bluuebunny/crossref_metadata_2025 huggingface dataset:
The geometry of the neural state space of decisions
Authors: Monsalve-Mercado Mauro M. , Miller Kenneth D.
Published: January 2025

How do populations of neurons collectively encode and process information during cognitive tasks? We analyze high-yield population recordings from the macaque lateral intraparietal area (LIP) during a reaction-time random-dot-motion direction-discrimination task. We find that the trajectories of neural population activity patterns during single decisions lie within a two-dimensional decision manifold. Reaction time systematically varies along one dimension of the manifold,i.e. slow and fast decisions trace distinct activity patterns. Trajectories transition from a deliberation stage, in which they are noisy and remain similar between the choices, to a commitment stage, in which they are far less noisy and diverge sharply for the different choices. The deliberation phase is pronounced for slower decisions and gradually diminishes as reaction time decreases. A mechanistic circuit model provides an explanation for the observed properties, and suggests the transition between stages represents a transition from more sensory-driven to more circuit-driven dynamics. It yields two striking predictions we verify in the data. First, whether neurons are more choice selective for slow or fast trials varies systematically with the retinotopic location of their response fields. Second, the slower the trial, the more saccades undershoot the choice target. The results highlight the flexible and adaptive recruitment of neurons and the role of intrinsic circuit dynamics in the population implementation of a cognitive task.
Transferring functional chromosomes between intergeneric yeast generates monochromosomal hybrids with improved phenotypes and transcriptional responses
Authors: Lyu Yilin , Song Kunfeng , Zhou Jungang , Chen Hao , Li Xueying C. , Yu Yao , Lu Hong
Published: January 2025

Interspecific hybrids can exhibit phenotypes that surpass those of their parents, known as heterosis, which is often of interest for industrial applications and evolutionary genetics research. However, constructing hybrids between distantly related species, such as intergeneric yeasts, presents technical challenges. In this study, we established a method to transfer individual chromosomes fromSaccharomyces cerevisiae(Sc) intoKluyveromyces marxianus(Km), an emerging model for bioproduction. The Sc chromosome of interest was circularized, genetically modified to carry Km centromeres and replication origins, and transformed into Km via protoplast transformation. With this method, we generated monochromosomal hybrids with eight Km chromosomes and Sc chromosome I or III. The Sc chromosomes exhibited normal replication, segregation, and active transcription in the hybrids. The hybrids displayed heterosis in flocculation and salt tolerance due to the overexpression ofFLO9andSPS22, respectively. Transcriptomic analysis revealed that bothcis-andtrans-regulatory changes contributed to the divergence of gene expression between the two species, with thecisandtranseffects often acting in a compensatory manner. Our strategy has potential applications in optimizing cell factories, constructing synthetic genomes, and advancing evolutionary research.

Teaser

A yeast hybrid containing an alien chromosome transferred from a distantly related species exhibits improved phenotypes.
Synaptic phosphoproteome modifications and cortical circuit dysfunction are linked to the early-stage progression of alpha-synuclein aggregation
Authors: Dutta Sayan , Hensel Jennifer , Scott Alicia , Mohallem Rodrigo , Rossitto Leigh-Ana M , Khan Hammad Furqan , Johnson Teshawn , Ferreira Christina R , Marmolejo Jackeline F. , Chen Xu , Jayant Krishna , Aryal Uma K. , Volpicelli-Daley Laura , Rochet Jean-Christophe
Published: January 2025

Cortical dysfunction is increasingly recognized as a major contributor to the non-motor symptoms associated with Parkinson’s disease (PD) and other synucleinopathies. Although functional alterations in cortical circuits have been observed in preclinical PD models, the underlying molecular mechanisms are unclear. To bridge this knowledge gap, we investigated tissue-level changes in the cortices of rats and mice treated with alpha-synuclein (aSyn) seeds using a multi-omics approach. Our study revealed significant phosphoproteomic changes, but not global proteomic or lipid profiling changes, in the rat sensorimotor cortex 3 months after intra-striatal injection with aSyn preformed fibrils (PFFs). Gene ontology analysis of the phosphoproteomic data indicated that PFF administration impacted pathways related to synaptic transmission and cytoskeletal organization. Similar phosphoproteomic perturbations were observed in the sensorimotor cortex of mice injected intrastriatally or intracortically with aSyn PFFs. Functional analyses demonstrated increased neuronal firing rates and enhanced spike-spike coherence in the sensorimotor cortices of PFF-treated mice, indicating seed-dependent cortical circuit dysfunction. Bioinformatic analysis of the altered phosphosites suggested the involvement of several kinases, including casein kinase-2 (CK2), which has been previously implicated in PD pathology. Collectively, these findings highlight the importance of phosphorylation-mediated signaling pathways in the cortical response to aSyn pathology spread in PD and related synucleinopathies, setting the stage for developing new therapeutic strategies.
Balancing Integration and Segregation: Structural Connectivity as a Driver of Brain Network Dynamics
Authors: Palma-Espinosa Javier , Orellana-Villouta Sebastian , Coronel-Oliveros Carlos , Maidana Jean Paul , Orio Patricio
Published: January 2025

