Khoon , Chow Pierce Kah Hoe , Mathur Sachin
Published: March 2024

The coronavirus disease 2019 (COVID-19) pandemic drove many healthcare systems worldwide to postpone elective surgery to increase healthcare capacity, manpower, and reduce infection risk to staff. The aim of this study was to assess the impact of an elective surgery postponement policy in response to the COVID-19 pandemic on surgical volumes and patient outcomes for three emergency bellwether procedures. A retrospective cohort study of patients who underwent any of the three emergency procedures [Caesarean section (CS), emergency laparotomy (EL), and open fracture (OF) fixation] between 1 January 2018 and 31 December 2021 was conducted using clinical and surgical data from electronic medical records. The volumes and outcomes of each surgery were compared across four time periods: pre-COVID (January 2018–January 2020), elective postponement (February–May 2020), recovery (June–November 2020), and postrecovery (December 2020–December 2021) using Kruskal–Wallis test and segmented negative binomial regression. There was a total of 3886, 1396, and 299 EL, CS, and OF, respectively. There was no change in weekly volumes of CS and OF fixations across the four time periods. However, the volume of EL increased by 47% [95% confidence interval: 26–71%, P = 9.13 × 10–7) and 52% (95% confidence interval: 25–85%, P = 3.80 × 10–5) in the recovery and postrecovery period, respectively. Outcomes did not worsen throughout the four time periods for all three procedures and some actually improved for EL from elective postponement onwards. Elective surgery postponement in the early COVID-19 pandemic did not affect volumes of emergency CS and OF fixations but led to an increase in volume for EL after the postponement without any worsening of outcomes.
Investigating eco-evolutionary processes of microbial community assembly in the wild using a model leaf litter system
Authors: Barbour Kristin M , Martiny Jennifer B H
Published: March 2024

Microbial communities are not the easiest to manipulate experimentally in natural ecosystems. However, leaf litter—topmost layer of surface soil—is uniquely suitable to investigate the complexities of community assembly. Here, we reflect on over a decade of collaborative work to address this topic using leaf litter as a model system in Southern California ecosystems. By leveraging a number of methodological advantages of the system, we have worked to demonstrate how four processes—selection, dispersal, drift, and diversification—contribute to bacterial and fungal community assembly and ultimately impact community functioning. Although many dimensions remain to be investigated, our initial results demonstrate that both ecological and evolutionary processes occur simultaneously to influence microbial community assembly. We propose that the development of additional and experimentally tractable microbial systems will be enormously valuable to test the role of eco-evolutionary processes in natural settings and their implications in the face of rapid global change.
Exploring the biocontrol potential of rocket (Eruca sativa) extracts and associated microorganisms against Verticillium wilt
Authors: Poulaki Eirini G , Karamichali Ioanna , Lianos Orestis , Alexopoulos Vasilis , Dimitrakas Vasilis , Amourgis Grigorios G , Tjamos Sotirios E
Published: March 2024

Aims

This study aimed to assess the impact of rocket (Eruca sativa) extract on Verticillium wilt in eggplants, explore rhizospheric microorganisms for disease biocontrol, and evaluate selected strains' induced systemic resistance (ISR) potential while characterizing their genomic and biosynthetic profiles.

Methods and results

Rocket extract application led to a significant reduction in Verticillium wilt symptoms in eggplants compared to controls. Isolated microorganisms from treated soil, including Paraburkholderia oxyphila EP1, Pseudomonas citronellolis EP2, Paraburkholderia eburnea EP3, and P. oxyphila EP4 and EP5, displayed efficacy against Verticillium dahliae, decreasing disease severity and incidence in planta. Notably, strains EP3 and EP4 triggered ISR in eggplants against V. dahliae. Genomic analysis unveiled shared biosynthetic gene clusters, such as ranthipeptide and non-ribosomal peptide synthetase-metallophore types, among the isolated strains. Additionally, metabolomic profiling of EP2 revealed the production of metabolites associated with amino acid metabolism, putative antibiotics, and phytohormones.

