bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioral plasticity shapes population aging patterns in a long-lived avian scavenger
Authors: Acácio Marta , Gahm Kaija , Anglister Nili , Vaadia Gideon , Hatzofe Ohad , Harel Roi , Efrat Ron , Nathan Ran , Pinter-Wollman Noa , Spiegel Orr
Published: August 2024

Studying the mechanisms shaping age-related changes in behavior (“behavioral aging”) is important for understanding population dynamics in our changing world. Yet, studies that capture within-individual behavioral changes in wild populations of long-lived animals are still scarce. Here, we used a 15-y GPS-tracking dataset of a social obligate scavenger, the griffon vulture (
Gyps fulvus
), to investigate age-related changes in movement and social behaviors, and disentangle the role of behavioral plasticity and selective disappearance in shaping such patterns. We tracked 142 individuals for up to 12 y and found a nonlinear increase in site fidelity with age: a sharp increase in site fidelity before sexual maturity (<5 y old), stabilization during adulthood (6 to 15 y), and a further increase at old age (>15 y). This pattern resulted from individuals changing behavior throughout their life (behavioral plasticity) and not from selective disappearance. Mature vultures increased the predictability of their movement routines and spent more nights at the most popular roosting sites compared to younger individuals. Thus, adults likely have a competitive advantage over younger conspecifics. These changes in site fidelity and movement routines were mirrored in changes to social behavior. Older individuals interacted less with their associates (decreasing average strength with age), particularly during the breeding season. Our results reveal a variety of behavioral aging patterns in long-lived species and underscore the importance of behavioral plasticity in shaping such patterns. Comprehensive longitudinal studies are imperative for understanding how plasticity and selection shape the persistence of wild animal populations facing human-induced environmental changes.
Gcn2 structurally mimics and functionally repurposes the HisRS enzyme for the integrated stress response
Authors: Bou-Nader Charles , Gaikwad Swati , Bahmanjah Soheila , Zhang Fan , Hinnebusch Alan G. , Zhang Jinwei
Published: August 2024

Protein kinase Gcn2 attenuates protein synthesis in response to amino acid starvation while stimulating translation of a transcriptional activator of amino acid biosynthesis. Gcn2 activation requires a domain related to histidyl-tRNA synthetase (HisRS), the enzyme that aminoacylates tRNA
His
. While evidence suggests that deacylated tRNA binds the HisRS domain for kinase activation, ribosomal P-stalk proteins have been implicated as alternative activating ligands on stalled ribosomes. We report crystal structures of the HisRS domain of
Chaetomium thermophilum
Gcn2 that reveal structural mimicry of both catalytic (CD) and anticodon-binding (ABD) domains, which in authentic HisRS bind the acceptor stem and anticodon loop of tRNA
His
. Elements for forming histidyl adenylate and aminoacylation are lacking, suggesting that Gcn2
HisRS
was repurposed for kinase activation, consistent with mutations in the CD that dysregulate yeast Gcn2 function. Substituting conserved ABD residues well positioned to contact the anticodon loop or that form a conserved ABD–CD interface impairs Gcn2 function in starved cells. Mimicry in Gcn2
HisRS
of two highly conserved structural domains for binding both ends of tRNA—each crucial for Gcn2 function—supports that deacylated tRNAs activate Gcn2 and exemplifies how a metabolic enzyme is repurposed to host new local structures and sequences that confer a novel regulatory function.
Design of dual port 9T SRAM cell with parallel processing and high performance computing
Authors: Chopra Yogita , Mittal Poornima
Published: August 2024

To meet industry requirements of higher transistor count SRAM cells this paper is proposing, a nine-transistor configuration static random access memory (SRAM) cell which is accessible by dual bit line and performing simultaneous read and write operations. The suggested 9T (P9T PS) cell is constructed at 32 nm CMOS and is operating at an operating voltage 0.9 V. To justify the refined performance of proposed design various analysis are carried out that shows the static noise margins (SNM) that occurs while executing the read operation is 0.368 V and hold operation by the cell is 0.364 V, while the write operation has an SNM of 0.422 V. The access time for write and read functions of the cell is found to be 1.2 nS and 4.5 nS respectively. The P9T PS SRAM is compared with other dual-port and single-port 9T SRAM cells is stand out to be pre-eminence in performance in terms of noise immunity, temperature variations, power consumption (static and dynamic both), power delay product (PDP), SNM to PDP and area ratio (SAPR) and electric quality matric. Total leakage power for P9T PS cell is found to be 22.1 nW. The P9T PS bit cell is also found to be power efficient as it is consuming minimal power for all of the operations. Area layout of the P9T (PS) is found to be 22.372 μm2. The results are also supported by the process corner variation analysis for four different corners. LT-spice software is used to carry out all the simulations and analysis.
Lie symmetry analysis, exact solutions and conservation laws of (3+1)-dimensional modified Wazwaz-Benjamin-Bona-Mahony equation
Authors: Yadav Sarasvati , Chauhan Vishal
Published: August 2024