The brain's ability to transition between functional states while maintaining both flexibility and stability is shaped by its structural connectivity. Understanding the relationship between brain structure and neural dynamics is a central challenge in neuroscience. Prior studies link neural dynamics to local noisy activity and mesoscale coupling mechanisms, but causal links at the whole-brain scale remain elusive. This study investigates how the balance between integration and segregation in brain networks influences their dynamical properties, focusing on multistability (switching between stable states) and metastability (transient stability over time). We analyzed a spectrum of network models, from highly segregated to highly integrated, using structural metrics like modularity, efficiency, and small-worldness. Simulating neural activity with a neural mass model and analyzing Functional Connectivity Dynamics (FCD), we found that segregated networks sustain dynamic synchronization patterns, while small-world networks, which balance local clustering and global efficiency, exhibit the richest dynamical behavior. Networks with intermediate small-worldness (omega) values showed peak dynamical richness, measured by variance in FCD and metastability. Using Mutual Information (MI), we quantified the structure-dynamics relationship, revealing that modularity is the strongest predictor of network dynamics, as modular architectures support transitions between dynamical states. These findings underscore the importance of the small-world architecture in brain networks, where the balance between local specialization and global integration fosters the dynamic complexity necessary for cognitive functions. By emphasizing the role of modularity, this study enhances understanding of how structural features shape neural dynamics and offers insights into disruptions linked to neurological disorders.
Wheat infection byFusarium graminearumspecies complex members is facilitated by a transcriptionally conserved non-ribosomal peptide synthetase gene cluster
Authors: Tralamazza Sabina Moser , Nielsen Mikkel Rank , Abraham Leen Nanchira , Atanasoff-Kardjalieff Anna K. , Glauser Gaetan , Sørensen Jens Laurids , Studt-Reinhold Lena , Corrêa Benedito , Croll Daniel
Published: January 2025

Biosynthetic gene clusters (BGCs) are often found in fungal pathogens and encode secondary (or specialized) metabolites that play crucial roles in host and niche adaptation. However, the regulatory dynamics and functions of these BGCs during host infection remain largely unknown. To address this gap, we employed interspecies comparative transcriptomics to identify BGCs involved in host-pathogen interactions mediated by theFusarium graminearumspecies complex (FGSC). We conducted joint transcriptomic and metabolomic analyses during wheat infection andin vitroexperiments with five members of the FGSC to understand gene regulation during host infection. Our findings revealed that expression regulation was predominantly species-specific, but we also identified a set of shared upregulated genes that were common to all five FGSC species showing enrichment for metabolic and pathogenicity-associated functions. We focused on jointly upregulated BGC during infection and identified a NRPS-like gene cluster named SM3. The cluster was highly conserved within FGSC and shared by the more distantF. sambucinumspecies complex. We show that inactivation of the BGC core gene significantly impairsF. graminearumsensu stricto (s.s.) spore production, reduces fungal spread and Fusarium Head Blight symptoms on wheat kernels. Our results highlight that comparative infection transcriptomes can reveal conserved metabolic functions mediating the host infection process of a plant pathogen.
AI regulation in healthcare around the world: what is the status quo?
Authors: Busch Felix , Geis Raym , Wang Yuan-Cheng , Kather Jakob Nikolas , Khori Noor Al , Makowski Marcus R , Kolawole Israel K , Truhn Daniel , Clements Warren , Gilbert Stephen , Adams Lisa C , Ortiz-Prado Esteban , Bressem Keno K
Published: January 2025

The rapid adoption of artificial intelligence (AI) raises challenges related to ethics, safety, equity, and governance that require robust regulatory frameworks. In most jurisdictions, AI-driven medical devices are already covered by existing medical device frameworks, although new AI-specific legislation may be required to address the challenges posed by recent advancements. This expert review focuses on frameworks and legislation explicitly tailored to AI, synthesizing research literature, government and intergovernmental framework programs, and online media coverage to provide an up-to-date assessment of global AI-specific regulation or strategies in healthcare as of December 2024. Our findings show that only 15.2% (n=30/197) of countries or territories have enacted legally binding AI-specific legislation, including the 27 member states of the European Union (EU) following the adoption of the EU AI Act. A further 9.1% (n=18/197) have drafted legislation, and 28.4% (n=56/197) have issued non-binding guidelines. Notably, 47.2% (n=93/197) of countries or territories do not have an AI-specific framework or legislation in place. Furthermore, our results highlight disparities between the Global North and South, with 60.3% (n=82/136) of Global South countries or territories lacking frameworks or legislation, compared to 18% (n=11/61) in the Global North. In conclusion, our work provides an overview of the status quo of AI regulation around the world, highlights disparities in the adoption of frameworks and legislation, and calls for the need for intergovernmental and regional cooperation.
Reconciling time and prediction error theories of associative learning
Authors: Hamou Noé , Gershman Samuel J , Reddy Gautam
Published: January 2025