Conclusions

The application of rocket extract resulted in a significant reduction in Verticillium wilt symptoms in eggplants, while the isolated microorganisms displayed efficacy against V. dahliae, inducing systemic resistance and revealing shared biosynthetic gene clusters, with metabolomic profiling highlighting potential disease-suppressing metabolites.
Rethinking the Legacy of a Medieval Hindu Commentator
Authors: Smith Jason W
Published: March 2024

Parimēlaḻakar was a commentator and scholar who lived around the late thirteenth century CE and wrote commentaries on two major works of Tamil literature: the Paripāṭal and Tirukkuṟaḷ. While Parimēlaḻakar has been regarded as both a hero and a villain in Tamil literary history, this article argues that he is neither hero nor villain, but a capacious thinker who sought to harmonise the Sanskrit and Tamil literary traditions. First, the article shows that Parimēlaḻakar’s Tirukkuṟaḷ commentary is a natural outgrowth of and response to the broad intellectual currents of his time, in which Tamil literary culture was deeply informed by Sanskrit. Second, the article examines Parimēlaḻakar alongside Paripperumāḷ, another Tirukkuṟaḷ commentator, to highlight the range of choices made by commentators in bridging the worlds of Sanskrit and Tamil during the first half of the second millennium. Ultimately, the article advocates on behalf of a more nuanced portrait of Parimēlaḻakar’s legacy.
Typing supernova remnant G352.7−0.1 using XMM–Newton X-ray observations
Authors: Dang Ling-Xiao , Zhou Ping , Sun Lei , Mao Junjie , Vink Jacco , Zhang Qian-Qian , Domček Vladimír
Published: March 2024

G352.7−0.1 is a mixed-morphology (MM) supernova remnant (SNR) with multiple radio arcs and has a disputed supernova origin. We conducted a spatially resolved spectroscopic study of the remnant with XMM–Newton X-ray data to investigate its explosion mechanism and explain its morphology. The global X-ray spectra of the SNR can be adequately reproduced using a metal-rich thermal plasma model with a temperature of ∼2 keV and ionization time-scale of ∼3 × 1010 cm−3 s. Through a comparison with various supernova nucleosynthesis models, we found that observed metal properties from Mg to Fe can be better described using core-collapse supernova models, while thermonuclear models fail to explain the observed high Mg/Si ratio. The best-fit supernova model suggests a ∼13 M⊙ progenitor star, consistent with previous estimates using the wind bubble size. We also discussed the possible mechanisms that may lead to SNR G352.7−0.1 being an MMSNR. By dividing the SNR into several regions, we found that the temperature and abundance do not significantly vary with regions, except for a decreased temperature and abundance in a region interacting with molecular clouds. The brightest X-ray emission of the SNR spatially matches with the inner radio structure, suggesting that the centrally filled X-ray morphology results from a projection effect.
scalepopgen: Bioinformatic Workflow Resources Implemented in Nextflow for Comprehensive Population Genomic Analyses
Authors: Upadhyay Maulik , Pogorevc Neža , Medugorac Ivica
Published: March 2024