In this paper, we study the (3+1)-dimensional modified Wazwaz-Benjamin-Bona-Mahony equation using Lie symmetry analysis. An optimal system is constructed with the help of a commutator table and an adjoint table. Similarity reductions are obtained on the basis of the optimal system, and the governing partial differential equation is transformed into another partial differential equations with a smaller number of independent variables. The solutions of these reduced partial differential equations give invariant solutions of the (3+1)-dimensional modified Wazwaz-Benjamin-Bona-Mahony equation. The 3D graphical plots are used to describe the dynamical characteristics of the solutions. Hence, by employing these graphs, physicists and mathematicians can more efficiently and successfully follow complex physical processes. Finally, self-adjoint is checked, and conservation laws are also deducted corresponding to each infinitesimal generator.
Enhancing GWOPS Capabilities for Coordinated Multi-Telescope Detection of Gravitational Wave Electromagnetic Counterparts
Authors: Ma Penghui , Xu Yunfei , Hu Jingwei , Zhang Zhen , Ge Liang , He Min , Li Shanshan , Mi Linying , Li Changhua , Fan Dongwei , Cui Chenzhou
Published: August 2024

The groundbreaking detection of gravitational waves (GWs) has ushered in a new era of astronomical observation, granting us access to cosmic phenomena that are imperceptible to electromagnetic waves. The inherently weak GW signals coupled with the substantial uncertainties in source localization pose significant challenges to the field of astronomy. In this paper, we introduce innovative strategies to enhance the efficiency of observing electromagnetic counterparts to GW events, thereby unlocking further secrets of the cosmos. We present a novel technique for designing observation targets and establishing priorities, progressing from the epicenter to the periphery within the boundaries of the GW error sky region. This method has significantly reduced the average slewing distance of telescopes by 41% compared to traditional methods, thus enhancing observational efficiency. Additionally, we have developed a collaborative observation strategy for telescope networks, allocating observation targets based on the field-of-view (FOV) sizes of individual telescopes. This ensures comprehensive coverage without redundancy, allowing a network of four telescopes to cover a sky area and accumulate observation probability more than four times that of a single telescope operating independently over an equivalent period. Building upon these strategies, we have significantly upgraded GWOPS, the GW Follow-up Observation Planning System developed by the China-VO team, to provide precise observational planning for large FOV (greater than 1 square degree) telescope networks. The system also features a web-based user interface that presents the GW error sky area and observation planning results in a graphical format, significantly improving user interaction and experience. The research presented herein equips astronomers with a robust toolkit, advancing the efficiency of searching for and studying electromagnetic counterparts to GW events, and heralding new frontiers in the research of astrophysics and cosmology.
Enhancing coherence by local parity-time symmetric operation under the non-Markovian environment
Authors: Leng Yang
Published: August 2024

The dynamic behavior of the relative entropy of coherence for a two-level system is systematically investigated within non-Markovian environment. We derive the exact expressions of relative entropy quantifying coherence for an exactly solving model consisting of single qubit interacting with independent structured reservoir. By employing local non-Hermitian operation, i.e. parity-time (

PT

) symmetric operation, we show that the vanished quantum coherence can be effectively restored under the non-Markovian regimes. Furthermore, the freezing phenomenon of the coherence can be detected by using the optimal

PT

symmetric operation strength within the non-Markovian environments.
Kernel heterogeneity improves sparseness of natural images representations
Authors: Ladret Hugo J , Casanova Christian , Udo Perrinet Laurent
Published: August 2024

Both biological and artificial neural networks inherently balance their performance with their operational cost, which characterizes their computational abilities. Typically, an efficient neuromorphic neural network is one that learns representations that reduce the redundancies and dimensionality of its input. For instance, in the case of sparse coding (SC), sparse representations derived from natural images yield representations that are heterogeneous, both in their sampling of input features and in the variance of those features. Here, we focused on this notion, and sought correlations between natural images’ structure, particularly oriented features, and their corresponding sparse codes. We show that representations of input features scattered across multiple levels of variance substantially improve the sparseness and resilience of sparse codes, at the cost of reconstruction performance. This echoes the structure of the model’s input, allowing to account for the heterogeneously aleatoric structures of natural images. We demonstrate that learning kernel from natural images produces heterogeneity by balancing between approximate and dense representations, which improves all reconstruction metrics. Using a parametrized control of the kernels’ heterogeneity of a convolutional SC algorithm, we show that heterogeneity emphasizes sparseness, while homogeneity improves representation granularity. In a broader context, this encoding strategy can serve as inputs to deep convolutional neural networks. We prove that such variance-encoded sparse image datasets enhance computational efficiency, emphasizing the benefits of kernel heterogeneity to leverage naturalistic and variant input structures and possible applications to improve the throughput of neuromorphic hardware.
The Spirit of the Game
Authors: Putz Paul Emory
Published: August 2024

The Spirit of the Game offers a cultural and intellectual history of the Christian athlete movement in the United States, an effort led by American Protestants over the course of the twentieth century to carve out a home within big-time sports. Bridging scholarship on sport history and religious history, it uses sports as a lens for understanding transformations and overlapping communities in American Protestantism, including mainline, evangelical, Southern Baptist, and Black Protestant institutions and leaders. The book begins in the 1920s and traces the story until the twenty-first century. It focuses especially on the formation and development of three major sports ministries—the Fellowship of Christian Athletes, Athletes in Action, and Pro Athletes Outreach—showing how those organizations established a lasting religious subculture within the sports industry. It also highlights the ways that conflict over issues like race, pluralism, gender, sexuality, theology, and politics honed the identity of the movement. Ultimately, the book argues that the leaders of the Christian athlete movement came to see sports as a form a middlebrow culture, a place for shaping future generations in a way that protected “traditional” American values while also allowing room for gradual change. In so doing, they turned commercialized athletics from what seemed in the 1920s like a potential rival for cultural authority into a means through which Protestants could maintain influence in a supposedly more secular American society.
The Terrific Urge to Win
Authors: Putz Paul Emory
Published: August 2024