Learning involves forming associations between sensory events that have a consistent temporal relationship. Influential theories based on prediction errors explain numerous behavioral and neurobiological observations but do not account for how animals measure the passage of time. Here, we propose a Bayesian theory for temporal causal learning, where the structure of inter-stimulus intervals is used to infer the singular cause of a rewarding stimulus. We show that a single assumption of timescale invariance, formulated as an hierarchical generative model, is sufficient to explain a puzzling set of learning phenomena, including the power-law dependence of acquisition on inter-trial intervals and timescale invariance in response profiles. A biologically plausible algorithm for inference recapitulates salient aspects of both timing and prediction error theories. The theory predicts neural signals with distinct dynamics that encode causal associations and temporal structure.
Understanding the consequences of unethical pro-organizational behavior: a dual pathway model from an actor-based perspective
Authors: Dadaboyev Sherzodbek Murodilla Ugli , Paek Soyon , Choi Sungwon , Farro Andrea C.
Published: January 2025

Purpose

The purpose of this study is to synthesize unethical pro-organizational behavior (UPB) research that has empirically examined consequences of UPB and to provide an actor-based perspective rooted in a dual pathway self-regulation model.

Design/methodology/approach

We first systematically reviewed the literature on the consequences of UPB. Given the duality of UPB (i.e. pro-organizational and unethical simultaneously), we followed with the theoretical development of a dual pathway model of UPB consequences and suggest propositions from an actor-based perspective.

Findings

We posited that the distinctive attributes of UPB give rise to corresponding and distinct employee attitudes and behaviors.

Originality/value

Taking an actor-based perspective and drawing on theories of moral self-regulation and self-consistency, we seek to (1) determine why some UPB actors’ self-evaluations of their UPBs focus on the pro-organizational nature of their behaviors versus the unethical nature of their behaviors (i.e. dual pathway) and (2) determine the potential consequences (i.e. actor’s behavioral and attitudinal responses) of each pathway.
Extending job crafting theory to precarious workers: a model of organizational job crafting for organizational justice
Authors: Kim Seon Mi
Published: January 2025

Purpose

This paper introduces and develops a conceptual model, “organizational job crafting,” to extend and apply job crafting theory to precarious workers.

Design/methodology/approach

This conceptual model incorporates the perspectives of organizational justice theory into job crafting theory to identify precarious workers’ unique job crafting motivation and processes in their work environment. The theory is developed by integrating and adjusting aspects of these two approaches.

Findings

This model invokes five propositions specifying (1) the impacts of organizational justice on individual motivations for job crafting, (2) the conditions for developing a shared perception of organizational justice, (3) the forms of organizational job crafting and (4) the individual and organizational effects of job crafting. Moderating conditions are identified, such as the level of connection to labor/community organizations.

Originality/value

This study extends established job crafting theory, enriching it by incorporating the precarious worker perspective. By connecting job crafting to organizational justice theories, this model opens the possibility that workers’ job crafting can produce not only personal enrichment or work efficiency but also contribute to organizational changes. The theoretical development handles issues blocked or hidden by the original constituent theoretical ingredients.
Human resource analytics adoption: a framework-based analysis, fuzzy Delphi method and fuzzy SWARA
Authors: Kardani Malekinezhad Mona , Rahimnia Fariborz , Eslami Ghasem , Farahi Mohammad Mahdi
Published: January 2025

Purpose

Human resource analytics (HRA) has recently received attention. However, its literature remains unknown and scattered due to both limited conceptual lenses and limited classification. So, this study is conducted to provide a comprehensive research analysis in this field.

Design/methodology/approach

Accordingly, 107 HRA studies, which were collected according to the Scientific Procedures and Rationales for Systematic Literature Reviews (SPAR-4-SLR) in the last 14 years (2010–2023), were analyzed in the first using the theory-context-characteristics-methods step to examine the evolution of HRA research. The study also develops a conceptual framework based on socio-technical system theory that shows the antecedents and outcomes of HRA adoption. In the second step, fuzzy Delphi and fuzzy step-wise weight assessment ratio analysis techniques were used to validate and refine the antecedents and outcomes obtained from the first step in such a way that experts’ opinions can be used and the existing knowledge body can be expanded.

Findings

In total, 30 antecedents and outcomes were confirmed based on the consensus of experts. Senior management support was identified as the most important antecedent and achieving organizational strategic outcomes as the most important outcomes of HRA adoption.

Originality/value

The study maps the current state of HRA studies, identifies directions for future studies by providing a state-of-the-art review of theories, antecedents, outcomes, contexts and methodologies and proposes a framework for HR managers and professionals to apply.
Ang tagapagtaguyod na anak for Filipino adults: an exploratory research
Authors: Quindoza Thessa Lonica Villamor , Malcampo Marie Chiela , Rungduin Teresita
Published: January 2025

Purpose

In Filipino culture, children often take on the role of family “breadwinner,” providing financial support and sharing family responsibilities. However, this role is typically viewed narrowly as that of a financial provider. To address this, this study explores the “Tagapagtaguyod na Anak,” aiming to offer a more nuanced and culturally relevant understanding of the broader responsibilities and dynamics involved in this role within Filipino families.