Population genomic analyses such as inference of population structure and identifying signatures of selection usually involve the application of a plethora of tools. The installation of tools and their dependencies, data transformation, or series of data preprocessing in a particular order sometimes makes the analyses challenging. While the usage of container-based technologies has significantly resolved the problems associated with the installation of tools and their dependencies, population genomic analyses requiring multistep pipelines or complex data transformation can greatly be facilitated by the application of workflow management systems such as Nextflow and Snakemake. Here, we present scalepopgen, a collection of fully automated workflows that can carry out widely used population genomic analyses on the biallelic single nucleotide polymorphism data stored in either variant calling format files or the plink-generated binary files. scalepopgen is developed in Nextflow and can be run locally or on high-performance computing systems using either Conda, Singularity, or Docker. The automated workflow includes procedures such as (i) filtering of individuals and genotypes; (ii) principal component analysis, admixture with identifying optimal K-values; (iii) running TreeMix analysis with or without bootstrapping and migration edges, followed by identification of an optimal number of migration edges; (iv) implementing single-population and pair-wise population comparison-based procedures to identify genomic signatures of selection. The pipeline uses various open-source tools; additionally, several Python and R scripts are also provided to collect and visualize the results. The tool is freely available at https://github.com/Popgen48/scalepopgen.
Ancient Mitogenomes Reveal the Maternal Genetic History of East Asian Dogs
Authors: Zhang Ming , Song Yanbo , Wang Caihui , Sun Guoping , Zhuang Lina , Guo Mingjian , Ren Lele , Wangdue Shargan , Dong Guanghui , Dai Qingyan , Cao Peng , Yang Ruowei , Liu Feng , Feng Xiaotian , Bennett E Andrew , Zhang Xiaoling , Chen Xi , Wang Fen , Luan Fengshi , Dong Wenbin , Lu Guoquan , Hao Daohua , Hou Hongwei , Wang Hui , Qiao Hong , Wang Zhongxin , Hu Xiaojun , He Wei , Xi Lin , Wang Weilin , Shao Jing , Sun Zhouyong , Yue Lianjian , Ding Yan , Tashi Norbu , Tsho Yang , Tong Yan , Yang Yangheshan , Zhu Shilun , Miao Bo , Wang Wenjun , Zhang Lizhao , Hu Songmei , Ni Xijun , Fu Qiaomei
Published: March 2024

Recent studies have suggested that dogs were domesticated during the Last Glacial Maximum (LGM) in Siberia, which contrasts with previous proposed domestication centers (e.g. Europe, the Middle East, and East Asia). Ancient DNA provides a powerful resource for the study of mammalian evolution and has been widely used to understand the genetic history of domestic animals. To understand the maternal genetic history of East Asian dogs, we have made a complete mitogenome dataset of 120 East Asian canids from 38 archaeological sites, including 102 newly sequenced from 12.9 to 1 ka BP (1,000 years before present). The majority (112/119, 94.12%) belonged to haplogroup A, and half of these (55/112, 49.11%) belonged to sub-haplogroup A1b. Most existing mitochondrial haplogroups were present in ancient East Asian dogs. However, mitochondrial lineages in ancient northern dogs (northeastern Eurasia and northern East Asia) were deeper and older than those in southern East Asian dogs. Results suggests that East Asian dogs originated from northeastern Eurasian populations after the LGM, dispersing in two possible directions after domestication. Western Eurasian (Europe and the Middle East) dog maternal ancestries genetically influenced East Asian dogs from approximately 4 ka BP, dramatically increasing after 3 ka BP, and afterwards largely replaced most primary maternal lineages in northern East Asia. Additionally, at least three major mitogenome sub-haplogroups of haplogroup A (A1a, A1b, and A3) reveal at least two major dispersal waves onto the Qinghai-Tibet Plateau in ancient times, indicating eastern (A1b and A3) and western (A1a) Eurasian origins.
ESI–MS analysis of Cu(I) binding to apo and Zn7 human metallothionein 1A, 2, and 3 identifies the formation of a similar series of metallated species with no individual isoform optimization for Cu(I)
Authors: Melenbacher Adyn , Stillman Martin J
Published: March 2024