This chapter shows how a group of mainline Protestants in the 1920s, with Amos Alonzo Stagg and Branch Rickey at the center, developed a “middlebrow” approach to engagement with sports. Stagg and Rickey contributed to the expansion of the two most popular team sports of the decade while also using their fame to advocate for Protestant causes. In this way, they offered reassurance that Protestant values still had a place within a changing postwar mass consumer society. They developed accommodationist strategies to maintain their faith within sports culture, insisting that even commercialized athletics could promote moral virtue. These strategies were crucial in the development of the cultural sensibilities and theological ideas that would shape the formation of the Christian athlete movement.
To Be an Athlete Is Different
Authors: Putz Paul Emory
Published: August 2024

This chapter analyzes the early growth and development of the Fellowship of Christian Athletes (FCA) as it navigated its place within mainline Protestantism and the sports industry. More than simply building a self-sustaining organization, the launch and development of the FCA initiated a movement. It also forged a new subculture within sports that provided spiritual services and support for athletes and coaches. Yet, debate and conflict over the direction of the FCA led its founder, Don McClanen, to depart from the organization he founded. This set the stage for the Christian athlete movement to develop in line with the desires of its booster-minded sports practitioners more than its mainline Protestant leaders.
Call It Sportianity
Authors: Putz Paul Emory
Published: August 2024

This chapter analyzes the creation and growth of new evangelical sports ministries, including Athletes in Action, Baseball Chapel, and Pro Athletes Outreach, from the 1960s into the 1970s. Through these ministries the Christian athlete movement expanded its reach into professional sports and also linked itself with a growing evangelical consumer culture gaining attention in American life. The new sports ministries clashed at times with the Fellowship of Christian Athletes (FCA), and the FCA also faced its own internal tensions over direction and purpose. These differences, however, could not overpower the ties that bound the Christian athlete movement together. Evangelicals successfully positioned themselves as the primary religious presence in big-time sports by assuming the roles that middlebrow Protestants had previously occupied, focusing on the therapeutic benefits of one’s personal faith, the defense of “traditional” Protestant values, and the promotion of gradual American progress.
Epilogue
Authors: Putz Paul Emory
Published: August 2024

In this epilogue the cultural meanings of Tim Tebow and Colin Kaepernick are examined in light of their place within the Christian athlete movement. By the 2000s, the Christian athlete movement was firmly established within big-time sports, and Tebow’s rise to prominence was an example of its influence and power. Tebow also represented the movement’s shift from its middlebrow mainline origins to Southern evangelical forms of Protestantism. Kaepernick, on the other hand, highlighted the growing racial diversity within big-time sports and the different understandings of American history held by Black Christian athletes and the white-led evangelical sports subculture. The rise of the Black Lives Matter movement, the election of Donald Trump, and the intensification of debates over race, religion, and American identity will continue to shape the Christian athlete movement as it navigates a future within both evangelicalism and sports.
Confession, Protest, and Apocalypse
Authors: Howarth Peter B
Published: August 2024

Ruth Witt-Diamant’s San Francisco Poetry Center fostered two often-opposed forms of the 1960s reading, the confessional and the anti-war protest, both suffused with a sense of imminent apocalypse. Allen Ginsberg first performed ‘Howl’ as naked self-revelation, but in performances at the Center it became a means to shame his audience for listening to him—a manoeuvre of reverse humiliation adopted from Robert Duncan’s Faust Foutu. Hearing Ginsberg while preparing his own reading at the Poetry Center in 1957, Robert Lowell recognized in the sharing of shame a new possibility for his readings, and the theatre of discomfort called ‘confessional poetry’ was born. But while Duncan and Denise Levertov scorned the emotiveness of confessional, they shared its apocalyptic sense of imminent judgement. Like Ginsberg’s early mentor Kenneth Rexroth, an advisor to the Poetry Center, Levertov could not resist using confessional’s shame-transferring techniques to expose the workings of the American war machine at every level, including herself reading.
The Golden Torah
Authors: Zavadivker Polly
Published: August 2024

When sacred objects and spaces fell victim to collateral damage and military atrocities, the Jewish Historical-Ethnographic Society in Petrograd waged a brief but dynamic campaign in 1916 to evacuate Jewish material heritage from front zones. Its organizers visited twenty-five shtetls near the front in provinces now part of Belarus and Ukraine. They rescued nearly 500 Torah scrolls and hundreds of manuscripts, community record books, ritual items, and other sacred objects. Despite these successes, the rescue campaign revealed and sharpened divisions and conflicts within Jewish society. The largely secular and nationalist “rescuers” treated the material heritage of Judaism as antiquities or folk creations, meant alternately for museum display, inspiration for secular art, and artifacts of national importance. The people and communities who possessed the same objects treated them with reverence and as sacred vessels. The history of the rescue campaign illuminates points of contact and conflict between diverse Jews in Russia during a time of transformative physical and cultural dislocation.
A History without an Ending
Authors: Zavadivker Polly
Published: August 2024