Design/methodology/approach

This exploratory study focused on single adult children aged 18–29 years and middle-aged parents aged 40–60 years old. Data were collected through semi-structured interviews and analyzed thematically to explore the phenomenon of “Tagapagtaguyod na anak.”

Findings

The findings reveal that “tagapagtaguyod na anak” provide financial, emotional and social support to their families. This role is shaped by parental expectations and the child’s volition. This role develops out of necessity and is influenced by the child’s understanding of family needs, a sense of responsibility, family values and gratitude (Utang na Loob). Implications for tagasalo personality and societal norms and intergenerational family dynamics are also discussed.

Originality/value

This study delved into the concept of “tagapagtaguyod na anak” in Filipino families, distinguishing it from the “tagasalo personality” identified by Carandang (1987) and Udarbe (2001). It highlights the distinct responsibilities of this role, emphasizing the influence of cultural norms, gender expectations and socioeconomic factors. Hence, it offers valuable insights into the Filipino family dynamics.
The Effect of Assisted Reproductive Technologies on Human Sex Ratios
Authors: Georgiou Ektoras X. , Mizrachi Yossi , Kelley Rebecca , Stock‐Myer Sharyn , Stevens John , Gardner David K. , Polyakov Alex
Published: January 2025

Background

Modern assisted reproductive technology (ART), including pre‐implantation genetic testing for aneuploidy (PGT‐A), has opened new avenues in understanding early embryonic events and has simultaneously raised questions about the impact of ART itself on sex ratios.

Aims

The primary aim was to investigate whether patient demographic characteristics, ovarian stimulation protocols or laboratory characteristics in ART influence sex ratios. The secondary aim was to relate the blastocyst sex ratio (BSR) to the corresponding secondary sex ratio (SSR) in our patient cohort.

Materials and Methods

We conducted a retrospective single‐centre cohort study on consecutive PGT‐A cycles from January 2019 to February 2022. We analysed demographic data, stimulation protocols, laboratory characteristics and pregnancy outcomes.

Results

The euploidy rate was 45.1% (2608/5777), BSR 1.07 and euploid BSR 1.03. There was no statistical difference in the ploidy status of XX and XY blastocysts and on multivariate logistic regression analysis, there was no association between euploidy and BSR or any other variables examined, including female age and stimulation protocol. The SSR was 1.02 (1294 embryo transfers) with no statistical difference in biochemical pregnancy (p = 0.41), clinical pregnancy (p = 0.56), miscarriage (p = 0.65) or live birth rates (p = 0.40) based on embryo sex.

Conclusions

Our study indicates that the euploid BSR is not skewed by sex, and there is no relationship between BSR and euploidy, patient characteristics or stimulation protocols. Pregnancy outcomes did not vary by sex, and the SSR was consistent with the SSR of the general Australian population at birth.
A Rare Case of Sigmoid‐Urachal Fistula in an Adult Male Resected Laparoscopically
Authors: Tomida Akihiro , Hattori Masaoki , Hirata Akihiro , Shibata Jumpei , Imataki Hiromitsu , Suzuki Marika , Shintomi Hideharu , Aono Keiya , Yoshihara Motoi
Published: January 2025

Fistulization involving both the sigmoid colon and urachus is exceedingly rare. While previous cases have often necessitated laparotomy due to the involvement of multiple organs, only one instance of successful laparoscopic surgery has been reported. Here, we present the second documented case of laparoscopic resection of a sigmoid‐urachal fistula. A 46‐year‐old male presented to our hospital with complaints of umbilical pain and discharge, subsequently diagnosed via CT scan as pyourachus, and conservatively managed with antibiotics. Approximately 1 year and 7 months later, a cutaneous ulcer developed below the left side of the umbilicus, accompanied by fecal discharge. Further investigation revealed a fistulous connection between the sigmoid colon and residual urachus as the underlying pathology. Utilizing laparoscopic techniques, we performed en bloc resection of the urachus, dome of the bladder, and sigmoid colon. The patient experienced an uneventful post‐operative recovery and was discharged after 9 days.
Is Hume's Law a valid argument against empirical bioethics?
Authors: Corsico Paolo
Published: January 2025

If “no ought from is,” how can bioethics be empirical? Despite the widespread recognition that we can integrate empirical and normative, Hume's Law is still often claimed to pose logical limitations to empirical bioethics. Is Hume's Law a valid argument against empirical bioethics? I argue that we have reasons to answer no. First, I outline and reject two unverified assumptions: that Hume’ s Law, the fact‐value distinction, and the naturalistic fallacy are roughly the same thing, and that Hume's Law is an undisputed meta‐ethical principle which dictates how to formulate normative statements. I then show how the interpretation of Hume's Law as establishing a logical gulf between facts and morality—rather than as clarifying the logical rules of normative argumentation—is dependent upon a non‐cognitivist interpretation of the Is‐Ought problem. I argue that the version of Hume's Law that stems from ethical non‐cognitivism is what is problematic for empirical bioethics. However, other interpretations are possible. We have two reasons to reject the thesis that Hume's Law is an argument against empirical bioethics. First, conflating meta‐ethics and applied ethics is problematic. Second, a non‐cognitivist interpretation of Hume's Law is likely to constitute an argument not only against empirical bioethics, but against all bioethics that claims to be situated within ethical cognitivism, be it empirical or philosophical. Lastly, I present two meta‐ethical postulates shared by empirical and philosophical bioethics. I call them: (1) the “bridge” postulate and (2) the “ethical cognitivism” postulate.
Mexican Immigration and the Decline of Transnationalism: A 30‐Year Retrospective
Authors: Jones Richard C.
Published: January 2025