Metallothioneins (MTs) are cysteine-rich proteins involved in metal homeostasis, heavy metal detoxification, and protection against oxidative stress. Whether the four mammalian MT isoforms exhibit different metal binding properties is not clear. In this paper, the Cu(I) binding properties of the apo MT1A, apo MT2, and apo MT3 are compared and the relative Cu(I) binding affinities are reported. In all three isoforms, Cu4, Cu6, and Cu10 species form cooperatively, and MT1A and MT2 also form a Cu13 species. The Cu(I) binding properties of Zn7-MT1A, Zn7-MT2, and Zn7-MT3 are compared systematically using isotopically pure 63Cu(I) and 68Zn(II). The species formed in each MT isoform were detected through electrospray ionization–mass spectrometry and further characterized using room temperature phosphorescence spectroscopy. The mixed metal Cu, Zn species forming in MT1A, MT2, and MT3 have similar stoichiometries and their emission spectral properties indicate that analogous clusters form in the three isoforms. Three parallel metallation pathways have been proposed through analysis of the detailed Cu, Zn speciation in MT1A, MT2, and MT3. Pathway ① results in Cu5Zn5-MT and Cu9Zn3-MT. Pathway ② involves Cu6Zn4-MT and Cu10Zn2-MT. Pathway ③ includes Cu8Zn4-MT. Speciation analysis indicates that Pathway ② is the preferred pathway for MT2. This is also evident in the phosphorescence spectra with the 750 nm emission from Cu6Zn4-MT being most prominent in MT2. We see no evidence for different MT isoforms being optimized or exhibiting preferences for certain metals. We discuss the probable stoichiometry for MTs in vivo based on the in vitro determined binding constants.
ARF4-mediated retrograde trafficking as a driver of chemoresistance in glioblastoma
Authors: Budhiraja Shreya , McManus Graysen , Baisiwala Shivani , Perrault Ella N , Cho Sia , Saathoff Miranda , Chen Li , Park Cheol H , Kazi Hasaan A , Dmello Crismita , Lin Peiyu , James C David , Sonabend Adam M , Heiland Dieter H , Ahmed Atique U
Published: March 2024

Background

Cellular functions hinge on the meticulous orchestration of protein transport, both spatially and temporally. Central to this process is retrograde trafficking, responsible for targeting proteins to the nucleus. Despite its link to many diseases, the implications of retrograde trafficking in glioblastoma (GBM) are still unclear.

Methods

To identify genetic drivers of TMZ resistance, we conducted comprehensive CRISPR-knockout screening, revealing ADP-ribosylation factor 4 (ARF4), a regulator of retrograde trafficking, as a major contributor.

Results

Suppressing ARF4 significantly enhanced TMZ sensitivity in GBM patient-derived xenograft (PDX) models, leading to improved survival rates (P < .01) in both primary and recurrent lines. We also observed that TMZ exposure stimulates ARF4-mediated retrograde trafficking. Proteomics analysis of GBM cells with varying levels of ARF4 unveiled the influence of this pathway on EGFR signaling, with increased nuclear trafficking of EGFR observed in cells with ARF4 overexpression and TMZ treatment. Additionally, spatially resolved RNA-sequencing of GBM patient tissues revealed substantial correlations between ARF4 and crucial nuclear EGFR (nEGFR) downstream targets, such as MYC, STAT1, and DNA-PK. Decreased activity of DNA-PK, a DNA repair protein downstream of nEGFR signaling that contributes to TMZ resistance, was observed in cells with suppressed ARF4 levels. Notably, treatment with DNA-PK inhibitor, KU-57788, in mice with a recurrent PDX line resulted in prolonged survival (P < .01), highlighting the promising therapeutic implications of targeting proteins reliant on ARF4-mediated retrograde trafficking.

Conclusions

Our findings demonstrate that ARF4-mediated retrograde trafficking contributes to the development of TMZ resistance, cementing this pathway as a viable strategy to overcome chemoresistance in GBM.
John Milton
Authors: Woods Susanne
Published: March 2024

John Milton (b. 1608–d. 1674) was a poet active in the republican and Reformation pamphleteering that led into the English Civil Wars and the mid-17th-century Commonwealth government. Completely blind by 1652, he continued to serve the Cromwell government as Latin Secretary, an office that made him his government’s chief propagandist to the European intellectual community. His political and religious views were highly controversial in his own time, even more after the Restoration of the Stuart monarchy (1660), but for nearly three hundred years after his death they were mostly deemphasized as his countrymen sought to celebrate the brilliance of his poetry, especially his epic Paradise Lost (1667, revised 1674). He is usually situated among the three greatest writers of middle and early modern English (along with Chaucer and Shakespeare), and despite some periods in which some or all of his work faced critical hostility, he has sustained the admiration of readers and writers into the present time. While it is impossible to be inclusive, this bibliography seeks to represent some of the best and most useful work on Milton, focusing primarily on the criticism of the current and last few generations. Included are all of the books from 2000 until the time of this publication that have won the Milton Society of America’s highest prize, the James Holly Hanford Award, and this is noted in the annotations; a number of earlier works that have sustained importance are also noted by their Hanford Awards. Also included are a few classic works, from the seventeenth through the mid-twentieth century, that provided the foundation for later work.
Founding Myths of the Americas
Authors: Buchenau Barbara
Published: March 2024