In 1918, Jewish communities in the lands of the former Russian Empire looked very different than they had in 1914. This book has illuminated some of the ramifications of World War I on the economic, social, political, cultural, and religious life East European Jewry. The concluding chapter summarizes some of the multiple changes and transformations in Jewish life wrought by the violence, revolution, and forced migration that occurred during the war. They include: the expansion of modern Jewish national schools, the entry of women into state and public service, the growth of a Yiddish civil society and Jewish populations outside the Pale in cities of the Russian interior, and the indefinite exile of Jews from their homelands as borders consolidated around new Soviet republics and East European nation-states whose political geographies shaped Jewish life during the interwar years, World War II, and the Holocaust.
Visual field loss and falls requiring hospitalisation: results from the eFOVID study
Authors: Manners Siobhan , Meuleners Lynn B , Ng Jonathon Q , Wood Joanne M , Morgan Bill , Morlet Nigel
Published: August 2024

Background

Visual fields are important for postural stability and ability to manoeuvre around objects.

Objective

Examine the association between visual field loss and falls requiring hospitalisation in adults aged 50 +.

Methods

Older adults aged 50+ with and without visual field loss were identified using a fields database obtained from a cross-section of ophthalmologists’ practices in Western Australia (WA). Data were linked to the Hospital Morbidity Data Collection and WA Hospital Mortality System to identify participants who experienced falls-related hospitalisations between 1990 and 2019. A generalised linear negative binomial regression model examined the association between falls requiring hospitalisation for those with and without field loss, based on the better eye mean deviation (mild: −2 to –6 dB, moderate: −6.01 dB to –12 dB, severe < −12.01 dB) in the most contemporaneous visual field test (3 years prior or if not available, 2 years after the fall), after adjusting for potential confounders.

Results

A total of 31 021 unique individuals of whom 6054 (19.5%) experienced 11 818 falls requiring hospitalisation during a median observation time of 14.1 years. Only mean deviation index of <−12.01 dB (severe) was significantly associated with an increased rate of falls requiring hospitalisations by 14% (adjusted IRR 1.14, 95% CI 1.0–1.25) compared with no field loss, after adjusting for potential confounders. Other factors included age, with those aged 80+ having an increased rate (IRR 29.16, 95% CI 21.39–39.84), other comorbid conditions (IRR 1.49, 95% CI 1.38–1.60) and diabetes (IRR 1.25, 95% CI 1.14–1.37). Previous cataract surgery was associated with a decreased rate of falls that required hospitalisations by 13% (IRR 0.87, 95% CI 0.81–0.95) compared with those who did not have cataract surgery.

Conclusion

The findings highlight the importance of continuous clinical monitoring of visual field loss and injury prevention strategies for older adults with visual field loss.
Outdoor artificial light-at-night and cardiometabolic disease risk: an urban perspective from the Catalan GCAT cohort study
Authors: Palomar-Cros Anna , Espinosa Ana , Bará Salva , Sánchez Alejandro , Valentín Antonia , Cirach Marta , Castaño-Vinyals Gemma , Papantoniou Kyriaki , Blay Natàlia , de Cid Rafael , Romaguera Dora , Kogevinas Manolis , Harding Barbara N
Published: August 2024

We investigated the association between outdoor artificial light-at-night (ALAN) exposure and cardiometabolic risk in the GCAT study. We included 9752 participants from Barcelona (59% women) and used satellite images (30 m resolution) and estimated photopic illuminance and the circadian regulation–relevant melanopic equivalent daylight illuminance (melanopic EDI). We explored the association between ALAN exposure and prevalent obesity, hypertension, and diabetes with logistic regressions and assessed the relationship with incident cardiometabolic diseases ascertained through electronic health records (mean follow-up 6.5 years) with Cox proportional hazards regressions. We observed an association between photopic illuminance and melanopic EDI and prevalent hypertension, odds ratio (OR) = 1.09 (95% CI, 1.01-1.16) and 1.08 (1.01-1.14) per interquartile range increase (0.59 and 0.16 lux, respectively). Both ALAN indicators were linked to incident obesity (hazard ratio [HR] = 1.29, 1.11-1.48 and 1.19, 1.05-1.34) and hemorrhagic stroke (HR = 1.73, 1.00-3.02 and 1.51, 0.99-2.29). Photopic illuminance was associated with incident hypercholesterolemia in all participants (HR = 1.17, 1.05-1.31) and with angina pectoris only in women (HR = 1.55, 1.03-2.33). Further research in this area and increased awareness on the health impacts of light pollution are needed. Results should be interpreted carefully since satellite-based ALAN data do not estimate total individual exposure.