The migration literature has established that transnationalism between origin and destination lessens over time for international migrants. This study asks whether this decline takes place for entire towns in the country of origin and what may be the causes of the decline. Household surveys by the author in two counties in central Zacatecas state, Mexico, in 1988 and again in 2018, provide some answers. Results document a decline in transnationalism and implicate assimilation of migrants in the United States and loss of prospects in rural Zacatecas as driving forces. Also, demographic modernisation and extra‐regional opportunities reduce migration and along with it, transnationalism.
Explaining Public Sector Corruption: The Hexagon Model
Authors: Thomann Eva , Ioannidis Giuliana , Zgaga Tiziano , Schwarz Frederic
Published: January 2025

Different disciplines ask why public sector corruption occurs, addressing diverse phenomena. However, how different approaches and factors at micro, meso, or macro levels relate to each other in causally complex, context‐dependent ways is seldom theorized. This article develops an integrated “Corruption Hexagon” model with six dimensions. The analytically relevant context provides a not directly causal background that influences the interplay of the pressure to act corruptly, the opportunity to benefit from corruption, the capability to exploit the opportunity, the supply of corruption, and the rationalization of one's corrupt behavior. Using secondary data from 23 European countries, we operationalize the Hexagon to explain differences in procurement‐related corruption risks. Results corroborate the Hexagon's expectations: whereas the circumstances enable corruption, their interplay with personal characteristics or rationalization triggers corruption. The Hexagon offers a flexible, context‐dependent, complexity‐informed model for cumulative research integrating different methods and theoretical assumptions about the agency underlying corruption.
Resonances of Feeling Alone: A Systematic Review Unveiling Older Persons' Loneliness and Its Mechanisms in Residential Care Facilities
Authors: Gill Amarjot S. , Sullivan Suzanne S.
Published: January 2025

Aim

To review older persons' lived experiences and perceptions of loneliness in residential care facilities and characterise mechanisms underlying their experiences through a comprehensive loneliness model.

Design

A systematic review synthesising qualitative research on the experiences of loneliness among older people living in residential care facilities.

Methods

This review followed Preferred Reporting Items for Systematic Reviews and Meta‐analyses guidelines with quality appraisal conducted using the Critical Appraisal Skills Programme checklist.

Data Sources

Articles published in English (2014–2024) from CINAHL, PubMed, PsycINFO and Web of Science.

Results

Sixteen articles met inclusion criteria, representing 357 participants across 10 countries and regions. Three core themes of loneliness were identified: relational and individualised loneliness experiences, perception and emotional distress and the influence of context and cognitive processes in modulating loneliness. A conceptual model delineating the mechanisms of older residents' loneliness in residential settings was developed.

Conclusion

This review highlights the influence of older persons' residential context and cognitive processes, particularly their perceptions, in triggering loneliness. The perceptions of reduced social control and insufficient social connections in residential settings exacerbate older persons' loneliness, precipitating distressing emotional responses and diminished quality of life.

Implications

Residential care facilities have a crucial responsibility in establishing a supportive atmosphere conducive to positive social engagement for older residents. Future research must explore strategic transformations of older persons' perceptions through mechanistic targets and tailored care plans to reshape their social expectations within the context of residential care facilities, potentially mitigating loneliness.

Impact

This review addresses the problem of understanding the mechanisms and experiences of loneliness among older persons in residential care facilities. The findings highlight the critical need for supportive social environments and targeted interventions in residential care settings to improve residents' well‐being and quality of life globally.

Reporting Method

Enhancing Transparency in Reporting the Synthesis of Qualitative Research statement.

Patient or Public Contribution

No patient or public contribution.
A preliminary ex vivo diffusion tensor imaging study of distinct aortic morphologies
Authors: Tornifoglio B. , Robinson S. T. , Levey R. E. , Stone A. J. , Campisi S. , Kerskens C. , Duffy G. P. , Avril S. , Lally C.
Published: January 2025