Myths constitute community, offering a sense of belonging, shared values and comparable stories of origins. Myths suggest universal validity, but they delegitimize those who are dehumanized in the process of certain commemorative actions. This dialectic thrives in the Americas: histories of migration and democratization are always also histories of slavery and settler colonialism. These conjunctions strengthen myth’s ability to serve as both social glue and exclusionary mechanism. Critical interventions seeking to demystify the foundational functions of myths often lead to revitalization rather than abolishment. Recent studies on United States history and society emphasize the coloniality of founding myths. In regional studies, across the Americas and in inter-American studies, however, there is a stronger focus on the positive effects of myths on social, political, and even economic cohesion. Founding myths represent collective values, allowing some groups of people to reinvent their sense of world and self, while forcing others into submission or opposition. Since it is in settings of uncertainty that myths stabilize a sense of self and world, the Americas, with their reiterative histories of migration, enslavement, dispossession, revolution, upheaval, liberation and national(ist) consolidation, offered ideal seedbeds for foundational mythmaking. Minding the ethical flexibility and normative impact of myths is a scholarly challenge. North American myths about heroic new men (much less women) in an empty land reinventing a new and a better humanity promised liberation to some at the cost of subjugating others. This bibliographical essay will show how settler-colonial histories of conquest, deracination, bondage, and nation-building pitted myths of individual liberation against myths of communal freedom. The most influential myth alive across the Americas holds that there is an endless possibility to reinvent oneself and the world. The second, quite embattled, myth concerns the epic life on frontiers: Is it a democratizing human experience, or does it dehumanize its most important agents? The mythopoetic fight over memories of enslavement and dispossession is the third, highly contested component of founding myths in the Americas. For Black and Indigenous people, journeys to freedom reveal the bitter ironies of seeking and granting liberation. Settler colonists and immigrants, however, unironically described their own experiences in the language of an abolition of dependency, mostly ignoring connections to slavery. These three distinctive myths of reinvention, border-crossing, and emancipation merge in an inter-American landscape of creolization and transculturation. Here, becoming a new person after experiencing a violent world in constant motion looks like a daily routine. Funded by the Deutsche Forschungsgemeinschaft (DFG - German Research Council), Project number 411017845, and the Thyssen Foundation, project number Az.20.22.0.026TL.
Archaeology and Class
Authors: Wurst LouAnn
Published: March 2024

The sources for this bibliography on archaeology and class would seem to be relatively few, since the term class seldom appears in archaeological literature. Class is more commonly encountered in other disciplines, such as sociology (see the Oxford Bibliographies in Sociology article “Class”), geography (see the Oxford Bibliographies in Geography article “Geography and Class”), political science (see the Oxford Bibliographies in Political Science article “Class in American Politics”), or history (see the Oxford Bibliographies in Atlantic History article “Class and Social Structure”). The subject of class is fraught with confusion and contradiction. Some see open discussion of class as impolite or rude and ignore or deny its importance. Others suggest that class may have been important in the past but is not any longer. Given the transformations in labor and loss of the manufacturing sector that gave class its basis, class is deemed irrelevant for understanding individual identity in the contemporary neoliberal world. On the other hand, some scholars argue that class is the most important concept for understanding human social relations past and present and has seldom been seriously confronted. These contradictory ideas stem from real theoretical differences that entail different definitions of class. Class is explicitly discussed mostly by Marxian scholars who have always used class to center their research, and by historical archaeologists who study the modern capitalist world where class is hard to ignore. Marxism is thought to have lost relevance with the collapse of the Soviet Union and fall of Berlin Wall, and the concept of class was discredited along with these events. The association of class with Marxism also means that the term has often been substituted with less dangerous ones or masked by others such as hierarchy, stratification, rank, inequality, or power. Regardless of the theoretical framing, the notion of class entails ideas of social group difference: in work or labor, wealth or property, status or prestige, control over surplus production, or power and authority. Because of these differences, class relations are inherently antagonistic and contradictory, and aspects of violence and class struggle are important to the idea of class.
Lu Xun
Authors: Cheng Eileen J.
Published: March 2024