This article is part of a Special Collection on Environmental Epidemiology.
AntiFormer: graph enhanced large language model for binding affinity prediction
Authors: Wang Qing , Feng Yuzhou , Wang Yanfei , Li Bo , Wen Jianguo , Zhou Xiaobo , Song Qianqian
Published: August 2024

Antibodies play a pivotal role in immune defense and serve as key therapeutic agents. The process of affinity maturation, wherein antibodies evolve through somatic mutations to achieve heightened specificity and affinity to target antigens, is crucial for effective immune response. Despite their significance, assessing antibody–antigen binding affinity remains challenging due to limitations in conventional wet lab techniques. To address this, we introduce AntiFormer, a graph-based large language model designed to predict antibody binding affinity. AntiFormer incorporates sequence information into a graph-based framework, allowing for precise prediction of binding affinity. Through extensive evaluations, AntiFormer demonstrates superior performance compared with existing methods, offering accurate predictions with reduced computational time. Application of AntiFormer to severe acute respiratory syndrome coronavirus 2 patient samples reveals antibodies with strong neutralizing capabilities, providing insights for therapeutic development and vaccination strategies. Furthermore, analysis of individual samples following influenza vaccination elucidates differences in antibody response between young and older adults. AntiFormer identifies specific clonotypes with enhanced binding affinity post-vaccination, particularly in young individuals, suggesting age-related variations in immune response dynamics. Moreover, our findings underscore the importance of large clonotype category in driving affinity maturation and immune modulation. Overall, AntiFormer is a promising approach to accelerate antibody-based diagnostics and therapeutics, bridging the gap between traditional methods and complex antibody maturation processes.
Estimating causal effects under non-individualistic treatments due to network entanglement
Authors: Toulis P , Volfovsky A , Airoldi E M
Published: August 2024

In many observational studies, the treatment assignment mechanism is not individualistic, as it allows the probability of treatment of a unit to depend on quantities beyond the unit’s covariates. In such settings, unit treatments may be entangled in complex ways. In this article, we consider a particular instance of this problem where the treatments are entangled by a social network among units. For instance, when studying the effects of peer interaction on a social media platform, the treatment on a unit depends on the change of the interactions network over time. A similar situation is encountered in many economic studies, such as those examining the effects of bilateral trade partnerships on countries’ economic growth. The challenge in these settings is that individual treatments depend on a global network that may change in a way that is endogenous and cannot be manipulated experimentally. In this paper, we show that classical propensity score methods that ignore entanglement may lead to large bias and wrong inference of causal effects. We then propose a solution that involves calculating propensity scores by marginalizing over the network change. Under an appropriate ignorability assumption, this leads to unbiased estimates of the treatment effect of interest. We also develop a randomization-based inference procedure that takes entanglement into account. Under general conditions on network change, this procedure can deliver valid inference without explicitly modelling the network. We establish theoretical results for the proposed methods and illustrate their behaviour via simulation studies based on real-world network data. We also revisit a large-scale observational dataset on contagion of online user behaviour, showing that ignoring entanglement may inflate estimates of peer influence.
Minimum spanning tree analysis of unimpaired individuals at risk of Alzheimer’s disease
Authors: García-Colomo Alejandra , López-Sanz David , Stam Cornelis J , Hillebrand Arjan , Carrasco-Gómez Martín , Spuch Carlos , Comis-Tuche María , Maestú Fernando
Published: August 2024

Identifying early and non-invasive biomarkers to detect individuals in the earliest stages of the Alzheimer’s disease continuum is crucial. As a result, electrophysiology and plasma biomarkers are emerging as great candidates in this pursuit due to their low invasiveness. This is the first magnetoencephalography study to assess the relationship between minimum spanning tree parameters, an alternative to overcome the comparability and thresholding problem issues characteristic of conventional brain network analyses, and plasma phosphorylated tau231 levels in unimpaired individuals, with different risk levels of Alzheimer’s disease. Seventy-six individuals with available magnetoencephalography recordings and phosphorylated tau231 plasma determination were included. The minimum spanning tree for the theta, alpha and beta bands for each subject was obtained, and the leaf fraction, tree hierarchy and diameter were calculated. To study the relationship between these topological parameters and phosphorylated tau231, we performed correlation analyses, for the whole sample and considering the two risk sub-groups separately. Increasing concentrations of phosphorylated tau231 were associated with greater leaf fraction and tree hierarchy values, along with lower diameter values, for the alpha and theta frequency bands. These results emerged for the whole sample and the higher risk group, but not for the lower risk group. Our results indicate that the network topology of cognitively unimpaired individuals with elevated plasma phosphorylated tau231 levels, a marker of Alzheimer’s disease pathology and amyloid-β accumulation, is already altered, shifting towards a more integrated network increasing its vulnerability and hub-dependency, mostly in the alpha band. This is indicated by increases in leaf fraction and tree hierarchy, along with reductions in diameter. These results match the initial trajectory proposed by theoretical models of disease progression and network disruption and suggest that changes in brain function and organization begin early on.
ETS1 deficiency in macrophages suppresses colorectal cancer progression by reducing the F4/80+TIM4+ macrophage population
Authors: Cao Yuanyuan , Guo Anning , Li Muxin , Ma Xinghua , Bian Xiaofeng , Chen YiRong , Zhang Caixia , Huang Shijia , Zhao Wei , Zhao Shuli
Published: August 2024