Changes in the microstructure of the aortic wall precede the progression of various aortic pathologies, including aneurysms and dissection. Current clinical decisions with regards to surgical planning and/or radiological intervention are guided by geometric features, such as aortic diameter, since clinical imaging lacks tissue microstructural information. The aim of this proof‐of‐concept work is to investigate a non‐invasive imaging method, diffusion tensor imaging (DTI), in ex vivo aortic tissue to gain insights into the microstructure. This study examines healthy, aneurysm and a type B chronic dissection aortae, via DTI. DTI‐derived metrics, such as the fractional anisotropy, mean diffusivity, helical angle and tractography, were examined in each morphology. The results from this work highlighted distinct differences in fractional anisotropy (healthy, 0.24 ± 0.008; aneurysmal, 0.19 ± 0.002; dissected, 0.13 ± 0.006) and a larger variation in the helical angle in the dissected aorta compared to healthy (39.28 ± 11.93° vs. 26.12 ± 4.60°, respectively). These differences were validated by histological characterisation. This study demonstrates the sensitivity of DTI to pathological changes in aortic tissue, highlighting the potential of this methodology to provide improved clinical insight.
Identification of the Novel HLA‐B*15:245:02Q Allele in a Chinese Individual
Authors: Xia Jiaan , Li Wangxia
Published: January 2025

HLA‐B*15:245:02Q differs from HLA‐B*15:01:01:01 by two nonsynonymous nucleotides exchanges in exon 3.
The New HLA‐B*44:384 Allele Characterised by Two Different Sequencing‐Based Typing Techniques
Authors: Dhuyser Adèle , Pérès Michaël , Morel Thomas , Clément Sandra , Aarnink Alice
Published: January 2025

The new allele HLA‐B*44:384 differs from HLA‐B*44:02:01:01 by one non‐synonymous nucleotide substitution in exon 2.
Identification of Two Novel HLA Class II Alleles, DPB1*1626:01Q and DRB1*11:337, by Next‐Generation Sequencing
Authors: Jiménez Noelia Jurado , Rodríguez‐Bayona Beatriz , Balas Antonio , Escribano María Francisca González
Published: January 2025

Description of two novel HLA class II alleles, DPB1*1626:01Q and DRB1*11:337 alleles.
Identification of the Novel HLA‐C*06:44:02 Allele by Next‐Generation Sequencing in a Serbian Individual
Authors: Jovanovic Barbara , Andric Zorana , Velickovic Danica , Kacaki Nikola , Lilic Marko
Published: January 2025

The novel HLA‐C*06:44:02 allele differs from HLA‐C*06:44:01 by one synonymous nucleotide substitution in exon 2.
Characterisation of the Novel HLA‐C*03:657 Allele in a Korean Individual by Next‐Generation Sequencing
Authors: Kim Sang Mook , Lee Jong‐Mok , Kim Chan‐Duck , Won Dong Il
Published: January 2025

HLA‐C*03:657 differs from HLA‐C*03:04:01:02 by one nucleotide substitution in codon 82 in exon 2.
The New HLA‐DRB1*07:159 Allele Characterised by Two Different Sequencing‐Based Typing Techniques
Authors: Dhuyser Adèle , Pérès Michaël , Morel Thomas , Clément Sandra , Aarnink Alice
Published: January 2025

The novel HLA‐DRB1*07:159 allele differs from HLA‐DRB1*07:01:01:01 by one non‐synonymous nucleotide substitution in exon 2.
Detection of the Novel HLA‐A*02:01:01:257 Allele by Pacific Biosciences HiFi Sequencing in a Chinese Individual
Authors: Han Yue , Liu Yundie , Wang Caili , Feng Shaoqing , Gao Peng
Published: January 2025

HLA‐A*02:01:01:257 differs from HLA‐A*02:01:01:01 by a single nucleotide substitution in intron 7.
The Americanization of Nigerian English spelling and punctuation
Authors: Olatoye Temitayo
Published: January 2025

Spelling is the most standardized level of language, and prescriptive spelling norms in former British colonies often advocate adherence to British spelling norms which differs from the local linguistic reality. Hence, recent research on the evolution of postcolonial Englishes and the Americanization of Englishes worldwide has questioned the appropriateness of such presumptions. This study presents a diachronic investigation of spelling variation and word‐level punctuation in written Nigerian English, using the Nigerian component of the International Corpus of English and the recently compiled Historical Corpus of Nigerian English. Results from frequency analyses and a multifactorial analysis not only highlight a strong preference for British norms but also indicate that American spelling patterns increasingly occurred in various registers of written Nigerian English in the late twentieth century. These findings suggest that the coexistence of British and American spelling norms is hardly a recent development in the evolution of Nigerian English.
Modified particle dynamics and thermodynamics in a traversable wormhole in bumblebee gravity
Authors: Filho A. A. Araújo , Reis J. A. A. S. , Övgün Ali
Published: January 2025

In this work, we analyze various phenomena influenced by the gravitational field in a bumblebee gravity solution, with a particular emphasis on a traversable wormhole for massless particle modes. Specifically, we calculate the index of refraction, group velocity, time delay, modified distances, and interparticle potential, demonstrating the possibility of photon-photon interactions due to the wormhole geometry. For the latter aspect, we also extend the analysis to massive particle modes, resulting in a “combination” of modified Yukawa- and Coulomb-like potentials. These calculations are shown to be dependent on the wormhole’s parameters, particularly the wormhole throat. In addition to these analyses, the Hawking temperature is derived using the trapping horizon method, yielding negative values. Furthermore, we derive the thermodynamic properties of photon-like modes by incorporating the modified dispersion relation arising from the wormhole geometry, focusing on non-interacting particle modes. Remarkably, all calculations are conducted in a fully analytical framework.
Wormhole solutions in deformed space-time
Authors: Sreekumar Harsha , Harikumar E.
Published: January 2025