Lu Xun (Zhou Shuren, b. 1881–d. 1936), the “father of modern Chinese literature” and “soul of the nation,” left his mark on 20th-century literature, culture, and politics. Well-known for his collections of short stories, Outcry (1923) and Hesitation (1926), he was also an accomplished scholar, cultural critic, poet, and a pioneer of literary forms. A book collector, translator, and editor, he avidly promoted the works of other artists and writers. Hailed as a leader of the New Culture Movement, he is often regarded as a radical iconoclast. Lu Xun’s relationship to both tradition and modernity, however, was ambivalent. A supporter of the New Culture reforms, he was also skeptical of new literary trends. Critical of tradition, he nonetheless harbored a lifelong affinity for classical Chinese literature, published scholarly works on the subject, and wrote classical-style poetry until the end of his life. Ever the skeptic, Lu Xun described himself as an “in-between”—zhongjian wu中間物—an intermediary who refused to identify with either the traditional or modern camp. He was relentlessly critical of others as he was of himself. His writings exposed a “crisis of representation” by questioning intellectuals’ ability to truly represent their subjects. Despite his skepticism, Lu Xun was driven by a radical hope: he wrote to expose the illnesses of society in the hope of finding remedies for them. His radically innovative style, and often complex and sometimes abstruse creative writings, were a product of his critical engagement with a large corpus of texts and ideas—classical and modern, domestic and foreign. Besides his short story collections, his creative works include prose poems in Wild Grass (1926), an experimental memoir Morning Blossoms Gathered at Dusk (1928), and a collection of rewrites of old fables, Old Tales Retold (1928). Beginning in 1926, Lu Xun immersed himself in Marxist theories. He became the titular leader of the League of Left-Wing Writers in 1930 and began promoting—though never writing—proletarian literature. Instead, he turned primarily to the form of polemical essay (zawen) in the last decade of his life, writing wry and penetrating critical social commentaries which he referred to as his “daggers and spears.” In his later years, he often lent his name to promoting the works of young writers and artists. Especially drawn to woodcut art—a form he felt was conducive to promoting the proletarian cause—Lu Xun became an active force behind the woodcut movement in the 1930s. The bibliography focuses primarily on English-language studies with some Chinese sources.
The Mismeasure of Music “On Computerized Music Listening and Analysis via Machine Learning”
Authors: Sturm Bob L. T. , Wiggins Geraint A.
Published: March 2024

The worthwhile application of computers to study music audio recording collections requires such systems to be engineered to have the appropriate sensitivities and knowledge. One approach to designing such systems is the use of machine learning with music recording datasets. We address two widely held assumptions in the engineering of such systems: 1) if a system reproduces all labels of a music recording dataset then it must have learned about music; and 2) if a system is being trained on a music recording dataset then it is being trained on music. In this chapter, we show that these assumptions are not true, and that machine learning with music recording datasets can result in music listening systems that may not be as successful as they appear. We propose several principles to guide the engineering of computerized music listening and analysis via machine learning.
The space of closed G2-structures. I. Connections
Authors: Xu Pengfei , Zheng Kai
Published: March 2024

In this article, we develop foundational theory for geometries of the space of closed G2-structures in a given cohomology class as an infinite-dimensional manifold. We construct Levi-Civita connections for Sobolev-type metrics, formulate geodesic equations and analyze the variational structures of torsion-free G2-structures under these Sobolev-type metrics.
Access to justice and multinational corporations: promoting privately driven transnational hybrid adjudication
Authors: Gulati Rishi
Published: March 2024