Tumor-associated macrophages (TAMs) take on pivotal and complex roles in the tumor microenvironment (TME); however, their heterogeneity in the TME remains incompletely understood. ETS proto-oncogene 1 (ETS1) is a transcription factor that is mainly expressed in lymphocytes. However, its expression and immunoregulatory role in colorectal cancer (CRC)-associated macrophages remain unclear. In the study, the expression levels of ETS1 in CD68+ macrophages in the CRC microenvironment were significantly higher than those in matched paracarcinoma tissues. Importantly, ETS1 increased the levels of chemokines C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 10 (CXCL10) in lipopolysaccharide-stimulated THP-1 cells. It also boosted the migration and invasion of CRC cells during the in vitro co-culture. In the ETS1 conditional knockout mouse model, ETS1 deficiency in macrophages ameliorated the histological changes in DSS-induced ulcerative colitis mouse models and prolonged the survival in an azomethane/dextran sodium sulfate (AOM/DSS)-induced CRC model. ETS1 deficiency in macrophages substantially inhibited tumor formation, reduced F4/80+TIM4+ macrophages in the mesenteric lymph nodes, and decreased CCL2 and CXCL10 protein levels in tumor tissues. Moreover, ETS1 deficiency in macrophages effectively prevented liver metastasis of CRC and reduced the infiltration of TAMs into the metastasis sites. Subsequent studies have indicated that ETS1 upregulated the expression of T-cell immunoglobulin mucin receptor 4 in macrophages through the signal transducer and activator of the transcription 1 signaling pathway activated by the autocrine action of CCL2/CXCL10. Collectively, ETS1 deficiency in macrophages potentiates antitumor immune responses by repressing CCL2 and CXCL10 expression, shedding light on potential therapeutic strategies for CRC.
Application of Diagnostic Stewardship to Fungal Polymerase Chain Reaction: Low Yield of Follow-up Testing on Plasma and Bronchoalveolar Lavage After a Negative Result
Authors: Wang Tong , Park Bosung , Anderson Gavin , Shaller Brian , Budvytiene Indre , Banaei Niaz
Published: August 2024

Background

Early diagnosis of invasive fungal disease is essential for optimizing management. Although the clinical utility of fungal polymerase chain reaction (PCR) testing on plasma and bronchoalveolar lavage (BAL) has been established, the role of follow-up testing remains unclear.

Methods

This was a retrospective single-center study. The yield of follow-up PCR for Aspergillus species, Mucorales agents, Fusarium species, Scedosporium species, dimorphic fungi, Pneumocystis jirovecii, and Candida species on plasma and/or BAL was measured at intervals of 1, 2, 3, and 4 weeks following a negative result.

Results

A total of 1389 follow-up tests on 406 plasma specimens from 264 patients and 983 BAL specimens from 431 patients were evaluated. Overall, the positivity rate at 1, 2, 3, and 4 weeks was 2.7% (4/148), 3.3% (4/123), 5.1% (4/78), and 3.5% (2/57), respectively, on plasma, and 0% (0/333), 0.3% (1/288), 0.4% (1/228), and 0.7% (1/134), respectively, on BAL. Conversions occurred with Aspergillus species, Mucorales agents, and Fusarium species PCR on plasma and Aspergillus species and P jirovecii PCR on BAL. All patients who converted were immunocompromised. Within 1 week of a prior negative test, 2 Aspergillus and 2 Mucorales PCRs were positive on plasma, and zero tests were positive on BAL. In week 1, only 1 Aspergillus species that was positive on day 7 was classified as probable fungal disease.

Conclusions

Fungal PCR follow-up testing on plasma and BAL within 4 weeks of a prior negative result was of low yield and rarely generated a positive result considered clinically significant in the first week.
HLA-DQA1*05 Associates With Anti-Tumor Necrosis Factor Immunogenicity and Low Adalimumab Trough Concentrations in Inflammatory Bowel Disease Patients From the SERENE Ulcerative Colitis and Crohn’s Disease Studies
Authors: Reppell Mark , Zheng Xiuwen , Dreher Ingeborg , Blaes Jonas , Regan Elina , Haslberger Tobias , Guay Heath , Pivorunas Valerie , Smaoui Nizar
Published: August 2024

Background and Aims

Anti-tumor necrosis factor (anti-TNF) therapies are commonly prescribed treatments for Crohn’s disease (CD) and ulcerative colitis (UC). Many patients treated with anti-TNF therapy eventually develop anti-drug antibodies (ADAs). Understanding the factors associated with immunogenicity in anti-TNF-treated patients can help guide treatment. The Humira SERENE studies were Phase 3 trials investigating adalimumab induction regimens in CD and UC patients.

Methods

We imputed alleles for 7 HLA genes in 1100 patients from the SERENE CD and SERENE UC trials. We then tested these alleles for association with time to immunogenicity. Subsequently, we tested loci significantly associated with immunogenicity for their association with patients who had consistently low drug serum concentrations.

Results

This study replicated the association of HLA-DQA1*05 with time to immunogenicity (hazard ratio [HR] 1.42, p = 2.22E-06). Specifically, HLA-DQA1*05:05 was strongly associated (HR 1.76, p = 2.02E-10) and we detected a novel association represented by HLA-DRB1*01:02 (HR 3.16, p = 2.92E-07). Carriage of HLA-DQA1*05:05 and HLA-DRB1*01:02 was associated with patients who experienced consistently low adalimumab trough concentrations (HLA-DQA1*05:05: odds ratio [OR] 1.98, p = 0.0049; HLA DRB1*01:02: OR 7.06, p = 7.44E-05).