We construct and analyse wormhole solutions in quantised space-time. The field equations are constructed from the deformed wormhole metric in the proper reference frame using tetrads. The spatial geometry of the wormhole is analysed in kappa space-time. Further, modifications to the conditions that ensure traversibility of the wormhole are studied and it is found that the necessity of the exotic matter persists in the non-commutative case as in the commutative space-time. Casimir energy is considered a possible source for exotic matter and it is shown that the time to pass through the wormhole as well as the amount of exotic matter required to create the wormhole reduce due to non-commutativity of space-time.
Source of instability in the rapid cycling synchrotron of the China spallation neutron source
Authors: Huang Liangsheng , Wang Sheng , Xu Shouyan , Liu Xingguang , Huang Mingyang , Liu Renhong , Tan Biao , Liu Hanyang , Rao Li , Han Yanliang
Published: January 2025

The rapid cycling synchrotron (RCS) of the China spallation neutron source accumulates 1.56

$$\times$$

×

$$10^{13}$$

10
13

protons and accelerates them from 80 MeV to 1.6 GeV at a repetition rate of 25 Hz, delivering a 100 kW proton beam to the target. Despite predictions that no instabilities would occur at high beam intensity, an unexpected coherent oscillation of the beam was observed during the beam commissioning. To confirm and address the instability, a series of systematic measurements and studies were conducted, revealing that the issue is a transverse coupled bunch instability and identifying a narrow-band impedance with a low frequency in the RCS. Further bench measurements confirmed that ceramic chambers with RF shields are the source of this impedance, which is consistent with the analysis of the experimental data. Based on these findings, a tune curve during the ramping process and chromaticity optimization have been implemented to completely mitigate the instability in the RCS at 100 kW.
Scientific Large Language Models: A Survey on Biological & Chemical Domains
Authors: Zhang Qiang , Ding Keyan , Lv Tianwen , Wang Xinda , Yin Qingyu , Zhang Yiwen , Yu Jing , Wang Yuhao , Li Xiaotong , Xiang Zhuoyi , Zhuang Xiang , Wang Zeyuan , Qin Ming , Zhang Mengyao , Zhang Jinlu , Cui Jiyu , Xu Renjun , Chen Hongyang , Fan Xiaohui , Xing Huabin , Chen Huajun
Published: January 2025

Large Language Models (LLMs) have emerged as a transformative power in enhancing natural language comprehension, representing a significant stride toward artificial general intelligence. The application of LLMs extends beyond conventional linguistic boundaries, encompassing specialized linguistic systems developed within various scientific disciplines. This growing interest has led to the advent of scientific LLMs, a novel subclass specifically engineered for facilitating scientific discovery. As a burgeoning area in the community of AI for Science, scientific LLMs warrant comprehensive exploration. However, a systematic and up-to-date survey introducing them is currently lacking. In this article, we endeavor to methodically delineate the concept of “scientific language,” whilst providing a thorough review of the latest advancements in scientific LLMs. Given the expansive realm of scientific disciplines, our analysis adopts a focused lens, concentrating on the biological and chemical domains. This includes an in-depth examination of LLMs for textual knowledge, small molecules, macromolecular proteins, genomic sequences, and their combinations, analyzing them in terms of model architectures, capabilities, datasets, and evaluation. Finally, we critically examine the prevailing challenges and point out promising research directions along with the advances of LLMs. By offering a comprehensive overview of technical developments in this field, this survey aspires to be an invaluable resource for researchers navigating the intricate landscape of scientific LLMs.
Abstract A004: Nodal Management in cancer treatment: Synergistic potential of immune checkpoint inhibitors
Authors: Koh Su-Jin
Published: January 2025

Lymph nodes (LNs) are critical components of the immune system, playing an essential role in the regulation of tumor immune surveillance and the progression of metastatic cancer. Recent advancements in immune checkpoint inhibitors (ICIs), including monoclonal antibodies targeting PD-1, PD-L1, and CTLA-4, have revolutionized cancer therapy by enhancing the immune system's ability to recognize and eliminate tumor cells. However, the interaction between immune checkpoint blockade (ICB) and lymphatic tissue, particularly the role of regional lymph nodes in treatment efficacy, remains insufficiently understood. This research explores the potential of combining immune checkpoint therapy with targeted strategies for managing nodal involvement in cancers. We aim to investigate the mechanisms by which tumor-infiltrating lymph nodes may either aid or hinder the response to ICBs, with a focus on the activation of anti-tumor immune responses within the nodal microenvironment. By examining how immune checkpoints impact tumor-associated lymphoid structures, we aim to identify strategies for improving regional lymph node management, including the use of neoadjuvant ICB, lymph node dissection, and lymph node-targeted drug delivery. The findings of this study may provide insights into optimizing immune checkpoint blockade therapies for cancers with extensive nodal metastasis and lead to novel therapeutic approaches that enhance regional immune responses while minimizing adverse effects. Ultimately, this research has the potential to contribute to a more personalized approach to cancer treatment, particularly for patients with advanced or metastatic disease, where nodal involvement is often a critical determinant of prognosis.