This chapter focuses on the delivery of justice to victims of corporate conduct through privately driven transnational hybrid dispute resolution mechanisms. The advent of such mechanisms is now evident through the creation of Meta’s Oversight Board (‘OSB’). How to incorporate such privately driven justice mechanisms in more conventional forms of legal ordering is an important question constituting the central inquiry of this reflection. Via the example of the OSB, this chapter highlights how some content moderation disputes between Meta, one of the most powerful technology companies today, and its users is being resolved using innovative private adjudicative mechanisms. It is then argued that forums like the OSB should be deferred to. But only if the quality of justice provided is consistent with international standards. Where those standards are met, the broad circulation of decisions made by privately driven adjudicative mechanisms should be promoted. This requires proactive, outcome driven, and coordinated international institutional action.
Artificial Intelligence in corporate governance: a few inquiries on the (non-)compliance of directors’ duties from a Portuguese law perspective
Authors: de Lima Igor Silva
Published: March 2024

It is widely accepted that directors’ duties encompass the duty to prepare and analyse information concerning the company’s business and affairs and market conditions and the duty to monitor and oversee the company’s actual and prospective economic and financial outlook. While exercising the so-called business judgment rule, directors shall question themselves as to whether the information reasonably available at the time a decision is to be made provides sufficient grounds to support it. They also must have in due regard the underlying business rationality of the decision concerned. The issue merits particular attention in the context of companies undergoing economic or financial distress in the vicinity of insolvency. Directors usually resort to assistance from internal staff and external advisors as well as to technological tools for performing managerial activities. There are a number of options of technologies that employ artificial intelligence (AI) and that have shown a high degree of certainty in predicting scenarios of economic or financial distress. However, directors are not exempted from potential accountability for actions taken in breach of their duties by simply employing AI technology. If, how, and to which extent the use of AI in corporate governance will affect the compliance of a director’s duties are questions yet to be addressed.
Analgesia and Sedation Use During Noninvasive Ventilation for Acute Respiratory Failure
Authors: Dunbar Peter J. , Peterson Ryan , McGrath Max , Pomponio Raymond , Kiser Tyree H. , Ho P. Michael , Vandivier R. William , Burnham Ellen L. , Moss Marc , Sottile Peter D. ,   for the Colorado Pulmonary Outcomes Research Group
Published: March 2024

OBJECTIVES:

To describe U.S. practice regarding administration of sedation and analgesia to patients on noninvasive ventilation (NIV) for acute respiratory failure (ARF) and to determine the association of this practice with odds of intubation or death.

DESIGN:

A retrospective multicenter cohort study.

SETTING:

A total of 1017 hospitals contributed data between January 2010 and September 2020 to the Premier Healthcare Database, a nationally representative healthcare database in the United States.

PATIENTS:

Adult (≥ 18 yr) patients admitted to U.S. hospitals requiring NIV for ARF.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We identified 433,357 patients on NIV of whom (26.7% [95% CI] 26.3%–27.0%) received sedation or analgesia. A total of 50,589 patients (11.7%) received opioids only, 40,646 (9.4%) received benzodiazepines only, 20,146 (4.6%) received opioids and benzodiazepines, 1.573 (0.4%) received dexmedetomidine only, and 2,639 (0.6%) received dexmedetomidine in addition to opioid and/or benzodiazepine. Of 433,357 patients receiving NIV, 50,413 (11.6%; 95% CI, 11.5–11.7%) patients underwent invasive mechanical ventilation on hospital days 2–5 or died on hospital days 2–30. Intubation was used in 32,301 patients (7.4%; 95% CI, 7.3–7.6%). Further, death occurred in 24,140 (5.6%; 95% CI, 5.5–5.7%). In multivariable analysis adjusting for relevant covariates, receipt of any medication studied was associated with increased odds of intubation or death. In inverse probability weighting, receipt of any study medication was also associated with increased odds of intubation or death (average treatment effect odds ratio 1.38; 95% CI, 1.35–1.40).

CONCLUSIONS:

The use of sedation and analgesia during NIV is common. Medication exposure was associated with increased odds of intubation or death. Further investigation is needed to confirm this finding and determine whether any subpopulations are especially harmed by this practice.