Conclusions

We found a significant association between alleles at genes in the human HLA locus and the formation of adalimumab immunogenicity and low adalimumab drug serum concentrations in large clinical studies of CD and UC patients. This work extends previous findings in CD to UC and directly shows a genetic association in patients with low drug concentrations. This work builds on existing literature to suggest that genetic screening could be a useful tool for clinicians concerned with patient anti-TNF immunogenicity.

Clinical Trial Registration Numbers

SERENE CD (NCT02065570), SERENE UC (NCT02065622).
Offence, Shakespeare, and Performance
Authors: Smialkowska Monika
Published: August 2024

Offence is a highly topical and much debated issue in contemporary Western societies. Fierce arguments rage between those who advocate mechanisms such as safe spaces, no platforming, and sensitivity readers to protect people from encountering offence, and those who maintain that curtailing the expression of offensive ideas stifles dialogue and impoverishes intellectual exchanges. This article sheds new light on the phenomenon of offence by examining it in the context of literary production, dissemination, and consumption. It focuses on drama as a performative genre, uniquely suited to embodying and interrogating emotions underpinning offensive exchanges. Through analysing representations of offence in several Shakespeare plays and discussing three actual or planned Shakespearean productions which caused offence to twenty-first-century audiences, it illuminates the ambiguities and contradictions inherent in defining offence. In particular, it demonstrates how difficult it is to determine agency in offensive exchanges: to establish who ‘owns’ offence, whether it originates with the offender or the offended party, and who has the right to decide what its consequences should be. Simultaneously, it argues that offence includes an element of social performance, as we do not only feel but also act offended. Because of the performative nature of offence, theatre and drama theory offer us a perfect laboratory and vocabulary for engaging with this vital issue.
Commercial fishery no-take zones for African penguins minimize fisheries losses at the expense of conservation gains
Authors: McInnes Alistair M , Weideman Eleanor A , Carpenter-Kling Tegan , Barham Peter , Christian Murray , Day Kirsten , Glencross Jacqueline S , Hagen Christina , Kock Alison , Lawrence Cloverley , Ludynia Katrin , Makhado Azwianewi , Pichegru Lorien , Shannon Lynne , Sherley Richard B , Smith Craig , Steinfurth Antje , Stander Nicky , Upfold Leshia , Waller Lauren
Published: August 2024

The African penguin population has declined precipitously in recent decades, and if current rates of decline persist, this species could become extinct in the wild by 2035. Resource extraction of small pelagic fish prey by the purse-seine fishery around African penguin breeding colonies has been identified as a demographically meaningful threat to African penguins. Consequently, long-term, effective no-take zones around breeding colonies have been endorsed by an expert panel of scientists constituted by the South African government. Here, we consider the six largest South African penguin colonies that currently hold 76% of the global population. We evaluate the adequacy of different no-take zone options using a trade-off mechanism recommended by the expert panel. For all six colonies except Bird Island, Algoa Bay, which is subject to the least fishing pressure, the current no-take zone delineations are assessed as having little benefit to the African penguin and little to no cost to the purse-seine fishery. Four of the six current no-take zones include ≤50% of the African penguins’ core foraging areas. Alternative no-take zones that approximate a more balanced trade-off offer more impactful alternatives to the current fisheries restrictions. Given the urgent need to implement evidence-based conservation interventions for the endangered African penguin, we recommend the substitution of the current no-take zones with those proposed herein.
Generic reasoning: A programmatic sketch
Authors: Faroldi Federico L G
Published: August 2024

A single significant instance may support general conclusions, with possible exceptions being tolerated. This is the case in practical human reasoning (e.g. moral and legal normativity: general rules tolerating exceptions), in theoretical human reasoning engaging with external reality (e.g. empirical and social sciences: the use of case studies and model organisms) and in abstract domains (possibly mind-unrelated, e.g. pure mathematics: the use of arbitrary objects). While this has been recognized in modern times, such a process is not captured by current models of supporting general conclusions. This paper articulates the thesis that there is a kind of reasoning, generic reasoning, previously unrecognized as an independent type of reasoning. A theory of generic reasoning explains how a single significant instance may support general conclusions, with possible exceptions being tolerated. This paper will adopt, as a working hypothesis, that generic reasoning is irreducible to currently recognized kinds of ‘pure’ reasoning. The aim is to understand generic reasoning, both theoretically and in its applications.
Biesta’s world-centred education: subjectification revisited?
Authors: Guillemin Elodie
Published: August 2024