Citation Format: Su-Jin Koh. Nodal Management in cancer treatment: Synergistic potential of immune checkpoint inhibitors. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A004.
Abstract A005: 18F-Fluorthanatrace PARP inhibitor PET tracer: Potential implications for theranostics
Authors: Lin Lilie , Hammad Mahmoud , Wong Franklin , Yap Timothy A.
Published: January 2025

Objective: PARP (poly [ADP-ribose] polymerase) inhibitors are approved for a variety of malignancies including those with a breast, prostate, and ovarian carcinoma, particularly in the setting of a germline or somatic pathogenic BRCA mutation. There is active interest in the development of theranostics including those with a PARP inhibitor backbone. Methods: We evaluate a novel PARP inhibitor (PARPi) PET tracer 18-Fluorine [18F] Fluorthanatrace (FTT). Patients with primary or metastatic solid tumors with measurable disease initiating therapy with a PARP inhibitor monotherapy or in combination with another systemic agent were eligible. Patients underwent 18F-FTT PET/CT prior to initiation of PARPi and a second 18F-FTT PET 2-4 weeks after initiation of a PARP inhibitor. Hematologic toxicity on PARPi monotherapy or combination was assessed using the CTCAEv5.0 criteria. Regions of interest were drawn over the uninvolved bone marrow (usually taken at L3) and normal muscle to obtain the maximum standardized uptake value. Bone marrow to muscle ratio (B/M) was calculated at baseline and on PARPi. Spearman rank correlation coefficient was used. Results: A total of 21 patients were enrolled and underwent 18F-FTT PET. Patients had a median of 0 (range 0-7) prior lines of systemic therapy. The primary disease site included breast (9), ovary (6), primary peritoneal (1), pancreas (1)and other (4). Measurable uptake of 18F-FTT within the tumor and bone marrow was observed in all patients. Median L3 SUVmax at baseline was 4.3 (range 2.1-11.8) vs. 2.33 (range 1.4-2.9) while on PARP inhibitor. Baseline B/M was associated with highest grade hematologic toxicity in patients (n=10) who received talazoparib monotherapy or combination (r=0.65, p=0.042). While B/M was not associated with hematologic toxicity in patients (n=11) who received olaparib monotherapy or combination (r=0.098, p=0.77). Conclusions: 18F-FTT PET can measure target engagement of PARP inhibitors in bone marrow and may have implications for PARP inhibitor-based theranostics and dosing. Results suggest there may be differential impact of different PARPi on bone marrow and should be considered when selecting a backbone for theranostics.

Citation Format: Lilie Lin, Mahmoud Hammad, Franklin Wong, Timothy A. Yap. 18F-Fluorthanatrace PARP inhibitor PET tracer: Potential implications for theranostics. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A005.
Abstract A009: Targeting DNA damage responsive pathways in cancer therapy
Authors: Chen Junjie
Published: January 2025

DNA double strand breaks (DSBs) result in activation of several key DNA damage response (DDR) kinases including ATM, ATR, and DNA-PK. These protein kinases not only promote DNA damage-induced checkpoint control, but also facilitate DSB repair in humans. Thus, these DDR kinases have become promising drug targets for cancer therapy. However, the benefits of targeting DDR kinases remain to be realized, in part due to the lack of predictive biomarkers. By undertaking CRISPR screens with inhibitors targeting key DDR kinases, we obtained a global and unbiased view of genetic interactions with DDR inhibition. Additionally, we compared the synergistic effects of combining different DDR inhibitors and found that ATM and PARP inhibitors showed remarkable synergy, which depends on the dominant negative function of ATM inhibition. Moreover, to provide comprehensive and unbiased perspective of DDR signaling pathways, we performed 30 fluorescence-activated cell sorting–based genome-wide CRISPR screens with antibodies recognizing distinct endogenous DNA damage–signaling proteins to identify new regulators involved in DNA damage response (DDR). We discovered that proteasome-mediated processing is an early and prerequisite event for cells to trigger camptothecin- and etoposide-induced DDR signaling. Furthermore, we identified PRMT1 and PRMT5 as new modulators that regulate ATM protein level. Additionally, we discovered that GNB1L is a master regulator of DDR signaling via its role as a co-chaperone for PIKK proteins. Collectively, these screens offer a rich resource for further investigation of DDR, which may provide insight into strategies of targeting these DDR pathways to improve therapeutic outcomes. More recently, we have adopted dTAG technology for the investigation of many essential DDR and replication proteins, which provide mechanistic insights into the roles of these essential proteins in genome maintenance. Additionally, we have expanded FACS-based screens for the studies of other cancer-associated pathways and explored key biological processes critical for cancer progression in vivo. These studies will facilitate the development of better therapies for cancer patients.

Citation Format: Junjie Chen. Targeting DNA damage responsive pathways in cancer therapy. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A009.