This article explores Biesta’s recent revisiting of his iconic and at times contested notion of education as subjectification. First, I look at how Biesta presents his notion by attending to his answers to the criticisms it has faced concerning elusiveness, oversimplification, and self-centredness. Then, going beyond the declarative level, I explore a concrete example of education as subjectification from Biesta’s 2022 book, World-Centred Education. Analysing the example of Homer Lane and Jason, I examine the ambivalence between Biesta’s explicit statements on subjectification as a form of spontaneous and noncoercive teaching aimed at cultivating freedom and the more complex picture that emerges from a close reading of the original story. From this analysis, I find important conceptual limitations to education as subjectification: it could conceal part of the institutional context of education and the teacher’s active role, and also reduce freedom to an individualistic concept. I thus conclude by suggesting that the language of subjectification should always be engaged with critically—but never in isolation—and with a stereoscopic optic in mind.
Multi-institutional prospective observational study of radiotherapy for metastatic bone tumor
Authors: Harada Hideyuki , Shikama Naoto , Notsu Akifumi , Shirato Hiroki , Yamada Kazunari , Uezono Haruka , Koide Yutaro , Kubota Hikaru , Yamazaki Takuya , Ito Kei , Heianna Joichi , Okada Yukinori , Tonari Ayako , Katoh Norio , Wada Hitoshi , Ejima Yasuo , Yoshida Kayo , Kosugi Takashi , Takahashi Shigeo , Komiyama Takafumi , Uchida Nobue , Miwa Misako , Watanabe Miho , Nagakura Hisayasu , Ikeda Hiroko , Saito Tetsuo , Asakawa Isao , Takahashi Takeo , Shigematsu Naoyuki
Published: August 2024

Purpose of this study is to evaluate patient characteristics, treatments and outcomes in bone metastasis radiotherapy practice. Patients for whom radiotherapy for bone metastasis was planned at 26 institutions in Japan between December 2020 and March 2021 were consecutively registered in this prospective, observational study. Study measures included patient characteristics, pain relief, skeletal-related events (SREs), overall survival and incidence of radiation-related adverse events. Pain was evaluated using a numerical rating scale (NRS) from 0 to 10. Irradiated dose was analyzed by the biologically effective dose (BED) assuming α/β = 10. Overall, 232 patients were registered; 224 patients and 302 lesions were fully analyzed. Eastern Cooperative Oncology Group Performance Status was 0/1/2/3/4 in 23%/38%/22%/13%/4%; 59% of patients had spinal metastases and 84% had painful lesions (NRS ≥ 2). BED was <20 Gy (in 27%), 20–30 Gy (24%), 30–40 Gy (36%) and ≥ 40 Gy (13%); 9% of patients were treated by stereotactic body radiotherapy. Grade 3 adverse events occurred in 4% and no grade 4–5 toxicity was reported. Pain relief was achieved in 52% at 2 months. BED is not related to pain relief. The cumulative incidence of SREs was 6.5% (95% confidence interval (CI) 3.1–9.9) at 6 months; no factors were significantly associated with SREs. With spinal lesions, 18% of patients were not ambulatory at baseline and 50% of evaluable patients in this group could walk at 2 months. The 6-month overall survival rate was 70.2% (95% CI 64.2–76.9%). In conclusion, we report real-world details of radiotherapy in bone metastasis.
Mapping socio-economic status using mixed data: a hierarchical Bayesian approach
Authors: Virgili-Gervais Gabrielle , Schmidt Alexandra M , Bixby Honor , Cavanaugh Alicia , Owusu George , Agyei-Mensah Samuel , Robinson Brian , Baumgartner Jill
Published: August 2024

We propose a Bayesian hierarchical model to estimate a socio-economic status (SES) index based on mixed dichotomous and continuous variables. In particular, we extend Quinn’s ([2004]. Bayesian factor analysis for mixed ordinal and continuous responses. Political Analysis, 12(4), 338–353. https://doi.org/10.1093/pan/mph022) and Schliep and Hoeting’s ([2013]. Multilevel latent Gaussian process model for mixed discrete and continuous multivariate response data. Journal of Agricultural, Biological, and Environmental Statistics, 18(4), 492–513. https://doi.org/10.1007/s13253-013-0136-z) factor analysis models for mixed dichotomous and continuous variables by allowing a spatial hierarchical structure of key parameters of the model. Unlike most SES assessment models proposed in the literature, the hierarchical nature of this model enables the use of census observations at the household level without needing to aggregate any information a priori. Therefore, it better accommodates the variability of the SES between census tracts and the number of households per area. The proposed model is used in the estimation of a socio-economic index using 10% of the 2010 Ghana census in the Greater Accra Metropolitan area. Out of the 20 observed variables, the number of people per room, access to water piping and flushable toilets differentiated high and low SES areas the best.
Joint Venture Disputes
Authors: Timothy A
Published: August 2024

This chapter examines how joint venture disputes typically arise between the parties to the joint venture. The use of industry custom and practice (to the extent that it can be proved to exist) in resolving joint venture disputes is considered in this chapter, as is the role which case law takes in shaping joint venture disputes in the energy and natural resource sectors. This chapter goes on to consider, by reference to certain arbitration awards, the factors which tribunals have taken into consideration in reaching their decisions on international joint venture disputes. This chapter concludes with a review of the fora which are most commonly utilized for the resolution of joint venture disputes, and the kinds of issues which are the most recurring in relation to joint venture disputes.
Accounting Procedure
Authors: Timothy A
Published: August 2024

This chapter considers where the accounting provisions have caused disputes to arise. This relates principally, but not exclusively, to disputes in joint ventures governed by a joint operating agreement (JOA), where there are controversies over the level of costs incurred. The cases reviewed demonstrate that a number of issues can give rise to disputes. This includes the nature of costs that can be charged to the joint account, how they should be shared and the ability of the non-operators to review and audit the costs charged. In many cases, the rights to charge costs and to audit those costs are subject to express time limits and the precise application of these time limits is addressed in the cases condisdered in this chapter.